Pyroptosis,a form of programmed cell death primarily mediated by gasdermin D(GSD-MD),plays a crucial role in infections and inflammatory responses.Although the OTU deubiquiti-nase 4(OTUD4)has shown its importance in various cellular processes,its specific function in py-roptosis remains unclear,which necessitates a deeper understanding of its role.This study aims to explore the role of OTUD4 in regulating GSDMD-mediated pyroptosis.Through experiments inclu-ding cell transfection,lactate dehydrogenase(LDH)release assays,co-immunoprecipitation(Co-IP),and Western blot(WB)analysis,we investigated the interaction between OTUD4 and GSD-MD and their influence on GSDMD-mediated pyroptosis.Our results indicated that OTUD4 could bind to GSDMD,significantly reduce Caspase-1-mediated cleavage of GSDMD,and lower protein levels of GSDMD-p30,thereby inhibiting pyroptosis.Conversely,the enzymatically inactive mutant of OTUD4(C45A)exhibited a markedly diminished inhibitory effect on pyroptosis.Furthermore,OTUD4 also demonstrated a significant inhibitory effect on pyroptosis in porcine cells.In conclu-sion,this study reveals that OTUD4 can inhibit GSDMD-p30-mediated pyroptosis through its deu-biquitinating activity,highlighting the critical function of OTUD4 in the regulation of pyroptosis and suggesting a potential target for the development of new therapeutic strategies.

Pyroptosis,a form of programmed cell death primarily mediated by gasdermin D(GSD-MD),plays a crucial role in infections and inflammatory responses.Although the OTU deubiquiti-nase 4(OTUD4)has shown its importance in various cellular processes,its specific function in py-roptosis remains unclear,which necessitates a deeper understanding of its role.This study aims to explore the role of OTUD4 in regulating GSDMD-mediated pyroptosis.Through experiments inclu-ding cell transfection,lactate dehydrogenase(LDH)release assays,co-immunoprecipitation(Co-IP),and Western blot(WB)analysis,we investigated the interaction between OTUD4 and GSD-MD and their influence on GSDMD-mediated pyroptosis.Our results indicated that OTUD4 could bind to GSDMD,significantly reduce Caspase-1-mediated cleavage of GSDMD,and lower protein levels of GSDMD-p30,thereby inhibiting pyroptosis.Conversely,the enzymatically inactive mutant of OTUD4(C45A)exhibited a markedly diminished inhibitory effect on pyroptosis.Furthermore,OTUD4 also demonstrated a significant inhibitory effect on pyroptosis in porcine cells.In conclu-sion,this study reveals that OTUD4 can inhibit GSDMD-p30-mediated pyroptosis through its deu-biquitinating activity,highlighting the critical function of OTUD4 in the regulation of pyroptosis and suggesting a potential target for the development of new therapeutic strategies.

Objective:To analyze the clinical, genetic mutation characteristics, and treatment prognosis of type 2A hereditary hemochromatosis (HH) in China.Methods:Peripheral blood samples and clinical data of patients with primary iron overload were collected through the China Registry of Genetic/Metabolic Liver Disease from June 2015 to November 2023. HH-related genes were detected by Sanger sequencing. Clinical characteristics and gene mutation characteristics of HH patients carrying HJV gene mutations were analyzed.Results:Among the 37 cases with primary iron overload, ten cases (27.0%, 10/37) had detectable HJV gene mutations, which included four homozygous mutations, five compound heterozygous mutations, and one monoheterozygous mutation. p.Q6H and p.C321X (80.0%, 8/10) were the most common mutated sites. The average age of onset was 30.7±14.7 years. The age of diagnosis was 35.7±16.2 years, with male-to-female ratio of 7:3. Ferritin and transferrin saturation were (5 267±905) ng/ml, and 94.3%±1.2%, respectively. Magnetic resonance imaging showed iron overload in the liver, pancreas, and myocardium. Liver biopsy showed diffuse iron deposition within hepatocytes. All ten cases had elevated transaminases; one case (1/10, 10.0%) had liver cirrhosis; four cases (4/10, 40.0%) had heart failure and arrhythmia; five cases (5/10, 50.0%) had diabetes; six cases (6/10, 60.0%) had hypogonadism; six cases (6/10, 60.0%) had skin pigmentation; and six cases (6/10, 60.0%) had fatigue symptoms. All six cases underwent bloodletting therapy, and ferritin levels dropped to about 100 ng/ml. Two cases of oral administration of the iron chelator deferasirox did not meet the ferritin level standard, and one case died from acute heart failure following a confirmed diagnosis during hospitalization.Conclusion:The HJV gene may be one of the main pathogenic genes of HH in China. The p.Q6H and p.C321X mutations were one of the hotspot mutations. The onset age of HJV gene-related HH was between 20 and 30 years old, and their condition was severe. Therefore, early bloodletting treatment can have a favorable outcome.

Using big data and artificial intelligence to establish a multi-point monitoring, early warning, and disposal system to achieve early warning and intervention of infectious disease outbreaks is an important means of controlling the spread of the epidemic. Taking Xiaoshan district as an example, this study analyzes the monitoring contents, warning methods, and application effectiveness of the infectious disease monitoring, early warning and disposal system. Based on Xiaoshan′s health big data resources, the system starts with syndrome, disease diagnosis and etiology. Through advanced technologies such as artificial intelligence and block chain, it realizes early identification of infectious disease outbreaks, data fusion, multi-cross collaboration, and closed-loop management. It has improved the sensitivity of clustered outbreaks monitoring and the effectiveness of epidemic disposal and provided a reference for grassroots disease prevention and control departments to establish an infectious disease monitoring and early warning system.

Using big data and artificial intelligence to establish a multi-point monitoring, early warning, and disposal system to achieve early warning and intervention of infectious disease outbreaks is an important means of controlling the spread of the epidemic. Taking Xiaoshan district as an example, this study analyzes the monitoring contents, warning methods, and application effectiveness of the infectious disease monitoring, early warning and disposal system. Based on Xiaoshan′s health big data resources, the system starts with syndrome, disease diagnosis and etiology. Through advanced technologies such as artificial intelligence and block chain, it realizes early identification of infectious disease outbreaks, data fusion, multi-cross collaboration, and closed-loop management. It has improved the sensitivity of clustered outbreaks monitoring and the effectiveness of epidemic disposal and provided a reference for grassroots disease prevention and control departments to establish an infectious disease monitoring and early warning system.

Citri Reticulatae Pericarpium is a commonly used traditional Chinese medicine in China. By referring to herbal monographs and related research documents， and comparing all editions of Chinese Pharmacopoeia and local processing specifications， the processing history， modern processing specifications， study on chemical constituents and pharmacological effects before and after processing of Citri Reticulatae Pericarpium were summarized. It was found that the processing methods of Citri Reticulatae Pericarpium in the past dynasties were mainly cleansing， cutting and frying. The processing methods of Citri Reticulatae Pericarpium included in all editions of Chinese Pharmacopoeia were all cleansing and cutting. In modern local processing specifications， there were mainly processing methods such as frying， steaming and carbonizing. The components of Citri Reticulatae Pericarpium were mainly volatile oil and flavonoids. After processing， the total amount of volatile oil generally decreased， and the contents and compositions of volatile oil and flavonoids also changed. It may be the main reason for the difference of efficacy before and after processing. At present， the optimization of processing technology of Citri Reticulatae Pericarpium mainly focuses on steaming， processing with vinegar and baking. Pharmacological research on Citri Reticulatae Pericarpium mainly focuses on reducing blood lipid， relieving cough， relieving asthma and resolving phlegm， and inhibiting pulmonary fibrosis. The current research on the processing methods of Citri Reticulatae Pericarpium is not in-depth enough， the material basis of many processing methods has not been clarified， and the research on the efficacy before and after processing is not in-depth enough. Further research is needed to clarify the material basis and mechanism after the processing of Citri Reticulatae Pericarpium， so as to standardize the processing method and establish specific quality standards.

As a traditional Chinese medicinal material， Citri Sarcodactylis Fructus is often used as medicine after steaming to reduce its pungency and give full play to its medicinal effects. By consulting the relevant literature， this paper intends to sort out the related researches on the processing history， modern processing standard records， flavor and meridian tropism， efficacy， processing and taking methods， processing technology， chemical composition， pharmacological effects and quality analysis of Citri Sarcodactylis Fructus. It is found that the processing methods of Citri Sarcodactylis Fructus in the past dynasties are mainly roasting， distilled into dew， aging， frying， salting and steaming， of which steaming is the most common. In modern times， steaming is mainly used in Guangdong and Sichuan. The descriptions of flavor and meridian tropism and efficacy of Citri Sarcodactylis Fructus in the past dynasties are basically consistent with the modern descriptions. Its taste is pungent， bitter and acidic， and it is warm in nature. It belongs to the liver， spleen， stomach and lung meridians. Citri Sarcodactylis Fructus contains volatile oil， flavonoids and their glycosides， coumarins and limonins and other compounds. In recent years， high performance liquid chromatography （HPLC）， gas chromatography-mass spectrometry （GC-MS） and ultra performance liquid chromatography-mass spectrometry （UPLC-MS） and other methods are commonly used for the chemical composition analysis. Citri Sarcodactylis Fructus has the activities of relieving cough， reducing phlegm， relieving asthma， anti-inflammation， anti-bacteria and anti-oxidation， etc. After processing， its volatile and non-volatile components， and pharmacological effects all have a certain change. However， the current research on processing of Citri Sarcodactylis Fructus is not in-depth enough. It is necessary to further analyze the material basis of steaming to reduce dryness， explore its dryness medicinal substances and dryness-effect quantitative correlation， so as to clarify its processing mechanism， and provide basis for the subsequent processing research， resource development and comprehensive application of Citri Sarcodactylis Fructus in the future.

Objective:To describe the differences in body mass index (BMI) distribution in adult twins registered in Chinese National Twin Registry (CNTR), and provide evidence for the risk factor analysis and prevention and control of overweight or obesity.Methods:A total of 32 725 twin pairs aged 18 years and above who completed the questionnaire survey during 2010-2018 and had complete registered information in CNTR and normal body weight and length were included in the analysis on the population and region specific distributions of BMI of twin pairs and the difference in BMI in twin pairs.Results:The twin pairs included in the analysis were aged (34.6±12.4) years, the twin pairs of same gender accounted for 79.7%. The average BMI was 22.5 kg/m 2. The overall prevalence of obesity and overweight was 4.9% and 23.7%, respectively. Participants who were men, 50-59 years old, married, had lower education level, and lived in northern China had higher overweight rate and obesity rate ( P<0.001). The difference in overweight or obesity prevalence between monozygotic (MZ) twin pars and dizygotic (DZ) twin pairs was not significant, but firstborn twin pairs had slightly higher rates of overweight and obesity than later-born twin pairs ( P<0.05). The analysis in same gender-twin pairs indicated that the difference in BMI was associated with age (trend test: P<0.001), and the difference was more obvious in DZ twin pair in MZ pair and this difference increased with age. The concordant rate of BMI was higher in MZ twin pairs than DZ twin pairs ( P<0.05). Conclusion:The distribution of BMI of twin pairs varied with population and region and BMI varied with age due to its genetic nature.

Objective: To understand the epidemiological characteristics of foodborne disease outbreaks in schools in Zhejiang province, and to provide evidence for effective prevention and control of foodborne disease outbreaks in schools. Methods: A descriptive analysis was conducted on foodborne disease outbreaks in Zhejiang schools reported by the national foodborne disease outbreaks surveillance system from 2010 to 2019. Results: During the past 10 years, a total of 86 foodborne disease outbreaks in schools were reported, with 1 755 illnesses, 240 hospitalizations, and no deaths. Pathogenic bacteria and their toxins were the main causes of foodborne disease outbreaks in schools, accounting for 83.0%(44/53) of all identified causes. The top four types of pathogenic bacteria were Staphylococcus aureus, Salmonella, diarrheagenic Escherichia coli, and Bacillus cereus. Meat products and mixed foods were the main foods that caused the outbreaks, each accounting for 16.3%(14/86) of total incidents. High school cafeterias were places with the highest incidence, accounting for 38.4%(33/86) of the total. School concession stands caused the largest number of hospitalizations, accounting for 37.1%(89/240) of the total. The peak month of foodborne disease outbreaks in schools was September, followed by June, May, and October. Crosscontamination and improper storage were the main causes of foodborne disease outbreaks in schools. Conclusion Bacterial foodborne disease is a major food safety issue in schools in Zhejiang Province. In summer and fall, school cafeterias and food stores should take effective measures to prevent bacterial foodborne disease outbreaks caused by cross-contamination and improper storage of high-risk foods such as meat products and cold-processed bakeries.

Objective To compare the diversity of mitochondrial genomes of Angiostrongylus cantonensis in the mainland of China. Methods According to the population genetic of A. cantonensis,seven female worms were selected to characterize the mi-tochondrial(MT)genomes. Twelve primer pairs based on known MT genome(GQ398121)were used for PCR. The target frag-ments were sequenced and aligned. The gene localization,genome structure,composition of nucleotide,distribution of variable sites,and phylogeny were analyzed by employing multiple softwares. Results Five distinct types were identified from seven com-plete MT genomes. They were similar in size and structure,i.e.,ranging 13 491-13 502 bp,including 12 protein-coding genes,2 ribosomal genes,22 tRNA genes,and 2 major non-coding regions. All the genes were localized at the same strand and had the same transcription direction. A total of 745 variable sites were identified,accounting for 5.5%. Among the variable sites,59 were deletion/insert mutations,105 transversions,and 581 transitions. The variable sites distributed evenly at the complete genome. Conclusion The study reveals the mutation profile in the whole MT genome of A. cantonensis and thus will facilitate the develop-ment of intraspecific differential diagnosis.