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 Exploring the mechanism of"Wushen acupuncture"in alleviating chronic fatigue in rats from the perspective of mitophagy.Methods Forty male Wistar rats were randomly allocated into a normal group and a modeling group,where the latter employed a protocol combining exhaustive swimming with tail-clamping stimuli to induce a rat model of chronic fatigue.Post-modeling,the normal group was subdivided randomly into a blank group and a presumed control group with specifics requiring clarification.Meanwhile,the modeling group was further randomized into a model group,a"Wushen acupuncture"group that underwent acupuncture at the Baihui and Sishencong points,and a non-acupoint control group,in which acupuncture was applied to 5 mm behind houshencong which is non-meridian,non-acupoint sites on the rats' heads and necks.The modeling and treatment outcomes in rats are assessed via the tail suspension test.Protein relative expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK),mammalian target of rapamycin(mTOR),and peroxisome proliferator-activated receptor γ coactivator 1-alpha(PGC-1α)in rat skeletal muscle were detected using Western blot.Meanwhile,the relative mRNA expression levels of PTEN induced putative kinase 1(PINK1)and Parkin were measured by Real-Time PCR.Results In contrast to the baseline cohort,rats in the induced fatigue model displayed a reduction in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).When juxtaposed against the fatigue-induced model group,the"Wushen acupuncture"intervention cohort manifested a substantial increase in these behavioral parameters(P<0.05).Furthermore,relative to the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed a decrease in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).Versus the baseline group,the fatigue-induced model cohort demonstrated a marked decrease in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA in skeletal muscle tissue(P<0.05),alongside an increase in mTOR protein expression(P<0.05).Compared to the fatigue-induced model group,the"Wushen acupuncture"intervention led to an increase in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and a decrease in mTOR protein expression(P<0.05).When juxtaposed against the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed decreased relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and increased mTOR protein expression(P<0.05).Conclusion The"Wushen acupuncture"have been shown to enhance the alleviation of chronic fatigue symptoms in rat models and modulate the functionality of mitochondrial autophagy.This therapeutic effect is believed to be mechanistically linked to the regulation of both the PINK1/Parkin pathway and the AMPK/mTOR signaling cascade.

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.

In recent years, potato scab caused by pathogenic Streptomyces spp. has become widespread globally, with increasing damage severely compromising the commercial value and storability of tubers. The pathogens are transmitted through the soil and seeds of potato, while existing control technologies have demonstrated limited efficacy in preventing the colonization and spread of pathogens, which pose a critical bottleneck in the sustainable development of the potato industry. This study systematically examines the pathogen characteristics and pathogenic mechanisms, evaluates the impacts of soil nutrients and microbial community structure on disease severity, and analyzes limitations in current chemical control, biological control, and disease-resistant variety breeding approaches. We propose an integrated control strategy of disease-resistant varieties, phosphorus fertilizer reduction, fertilizer efficiency enhancement, and phosphorus-soluble antagonistic fungicides, aiming to provide novel research perspectives for achieving effective prevention and control of potato scab.
Solanum tuberosum/microbiology* ; Plant Diseases/prevention & control* ; Streptomyces/pathogenicity* ; Disease Resistance ; Fungicides, Industrial/pharmacology* ; Fertilizers ; Soil Microbiology

Objectives:To analyze whether there is a causal relationship between plasma proteins and the risk of coronary atherosclerosis(CAS)based on a two-sample Mendelian randomization(MR)analysis and to identify potential therapeutic targets for CAS.Methods:Single nucleotide polymorphisms(SNP)associated with plasma proteins from the UK Biobank Pharmacoproteomics Program(UKB-PPP)database were used as instrumental variables and outcome data were obtained from genome-wide association study databases.The Wald ratio method and inverse variance weighted(IVW)method in two-sample MR were employed as the primary approaches to assess the causal relationship between plasma proteins and CAS.Colocalization analysis was conducted as a sensitivity analysis to ensure the robustness of the MR findings.Results:A total of 132 plasma proteins were found to have causal associations with an increased risk of CAS.Colocalization analysis revealed that 12 plasma proteins shared genetic variants with CAS.Among them,Proprotein convertase subtilise/kexin type 9(PCSK9)(OR=1.23,95%CI:1.15-1.32,P<0.01)and neurocan(NCAN)(OR=1.35,95%CI:1.21-1.52,P<0.01)exhibited posterior probability of hypothesis4(PPH4)values<0.80 in the colocalization analysis,indicating strong support for colocalization and suggesting their potential as primary plasma protein drug targets for CAS.Conclusions:PCSK9 is associated with an increased risk of CAS and is confirmed as a therapeutic target for CAS.NCAN emerges as another potential therapeutic target for CAS.

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.

Objective Exploring the mechanism of"Wushen acupuncture"in alleviating chronic fatigue in rats from the perspective of mitophagy.Methods Forty male Wistar rats were randomly allocated into a normal group and a modeling group,where the latter employed a protocol combining exhaustive swimming with tail-clamping stimuli to induce a rat model of chronic fatigue.Post-modeling,the normal group was subdivided randomly into a blank group and a presumed control group with specifics requiring clarification.Meanwhile,the modeling group was further randomized into a model group,a"Wushen acupuncture"group that underwent acupuncture at the Baihui and Sishencong points,and a non-acupoint control group,in which acupuncture was applied to 5 mm behind houshencong which is non-meridian,non-acupoint sites on the rats' heads and necks.The modeling and treatment outcomes in rats are assessed via the tail suspension test.Protein relative expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK),mammalian target of rapamycin(mTOR),and peroxisome proliferator-activated receptor γ coactivator 1-alpha(PGC-1α)in rat skeletal muscle were detected using Western blot.Meanwhile,the relative mRNA expression levels of PTEN induced putative kinase 1(PINK1)and Parkin were measured by Real-Time PCR.Results In contrast to the baseline cohort,rats in the induced fatigue model displayed a reduction in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).When juxtaposed against the fatigue-induced model group,the"Wushen acupuncture"intervention cohort manifested a substantial increase in these behavioral parameters(P<0.05).Furthermore,relative to the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed a decrease in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).Versus the baseline group,the fatigue-induced model cohort demonstrated a marked decrease in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA in skeletal muscle tissue(P<0.05),alongside an increase in mTOR protein expression(P<0.05).Compared to the fatigue-induced model group,the"Wushen acupuncture"intervention led to an increase in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and a decrease in mTOR protein expression(P<0.05).When juxtaposed against the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed decreased relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and increased mTOR protein expression(P<0.05).Conclusion The"Wushen acupuncture"have been shown to enhance the alleviation of chronic fatigue symptoms in rat models and modulate the functionality of mitochondrial autophagy.This therapeutic effect is believed to be mechanistically linked to the regulation of both the PINK1/Parkin pathway and the AMPK/mTOR signaling cascade.

Objectives:To analyze whether there is a causal relationship between plasma proteins and the risk of coronary atherosclerosis(CAS)based on a two-sample Mendelian randomization(MR)analysis and to identify potential therapeutic targets for CAS.Methods:Single nucleotide polymorphisms(SNP)associated with plasma proteins from the UK Biobank Pharmacoproteomics Program(UKB-PPP)database were used as instrumental variables and outcome data were obtained from genome-wide association study databases.The Wald ratio method and inverse variance weighted(IVW)method in two-sample MR were employed as the primary approaches to assess the causal relationship between plasma proteins and CAS.Colocalization analysis was conducted as a sensitivity analysis to ensure the robustness of the MR findings.Results:A total of 132 plasma proteins were found to have causal associations with an increased risk of CAS.Colocalization analysis revealed that 12 plasma proteins shared genetic variants with CAS.Among them,Proprotein convertase subtilise/kexin type 9(PCSK9)(OR=1.23,95%CI:1.15-1.32,P<0.01)and neurocan(NCAN)(OR=1.35,95%CI:1.21-1.52,P<0.01)exhibited posterior probability of hypothesis4(PPH4)values<0.80 in the colocalization analysis,indicating strong support for colocalization and suggesting their potential as primary plasma protein drug targets for CAS.Conclusions:PCSK9 is associated with an increased risk of CAS and is confirmed as a therapeutic target for CAS.NCAN emerges as another potential therapeutic target for CAS.

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.

Surgery is an important treatment for the anterior mediastinal disease. With the rapid development of minimally invasive techniques, complete resection of the lesion in most patients with thymic disease can be achieved through thoracoscopic surgery. Practice has proved that the three-port resection of anterior mediastinal thymus disease via the subxiphoid approach is an ideal surgical method for the treatment of anterior mediastinal thymic tumors at present, which has strong popularization and popularity and can benefit the patients. The procedure focuses primarily on the anterior and upper mediastinum and can thoroughly expose the anatomy of the mediastinum and both sides, with minimal intraoperative bleeding, high safety, minimal trauma and postoperative pain, and a short hospital stay. It has clear advantages over conventional thoracic open-heart surgery and transversal resection. However, the surgical approach and field of view, and intraoperative precautions of this procedure are completely different from those of previous thoracoscopic procedures, and from the subxiphoid single-port approach adopted by other centers. Based on 10 years of surgical experience at our center, a modular mode of surgical operation has been developed and its procedure has been standardized. This paper will share and discuss relevant operational points and experiences.