ObjectiveTo investigate the changing trends of the incidence rate， prevalence rate， mortality rate， and disability-adjusted life years （DALYs） of benign hepatobiliary and pancreatic diseases among people aged 15 — 39 years in China in 1990 — 2021. MethodsThe data of 2021 Global Burden of Disease Study were downloaded to obtain the epidemiological data of liver fibrosis/chronic liver disease， benign gallbladder/biliary tract diseases， and pancreatitis among people aged 15 — 39 years in China， and estimated annual percentage change （EAPC） was calculated to assess the changing trends of incidence， prevalence， mortality， and DALY rates. The Bayesian age-period-cohort model was used to predict the incidence and mortality rates from 2022 to 2030. ResultsIn 2021， there were 10 448 778 new cases of benign hepatobiliary and pancreatic diseases among the individuals aged 15 — 39 years in China， which was increased by 3.8% compared with the data in 1990， while the numbers of prevalent cases， deaths， and DALYs were reduced by 20.4%， 59.6%， and 50.2%， respectively. In 2021， the age-standardized incidence rates of liver fibrosis/chronic liver disease， benign gallbladder/biliary tract diseases， and pancreatitis were 1 104.40/100 000， 1 045.05/100 000， and 16.64/100 000， respectively； the age-standardized prevalence rates were 20 592.37/100 000， 2 364.85/100 000， and 9.43/100 000， respectively； the age-standardized mortality rates were 1.61/100 000， 0.04/100 000， and 0.18/100 000， respectively. From 1990 to 2021， there was a tendency of increase in the age-standardized incidence rate of liver fibrosis/chronic liver disease （EAPC=0.43， 95% confidence interval ［CI］： 0.23 — 0.63）， and there was also a tendency of increase in the age-standardized incidence and prevalence rates of benign gallbladder/biliary tract diseases （incidence rate： EAPC=1.07， 95%CI： 0.91 — 1.24； prevalence rate： EAPC=0.75， 95%CI： 0.59 — 0.89）， while there was a tendency of reduction in the age-standardized mortality rate of all three disease categories. Predictions for 2022 — 2030 indicated a potential reduction in the incidence rate of benign gallbladder/biliary tract diseases and an increase in the incidence rate of pancreatitis. ConclusionThere has been an overall upward trend in the incidence rate of liver fibrosis/chronic liver disease and gallbladder/biliary tract diseases over the past three decades， and it is needed to pay attention to the disease burden of benign hepatobiliary diseases among the people aged 15 — 39 years in China.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

BackgroundAs a high prevalence disorder， schizophrenia has caused significant burden to family and society due to the impairment of occupational and social function. Currently， the dominant vocational training model in China follows a paternalistic， clinician-led decision-making approach. Although it improves patients' social function to some extent， it undermines their autonomy and treatment adherence. Therefore， it is urgently necessary to explore a new intervention method to enhance treatment compliance and social function in patients. ObjectiveTo explore the impact of shared decision-making oriented vocational training on social function in hospitalized schizophrenia patients， so as to provide references for rehabilitation interventions. MethodsA total of 68 patients diagnosed with schizophrenia according to the International Classification of Diseases， tenth edition （ICD-10） criteria were consecutively enrolled from January to June 2024 at The Third People's Hospital of Wenjiang Distric， Chengdu. Participants were randomly allocated into the research group （n=34） and the control group （n=34） using a random number table method. Both groups received routine rehabilitation training， while the research group received shared decision-making oriented vocational training for 12 weeks， 2 times a week for 2 hours each time. Before and at the 4^th and 12^th week of intervention， two groups were evaluated by General Self-Efficacy Scale （GSES）， Stigma Scale for Mental Illness （SSMI）， Scale of Social function of Psychosis Inpatients （SSFPI） and Inpatient Psychiatric Rehabilitation Outcome Scale （IPROS）. ResultsA total of 63 participants completed the study， with 30 cases in the research group and 33 cases in the control group. Repeated measures ANOVA revealed statistically significant time effects and interaction effects in both groups for GSES， SSMI， SSFPI and IPROS scores （F=20.451， 16.022； 26.193， 12.944； 23.957， 5.023； 11.776， 3.985， P<0.05 or 0.01）， while no significant group effects were observed （F=0.188， 0.742， 1.878， 0.474， P>0.05）. At the 12^th week of intervention， there were statistically significant differences in GSES， SSMI， SSFPI and IPROS scores between the two groups. ConclusionShared decision-making oriented vocational training may help to improve social function in patients with schizophrenia. ［Funded by 2023 Chengdu Medical Research Project （number， 2023468）］

Objective To explore the influencing factors of coronary artery lesion severity in patients with acute coronary syndrome (ACS). Methods Clinical data of ACS patients admitted to Zhongshan Hospital, Fudan University from December 2017 to December 2019 were consecutively collected. The modified Gensini score was used to assess the severity of coronary artery lesions. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with coronary artery lesion severity. Results A total of 1 689 ACS patients were included, with an average age of (64.04±11.45) years; 1 353 (80.11%) were male, and the mean modified Gensini score was (8.12±4.03). Multivariate linear regression analysis revealed that sex (β＝0.97, P＝0.001), age (β＝0.03, P＝0.021), estimated glomerular filtration rate (eGFR; β＝－0.03, P＜0.001), low-density lipoprotein cholesterol (LDL-C; β＝0.58, P＜0.001), apolipoprotein A1 (Apo A1; β＝－1.28, P＝0.012), lipoprotein(a) [Lp(a); β＝0.001, P＝0.033], and glycated hemoglobin A_1C (HbA_1C; β＝0.45, P＜0.001) were independent influencing factors of the modified Gensini score. Conclusions Metabolic indicators, including Apo A1, LDL-C, HbA_1C, and Lp(a), may serve as risk factors for coronary artery lesion severity in ACS patients, with Apo A1 demonstrating the strongest impact.

Aim To study the role and mechanism of ML210 in glioma.Methods The cell viability was detected by CCK8 assay.The percentage of dead cells was detected by SYTOXstaining.The role of ferroptosis-signaling pathway in gliomas was detected bygenomics.Cell proliferation was observed by EdU staining and clone formation assay.Cell migration ability was detec-ted by scratch healing assay.The apoptosis was detec-ted by flow cytometry.Cell mitochondrial function was assesses by JC-1 staining.The mechanism of action of ML210 was detected by molecular docking coupled with immunoblotting assay(Western blot).The levels of ROS,MDA were observed by ELISA.Results Compared with the control group,ML210 treatment dose-dependently decreased glioma cell viability,in-hibited cell proliferation,migration,and increased cell apoptosis and mitochondrial dysfunction,which were reversed by ferroptosis antagonists.Gene microarray screening showed that 688 genes of the ferroptosissig-naling pathway were aberrant and 10 signaling path-ways were altered in gliomas.Molecular docking re-sults showed that ML210 binding to GPX4 significantly inhibited the protein expression level of GPX4 and pro-moted the elevation of ROS and MDA levels.Conclu-sions ML210 produces anti-glioma cells via GPX4-mediated ferroptosis pathway.

Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.

Objective:To study the development status and characteristics of the Traditional Chinese Medicine(TCM)service capacity of primary medical institutions(referred as primary)in Beijing.Methods:The case-base aggregation method was used to analyze the total amount,distribution,and development changes of total TCM costs in primary healthcare institutions in Beijing.Results:From 2019 to 2023,the average annual growth rate of the TCM costs of primary healthcare institutions in Beijing was 10.09％,and the proportion in total TCM costs increased from 16.01％to 18.19％.The average annual growth rate of the TCM costs of community health service centers(stations)was 11.78％,but there were negative growths in outpatient departments,clinics,and village clinics.The proportion of the primary TCM costs in its health costs increased from 29.16％to 32.56％.The average annual growth rate of income from primary herbal medicines and processed Chinese medicines were 16.75％and 10.13％.Conclusion:The primary TCM undertaking has developed steadily,and Beijing should continue to guide high-quality TCM resources to sink.Multiple measures should be taken to promote the development of TCM in outpatient departments,clinics,and village clinics.The coordination between prices and medical insurance reimbursement and payment methods should be strengthened.Supervision over the quality and use of Chinese medicine should be strengthened,and the technical service capabilities of primary TCM should be enhanced.

Objective To establish a transgenic mouse model of facioscapulohumeral muscular dystrophy(FSHD)using tamoxifen induction and Myf6-CreERT2 and FLExDUX4 mice.Methods Dual transgenic(M6D4/+)mice were generated by crossbreeding Myf6-CreERT2 hemizygous and FLExDUX4 hemizygous mice.Full-length DUX4(DUX4-fl)expression was induced by tamoxifen starting at 3 weeks old.The disease model was evaluated at 9 weeks old by assessing changes in body mass,four-limb strength,inverted screen test,skeletal muscle weight ratio,hematoxylin/eosin,Picrosirius Red,and immunofluorescent staining of skeletal muscle paraffin sections,quantitative real-time polymerase chain reaction(RT-PCR),and RNA-sequencing(RNA-seq)of skeletal muscle.Results Dual transgenic heterozygous mice(M6D4/+)were successfully obtained.These mice exhibited significant physiological and pathological changes at 9 weeks,including delayed weight gain,reduced four-limb strength and endurance,decreased skeletal muscle weight ratio,and increases in centrally nucleated muscle fibers and fibrosis.Expression levels of DUX4 and its targeted genes were significantly up-regulated in skeletal muscle,as demonstrated by RT-PCR.RNA-seq revealed up-regulation of immune regulation-,interleukin-6,and tumor necrosis factor-related genes and down-regulation of skeletal muscle development-and differentiation-related genes.Conclusions M6D4/+mice effectively simulated the skeletal muscle phenotype of FSHD and thus provide a good animal model for research into the pathogenesis,intervention,and treatment of FSHD.

To investigate the phenotype and genomic characterization of a mucoid-type Salmonella Saintpaul ST50 isolate from a urinary tract infection patient,promoting clinical diagnosis and treatment for urinary tract infections caused by Salmo-nella spp.Culture-based quantitative counts of midstream urine sample from the patient were conducted,and further biochemi-cal identification,mass spectrometry detection,serum agglutination test and antimicrobial susceptibility test(AST)were con-ducted on Salmonella isolate(2024JD5).Whole-genome sequencing(WGS)was performed on isolate 2024JD5 to predict sero-type,multilocus sequence type(MLST),resistance genes,and virulence genes.Two smooth-type of Salmonella Saintpaul ST50 were selected as comparative genomic reference strains from the Chinese local Salmonella genome database.The literature reviews of global Salmonella serotype of urinary tract infection were summarized.Specific serum agglutination confir-mation of isolate 2024JD5 failed due to characterization of the mucus type.The strain 2024JD5 was predicted as Salmonella Saintpaul(4,5,12:e,h:1,2)ST50 using WGS,and was resistant to ciprofloxacin,nalidixic acid,chloramphenicol and tetracy-cline with carrying aminoglycoside resistance genes aac(6')-Ⅰaa and aph(3)-Ⅱa,chloramphenicol resistance gene floR,tetra-cycline resistance gene tet,quinolone resistance gene qnrS1,and S83Y substitution in the gyrA gene was found in the quinolo-ne resistance determination region(QRDR).In addition,the strain 2024JD4 carried six types of non-plasmid-based mobile ge-netic elements and 144 virulence genes,including 71 secretion transporter genes and 58 fimbriae adhesion genes,respectively.Four types of fimbriae regulatory genes(csgB,csgC,fimW,fimY)were absent in comparison with smooth-type Salmonella Saintpaul.The literature reviews showed Salmonella Saintpaul was currently a rare Salmonella serotype in cases of urinary tract infections worldwide.Salmonella Saintpaul ST50 with mucoid-type is the pathogen of urinary tract infection with multi-drug resistant phenotypic and genotypic characteristics,and the high mucoid expression may be related to the compensatory mechanism of fimbriae regulatory genes absence in urinary tract colonization and adaptation.WGS combined with the Chinese local Salmonella genome database can effectively solve the diagnosis and biosafety assessments of rare Salmonella phenotypes.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.