Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hip...Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.展开更多
BACKGROUND Colorectal high-grade neuroendocrine neoplasms(HGNENs)are rare and constitute less than 1%of all colorectal malignancies.Based on their morphological differentiation and proliferation identity,these neoplas...BACKGROUND Colorectal high-grade neuroendocrine neoplasms(HGNENs)are rare and constitute less than 1%of all colorectal malignancies.Based on their morphological differentiation and proliferation identity,these neoplasms present heterogeneous clinicopathologic features.Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial.AIM To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy.METHODS This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019.The clinicopathologic characteristics and follow-up data were carefully collected from their medical records,outpatient reexaminations,and telephone interviews.A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease.RESULTS According to the latest recommendations for the classification and nomenclature of colorectal HGNENs,61(84.7%)patients in our cohort had poorly differentiated neoplasms,which were categorized as high-grade neuroendocrine carcinomas(HGNECs),and the remaining 11(15.3%)patients had well differentiated neoplasms,which were categorized as high-grade neuroendocrine tumors(HGNETs).Most of the neoplasms(63.9%)were located at the rectum.More than half of the patients(51.4%)presented with distant metastasis at the date of diagnosis.All patients were followed for a median duration of 15.5 mo.In the entire cohort,the median survival time was 31 mo,and the 3-year and 5-year survival rates were 44.3%and 36.3%,respectively.Both the univariate and multivariate analyses demonstrated that increasing age,HGNEC type,and distant metastasis were risk factors for poor clinical outcomes.CONCLUSION Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes.However,patients with younger age,good morphological differentiation,and without metastatic disease can have a relatively favorable prognosis.展开更多
Objective:The objective of the study is to investigate the psychological status of nursing staff both working on nonfront line and on the front line during the epidemic period of COVID‑19 and to analyze the influencin...Objective:The objective of the study is to investigate the psychological status of nursing staff both working on nonfront line and on the front line during the epidemic period of COVID‑19 and to analyze the influencing factors related to mental health state,as well as to provide targeted psychological intervening measures for nursing staff in the face of this major public health event.Methods:We used data from January 28,2019,to February 08,2020,on the number of cases who worked in the 3A‑level hospital as nonfront‑line nurses(n=29,54%)and those who worked in Wuhan infectious hospital as the front‑line supporters(n=25,46%)came from the 3A‑level hospital.The participants completed the symptom checklist 90,and the researchers recorded data on demographics,psychological status,and the influencing factors.Results:In our baseline scenario,we estimated that the total symptom index was 1.676±0.654 for nurses who worked on the front line,1.260±0.304 for those who worked as the front‑line reserve nurses,and was 1.486±0.647 for those who worked as the nonfront‑line nurses.The results of correlation analysis show that the factors related to the psychological status of nurses include age,professional title,marital status,and family support;different factors have different effects on psychological status.Conclusion:In the face of major public health emergencies,both front‑line nursing staff and nonfront‑line staff are confronted with different degrees of psychological stress,so effective psychological support should be given to improve the working efficiency and enthusiasm of nurses.展开更多
Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and bra...Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.展开更多
Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are f...Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are few reports on the mechanism of action of the TBZPy photodynamic.Previous studies revealed that photodynamic therapy(PDT)could induce endoplasmic reticulum stress by acting on the endoplasmic reticulum.Therefore,in this study,we investigated the effects of endoplasmic reticulum stress induced by TBZPy-PDT in treating High-risk human papillomavirus(HR-HPV)infection and their underlying mechanisms.Methods:The human cervical cancer cell line HeLa(containing whole genome of HR-HPV18)was treated with TBZPy-PDT.Cell migration,invasion,and colony-forming ability were evaluated using wound-healing,Transwell invasion,and colonyforming assays,respectively.Through western blot analysis,we determined the level of expression of the PI3K/AKT and PERK/eIF2αpathway proteins and the proteins associated with calcium trafficking and apoptosis.The calcium levels in the cytoplasm were detected via flow cytometry.Results:The result shows that TBZPy-PDT could inhibite the migration,invasion,and colony forming ability of infected HeLa cells by downregulating the PI3K/AKT pathway in vitro.And we found that TBZPy-PDT induced endoplasmic reticulum stress-specific apoptosis via the PERK/eIF2αpathway.Moreover,TBZPy-PDT increased the levels of calcium and calmodulin,while decreasing the levels of endoplasmic reticulum calcium-binding proteins.Conclusions:TBZPy-PDT is effective on treating human papillomavirus-infected cells.Targeting the PI3K/AKT and PERK/eIF2αpathways and the endoplasmic reticulum stress process may help improve the effects of TBZPy-PDT for treating high-risk human papillomavirus infection.展开更多
BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GI...BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GIST(17 male and 2 female,median age 62 years).GC was most often located in the lower third of the stomach.GIST was diagnosed preoperatively in four patients.GIST was most often located in the gastric body(n=8,42%).The most common growth pattern in GIST was extraluminal(n=12,63%).The positive expression rates of CD117 and CD34 in GIST were 100% and 95%,respectively.Most patients with GIST(n=17,89%)were very low or low risk.There was no recurrence of GIST during follow-up.The 3-year cumulative survival rate was 73.9%,and the 5-year cumulative survival rate was 59.2%.The combined analysis of this study and literature reports(47 reports,157 patients)found that GC and GIST were usually located in the lower third(42%)and middle third(51%)of the stomach.GC was usually early(stage I:42%),poorly differentiated(42%)intestinal-type adenocarcinoma(51%).GISTs were primarily small in diameter(median:1.2 cm)and very low or low risk(89%).CONCLUSION Synchronous GC and GIST may not be rare.They have specific clinicopathological characteristics,and may have mutual inhibition in pathogenesis and progression.展开更多
Objective: Breast cancer is a major cancer threatening the health of women globally. To elucidate the effect ofthe circHIAT1/miR-19a-3p/phosphatase and tensin homolog (PTEN) axis on regulating the malignant phenotype ...Objective: Breast cancer is a major cancer threatening the health of women globally. To elucidate the effect ofthe circHIAT1/miR-19a-3p/phosphatase and tensin homolog (PTEN) axis on regulating the malignant phenotype ofbreast cancer cells. Methods: The mRNA expression pattern of circHIAT1, miR-19a-3p, and PTEN was checked byreal-time quantitative polymerase chain reaction. Then, the knockdown assay was carried out to explore the effect ofcircHIAT1 and miR-19a-3p on breast cancer. The relative cell experiments, including MTT assay, scratch assay,transwell invasion assay, and flow cytometry analysis, were conducted to verify the influence of circHIAT1 and miR-19a-3p on breast cancer cells. Results: The levels of PTEN and circHIAT1 were reduced, while that of miR-19a-3pwas elevated in breast cancer tissues and cells. MiR-19a-3p was proved to be the target gene of circHIAT1 via a dualluciferase experiment, which could also modulate the PTEN mRNA level. Overexpression of circHIAT1 was able toundermine the growth, migratory ability, and invasiveness in breast cancer cells, which could be antagonized by miR-19a-3p mimic. The inhibition of miR-19a-3p in vitro also impaired the malignancy of breast cancer, which dependedon the modulation of PTEN expression. Conclusion: CircHIAT1 controls the PTEN expression level in cells of breastcancer by negatively regulating miR-19a-3p. This mechanism controls the growth, invasion, and migration of breastcancer.展开更多
BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore th...BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively.Immunohistochemical staining(IHC)was used to detect the expression of NPAS2 protein in GC and adjacent tissues.Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC,and a nomogram prediction model was established.The receiver operating characteristic(ROC)curve,the ROC area under the curve,the calibration curve,and C-index were used to evaluate the predictive effectiveness of the model.Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%,which was significantly higher than 30.69%in adjacent tissues.The high expression of NPAS2 was correlated with tumor-node-metastasis(TNM)stage(P<0.05),pN stage(P<0.05),metastasis(P<0.05),venous invasion(P<0.05),lymphatic invasion(P<0.05),and lymph node positive(P<0.05)of GC.Kaplan Meier survival analysis showed that the 3-year overall survival(OS)of patients with high NPAS2 expression was significantly shortened(P<0.0001).Univariate and multivariate COX regression analysis showed that TNM stage(P=0.009),metastasis(P=0.009),and NPAS2 expression(P=0.020)were independent prognostic factors of OS in GC patients for 3 years.The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740(95%CI:0.713-0.767).Furthermore,subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group(P<0.0001).CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients.Therefore,the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation.Notably,the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.展开更多
Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for ...Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for activation, and calpain or 2, which requires millimolar Ca<sup>2+</sup> for activation. The presence of other calpains is tissue specific. Atherosclerosis (AS) is an important risk factor for cerebral infarction, coronary heart disease and peripheral vascular disease. It was originally thought that AS was caused by impaired lipid metabolism. This research briefly reviewed Calpain Family, the structure and activation mechanism of calpain1, Calpains in the pathogenesis of atherosclerosis, NLRP3 structural characteristics and activation, ROS/NLRP3 inflammasome activation mechanism and ROS/NLRP3 inflammasome in atherosclerosis. The research showed that the Calpain-1 may play an important role in mitochondrial ROS/NLRP3 inflammasome in atherosclerosis.展开更多
Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management...Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.展开更多
AIM: To investigate the roles of Golgi protein(GP) 73 in the regulation of cell proliferation and apoptosis. METHODS: Stealth RNAi targeting GP73 gene sequence was used to silence its expression in Hep G2 cells and Be...AIM: To investigate the roles of Golgi protein(GP) 73 in the regulation of cell proliferation and apoptosis. METHODS: Stealth RNAi targeting GP73 gene sequence was used to silence its expression in Hep G2 cells and Bel7402 cells. Stealth RNAi effects were assessed by reverse transcriptase polymerase chain reaction and ELISA. Cell proliferation assay and cell cycle analysis were assessed by MTT assay and flow cytometry. Apoptosis was assessed by flow cytometry andtransmission electron microscopy. Apoptosis-related proteins were assessed by western immunoblot analysis.RESULTS: Stealth RNAi targeting GP73 gene sequence markedly reduced the expression of GP73 gene. The reduction of GP73 in Hep G2 cells and Bel7402 cells inhibited cell proliferation and induced apoptosis, however, terminal apoptosis occurred in Hep G2 cells, but early apoptosis occurred in Bel7402 cells. Reduced expression of GP73 gene might lead to a reduction in Bcl-2/Bax ratio, an increase in cytochrome c, but a reduction in capase-3.CONCLUSION: GP73 might play an important role in proliferation and apoptosis in hepatocellular carcinoma cells.展开更多
Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years...Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years, but the problems, including difficult diagnosis at early stage, quick progression, and poor prognosis remain unsolved. Surgical resection is the mainstay of the treatment for HCC. However, 70%-80% of HCC patients are diagnosed at an advanced stage when most are ineligible for potentially curative therapies such as surgical resection and liver transplantation. In recent years, non-surgical management for unrespectable HCC, such as percutaneous ethanol injection, percutaneous microwave coagulation therapy, percutaneous radiofrequency ablation, transcatheter arterial chemoembolization, radiotherapy, chemotherapy, biotherapy, and hormonal therapy have been developed. These therapeutic options, either alone or in combination, have been shown to control tumor growth, prolong survival time, and improve quality of life to some extent. This review covers the current status and progress of non-surgical management for HCC.展开更多
AIM: To explore the correlation between several blood cell-associated inflammatory indices including mean platelet volume(MPV), platelet distribution width(PDW), neutrophil to lymphocyte ratio(NLR) and platelet-lympho...AIM: To explore the correlation between several blood cell-associated inflammatory indices including mean platelet volume(MPV), platelet distribution width(PDW), neutrophil to lymphocyte ratio(NLR) and platelet-lymphocyte ratio(PLR), and the presence and severity of diabetic retinopathy(DR). METHODS: We searched for eligible studies from PubMed, EMBASE, Web of Science and CNKI up to December 13, 2017. Standardized mean difference(SMD) calculated with confidence interval(CI) of 95% was used to estimate the values of those indices. RESULTS: A total of 31 studies were included in the present Meta-analysis. As compared with type 2 diabetes mellitus(T2 DM) patients without DR, the values of MPV, PDW, NLR, and PLR were higher in patients with DR(SMD=0.67; 95%CI: 0.36 to 0.98; SMD=0.51; 95%CI: 0.27 to 0.75; SMD=0.77; 95%CI: 0.49 to 1.05 and SMD=1.18; 95%CI: 0.07 to 2.28). Additionally, it was also observed that MPV was closely correlated with the severity of DR. CONCLUSION: MPV, PDW, NLR, and PLR could be recommended as diagnostic biomarkers for DR, and MPV could be applied to assess the severity of DR.展开更多
Spinal cord injury can lead to severe motor,sensory and autonomic nervous dysfunctions.However,there is currently no effective treatment for spinal cord injury.Neural stem cells and progenitor cells,bone marrow mesenc...Spinal cord injury can lead to severe motor,sensory and autonomic nervous dysfunctions.However,there is currently no effective treatment for spinal cord injury.Neural stem cells and progenitor cells,bone marrow mesenchymal stem cells,olfactory ensheathing cells,umbilical cord blood stem cells,adipose stem cells,hematopoietic stem cells,oligodendrocyte precursor cells,macrophages and Schwann cells have been studied as potential treatments for spinal cord injury.These treatments were mainly performed in animals.However,subtle changes in sensory function,nerve root movement and pain cannot be fully investigated with animal studies.Although these cell types have shown excellent safety and effectiveness in various animal models,sufficient evidence of efficacy for clinical translation is still lacking.Cell transplantation should be combined with tissue engineering scaffolds,local drug delivery systems,postoperative adjuvant therapy and physical rehabilitation training as part of a comprehensive treatment plan to provide the possibility for patients with SCI to return to normal life.This review summarizes and analyzes the clinical trials of cell transplantation therapy in spinal cord injury,with the aim of providing a rational foundation for the development of clinical treatments for spinal cord injury.展开更多
AIM: To investigate the effects of superoxide dismutase (SOD) polymorphisms (rs4998557 , rs4880), Helicobacter pylori (H. pylori ) infection and environmental factors in gastric cancer (GC) and malignant potential of ...AIM: To investigate the effects of superoxide dismutase (SOD) polymorphisms (rs4998557 , rs4880), Helicobacter pylori (H. pylori ) infection and environmental factors in gastric cancer (GC) and malignant potential of gastric precancerous lesions (GPL). METHODS: Copper-zinc superoxide dismutase (SOD1, CuZn-SOD)-G7958A (rs4998557 ) and manganese superoxide dismutase (SOD2, Mn-SOD)-Val16Ala (rs4880 ) polymorphisms were genotyped by SNaPshot multiplex polymerase chain reaction (PCR) in 145 patients with GPL (87 cases of gastric ulcer, 33 cases of gastric polyps and 25 cases of atrophic gastritis), 140 patients with GC and 147 healthy controls. H. pylori infection was detected by immunoblotting analysis. RESULTS: The SOD1-7958A allele was associated with a higher risk of gastric cancer [odds ratio (OR) = 3.01, 95% confidence intervals (95% CI): 1.83-4.95]. SOD216Ala/Val genotype was a risk factor for malignant potential of GPL (OR = 2.04, 95% CI: 1.19-3.49). SOD216Ala/genotype increased the risk of gastric cancer (OR = 2.85, 95% CI: 1.66-4.89). SOD1-7958A/genotype, SOD2-16Ala/genotype, alcohol drinking, positive family history and type Ⅰ H. pylori infection were associated with risk of gastric cancer, and there were additive interactions between the two genotypes and the other three risk factors. SOD2-16Ala/Val genotype and positive family history were associated with malignant potential of GPL and jointly contributed to a higher risk for malignant potential of GPL (OR = 7.71, 95% CI: 2.10-28.22). SOD1-7958A/genotype and SOD2-16Ala/genotype jointly contributed to a higher risk for gastric cancer (OR = 6.43, 95% CI: 3.20-12.91). CONCLUSION: SOD1-7958A/and SOD2-16Ala/-genotypes increase the risk of gastric cancer in Chinese Han population. SOD2-16Ala/-genotype is associated with malignant potential of GPL.展开更多
Rhodioloside has been shown to protect cells from hypoxia injury,and bone marrow mesenchymal stem cells have a good effect on tissue repair.To study the effects of rhodioloside and bone marrow mesenchymal stem cells o...Rhodioloside has been shown to protect cells from hypoxia injury,and bone marrow mesenchymal stem cells have a good effect on tissue repair.To study the effects of rhodioloside and bone marrow mesenchymal stem cells on spinal cord injury,a rat model of spinal cord injury was established using the Infinite Horizons method.After establishing the model,the rats were randomly divided into five groups.Rats in the control group were intragastrically injected with phosphate buffered saline(PBS)(5μL).PBS was injected at 6 equidistant points around 5 mm from the injury site and at a depth of 5 mm.Rats in the rhodioloside group were intragastrically injected with rhodioloside(5 g/kg)and intramuscularly injected with PBS.Rats in the mesenchymal stem cell(MSC)group were intramuscularly injected with PBS and intramuscularly with MSCs(8×10^6/mL in a 50-μL cell suspension).Rats in the Ad-HIF-MSC group were intragastrically injected with PBS and intramuscularly injected with HIF-1 adenovirus-infected MSCs.Rats in the rhodioloside+Ad-HIF-MSC group were intramuscularly injected with MSCs infected with the HIF-1 adenovirus and intragastrically injected with rhodioloside.One week after treatment,exercise recovery was evaluated with a modified combined behavioral score scale.Hematoxylin-eosin staining and Pischingert’s methylene blue staining were used to detect any histological or pathological changes in spinal cord tissue.Levels of adenovirus IX and Sry mRNA were detected by real-time quantitative polymerase chain reaction and used to determine the number of adenovirus and mesenchymal stem cells that were transfected into the spinal cord.Immunohistochemical staining was applied to detect HIF-1 protein levels in the spinal cord.The results showed that:(1)compared with the other groups,the rhodioloside+Ad-HIF-MSC group exhibited the highest combined behavioral score(P<0.05),the most recovered tissue,and the greatest number of neurons,as indicated by Pischingert’s methylene blue staining.(2)Compared with the PBS group,HIF-1 protein expression was greater in the rhodioloside group(P<0.05).(3)Compared with the Ad-HIF-MSC group,Sry mRNA levels were higher in the rhodioloside+Ad-HIF-MSC group(P<0.05).These results confirm that rhodioloside combined with bone marrow mesenchymal stem cells can promote the recovery of spinal cord injury and activate the HIF-1 pathway to promote the survival of bone marrow mesenchymal stem cells and repair damaged neurons within spinal cord tissue.This experiment was approved by the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine,China(approval No.2015KYLL029)in June 2015.展开更多
Objective Isoliquiritigenin(ISL),a licorice chalconoid,is considered to be a bioactive agent with chemopreventive potential.This study investigates the mechanisms involved in ISL-induced apoptosis in human cervical ca...Objective Isoliquiritigenin(ISL),a licorice chalconoid,is considered to be a bioactive agent with chemopreventive potential.This study investigates the mechanisms involved in ISL-induced apoptosis in human cervical carcinoma HeLa cells.Methods Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide(MTT)assay.Apoptosis was determined by flow cytometry using an Annexin V-FITC Apoptosis Detection Kit.The intracellular ROS levels were assessed using a 2,7-dichlorofluorescein probe assay.The mitochondrial membrane potential was measured with the dual-emission potential-sensitive probe 5,5',6,6'-tetra-chloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide(JC-1).The degradation of poly-ADP-ribose polymerase(PARP)protein,the phosphorylation of PKR-like ER kinase(PERK),the phosphorylation of the α-subunit of eukaryotic initiation factor 2(eIF2α),the expression of the 78 kD glucose-regulated protein(GRP 78),and the activation of caspase-12 were analyzed via western blot analysis.Results ISL significantly inhibited the proliferation,the increase in ROS levels and apoptotic rates of HeLa cells in a concentration-dependent manner.Moreover,ISL induced mitochondrial dysfunction,caspase activation,and PARP cleavage,which displayed features of mitochondria dependent on apoptotic signals.Besides,exposure of HeLa cells to ISL triggered endoplasmic reticulum(ER)stress,as indicated by the increase in p-eIF2α and GRP78 expression,ER stress-dependent apoptosis is caused by the activation of ER-specific caspase-12.Conclusion The findings from our study suggest that ISL-induced oxidative stress causes HeLa cell apoptosis via the mitochondrion-dependent and the ER stress-triggered signaling pathways.展开更多
AIM:To investigate the mechanisms by which Cskbinding protein(CBP)inhibits tumor progression in esophageal carcinoma.METHODS:A CBP overexpressing esophageal carcinoma cell line(TE-1)was established.The growth,invasion...AIM:To investigate the mechanisms by which Cskbinding protein(CBP)inhibits tumor progression in esophageal carcinoma.METHODS:A CBP overexpressing esophageal carcinoma cell line(TE-1)was established.The growth,invasion,and migration of CBP-TE-1 cells,as well as the expression of Src were then determined and compared with those in normal TE-1 cells.RESULTS:The expression of Src was decreased by the overexpression of CBP in TE-1 cells.The growth,invasion,and migration of TE-1 cells were decreased by the overexpression of CBP.CONCLUSION:This study indicates that CBP may decrease the metastasis of esophageal carcinoma by inhibiting the activation of Src.CBP may be a potential tumor suppressor and targeting the CBP gene may be an alternative strategy for the development of therapies for esophageal carcinoma.展开更多
AIM: To study the expression level and localization of insulin-like growth factor -I receptor (IGF-IR) in HepG2 cells and Chang liver cells, and to observe the effect of anti-IGF-IR monoclonal antibody (αIR3) on the ...AIM: To study the expression level and localization of insulin-like growth factor -I receptor (IGF-IR) in HepG2 cells and Chang liver cells, and to observe the effect of anti-IGF-IR monoclonal antibody (αIR3) on the growth of HepG2 cells. METHODS: The expression of IGF-IR in HepG2 cells and Chang liver cells was detected by immunohistochemistry. The influences of aIR3 on proliferation and apoptosis were examined by the 3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and electron microscopy, respectively. Flow cytometry (FCM) was applied for the analysis of cell cycle and apoptosis was observed under electron microscope. RESULTS: IGF-IR was located in the membranes of both HepG2 and Chang liver cell lines, and the expression level of IGF-IR was higher in HepG2 cells than in Chang liver cells. Treated with 0.1μg/mLαIR3 for 48 h in vitro, the cell growth index (GI) of HepG2 cells was significantly higher than that of control (103.41% vs 100%, P<0.01). However, the aIR3 for 24 h at final concentration of 4.0μg/mL made the GI of HepG2 cells lower than that of control (93.37% vs 100%, P < 0.01). Compared with control, treated with aIR3 for 48 h at final concentrations ranging from 1.0μg/mL to 4.0μg/mL markedly reduced the GIs of HepG2 cells (97.63%, 97.16%, 95.13%, 92.53% vs 100%, P < 0.05 or P < 0.01), treated withαIR3 for 72 h at final concentrations ranging from 0.2μg/mL to 4.0μg/mL decreased the GIs of HepG2 cells obviously (95%, 91.63%, 90.77%, 89.84%, 88.51% vs 100%, P<0.01), and treated with aIR3 for 96 h at final concentrations ranging from 0.5μg/mL to 4.0μg/mL made GIs of HepG2 cells lower significantly (88.86%, 83.97%, 79.81%, 77.24%, 70.51% vs 100%, P<0.05 or P<0.01). Moreover, treated withαIR3 from 24 h to 96 h at final concentrations ranging from 0.2μg/mL to 4.0μg/mL reduced the GI of HepG2 cells from 97.63% to 70.51% in a dose- and time-dependent manner. Also,αIR3 treatment for 72 h at final concentration from 0.5μg/mL to 2.0μg/mL increased the proportion of G0/G1 phase cells(61.73%, 67.1%, 83.7%,76.87% vs 44.47%, P<0.01) and significantly decreased that of S phase cells(28.63%, 25.13%, 15.63%, 23.13% vs 53.17%, P<0.01), in contrast to the proportion of G2/M phase cells. The apoptotic rates of HepG2 cells were increased more than that of control (7.83%, 16.13%, 21.1%, 37.73% vs 4.13%, P< 0.01). CONCLUSION: The malignant cell phenotype of human hepatocarcinoma cell is related to overexpression of IGF-IR. The blockage of IGF-IR with aaaaaIR3 may contribute to the inhibition of proliferation and induction of apoptosis in HepG2 cells.展开更多
基金supported by the National Natural Science Foundation of China,No.91849104(to YW)。
文摘Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.
基金Supported by the Medicine and Health Technology Innovation Project of Chinese Academy of Medical Sciences,No.2017-12M-1-006
文摘BACKGROUND Colorectal high-grade neuroendocrine neoplasms(HGNENs)are rare and constitute less than 1%of all colorectal malignancies.Based on their morphological differentiation and proliferation identity,these neoplasms present heterogeneous clinicopathologic features.Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial.AIM To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy.METHODS This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019.The clinicopathologic characteristics and follow-up data were carefully collected from their medical records,outpatient reexaminations,and telephone interviews.A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease.RESULTS According to the latest recommendations for the classification and nomenclature of colorectal HGNENs,61(84.7%)patients in our cohort had poorly differentiated neoplasms,which were categorized as high-grade neuroendocrine carcinomas(HGNECs),and the remaining 11(15.3%)patients had well differentiated neoplasms,which were categorized as high-grade neuroendocrine tumors(HGNETs).Most of the neoplasms(63.9%)were located at the rectum.More than half of the patients(51.4%)presented with distant metastasis at the date of diagnosis.All patients were followed for a median duration of 15.5 mo.In the entire cohort,the median survival time was 31 mo,and the 3-year and 5-year survival rates were 44.3%and 36.3%,respectively.Both the univariate and multivariate analyses demonstrated that increasing age,HGNEC type,and distant metastasis were risk factors for poor clinical outcomes.CONCLUSION Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes.However,patients with younger age,good morphological differentiation,and without metastatic disease can have a relatively favorable prognosis.
基金Financial support and sponsorship This work was supported by the Lanzhou city science and technology project:Psychological Intervention Study of COVID‑19 Isolation and Protection Medical Workers by Mindfulness Behavior Delivery.
文摘Objective:The objective of the study is to investigate the psychological status of nursing staff both working on nonfront line and on the front line during the epidemic period of COVID‑19 and to analyze the influencing factors related to mental health state,as well as to provide targeted psychological intervening measures for nursing staff in the face of this major public health event.Methods:We used data from January 28,2019,to February 08,2020,on the number of cases who worked in the 3A‑level hospital as nonfront‑line nurses(n=29,54%)and those who worked in Wuhan infectious hospital as the front‑line supporters(n=25,46%)came from the 3A‑level hospital.The participants completed the symptom checklist 90,and the researchers recorded data on demographics,psychological status,and the influencing factors.Results:In our baseline scenario,we estimated that the total symptom index was 1.676±0.654 for nurses who worked on the front line,1.260±0.304 for those who worked as the front‑line reserve nurses,and was 1.486±0.647 for those who worked as the nonfront‑line nurses.The results of correlation analysis show that the factors related to the psychological status of nurses include age,professional title,marital status,and family support;different factors have different effects on psychological status.Conclusion:In the face of major public health emergencies,both front‑line nursing staff and nonfront‑line staff are confronted with different degrees of psychological stress,so effective psychological support should be given to improve the working efficiency and enthusiasm of nurses.
基金supported by the National Natural Science Foundation of China(81825011,81930038,81961160738)Program of Shanghai Academic/Technology Research Leader(22XD1400800)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19030200)。
文摘Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.
基金supported by the Natural Science Foundation of Gansu Province(22JR5RA496,22JR5RA955)Talent Innovation and Entrepreneurship Project of Lanzhou City(2022-RC-49)+4 种基金Talent Innovation and Entrepreneurship Project of Chengguan District(2022-rc-7)Foundation of Lanzhou University Second Hospital(CYXZ2022-22)Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital(CY2021-QN-A02)Fundamental Research Funds for the Central Universities(lzujbky-2022-50)Project of Gansu Province Health Commission(GSWSKY2022-02)Innovation Fund for Colleges and Universities(2021B-046).
文摘Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are few reports on the mechanism of action of the TBZPy photodynamic.Previous studies revealed that photodynamic therapy(PDT)could induce endoplasmic reticulum stress by acting on the endoplasmic reticulum.Therefore,in this study,we investigated the effects of endoplasmic reticulum stress induced by TBZPy-PDT in treating High-risk human papillomavirus(HR-HPV)infection and their underlying mechanisms.Methods:The human cervical cancer cell line HeLa(containing whole genome of HR-HPV18)was treated with TBZPy-PDT.Cell migration,invasion,and colony-forming ability were evaluated using wound-healing,Transwell invasion,and colonyforming assays,respectively.Through western blot analysis,we determined the level of expression of the PI3K/AKT and PERK/eIF2αpathway proteins and the proteins associated with calcium trafficking and apoptosis.The calcium levels in the cytoplasm were detected via flow cytometry.Results:The result shows that TBZPy-PDT could inhibite the migration,invasion,and colony forming ability of infected HeLa cells by downregulating the PI3K/AKT pathway in vitro.And we found that TBZPy-PDT induced endoplasmic reticulum stress-specific apoptosis via the PERK/eIF2αpathway.Moreover,TBZPy-PDT increased the levels of calcium and calmodulin,while decreasing the levels of endoplasmic reticulum calcium-binding proteins.Conclusions:TBZPy-PDT is effective on treating human papillomavirus-infected cells.Targeting the PI3K/AKT and PERK/eIF2αpathways and the endoplasmic reticulum stress process may help improve the effects of TBZPy-PDT for treating high-risk human papillomavirus infection.
文摘BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GIST(17 male and 2 female,median age 62 years).GC was most often located in the lower third of the stomach.GIST was diagnosed preoperatively in four patients.GIST was most often located in the gastric body(n=8,42%).The most common growth pattern in GIST was extraluminal(n=12,63%).The positive expression rates of CD117 and CD34 in GIST were 100% and 95%,respectively.Most patients with GIST(n=17,89%)were very low or low risk.There was no recurrence of GIST during follow-up.The 3-year cumulative survival rate was 73.9%,and the 5-year cumulative survival rate was 59.2%.The combined analysis of this study and literature reports(47 reports,157 patients)found that GC and GIST were usually located in the lower third(42%)and middle third(51%)of the stomach.GC was usually early(stage I:42%),poorly differentiated(42%)intestinal-type adenocarcinoma(51%).GISTs were primarily small in diameter(median:1.2 cm)and very low or low risk(89%).CONCLUSION Synchronous GC and GIST may not be rare.They have specific clinicopathological characteristics,and may have mutual inhibition in pathogenesis and progression.
基金All experimental procedures were conducted in accordance with Animal Ethics Procedures and Guidelines of the Animal Center,Yunnan University Animal Ethics Committee(Ethics Review Number:YNU20220296).
文摘Objective: Breast cancer is a major cancer threatening the health of women globally. To elucidate the effect ofthe circHIAT1/miR-19a-3p/phosphatase and tensin homolog (PTEN) axis on regulating the malignant phenotype ofbreast cancer cells. Methods: The mRNA expression pattern of circHIAT1, miR-19a-3p, and PTEN was checked byreal-time quantitative polymerase chain reaction. Then, the knockdown assay was carried out to explore the effect ofcircHIAT1 and miR-19a-3p on breast cancer. The relative cell experiments, including MTT assay, scratch assay,transwell invasion assay, and flow cytometry analysis, were conducted to verify the influence of circHIAT1 and miR-19a-3p on breast cancer cells. Results: The levels of PTEN and circHIAT1 were reduced, while that of miR-19a-3pwas elevated in breast cancer tissues and cells. MiR-19a-3p was proved to be the target gene of circHIAT1 via a dualluciferase experiment, which could also modulate the PTEN mRNA level. Overexpression of circHIAT1 was able toundermine the growth, migratory ability, and invasiveness in breast cancer cells, which could be antagonized by miR-19a-3p mimic. The inhibition of miR-19a-3p in vitro also impaired the malignancy of breast cancer, which dependedon the modulation of PTEN expression. Conclusion: CircHIAT1 controls the PTEN expression level in cells of breastcancer by negatively regulating miR-19a-3p. This mechanism controls the growth, invasion, and migration of breastcancer.
文摘BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively.Immunohistochemical staining(IHC)was used to detect the expression of NPAS2 protein in GC and adjacent tissues.Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC,and a nomogram prediction model was established.The receiver operating characteristic(ROC)curve,the ROC area under the curve,the calibration curve,and C-index were used to evaluate the predictive effectiveness of the model.Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%,which was significantly higher than 30.69%in adjacent tissues.The high expression of NPAS2 was correlated with tumor-node-metastasis(TNM)stage(P<0.05),pN stage(P<0.05),metastasis(P<0.05),venous invasion(P<0.05),lymphatic invasion(P<0.05),and lymph node positive(P<0.05)of GC.Kaplan Meier survival analysis showed that the 3-year overall survival(OS)of patients with high NPAS2 expression was significantly shortened(P<0.0001).Univariate and multivariate COX regression analysis showed that TNM stage(P=0.009),metastasis(P=0.009),and NPAS2 expression(P=0.020)were independent prognostic factors of OS in GC patients for 3 years.The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740(95%CI:0.713-0.767).Furthermore,subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group(P<0.0001).CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients.Therefore,the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation.Notably,the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.
文摘Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for activation, and calpain or 2, which requires millimolar Ca<sup>2+</sup> for activation. The presence of other calpains is tissue specific. Atherosclerosis (AS) is an important risk factor for cerebral infarction, coronary heart disease and peripheral vascular disease. It was originally thought that AS was caused by impaired lipid metabolism. This research briefly reviewed Calpain Family, the structure and activation mechanism of calpain1, Calpains in the pathogenesis of atherosclerosis, NLRP3 structural characteristics and activation, ROS/NLRP3 inflammasome activation mechanism and ROS/NLRP3 inflammasome in atherosclerosis. The research showed that the Calpain-1 may play an important role in mitochondrial ROS/NLRP3 inflammasome in atherosclerosis.
基金suppor ted by the National Key Research and Development Plan of China(Technology helps Economy 2020,2016YFC0106300)the National Natural Science Foundation of China(82174230)the Major Program Fund of Technical Innovation Project of Department of Science and Technology of Hubei Province(2016ACAl52)。
文摘Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.
基金Supported by The Grant from Gansu Provincial-level Key Laboratory of Digestive System Tumors Open projects Research Fund,No.lzujbky-2011-t03
文摘AIM: To investigate the roles of Golgi protein(GP) 73 in the regulation of cell proliferation and apoptosis. METHODS: Stealth RNAi targeting GP73 gene sequence was used to silence its expression in Hep G2 cells and Bel7402 cells. Stealth RNAi effects were assessed by reverse transcriptase polymerase chain reaction and ELISA. Cell proliferation assay and cell cycle analysis were assessed by MTT assay and flow cytometry. Apoptosis was assessed by flow cytometry andtransmission electron microscopy. Apoptosis-related proteins were assessed by western immunoblot analysis.RESULTS: Stealth RNAi targeting GP73 gene sequence markedly reduced the expression of GP73 gene. The reduction of GP73 in Hep G2 cells and Bel7402 cells inhibited cell proliferation and induced apoptosis, however, terminal apoptosis occurred in Hep G2 cells, but early apoptosis occurred in Bel7402 cells. Reduced expression of GP73 gene might lead to a reduction in Bcl-2/Bax ratio, an increase in cytochrome c, but a reduction in capase-3.CONCLUSION: GP73 might play an important role in proliferation and apoptosis in hepatocellular carcinoma cells.
文摘Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years, but the problems, including difficult diagnosis at early stage, quick progression, and poor prognosis remain unsolved. Surgical resection is the mainstay of the treatment for HCC. However, 70%-80% of HCC patients are diagnosed at an advanced stage when most are ineligible for potentially curative therapies such as surgical resection and liver transplantation. In recent years, non-surgical management for unrespectable HCC, such as percutaneous ethanol injection, percutaneous microwave coagulation therapy, percutaneous radiofrequency ablation, transcatheter arterial chemoembolization, radiotherapy, chemotherapy, biotherapy, and hormonal therapy have been developed. These therapeutic options, either alone or in combination, have been shown to control tumor growth, prolong survival time, and improve quality of life to some extent. This review covers the current status and progress of non-surgical management for HCC.
文摘AIM: To explore the correlation between several blood cell-associated inflammatory indices including mean platelet volume(MPV), platelet distribution width(PDW), neutrophil to lymphocyte ratio(NLR) and platelet-lymphocyte ratio(PLR), and the presence and severity of diabetic retinopathy(DR). METHODS: We searched for eligible studies from PubMed, EMBASE, Web of Science and CNKI up to December 13, 2017. Standardized mean difference(SMD) calculated with confidence interval(CI) of 95% was used to estimate the values of those indices. RESULTS: A total of 31 studies were included in the present Meta-analysis. As compared with type 2 diabetes mellitus(T2 DM) patients without DR, the values of MPV, PDW, NLR, and PLR were higher in patients with DR(SMD=0.67; 95%CI: 0.36 to 0.98; SMD=0.51; 95%CI: 0.27 to 0.75; SMD=0.77; 95%CI: 0.49 to 1.05 and SMD=1.18; 95%CI: 0.07 to 2.28). Additionally, it was also observed that MPV was closely correlated with the severity of DR. CONCLUSION: MPV, PDW, NLR, and PLR could be recommended as diagnostic biomarkers for DR, and MPV could be applied to assess the severity of DR.
基金supported by 2019 Scientific Research Project of Traditional Chinese Medicine in Gansu Province of China,No.GZK-2019-46(to XWK and YBL)。
文摘Spinal cord injury can lead to severe motor,sensory and autonomic nervous dysfunctions.However,there is currently no effective treatment for spinal cord injury.Neural stem cells and progenitor cells,bone marrow mesenchymal stem cells,olfactory ensheathing cells,umbilical cord blood stem cells,adipose stem cells,hematopoietic stem cells,oligodendrocyte precursor cells,macrophages and Schwann cells have been studied as potential treatments for spinal cord injury.These treatments were mainly performed in animals.However,subtle changes in sensory function,nerve root movement and pain cannot be fully investigated with animal studies.Although these cell types have shown excellent safety and effectiveness in various animal models,sufficient evidence of efficacy for clinical translation is still lacking.Cell transplantation should be combined with tissue engineering scaffolds,local drug delivery systems,postoperative adjuvant therapy and physical rehabilitation training as part of a comprehensive treatment plan to provide the possibility for patients with SCI to return to normal life.This review summarizes and analyzes the clinical trials of cell transplantation therapy in spinal cord injury,with the aim of providing a rational foundation for the development of clinical treatments for spinal cord injury.
基金Supported by National Natural Science Foundation of China,No. 30870364
文摘AIM: To investigate the effects of superoxide dismutase (SOD) polymorphisms (rs4998557 , rs4880), Helicobacter pylori (H. pylori ) infection and environmental factors in gastric cancer (GC) and malignant potential of gastric precancerous lesions (GPL). METHODS: Copper-zinc superoxide dismutase (SOD1, CuZn-SOD)-G7958A (rs4998557 ) and manganese superoxide dismutase (SOD2, Mn-SOD)-Val16Ala (rs4880 ) polymorphisms were genotyped by SNaPshot multiplex polymerase chain reaction (PCR) in 145 patients with GPL (87 cases of gastric ulcer, 33 cases of gastric polyps and 25 cases of atrophic gastritis), 140 patients with GC and 147 healthy controls. H. pylori infection was detected by immunoblotting analysis. RESULTS: The SOD1-7958A allele was associated with a higher risk of gastric cancer [odds ratio (OR) = 3.01, 95% confidence intervals (95% CI): 1.83-4.95]. SOD216Ala/Val genotype was a risk factor for malignant potential of GPL (OR = 2.04, 95% CI: 1.19-3.49). SOD216Ala/genotype increased the risk of gastric cancer (OR = 2.85, 95% CI: 1.66-4.89). SOD1-7958A/genotype, SOD2-16Ala/genotype, alcohol drinking, positive family history and type Ⅰ H. pylori infection were associated with risk of gastric cancer, and there were additive interactions between the two genotypes and the other three risk factors. SOD2-16Ala/Val genotype and positive family history were associated with malignant potential of GPL and jointly contributed to a higher risk for malignant potential of GPL (OR = 7.71, 95% CI: 2.10-28.22). SOD1-7958A/genotype and SOD2-16Ala/genotype jointly contributed to a higher risk for gastric cancer (OR = 6.43, 95% CI: 3.20-12.91). CONCLUSION: SOD1-7958A/and SOD2-16Ala/-genotypes increase the risk of gastric cancer in Chinese Han population. SOD2-16Ala/-genotype is associated with malignant potential of GPL.
基金supported by the National High Technology Research and Development Program of China (863 Program), No. 2015CB755400 (to XQH)
文摘Rhodioloside has been shown to protect cells from hypoxia injury,and bone marrow mesenchymal stem cells have a good effect on tissue repair.To study the effects of rhodioloside and bone marrow mesenchymal stem cells on spinal cord injury,a rat model of spinal cord injury was established using the Infinite Horizons method.After establishing the model,the rats were randomly divided into five groups.Rats in the control group were intragastrically injected with phosphate buffered saline(PBS)(5μL).PBS was injected at 6 equidistant points around 5 mm from the injury site and at a depth of 5 mm.Rats in the rhodioloside group were intragastrically injected with rhodioloside(5 g/kg)and intramuscularly injected with PBS.Rats in the mesenchymal stem cell(MSC)group were intramuscularly injected with PBS and intramuscularly with MSCs(8×10^6/mL in a 50-μL cell suspension).Rats in the Ad-HIF-MSC group were intragastrically injected with PBS and intramuscularly injected with HIF-1 adenovirus-infected MSCs.Rats in the rhodioloside+Ad-HIF-MSC group were intramuscularly injected with MSCs infected with the HIF-1 adenovirus and intragastrically injected with rhodioloside.One week after treatment,exercise recovery was evaluated with a modified combined behavioral score scale.Hematoxylin-eosin staining and Pischingert’s methylene blue staining were used to detect any histological or pathological changes in spinal cord tissue.Levels of adenovirus IX and Sry mRNA were detected by real-time quantitative polymerase chain reaction and used to determine the number of adenovirus and mesenchymal stem cells that were transfected into the spinal cord.Immunohistochemical staining was applied to detect HIF-1 protein levels in the spinal cord.The results showed that:(1)compared with the other groups,the rhodioloside+Ad-HIF-MSC group exhibited the highest combined behavioral score(P<0.05),the most recovered tissue,and the greatest number of neurons,as indicated by Pischingert’s methylene blue staining.(2)Compared with the PBS group,HIF-1 protein expression was greater in the rhodioloside group(P<0.05).(3)Compared with the Ad-HIF-MSC group,Sry mRNA levels were higher in the rhodioloside+Ad-HIF-MSC group(P<0.05).These results confirm that rhodioloside combined with bone marrow mesenchymal stem cells can promote the recovery of spinal cord injury and activate the HIF-1 pathway to promote the survival of bone marrow mesenchymal stem cells and repair damaged neurons within spinal cord tissue.This experiment was approved by the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine,China(approval No.2015KYLL029)in June 2015.
基金supported by the National Natural Science Foundation of China (No. 30960451)Major State Basic Research Development Program (2010CB535003)the Xinjiang production and construction corps funds for distinguished young scientists to ZHENG Qiu Sheng,international cooperation projects (2012BC001)
文摘Objective Isoliquiritigenin(ISL),a licorice chalconoid,is considered to be a bioactive agent with chemopreventive potential.This study investigates the mechanisms involved in ISL-induced apoptosis in human cervical carcinoma HeLa cells.Methods Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide(MTT)assay.Apoptosis was determined by flow cytometry using an Annexin V-FITC Apoptosis Detection Kit.The intracellular ROS levels were assessed using a 2,7-dichlorofluorescein probe assay.The mitochondrial membrane potential was measured with the dual-emission potential-sensitive probe 5,5',6,6'-tetra-chloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide(JC-1).The degradation of poly-ADP-ribose polymerase(PARP)protein,the phosphorylation of PKR-like ER kinase(PERK),the phosphorylation of the α-subunit of eukaryotic initiation factor 2(eIF2α),the expression of the 78 kD glucose-regulated protein(GRP 78),and the activation of caspase-12 were analyzed via western blot analysis.Results ISL significantly inhibited the proliferation,the increase in ROS levels and apoptotic rates of HeLa cells in a concentration-dependent manner.Moreover,ISL induced mitochondrial dysfunction,caspase activation,and PARP cleavage,which displayed features of mitochondria dependent on apoptotic signals.Besides,exposure of HeLa cells to ISL triggered endoplasmic reticulum(ER)stress,as indicated by the increase in p-eIF2α and GRP78 expression,ER stress-dependent apoptosis is caused by the activation of ER-specific caspase-12.Conclusion The findings from our study suggest that ISL-induced oxidative stress causes HeLa cell apoptosis via the mitochondrion-dependent and the ER stress-triggered signaling pathways.
基金National Natural Science Foundation project.Project name:research on the correlation of schizophrenic patients’hazard evaluation and the functional magnetic resonance resting state(project code:81371500)twelfth 5 year national science and technology support program(forensic identification key technology research).Sub-project(research on the risk assessment of violence in mental patients)(project code:2012BAK16B04)
基金Supported by Gansu Provincial Natural Science Foundation,No.1308RJZA188the Fundamental Research Funds for the Central Universities,No.lzujbky-2011-T03-16
文摘AIM:To investigate the mechanisms by which Cskbinding protein(CBP)inhibits tumor progression in esophageal carcinoma.METHODS:A CBP overexpressing esophageal carcinoma cell line(TE-1)was established.The growth,invasion,and migration of CBP-TE-1 cells,as well as the expression of Src were then determined and compared with those in normal TE-1 cells.RESULTS:The expression of Src was decreased by the overexpression of CBP in TE-1 cells.The growth,invasion,and migration of TE-1 cells were decreased by the overexpression of CBP.CONCLUSION:This study indicates that CBP may decrease the metastasis of esophageal carcinoma by inhibiting the activation of Src.CBP may be a potential tumor suppressor and targeting the CBP gene may be an alternative strategy for the development of therapies for esophageal carcinoma.
基金Supported by the Gansu Province's Natural Science Fund, No.ZS021-A25-079-Y
文摘AIM: To study the expression level and localization of insulin-like growth factor -I receptor (IGF-IR) in HepG2 cells and Chang liver cells, and to observe the effect of anti-IGF-IR monoclonal antibody (αIR3) on the growth of HepG2 cells. METHODS: The expression of IGF-IR in HepG2 cells and Chang liver cells was detected by immunohistochemistry. The influences of aIR3 on proliferation and apoptosis were examined by the 3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and electron microscopy, respectively. Flow cytometry (FCM) was applied for the analysis of cell cycle and apoptosis was observed under electron microscope. RESULTS: IGF-IR was located in the membranes of both HepG2 and Chang liver cell lines, and the expression level of IGF-IR was higher in HepG2 cells than in Chang liver cells. Treated with 0.1μg/mLαIR3 for 48 h in vitro, the cell growth index (GI) of HepG2 cells was significantly higher than that of control (103.41% vs 100%, P<0.01). However, the aIR3 for 24 h at final concentration of 4.0μg/mL made the GI of HepG2 cells lower than that of control (93.37% vs 100%, P < 0.01). Compared with control, treated with aIR3 for 48 h at final concentrations ranging from 1.0μg/mL to 4.0μg/mL markedly reduced the GIs of HepG2 cells (97.63%, 97.16%, 95.13%, 92.53% vs 100%, P < 0.05 or P < 0.01), treated withαIR3 for 72 h at final concentrations ranging from 0.2μg/mL to 4.0μg/mL decreased the GIs of HepG2 cells obviously (95%, 91.63%, 90.77%, 89.84%, 88.51% vs 100%, P<0.01), and treated with aIR3 for 96 h at final concentrations ranging from 0.5μg/mL to 4.0μg/mL made GIs of HepG2 cells lower significantly (88.86%, 83.97%, 79.81%, 77.24%, 70.51% vs 100%, P<0.05 or P<0.01). Moreover, treated withαIR3 from 24 h to 96 h at final concentrations ranging from 0.2μg/mL to 4.0μg/mL reduced the GI of HepG2 cells from 97.63% to 70.51% in a dose- and time-dependent manner. Also,αIR3 treatment for 72 h at final concentration from 0.5μg/mL to 2.0μg/mL increased the proportion of G0/G1 phase cells(61.73%, 67.1%, 83.7%,76.87% vs 44.47%, P<0.01) and significantly decreased that of S phase cells(28.63%, 25.13%, 15.63%, 23.13% vs 53.17%, P<0.01), in contrast to the proportion of G2/M phase cells. The apoptotic rates of HepG2 cells were increased more than that of control (7.83%, 16.13%, 21.1%, 37.73% vs 4.13%, P< 0.01). CONCLUSION: The malignant cell phenotype of human hepatocarcinoma cell is related to overexpression of IGF-IR. The blockage of IGF-IR with aaaaaIR3 may contribute to the inhibition of proliferation and induction of apoptosis in HepG2 cells.
