Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation ...Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT.Regional citrate anticoagulation(RCA)has been shown to potentially be safer and more effective,and is now recommended as the preferred anticoagulant method for CRRT.However,there is still a lack of unified standards for RCA management in the world,and there are many problems in using this method in clinical practice.The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association(CMDA)organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues,including the advantages and disadvantages of RCA in CRRT anticoagulation,the principle of RCA,parameter settings for RCA,monitoring of RCA(mainly metabolic acid-base disorders),and special issues during RCA.Based on the latest available research evidence as well as the paneled experts'clinical experience,considering the generalizability,suitability,and potential resource utilization,while also balancing clinical advantages and disadvantages,a total of 16 guideline recommendations were formed from the experts'consensus.展开更多
Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehe...Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management.In this study,we aim to identify a panel of signature genes closely associated with LUSC,which can provide novel insights into the progression of LUSC.Gene expression profiles were retrieved from public resources including gene expression omnibus(GEO)and the cancer genome atlas(TCGA)database.Differentially expressed genes(DEGs)between LUSC specimens and normal lung tissues were identified by bioinformatics analyses.A total of 66 DEGs were identified based on two cohorts of data.CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN,ABI3BP,MAMDC2,FGF7,FAM107A,SPARCL1,DCN,COL14A1,and MFAP4 and CHRDL1,which showed significant downregulation in LUSC.Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment.Together,our data revealed novel candidate tumor-suppressor genes in LUSC,suggesting previously unappreciated mechanisms in the progression of LUSC.展开更多
BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical valu...BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical value.AIM To identify potential DNA methylation markers specific to ADE and CRC.METHODS Here,we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.RESULTS Comparing 22 CRC and 25 ADE samples,global methylation was higher in the former,but both showed similar methylation patterns regarding differentially methylated gene positions,chromatin signatures,and repeated elements.High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC.Combined with RNA-seq gene expression data,we identified 14 methylation-regulated differentially expressed genes,of which only AGTR1 and NECAB1 methylation had prognostic significance.CONCLUSION Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC,suggesting prognostic biomarkers for CRC.展开更多
BACKGROUND Pyroptosis impacts the development of malignant tumors,yet its role in colorectal cancer(CRC)prognosis remains uncertain.AIM To assess the prognostic significance of pyroptosis-related genes and their assoc...BACKGROUND Pyroptosis impacts the development of malignant tumors,yet its role in colorectal cancer(CRC)prognosis remains uncertain.AIM To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration.METHODS Gene expression data were obtained from The Cancer Genome Atlas(TCGA)and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus(GEO).Pyroptosis-related gene expression in cell clusters was analyzed,and enrichment analysis was conducted.A pyroptosis-related risk model was developed using the LASSO regression algorithm,with prediction accuracy assessed through K-M and receiver operating characteristic analyses.A nomo-gram predicting survival was created,and the correlation between the risk model and immune infiltration was analyzed using CIBERSORTx calculations.Finally,the differential expression of the 8 prognostic genes between CRC and normal samples was verified by analyzing TCGA-COADREAD data from the UCSC database.RESULTS An effective pyroptosis-related risk model was constructed using 8 genes-CHMP2B,SDHB,BST2,UBE2D2,GJA1,AIM2,PDCD6IP,and SEZ6L2(P<0.05).Seven of these genes exhibited differential expression between CRC and normal samples based on TCGA database analysis(P<0.05).Patients with higher risk scores demonstrated increased death risk and reduced overall survival(P<0.05).Significant differences in immune infiltration were observed between low-and high-risk groups,correlating with pyroptosis-related gene expression.CONCLUSION We developed a pyroptosis-related prognostic model for CRC,affirming its correlation with immune infiltration.This model may prove useful for CRC prognostic evaluation.展开更多
Background Obsessive-compulsive disorder(OCD)is considered a very debilitating disorder with severe loss of quality of life and income.Aims This study estimates the quality of life and economic consequences of OCD in ...Background Obsessive-compulsive disorder(OCD)is considered a very debilitating disorder with severe loss of quality of life and income.Aims This study estimates the quality of life and economic consequences of OCD in China.Methods The research team interviewed 639 patients with OCD in 13 hospitals in 12 cities in China.The direct method was used to get the direct cost of OCD.Indirect costs associated with OCD were estimated using the human capital approach.Linear regression analysis was conducted for quality of life and generalised linear model analysis was conducted for total cost.Sensitivity analysis was used to analyse the uncertainty of total cost.Results The mean quality of life score for OCD was 52.78(20.46).The annual total cost of OCD per capita was 24503.78(95%CI:22621.53 to 26386.03)renminbi(RMB)(US$3465.88(95%CI:US$3199.65 to US$3732.11)).The annual cost of OCD in China was estimated to be 37.74 billion(95%CI:34.95 billion to 40.53 billion)RMB(equal to US$5.34 billion(95%CI:US$4.94 billion to US$5.73 billion)).Sensitivity analysis showed that the total annual cost of OCD in China was between 23.15 billion RMB(US$3.27 billion)and 370.00 billion RMB(US$52.33 billion).Worse social function status,more psychiatric symptoms and higher Yale Brown Obsessive-Compulsive Scale(Y-BOCS)score were associated with worse quality of life.The numbers of clinic visits and hospitalisations,socioeconomic status,education,Y-BOCS scores and age were found to be significantly associated with total cost.Conclusions OCD is associated with low quality of life and high costs in China.The findings call for concerted efforts to improve services for patients with OCD.Improvements may include early detection and diagnosis,the provision of evidence-based treatments and relapse prevention strategies.展开更多
BACKGROUND Whether regional lymphadenectomy(RL)should be routinely performed in patients with T1b gallbladder cancer(GBC)remains a subject of debate.AIM To investigate whether RL can improve the prognosis of patients ...BACKGROUND Whether regional lymphadenectomy(RL)should be routinely performed in patients with T1b gallbladder cancer(GBC)remains a subject of debate.AIM To investigate whether RL can improve the prognosis of patients with T1b GBC.METHODS We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China.The logrank test and Cox proportional hazards model were used to compare the overall survival(OS)of patients who underwent cholecystectomy(Ch)+RL and those who underwent Ch only.To investigate whether combined hepatectomy(Hep)improved OS in T1b patients,we studied patients who underwent Ch+RL to compare the OS of patients who underwent combined Hep and patients who did not.RESULTS Of the 121 patients(aged 61.9±10.1 years),77(63.6%)underwent Ch+RL,and 44(36.4%)underwent Ch only.Seven(9.1%)patients in the Ch+RL group had lymph node metastasis.The 5-year OS rate was significantly higher in the Ch+RL group than in the Ch group(76.3%vs 56.8%,P=0.036).Multivariate analysis showed that Ch+RL was significantly associated with improved OS(hazard ratio:0.51;95%confidence interval:0.26-0.99).Among the 77 patients who underwent Ch+RL,no survival improvement was found in patients who underwent combined Hep(5-year OS rate:79.5%for combined Hep and 76.1%for no Hep;P=0.50).CONCLUSION T1b GBC patients who underwent Ch+RL had a better prognosis than those who underwent Ch.Hep+Ch showed no improvement in prognosis in T1b GBC patients.Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines,RL was only performed in 63.6%of T1b GBC patients.Routine Ch+RL should be advised in T1b GBC.展开更多
Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activiti...Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities.Olfactory receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods Clinical and molecular information from The Cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for immunotherapy.The Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation cohorts.Results OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal programs.Compared to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related proteins.The clustering performed well in the internal and 5 external validation cohorts.Based on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment response.In addition,the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients.The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts.Conclusion Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC.ORIGs can be applied to molecularly stratify patients,and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.展开更多
Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is ur...Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.展开更多
Background Non-suicidal self-injury(NSSI)is a frequent and prominent phenomenon in major depressive disorder(MDD).Even though its prevalence and risk factors are relatively well understood,the potential mechanisms of ...Background Non-suicidal self-injury(NSSI)is a frequent and prominent phenomenon in major depressive disorder(MDD).Even though its prevalence and risk factors are relatively well understood,the potential mechanisms of NSSI in MDD remain elusive.Aims To review present evidence related to the potential mechanisms of NSSI in MDD.Methods According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines,articles for this systematic review were searched on Medline(through PubMed),Embase(through Elsevier),PsycINFO(through OVID)and Web of Science databases for English articles,as well as China National Knowledge Infrastructure(CNKI),SinoMed,Wanfang Data,and the Chongqing VIP Chinese Science and Technology Periodical(VIP)Databases for Chinese articles published from the date of inception to 2 August 2022.Two researchers(BW,HZ)independently screened studies based on inclusion and exclusion criteria and assessed their quality.Results A total of 25157 studies were searched.Only 25 of them were ultimately included,containing 3336 subjects(1535 patients with MDD and NSSI,1403 patients with MDD without NSSI and 398 HCs).Included studies were divided into 6 categories:psychosocial factors(11 studies),neuroimaging(8 studies),stress and hypothalamic-pituitary-adrenal(HPA)axis(2 studies),pain perception(1 study),electroencephalogram(EEG)(2 studies)and epigenetics(1 study).Conclusions This systematic review indicates that patients with MDD and NSSI might have specific psychosocial factors,aberrant brain functions and neurochemical metabolisms,HPA axis dysfunctions,abnormal pain perceptions and epigenetic alterations.展开更多
In recent years,the relationship between intestinal flora and liver disease has become an important research direction of liver diseases.A growing body of evidence indicates that gut bacteria play a key role in the pa...In recent years,the relationship between intestinal flora and liver disease has become an important research direction of liver diseases.A growing body of evidence indicates that gut bacteria play a key role in the pathophysiology of liver disease,this article combed the at home and abroad in recent years,the changes of intestinal flora and autoimmune liver disease,alcoholic liver disease,fatty liver disease related to metabolism,hepatitis b viral hepatitis,cirrhosis and liver cancer occurrence and progress of relationship of related research,And the new progress of regulating intestinal microecology in the treatment of liver diseases.Dysregulation of intestinal flora plays an important role in the occurrence and development of liver diseases.Regulating intestinal flora to improve the prognosis of liver diseases will be an important development direction in the future.展开更多
AIM:To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension(OH)in clinical practice in China.METHODS:This post-marketing observational study included patients who received ta...AIM:To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension(OH)in clinical practice in China.METHODS:This post-marketing observational study included patients who received tafluprost to lower intraocular pressure(IOP)within 30d between September 2017 and March 2020 in 20 hospitals in China.Adverse drug reactions(ADRs)during tafluprost treatment and within 30d after the treatment were collected.RESULTS:A total of 2544 patients were included in this study,of them 58.5%(1488/2544)had primary open angle glaucoma(POAG),21.9%(556/2544)had OH and 19.7%(500/2544)used tafluprost for other reasons.Of 359 ADRs occurred in 10.1%(258/2544)patients,and no serious adverse event occurred.The most common ADR was conjunctival hyperemia(128 ADRs in 124 patients,4.9%).Totally 1670 participants(65.6%)combined tafluprost with carbonic anhydrase inhibitors(CAIs;37.1%,620/1670),sympathomimetics(33.5%,559/1670),β-blockers(33.2%,555/1670),other prostaglandin analogs(PGAs;15.6%,260/1670)and other eye drops(15.1%,253/1670).The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs(23 ADRs in 23 patients,8.8%,23/260)and the lowest was in combination with CAIs(16 ADRs in 16 patients,2.6%,16/620).Tafluprost was applied in primary angle-closure glaucoma(41.6%,208/500),after glaucoma surgery(17.8%,89/500)and after non-glaucoma surgery(15.8%,79/500).CONCLUSION:Tafluprost is safe for POAG and OH,and tolerable when combined with other eye drops and under various clinical circumstances.展开更多
Electroacupuncture for the treatment of spinal cord injury has a good clinical curative effect, but the underlying mechanism is unclear. In our experiments, the spinal cord of adult Sprague-Dawley rats was clamped for...Electroacupuncture for the treatment of spinal cord injury has a good clinical curative effect, but the underlying mechanism is unclear. In our experiments, the spinal cord of adult Sprague-Dawley rats was clamped for 60 seconds. Dazhui(GV14) and Mingmen(GV4) acupoints of rats were subjected to electroacupuncture. Enzyme-linked immunosorbent assay revealed that the expression of serum inflammatory factors was apparently downregulated in rat models of spinal cord injury after electroacupuncture. Hematoxylin-eosin staining and immunohistochemistry results demonstrated that electroacupuncture contributed to the proliferation of neural stem cells in rat injured spinal cord, and suppressed their differentiation into astrocytes. Real-time quantitative PCR and western blot assays showed that electroacupuncture inhibited activation of the Notch signaling pathway induced by spinal cord injury. These findings indicate that electroacupuncture repaired the injured spinal cord by suppressing the Notch signaling pathway and promoting the proliferation of endogenous neural stem cells.展开更多
AIM: To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus (HBV) replication in different clinical stages of chronic HBV infection.METHODS: A total of 422 patients w...AIM: To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus (HBV) replication in different clinical stages of chronic HBV infection.METHODS: A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages: immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. SerumHBV DNA load was assessed by quantitative real-time polymerase chain reaction.RESULTS: CD8+ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages (36.87 ± 7.58 vs 34.37 ± 9.07, 36.87 ± 7.58 vs 28.09 ± 5.64, P < 0.001). The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8+ T-cells than CD4+ T-cells (36.87 ± 7.58 vs 30.23 ± 6.35, 34.37 ± 9.07 vs 30.92 ± 7.40, P < 0.01), whereas the peripheral blood in patients at the immune-inactive carrier stage and in normal controls contained less CD8+ T-cells than CD4+ T-cells (28.09 ± 5.64 vs 36.85 ± 6.06, 24.02 ± 4.35 vs 38.94 ± 3.39, P < 0.01). ANOVA linear trend test showed that CD8+ T-cells were signif icantly increased in patients with a high viral load (39.41 ± 7.36, 33.83 ± 7.50, 31.81 ± 5.95 and 26.89 ± 5.71, P < 0.001), while CD4+ T-cells were signif icantly increased in patients with a low HBV DNA load (37.45 ± 6.14, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P < 0.001). Multiple regression analysis displayed that log copies of HBV DNA still maintained its highly signif icant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3+, CD4+ and CD8+ cells and CD4+/CD8+ ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation.CONCLUSION: Differences in peripheral T-cell subpopulation profi les can be found in different clinical stages of chronic HBV infection. T-cell impairment is signifi cantly associated with HBV load.展开更多
AIM: To investigate peripheral T-lymphocyte sub-population profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB).METHODS: Distribution of T-lymphocyte subpopul...AIM: To investigate peripheral T-lymphocyte sub-population profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB).METHODS: Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction (PCR). The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed.RESULTS: CHB patients had significantly decreased CD3+ and CD4+ cells and CD4+/CD8+ ratio, and increased CD8+ cells compared with uninfected controls (55.44 ± 12.39 vs 71.07 ± 4.76, 30.92 ± 7.48 vs 38.94 ± 3.39, 1.01 ± 0.49 vs 1.67 ± 0.33, and 34.39 ± 9.22 vs 24.02 ± 4.35; P < 0.001, respectively). Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load, presence of serum hepatitis B e antigen (HBeAg) expression, liver disease severity, history of maternal HBV infection, and young age at HBV infection, all with P < 0.01. There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations (linear trend test P < 0.001). There was a negative correlation between the levels of CD3+ and CD4+ cells and CD4+/CD8+ ratio and serum level of viral load in CHB patients (r = -0.68, -0.65 and -0.75, all P < 0.0001), and a positive correlation between CD8+ cells and viral load (r = 0.70, P < 0.0001). There was a significant decreasing trend in CD3+ and CD4+ cells and CD4+/CD8+ ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection (linear trend test P < 0.01). In multiple regression (after adjustment for age at HBV infection, maternal HBV infection status and hepatocyte damage severity) log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations, and was the strongest predictor of variation in CD3+, CD4+, CD8+ cells and CD4+/CD8+ ratio. However, the effect of HBeAg was not significant.CONCLUSION: T-lymphocyte failure was signifi-cantly associated with viral replication level. The substantial linear dose-response relationship and strong independent predictive effect of viral load on T-lymphocyte subpopulations suggests the possibility of a causal relationship between them, and indicates the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients.展开更多
AIM: To evaluate whether sorafenib use after resection impacts tumor relapse and survival in Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC).METHODS: This retrospective study enrolled 36 male...AIM: To evaluate whether sorafenib use after resection impacts tumor relapse and survival in Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC).METHODS: This retrospective study enrolled 36 male BCLC stage C HCC patients with portal vein thrombus and Child-Pugh class A liver function. Twentyfour patients received only surgical resection(SR), and 12 patients received oral sorafenib within 30 d after surgery. The primary outcomes were time to progression(TTP)(the time from surgical resection until HCC recurrence or extrahepatic metastases) and overall survival(OS). The secondary outcome was the rate of postoperative recurrence or metastasis. TTP and OS were analyzed using Kaplan Meier curves.RESULTS: There were no significant differences between the two groups in the serum levels of alpha-fetoprotein, copies of hepatitis B virus-DNA, preoperative laboratory results, degree of hepatic fibrosis, types of portal vein tumor thrombus, number of satellite lesions, tumor diameter, pathological results, volume of blood loss, volume of blood transfusion, or surgery time(all P > 0.05). Patients in the SR + sorafenib group had a significantly longer TTP(29 mo vs 22 mo, P = 0.041) and a significantly longer medianOS(37 mo vs 30 mo, P = 0.01) compared to patients in the SR group. The SR group had 18 cases(75%) of recurrence/metastasis while the SR + sorafenib group had six cases(50%) of recurrence/metastasis. A total of 19 patients died after surgery(five in the SR + sorafenib group and 14 in the SR group). The most common sorafenib-related adverse events were skin reactions, diarrhea, and hypertension, all of which were resolved with treatment.CONCLUSION: Sorafenib after SR was well-tolerated. Patients who received sorafenib after SR had better outcomes compared to patients who received only SR.展开更多
Objective:To investigate the effect of BMSCs transplantation plus hyperbaric oxygen(HBO)on repair of rat SCI.Methods:Seventy five male rats were divided randomly into five groups:sham,vehicle.BMSCs transplantation gro...Objective:To investigate the effect of BMSCs transplantation plus hyperbaric oxygen(HBO)on repair of rat SCI.Methods:Seventy five male rats were divided randomly into five groups:sham,vehicle.BMSCs transplantation group,combination group,15 rats in each group.Every week after the SCI onset,all animals were evaluated for behavior outcome by Basso-BeattleBresnahan(BBB) score and inclined plane test.Axon recovery was examined with focal spinal cord tissue by electron microscope at 6 weeks after the SCI onset.HE staining and BrdU staining were performed to examine the BMSCs and lesion post injury.Somatosensory evoked potential(SEP) testing was performed to detect the recovery of neural conduction.Results from the behavior tests from combination group were significant higher than rats which received only transplantation or HBO treatment.Results from histopathology showed favorable recovery from combination group than other treatment groups.The number of BrdU+ in combination group were measureable more than transplantation group(P<0.05).The greatest decrease in TNF-α,IL-1β,IL-6.IFN-α determined by Elisa assay in combination group were evident too.Conclusions:BMSCs transplantation can promote the functional recovery of rat hind limbs after SCI,and its combination with HBO has a synergistic effect.展开更多
An efficient screening assay was developed and validated for simultaneous assessment of compound-mediated inhibition of six major human cytochrome P450(CYP) enzymes.This method employed a cocktail of six probe substra...An efficient screening assay was developed and validated for simultaneous assessment of compound-mediated inhibition of six major human cytochrome P450(CYP) enzymes.This method employed a cocktail of six probe substrates(i.e.,phenacetin.amodiaquine.diclofenac,S-mephenytoin,dextromethorphan and midazolam for CYP1A2,2C8.2C9,2C19,2D6 and 3A4.respectively) as well as individual prototypical inhibitors of the six CYP enzymes in human liver microsomes under optimized incubation conditions.The corresponding marker metabolites(i.e.,acetaminophen,N-deselhylamodiaquine,4-OH-diclofenac.4-OH-Smephenytoin,dextrorphan and 1-OH-midazolam) in the incubates were quantified using LC-MS/MS methods either by an internal standaid(IS) calibration curve or a simplified analyte-to-IS peak area ratio approach.The results showed that the IC_(50) values determined by the cocktail approach were in good agreement with those obtained by the individual substrate approach as well as those reported in the literature.Besides,no remarkable difference was observed between the two quantification approaches.In conclusion,this new cocktail assay can be used for reliable screening of compound-mediated CYP inhibition.展开更多
Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase(JNK) participates in the apoptosis of retinal ganglion cells in gl...Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase(JNK) participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by photocoagulation using the laser ignition method. Results showed significant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 m RNA expression in the retina. These data indicated that the increased expression of JNK3 m RNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.展开更多
Inflammatory responses,including glial cell activation and peripheral immune cell infiltration,are involved in the pathogenesis of Parkinson’s disease(PD).These inflammatory responses appear to be closely related to ...Inflammatory responses,including glial cell activation and peripheral immune cell infiltration,are involved in the pathogenesis of Parkinson’s disease(PD).These inflammatory responses appear to be closely related to the release of extracellular vesicles,such as exosomes.However,the relationships among different forms of glial cell activation,synuclein dysregulation,mitochondrial dysfunction,and exosomes are complicated.This review discusses the multiple roles played by exosomes in PD-associated inflammation and concludes that exosomes can transport toxicα-synuclein oligomers to immature neurons and into the extracellular environment,inducing the oligomerization ofα-synuclein in normal neurons.Misfoldedα-synuclein causes microglia and astrocytes to activate and secrete exosomes.Glial cell-derived exosomes participate in communications between glial cells and neurons,triggering anti-stress and anti-inflammatory responses,in addition to axon growth.The production and release of mitochondrial vesicles and exosomes establish a new mechanism for linking mitochondrial dysfunction to systemic inflammation associated with PD.Given the relevance of exosomes as mediators of neuron-glia communication in neuroinflammation and neuropathogenesis,new targeted treatment strategies are currently being developed that use these types of extracellular vesicles as drug carriers.Exosome-mediated inflammation may be a promising target for intervention in PD patients.展开更多
AIM: To observe the efficiency and safety of thymosin-α1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis. METHODS: Sixty-two patients were randomly divided into groups ...AIM: To observe the efficiency and safety of thymosin-α1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis. METHODS: Sixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-α1, twice a week (T-α1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-α) each day for fifteen days, then three times weekly (IFN-α group) for six months. The results between two groups treated with and the group untreated with IFN-α which was followed up for 12 mo (historical control group consisting of 30 patients) were compared, and three groups were comparable between each other (P > 0.05) at baseline (age, sex, clinical history, biochemical, and serological parameters). RESULTS: At the end of treatment, complete response, which was defined as alanine aminotransferase (ALT) normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 (31.0%) patients in the T-α1 group and in 15 of 33 (45.5%) patients in the IFN-α group (c2 = 1.36, P >0.05). After a follow-up period of six months, a complete response was observed in 14 of 29 (48.3%) patients in the T-α1 group and in 9 of 33 (27.3%) patients in the IFN-α group (c2 = 2.93, P > 0.05). Compared with the results observed in the historical control (HC) group untreated with IFN-α which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-α group at the end of therapy (1 of 30 vs 15 of 33, c2 = 14.72, P < 0.001) and in the T-α1 group at the end of follow-up (1 of 30 vs 14 of 29, c2 = 15.71, P < 0.001). In T-α1 and IFN-α treatment groups, the area under (the plasma concentration time) curve (AUC) of negative HBV DNA and HBeAg was 34%, 17%, 31% and 19% smaller than that in the HC group. By the end of the follow- up period, the proportions of ALT normalization and negative HBV DNA in the T-α1 group were significantly higher than those in the IFN-α and HC groups. The odds of ALT normalization and negative HBV DNA at the end of the follow-up was three-fold higher in the T-α1 group than in the IFN-α group. Unlike IFN-α, T-α1 was well tolerated by all patients, and no side effects appeared in T-α1 group.CONCLUSION: The results suggest that a 6-mo course of T-α1 therapy is effective and safe in patients with chronic hepatitis B. T-α1 is able to reduce HBV replication in patients with chronic hepatitis B. Furthermore, T-α1 is better tolerated than IFN-α and can gradually induce more sustained ALT normalization and HBV DNA and HBeAg loss. However, a response rate of 48.3% is still less ideal. A more effective therapeutic approach warrants further study.展开更多
文摘Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT.Regional citrate anticoagulation(RCA)has been shown to potentially be safer and more effective,and is now recommended as the preferred anticoagulant method for CRRT.However,there is still a lack of unified standards for RCA management in the world,and there are many problems in using this method in clinical practice.The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association(CMDA)organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues,including the advantages and disadvantages of RCA in CRRT anticoagulation,the principle of RCA,parameter settings for RCA,monitoring of RCA(mainly metabolic acid-base disorders),and special issues during RCA.Based on the latest available research evidence as well as the paneled experts'clinical experience,considering the generalizability,suitability,and potential resource utilization,while also balancing clinical advantages and disadvantages,a total of 16 guideline recommendations were formed from the experts'consensus.
基金Department of Science and Technology of Yunnan Province,Provincial Basic Research Program(Kunkun-Medical Joint Special Project),202101AY070001-134Yunnan Provincial Department of Science and Technology,Yunnan Provincial Gerontology Research Center,202102AA310069Yunnan Provincial Department of Science and Technology-Kunming Medical University Basic Research Joint Special Key Project,202201AY070001-136.
文摘Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management.In this study,we aim to identify a panel of signature genes closely associated with LUSC,which can provide novel insights into the progression of LUSC.Gene expression profiles were retrieved from public resources including gene expression omnibus(GEO)and the cancer genome atlas(TCGA)database.Differentially expressed genes(DEGs)between LUSC specimens and normal lung tissues were identified by bioinformatics analyses.A total of 66 DEGs were identified based on two cohorts of data.CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN,ABI3BP,MAMDC2,FGF7,FAM107A,SPARCL1,DCN,COL14A1,and MFAP4 and CHRDL1,which showed significant downregulation in LUSC.Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment.Together,our data revealed novel candidate tumor-suppressor genes in LUSC,suggesting previously unappreciated mechanisms in the progression of LUSC.
基金the National Natural Science Foundation of China,No.81960504the“Xingdian Talents”Support Project of Yunnan Province,No.RLQB20200002+2 种基金the Medical Discipline Reserve Talents of Yunnan Province,No.H-2018015the Applied Basic Research Projects-Union Foundation of Kunming Medical University,No.2017FE467(-132)the Talent Introduction Project of Hubei Polytechnic University,No.21xjz34R。
文摘BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical value.AIM To identify potential DNA methylation markers specific to ADE and CRC.METHODS Here,we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.RESULTS Comparing 22 CRC and 25 ADE samples,global methylation was higher in the former,but both showed similar methylation patterns regarding differentially methylated gene positions,chromatin signatures,and repeated elements.High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC.Combined with RNA-seq gene expression data,we identified 14 methylation-regulated differentially expressed genes,of which only AGTR1 and NECAB1 methylation had prognostic significance.CONCLUSION Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC,suggesting prognostic biomarkers for CRC.
基金Supported by the National Natural Science Foundation of China,No.81960100Applied Basic Foundation of Yunnan Province,No.202001AY070001-192+2 种基金Young and Middle-aged Academic and Technical Leaders Reserve Talents Program in Yunnan Province,No.202305AC160018Yunnan Revitalization Talent Support Program,No.RLQB20200004 and No.RLMY20220013and Yunnan Health Training Project of High-Level Talents,No.H-2017002。
文摘BACKGROUND Pyroptosis impacts the development of malignant tumors,yet its role in colorectal cancer(CRC)prognosis remains uncertain.AIM To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration.METHODS Gene expression data were obtained from The Cancer Genome Atlas(TCGA)and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus(GEO).Pyroptosis-related gene expression in cell clusters was analyzed,and enrichment analysis was conducted.A pyroptosis-related risk model was developed using the LASSO regression algorithm,with prediction accuracy assessed through K-M and receiver operating characteristic analyses.A nomo-gram predicting survival was created,and the correlation between the risk model and immune infiltration was analyzed using CIBERSORTx calculations.Finally,the differential expression of the 8 prognostic genes between CRC and normal samples was verified by analyzing TCGA-COADREAD data from the UCSC database.RESULTS An effective pyroptosis-related risk model was constructed using 8 genes-CHMP2B,SDHB,BST2,UBE2D2,GJA1,AIM2,PDCD6IP,and SEZ6L2(P<0.05).Seven of these genes exhibited differential expression between CRC and normal samples based on TCGA database analysis(P<0.05).Patients with higher risk scores demonstrated increased death risk and reduced overall survival(P<0.05).Significant differences in immune infiltration were observed between low-and high-risk groups,correlating with pyroptosis-related gene expression.CONCLUSION We developed a pyroptosis-related prognostic model for CRC,affirming its correlation with immune infiltration.This model may prove useful for CRC prognostic evaluation.
基金This research was supported by grants from the Shanghai Municipal Health Commission(SMHC)(2019ZB0201)Shanghai Clinical Research Center for Mental Health(19MC1911100)SMHC Clinical Research Center(CRC2018ZD03).
文摘Background Obsessive-compulsive disorder(OCD)is considered a very debilitating disorder with severe loss of quality of life and income.Aims This study estimates the quality of life and economic consequences of OCD in China.Methods The research team interviewed 639 patients with OCD in 13 hospitals in 12 cities in China.The direct method was used to get the direct cost of OCD.Indirect costs associated with OCD were estimated using the human capital approach.Linear regression analysis was conducted for quality of life and generalised linear model analysis was conducted for total cost.Sensitivity analysis was used to analyse the uncertainty of total cost.Results The mean quality of life score for OCD was 52.78(20.46).The annual total cost of OCD per capita was 24503.78(95%CI:22621.53 to 26386.03)renminbi(RMB)(US$3465.88(95%CI:US$3199.65 to US$3732.11)).The annual cost of OCD in China was estimated to be 37.74 billion(95%CI:34.95 billion to 40.53 billion)RMB(equal to US$5.34 billion(95%CI:US$4.94 billion to US$5.73 billion)).Sensitivity analysis showed that the total annual cost of OCD in China was between 23.15 billion RMB(US$3.27 billion)and 370.00 billion RMB(US$52.33 billion).Worse social function status,more psychiatric symptoms and higher Yale Brown Obsessive-Compulsive Scale(Y-BOCS)score were associated with worse quality of life.The numbers of clinic visits and hospitalisations,socioeconomic status,education,Y-BOCS scores and age were found to be significantly associated with total cost.Conclusions OCD is associated with low quality of life and high costs in China.The findings call for concerted efforts to improve services for patients with OCD.Improvements may include early detection and diagnosis,the provision of evidence-based treatments and relapse prevention strategies.
基金National Natural Science Foundation of China(General Program),No.31620103910National Natural Science Foundation of China(Key Program),No.81874181+3 种基金National Health Commission of China,No.2019ZX09301158Shanghai Municipal Commission of Economy and Informatization,No.2019RGZN01096Shanghai Shenkang Hospital Development Center,No.12018107and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.19XHCR13D.
文摘BACKGROUND Whether regional lymphadenectomy(RL)should be routinely performed in patients with T1b gallbladder cancer(GBC)remains a subject of debate.AIM To investigate whether RL can improve the prognosis of patients with T1b GBC.METHODS We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China.The logrank test and Cox proportional hazards model were used to compare the overall survival(OS)of patients who underwent cholecystectomy(Ch)+RL and those who underwent Ch only.To investigate whether combined hepatectomy(Hep)improved OS in T1b patients,we studied patients who underwent Ch+RL to compare the OS of patients who underwent combined Hep and patients who did not.RESULTS Of the 121 patients(aged 61.9±10.1 years),77(63.6%)underwent Ch+RL,and 44(36.4%)underwent Ch only.Seven(9.1%)patients in the Ch+RL group had lymph node metastasis.The 5-year OS rate was significantly higher in the Ch+RL group than in the Ch group(76.3%vs 56.8%,P=0.036).Multivariate analysis showed that Ch+RL was significantly associated with improved OS(hazard ratio:0.51;95%confidence interval:0.26-0.99).Among the 77 patients who underwent Ch+RL,no survival improvement was found in patients who underwent combined Hep(5-year OS rate:79.5%for combined Hep and 76.1%for no Hep;P=0.50).CONCLUSION T1b GBC patients who underwent Ch+RL had a better prognosis than those who underwent Ch.Hep+Ch showed no improvement in prognosis in T1b GBC patients.Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines,RL was only performed in 63.6%of T1b GBC patients.Routine Ch+RL should be advised in T1b GBC.
基金the Wuhan University Medical Faculty Innovation Seed Fund Cultivation Project(No.TFZZ2018025)the Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province(No.CXPJJH12000001-2020313)the National Natural Science Foundation of China(No.81670123 and No.81670144).
文摘Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities.Olfactory receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods Clinical and molecular information from The Cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for immunotherapy.The Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation cohorts.Results OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal programs.Compared to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related proteins.The clustering performed well in the internal and 5 external validation cohorts.Based on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment response.In addition,the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients.The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts.Conclusion Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC.ORIGs can be applied to molecularly stratify patients,and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.
基金funded by the Department of Education of Yunnan Province(No.2021J0244).
文摘Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.
基金This study was funded by Shanghai Science and Technology Committee(grant no.20ZR1448500,YDZX20213100001003,22YF1439100)the National Natural Science Foundation of China(grant no.82201678).
文摘Background Non-suicidal self-injury(NSSI)is a frequent and prominent phenomenon in major depressive disorder(MDD).Even though its prevalence and risk factors are relatively well understood,the potential mechanisms of NSSI in MDD remain elusive.Aims To review present evidence related to the potential mechanisms of NSSI in MDD.Methods According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines,articles for this systematic review were searched on Medline(through PubMed),Embase(through Elsevier),PsycINFO(through OVID)and Web of Science databases for English articles,as well as China National Knowledge Infrastructure(CNKI),SinoMed,Wanfang Data,and the Chongqing VIP Chinese Science and Technology Periodical(VIP)Databases for Chinese articles published from the date of inception to 2 August 2022.Two researchers(BW,HZ)independently screened studies based on inclusion and exclusion criteria and assessed their quality.Results A total of 25157 studies were searched.Only 25 of them were ultimately included,containing 3336 subjects(1535 patients with MDD and NSSI,1403 patients with MDD without NSSI and 398 HCs).Included studies were divided into 6 categories:psychosocial factors(11 studies),neuroimaging(8 studies),stress and hypothalamic-pituitary-adrenal(HPA)axis(2 studies),pain perception(1 study),electroencephalogram(EEG)(2 studies)and epigenetics(1 study).Conclusions This systematic review indicates that patients with MDD and NSSI might have specific psychosocial factors,aberrant brain functions and neurochemical metabolisms,HPA axis dysfunctions,abnormal pain perceptions and epigenetic alterations.
基金National Natural Science Foundation of China (No.8176011)。
文摘In recent years,the relationship between intestinal flora and liver disease has become an important research direction of liver diseases.A growing body of evidence indicates that gut bacteria play a key role in the pathophysiology of liver disease,this article combed the at home and abroad in recent years,the changes of intestinal flora and autoimmune liver disease,alcoholic liver disease,fatty liver disease related to metabolism,hepatitis b viral hepatitis,cirrhosis and liver cancer occurrence and progress of relationship of related research,And the new progress of regulating intestinal microecology in the treatment of liver diseases.Dysregulation of intestinal flora plays an important role in the occurrence and development of liver diseases.Regulating intestinal flora to improve the prognosis of liver diseases will be an important development direction in the future.
基金Supported by Santen Pharmaceutical(China)Co.,Ltd.
文摘AIM:To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension(OH)in clinical practice in China.METHODS:This post-marketing observational study included patients who received tafluprost to lower intraocular pressure(IOP)within 30d between September 2017 and March 2020 in 20 hospitals in China.Adverse drug reactions(ADRs)during tafluprost treatment and within 30d after the treatment were collected.RESULTS:A total of 2544 patients were included in this study,of them 58.5%(1488/2544)had primary open angle glaucoma(POAG),21.9%(556/2544)had OH and 19.7%(500/2544)used tafluprost for other reasons.Of 359 ADRs occurred in 10.1%(258/2544)patients,and no serious adverse event occurred.The most common ADR was conjunctival hyperemia(128 ADRs in 124 patients,4.9%).Totally 1670 participants(65.6%)combined tafluprost with carbonic anhydrase inhibitors(CAIs;37.1%,620/1670),sympathomimetics(33.5%,559/1670),β-blockers(33.2%,555/1670),other prostaglandin analogs(PGAs;15.6%,260/1670)and other eye drops(15.1%,253/1670).The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs(23 ADRs in 23 patients,8.8%,23/260)and the lowest was in combination with CAIs(16 ADRs in 16 patients,2.6%,16/620).Tafluprost was applied in primary angle-closure glaucoma(41.6%,208/500),after glaucoma surgery(17.8%,89/500)and after non-glaucoma surgery(15.8%,79/500).CONCLUSION:Tafluprost is safe for POAG and OH,and tolerable when combined with other eye drops and under various clinical circumstances.
基金supported by the Major Special Project of Scientific Research Fund of Yunnan Provincial Education Department of China,No.zd2012001
文摘Electroacupuncture for the treatment of spinal cord injury has a good clinical curative effect, but the underlying mechanism is unclear. In our experiments, the spinal cord of adult Sprague-Dawley rats was clamped for 60 seconds. Dazhui(GV14) and Mingmen(GV4) acupoints of rats were subjected to electroacupuncture. Enzyme-linked immunosorbent assay revealed that the expression of serum inflammatory factors was apparently downregulated in rat models of spinal cord injury after electroacupuncture. Hematoxylin-eosin staining and immunohistochemistry results demonstrated that electroacupuncture contributed to the proliferation of neural stem cells in rat injured spinal cord, and suppressed their differentiation into astrocytes. Real-time quantitative PCR and western blot assays showed that electroacupuncture inhibited activation of the Notch signaling pathway induced by spinal cord injury. These findings indicate that electroacupuncture repaired the injured spinal cord by suppressing the Notch signaling pathway and promoting the proliferation of endogenous neural stem cells.
文摘AIM: To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus (HBV) replication in different clinical stages of chronic HBV infection.METHODS: A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages: immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. SerumHBV DNA load was assessed by quantitative real-time polymerase chain reaction.RESULTS: CD8+ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages (36.87 ± 7.58 vs 34.37 ± 9.07, 36.87 ± 7.58 vs 28.09 ± 5.64, P < 0.001). The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8+ T-cells than CD4+ T-cells (36.87 ± 7.58 vs 30.23 ± 6.35, 34.37 ± 9.07 vs 30.92 ± 7.40, P < 0.01), whereas the peripheral blood in patients at the immune-inactive carrier stage and in normal controls contained less CD8+ T-cells than CD4+ T-cells (28.09 ± 5.64 vs 36.85 ± 6.06, 24.02 ± 4.35 vs 38.94 ± 3.39, P < 0.01). ANOVA linear trend test showed that CD8+ T-cells were signif icantly increased in patients with a high viral load (39.41 ± 7.36, 33.83 ± 7.50, 31.81 ± 5.95 and 26.89 ± 5.71, P < 0.001), while CD4+ T-cells were signif icantly increased in patients with a low HBV DNA load (37.45 ± 6.14, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P < 0.001). Multiple regression analysis displayed that log copies of HBV DNA still maintained its highly signif icant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3+, CD4+ and CD8+ cells and CD4+/CD8+ ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation.CONCLUSION: Differences in peripheral T-cell subpopulation profi les can be found in different clinical stages of chronic HBV infection. T-cell impairment is signifi cantly associated with HBV load.
文摘AIM: To investigate peripheral T-lymphocyte sub-population profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB).METHODS: Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction (PCR). The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed.RESULTS: CHB patients had significantly decreased CD3+ and CD4+ cells and CD4+/CD8+ ratio, and increased CD8+ cells compared with uninfected controls (55.44 ± 12.39 vs 71.07 ± 4.76, 30.92 ± 7.48 vs 38.94 ± 3.39, 1.01 ± 0.49 vs 1.67 ± 0.33, and 34.39 ± 9.22 vs 24.02 ± 4.35; P < 0.001, respectively). Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load, presence of serum hepatitis B e antigen (HBeAg) expression, liver disease severity, history of maternal HBV infection, and young age at HBV infection, all with P < 0.01. There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations (linear trend test P < 0.001). There was a negative correlation between the levels of CD3+ and CD4+ cells and CD4+/CD8+ ratio and serum level of viral load in CHB patients (r = -0.68, -0.65 and -0.75, all P < 0.0001), and a positive correlation between CD8+ cells and viral load (r = 0.70, P < 0.0001). There was a significant decreasing trend in CD3+ and CD4+ cells and CD4+/CD8+ ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection (linear trend test P < 0.01). In multiple regression (after adjustment for age at HBV infection, maternal HBV infection status and hepatocyte damage severity) log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations, and was the strongest predictor of variation in CD3+, CD4+, CD8+ cells and CD4+/CD8+ ratio. However, the effect of HBeAg was not significant.CONCLUSION: T-lymphocyte failure was signifi-cantly associated with viral replication level. The substantial linear dose-response relationship and strong independent predictive effect of viral load on T-lymphocyte subpopulations suggests the possibility of a causal relationship between them, and indicates the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients.
文摘AIM: To evaluate whether sorafenib use after resection impacts tumor relapse and survival in Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC).METHODS: This retrospective study enrolled 36 male BCLC stage C HCC patients with portal vein thrombus and Child-Pugh class A liver function. Twentyfour patients received only surgical resection(SR), and 12 patients received oral sorafenib within 30 d after surgery. The primary outcomes were time to progression(TTP)(the time from surgical resection until HCC recurrence or extrahepatic metastases) and overall survival(OS). The secondary outcome was the rate of postoperative recurrence or metastasis. TTP and OS were analyzed using Kaplan Meier curves.RESULTS: There were no significant differences between the two groups in the serum levels of alpha-fetoprotein, copies of hepatitis B virus-DNA, preoperative laboratory results, degree of hepatic fibrosis, types of portal vein tumor thrombus, number of satellite lesions, tumor diameter, pathological results, volume of blood loss, volume of blood transfusion, or surgery time(all P > 0.05). Patients in the SR + sorafenib group had a significantly longer TTP(29 mo vs 22 mo, P = 0.041) and a significantly longer medianOS(37 mo vs 30 mo, P = 0.01) compared to patients in the SR group. The SR group had 18 cases(75%) of recurrence/metastasis while the SR + sorafenib group had six cases(50%) of recurrence/metastasis. A total of 19 patients died after surgery(five in the SR + sorafenib group and 14 in the SR group). The most common sorafenib-related adverse events were skin reactions, diarrhea, and hypertension, all of which were resolved with treatment.CONCLUSION: Sorafenib after SR was well-tolerated. Patients who received sorafenib after SR had better outcomes compared to patients who received only SR.
基金supported by a grant from Yun Nan province united foundation(2008CD006)Yun Nan province education department foundation(2011y184)
文摘Objective:To investigate the effect of BMSCs transplantation plus hyperbaric oxygen(HBO)on repair of rat SCI.Methods:Seventy five male rats were divided randomly into five groups:sham,vehicle.BMSCs transplantation group,combination group,15 rats in each group.Every week after the SCI onset,all animals were evaluated for behavior outcome by Basso-BeattleBresnahan(BBB) score and inclined plane test.Axon recovery was examined with focal spinal cord tissue by electron microscope at 6 weeks after the SCI onset.HE staining and BrdU staining were performed to examine the BMSCs and lesion post injury.Somatosensory evoked potential(SEP) testing was performed to detect the recovery of neural conduction.Results from the behavior tests from combination group were significant higher than rats which received only transplantation or HBO treatment.Results from histopathology showed favorable recovery from combination group than other treatment groups.The number of BrdU+ in combination group were measureable more than transplantation group(P<0.05).The greatest decrease in TNF-α,IL-1β,IL-6.IFN-α determined by Elisa assay in combination group were evident too.Conclusions:BMSCs transplantation can promote the functional recovery of rat hind limbs after SCI,and its combination with HBO has a synergistic effect.
文摘An efficient screening assay was developed and validated for simultaneous assessment of compound-mediated inhibition of six major human cytochrome P450(CYP) enzymes.This method employed a cocktail of six probe substrates(i.e.,phenacetin.amodiaquine.diclofenac,S-mephenytoin,dextromethorphan and midazolam for CYP1A2,2C8.2C9,2C19,2D6 and 3A4.respectively) as well as individual prototypical inhibitors of the six CYP enzymes in human liver microsomes under optimized incubation conditions.The corresponding marker metabolites(i.e.,acetaminophen,N-deselhylamodiaquine,4-OH-diclofenac.4-OH-Smephenytoin,dextrorphan and 1-OH-midazolam) in the incubates were quantified using LC-MS/MS methods either by an internal standaid(IS) calibration curve or a simplified analyte-to-IS peak area ratio approach.The results showed that the IC_(50) values determined by the cocktail approach were in good agreement with those obtained by the individual substrate approach as well as those reported in the literature.Besides,no remarkable difference was observed between the two quantification approaches.In conclusion,this new cocktail assay can be used for reliable screening of compound-mediated CYP inhibition.
基金supported by grants from the Youth Foundation of Luzhou Medical College of Luzhou City of Sichuan Province of China,No.[2010]108the Talent Fund of the Affiliated Hospital of Luzhou Medical College of Luzhou City of Sichuan Province of China,No.[2011]43
文摘Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase(JNK) participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by photocoagulation using the laser ignition method. Results showed significant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 m RNA expression in the retina. These data indicated that the increased expression of JNK3 m RNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.
基金supported by the National Natural Science Foundation of China,No.81960242(to XLY)Yunnan Applied Basic Research Project of Yunnan Province of China,Nos.2019FE001-048(to XLY),202001AT070001(to XLY),“One Hundred Young and Middle-aged Academic and Technical Backbone”Training Program of Kunming Medical University,No.60118260105(to XLY)Miaozi Project in Science and Technology Innovation Program of Sichuan Province,No.2020JDRC0057(to HYH).
文摘Inflammatory responses,including glial cell activation and peripheral immune cell infiltration,are involved in the pathogenesis of Parkinson’s disease(PD).These inflammatory responses appear to be closely related to the release of extracellular vesicles,such as exosomes.However,the relationships among different forms of glial cell activation,synuclein dysregulation,mitochondrial dysfunction,and exosomes are complicated.This review discusses the multiple roles played by exosomes in PD-associated inflammation and concludes that exosomes can transport toxicα-synuclein oligomers to immature neurons and into the extracellular environment,inducing the oligomerization ofα-synuclein in normal neurons.Misfoldedα-synuclein causes microglia and astrocytes to activate and secrete exosomes.Glial cell-derived exosomes participate in communications between glial cells and neurons,triggering anti-stress and anti-inflammatory responses,in addition to axon growth.The production and release of mitochondrial vesicles and exosomes establish a new mechanism for linking mitochondrial dysfunction to systemic inflammation associated with PD.Given the relevance of exosomes as mediators of neuron-glia communication in neuroinflammation and neuropathogenesis,new targeted treatment strategies are currently being developed that use these types of extracellular vesicles as drug carriers.Exosome-mediated inflammation may be a promising target for intervention in PD patients.
文摘AIM: To observe the efficiency and safety of thymosin-α1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis. METHODS: Sixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-α1, twice a week (T-α1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-α) each day for fifteen days, then three times weekly (IFN-α group) for six months. The results between two groups treated with and the group untreated with IFN-α which was followed up for 12 mo (historical control group consisting of 30 patients) were compared, and three groups were comparable between each other (P > 0.05) at baseline (age, sex, clinical history, biochemical, and serological parameters). RESULTS: At the end of treatment, complete response, which was defined as alanine aminotransferase (ALT) normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 (31.0%) patients in the T-α1 group and in 15 of 33 (45.5%) patients in the IFN-α group (c2 = 1.36, P >0.05). After a follow-up period of six months, a complete response was observed in 14 of 29 (48.3%) patients in the T-α1 group and in 9 of 33 (27.3%) patients in the IFN-α group (c2 = 2.93, P > 0.05). Compared with the results observed in the historical control (HC) group untreated with IFN-α which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-α group at the end of therapy (1 of 30 vs 15 of 33, c2 = 14.72, P < 0.001) and in the T-α1 group at the end of follow-up (1 of 30 vs 14 of 29, c2 = 15.71, P < 0.001). In T-α1 and IFN-α treatment groups, the area under (the plasma concentration time) curve (AUC) of negative HBV DNA and HBeAg was 34%, 17%, 31% and 19% smaller than that in the HC group. By the end of the follow- up period, the proportions of ALT normalization and negative HBV DNA in the T-α1 group were significantly higher than those in the IFN-α and HC groups. The odds of ALT normalization and negative HBV DNA at the end of the follow-up was three-fold higher in the T-α1 group than in the IFN-α group. Unlike IFN-α, T-α1 was well tolerated by all patients, and no side effects appeared in T-α1 group.CONCLUSION: The results suggest that a 6-mo course of T-α1 therapy is effective and safe in patients with chronic hepatitis B. T-α1 is able to reduce HBV replication in patients with chronic hepatitis B. Furthermore, T-α1 is better tolerated than IFN-α and can gradually induce more sustained ALT normalization and HBV DNA and HBeAg loss. However, a response rate of 48.3% is still less ideal. A more effective therapeutic approach warrants further study.