Effects of Incretin-based Therapies on Weight-related Indicators among Patients with Type 2 Diabetes: A Network Meta-analysis

Objective To evaluate the effects of incretin-based therapies on body weight as the primary outcome,as well as on body mass index(BMI)and waist circumference(WC)as secondary outcomes.Methods Databases including Medline,Embase,the Cochrane Library,and clinicaltrials.gov(www.clinicaltrials.gov)were searched for randomized controlled trials(RCTs).Standard pairwise meta-analysis and network meta-analysis(NMA)were both carried out.The risk of bias(ROB)tool recommended by the Cochrane handbook was used to assess the quality of studies.Subgroup analysis,sensitivity analysis,meta-regression,and quality evaluation based on the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)were also performed.Results A total of 292 trials were included in this study.Compared with placebo,dipeptidyl-peptidase IV inhibitors(DPP-4 Is)increased weight slightly by 0.31 kg[95%confidence interval(CI):0.05,0.58]and had negligible effects on BMI and WC.Compared with placebo,glucagon-like peptide-1 receptor agonists(GLP-1 RAs)lowered weight,BMI,and WC by-1.34 kg(95%CI:-1.60,-1.09),-1.10 kg/m2(95%CI:-1.42,-0.78),and-1.28 cm(95%CI:-1.69,-0.86),respectively.Conclusion GLP-1 RAs were more effective than DPP-4 Is in lowering the three indicators.Overall,the effects of GLP-1 RAs on weight,BMI,and WC were favorable.

Impact of National Centralized Drug Procurement Policy on Antiviral Utilization and Expenditure for Hepatitis B in China

Background and Aims:The National Centralized Drug Procurement(NCDP)policy was launched in China's Mainland in April 2019,with entecavir(ETV)and tenofovir disoproxil fumarate(TDF)being included in the procurement list.We conducted the current study to investigate the impact of the NCDP policy on the utilization and expenditures of antiviral therapy for chronic hepatitis B(CHB)in China.Methods:Procurement records,including monthly purchase volume,expenditure,and price of nucleos(t)ide analogs(NAs),were derived from the National Healthcare Security Administration from April 2018 to March 2021.The changes in volumes and expenditures of the first-line NAs and bid-winning products were calculated.The effects of price,volume,and structure related to drug expenditure were calculated by the Addis and Magrini(AM)Index System Analysis.Results:The purchase volume of NAs significantly increased from 134.3 to 318.3 million DDDs,whereas the expenditure sharply decreased from 1,623.41 to 490.43 million renminbi(RMB)or 241.94 to 73.09 million US dollars(USD).The proportions of firstline NAs rose from 72.51%(ETV:69.00%,TDF:3.51%)to 94.97%(ETV:77.42%,TDF:17.55%).AM analysis showed that the NCDP policy decreased the expenditure of all NAs(S=0.91)but increased that of the first-line NAs in the bidwinning list(S=1.13).Assuming the population size of CHB patients remains stable and a compliance rate of≥75%,the proportion of CHB patients receiving first-line antiviral therapy would increase from 6.36–8.48%to 11.56–15.41%.Conclusions:The implementation of the NCDP policy significantly increased the utilization of first-line NAs for CHB patients at a lower expenditure.The findings provided evidence for optimizing antiviral therapy strategy and allocating medical resources in China.

Baseline Hepatitis B Virus DNA Level is a Promising Factor for Predicting the 3^rd Month Virological Response to Entecavir Therapy： A Study of Strict Defined Hepatitis B virus Induced Cirrhosis

Background： Cirrhosis is a common complication of chronic hepatitis B. It remains unclear if viral and biochemical parameters at baseline affect virological response to entecavir and therefore warrant investigation. In the present study, we aimed to eval uate the efficacy of entecavir therapy by monitoring virological response at the end of the 3^rd month of treatment and try to figure out whether baseline factors could help predict it in a cohort of hepatitis B virus （HBV） compensated cirrhosis patients and to determine the cut-off value of a predicting parameter.Methods： A total of 91 nucleos（t）ide-naive patients with HBV induced cirrhosis （compensatory stage） were enrolled in a prospective cohort. HBV DNA and alanine aminotransferase （ALT） were tested at baseline and monitored every 3-6 months after starting therapy. Results： Of all 91 patients, the median follow-up time was 12 （9-24） months. Overall, 64 patients （70.3%） achieved virological response in the 3^rd month. Univariate analysis showed that the 3^rd month virological response can be predicted by baseline HBV DNA levels （P 〈 0.001, odds ratio [OR]： 2.13, 95% confidence interval [CI]： 1.44-3.15）, ALT value （P = 0.023, OR： 1.01, 95% CI： 1.00 1.01 ） and hepatitis B e antigen （HBeAg） negativity （P = 0.016, OR： 0.30, 95% CI： 0.11-0.80）. Multiple regression analysis showed baseline H BV DNA level was the only parameter related to full virological response. Higher baseline HBV DNA strata indicated a higher probability that HBV DNA remains detectable at the 3^rd month （P = 0.001）. Area under receiver operating characteristic curve for determining the 3^rd month virological response by baseline HBV DNA was 77.6% （95% CI： 66.7-85.2%）, with a best cut-offvalue of 5.8 log10. Conclusions： Baseline HBV DNA, HBeAg negativity, and ALT were independent factors contributing to virological response at the 3^rt month. Further, multiple regression showed that HBV DNA level was the only parameter predicting full virological response as early as the 3^rd month, in this cirrhosis cohort.

Regression of liver fibrosis: evidence and challenges

It has been reported that liver fibrosis could be reversed after eliminating liver injuries.This article systematically summarizes the evidence of fibrosis regression based on histology,liver stiffness,and serum biomarkers,and discusses several clinically relevant challenges.Evidence from liver biopsy has been regarded as the gold standard in the assessment of fibrosis regression.Semiquantitative staging and grading systems are traditionally and routinely used to define regression.Recently,the predominantly regressive,indeterminate,and predominantly progressive score was proposed,based on the regressive features from“hepatic repair complex”,to provide additional information regarding the quality of fibrosis.For non-invasive assessment,although liver stiffness and serum biomarkers could be applied to reflect the dynamic changes of liver fibrosis,other confounding factors such as liver inflammation have to be considered.In conclusion,both histology and non-invasive methods can provide evidence regarding fibrosis regression.The predictive value of fibrosis regression in long-term prognosis warrants further investigation.

Negative association of time in range and urinary albumin excretion rate in patients with type 2 diabetes mellitus:a retrospective study of inpatients

Background:Time in range(TIR)refers to the time an individual spends within their target glucose range,which now has been popularized as an important metric to classify glycemic management and also recognized as an important outcome of current diabetes therapies.This study aimed to investigate the association between TIR and the severity of the urinary albumin excretion rate(UAER)in patients with type 2 diabetes mellitus(T2DM).Methods:We retrospectively analyzed the data of 1014 inpatients with T2DM at the Department of Endocrinology and Metabolism of Peking University International Hospital,China.TIR was defined as the percentage of blood glucose within the target range of 3.90-10.00 mmol/L.Urine samples for assessment of UAER were collected for 3 consecutive days from the start of hospitalization.Results:The TIR values for patients with normal urine levels of albumin,microalbuminuria,and macroalbuminuria were 70%±20%,50%±20%,and 30%±20%,respectively(allP<0.001).The patients were stratified according to quartiles of TIR as follows:quartile(Q)1,<55%;Q2,55%-72%;Q3,73%-83%;and Q4,>83%.The incidences of microalbuminuria in Q1,Q2,Q3,and Q4 were 41.1%,21.6%,7.1%,and 5.5%(allP<0.001),respectively.The respective incidences of macroalbuminuria were 24.2%,1.1%,1.4%,and 0%(allP<0.001).In multinomial logistic regression analyses,TIR was significantly correlated with microalbuminuria(odds ratio[OR]0.58,95%confidence interval[CI]:0.52-0.65,P<0.001)and macroalbuminuria(OR 0.26,95%CI:0.18-0.38,P<0.001)after adjusting for age,sex,body mass index,diabetes duration,systolic blood pressure,and levels of triglycerides,glycosylated hemoglobin A1c,and creatinine.Conclusion:The proportion of blood glucose in TIR is closely related to the severity of UAER in patients with T2DM.

Comparative effectiveness and safety of 32 pharmacological interventions recommended by guidelines for coronavirus disease 2019:a systematic review and network meta-analysis combining 66 trials

Background:The global pandemic coronavirus disease 2019(COVID-19)has become a major public health problem and presents an unprecedented challenge.However,no specific drugs were currently proven.This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19.Methods:Medline,Embase,the Cochrane Library,and clinicaltrials.gov were searched for randomized controlled trials(RCTs)in patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)/SARS-CoV.Random-effects network metaanalysis within the Bayesian framework was performed,followed by the Grading of Recommendations Assessment,Development,and Evaluation system assessing the quality of evidence.The primary outcome of interest includes mortality,cure,viral negative conversion,and overall adverse events(OAEs).Odds ratio(OR)with 95%confidence interval(CI)was calculated as the measure of effect size.Results:Sixty-six RCTs with 19,095 patients were included,involving standard of care(SOC),eight different antiviral agents,six different antibiotics,high and low dose chloroquine(CQ_HD,CQ_LD),traditional Chinese medicine(TCM),corticosteroids(COR),and other treatments.Compared with SOC,a significant reduction of mortality was observed for TCM(OR=0.34,95%CI:0.20–0.56,moderate quality)and COR(OR=0.84,95%CI:0.75–0.96,low quality)with improved cure rate(OR=2.16,95%CI:1.60–2.91,low quality for TCM;OR=1.17,95%CI:1.05–1.30,low quality for COR).However,an increased risk of mortality was found for CQ_HD vs.SOC(OR=3.20,95%CI:1.18–8.73,low quality).TCM was associated with decreased risk of OAE(OR=0.52,95%CI:0.38–0.70,very low quality)but CQ_HD(OR=2.51,95%CI:1.20–5.24)and interferons(IFN)(OR=2.69,95%CI:1.02–7.08)vs.SOC with very low quality were associated with an increased risk.Conclusions:COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care.CQ_HD might increase the risk of mortality.CQ,IFN,and other antiviral agents could increase the risk of OAEs.The current evidence is generally uncertain with low-quality and further high-quality trials are needed.

Detection of Hepatitis B Virus M204V Mutation Quantitatively via Real-time PCR

Background and Aims:Drug-resistant DNA mutations of the hepatitis B virus(HBV)affect treatment response in chronic hepatitis B patients.We have established a new,sensitive,specific,accurate and convenient real-time PCR method to detect HBV mutations quantitatively.Methods:Blood samples were collected from patients showing viral breakthrough,primary nonresponse,or poor response during treatment,and mutations were detected via direct sequencing to assess our method.A plasmid containing the M204V mutation was synthesized and standard curves plotted.Results:The determination coefficient for linear correlation between Ct and log plasmid copy numbers was 0.996,where Ct value was−3.723log(DNA concentration)+48.647.Coefficients of variation indicated good reproducibility.Correctness was within tolerable bias.Limit of detection was 103 copies/mL.Specificity,accuracy,positive predictive value and negative predictive value were 92.86%,100%,96.88%,100%and 94.74%,respectively.Conclusions:These results show that our method can be used to detect HBV M204V mutations with the advantages of sensitivity,specificity and efficiency,providing a new choice for monitoring drug resistance.

Overexpression of Hepcidin Alleviates Steatohepatitis and Fibrosis in a Diet-induced Nonalcoholic Steatohepatitis

Background and Aims:Iron overload can contribute to the progression of nonalcoholic fatty liver disease(NAFLD)to nonalcoholic steatohepatitis(NASH).Hepcidin(Hamp),which is primarily synthesized in hepatocytes,is a key reg-ulator of iron metabolism.However,the role of Hamp in NASH remains unclear.Therefore,we aimed to elucidate the role of Hamp in the pathophysiology of NASH.Methods:Male mice were fed a choline-deficient L-amino acid-defined(CDAA)diet for 16 weeks to establish the mouse NASH model.A choline-supplemented amino acid-defined(CSAA)diet was used as the control diet.Recombinant adeno-asso-ciated virus genome 2 serotype 8 vector expressing Hamp(rAAV2/8-Hamp)or its negative control(rAAV2/8-NC)was administered intravenously at week 8 of either the CDAA or CSAA diet.Results:rAAV2/8-Hamp treatment markedly decreased liver weight and improved hepatic steatosis in the CDAA-fed mice,accompanied by changes in lipogenesis-related genes and adiponectin expression.Compared with the control group,rAAV2/8-Hamp therapy attenuated liver damage,with mice exhibiting reduced histological NAFLD inflammation and fibrosis,as well as lower levels of liver enzymes.Moreover,α-smooth muscle actin-positive acti-vated hepatic stellate cells(HSCs)and CD68-postive mac-rophages increased in number in the CDAA-fed mice,which was reversed by rAAV2/8-Hamp treatment.Consistent with the in vivo findings,overexpression of Hamp increased adi-ponectin expression in hepatocytes and Hamp treatment inhibited HSC activation.Conclusions:Overexpression of Hamp using rAAV2/8-Hamp robustly attenuated liver stea-tohepatitis,inflammation,and fibrosis in an animal model of NASH,suggesting a potential therapeutic role for Hamp.

Chinese guidelines for the application of colon cancer staging recognition systems based on artificial intelligence platforms (2021)

The incidence and mortality of colon cancer in China are increasing each year.At present,treatment selection for colon cancer patients mainly depends on imaging results,which require a large number of radiologists to interpret.In China,there is a shortage and uneven distribution of experienced radiologists,which leads to delays and bias in the evaluation of imaging data.Based on these considerations,the Colorectal Surgery Group of the Surgery Branch of the Chinese Medical Association in collaboration with experts at Beihang University has independently developed an artificial intelligence(AI)-based recognition system for the preoperative determination of colon cancer stage to partially replace the work of and relieve the pressure on radiologists.These guidelines aim to standardize the use of AI-based recognition systems in the preoperative staging of colon cancer and guide their clinical application.