Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

Employing bibliometric methods and adhering to principles of textual research， this study systematically investigated prescription source， formula name， composition evolution， dose evolution， origin， processing， ancient and modern applications of Xiaofengsan. Xiaofengsan， also known as Renshen Xiaofengsan and Chantui Xiaofengsan， was first recorded in the Taiping Huimin Hejijufang（hereafter referred to as Jufang） of the Southern Song dynasty. The formula composition included Schizonepetae Spica， Glycyrrhizae Radix et Rhizoma， Chuanxiong Rhizoma， Notoptery Rhizoma et Radix， Bombyx Batryticatus， Saposhnikoviae Radix， Poria， Cicadae Periostracum， Pogostemonis Herba， Ginseng Radix et Rhizoma， Magnoliae Officinalis Cortex and Citri Reticulatae Pericarpium， a total of 12 medicinal materials. In terms of the evolution of formula composition， formulas across dynasties largely aligned with those recorded in Jufang， with only minor variations in application. The results of the formula dosage research indicated that one dose of medication in Jufang corresponded to the following modern dosages：Schizonepetae Spica of 82.6 g， Glycyrrhizae Radix et Rhizoma of 82.6 g， Chuanxiong Rhizoma of 82.6 g， Notoptery Rhizoma et Radix of 82.6 g， Bombyx Batryticatus of 82.6 g， Saposhnikoviae Radix of 82.6 g， Poria of 82.6 g， Cicadae Periostracum of 82.6 g， Pogostemonis Herba of 82.6 g， Ginseng Radix et Rhizoma of 82.6 g， Magnoliae Officinalis Cortex of 20.65 g and Citri Reticulatae Pericarpium of 20.65 g， the origins of all the constituent drugs were consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The results of the investigation into the decoction method indicated that the aforementioned drugs should be finely ground into powder（pass through the No.5 sieve）， and 8.26 g was taken for each dose， which was taken with the clear liquid obtained by steeping tea leaves in boiling water for several minutes. This mixture was administered three times daily， 30 min after meals. The ancient functional indications of this formula mainly involved dispelling wind-heat， eliminating pathogenic factors and regulating the middle Jiao. It primarily treated all wind-heat syndromes manifesting as skin diseases， predominantly affecting the upper body， especially the head and face. The diseases involved in modern applications were mostly dermatological diseases， including urticaria， eczema， atopic dermatitis and others. In this paper， by combing the relevant ancient literature， the key information of Xiaofengsan was textual researched， in order to provide reference for the modern application and development of this formula.

Objective: To investigate the situation and influencing factors of school bullying experienced by primary and middle school students, so as to provide the basis for formulating school bullying intervention measures and promoting students' physical and mental health development. Methods: All the counties (cities, districts) in Zhejiang Province were stratified to urban and suburban areas, primary, junior high and senior high school students were selected using a stratified cluster sampling method. Basic information, lifestyle and school bullying were collected through questionnaire surveys. Factors affecting school bullying experienced by primary and middle school students were analyzed using a multivariable logistic regression model. Results: Totally 137 846 valid questionnaires were recovered, with an effective recovery rate of 97.17%. There were 72 526 males (52.61%) and 65 320 females (47.39%). There were 47 561 primary school students (34.50%), 47 701 junior high school students (34.61%) and 42 584 senior high school students (30.89%). A total of 3 987 students suffered from school bullying, accounting for 2.89%. The proportions of being maliciously teased, being intentionally excluded from group activities/isolated, being teased about physical defects or appearance, being hit/kicked/pushed/shoved/locked in a room, being threatened, and being extorted for money were 2.04%, 1.18%, 1.11%, 0.86%, 0.84% and 0.83%, respectively. Multivariable logistic regression analysis showed that the students who were males (OR=1.122, 95%CI: 1.048-1.202), lived in suburban areas (OR=1.322, 95%CI: 1.233-1.418), lived in areas with medium (OR=1.086, 95%CI: 1.006-1.173) or underdeveloped (OR=1.298, 95%CI: 1.191-1.415) economic level, had higher academic levels (junior high school, OR=1.380, 95%CI: 1.270-1.499; senior high school, OR=1.210, 95%CI: 1.083-1.351), lived on campus (OR=1.489, 95%CI: 1.372-1.616), engaged in fights (OR=6.029, 95%CI: 5.585-6.509), attempted to smoke (OR=1.320, 95%CI: 1.128-1.545), drank (OR=1.735, 95%CI: 1.575-1.912), were scolded and beaten by parents (OR=1.972, 95%CI: 1.822-2.135) and were obese (OR=1.240, 95%CI: 1.132-1.360) were more likely to experience school bullying. Conclusion The harm of school bullying to the physical and mental health of primary and middle school students should be taken seriously, and active policy measures should be adopted to strengthen intervention.

Objective To explore the effectiveness of"near peer learning"(NPL)in the electromyo-graphy(EMG)teaching module for neurology residents.Methods The Department of Neurology,Peking Union Medical College Hospital implemented an NPL instructional design for a course on EMG for residents from November 2020 to March 2024.This teaching session was held annually,in which senior residents in-structed juniors who were 1 or 2 years earlier in their training.The residents participated in the pre-course/post-course tests and completed a feedback survey at the end of the session.This evaluation method was used to un-derstand the effectiveness of the NPL intervention in EMG teaching.Results Over four years,a total of 83 residents participated.Among them,there were 24 postdoctoral students,52 postgraduates and 7 junior resi-dents.The results showed that the post-course test scores were significantly improved compared with pre-course test scores(74.33±2.43 vs.70.11±2.49,P=0.005),with the most remarkable improvements seen for"tu-tees"(73.84±20.53 vs.70.29±21.46,P=0.020),postgraduates(74.04±22.51 vs.68.97±21.40,P=0.009),first-year residents(70.19±4.02 vs.63.59±3.59,P=0.040)and first-time participating resi-dents(65.23±3.24 vs.60.97±3.21,P=0.030).The post-program feedback showed that both tutors and tu-tees thought highly of NPL,believing that it enabled them to gain knowledge and helped them to improve teaching skills.Conclusions The NPL intervention is suitable for the teaching of EMG,because of its contri-bution to knowledge acquisition and basic clinical skills improvement.The NPL is worth replicating in other teaching and learning programs.

Rheumatic diseases are a group of chronic disorders characterized by abnormalities in the immune system,while portal hypertension occurs due to increased blood flow or heightened resistance in the portal venous system or obstruction of hepatic venous outflow.Both rheumatic diseases and their medications can lead to noncirrhotic portal hypertension.The hypercoagulable state associated with rheumatic diseases can result in thrombosis within the portal and hepatic venous systems,and damage to the intrahepatic portal system and hepatic sinusoidal endothelial system can lead to porto-sinusoidal vascular disease and hepatic sinusoidal obstruction syndrome.Moreover,drugs used for the treatment of rheumatic diseases may cause liver parenchymal injury,which further leads to liver fibrosis and cirrhosis,or they may damage the hepatic vascular endothelium and thus cause noncirrhotic portal hypertension.This article elaborates on the mechanisms and characteristics by which common rheumatic diseases and their therapeutic agents lead to portal hypertension,in order to provide insights and assistance for clinical diagnosis,treatment,and follow-up monitoring.

Liposomes serve as critical carriers for drugs and vaccines,with their biological effects influenced by their size.The microfluidic method,renowned for its precise control,reproducibility,and scalability,has been widely employed for liposome preparation.Although some studies have explored factors affecting liposomal size in microfluidic processes,most focus on small-sized liposomes,predominantly through experimental data analysis.However,the production of larger liposomes,which are equally significant,remains underexplored.In this work,we thoroughly investigate multiple variables influencing liposome size during microfluidic preparation and develop a machine learning(ML)model capable of accurately predicting liposomal size.Experimental validation was conducted using a staggered herringbone micromixer(SHM)chip.Our findings reveal that most investigated variables significantly influence liposomal size,often interrelating in complex ways.We evaluated the predictive performance of several widely-used ML algorithms,including ensemble methods,through cross-validation(CV)for both lipo-some size and polydispersity index(PDI).A standalone dataset was experimentally validated to assess the accuracy of the ML predictions,with results indicating that ensemble algorithms provided the most reliable predictions.Specifically,gradient boosting was selected for size prediction,while random forest was employed for PDI prediction.We successfully produced uniform large(600 nm)and small(100 nm)liposomes using the optimised experimental conditions derived from the ML models.In conclusion,this study presents a robust methodology that enables precise control over liposome size distribution,of-fering valuable insights for medicinal research applications.

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Hypertrophic cardiomyopathy (HCM) due to a truncating variant of ALPK3 gene. METHODS: A 44-year-old male admitted to Taizhou Hospital of Zhejiang Province on December 29, 2018 was selected as the study subject. Whole-exome sequencing (WES) was carried out, and candidate variant was interpreted by following the guidelines from the American College of Medical Genetics and Genomics (ACMG). For ALPK3 was considered an autosomal recessive gene, the WES results was considered insufficient to explain his phenotype. In April 2023, the proband's WES data were re-analyzed using updated annotation pipelines, and peripheral blood samples were collected from his first-degree relatives (mother and brother) for Sanger sequencing validation. Conservation analysis and protein structural modeling were performed to assess the impact of the variant. Clinical evaluation and genetic counseling were provided to the proband's family members. Relevant literature on ALPK3tv-induced HCM patients were searched in Wanfang Data Knowledge Service Platform, CNKI, and PubMed database using "ALPK3" and "hypertrophic cardiomyopathy" as keywords. Clinical characteristics of HCM patients with heterozygous ALPK3tv variants were summarized and compared with the clinical characteristics of HCM patients with positive sarcomere-associated gene variants (SARC+). This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Ethics No.: K20230314). RESULTS: The proband was a 44-year-old male who was transferred to our institution on December 29, 2018 due to "chest tightness and pain for 6 months, exacerbated for 2 days". Emergency coronary angiography was performed, which led to a preliminary diagnosis of "acute coronary syndrome", and the patient was admitted to the Cardiology Department for treatment. Based on electrocardiogram and echocardiogram findings, the diagnosis was revised as HCM. The patient's condition has stabilized post-coronary angiography, and he was discharged with improved condition. On January 2019, WES was conducted to determine the etiology of the proband's HCM. WES results identified a novel heterozygous c.2156dupC (p.Pro720ThrfsTer53) truncating variant in the ALPK3 gene. At that time, the inheritance pattern could not explain the phenotype. In 2022, a literature indicated that heterozygous ALPK3tv could lead to autosomal dominant HCM. Consequently, in April 2023, the proband's whole-exome data were re-annotated, revealing changes in the transcript and protein versions, with the updated site annotated as ALPK3 (NM_020778.5): c.1550dupC (p.Pro518ThrfsTer53). Sanger sequencing confirmed that the proband's mother and brother also carried this variant. The mother exhibited obstructive HCM, while the brother showed no related phenotype. Bioinformatics analysis demonstrated conservation of this site across multiple species, and the variant has resulted in the loss of a protein domain. Based on ACMG guidelines, the variant was classified as likely pathogenic. Literature review and Bayesian calculation further elevated the pathogenicity rating, indicating that this variant was the cause of HCM in the patient. Literature study revealed distinctions between HCM caused by this variant type and SARC+ HCM. The age of onset among heterozygous ALPK3tv patients was delayed by approximately 10 years compared to SARC+ patients. Both forms of HCM exhibited a male predominance, which was particularly marked in individuals with ALPK3tv. Electrocardiographic left ventricular hypertrophy was more prevalent in heterozygous ALPK3tv patients than in SARC+ patients. The incidence of apical or concentric hypertrophy patterns was higher in heterozygous ALPK3tv patients compared to asymmetric septal hypertrophy, which predominated in SARC+ patients. ALPK3tv patients exhibited lower penetrance and later onset compared to SARC+ patients. A positive correlation between left ventricular wall thickness and age was noted in female patients only. CONCLUSION In this pedigree, the proband has presented with HCM, characterized by echocardiographic evidence of apical left ventricular hypertrophy without significant outflow tract obstruction or extracardiac phenotypes. Although his mother and brother had carried the same heterozygous ALPK3 (NM_020778.5) c.1550dupC (p.Pro518ThrfsTer53), the mother exhibited severe obstructive HCM, while the brother was asymptomatic, suggesting incomplete or age-dependent penetrance within the family. This study has enriched the evidence for the pathogenicity of ALPK3tv among Chinese HCM pedigrees and underscored the importance of periodic literature reviews and genetic re-analysis for unresolved genetic testing results.
Humans ; Male ; Pedigree ; Adult ; Cardiomyopathy, Hypertrophic/genetics* ; Heterozygote ; Asian People/genetics* ; Exome Sequencing ; Mutation ; China ; Female ; East Asian People

[Purpose]To analyze the trends of mortality and disease burden of gastric cancer among residents aged 30 and above from 2009 to 2023 in Wuxi City of Jiangsu Province and to estimate the age-period-cohort effect.[Methods]The gastric cancer mortality data from 2009 to 2023 were collected from Wuxi Death Registration System,and the crude mortality rate,age-standardized mortality rate,years of life lost(YLL)and YLL rate were calculated.The average annual percen-tage change(AAPC)was calculated with Joinpoint regression to analyze the trends of mortality and YLL rate of gastric cancer.The age-period-cohort model was used to analyze the effect of age,pe-riod and birth cohort on gastric cancer mortality.[Results]From 2009 to 2023,there were 32 348 gastric cancer deaths in Wuxi,the crude mortality rate was 44.24/105,and the age-standard mor-tality rate was 25.10/105,with a total YLL of 681 618.33 person-years.The crude mortality rate,age-standardized mortality rate and YLL rate showed decreasing trends,with AAPC of-1.77％(95％CI:-2.10％～-1.43％),-4.59％(95％CI:-4.97％～-4.20％)and-2.14％(95％CI:-2.56％～-1.74％),respectively.From 2009 to 2023,crude mortality rate,age-tandardized mortality rate,YLL in men were higher than those in women,and the decline rates of all indicators in women were faster than those in men.The age effect showed that the overall risk of gastric cancer death increased with age;the period effect showed a gradual decrease in the mortality risk and death burden of gastric cancer over time;the cohort effect showed that the later born cohort had a lower risk of death and death burden.[Conclusion]From 2009 to 2023,the disease burden of gastric cancer mortality in Wuxi showed a decreasing trend,with age and sex being the primary influencing factors.In the future,emphasis should be placed on gastric cancer screening and early intervention in middle-aged and elderly men.

Objective:To analyze the results of Healthy Zhejiang assessment and reveal the weakness in the process of Healthy Zhejiang construction,in order to propose suggestions for promoting the high-quality of Healthy Zhejiang construction.Methods:Descriptive statistics were used to analyze the points-deduction rates of the assessment indicators of Healthy Zhejiang in 90 counties(county-level cities and districts)of Zhejiang Province and non-parametric tests were used to analyze the results of Healthy Zhejiang assessment from 2020 to 2023.Results:The overall effect of Healthy Zhejiang construction from 2020 to 2023 was remarkable,but there were inadequacies and weakness in four aspects:residents'proactive health awareness,primary healthcare service capacity,healthy living environments,and the construction and management of sports facilities.Conclusions:It is still necessary to formulate multifaceted health education program,strengthen the construction of the primary healthcare service system,improve the collection,transportation and disposal system of rural domestic waste,and continuously promote the high-quality development of public sports service.