Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and manageme...Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.展开更多
BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneum...BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.展开更多
BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic a...BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.展开更多
Objective:To analyze the clinical efficacy,progression-free survival,and safety of anlotinib in the treatment of advanced lung cancer.Methods:A retrospective analysis was conducted using data from 60 patients with adv...Objective:To analyze the clinical efficacy,progression-free survival,and safety of anlotinib in the treatment of advanced lung cancer.Methods:A retrospective analysis was conducted using data from 60 patients with advanced lung cancer treated with anlotinib from May 2019 to May 2021.This analysis aimed to comprehensively evaluate the clinical efficacy,progression-free survival,and adverse reactions of anlotinib.Results:The median progression-free survival(PFS)for the 60 patients was 5.79 months,with an overall response rate(ORR)of 21%and a disease control rate(DCR)of 90%.In the first-line group,the median PFS was 6.20 months,ORR was 76.92%,and DCR was 84.61%.The second-line group showed a median PFS of 6.30 months,ORR of 28.57%,and DCR of 90.48%.In the third-line group,the median PFS was 5.34 months,ORR was 19.23%,and DCR was 92.30%.The single-agent group exhibited a median PFS of 5.09 months,ORR of 23.33%,and DCR of 76.67%.In the combination group,the median PFS was 6.53 months,ORR was 46.67%,and DCR was 100%.The combination group demonstrated a significantly higher medication effect than the single-drug group,and adverse drug reactions were mostly grade 1-2.Conclusion:Anlotinib exhibits a better disease control rate and survival benefit in the treatment of advanced lung cancer.The combination effect is superior to monotherapy,with relatively controllable adverse effects.展开更多
Jing Medicine, as an important part of China’s ethnic medicine and culture, is characterized by its unique theories, rich content, and abundant resources, showcasing distinctive features of minority regions. The Jing...Jing Medicine, as an important part of China’s ethnic medicine and culture, is characterized by its unique theories, rich content, and abundant resources, showcasing distinctive features of minority regions. The Jing ethnic group is distributed in coastal and border areas of China, and after thousands of years of development, it has formed a rich marine-oriented medical system in the struggle against the environment and diseases, displaying unique medication characteristics and clinical efficacy. According to Jing Medicine, the human body is an organic whole that is unified with the natural and social environment. It believes that the heavens and earth are the spirits of all things, and all things possess spiritual energy, which is closely connected to the human body’s spiritual energy. The utilization of marine organisms in medicine is the greatest feature of Jing Medicine, and it is a common approach used by the local population for disease prevention and treatment. To further explore Jing Medicine, improve the repository of ethnic medicine culture, and address the insufficient understanding of Jing Medicine in traditional Chinese medicine culture, this article provides a comprehensive review of the distinctive diagnostic and therapeutic theories, techniques, and applications of internal and external treatments in Jing Medicine.展开更多
It has been reported that COVID-19 patients are categorized into four groups:the mild types defined as mild clinical symptoms restricted within upper respiratory tract infection,the moderate ones defined as fever and ...It has been reported that COVID-19 patients are categorized into four groups:the mild types defined as mild clinical symptoms restricted within upper respiratory tract infection,the moderate ones defined as fever and respiratory symptoms with radiological findings of pneumonia without the severe or critical features,the severe ones defined as the respiratory failure and the rapid disease progression,and the critical ones defined as septic shock and multiple organ failure requiring mechanical ventilation and circulatory support.展开更多
It is difficult to identify suspected cases of atypical patients with coronavirus disease 2019(COVID-19),and data on severe or critical patients are scanty.This retrospective study presents the clinical,laboratory,and...It is difficult to identify suspected cases of atypical patients with coronavirus disease 2019(COVID-19),and data on severe or critical patients are scanty.This retrospective study presents the clinical,laboratory,and radiological profiles,treatments,and outcomes of atypical COVID-19 patients without respiratory symptoms or fever at onset.The study examined ten atypical patients out of 909 severe or critical patients diagnosed with COVID-19 in Wuhan Union Hospital West Campus between 25 January 2020 and 10 February 2020.Data were obtained from the electronic medical records of severe or critical patients without respiratory symptoms or fever at onset.Outcomes were followed up to discharge or death.Among 943 COVID-19 patients,909(96.4%)were severe or critical type.Of the severe or critical patients,ten(1.1%)presented without respiratory symptoms or fever at admission.The median age of the ten participants was 63 years(interquartile range(IQR):57–72),and seven participants were men.The median time from symptom onset to admission was 14 d(IQR:7–20).Eight of the ten patients had chronic diseases.The patients had fatigue(n=5),headache or dizziness(n=4),diarrhea(n=5),anorexia(n=3),nausea or vomiting(n=3),and eye discomfort(n=1).Four patients were found to have lymphopenia.Imaging examination revealed that nine patients had bilateral pneumonia and one had unilateral pneumonia.Eventually,two patients died and eight were discharged.In the discharged patients,the median time from admission to discharge lasted 24 d(IQR:13–43).In summary,some severe or critical COVID-19 patients were found to have no respiratory symptoms or fever at onset.All such atypical cases should be identified and quarantined as early as possible,since they tend to have a prolonged hospital stay or fatal outcomes.Chest computed tomography(CT)scan and nucleic acid detection should be performed immediately on close contacts of COVID-19 patients to screen out those with atypical infections,even if the contacts present without respiratory symptoms or fever at onset.展开更多
BACKGROUND The interruption of mother-to-child transmission(MTCT)is considered important to decrease the individual and population morbidity of hepatitis B virus(HBV)infection as well as the global burden of hepatitis...BACKGROUND The interruption of mother-to-child transmission(MTCT)is considered important to decrease the individual and population morbidity of hepatitis B virus(HBV)infection as well as the global burden of hepatitis B.Serum vitamin D(VD)is associated with hepatitis B.AIM To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene(VDR SNPs)are associated with the efficacy of tenofovir disoproxil fumarate(TDF)in the prevention of MTCT in pregnant women with high HBV viral loads.METHODS Thirty-eight pregnant women who were at high risk for MTCT of HBV(those with an HBV DNA level≥2×10^(5)IU/mL during 12-24 wk of gestation)receiving antiviral therapy of TDF between June 1,2019 and June 30,2021 in Mianyang were included in this retrospective study.The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery.To further characterize the clinical relevance of maternal serum HBV DNA levels,we stratified patients according to HBV DNA level as follows:Those with levels<2×10_(5)(full responder group)vs those levels≥2×10^(5)IU/mL(partial responder group)at delivery.Serum levels of 25-hydroxyvitamin D[25(OH)D],liver function markers,virological parameters,VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF.The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups.Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery.Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery.RESULTS A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study.The MTCT rate was 0%.No mother achieved hepatitis B e antigen or hepatitis B surface antigen(HBsAg)clearance at delivery.Twenty-three(60.5%)participants were full responders,and 15(39.5%)participants were partial responders according to antiviral efficacy.The present study showed that a high percentage(76.3%)of pregnant women with high HBV viral loads had deficient(<20 ng/mL)or insufficient(≥20 but<31 ng/mL)VD levels.Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline(25.44±9.42 vs 17.66±5.34 ng/mL,P=0.006)and delivery(26.76±8.59 vs 21.24±6.88 ng/mL,P=0.044).Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels[log(10)IU/mL]at delivery after TDF therapy(r=-0.345,P=0.034).In a multiple linear regression analysis,maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels(P<0.0001,β=-0.446),BMI(P=0.03,β=-0.245),baseline maternal log10 HBsAg levels(P=0.05,β=0.285)and cholesterol levels at delivery(P=0.015,β=0.341).Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels(OR=1.23,95%CI:1.04-1.44),maternal VDR Cdx2 TT(OR=0.09,95%CI:0.01-0.88)and cholesterol levels at delivery(OR=0.39,95%CI:0.17-0.87)were associated with targeted antiviral effects(maternal HBV DNA levels<2×10^(5) at delivery).CONCLUSION Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads.Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.展开更多
BACKGROUND Lung invasive mucinous adenocarcinoma(LIMA),formerly referred to as mucinous bronchioloalveolar carcinoma,is a rare disease that usually presents as bilateral lung infiltration,is unsuitable for surgery and...BACKGROUND Lung invasive mucinous adenocarcinoma(LIMA),formerly referred to as mucinous bronchioloalveolar carcinoma,is a rare disease that usually presents as bilateral lung infiltration,is unsuitable for surgery and radiotherapy,and shows poor response to conventional chemotherapy.CASE SUMMARY We report a 56-year-old Chinese man with a history of smoking and epidermal growth factor receptor mutation-positivity who was initially misdiagnosed as severe pneumonia,but was ultimately diagnosed as a case of invasive mucinous adenocarcinoma of the lung by computed tomography-guided percutaneous lung biopsy.Bronchorrhea and dyspnea were improved within 24 h after initiation of gefitinib therapy and the radiographic signs of bilateral lung consolidation showed visible improvement within 30 d.After more than 11 months of treatment,there is no evidence of recurrence or severe adverse events.CONCLUSION Although the precise mechanism of the antitumor effects of gefitinib are not clear,our experience indicates an important role of the drug in LIMA and provides a reference for the diagnosis and treatment of this disease.展开更多
Objective:To evaluate the clinical safety and efficacy of Lianhuaqingwen(LHQW)capsules in patients with high-risk common type COVID-19 pneumonia.Methods:A retrospective multicenter study on 383 high-risk common type C...Objective:To evaluate the clinical safety and efficacy of Lianhuaqingwen(LHQW)capsules in patients with high-risk common type COVID-19 pneumonia.Methods:A retrospective multicenter study on 383 high-risk common type COVID-19 pneumonia cases was conducted.Patients were categorized as the standard treatment(SDT)group(n=168)and the LHQW+SDT group(n=215).The primary endpoint was the rate of symptom(fever,fatigue,coughing)recovery and the secondary endpoints included the time to symptom recovery,the proportion of patients with improvement in chest CT images,the proportion of patients with clinical cure,the timing and rate of negative conversion of SARS-CoV-2 RNA assay.Results:The recovery rate was significantly higher in the LHQW+SDT group as compared with the SDT group(89.7%vs.72.0%,P<0.01).The combined use of LHQW+SDT also showed shorter time for symptom recovery,as well as shorter time for individual symptom of fever,fatigue and coughing recovery than use of SDT alone.A higher proportion of patients in the LHQW+SDT group with improvements in chest CT images and clinical cure(77.7%vs.57.1%,P<0.01)but the proportion of patients deteriorating to severe cases(1%vs.25%,P<0.01)in this group was significant lower than those in the SDT group.No significant difference in negative conversion rate of viral assay results was observed(76.8%vs.75.0%,P>0.05).No serious adverse events were reported.Conclusions:LHQW capsules could be recommended to ameliorate clinical symptoms and reduce the rate of deteriorating to severe cases for high-risk common type COVID-19 pneumonia.展开更多
BACKGROUND Complement overactivation is a major driver of lupus nephritis(LN).Impaired interactions of C-reactive protein(CRP)with complement factor H(CFH)have been shown as a pathogenic mechanism that contributes to ...BACKGROUND Complement overactivation is a major driver of lupus nephritis(LN).Impaired interactions of C-reactive protein(CRP)with complement factor H(CFH)have been shown as a pathogenic mechanism that contributes to the overactivation of complement in LN.However,genetic variations of neither CRP nor CFH show consistent influences on the risk of LN.AIM To examine whether genetic variations of CRP and CFH in combination can improve the risk stratification in Chinese population.METHODS We genotyped six CRP single nucleotide polymorphisms(SNPs)(rs1205,rs3093062,rs2794521,rs1800947,rs3093077,and rs1130864)and three CFH SNPs(rs482934,rs1061170,and rs1061147)in 270 LN patients and 303 healthy subjects.RESULTS No linkage was found among CRP and CFH SNPs,indicating lack of genetic interactions between the two genes.Moreover,CRP and CFH SNPs,neither individually nor in combination,are associated with the risk or clinical manifestations of LN.Given the unambiguous pathogenic roles of the two genes.CONCLUSION These findings suggest that the biological effects of most genetic variations of CRP and CFH on their expressions or activities are not sufficient to influence the disease course of LN.展开更多
Objective:To investigate the expression level,clinical prognosis,genetic changes,methylation value,biological function and immunomodulatory effects of PHF19 in lung adenocarcinoma.Methods:Based on the RNA cohort data ...Objective:To investigate the expression level,clinical prognosis,genetic changes,methylation value,biological function and immunomodulatory effects of PHF19 in lung adenocarcinoma.Methods:Based on the RNA cohort data of lung adenocarcinoma in the Cancer Genome Atlas(TCGA)database,the expression difference of PHF19 between lung adenocarcinoma and normal tissues and the relationship between the expression level and the prognosis of patients were analyzed by using TIMER database and UALCAN database.The gene mutation of PHF19 in lung adenocarcinoma was analyzed in cBioPortal database and TIMER database.The promoter methylation level of PHF19 in lung adenocarcinoma was analyzed in UALCAN database.The enrichment of PHF19 co-expression gene was analyzed in LinkedOmics database and KEGG database.The correlation between the expression of PHF19 in lung adenocarcinoma and the level of immunoinfiltration was explored in the TIMER database.Results:The expression of PHF19 in lung adenocarcinoma tissues was up-regulated,and its high expression was significantly correlated with the pathological stage,lymph node metastasis and shortened overall survival of lung adenocarcinoma patients.Genetic variation was found in 0.9%of patients,amplification and missense mutation were the most common mutations,and TP53 mutation could lead to the high expression of PHF19.The promoter methylation level of PHF19 significantly decreased in lung adenocarcinoma.The function of PHF19 was focused on the process of cell mitosis and cell cycle.The expression level of PHF19 was significantly correlated with tumor immune cell infiltration and immune checkpoint expression.Conclusion:PHF19 can be used as a marker of poor prognosis of lung adenocarcinoma and plays an important role in the occurrence and development of lung adenocarcinoma.展开更多
BACKGROUND At present,understanding of the most effective ventilation methods for treating chronic obstructive pulmonary disease(COPD)patients experiencing acute worsening symptoms and respiratory failure remains rela...BACKGROUND At present,understanding of the most effective ventilation methods for treating chronic obstructive pulmonary disease(COPD)patients experiencing acute worsening symptoms and respiratory failure remains relatively limited.This report analyzed the efficiency and side effects of various ventilation techniques used for individuals experiencing an acute COPD exacerbation.AIM To determine whether pressure-controlled ventilation(PCV)can lower peak airway pressures(PAPs)and reduce the incidence of barotrauma compared to volume-controlled ventilation(VCV),without compromising clinical outcomes and oxygenation parameters.METHODS We have evaluated 600 patients who were hospitalized due to a severe COPD exacerbation,with 400 receiving mechanical ventilation for the respiratory failure.The participants were divided into two different groups,who were administered either VCV or PCV,along with appropriate management.We thereafter observed patients'attributes,clinical factors,and laboratory,radiographic,and arterial blood gas evaluations at the start and during their stay in the intensive care unit(ICU).We have also employed appropriate statistical methods for the data analysis.RESULTS Both the VCV and PCV groups experienced significant enhancements in the respiratory rate,tidal volume,and arterial blood gas values during their time in the ICU.However,no significant distinctions were detected between the groups in terms of oxygenation indices(partial pressures of oxygen/raction of inspired oxygen ratio)and partial pressures of carbon dioxide improvements.There was no considerable disparity observed between the VCV and PCV groups in the hospital mortality(32%vs 28%,P=0.53),the number of days of ICU stay[median interquartile range(IQR):9(6-14)d vs 8(5-13)d,P=0.41],or the duration of the mechanical ventilation[median(IQR):6(4-10)d vs 5(3-9)d,P=0.47].The PCV group displayed lower PAPs compared to the VCV group(P<0.05)from the beginning of mechanical ventilation until extubation or ICU departure.The occurrence of barotrauma was considerably lower in the PCV group in comparison to the VCV group(6%vs 16%,P=0.03).CONCLUSION Both VCV and PCV were found to be effective in treating patients with acute COPD exacerbation.However,PCV was associated with lower PAPs and a significant decrease in barotrauma,thus indicating that it might be a safer ventilation method for this group of patients.However,further large-scale study is necessary to confirm these findings and to identify the best ventilation approach for patients experiencing an acute COPD exacerbation.展开更多
Objective:Investigating the effects of miR-873 on apoptosis and autophagy in bronchial epithelial cells,as well as its regulatory role on Beclin1.Methods:Following transfection of miR-873 mimic into 16HBE cells for 48...Objective:Investigating the effects of miR-873 on apoptosis and autophagy in bronchial epithelial cells,as well as its regulatory role on Beclin1.Methods:Following transfection of miR-873 mimic into 16HBE cells for 48 hours,the mRNA level of miR-873 was quantified by qRT-PCR,and cell viability was evaluated by CCK-8 assay.The levels of IL-2,IL-6,IL-10,and TNF-αin the cell supernatant were determined using ELISA assay,while cell apoptosis was detected by TUNEL staining.LC-3 protein expression was examined by immunofluorescence,and mRNA and protein expression levels of Beclin1 were analyzed by qRT-PCR and Western blot,respectively.Moreover,dual-luciferase reporter gene technology was employed to investigate the binding site between miR-873 and Beclin1.Results:Transfection of miR-873 mimic into 16HBE cells significantly upregulated the mRNA level of miR-873,which led to the inhibition of cell proliferation and the promotion of secretion of pro-inflammatory cytokines IL-2,IL-6,and TNF-α,while suppressing the secretion of anti-inflammatory cytokine IL-10.Moreover,miR-873 induced cell apoptosis and inhibited the expression of LC-3.Dual-luciferase reporter gene assay further confirmed the presence of binding sites between miR-873 and Beclin1 gene.Besides,miR-873 could target and suppress the mRNA and protein expression levels of Beclin1.Conclusion:miR-873 might modulate cell autophagy by targeting the Beclin1 gene,which can potentially promote inflammation and apoptosis in bronchial epithelial cells.展开更多
Objective:Investigating the inhibitory effect of Huayu Lifyei Formula on bleomycininduced rat pulmonary fibrosis and its impact on the expression of miR-27a andα-SMA.Methods:Wistar rats were arbitrarily classified in...Objective:Investigating the inhibitory effect of Huayu Lifyei Formula on bleomycininduced rat pulmonary fibrosis and its impact on the expression of miR-27a andα-SMA.Methods:Wistar rats were arbitrarily classified into a normal group,a model group,and a group treated with Huayu Lifyei Formula,each consisting of ten rats.Pulmonary fibrosis rat model was established by injecting bleomycin.Subsequent to the modeling,the Huayu Lifyei Formula treatment group was administered Huayu Lifyei Formula via gavage for a period of 7 days.Rats were sacrificed on the 14th day after modeling.The right lung was taken for HE staining,Masson staining,and immunohistochemical observation of alpha-smooth muscle actin(α-SMA)expression.The expression of miR-27a was measured by qRT-PCR,with the miR-27a binding site on ACTA2(the gene encodingα-SMA protein)confirmed using dualluciferase reporter gene technology.Results:When compared to the model group,the Huayu Lifyei Formula treatment group showed considerable alleviation of pathological morphological changes in lung tissue,with significant reductions in alveolitis,fibrosis,collagen deposition in lung tissue,and the expression ofα-SMA protein.Meanwhile,the expression of miR-27a in the Huayu Lifyei Formula treatment group significantly increased,and the dual-luciferase reporter gene confirmed the binding site of miR-27a with the ACTA2 gene.Conclusion:Huayu Lifyei Formula can inhibit bleomycin-induced pulmonary fibrosis in rats,and its mechanism may be related to the promotion of miR-27a expression.展开更多
Coronavirus disease 2019(COVID-19)is the third severe acute respiratory disease of the 21st century and the most aggressive global pandemic to date.The whole population has been susceptible to the disease,particularly...Coronavirus disease 2019(COVID-19)is the third severe acute respiratory disease of the 21st century and the most aggressive global pandemic to date.The whole population has been susceptible to the disease,particularly the emerging variants of the virus.The core pathophysiological mechanism is viral sepsis that can lead to the respiratory tract disorders and even systemic disorders such as cytokine release syndrome,thrombosis,abnormal angiogenesis,and multiple organ dysfunction.Despite only few licensed treatments to date,rapid advances have been made in exploring the effectiveness and safety of pharmacological interventions and vaccines.However,three pillars of preventative and control measures-proactive contact tracing,wearing facial masks,and social distancing-are essential to combat the ongoing pandemic.As the number of patients recovering from COVID-19 rapidly increases,the world has entered the era of caring for patients during the convalescence phase.This phase still represents a largely unmet medical need globally.展开更多
The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodi...The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.展开更多
BACKGROUND Coronavirus disease 2019(COVID-19)caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak in China,constitutes a Public Health Emergency of International Concern.It is well known t...BACKGROUND Coronavirus disease 2019(COVID-19)caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak in China,constitutes a Public Health Emergency of International Concern.It is well known that COVID-19 patients may have increased serum lactate dehydrogenase(LDH)levels in the early stage.The clinical changes in LDH may have predictive value in disease evolution and prognosis in critically ill COVID-19 patients.AIM To examine serum LDH and clinical characteristics in patients with COVID-19 and their predictive value for prognosis.METHODS This retrospective study analyzed the clinical data of forty-seven critical COVID-19 patients in the intensive care unit of the Third People's Hospital of Yichang City from January 27 to March 25,2020 and divided them into survivors and nonsurvivors.The patients were diagnosed according to the World Health Organization interim guidance and critical cases met any one of the following criteria:Respiratory failure and required mechanical ventilation,the occurrence of shock,and the combined failure of other organs that required intensive care unit monitoring and treatments,according to the diagnostic criteria of critical COVID-19.Clinical data including symptoms,detection of SARS-CoV-2,chest computed tomography(CT)images,changes in serum LDH in different clinical phases,and prognosis were collected.Statistical analysis of the data was performed.Continuous variables were expressed as median(interquartile range)and compared with the Mann-Whitney U test.Categorical variables were compared with the Chi-square test.Survival data were analyzed using Kaplan-Meier survival curves and log-rank tests.RESULTS According to chest CT images,we observed the alveolitis and fibrosis stages in all critical patients in this study.Most non-survivors died in the fibrosis stage.Nonsurvivors had fewer days of hospitalization,shorter disease duration,shorter duration of alveolitis and fibrosis,and had dyspnea symptoms at disease onset(P=0.05).Both first and lowest LDH values in the alveolitis stage were more pronounced in non-survivors than in survivors(449.0 U/L vs 288.0 U/L,P=0.0243;445.0 U/L vs 288.0 U/L,P=0.0199,respectively),while the first,lowest and highest values of serum LDH in non-survivors were all significantly increased compared to survivors in the fibrosis phase(449.0 U/L vs 225.5 U/L,P=0.0028;432.0 U/L vs 191.0 U/L,P=0.0007;1303.0 U/L vs 263.5 U/L,P=0.0001,respectively).The cut-off points of first LDH values in the alveolitis and fibrosis phase for distinction of non-survivors from survivors were 397.0 U/L and 263.0 U/L,respectively.In the fibrosis stage,non-survivors had more days with high LDH than survivors(7.0 d vs 0.0 d,P=0.0002).Importantly,patients with high LDH had a significantly shorter median survival time than patients with low LDH in the alveolitis phase(22.0 d vs 36.5 d,P=0.0002),while patients with high LDH also had a significantly shorter median survival time than patients with low LDH in the fibrosis phase(27.5 d vs 40.0 d,P=0.0008).The proportion of non-survivors with detectable SARS-CoV-2 until death in the alveolitis stage was significantly increased compared with that in the fibrosis stage(100%vs 35.7%,P=0.0220).CONCLUSION High LDH and dyspnea symptoms were positive predictors of an adverse outcome in critical COVID-19.The rapid progressive fibrosis stage was more perilous than the alveolitis stage,even if SARS-CoV-2 is undetectable.展开更多
Access block,known as exit block or boarding,is defined as a situation in which patients who are admitted or planned for admission remain in the emergency department(ED)as they are unable to be transferred to an inpat...Access block,known as exit block or boarding,is defined as a situation in which patients who are admitted or planned for admission remain in the emergency department(ED)as they are unable to be transferred to an inpatient unit within a reasonable time frame(no longer than 8 hours).[1,2]Access block often occurs due to insufficient hospital capacity and is a major issue in emergency medicine.[3]展开更多
Lung cancer is the most common and fatal malignant disease worldwide and has the highest mortality rate among tumor-related causes of death.Early diagnosis and precision medicine can significantly improve the survival...Lung cancer is the most common and fatal malignant disease worldwide and has the highest mortality rate among tumor-related causes of death.Early diagnosis and precision medicine can significantly improve the survival rate and prognosis of lung cancer patients.At present,the clinical diagnosis of lung cancer is challenging due to a lack of effective non-invasive detection methods and biomarkers,and treatment is primarily hindered by drug resistance and high tumor heterogeneity.Liquid biopsy is a method for detecting circulating biomarkers in the blood and other body fluids containing genetic information from primary tumor tissues.Bronchoalveolar lavage fluid(BALF)is a potential liquid biopsy medium that is rich in a variety of bioactive substances and cell components.BALF contains information on the key characteristics of tumors,including the tumor subtype,gene mutation type,and tumor environment,thus BALF may be used as a diagnostic supplement to lung biopsy.In this review,the current research on BALF in the diagnosis,treatment,and prognosis of lung cancer is summarized.The advantages and disadvantages of different components of BALF,including cells,cell-free DNA,extracellular vesicles,and micro RNA are introduced.In particular,the great potential of extracellular vesicles in precision diagnosis and detection of drug-resistant for lung cancer is highlighted.In addition,the performance of liquid biopsies with different body fluid sources in lung cancer detection are compared to facilitate more selective studies involving BALF,thereby promoting the application of BALF for precision medicine in lung cancer patients in the future.展开更多
文摘Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.
基金approved by the Ethics Committee of the Third Xiangya Hospital in accordance with the Declaration of Helsinki(No.24029).
文摘BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.
文摘BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.
基金Key R&D Program of Yan’an Municipal Bureau of Science and Technology(Project No.2021YF-21)。
文摘Objective:To analyze the clinical efficacy,progression-free survival,and safety of anlotinib in the treatment of advanced lung cancer.Methods:A retrospective analysis was conducted using data from 60 patients with advanced lung cancer treated with anlotinib from May 2019 to May 2021.This analysis aimed to comprehensively evaluate the clinical efficacy,progression-free survival,and adverse reactions of anlotinib.Results:The median progression-free survival(PFS)for the 60 patients was 5.79 months,with an overall response rate(ORR)of 21%and a disease control rate(DCR)of 90%.In the first-line group,the median PFS was 6.20 months,ORR was 76.92%,and DCR was 84.61%.The second-line group showed a median PFS of 6.30 months,ORR of 28.57%,and DCR of 90.48%.In the third-line group,the median PFS was 5.34 months,ORR was 19.23%,and DCR was 92.30%.The single-agent group exhibited a median PFS of 5.09 months,ORR of 23.33%,and DCR of 76.67%.In the combination group,the median PFS was 6.53 months,ORR was 46.67%,and DCR was 100%.The combination group demonstrated a significantly higher medication effect than the single-drug group,and adverse drug reactions were mostly grade 1-2.Conclusion:Anlotinib exhibits a better disease control rate and survival benefit in the treatment of advanced lung cancer.The combination effect is superior to monotherapy,with relatively controllable adverse effects.
文摘Jing Medicine, as an important part of China’s ethnic medicine and culture, is characterized by its unique theories, rich content, and abundant resources, showcasing distinctive features of minority regions. The Jing ethnic group is distributed in coastal and border areas of China, and after thousands of years of development, it has formed a rich marine-oriented medical system in the struggle against the environment and diseases, displaying unique medication characteristics and clinical efficacy. According to Jing Medicine, the human body is an organic whole that is unified with the natural and social environment. It believes that the heavens and earth are the spirits of all things, and all things possess spiritual energy, which is closely connected to the human body’s spiritual energy. The utilization of marine organisms in medicine is the greatest feature of Jing Medicine, and it is a common approach used by the local population for disease prevention and treatment. To further explore Jing Medicine, improve the repository of ethnic medicine culture, and address the insufficient understanding of Jing Medicine in traditional Chinese medicine culture, this article provides a comprehensive review of the distinctive diagnostic and therapeutic theories, techniques, and applications of internal and external treatments in Jing Medicine.
文摘It has been reported that COVID-19 patients are categorized into four groups:the mild types defined as mild clinical symptoms restricted within upper respiratory tract infection,the moderate ones defined as fever and respiratory symptoms with radiological findings of pneumonia without the severe or critical features,the severe ones defined as the respiratory failure and the rapid disease progression,and the critical ones defined as septic shock and multiple organ failure requiring mechanical ventilation and circulatory support.
基金This research was supported by the National Natural Science Foundation of China(82041018,81770096,81700091,and 81800094)the National Science and Technology Major Project of the Ministry of Science and Technology of China(2019ZX09301001)+1 种基金the National Key Research and Development Program of the Ministry of Science and Technology of China(2020YFC0844300)the Fundamental Research Funds for the Central Universities(China)(2020kfyXGYJ011).
文摘It is difficult to identify suspected cases of atypical patients with coronavirus disease 2019(COVID-19),and data on severe or critical patients are scanty.This retrospective study presents the clinical,laboratory,and radiological profiles,treatments,and outcomes of atypical COVID-19 patients without respiratory symptoms or fever at onset.The study examined ten atypical patients out of 909 severe or critical patients diagnosed with COVID-19 in Wuhan Union Hospital West Campus between 25 January 2020 and 10 February 2020.Data were obtained from the electronic medical records of severe or critical patients without respiratory symptoms or fever at onset.Outcomes were followed up to discharge or death.Among 943 COVID-19 patients,909(96.4%)were severe or critical type.Of the severe or critical patients,ten(1.1%)presented without respiratory symptoms or fever at admission.The median age of the ten participants was 63 years(interquartile range(IQR):57–72),and seven participants were men.The median time from symptom onset to admission was 14 d(IQR:7–20).Eight of the ten patients had chronic diseases.The patients had fatigue(n=5),headache or dizziness(n=4),diarrhea(n=5),anorexia(n=3),nausea or vomiting(n=3),and eye discomfort(n=1).Four patients were found to have lymphopenia.Imaging examination revealed that nine patients had bilateral pneumonia and one had unilateral pneumonia.Eventually,two patients died and eight were discharged.In the discharged patients,the median time from admission to discharge lasted 24 d(IQR:13–43).In summary,some severe or critical COVID-19 patients were found to have no respiratory symptoms or fever at onset.All such atypical cases should be identified and quarantined as early as possible,since they tend to have a prolonged hospital stay or fatal outcomes.Chest computed tomography(CT)scan and nucleic acid detection should be performed immediately on close contacts of COVID-19 patients to screen out those with atypical infections,even if the contacts present without respiratory symptoms or fever at onset.
基金Supported by the Key Research and Development Projects in Sichuan Province,No.2021YFS0168the National Scientific and Technological Major Project for Infectious Diseases Control in China,No.2018ZX10715-003.
文摘BACKGROUND The interruption of mother-to-child transmission(MTCT)is considered important to decrease the individual and population morbidity of hepatitis B virus(HBV)infection as well as the global burden of hepatitis B.Serum vitamin D(VD)is associated with hepatitis B.AIM To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene(VDR SNPs)are associated with the efficacy of tenofovir disoproxil fumarate(TDF)in the prevention of MTCT in pregnant women with high HBV viral loads.METHODS Thirty-eight pregnant women who were at high risk for MTCT of HBV(those with an HBV DNA level≥2×10^(5)IU/mL during 12-24 wk of gestation)receiving antiviral therapy of TDF between June 1,2019 and June 30,2021 in Mianyang were included in this retrospective study.The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery.To further characterize the clinical relevance of maternal serum HBV DNA levels,we stratified patients according to HBV DNA level as follows:Those with levels<2×10_(5)(full responder group)vs those levels≥2×10^(5)IU/mL(partial responder group)at delivery.Serum levels of 25-hydroxyvitamin D[25(OH)D],liver function markers,virological parameters,VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF.The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups.Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery.Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery.RESULTS A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study.The MTCT rate was 0%.No mother achieved hepatitis B e antigen or hepatitis B surface antigen(HBsAg)clearance at delivery.Twenty-three(60.5%)participants were full responders,and 15(39.5%)participants were partial responders according to antiviral efficacy.The present study showed that a high percentage(76.3%)of pregnant women with high HBV viral loads had deficient(<20 ng/mL)or insufficient(≥20 but<31 ng/mL)VD levels.Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline(25.44±9.42 vs 17.66±5.34 ng/mL,P=0.006)and delivery(26.76±8.59 vs 21.24±6.88 ng/mL,P=0.044).Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels[log(10)IU/mL]at delivery after TDF therapy(r=-0.345,P=0.034).In a multiple linear regression analysis,maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels(P<0.0001,β=-0.446),BMI(P=0.03,β=-0.245),baseline maternal log10 HBsAg levels(P=0.05,β=0.285)and cholesterol levels at delivery(P=0.015,β=0.341).Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels(OR=1.23,95%CI:1.04-1.44),maternal VDR Cdx2 TT(OR=0.09,95%CI:0.01-0.88)and cholesterol levels at delivery(OR=0.39,95%CI:0.17-0.87)were associated with targeted antiviral effects(maternal HBV DNA levels<2×10^(5) at delivery).CONCLUSION Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads.Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.
基金Supported by the Science and Technology Research Project of Sichuan Provincial Administration of Traditional Chinese Medicine,No.2021MS164Scientific research project of Sichuan Medical Association,No.S21012。
文摘BACKGROUND Lung invasive mucinous adenocarcinoma(LIMA),formerly referred to as mucinous bronchioloalveolar carcinoma,is a rare disease that usually presents as bilateral lung infiltration,is unsuitable for surgery and radiotherapy,and shows poor response to conventional chemotherapy.CASE SUMMARY We report a 56-year-old Chinese man with a history of smoking and epidermal growth factor receptor mutation-positivity who was initially misdiagnosed as severe pneumonia,but was ultimately diagnosed as a case of invasive mucinous adenocarcinoma of the lung by computed tomography-guided percutaneous lung biopsy.Bronchorrhea and dyspnea were improved within 24 h after initiation of gefitinib therapy and the radiographic signs of bilateral lung consolidation showed visible improvement within 30 d.After more than 11 months of treatment,there is no evidence of recurrence or severe adverse events.CONCLUSION Although the precise mechanism of the antitumor effects of gefitinib are not clear,our experience indicates an important role of the drug in LIMA and provides a reference for the diagnosis and treatment of this disease.
基金This project was supported by the Education Department of Hainan Province(grant No.:Hnky2022ZD-11)Hainan Provincial Natural Science Foundation of China(grant No.:822MS176)+1 种基金Hainan Provincial Natural Science Foundation of China(grant No.:GHYF2022011,ZDKJ2021036,ZDYF2020223 and 820CXTD448)the National Natural Science Foundation of China(grant No.82160012,82260001).
文摘Objective:To evaluate the clinical safety and efficacy of Lianhuaqingwen(LHQW)capsules in patients with high-risk common type COVID-19 pneumonia.Methods:A retrospective multicenter study on 383 high-risk common type COVID-19 pneumonia cases was conducted.Patients were categorized as the standard treatment(SDT)group(n=168)and the LHQW+SDT group(n=215).The primary endpoint was the rate of symptom(fever,fatigue,coughing)recovery and the secondary endpoints included the time to symptom recovery,the proportion of patients with improvement in chest CT images,the proportion of patients with clinical cure,the timing and rate of negative conversion of SARS-CoV-2 RNA assay.Results:The recovery rate was significantly higher in the LHQW+SDT group as compared with the SDT group(89.7%vs.72.0%,P<0.01).The combined use of LHQW+SDT also showed shorter time for symptom recovery,as well as shorter time for individual symptom of fever,fatigue and coughing recovery than use of SDT alone.A higher proportion of patients in the LHQW+SDT group with improvements in chest CT images and clinical cure(77.7%vs.57.1%,P<0.01)but the proportion of patients deteriorating to severe cases(1%vs.25%,P<0.01)in this group was significant lower than those in the SDT group.No significant difference in negative conversion rate of viral assay results was observed(76.8%vs.75.0%,P>0.05).No serious adverse events were reported.Conclusions:LHQW capsules could be recommended to ameliorate clinical symptoms and reduce the rate of deteriorating to severe cases for high-risk common type COVID-19 pneumonia.
文摘BACKGROUND Complement overactivation is a major driver of lupus nephritis(LN).Impaired interactions of C-reactive protein(CRP)with complement factor H(CFH)have been shown as a pathogenic mechanism that contributes to the overactivation of complement in LN.However,genetic variations of neither CRP nor CFH show consistent influences on the risk of LN.AIM To examine whether genetic variations of CRP and CFH in combination can improve the risk stratification in Chinese population.METHODS We genotyped six CRP single nucleotide polymorphisms(SNPs)(rs1205,rs3093062,rs2794521,rs1800947,rs3093077,and rs1130864)and three CFH SNPs(rs482934,rs1061170,and rs1061147)in 270 LN patients and 303 healthy subjects.RESULTS No linkage was found among CRP and CFH SNPs,indicating lack of genetic interactions between the two genes.Moreover,CRP and CFH SNPs,neither individually nor in combination,are associated with the risk or clinical manifestations of LN.Given the unambiguous pathogenic roles of the two genes.CONCLUSION These findings suggest that the biological effects of most genetic variations of CRP and CFH on their expressions or activities are not sufficient to influence the disease course of LN.
基金Natural Science Foundation of Shanxi Province(201901D111391)。
文摘Objective:To investigate the expression level,clinical prognosis,genetic changes,methylation value,biological function and immunomodulatory effects of PHF19 in lung adenocarcinoma.Methods:Based on the RNA cohort data of lung adenocarcinoma in the Cancer Genome Atlas(TCGA)database,the expression difference of PHF19 between lung adenocarcinoma and normal tissues and the relationship between the expression level and the prognosis of patients were analyzed by using TIMER database and UALCAN database.The gene mutation of PHF19 in lung adenocarcinoma was analyzed in cBioPortal database and TIMER database.The promoter methylation level of PHF19 in lung adenocarcinoma was analyzed in UALCAN database.The enrichment of PHF19 co-expression gene was analyzed in LinkedOmics database and KEGG database.The correlation between the expression of PHF19 in lung adenocarcinoma and the level of immunoinfiltration was explored in the TIMER database.Results:The expression of PHF19 in lung adenocarcinoma tissues was up-regulated,and its high expression was significantly correlated with the pathological stage,lymph node metastasis and shortened overall survival of lung adenocarcinoma patients.Genetic variation was found in 0.9%of patients,amplification and missense mutation were the most common mutations,and TP53 mutation could lead to the high expression of PHF19.The promoter methylation level of PHF19 significantly decreased in lung adenocarcinoma.The function of PHF19 was focused on the process of cell mitosis and cell cycle.The expression level of PHF19 was significantly correlated with tumor immune cell infiltration and immune checkpoint expression.Conclusion:PHF19 can be used as a marker of poor prognosis of lung adenocarcinoma and plays an important role in the occurrence and development of lung adenocarcinoma.
文摘BACKGROUND At present,understanding of the most effective ventilation methods for treating chronic obstructive pulmonary disease(COPD)patients experiencing acute worsening symptoms and respiratory failure remains relatively limited.This report analyzed the efficiency and side effects of various ventilation techniques used for individuals experiencing an acute COPD exacerbation.AIM To determine whether pressure-controlled ventilation(PCV)can lower peak airway pressures(PAPs)and reduce the incidence of barotrauma compared to volume-controlled ventilation(VCV),without compromising clinical outcomes and oxygenation parameters.METHODS We have evaluated 600 patients who were hospitalized due to a severe COPD exacerbation,with 400 receiving mechanical ventilation for the respiratory failure.The participants were divided into two different groups,who were administered either VCV or PCV,along with appropriate management.We thereafter observed patients'attributes,clinical factors,and laboratory,radiographic,and arterial blood gas evaluations at the start and during their stay in the intensive care unit(ICU).We have also employed appropriate statistical methods for the data analysis.RESULTS Both the VCV and PCV groups experienced significant enhancements in the respiratory rate,tidal volume,and arterial blood gas values during their time in the ICU.However,no significant distinctions were detected between the groups in terms of oxygenation indices(partial pressures of oxygen/raction of inspired oxygen ratio)and partial pressures of carbon dioxide improvements.There was no considerable disparity observed between the VCV and PCV groups in the hospital mortality(32%vs 28%,P=0.53),the number of days of ICU stay[median interquartile range(IQR):9(6-14)d vs 8(5-13)d,P=0.41],or the duration of the mechanical ventilation[median(IQR):6(4-10)d vs 5(3-9)d,P=0.47].The PCV group displayed lower PAPs compared to the VCV group(P<0.05)from the beginning of mechanical ventilation until extubation or ICU departure.The occurrence of barotrauma was considerably lower in the PCV group in comparison to the VCV group(6%vs 16%,P=0.03).CONCLUSION Both VCV and PCV were found to be effective in treating patients with acute COPD exacerbation.However,PCV was associated with lower PAPs and a significant decrease in barotrauma,thus indicating that it might be a safer ventilation method for this group of patients.However,further large-scale study is necessary to confirm these findings and to identify the best ventilation approach for patients experiencing an acute COPD exacerbation.
基金National Natural Science Foundation of China(No.82160011)。
文摘Objective:Investigating the effects of miR-873 on apoptosis and autophagy in bronchial epithelial cells,as well as its regulatory role on Beclin1.Methods:Following transfection of miR-873 mimic into 16HBE cells for 48 hours,the mRNA level of miR-873 was quantified by qRT-PCR,and cell viability was evaluated by CCK-8 assay.The levels of IL-2,IL-6,IL-10,and TNF-αin the cell supernatant were determined using ELISA assay,while cell apoptosis was detected by TUNEL staining.LC-3 protein expression was examined by immunofluorescence,and mRNA and protein expression levels of Beclin1 were analyzed by qRT-PCR and Western blot,respectively.Moreover,dual-luciferase reporter gene technology was employed to investigate the binding site between miR-873 and Beclin1.Results:Transfection of miR-873 mimic into 16HBE cells significantly upregulated the mRNA level of miR-873,which led to the inhibition of cell proliferation and the promotion of secretion of pro-inflammatory cytokines IL-2,IL-6,and TNF-α,while suppressing the secretion of anti-inflammatory cytokine IL-10.Moreover,miR-873 induced cell apoptosis and inhibited the expression of LC-3.Dual-luciferase reporter gene assay further confirmed the presence of binding sites between miR-873 and Beclin1 gene.Besides,miR-873 could target and suppress the mRNA and protein expression levels of Beclin1.Conclusion:miR-873 might modulate cell autophagy by targeting the Beclin1 gene,which can potentially promote inflammation and apoptosis in bronchial epithelial cells.
基金Hainan General Hospital National Natural Science Foundation Cultivation 530 Project Youth Project (No.2021QNXM10)National Natural Science Foundation of China (No.82160011)。
文摘Objective:Investigating the inhibitory effect of Huayu Lifyei Formula on bleomycininduced rat pulmonary fibrosis and its impact on the expression of miR-27a andα-SMA.Methods:Wistar rats were arbitrarily classified into a normal group,a model group,and a group treated with Huayu Lifyei Formula,each consisting of ten rats.Pulmonary fibrosis rat model was established by injecting bleomycin.Subsequent to the modeling,the Huayu Lifyei Formula treatment group was administered Huayu Lifyei Formula via gavage for a period of 7 days.Rats were sacrificed on the 14th day after modeling.The right lung was taken for HE staining,Masson staining,and immunohistochemical observation of alpha-smooth muscle actin(α-SMA)expression.The expression of miR-27a was measured by qRT-PCR,with the miR-27a binding site on ACTA2(the gene encodingα-SMA protein)confirmed using dualluciferase reporter gene technology.Results:When compared to the model group,the Huayu Lifyei Formula treatment group showed considerable alleviation of pathological morphological changes in lung tissue,with significant reductions in alveolitis,fibrosis,collagen deposition in lung tissue,and the expression ofα-SMA protein.Meanwhile,the expression of miR-27a in the Huayu Lifyei Formula treatment group significantly increased,and the dual-luciferase reporter gene confirmed the binding site of miR-27a with the ACTA2 gene.Conclusion:Huayu Lifyei Formula can inhibit bleomycin-induced pulmonary fibrosis in rats,and its mechanism may be related to the promotion of miR-27a expression.
基金supported by the following grants and funding:the National Science Foundation-Outstanding Youth Fund(No.82222001)the Emergency Key Program of Guangzhou Laboratory(Grant No.EKPG22-02)+2 种基金the Guangzhou Institute for Respiratory Health Open Project(funded by China Evergrande Group)with Project No,2020GIRHHMS09 and 2020GIRHHMS19the Zhongnanshan Medical Foundation of Guangdong Province(funding number not applicable)the Penghua Care Fund to the Medical Pioneers against Covid-19 of Shenzhen Social Commonweal Foundation(funding number not applicable,Guan W J).
文摘Coronavirus disease 2019(COVID-19)is the third severe acute respiratory disease of the 21st century and the most aggressive global pandemic to date.The whole population has been susceptible to the disease,particularly the emerging variants of the virus.The core pathophysiological mechanism is viral sepsis that can lead to the respiratory tract disorders and even systemic disorders such as cytokine release syndrome,thrombosis,abnormal angiogenesis,and multiple organ dysfunction.Despite only few licensed treatments to date,rapid advances have been made in exploring the effectiveness and safety of pharmacological interventions and vaccines.However,three pillars of preventative and control measures-proactive contact tracing,wearing facial masks,and social distancing-are essential to combat the ongoing pandemic.As the number of patients recovering from COVID-19 rapidly increases,the world has entered the era of caring for patients during the convalescence phase.This phase still represents a largely unmet medical need globally.
文摘The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.
基金Supported by National Natural Science Foundation of China,No.81800070Development Fund Program of Fujian Provincial Health and Family Planning Commission,China,No.2017-1-43.
文摘BACKGROUND Coronavirus disease 2019(COVID-19)caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak in China,constitutes a Public Health Emergency of International Concern.It is well known that COVID-19 patients may have increased serum lactate dehydrogenase(LDH)levels in the early stage.The clinical changes in LDH may have predictive value in disease evolution and prognosis in critically ill COVID-19 patients.AIM To examine serum LDH and clinical characteristics in patients with COVID-19 and their predictive value for prognosis.METHODS This retrospective study analyzed the clinical data of forty-seven critical COVID-19 patients in the intensive care unit of the Third People's Hospital of Yichang City from January 27 to March 25,2020 and divided them into survivors and nonsurvivors.The patients were diagnosed according to the World Health Organization interim guidance and critical cases met any one of the following criteria:Respiratory failure and required mechanical ventilation,the occurrence of shock,and the combined failure of other organs that required intensive care unit monitoring and treatments,according to the diagnostic criteria of critical COVID-19.Clinical data including symptoms,detection of SARS-CoV-2,chest computed tomography(CT)images,changes in serum LDH in different clinical phases,and prognosis were collected.Statistical analysis of the data was performed.Continuous variables were expressed as median(interquartile range)and compared with the Mann-Whitney U test.Categorical variables were compared with the Chi-square test.Survival data were analyzed using Kaplan-Meier survival curves and log-rank tests.RESULTS According to chest CT images,we observed the alveolitis and fibrosis stages in all critical patients in this study.Most non-survivors died in the fibrosis stage.Nonsurvivors had fewer days of hospitalization,shorter disease duration,shorter duration of alveolitis and fibrosis,and had dyspnea symptoms at disease onset(P=0.05).Both first and lowest LDH values in the alveolitis stage were more pronounced in non-survivors than in survivors(449.0 U/L vs 288.0 U/L,P=0.0243;445.0 U/L vs 288.0 U/L,P=0.0199,respectively),while the first,lowest and highest values of serum LDH in non-survivors were all significantly increased compared to survivors in the fibrosis phase(449.0 U/L vs 225.5 U/L,P=0.0028;432.0 U/L vs 191.0 U/L,P=0.0007;1303.0 U/L vs 263.5 U/L,P=0.0001,respectively).The cut-off points of first LDH values in the alveolitis and fibrosis phase for distinction of non-survivors from survivors were 397.0 U/L and 263.0 U/L,respectively.In the fibrosis stage,non-survivors had more days with high LDH than survivors(7.0 d vs 0.0 d,P=0.0002).Importantly,patients with high LDH had a significantly shorter median survival time than patients with low LDH in the alveolitis phase(22.0 d vs 36.5 d,P=0.0002),while patients with high LDH also had a significantly shorter median survival time than patients with low LDH in the fibrosis phase(27.5 d vs 40.0 d,P=0.0008).The proportion of non-survivors with detectable SARS-CoV-2 until death in the alveolitis stage was significantly increased compared with that in the fibrosis stage(100%vs 35.7%,P=0.0220).CONCLUSION High LDH and dyspnea symptoms were positive predictors of an adverse outcome in critical COVID-19.The rapid progressive fibrosis stage was more perilous than the alveolitis stage,even if SARS-CoV-2 is undetectable.
基金supported by the Project of Science and Technology Commission of Jiading,Shanghai(JDKW-2016-W03)the Scientific Research Projects of the Shanghai Municipal Health Commission for Youths(20204Y0016)+1 种基金the National Natural Science Foundation of China(72174041)。
文摘Access block,known as exit block or boarding,is defined as a situation in which patients who are admitted or planned for admission remain in the emergency department(ED)as they are unable to be transferred to an inpatient unit within a reasonable time frame(no longer than 8 hours).[1,2]Access block often occurs due to insufficient hospital capacity and is a major issue in emergency medicine.[3]
基金supported by grants from the National Natural Science Foundation of China(Grant No.82173182)the Sichuan Science and Technology Program(Grant No.2021YJ0117 to Weiya Wang+1 种基金Grant No.2023NSFSC1939 to Dan Liu)the 1·3·5 project for Disciplines of Excellence–Clinical Research Incubation Project,West China Hospital,Sichuan University(Grant Nos.2019HXFH034 and ZYJC21074)。
文摘Lung cancer is the most common and fatal malignant disease worldwide and has the highest mortality rate among tumor-related causes of death.Early diagnosis and precision medicine can significantly improve the survival rate and prognosis of lung cancer patients.At present,the clinical diagnosis of lung cancer is challenging due to a lack of effective non-invasive detection methods and biomarkers,and treatment is primarily hindered by drug resistance and high tumor heterogeneity.Liquid biopsy is a method for detecting circulating biomarkers in the blood and other body fluids containing genetic information from primary tumor tissues.Bronchoalveolar lavage fluid(BALF)is a potential liquid biopsy medium that is rich in a variety of bioactive substances and cell components.BALF contains information on the key characteristics of tumors,including the tumor subtype,gene mutation type,and tumor environment,thus BALF may be used as a diagnostic supplement to lung biopsy.In this review,the current research on BALF in the diagnosis,treatment,and prognosis of lung cancer is summarized.The advantages and disadvantages of different components of BALF,including cells,cell-free DNA,extracellular vesicles,and micro RNA are introduced.In particular,the great potential of extracellular vesicles in precision diagnosis and detection of drug-resistant for lung cancer is highlighted.In addition,the performance of liquid biopsies with different body fluid sources in lung cancer detection are compared to facilitate more selective studies involving BALF,thereby promoting the application of BALF for precision medicine in lung cancer patients in the future.
