Gender disparities and woman-specific trends in Barrett’s esophagus in the United States:An 11-year nationwide populationbased study

BACKGROUND Barrett's esophagus(BE)is a known premalignant precursor to esophageal adenocarcinoma(EAC).The prevalence rates continue to rise in the United States,but many patients who are at risk of EAC are not screened.Current practice guidelines include male gender as a predisposing factor for BE and EAC.The population-based clinical evidence regarding female gender remains limited.AIM To study comparative trends of gender disparities in patients with BE in the United States.METHODS A nationwide retrospective study was conducted using the 2009-2019 National Inpatient Sample(NIS)database.Patients with a primary or secondary diagnosis code of BE were identified.The major outcome of interest was determining the gender disparities in patients with BE.Trend analysis for respective outcomes for females was also reported to ascertain any time-based shifts.RESULTS We identified 1204190 patients with BE for the study period.Among the included patients,717439(59.6%)were men and 486751(40.4%)were women.The mean age was higher in women than in men(67.1±0.4 vs 66.6±0.3 years,P<0.001).The rate of BE per 100000 total NIS hospitalizations for males increased from 144.6 in 2009 to 213.4 in 2019(P<0.001).The rate for females increased from 96.8 in 2009 to 148.7 in 2019(P<0.001).There was a higher frequency of obesity among women compared to men(17.4%vs 12.6%,P<0.001).Obesity prevalence among females increased from 12.3%in 2009 to 21.9%in 2019(P<0.001).A lower prevalence of smoking was noted in women than in men(20.8%vs 35.7%,P<0.001).However,trend analysis showed an increasing prevalence of smoking among women,from 12.9%in 2009 to 30.7%in 2019(P<0.001).Additionally,there was a lower prevalence of alcohol abuse,Helicobacter pylori(H.pylori),and diabetes mellitus among females than males(P<0.001).Trend analysis showed an increasing prevalence of alcohol use disorder and a decreasing prevalence of H.pylori and diabetes mellitus among women(P<0.001).CONCLUSION The prevalence of BE among women has steadily increased from 2009 to 2019.The existing knowledge concerning BE development has historically focused on men,but our findings show that the risk in women is not insignificant.

Autologous hematopoietic stem cell transplantation conditioning regimens and chimeric antigen receptor T cell therapy in various diseases

Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malignancies;however,despite being efficacious in various instances,negative consequences have also been recorded.Multiple conditioning regimens were extracted from various literature searches from databases like PubMed,Google scholar,EMBASE,and Cochrane.Conditioning regimens for each disease were compared by using various end points such as overall survival(OS),progression free survival(PFS),and leukemia free survival(LFS).Variables were presented on graphs and analyzed to conclude a more efficacious conditioning regimen.In multiple myeloma,the most effective regimen was high dose melphalan(MEL)given at a dose of 200/mg/m2.The comparative results of acute myeloid leukemia were presented and the regimens that proved to be at an admirable position were busulfan(BU)+MEL regarding OS and BU+VP16 regarding LFS.In case of acute lymphoblastic leukemia(ALL),BU,fludarabine,and etoposide(BuFluVP)conferred good disease control not only with a paramount improvement in survival rate but also low risk of recurrence.However,for ALL,chimeric antigen receptor(CAR)T cell therapy was preferred in the context of better OS and LFS.With respect to Hodgkin’s lymphoma,mitoxantrone(MITO)/MEL overtook carmustine,VP16,cytarabine,and MEL in view of PFS and vice versa regarding OS.Non-Hodgkin’s lymphoma patients were administered MITO(60 mg/m2)and MEL(180 mg/m2)which showed promising results.Lastly,amyloidosis was considered,and the regimen that proved to be competent was MEL 200(200 mg/m2).This review article demonstrates a comparison between various conditioning regimens employed in different diseases.

Sedation reversal trends at outpatient ambulatory endoscopic center vs in-hospital ambulatory procedure center using a triage protocol

BACKGROUND Routine outpatient endoscopy is performed across a variety of outpatient settings.A known risk of performing endoscopy under moderate sedation is the potential for over-sedation,requiring the use of reversal agents.More needs to be reported on rates of reversal across different outpatient settings.Our academic tertiary care center utilizes a triage tool that directs higher-risk patients to the in-hospital ambulatory procedure center(APC)for their procedure.Here,we report data on outpatient sedation reversal rates for endoscopy performed at an inhospital APC vs at a free-standing ambulatory endoscopy digestive health center(AEC-DHC)following risk stratification with a triage tool.AIM To observe the effect of risk stratification using a triage tool on patient outcomes,primarily sedation reversal events.METHODS We observed all outpatient endoscopy procedures performed at AEC-DHC and APC from April 2013 to September 2019.Procedures were stratified to their respective sites using a triage tool.We evaluated each procedure for which sedation reversal with flumazenil and naloxone was recorded.Demographics and characteristics recorded include patient age,gender,body mass index(BMI),American Society of Anesthesiologists(ASA)classification,procedure type,and reason for sedation reversal.RESULTS There were 97366 endoscopic procedures performed at AEC-DHC and 22494 at the APC during the study period.Of these,17 patients at AEC-DHC and 9 at the APC underwent sedation reversals(0.017%vs 0.04%;P=0.06).Demographics recorded for those requiring reversal at AEC-DHC vs APC included mean age(53.5±21 vs 60.4±17.42 years;P=0.23),ASA class(1.66±0.48 vs 2.22±0.83;P=0.20),BMI(27.7±6.7 kg/m^(2) vs 23.7±4.03 kg/m^(2);P=0.06),and female gender(64.7%vs 22%;P=0.04).The mean doses of sedative agents and reversal drugs used at AEC-DHC vs APC were midazolam(5.9±1.7 mg vs 8.9±3.5 mg;P=0.01),fentanyl(147.1±49.9μg vs 188.9±74.1μg;P=0.10),flumazenil(0.3±0.18μg vs 0.17±0.17μg;P=0.13)and naloxone(0.32±0.10 mg vs 0.28±0.12 mg;P=0.35).Procedures at AEC-DHC requiring sedation reversal included colonoscopies(n=6),esophagogastroduodenoscopy(EGD)(n=9)and EGD/colonoscopies(n=2),whereas APC procedures included EGDs(n=2),EGD with gastrostomy tube placement(n=1),endoscopic retrograde cholangiopancreatography(n=2)and endoscopic ultrasound's(n=4).The indications for sedation reversal at AEC-DHC included hypoxia(n=13;76%),excessive somnolence(n=3;18%),and hypotension(n=1;6%),whereas,at APC,these included hypoxia(n=7;78%)and hypotension(n=2;22%).No sedation-related deaths or long-term post-sedation reversal adverse outcomes occurred at either site.CONCLUSION Our study highlights the effectiveness of a triage tool used at our tertiary care hospital for risk stratification in minimizing sedation reversal events during outpatient endoscopy procedures.Using a triage tool for risk stratification,low rates of sedation reversal can be achieved in the ambulatory settings for EGD and colonoscopy.

Predicting short-term thromboembolic risk following Roux-en-Y gastric bypass using supervised machine learning

BACKGROUND Roux-en-Y gastric bypass(RYGB)is a widely recognized bariatric procedure that is particularly beneficial for patients with class III obesity.It aids in significant weight loss and improves obesity-related medical conditions.Despite its effectiveness,postoperative care still has challenges.Clinical evidence shows that venous thromboembolism(VTE)is a leading cause of 30-d morbidity and mortality after RYGB.Therefore,a clear unmet need exists for a tailored risk assessment tool for VTE in RYGB candidates.AIM To develop and internally validate a scoring system determining the individualized risk of 30-d VTE in patients undergoing RYGB.METHODS Using the 2016–2021 Metabolic and Bariatric Surgery Accreditation Quality Improvement Program,data from 6526 patients(body mass index≥40 kg/m^(2))who underwent RYGB were analyzed.A backward elimination multivariate analysis identified predictors of VTE characterized by pulmonary embolism and/or deep venous thrombosis within 30 d of RYGB.The resultant risk scores were derived from the coefficients of statistically significant variables.The performance of the model was evaluated using receiver operating curves through 5-fold cross-validation.RESULTS Of the 26 initial variables,six predictors were identified.These included a history of chronic obstructive pulmonary disease with a regression coefficient(Coef)of 2.54(P<0.001),length of stay(Coef 0.08,P<0.001),prior deep venous thrombosis(Coef 1.61,P<0.001),hemoglobin A1c>7%(Coef 1.19,P<0.001),venous stasis history(Coef 1.43,P<0.001),and preoperative anticoagulation use(Coef 1.24,P<0.001).These variables were weighted according to their regression coefficients in an algorithm that was generated for the model predicting 30-d VTE risk post-RYGB.The risk model's area under the curve(AUC)was 0.79[95%confidence interval(CI):0.63-0.81],showing good discriminatory power,achieving a sensitivity of 0.60 and a specificity of 0.91.Without training,the same model performed satisfactorily in patients with laparoscopic sleeve gastrectomy with an AUC of 0.63(95%CI:0.62-0.64)and endoscopic sleeve gastroplasty with an AUC of 0.76(95%CI:0.75-0.78).CONCLUSION This simple risk model uses only six variables to assist clinicians in the preoperative risk stratification of RYGB patients,offering insights into factors that heighten the risk of VTE events.

Statins decrease the risk of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease:A systematic review and meta-analysis

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma(HCC).Recent clinical evidence indicates the potential benefits of statins in cancer chemoprevention and therapeutics.However,it is still unclear if these drugs can lower the specific risk of HCC among patients with MASLD.AIM To investigate the impact of statin use on the risk of HCC development in patients with MASLD.METHODS A systematic review and meta-analysis of all the studies was performed that measured the effect of statin use on HCC occurrence in patients with MASLD.The difference in HCC risk between statin users and non-users was calculated among MASLD patients.We also evaluated the risk difference between lipophilic versus hydrophilic statins and the effect of cumulative dose on HCC risk reduction.RESULTS A total of four studies consisting of 291684 patients were included.MASLD patients on statin therapy had a 60%lower pooled risk of developing HCC compared to the non-statin group[relative risk(RR)=0.40,95%CI:0.31-0.53,I2=16.5%].Patients taking lipophilic statins had a reduced risk of HCC(RR=0.42,95%CI:0.28-0.64),whereas those on hydrophilic statins had not shown the risk reduction(RR=0.57,95%CI:0.27-1.20).The higher(>600)cumulative defined daily doses(cDDD)had a 70%reduced risk of HCC(RR=0.30,95%CI:0.21-0.43).There was a 29%(RR=0.71,95%CI:0.55-0.91)and 43%(RR=0.57,95%CI:0.40-0.82)decreased risk in patients receiving 300-599 cDDD and 30-299 cDDD,respectively.CONCLUSION Statin use lowers the risk of HCC in patients with MASLD.The higher cDDD and lipophilicity of statins correlate with the HCC risk reduction.

Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has posed a major public health concern worldwide.Patients with comorbid conditions are at risk of adverse outcomes following COVID-19.Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection.It could lead to higher rates of inpatient complications and mortality in this patient population.However,studies on COVID-19 outcomes in liver transplant(LT)recipients have yielded inconsistent findings.AIM To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States.METHODS We conducted a retrospective cohort study using the 2019–2020 National Inpatient Sample database.Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classi-fication of Diseases,Tenth Revision coding system.The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic.Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients.RESULTS A total of 15720 hospitalized LT recipients were included.Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection.In both cohorts,the median admission age was 57 years.The linear trends for LT hospitalizations did not differ significantly before and during the pandemic(P=0.84).The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020.Compared to the pre-pandemic period,a higher association was noted between LT recipients and in-hospital mortality during the pandemic,with an odds ratio(OR)of 1.69[95% confidence interval(CI):1.55-1.84),P<0.001].The frequency of transplant rejections among hospitalized LT recipients increased from 0.2%to 3.6% between January 2019 and December 2020.LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic[OR:1.53(95%CI:1.26-1.85),P<0.001].CONCLUSION The hospitalization rates for LT recipients were comparable before and during the pandemic.Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.

Early versus delayed necrosectomy in pancreatic necrosis:A population-based cohort study on readmission,healthcare utilization,and in-hospital mortality

BACKGROUND Acute necrotizing pancreatitis is a severe and life-threatening condition.It poses a considerable challenge for clinicians due to its complex nature and the high risk of complications.Several minimally invasive and open necrosectomy procedures have been developed.Despite advancements in treatment modalities,the optimal timing to perform necrosectomy lacks consensus.AIM To evaluate the impact of necrosectomy timing on patients with pancreatic necrosis in the United States.METHODS A national retrospective cohort study was conducted using the 2016-2019 Nationwide Readmissions Database.Patients with non-elective admissions for pancreatic necrosis were identified.The participants were divided into two groups based on the necrosectomy timing:The early group received intervention within 48 hours,whereas the delayed group underwent the procedure after 48 hours.The various intervention techniques included endoscopic,percutaneous,or surgical necrosectomy.The major outcomes of interest were 30-day readmission rates,healthcare utilization,and inpatient mortality.RESULTS A total of 1309 patients with pancreatic necrosis were included.After propensity score matching,349 cases treated with early necrosectomy were matched to 375 controls who received delayed intervention.The early cohort had a 30-day readmission rate of 8.6% compared to 4.8%in the delayed cohort(P=0.040).Early necrosectomy had lower rates of mechanical ventilation(2.9%vs 10.9%,P<0.001),septic shock(8%vs 19.5%,P<0.001),and in-hospital mortality(1.1%vs 4.3%,P=0.01).Patients in the early intervention group incurred lower healthcare costs,with median total charges of $52202 compared to$147418 in the delayed group.Participants in the early cohort also had a relatively shorter median length of stay(6 vs 16 days,P<0.001).The timing of necrosectomy did not significantly influence the risk of 30-day readmission,with a hazard ratio of 0.56(95%confidence interval:0.31-1.02,P=0.06).CONCLUSION Our findings show that early necrosectomy is associated with better clinical outcomes and lower healthcare costs.Delayed intervention does not significantly alter the risk of 30-day readmission.

Association between acute peripancreatic fluid collections and early readmission in acute pancreatitis:A propensity-matched analysis

BACKGROUND Patients with acute pancreatitis(AP)frequently experience hospital readmissions,posing a significant burden to healthcare systems.Acute peripancreatic fluid collection(APFC)may negatively impact the clinical course of AP.It could worsen symptoms and potentially lead to additional complications.However,clinical evidence regarding the specific association between APFC and early readmission in AP remains scarce.Understanding the link between APFC and readmission may help improve clinical care for AP patients and reduce healthcare costs.AIM To evaluate the association between APFC and 30-day readmission in patients with AP.METHODS This retrospective cohort study is based on the Nationwide Readmission Database for 2016-2019.Patients with a primary diagnosis of AP were identified.Participants were categorized into those with and without APFC.A 1:1 propensity score matching for age,gender,and Elixhauser comorbidities was performed.The primary outcome was early readmission rates.Secondary outcomes included the incidence of inpatient complications and healthcare utilization.Unadjusted analyses used Mann-Whitney U andχ2 tests,while Cox regression models assessed 30-day readmission risks and reported them as adjusted hazard ratios(aHR).Kaplan-Meier curves and log-rank tests verified readmission risks.RESULTS A total of 673059 patients with the principal diagnosis of AP were included.Of these,5.1%had APFC on initial admission.After propensity score matching,each cohort consisted of 33914 patients.Those with APFC showed a higher incidence of inpatient complications,including septic shock(3.1%vs 1.3%,P<0.001),portal venous thrombosis(4.4%vs 0.8%,P<0.001),and mechanical ventilation(1.8%vs 0.9%,P<0.001).The length of stay(LOS)was longer for APFC patients[4(3-7)vs 3(2-5)days,P<0.001],as were hospital charges($29451 vs$24418,P<0.001).For 30-day readmissions,APFC patients had a higher rate(15.7%vs 6.5%,P<0.001)and a longer median readmission LOS(4 vs 3 days,P<0.001).The APFC group also had higher readmission charges($28282 vs$22865,P<0.001).The presence of APFC increased the risk of readmission twofold(aHR 2.52,95%confidence interval:2.40-2.65,P<0.001).The independent risk factors for 30-day readmission included female gender,Elixhauser Comorbidity Index≥3,chronic pulmonary diseases,chronic renal disease,protein-calorie malnutrition,substance use disorder,depression,portal and splenic venous thrombosis,and certain endoscopic procedures.CONCLUSION Developing APFC during index hospitalization for AP is linked to higher readmission rates,more inpatient complications,longer LOS,and increased healthcare costs.Knowing predictors of readmission can help target high-risk patients,reducing healthcare burdens.

Insight into generation of induced mesenchymal stem cells from induced pluripotent cells

Mesenchymal stem cells(MSCs)have the potential for use in cell-based regenerative therapies.Currently,hundreds of clinical trials are using MSCs for the treatment of various diseases.However,MSCs are low in number in adult tissues;they show heterogeneity depending upon the cell source and exhibit limited proliferative potential and early senescence in in vitro cultures.These factors negatively impact the regenerative potential of MSCs and therefore restrict their use for clinical applications.As a result,novel methods to generate induced MSCs(iMSCs)from induced pluripotent stem cells have been explored.The development and optimization of protocols for generation of iMSCs from induced pluripotent stem cells is necessary to evaluate their regenerative potential in vivo and in vitro.In addition,it is important to compare iMSCs with primary MSCs(isolated from adult tissues)in terms of their safety and efficacy.Careful investigation of the properties of iMSCs in vitro and their long term behavior in animals is important for their translation from bench to bedside.

Racial and gender-based disparities and trends in common psychiatric conditions in liver cirrhosis hospitalizations:A ten-year United States study

BACKGROUND Chronic liver disease is associated with various neuropsychiatric conditions.There are currently no large studies assessing and comparing the prevalence of psy-chiatric illnesses based on patient profiles and the etiology of cirrhosis.AIM To examine the trends of hospitalizations among psychiatric conditions in cirrhosis.METHODS We used the National Inpatient Sample database 2016-2019 for the primary diagnosis of liver cirrhosis.The outcomes included the prevalence,trends,and associations of psychiatric diagnoses in these hospitalizations.Chi-square for categorical variables and the Wilcoxon rank test for continuous variables were utilized.RESULTS The prevalence of generalized anxiety disorder(GAD)in liver cirrhosis hospitalizations increased from 0.17%in 2009 to 0.92%in 2019(P<0.001).The prevalence of depression increased from 7%in 2009 to 12%in 2019(P<0.001).Attention deficit hyperactivity disorder(ADHD)prevalence increased from 0.06%to 0.24%.The prevalence of schizophrenia increased from 0.59%to 0.87%(P<0.001).Schizoaffective disorder prevalence increased from 0.10%to 0.35%(P<0.001).Posttraumatic stress disorder(PTSD)prevalence displayed increasing trends from 0.36%in 2009 to 0.93%in 2019(P<0.001).The prevalence of suicidal ideation increased from 0.23%to 0.56%in 2019.Cirrhosis related to alcoholic liver disease[adjusted odds ratios(aOR)1.18,95%CI 1.08-1.29,P<0.001]and non-alcoholic fatty liver disease(NAFLD)(aOR 1.14,95%CI 1.01-1.28,P=0.025)was associated with depression more than other causes.Alcohol-and NAFLD-associated cirrhosis had a stronger link to psychiatric disorders.Females had a higher association with GAD(aOR 2.56,95%CI 2.14-3.06,P<0.001),depression(aOR 1.78,95%CI 1.71-1.84,P<0.001),bipolar disorder(aOR 1.64,95%CI 1.52-1.77,P<0.001]and chronic fatigue(aOR 2.31,95%CI 1.31-4.07,P<0.001)when compared to males.Blacks,Hispanics,and Asian/Native Americans had a significantly lower association with GAD,depression,bipolar disorder,PTSD,and ADHD when compared to the white race.CONCLUSION The prevalence of psychiatric comorbidities in liver cirrhosis hospitalizations has increased over the last decade.Females had a higher association with psychiatric disorders compared to males.Blacks,Hispanics,and Asian/Native Americans had lower associations with psychiatric comorbidities compared to the white race.

Association between alcohol-associated cirrhosis and inpatient complications among COVID-19 patients:A propensity-matched analysis from the United

BACKGROUND Alcohol-associated cirrhosis(AC)contributes to significant liver-related mortality in the United States.It is known to cause immune dysfunction and coagulation abnormalities.Patients with comorbid conditions like AC are at risk of worse clinical outcomes from coronavirus disease 2019(COVID-19).The specific association between AC and COVID-19 mortality remains inconclusive,given the lack of robust clinical evi-dence from prior studies.AIM To study the predictors of mortality and the outcomes of AC in patients hospitalized with COVID-19 in the United States.METHODS We conducted a retrospective cohort study using the National Inpatient Sample(NIS)database 2020.Patients were identified with primary COVID-19 hospitalizations based on an underlying diagnosis of AC.A matched comparison cohort of COVID-19 patients without AC was identified after 1:N propensity score matching based on baseline sociodemographic characteristics and Elixhauser comorbidities.Primary outcomes included median length of stay,median inpatient charges,and in-hospital mortality.Secondary outcomes included a prevalence of systemic complications.RESULTS A total of 1325 COVID-19 patients with AC were matched to 1135 patients without AC.There was no difference in median length of stay and hospital charges in COVID-19 patients with AC compared to non-AC(P>0.05).There was an increased prevalence of septic shock(5.7%vs 4.1%),ventricular fibrillation/ventricular flutter(0.4%vs 0%),atrial fibrillation(13.2%vs 8.8%),atrial flutter(8.7%vs 4.4%),first-degree atrioventricular nodal block(0.8%vs 0%),upper extremity venous thromboembolism(1.5%vs 0%),and variceal bleeding(3.8%vs 0%)in the AC cohort compared to the non-AC cohort(P<0.05).There was no difference in inpatient mortality in COVID-19 patients with non-AC compared to AC,with an odds ratio of 0.97(95%confidence interval:0.78-1.22,P=0.85).Predictors of mortality included advanced age,cardiac arrhythmias,coagulopathy,protein-calorie malnutrition,fluid and electrolyte disorders,septic shock,and upper extremity venous thromboembolism.CONCLUSION AC does not increase mortality in patients hospitalized with COVID-19.There is an increased association between inpatient complications among COVID-19 patients with AC compared to non-AC.

Network pharmacology analysis combined with experimental verification of the molecular mechanism of Xihuang pill in treating liver cancer

Background:Xihuang pill is a kind of traditional Chinese medicine,which has been widely used in the treatment of kinds of cancer.However,there is still a lack of systematic understanding of the molecular mechanism of Xihuang pill in the treatment of liver cancer.In this work,we aim to explore the molecular mechanism of Xihuang pill in treating liver cancer.Methods:The functional components in Xihuang pill were collected from Traditional Chinese Medicine Database and Analysis Platform.The target genes of these components were also collected using Traditional Chinese Medicine Database and Analysis Platform.The target genes of liver cancer were predicted using GeneCards database.The intersecting genes were then analyzed with Venn diagrams.Kyoto Encyclopedia of Genes and Genomes and Database for Annotation,Visualization,and Integrated Discovery were used to analyze the pathway.Then,cell counting kit-8 was used to measure the half-maximal inhibitory concentration of Xihuang pills.The living dead cell staining method was used to observe the survival of cells.HepG2 cell apoptosis was tested by flow cytometry with fluorescein isothiocyanate/propidium iodide double staining method,and then the mitochondrial damage was also detected by flow cytometry.The expression of target genes was detected by quantitative real-time polymerase chain reaction.Results:A total of 130 compounds and 198 genes were identified as potential active ingredients and putative liver cancer‑related targets.We obtained 1,899 disease targets and 297 transcriptome targets from the database.Six drug-disease intersecting genes,CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3 were obtained.They are enrichment in apoptosis,PI3K-AKT signaling pathway,MAPK signaling pathway,pathways in cancer and p53 signaling pathway.Besides,it was found that the apoptosis rate of the HepG2 cells in Xihuang pill treated group was significantly higher than that of the control group.And the apoptosis rate gradually increased in a dose dependent manner of Xihuang pill treatment.Xihuang pill also induced the mitochondrial membrane potential damage.Compared with the control group,the expression level of CCNB1 and BIRC5 was induced,while the expression level of IGF2 was reduced after Xihuang pill treatment.Conclusion:Xihuang pill may act on six proteins(CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3)and cover multiple pathways to form a therapeutic network to treat liver cancer.

巴基斯坦原发性耐多药结核病流行情况

背景:巴基斯坦是世界第6位结核病高负担国家。据世界卫生组织(WHO)估计,巴基斯坦结核病发病率为181/10万,全国每年新增结核病患者28.6万例。来自于医院的资料表明:巴基斯坦耐多药结核病(MDR-TB)问题已十分严重,急需在社区水平对耐多药结核病的严重程度开展评估。本研究为针对巴基斯坦耐药结核病流行状况开展的横段面研究,所使用的痰标本来自于巴基斯坦全国742例未经治疗的新诊断的肺结核患者。目的:评估巴基斯坦原发性耐药的流行情况结果:在672例痰培养阳性患者中,有76例(11.3%)出现了对1种或多种抗结核药物耐药。36例(5.4%)患者对链霉素(10μg/ml)耐药; 51例(7.6%)患者对异烟肼(1μg/ml)耐药;15例(2.2%)患者对利福平(5μg/ml)耐药;12例(1.8%)患者对乙胺丁醇(10μg/ml)耐药;22例(3.3%)患者对吡嗪酰胺耐药。有46例(6.8%)患者痰标本中分离的结核菌株耐1种抗结核药物, 10例(1.5%)同时耐2种抗结核药物,12例(1.8%)同时耐3种抗结核药物,6例(0.9%)同时耐4种抗结核药物,2例(0.3%)同时耐全部5种抗结核一线药。原发性耐多药率为1.8%,(n= 12)(异烟肼1μg/ml,利福平5μg/ml)。结论:研究结果表明,巴基斯坦原发性耐多药率<2%,需要进一步实施有效的DOTS策略。

Incidence, mortality, and risk factors of immunotherapy-associated hepatotoxicity: A nationwide hospitalization analysis

Background and aims Anti-neoplastic immunotherapy has revolutionized cancer management;however,its safety profile with respect to liver-related injury remains largely unexplored.Herein,we analyzed a United States national database to determine the incidence,mortality,and predictors of hepatotoxicity in the setting of anti-neoplastic immunotherapy.Methods This was a nationwide retrospective study of hospital encounters from 2011 to 2014 using the National Inpatient Sample(NIS)database.We utilized the International Classification of Diseases,Ninth Revision(ICD-9)coding system to identify all adult patients who underwent anti-neoplastic immunotherapy during hospitalization.The primary outcome was the incidence of hepatotoxicity during the same hospitalization.Secondary outcomes included in-hospital mortality as well as socioeconomic and ethno-racial predictors of hepatotoxicity.Analyses were performed using IBM SPSS Statistics 23.0.Results The sample included 3002 patients who underwent inpatient anti-neoplastic immunotherapy.The incidence of hepatotoxicity was 10.1%,which was significantly higher as compared to a matched inpatient population(adjusted odds ratio(aOR)4.93,95%confidence interval(CI):3.80–6.40,P=0.001).No significant mortality difference was seen in those that developed hepatotoxicity compared to those who did not(aOR 0.47,95%CI:0.03–8.03,P=0.612).Age under 60(aOR 1.56,95%CI:1.23–1.78,P=0.050)and white race(aOR 1.85,95%CI:1.35–2.04,P<0.010)were independent risk factors for developing immunotherapy-associated hepatotoxicity.Conclusions In this large,nationwide database analysis,we found that anti-neoplastic immunotherapy was associated with a nearly five-fold risk of in-hospital hepatotoxicity as compared to a matched inpatient population,though without an associated mortality difference.Additionally,younger age and white race were identified as predictors of immunotherapy-associated hepatotoxicity.Heightened vigilance and prospective investigation of the risk factors and liver-related adverse effects of anti-neoplastic immunotherapy are warranted.