AIM:To evaluate the application effec-tiveness of a Bayesian mixture model based on the principal stratum strategy for estimating the com-plier average causal effect(CACE)in clinical trials with non-compliance.METHODS:Using a non-infe-riority randomized controlled trial investigating a novel drug for primary type 2 diabetes mellitus(non-inferiority margin:-0.4)as a case study,the primary analysis applied a Bayesian mixture model under the monotonicity assumption to estimate CACE of between-group differences in glycated he-moglobin(HbA1c)changes within the compliant stratum,followed by non-inferiority testing.Sensi-tivity analyses included a Bayesian mixture model relaxing the monotonicity assumption and compar-ing results with per-protocol set(PPS)analysis.RE-SULTS:In the primary analysis,the posterior mean of CACE for HbA1c change in the compliant stratum was 0.081％,with a one-sided 97.5％credible inter-val lower bound of-0.124,exceeding the non-infe-riority margin(-0.4％),supporting the non-inferiori-ty efficacy of the novel drug in the compliant stra-tum(P(H1|Data)=1).Consistent findings were ob-served in PPS analyses(estimated effect:0.136％;one-sided 97.5％credible interval lower bound:-0.069％),further validating methodological robust-ness.CONCLUSION:In clinical trials with noncom-pliance as an intercurrent event,the Bayesian mix-ture model under the principal stratum strategy ef-fectively adjusts for compliance-related bias and yields conservative,robust estimates of causal ef-fects,supporting its value in efficacy evaluation un-der complex compliance scenarios.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

INTRODUCTION: Acute severe ulcerative colitis (ASUC) is a significant cause of disease morbidity. One-third of patients with ASUC are steroid refractory. Rescue therapy may not successfully induce remission, necessitating colectomy. We aimed to identify predictors of rescue therapy and colectomy in ASUC assessed within 24 h of admission for early risk stratification. METHODS: We conducted a retrospective cohort study of 58 admissions for ASUC among 47 patients from August 2002 to January 2022. Serum biomarkers assessed were measured on admission. Primary outcomes were the need for rescue therapy during the same admission and colectomy within 1 year of admission. RESULTS: Rescue therapy (all with infliximab) was given in 20 (34.5%) of the admissions. Colectomy was done within 1 year for nine (15.5%) of the admissions. An elevated C-reactive protein (CRP) of >30 mg/L (relative risk [RR] 1.63), a CRP-albumin ratio of >0.85 (RR 1.63), and a composite factor of both CRP > 30 mg/L and age ≥60 years (RR 2.37) were significantly associated with the need for rescue therapy. Hypoalbuminaemia ≤ 25 g/L (RR 4.35) and the use of biologics at presentation (RR 1.54) were significantly associated with colectomy within 1 year of admission, while a CRP of ≥ 80 mg/L was a significant protective factor (RR 0.70). CONCLUSION Patients with ASUC who have elevated CRP or CRP-albumin ratio on admission should be considered at risk for steroid-refractory disease. Those with hypoalbuminaemia on admission and using biologics at presentation are more likely to require colectomy in the first year after admission for ASUC.
Humans ; Colitis, Ulcerative/therapy* ; Colectomy ; Retrospective Studies ; Male ; Female ; Middle Aged ; Adult ; C-Reactive Protein/metabolism* ; Infliximab/therapeutic use* ; Biomarkers/blood* ; Acute Disease ; Aged ; Severity of Illness Index ; Treatment Outcome

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

AIM:To evaluate the application effec-tiveness of a Bayesian mixture model based on the principal stratum strategy for estimating the com-plier average causal effect(CACE)in clinical trials with non-compliance.METHODS:Using a non-infe-riority randomized controlled trial investigating a novel drug for primary type 2 diabetes mellitus(non-inferiority margin:-0.4)as a case study,the primary analysis applied a Bayesian mixture model under the monotonicity assumption to estimate CACE of between-group differences in glycated he-moglobin(HbA1c)changes within the compliant stratum,followed by non-inferiority testing.Sensi-tivity analyses included a Bayesian mixture model relaxing the monotonicity assumption and compar-ing results with per-protocol set(PPS)analysis.RE-SULTS:In the primary analysis,the posterior mean of CACE for HbA1c change in the compliant stratum was 0.081％,with a one-sided 97.5％credible inter-val lower bound of-0.124,exceeding the non-infe-riority margin(-0.4％),supporting the non-inferiori-ty efficacy of the novel drug in the compliant stra-tum(P(H1|Data)=1).Consistent findings were ob-served in PPS analyses(estimated effect:0.136％;one-sided 97.5％credible interval lower bound:-0.069％),further validating methodological robust-ness.CONCLUSION:In clinical trials with noncom-pliance as an intercurrent event,the Bayesian mix-ture model under the principal stratum strategy ef-fectively adjusts for compliance-related bias and yields conservative,robust estimates of causal ef-fects,supporting its value in efficacy evaluation un-der complex compliance scenarios.

Objective To make the cost-effectiveness analysis of pembrolizumab and platinum chemotherapy as the first-line treatment for advanced non-small cell lung cancer(NSCLC)in the population with tumor proportion score(TPS)≥1%of PD-L1,and provide some reference for the clinical use and future price negotiation of pembrolizumab.Methods Based on Pubmed database,the published RCT literatures of pembrolizumab were analyzed,and the survival data were extracted,combined with the treatment plan of a tertiary hospital,the Markov model were established to simulate the cost and health effectiveness of patients for twenty years,and the stability of the model was tested by one-way sensitivity analysis and probability sensitivity analysis.Results Twenty years later,the cost-effectiveness ratio of pembrolizumab group and chemotherapy group was ￥58 517.60/quality adjusted life month(QALM)and ￥41 213.08/QALM.Compared with the chemotherapy group,the incremental cost effective ratio(ICER)was ￥104 485.36/QALM.Conclusion When the willingness to pay(WTP)value was ￥30 902/QALM,the pembrolizumab therapy was not more cost-effective advantages than platinum chemotherapy,and the sensitivity analysis showed that the results of the model were relatively stable.

Objective·To detect the effects of propofol sedation on cognitive function in rats and its mechanism. Methods?·?Forty-eight SD rats were randomly divided into three groups, i.e. control group, 100?mg/kg group and 300?mg/kg group. Rats were administrated intraperitoneally with propofol (10?mg/mL, 100?mg/kg or 300?mg/kg). The mRNA levels of brain derived neurotropic factor (BDNF)-TrkB/p75 signal molecules in rat hippocampus were evaluated by realtime PCR 45 min after propofol treatment. Learning and memory ability was examined by inhibitory avoidance (IA) test after propofol treatment. Results?·?The mRNA levels of BDNF in the hippocampal tissue were (1.20±0.13) fold (P=0.002) and (88±12) % (P=0.044) of that in control group, respectively, in 100?mg/kg group and 300?mg/kg group after injection of propofol. The mRNA levels of TrkB were (1.01±0.11) fold ( P=0.982) and (86±11) % (P=0.018) of that in control group, respectively, in 100?mg/kg group and 300?mg/kg group. The mRNA levels of p75 were (1.02±0.10) fold (P=0.778) and (1.59±0.18) fold (P=0.000) of that in control group, respectively, in 100?mg/kg group and 300?mg/kg group. There was no significant difference of the 24 h IA memory retention latency between 100?mg/kg group and control group. The 24 h IA memory retention latency in 300?mg/kg group was significantly decreased compared with control group (P=0.028) and 100?mg/kg group (P=0.020). Conclusion?·?Propofol dose-dependently regulates the expression of BDNF-TrkB/p75 signal molecules, and high dose propofol may reduce cognitive function via BDNF-TrkB/p75 signal.

BACKGROUNDParoxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder characterized by recurrent dystonic or choreoathetoid attacks triggered by sudden voluntary movements. Under the condition of psychological burden, some patients' attacks may get worsened with longer duration and higher frequency. This study aimed to assess nonmotor symptoms and quality of life of patients with PKD in a large population.

METHODSWe performed a cross-sectional survey in 165 primary PKD patients from August 2008 to October 2016 in Rui Jin Hospital, using Symptom Check List-90-Revised (SCL-90-R), World Health Organization Quality of Life-100 (WHOQoL-100), Self-Rating Depression Scale, and Self-Rating Anxiety Scale. We evaluated the differences of SCL-90-R and WHOQOL-100 scores in patients and Chinese normative data (taken from literature) by using the unpaired Student's t-test. We applied multivariate linear regression to analyze the relationships between motor manifestations, mental health, and quality of life among PKD patients.

RESULTSCompared with Chinese normative data taken from literature, patients with PKD exhibited significantly higher (worse) scores across all SCL-90-R subscales (somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism; P= 0.000 for all) and significantly lower (worse) scores of five domains in WHOQoL-100 (physical domain, psychological domain, independence domain, social relationship domain, and general quality of life; P= 0.000 for all). Nonremission of dyskinesia episodes (P = 0.011) and higher depression score (P = 0.000) were significantly associated with lower levels of quality of life. The rates of depression and anxiety in patients with PKD were 41.2% (68/165) and 26.7% (44/165), respectively.

CONCLUSIONSDepression, anxiety, and low levels of quality of life were prevalent in patients with PKD. Co-occurrence of depression and anxiety was common among these patients. Regular mental health interventions could set depression and anxiety as intervention targets. Considering that the motor episodes could be elicited by voluntary movements and sometimes also by emotional stress, and that symptoms may get worsened with longer duration and higher frequency when patients are stressed out, intervention or treatment of depression and anxiety might improve the motor symptoms and overall quality of life in PKD patients.

Exons ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Mutation ; Pedigree ; Spastic Paraplegia, Hereditary ; etiology ; genetics

In the 1960s, modern science began involving the essence of heat syndrome, but there have still no in-depth systematic studies on pathological mechanisms of heat syndrome and action mechanisms of cold and cool herbs. In this study, the animal model with heat syndrome was set up by feeding herbs with hot property, and then cold and cool herbs was applied in the experimental therapy. The two-dimensional electrophoresis and mass spectrometry technologies were adopted to compare the liver mitochondria proteome of the rats of the heat syndrome model and the ones treated with cold and cool herbs, so as to discover specificity-related proteins after heat syndrome and treatment with cold and cool herbs.
Animals ; Carbohydrate Metabolism ; drug effects ; Cold Temperature ; Drugs, Chinese Herbal ; pharmacology ; Energy Metabolism ; drug effects ; Hot Temperature ; Lipid Metabolism ; drug effects ; Male ; Mitochondria, Liver ; drug effects ; metabolism ; Proteome ; metabolism ; Rats ; Rats, Sprague-Dawley