Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeuti...Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.展开更多
BACKGROUND Studies have demonstrated that patients who have experienced acute coronary syndrome(ACS)have an increased risk of developing posttraumatic stress disorder(PTSD)and experiencing worse survival outcomes than...BACKGROUND Studies have demonstrated that patients who have experienced acute coronary syndrome(ACS)have an increased risk of developing posttraumatic stress disorder(PTSD)and experiencing worse survival outcomes than those who do not develop PTSD.Nevertheless,the prevalence rates of PTSD following ACS vary widely across studies,and it is noteworthy that in most cases,the diagnosis of PTSD was based on self-report symptom questionnaires,rather than being established by psychiatrists.Additionally,the individual characteristics of patients who develop PTSD after ACS can differ widely,making it difficult to identify any consistent patterns or predictors of the disorder.AIM To investigate the prevalence of PTSD among a large sample of patients undergoing cardiac rehabilitation(CR)after ACS,as well as their characteristics in comparison to a control group.METHODS The participants of this study are patients who have experienced ACS with or without undergoing percutaneous coronary intervention and are enrolled in a 3-wk CR program at the largest CR center in Croatia,the Special Hospital for Medical Rehabilitation Krapinske Toplice.Patient recruitment for the study took place over the course of one year,from January 1,2022,to December 31,2022,with a total of 504 participants.The expected average follow-up period for patients included in the study is about 18 mo,and currently ongoing.Using self-assessment questionnaire for PTSD criteria and clinical psychiatric interview,a group of patients with a PTSD diagnosis was identified.From the participants who do not have a PTSD diagnosis,patients who would match those with a PTSD diagnosis in terms of relevant clinical and medical stratification variables and during the same rehabilitation period were selected to enable comparability of the two groups.RESULTS A total of 507 patients who were enrolled in the CR program were approached to participate in the study.Three patients declined to participate in the study.The screening PTSD Checklist-Civilian Version questionnaire was completed by 504 patients.Out of the total sample of 504 patients,74.2%were men(n=374)and 25.8%were women(n=130).The mean age of all participants was 56.7 years(55.8 for men and 59.1 for women).Among the 504 participants who completed the screening questionnaire,80 met the cutoff criteria for the PTSD and qualified for further evaluation(15.9%).All 80 patients agreed to a psychiatric interview.Among them,51 patients(10.1%)were diagnosed with clinical PTSD by a psychiatrist according to Diagnostic and Statistical Manual of Mental Disorders criteria.Among the variables analyzed,there was a noticeable difference in the percentage of theoretical maximum achieved on exercise testing between the PTSD and non-PTSD groups.Non-PTSD group achieved a significantly higher percentage of their maximum compared to the PTSD group(P=0.035).CONCLUSION The preliminary results of the study indicate that a significant proportion of patients with PTSD induced by ACS are not receiving adequate treatment.Furthermore,the data suggest that these patients may exhibit reduced physical activity levels,which could be one of the possible underlying mechanisms in observed poor cardiovascular outcomes in this population.Identifying cardiac biomarkers is crucial for identifying patients at risk of developing PTSD and may derive benefits from personalized interventions based on the principles of precision medicine in multidisciplinary CR programs.展开更多
Background:With the rapid development of the world’s technology,the connection and integration between traditional medicine and modern machine learning technology are increasingly close.In this study,we aimed to anal...Background:With the rapid development of the world’s technology,the connection and integration between traditional medicine and modern machine learning technology are increasingly close.In this study,we aimed to analyze publications on machine learning in traditional medicine by using bibliometric methods and explore global trends in the field.Methods:Relevant research on machine learning in traditional medicine extracted from the Web of Science Core Collection database.Bibliometric analysis and visualization were performed using the Bibliometrix package in R software.Global trends,source journals,authorship,and thematic keywords analysis were performed in this study.Results:From 2012 to 2022,a total of 282 publications on machine learning in traditional medicine were identified and analyzed.The average annual growth rate of the publications was 13.35%.China had the largest contribution in this field(53.9%),followed by the United States(32.6%).IEEE Access had the largest number of published articles,with a total of 15 articles.Calvin Yu-Chian Chen,Xiao-juan Hu and Jue Wang were the main researchers in this field.Shanghai University of Traditional Chinese Medicine and University of California,San Francisco were the main research institutions.Conclusion:This study provides information on research trends in machine learning in traditional medicine to better understand research hotspots and future developments in this field.According to current global trends,the number of publications in this field will gradually increase.China currently dominated the field.Applied research of machine learning techniques may be the next hot topic in this field and deserves further attention.展开更多
Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amy...Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amyotrophic lateral sclerosis is still a long one.According to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways.The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis.Here,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis.In addition,we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis.Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.展开更多
Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods...Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival analysis.Simultaneously,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of PC.The small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell lines.Results:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell proliferation.Wound healing and Transwell assays revealed that MND1 knockdown reduced cell migration and invasion.Flow cytometry revealed that inhibiting MND1 hindered the cell cycle.Furthermore,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of MND1.Notably,MND1 had a positive effect on H2AFX expression in PC cells.Elevated MND1 expression suggests the low overall survival rate of individuals diagnosed with PC.Conclusion:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.展开更多
BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is ...BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.展开更多
AIM: To verify the validity of the International Ascites Club guidelines for treatment of spontaneous bacterial peritonitis (SBP) in clinical practice. METHODS: All SBP episodes occurring in a group of consecutive cir...AIM: To verify the validity of the International Ascites Club guidelines for treatment of spontaneous bacterial peritonitis (SBP) in clinical practice. METHODS: All SBP episodes occurring in a group of consecutive cirrhotics were managed accordingly and included in the study. SBP was diagnosed when the ascitic fluid polymorphonuclear (PMN) cell count was > 250 cells/mm3, and empirically treated with cefotaxime. RESULTS: Thirty-eight SBP episodes occurred in 32 cirrhotics (22 men/10 women; mean age: 58.6 ± 11.2 years). Prevalence of SBP, in our population, was 17%. Ascitic fluid culture was positive in nine (24%) cases only. Eleven episodes were nosocomial and 71% community-acquired. Treatment with cefotaxime was successful in 59% of cases, while 41% of episodes required a modification of the initial antibiotic therapy because of a less-than 25% decrease in ascitic PMN count at 48 h. Change of antibiotic therapy led to the resolution of infection in 87% of episodes. Among the cases with positive culture, the initial antibiotic therapy with cefotaxime failed at a percentage (44%) similar to that of the whole series. In these cases, the isolated organisms were either resistant or with an inherent insufficient susceptibility to cefotaxime. CONCLUSION: In clinical practice, ascitic PMN count is a valid tool for starting a prompt antibiotic treatment andevaluating its efficacy. The initial treatment with cefotaxime failed more frequently than expected. An increase in healthcare-related infections with antibiotic-resistant pathogens may explain this finding. A different first-line antibiotic treatment should be investigated.展开更多
Esophageal squamous cell carcinoma(ESCC)and esophagogastric junction adenocarcinoma(EGJA)are the two main types of gastrointestinal cancers that pose a huge threat to human health.ESCC remains one of the most common m...Esophageal squamous cell carcinoma(ESCC)and esophagogastric junction adenocarcinoma(EGJA)are the two main types of gastrointestinal cancers that pose a huge threat to human health.ESCC remains one of the most common malignant diseases around the world.In contrast to the decreasing prevalence of ESCC,the incidence of EGJA is rising rapidly.Early detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these cancers.Current approaches for early diagnosis mainly depend on invasive and costly endoscopy.Non-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of patients.Tumor-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis,making them promising biomarkers for early detection and monitoring of ESCC and EGJA.In this review,we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.展开更多
AIM:To evaluate the prevalence of Helicobacter pylori(H.pylori ) babA2 ,babB and a recombinant gene between babA2 and babB(babA2/B ),and their role in the development of atrophic gastritis in Costa Rican and Japanese ...AIM:To evaluate the prevalence of Helicobacter pylori(H.pylori ) babA2 ,babB and a recombinant gene between babA2 and babB(babA2/B ),and their role in the development of atrophic gastritis in Costa Rican and Japanese clinical isolates.METHODS:A total of 95 continuous H.pylori-positive Costa Rican(41 males and 54 females;mean age,50.65 years;SD,± 13.04 years) and 95 continuous H.pylori-positive Japanese(50 males and 45 females;mean age,63.43;SD,± 13.21 years) patients underwent upper endoscopy from October 2005 to July 2006.They were enrolled for the polymerase chain reaction(PCR)-based genotyping of the H.pylori babA2 ,babB and babA2/B genes.Statistical analysis was performed using the χ2 test and the Fisher's exact probability test and multivariate analysis was performed by logistic regression adjusting for gender and age.P < 0.05 was regarded as statistically significant.RESULTS:The PCR-based genotyping of 95 Costa Rican and 95 Japanese isolates showed a higher prevalence of babA2 in Japan(96.8%) than in Costa Rica(73.7%),while that of babA2/B was higher in Costa Rica(11.6%) than in Japan(1.1%).In Costa Rican isolates only,babA2 was significantly associated with atrophic gastritis(P = 0.01).CONCLUSION:These results suggest that the status of babA2 and babA2/B shows geographic differences,and that babA2 has clinical relevance in Costa Rica.展开更多
Transcorneal electrical stimulation(TES) is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally invas...Transcorneal electrical stimulation(TES) is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally invasive and readily applicable in a routine manner.Series of animal experiments have shown that TES protects the retinal neuron from traumatic or genetic induced degeneration. These laboratory evidences support its utilization in ophthalmological therapies against various retinal and optical diseases including retinitis pigmentosa(RP), traumatic optic neuropathy,anterior ischemic optic neuropathy(AION), and retinal artery occlusions(RAOs). Several pioneering explorations sought to clarify the functional mechanism underlying the neuroprotective effects of TES. It seems that the neuroprotective effects should not be attributed to a solitary pathway, on the contrary, multiple mechanisms might contribute collectively to maintain cellular homeostasis and promote cell survival in the retina. More precise evaluations via functional and morphological techniques would determine the exact mechanism underlying the remarkable neuroprotective effect of TES. Further studies to determine the optimal parameters and the long-term stability of TES are crucial to justify the clinical significance and to establish TES as a popularized therapeutic modality against retinal and optic neuropathy.展开更多
BACKGROUND The burden of chronic kidney disease(CKD)is rising rapidly globally.Fluid overload(FO),an independent predictor of mortality in CKD,should be accurately assessed to guide estimation of the volume of fluid t...BACKGROUND The burden of chronic kidney disease(CKD)is rising rapidly globally.Fluid overload(FO),an independent predictor of mortality in CKD,should be accurately assessed to guide estimation of the volume of fluid to be removed during haemodialysis(HD).Clinical score(CS)and bio-impedance analysis(BIA)have been utilized in assessment of FO and BIA has demonstrated reproducibility and accuracy in determination of fluid status in patients on HD.There is need to determine the performance of locally-developed CSs in fluid status assessment when evaluated against BIA.AIM To assess the hydration status of patients on maintenance HD using BIA and a CS,as well as to evaluate the performance of that CS against BIA in fluid status assessment.METHODS This was a single-centre,hospital-based cross-sectional study which recruited adult patients with CKD who were on maintenance HD at Kenyatta National Hospital.The patients were aged 18 years and above and had been on maintenance HD for at least 3 mo.Those with pacemakers,metallic implants,or bilateral limbs amputations were excluded.Data on the patients’clinical history,physical examination,and chest radiograph findings were collected.BIA was performed on each of the study participants using the Quantum®II bio-impedance analyser manufactured by RJL Systems together with the BC 4®software.In evaluating the performance of the CS,BIA was considered as the gold standard test.A 2-by-2 table of the participants’fluid status at each of the CS values obtained compared to their paired BIA results was constructed(either++,+-,--or-+for FO using the CS and BIA,respectively).The results from this 2-by-2 table were used to compute the sensitivity and specificity of the CS at the various reference points and subsequently plot a receiver operating characteristic(ROC)curve that was used to determine the best cut-off point.Those above and below the best CS cut-off point as determined by the ROC were classified as being positive and negative for FO,respectively.The proportions of participants diagnosed with FO by the CS and BIA,respectively,were computed and summarized in a 2-by-2 contingency table for comparison.McNemar’s chi-squared test was used to assess any statistically significant difference in proportions of patients diagnosed as having FO by CS and BIA.Logistic regression analysis was conducted to assess whether the variables for the duration of dialysis,the number of missed dialysis sessions,advisement by health care professional on fluid or salt intake,actual fluid intake,the number of anti-hypertensives used,or body mass index were associated with a patient’s odds of having FO as diagnosed by BIA.RESULTS From 100 patients on maintenance HD screened for eligibility,80 were recruited into this study.Seventy-one(88.75%)patients were fluid overloaded when evaluated using BIA with mean extracellular volume of 3.02±1.79 L as opposed to the forty-seven(58.25%)patients who had FO when evaluated using the CS.The difference was significant,with a P value of<0.0001(95%confidence interval:0.1758-0.4242).Using CS,values above 4 were indicative of FO while values less than or equal to 4 denoted the best cut-off for no FO.The sensitivity and specificity for the CS were 63%and 78%respectively.None of the factors evaluated for association with FO showed statistical significance on the multivariable logistic regression model.CONCLUSION FO is very prevalent in patients on chronic HD at the Kenyatta National Hospital.CS detects FO less frequently when compared with BIA.The sensitivity and specificity for the CS were 63%and 78%respectively.None of the factors evaluated for association with FO showed statistical significance on the multivariable logistic regression model.展开更多
Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, w...Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal展开更多
AIM: To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings. METHODS: We studied 81 patients with hepatic iron overload not exp...AIM: To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings. METHODS: We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes. The metabolic syndrome (MS) was defined according to ATPⅢ criteria. Iron overload was assessed by liver biopsy. Liver histology was evaluated by Ishak's score and iron accumulation by Deugnier's score; steatosis was diagnosed when present in ≥ 5% of hepatocytes. RESULTS: According to transferrin saturation levels, we observed significant differences in the amount of hepatic iron overload and iron distribution, as well as the number of metabolic abnormalities. Using Receiving Operating Curve analysis, we found that the presence of two components of the MS differentiatedtwo groups with a statistically significant different hepatic iron overload (P < 0.0001). Patients with ≥ 2 metabolic alterations and steatosis had lower amount of hepatic iron, lower transferrin saturation and higher sinusoidal iron than patients with < 2 MS components and absence of steatosis. CONCLUSION: In our patients, the presence of ≥ 2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation, suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation. These patients may have the typical dysmetabolic iron overload syndrome. By contrast, patients with transferrin saturation ≥ 60% had more severe iron overload, few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.展开更多
AIM: To describe the establishment of a Danish inflammatory bowel diseases(IBD) twin cohort with focus on concordance of treatment and inflammatory markers.METHODS: We identified MZ twins, likely to be discordant or c...AIM: To describe the establishment of a Danish inflammatory bowel diseases(IBD) twin cohort with focus on concordance of treatment and inflammatory markers.METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the-80 ℃ mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria.RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62(39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU(IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 μg/g in 2 participants, and above 50 μg/g in a further 5 participants.CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins.展开更多
Pott’s spine,commonly known as spinal tuberculosis(TB),is an extrapulmonary form of TB caused by Mycobacterium TB.Pott’s paraplegia occurs when the spine is involved.Spinal TB is usually caused by the hematogenous s...Pott’s spine,commonly known as spinal tuberculosis(TB),is an extrapulmonary form of TB caused by Mycobacterium TB.Pott’s paraplegia occurs when the spine is involved.Spinal TB is usually caused by the hematogenous spread of infection from a central focus,which can be in the lungs or another location.Spinal TB is distinguished by intervertebral disc involvement caused by the same segmental arterial supply,which can result in severe morbidity even after years of approved therapy.Neurological impairments and spine deformities are caused by progressive damage to the anterior vertebral body.The clinical,radiographic,microbiological,and histological data are used to make the diagnosis of spinal TB.In Pott’s spine,combination multidrug antitubercular therapy is the basis of treatment.The recent appearance of multidrug-resistant/extremely drug-resistant TB and the growth of human immunodeficiency virus infection have presented significant challenges in the battle against TB infection.Patients who come with significant kyphosis or neurological impairments are the only ones who require surgical care.Debride-ment,fusion stabilization,and correction of spinal deformity are the cornerstones of surgical treatment.Clinical results for the treatment of spinal TB are generally quite good with adequate and prompt care.展开更多
BACKGROUND Specific pulmonary infection could seriously threaten the health of pilots and their companions.The consequences are serious.We investigated the clinical diagnosis,treatment,and medical identification of sp...BACKGROUND Specific pulmonary infection could seriously threaten the health of pilots and their companions.The consequences are serious.We investigated the clinical diagnosis,treatment,and medical identification of specific pulmonary infections in naval pilots.CASE SUMMARY We analyzed the medical waiver and clinical data of four pilots with specific pulmonary infections,who had accepted treatment at the Naval Medical Center of Chinese People’s Liberation Army between January 2020 and November 2021,including three cases of tuberculosis and one of cryptococcal pneumonia.All cases underwent a series of comprehensive treatment courses.Three cases successfully obtained medical waiver for flight after being cured,while one was grounded after reaching the maximum flight life after being cured.CONCLUSION Chest computed tomography scanning should be used instead of chest radiography in pilots’physical examination.Most pilots with specific pulmonary infection can be cured and return to flight.展开更多
Triple-negative breast cancer(TNBC)is characterized by fast growth,high metastasis,high invasion,and a lack of therapeutic targets.Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC ma...Triple-negative breast cancer(TNBC)is characterized by fast growth,high metastasis,high invasion,and a lack of therapeutic targets.Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC malignant progression.It is well known that the long noncoding RNA AFAP1-AS1 plays a crucial role in various tumors,but whether AFAP1-AS1 is involved in the mitosis of TNBC cells remains unknown.In this study,we investigated the functional mechanism of AFAP1-AS1 in targeting Polo-like Kinase 1(PLK1)activation and participating in mitosis of TNBC cells.We detected the expression of AFAP1-AS1 in the TNBC patient cohort and primary cells by in situ hybridization(ISH),northern blot,fluorescent in situ hybridization(FISH)and cell nucleus/cytoplasm RNA fraction isolation.High AFAP1-AS1 expression was negatively correlated with overall survival(OS),disease-free survival(DFS),metastasis-free survival(MFS)and recurrence-free survival(RFS)in TNBC patients.We explored the function of AFAP1-AS1 by transwell,apoptosis,immunofluorescence(IF)and patient-derived xenograft(PDX)models in vitro and in vivo.We found that AFAP1-AS1 promoted TNBC primary cell survival by inhibiting mitotic catastrophe and increased TNBC primary cell growth,migration and invasion.Mechanistically,AFAP1-AS1 activated phosphorylation of the mitosis-associated kinase PLK1 protein.Elevated levels of AFAP1-AS1 in TNBC primary cells increased PLK1 pathway downstream gene expression,such as CDC25C,CDK1,BUB1 and TTK.More importantly,AFAP1-AS1 increased lung metastases in a mouse metastasis model.Taken together,AFAP1-AS1 functions as an oncogene that activates the PLK1 signaling pathway.AFAP1-AS1 could be used as a potential prognostic marker and therapeutic target for TNBC.展开更多
Patient-derived tumor xenograft(PDX)models,a method involving the surgical extraction of tumor tissues from cancer patients and subsequent transplantation into immunodeficient mice,have emerged as a pivotal approach i...Patient-derived tumor xenograft(PDX)models,a method involving the surgical extraction of tumor tissues from cancer patients and subsequent transplantation into immunodeficient mice,have emerged as a pivotal approach in translational research,particularly in advancing precision medicine.As the first stage of PDX development,the patient-derived orthotopic xenograft(PDOX)models implant tumor tissue in mice in the corresponding anatomical locations of the patient.The PDOX models have several advantages,including high fidelity to the original tumor,heightened drug sensitivity,and an elevated rate of successful transplantation.However,the PDOX models present significant challenges,requiring advanced surgical techniques and resourceintensive imaging technologies,which limit its application.And then,the humanized mouse models,as well as the zebrafish models,were developed.Humanized mouse models contain a human immune environment resembling the tumor and immune system interplay.The humanized mouse models are a hot topic in PDX model research.Regarding zebrafish patient-derived tumor xenografts(zPDX)and patient-derived organoids(PDO)as promising models for studying cancer and drug discovery,zPDX models are used to transplant tumors into zebrafish as novel personalized medical animal models with the advantage of reducing patient waiting time.PDO models provide a cost-effective approach for drug testing that replicates the in vivo environment and preserves important tumor-related information for patients.The present review highlights the functional characteristics of each new phase of PDX and provides insights into the challenges and prospective developments in this rapidly evolving field.展开更多
BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A grow...BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS,also known as‘gut dysbiosis’.Fecal microbiota transplantation(FMT)has been suggested as a treatment for IBS.AIM To assess the efficacy and safety of FMT for the treatment of IBS.METHODS We searched Cochrane Central,MEDLINE,EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials(RCTs)investigating the effectiveness of FMT compared to placebo(including autologous FMT)in treating IBS.The primary outcome was the number of patients with improvements of symptoms measured using a validated,global IBS symptoms score.Secondary outcomes were changes in quality-of-life scores,non-serious and serious adverse events.Risk ratios(RR)and corresponding 95%CI were calculated for dichotomous outcomes,as were the mean differences(MD)and 95%CI for continuous outcomes.The Cochrane risk of bias tool was used to assess the quality of the trials.GRADE criteria were used to assess the overall quality of the evidence.RESULTS Eight RCTs(484 participants)were included in the review.FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo(RR 1.19,95%CI:0.68-2.10).Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group(RR 1.17,95%CI:0.63-2.15).One serious adverse event occurred in the FMT group and two in the placebo group(RR 0.42,95%CI:0.07-2.60).Endoscopic FMT delivery resulted in a significant improvement in symptoms,while capsules did not.FMT did not improve the quality of life of IBS patients but,instead,appeared to reduce it,albeit non significantly(MD-6.30,95%CI:-13.39-0.79).The overall quality of the evidence was low due to moderate-high inconsistency,the small number of patients in the studies,and imprecision.CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS.Larger trials are needed.展开更多
Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release o...Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson’s disease using 6-hydroxydopamine. When SH-SY5 Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson’s disease and in a mouse model of Parkinson’s disease. Next, we pretreated cell models of Parkinson’s disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson’s disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.展开更多
基金National Natural Science Foundation of China(Grant No.81273297)Shenyang Science and Technology Plan.Public Health R&D Special Project(21-173-9-67).
文摘Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.
文摘BACKGROUND Studies have demonstrated that patients who have experienced acute coronary syndrome(ACS)have an increased risk of developing posttraumatic stress disorder(PTSD)and experiencing worse survival outcomes than those who do not develop PTSD.Nevertheless,the prevalence rates of PTSD following ACS vary widely across studies,and it is noteworthy that in most cases,the diagnosis of PTSD was based on self-report symptom questionnaires,rather than being established by psychiatrists.Additionally,the individual characteristics of patients who develop PTSD after ACS can differ widely,making it difficult to identify any consistent patterns or predictors of the disorder.AIM To investigate the prevalence of PTSD among a large sample of patients undergoing cardiac rehabilitation(CR)after ACS,as well as their characteristics in comparison to a control group.METHODS The participants of this study are patients who have experienced ACS with or without undergoing percutaneous coronary intervention and are enrolled in a 3-wk CR program at the largest CR center in Croatia,the Special Hospital for Medical Rehabilitation Krapinske Toplice.Patient recruitment for the study took place over the course of one year,from January 1,2022,to December 31,2022,with a total of 504 participants.The expected average follow-up period for patients included in the study is about 18 mo,and currently ongoing.Using self-assessment questionnaire for PTSD criteria and clinical psychiatric interview,a group of patients with a PTSD diagnosis was identified.From the participants who do not have a PTSD diagnosis,patients who would match those with a PTSD diagnosis in terms of relevant clinical and medical stratification variables and during the same rehabilitation period were selected to enable comparability of the two groups.RESULTS A total of 507 patients who were enrolled in the CR program were approached to participate in the study.Three patients declined to participate in the study.The screening PTSD Checklist-Civilian Version questionnaire was completed by 504 patients.Out of the total sample of 504 patients,74.2%were men(n=374)and 25.8%were women(n=130).The mean age of all participants was 56.7 years(55.8 for men and 59.1 for women).Among the 504 participants who completed the screening questionnaire,80 met the cutoff criteria for the PTSD and qualified for further evaluation(15.9%).All 80 patients agreed to a psychiatric interview.Among them,51 patients(10.1%)were diagnosed with clinical PTSD by a psychiatrist according to Diagnostic and Statistical Manual of Mental Disorders criteria.Among the variables analyzed,there was a noticeable difference in the percentage of theoretical maximum achieved on exercise testing between the PTSD and non-PTSD groups.Non-PTSD group achieved a significantly higher percentage of their maximum compared to the PTSD group(P=0.035).CONCLUSION The preliminary results of the study indicate that a significant proportion of patients with PTSD induced by ACS are not receiving adequate treatment.Furthermore,the data suggest that these patients may exhibit reduced physical activity levels,which could be one of the possible underlying mechanisms in observed poor cardiovascular outcomes in this population.Identifying cardiac biomarkers is crucial for identifying patients at risk of developing PTSD and may derive benefits from personalized interventions based on the principles of precision medicine in multidisciplinary CR programs.
文摘Background:With the rapid development of the world’s technology,the connection and integration between traditional medicine and modern machine learning technology are increasingly close.In this study,we aimed to analyze publications on machine learning in traditional medicine by using bibliometric methods and explore global trends in the field.Methods:Relevant research on machine learning in traditional medicine extracted from the Web of Science Core Collection database.Bibliometric analysis and visualization were performed using the Bibliometrix package in R software.Global trends,source journals,authorship,and thematic keywords analysis were performed in this study.Results:From 2012 to 2022,a total of 282 publications on machine learning in traditional medicine were identified and analyzed.The average annual growth rate of the publications was 13.35%.China had the largest contribution in this field(53.9%),followed by the United States(32.6%).IEEE Access had the largest number of published articles,with a total of 15 articles.Calvin Yu-Chian Chen,Xiao-juan Hu and Jue Wang were the main researchers in this field.Shanghai University of Traditional Chinese Medicine and University of California,San Francisco were the main research institutions.Conclusion:This study provides information on research trends in machine learning in traditional medicine to better understand research hotspots and future developments in this field.According to current global trends,the number of publications in this field will gradually increase.China currently dominated the field.Applied research of machine learning techniques may be the next hot topic in this field and deserves further attention.
基金supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,and 82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,No.20192BAB205043Health and Family Planning Commission of Jiangxi Province,Nos.20181019 and 202210002(all to RX).
文摘Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amyotrophic lateral sclerosis is still a long one.According to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways.The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis.Here,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis.In addition,we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis.Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.
基金supported by grants from National Innovation Program for College Students(202210367076)Graduate Student Research Innovation Program of Bengbu Medical College(Byycxz22016)the National Natural Science Foundation of China(82072585),and the Key Research Project of Bengbu Medical College(No.2020byzd029).
文摘Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival analysis.Simultaneously,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of PC.The small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell lines.Results:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell proliferation.Wound healing and Transwell assays revealed that MND1 knockdown reduced cell migration and invasion.Flow cytometry revealed that inhibiting MND1 hindered the cell cycle.Furthermore,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of MND1.Notably,MND1 had a positive effect on H2AFX expression in PC cells.Elevated MND1 expression suggests the low overall survival rate of individuals diagnosed with PC.Conclusion:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.
基金Supported by National Natural Science Foundation of China,No.81470982.
文摘BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.
文摘AIM: To verify the validity of the International Ascites Club guidelines for treatment of spontaneous bacterial peritonitis (SBP) in clinical practice. METHODS: All SBP episodes occurring in a group of consecutive cirrhotics were managed accordingly and included in the study. SBP was diagnosed when the ascitic fluid polymorphonuclear (PMN) cell count was > 250 cells/mm3, and empirically treated with cefotaxime. RESULTS: Thirty-eight SBP episodes occurred in 32 cirrhotics (22 men/10 women; mean age: 58.6 ± 11.2 years). Prevalence of SBP, in our population, was 17%. Ascitic fluid culture was positive in nine (24%) cases only. Eleven episodes were nosocomial and 71% community-acquired. Treatment with cefotaxime was successful in 59% of cases, while 41% of episodes required a modification of the initial antibiotic therapy because of a less-than 25% decrease in ascitic PMN count at 48 h. Change of antibiotic therapy led to the resolution of infection in 87% of episodes. Among the cases with positive culture, the initial antibiotic therapy with cefotaxime failed at a percentage (44%) similar to that of the whole series. In these cases, the isolated organisms were either resistant or with an inherent insufficient susceptibility to cefotaxime. CONCLUSION: In clinical practice, ascitic PMN count is a valid tool for starting a prompt antibiotic treatment andevaluating its efficacy. The initial treatment with cefotaxime failed more frequently than expected. An increase in healthcare-related infections with antibiotic-resistant pathogens may explain this finding. A different first-line antibiotic treatment should be investigated.
基金Supported by the National Natural Science Foundation of China,No.31600632the Natural Science Foundation of Guangdong Province,No.2018A030307079
文摘Esophageal squamous cell carcinoma(ESCC)and esophagogastric junction adenocarcinoma(EGJA)are the two main types of gastrointestinal cancers that pose a huge threat to human health.ESCC remains one of the most common malignant diseases around the world.In contrast to the decreasing prevalence of ESCC,the incidence of EGJA is rising rapidly.Early detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these cancers.Current approaches for early diagnosis mainly depend on invasive and costly endoscopy.Non-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of patients.Tumor-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis,making them promising biomarkers for early detection and monitoring of ESCC and EGJA.In this review,we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.
基金Supported by (in part) A Grant-in-Aid for Scientific Research from the Ministry of Education,Science and Culture of Japan(21590631)the Project Research Fund from the Kochi University
文摘AIM:To evaluate the prevalence of Helicobacter pylori(H.pylori ) babA2 ,babB and a recombinant gene between babA2 and babB(babA2/B ),and their role in the development of atrophic gastritis in Costa Rican and Japanese clinical isolates.METHODS:A total of 95 continuous H.pylori-positive Costa Rican(41 males and 54 females;mean age,50.65 years;SD,± 13.04 years) and 95 continuous H.pylori-positive Japanese(50 males and 45 females;mean age,63.43;SD,± 13.21 years) patients underwent upper endoscopy from October 2005 to July 2006.They were enrolled for the polymerase chain reaction(PCR)-based genotyping of the H.pylori babA2 ,babB and babA2/B genes.Statistical analysis was performed using the χ2 test and the Fisher's exact probability test and multivariate analysis was performed by logistic regression adjusting for gender and age.P < 0.05 was regarded as statistically significant.RESULTS:The PCR-based genotyping of 95 Costa Rican and 95 Japanese isolates showed a higher prevalence of babA2 in Japan(96.8%) than in Costa Rica(73.7%),while that of babA2/B was higher in Costa Rica(11.6%) than in Japan(1.1%).In Costa Rican isolates only,babA2 was significantly associated with atrophic gastritis(P = 0.01).CONCLUSION:These results suggest that the status of babA2 and babA2/B shows geographic differences,and that babA2 has clinical relevance in Costa Rica.
基金Supported by the National Key Basic Research Program of China (973 Program, No. 2013CB967001)
文摘Transcorneal electrical stimulation(TES) is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally invasive and readily applicable in a routine manner.Series of animal experiments have shown that TES protects the retinal neuron from traumatic or genetic induced degeneration. These laboratory evidences support its utilization in ophthalmological therapies against various retinal and optical diseases including retinitis pigmentosa(RP), traumatic optic neuropathy,anterior ischemic optic neuropathy(AION), and retinal artery occlusions(RAOs). Several pioneering explorations sought to clarify the functional mechanism underlying the neuroprotective effects of TES. It seems that the neuroprotective effects should not be attributed to a solitary pathway, on the contrary, multiple mechanisms might contribute collectively to maintain cellular homeostasis and promote cell survival in the retina. More precise evaluations via functional and morphological techniques would determine the exact mechanism underlying the remarkable neuroprotective effect of TES. Further studies to determine the optimal parameters and the long-term stability of TES are crucial to justify the clinical significance and to establish TES as a popularized therapeutic modality against retinal and optic neuropathy.
文摘BACKGROUND The burden of chronic kidney disease(CKD)is rising rapidly globally.Fluid overload(FO),an independent predictor of mortality in CKD,should be accurately assessed to guide estimation of the volume of fluid to be removed during haemodialysis(HD).Clinical score(CS)and bio-impedance analysis(BIA)have been utilized in assessment of FO and BIA has demonstrated reproducibility and accuracy in determination of fluid status in patients on HD.There is need to determine the performance of locally-developed CSs in fluid status assessment when evaluated against BIA.AIM To assess the hydration status of patients on maintenance HD using BIA and a CS,as well as to evaluate the performance of that CS against BIA in fluid status assessment.METHODS This was a single-centre,hospital-based cross-sectional study which recruited adult patients with CKD who were on maintenance HD at Kenyatta National Hospital.The patients were aged 18 years and above and had been on maintenance HD for at least 3 mo.Those with pacemakers,metallic implants,or bilateral limbs amputations were excluded.Data on the patients’clinical history,physical examination,and chest radiograph findings were collected.BIA was performed on each of the study participants using the Quantum®II bio-impedance analyser manufactured by RJL Systems together with the BC 4®software.In evaluating the performance of the CS,BIA was considered as the gold standard test.A 2-by-2 table of the participants’fluid status at each of the CS values obtained compared to their paired BIA results was constructed(either++,+-,--or-+for FO using the CS and BIA,respectively).The results from this 2-by-2 table were used to compute the sensitivity and specificity of the CS at the various reference points and subsequently plot a receiver operating characteristic(ROC)curve that was used to determine the best cut-off point.Those above and below the best CS cut-off point as determined by the ROC were classified as being positive and negative for FO,respectively.The proportions of participants diagnosed with FO by the CS and BIA,respectively,were computed and summarized in a 2-by-2 contingency table for comparison.McNemar’s chi-squared test was used to assess any statistically significant difference in proportions of patients diagnosed as having FO by CS and BIA.Logistic regression analysis was conducted to assess whether the variables for the duration of dialysis,the number of missed dialysis sessions,advisement by health care professional on fluid or salt intake,actual fluid intake,the number of anti-hypertensives used,or body mass index were associated with a patient’s odds of having FO as diagnosed by BIA.RESULTS From 100 patients on maintenance HD screened for eligibility,80 were recruited into this study.Seventy-one(88.75%)patients were fluid overloaded when evaluated using BIA with mean extracellular volume of 3.02±1.79 L as opposed to the forty-seven(58.25%)patients who had FO when evaluated using the CS.The difference was significant,with a P value of<0.0001(95%confidence interval:0.1758-0.4242).Using CS,values above 4 were indicative of FO while values less than or equal to 4 denoted the best cut-off for no FO.The sensitivity and specificity for the CS were 63%and 78%respectively.None of the factors evaluated for association with FO showed statistical significance on the multivariable logistic regression model.CONCLUSION FO is very prevalent in patients on chronic HD at the Kenyatta National Hospital.CS detects FO less frequently when compared with BIA.The sensitivity and specificity for the CS were 63%and 78%respectively.None of the factors evaluated for association with FO showed statistical significance on the multivariable logistic regression model.
文摘Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal
基金Grant from the Association for the Study of Hemochromatosis and Iron Overload Disorders-ONLUS (P.T.), Monza
文摘AIM: To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings. METHODS: We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes. The metabolic syndrome (MS) was defined according to ATPⅢ criteria. Iron overload was assessed by liver biopsy. Liver histology was evaluated by Ishak's score and iron accumulation by Deugnier's score; steatosis was diagnosed when present in ≥ 5% of hepatocytes. RESULTS: According to transferrin saturation levels, we observed significant differences in the amount of hepatic iron overload and iron distribution, as well as the number of metabolic abnormalities. Using Receiving Operating Curve analysis, we found that the presence of two components of the MS differentiatedtwo groups with a statistically significant different hepatic iron overload (P < 0.0001). Patients with ≥ 2 metabolic alterations and steatosis had lower amount of hepatic iron, lower transferrin saturation and higher sinusoidal iron than patients with < 2 MS components and absence of steatosis. CONCLUSION: In our patients, the presence of ≥ 2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation, suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation. These patients may have the typical dysmetabolic iron overload syndrome. By contrast, patients with transferrin saturation ≥ 60% had more severe iron overload, few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.
基金Supported by Lundbeck foundation,Region of Southern Denmark,University of Southern Denmark,Hospital of Southern Jutland
文摘AIM: To describe the establishment of a Danish inflammatory bowel diseases(IBD) twin cohort with focus on concordance of treatment and inflammatory markers.METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the-80 ℃ mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria.RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62(39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU(IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 μg/g in 2 participants, and above 50 μg/g in a further 5 participants.CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins.
文摘Pott’s spine,commonly known as spinal tuberculosis(TB),is an extrapulmonary form of TB caused by Mycobacterium TB.Pott’s paraplegia occurs when the spine is involved.Spinal TB is usually caused by the hematogenous spread of infection from a central focus,which can be in the lungs or another location.Spinal TB is distinguished by intervertebral disc involvement caused by the same segmental arterial supply,which can result in severe morbidity even after years of approved therapy.Neurological impairments and spine deformities are caused by progressive damage to the anterior vertebral body.The clinical,radiographic,microbiological,and histological data are used to make the diagnosis of spinal TB.In Pott’s spine,combination multidrug antitubercular therapy is the basis of treatment.The recent appearance of multidrug-resistant/extremely drug-resistant TB and the growth of human immunodeficiency virus infection have presented significant challenges in the battle against TB infection.Patients who come with significant kyphosis or neurological impairments are the only ones who require surgical care.Debride-ment,fusion stabilization,and correction of spinal deformity are the cornerstones of surgical treatment.Clinical results for the treatment of spinal TB are generally quite good with adequate and prompt care.
基金Supported by Key Project of Medical Service Scientific Research of Navy Medical Center,No.20M2302.
文摘BACKGROUND Specific pulmonary infection could seriously threaten the health of pilots and their companions.The consequences are serious.We investigated the clinical diagnosis,treatment,and medical identification of specific pulmonary infections in naval pilots.CASE SUMMARY We analyzed the medical waiver and clinical data of four pilots with specific pulmonary infections,who had accepted treatment at the Naval Medical Center of Chinese People’s Liberation Army between January 2020 and November 2021,including three cases of tuberculosis and one of cryptococcal pneumonia.All cases underwent a series of comprehensive treatment courses.Three cases successfully obtained medical waiver for flight after being cured,while one was grounded after reaching the maximum flight life after being cured.CONCLUSION Chest computed tomography scanning should be used instead of chest radiography in pilots’physical examination.Most pilots with specific pulmonary infection can be cured and return to flight.
基金supported by the Natural Science Foundation of China(Nos.82002782,82202657)the Guangdong Basic and Applied Basic Research Foundation(2022A1515012021,2020A1515110930).
文摘Triple-negative breast cancer(TNBC)is characterized by fast growth,high metastasis,high invasion,and a lack of therapeutic targets.Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC malignant progression.It is well known that the long noncoding RNA AFAP1-AS1 plays a crucial role in various tumors,but whether AFAP1-AS1 is involved in the mitosis of TNBC cells remains unknown.In this study,we investigated the functional mechanism of AFAP1-AS1 in targeting Polo-like Kinase 1(PLK1)activation and participating in mitosis of TNBC cells.We detected the expression of AFAP1-AS1 in the TNBC patient cohort and primary cells by in situ hybridization(ISH),northern blot,fluorescent in situ hybridization(FISH)and cell nucleus/cytoplasm RNA fraction isolation.High AFAP1-AS1 expression was negatively correlated with overall survival(OS),disease-free survival(DFS),metastasis-free survival(MFS)and recurrence-free survival(RFS)in TNBC patients.We explored the function of AFAP1-AS1 by transwell,apoptosis,immunofluorescence(IF)and patient-derived xenograft(PDX)models in vitro and in vivo.We found that AFAP1-AS1 promoted TNBC primary cell survival by inhibiting mitotic catastrophe and increased TNBC primary cell growth,migration and invasion.Mechanistically,AFAP1-AS1 activated phosphorylation of the mitosis-associated kinase PLK1 protein.Elevated levels of AFAP1-AS1 in TNBC primary cells increased PLK1 pathway downstream gene expression,such as CDC25C,CDK1,BUB1 and TTK.More importantly,AFAP1-AS1 increased lung metastases in a mouse metastasis model.Taken together,AFAP1-AS1 functions as an oncogene that activates the PLK1 signaling pathway.AFAP1-AS1 could be used as a potential prognostic marker and therapeutic target for TNBC.
基金The Science,Technology and Innovation Commission of Shenzhen,Grant/Award Number:JCYJ20220531093213030。
文摘Patient-derived tumor xenograft(PDX)models,a method involving the surgical extraction of tumor tissues from cancer patients and subsequent transplantation into immunodeficient mice,have emerged as a pivotal approach in translational research,particularly in advancing precision medicine.As the first stage of PDX development,the patient-derived orthotopic xenograft(PDOX)models implant tumor tissue in mice in the corresponding anatomical locations of the patient.The PDOX models have several advantages,including high fidelity to the original tumor,heightened drug sensitivity,and an elevated rate of successful transplantation.However,the PDOX models present significant challenges,requiring advanced surgical techniques and resourceintensive imaging technologies,which limit its application.And then,the humanized mouse models,as well as the zebrafish models,were developed.Humanized mouse models contain a human immune environment resembling the tumor and immune system interplay.The humanized mouse models are a hot topic in PDX model research.Regarding zebrafish patient-derived tumor xenografts(zPDX)and patient-derived organoids(PDO)as promising models for studying cancer and drug discovery,zPDX models are used to transplant tumors into zebrafish as novel personalized medical animal models with the advantage of reducing patient waiting time.PDO models provide a cost-effective approach for drug testing that replicates the in vivo environment and preserves important tumor-related information for patients.The present review highlights the functional characteristics of each new phase of PDX and provides insights into the challenges and prospective developments in this rapidly evolving field.
文摘BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS,also known as‘gut dysbiosis’.Fecal microbiota transplantation(FMT)has been suggested as a treatment for IBS.AIM To assess the efficacy and safety of FMT for the treatment of IBS.METHODS We searched Cochrane Central,MEDLINE,EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials(RCTs)investigating the effectiveness of FMT compared to placebo(including autologous FMT)in treating IBS.The primary outcome was the number of patients with improvements of symptoms measured using a validated,global IBS symptoms score.Secondary outcomes were changes in quality-of-life scores,non-serious and serious adverse events.Risk ratios(RR)and corresponding 95%CI were calculated for dichotomous outcomes,as were the mean differences(MD)and 95%CI for continuous outcomes.The Cochrane risk of bias tool was used to assess the quality of the trials.GRADE criteria were used to assess the overall quality of the evidence.RESULTS Eight RCTs(484 participants)were included in the review.FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo(RR 1.19,95%CI:0.68-2.10).Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group(RR 1.17,95%CI:0.63-2.15).One serious adverse event occurred in the FMT group and two in the placebo group(RR 0.42,95%CI:0.07-2.60).Endoscopic FMT delivery resulted in a significant improvement in symptoms,while capsules did not.FMT did not improve the quality of life of IBS patients but,instead,appeared to reduce it,albeit non significantly(MD-6.30,95%CI:-13.39-0.79).The overall quality of the evidence was low due to moderate-high inconsistency,the small number of patients in the studies,and imprecision.CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS.Larger trials are needed.
基金supported by the National Natural Science Foundation of China,Nos. 81873742 (to KFK), 81901195 (to JBS)Nantong Technology Project,Nos. JC2020052 (to XSG),JCZ19087 (to XSG)。
文摘Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson’s disease using 6-hydroxydopamine. When SH-SY5 Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson’s disease and in a mouse model of Parkinson’s disease. Next, we pretreated cell models of Parkinson’s disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson’s disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.
