Objective To analyze the disease burden of chronic kidney diseases (CKD) attributed to high body mass index (BMI) in China from 1992 to 2021 and predict the disease burden for the next decade, and to provide evidence for the prevention and treatment of CKD. Methods Using the Global Burden of Disease (GBD) database and the Joinpoint model, the average annual percentage rate change (AAPC) of the mortality rate and disability-adjusted life year (DALY) rate was calculated to describe and analyze the CKD disease burden attributed to high BMI in China from 1992 to 2021. The ARIMA model was employed to predict and analyze the change trend of the CKD disease burden. Results From 1992 to 2021, the mortality rate and DALY rate attributed to high BMI-induced chronic kidney disease showed an upward trend. Compared to 1992, the attributed number of deaths increased by 324.38%, and DALYs increased by 268.56%; the mortality rate increased by 64.00%, and the DALY rate grew by 51.62%. From 1992 to 2021, the mortality rate and DALY rate for males were lower than those for females, but the growth rate for males exceeded that of females. From 1992 to 2021, the mortality rate and DALY rate of chronic kidney disease attributed to high BMI in China increased with age. The average annual change rate of chronic kidney disease attributed to high BMI in China from 1992 to 2021 (mortality rate: 1.40 per 100,000 (95% CI: 1.04–1.76), DALY rate: 1.43 per 100 000 (95% CI: 1.17–1.70)) was higher than thHuaiyin Normal University, Huai'anher social demographic index (SDI) regions. The ARIMA model predicted that the age-standardized mortality rate increased from 2.91 per 100 000 in 2022 to 3.05 per 100 000 in 2026, and the age-standardized DALY rate increased from 69.65 per 100 000 in 2022 to 73.58 per 100 000 in 2026. Conclusion Chronic kidney disease attributed to high BMI in China is on the rise, and it will continue to grow in the future. The focus of CKD prevention and control should be on males and the elderly, while active measures should be taken to reduce the occurrence and progression of chronic kidney disease.

Objective: To explore the longitudinal associations between dietary macronutrients and lung function in schoolaged children, so as to provide the nutritional research evidence for promoting children s lung health. Methods: In November 2021, two primary schools located in Chengdu, Sichuan Province were selected from the Southwest China Childhood Nutrition and Growth (SCCNG) cohort by a stratified cluster random sampling method, enrolling a total of 1 112 school aged children aged 8 to 13 years. At baseline, the dietary and sociodemographic characteristics of the children were assessed. One year later, the forced vital capacity (FVC) of the children was measured and converted into Z scores (FVC- Z ), while the vital capacity index (VCI) was also calculated. Generalized linear regression analysis was employed to examine the associations between dietary macronutrients and lung function, considering interactions with gender and age, followed by stratified analysis. Results: After adjusting for confounding factors, the analysis results of the generalized linear regression model showed that the carbohydrate energy ratio was negatively correlated with FVC- Z ( β =-0.02) and VCI ( β =-0.16), while the fat energy ratio showed a positive correlation with FVC- Z ( β =0.03) and VCI ( β =0.23) ( P <0.05). The protein energy ratio was positively correlated with FVC- Z ( β =0.09) and VCI ( β =0.60) specifically in girls ( P <0.05). Additionally, there was an interaction effect of age on the associations between macronutrients and lung function ( P <0.01); in children aged 8-9 and 10-11, the carbohydrate energy supply ratio was negatively correlated with FVC- Z ( β =-0.04, -0.03) and VCI ( β =-0.29, -0.21), and fat energy supply ratio was positively correlated with FVC- Z ( β =0.07, 0.05) and VCI ( β =0.46, 0.32) ( P <0.05). Conclusions There are age and sex differences in the association of dietary macronutrients with lung function, with a low carbohydrate, high fat diet promoting lung function in children. Additionally, protein intake appears to have a positive influence on the lung function of girls. The early school age period may represent a critical window for dietary interventions aimed at promoting lung health.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

Objective: To explore the differences in the gut microbiota of primary school students with different levels of sugar sweetened beverage intake, so as to provide scientific evidence for better identification of health risks in children and the development of targeted health policies. Methods: In June 2022, a total of 192 healthy primary school students from Chengdu were selected using a stratified cluster random sampling method. The sugar sweetened beverage intake was assessed through a dietary frequency questionnaire. Based on the median daily sugar sweetened beverage intake, primary school students were categorized into a low intake group ( n =96) and a high intake group ( n =96). The gut microbiota in fresh fecal samples from the two groups of primary school students was analyzed using 16S rRNA high throughput sequencing, and the diversity and community structure differences in the gut microbiota were compared. Results: Children in the low intake group had a sugar sweetened beverage intake of (21.3±1.6) mL/d, while the high intake group had an intake of (269.6±37.3) mL/d. Diversity analysis results showed that there were no statistically significant differences between the low intake and the high intake group in terms of α diversity metrics: Observed_otus index [298.50 (259.75, 342.25), 305.50 (244.25, 367.75)], Goods_coverage index [1.00 (1.00, 1.00), 1.00 (1.00, 1.00)], Chao index [304.18 (260.75, 348.78), 305.88 (245.68, 370.88)], Shannon index [5.88 (5.29, 6.45), 5.71 (4.89, 6.28)] and Simpson index [0.95 (0.91, 0.97), 0.94 (0.88, 0.97)] ( Z =-0.64, -0.76, -0.54, -1.76, -1.67, P >0.05). Furthermore, no statistically significant difference was observed in β diversity between the two groups ( R 2=0.006, P >0.05). At the genus level, the abundance of Blautia [0.033 (0.018, 0.055)] and Fusicatenibacter [0.009 (0.005, 0.015)] were higher in the low intake group compared to the high intake group [0.024 (0.013, 0.041),0.006 (0.003, 0.011)]and differences were statistically significant ( Z =-2.52, -2.81, P <0.05). LEfSe analysis highlighted intergroup differences primarily in Blautia, Fusicatenibacter and Sarcina( LDA= 3.56,3.12,3.53, P <0.05). Conclusions There is no significant difference in the diversity and overall structure of the gut microbiota in primary school students with different levels of sugar sweetened beverage intake. However, there are species variations at the genus level. The information can serve as a scientific basis for identifying health risks in primary school students and formulating targeted health strategies.

Abstract: In the present study, the compound XL-12 from our previous work was utilized as a lead compound. Through the optimization of the terminal phenyl ring, 12 target compounds were designed and synthesized. The structures of all target compounds were confirmed by 1H NMR, 13C NMR, and H RMS. In vitro enzyme activity assay showed that most compounds demonstrated significant inhibitory activity toward Bruton’s tyrosine kinase (BTK) and Janus kinase 3 (JAK3). Among them, compound I-3 exhibited moderate cell proliferation inhibitory activity toward Daudi cells and BaF3-JAK3 cells. In the evaluation of anti-inflammatory activity in vitro, compound I-3 could effectively inhibit the production of inflammatory factors IL-6; besides, it exhibited superior anti-inflammatory activity compared to ibrutinib in xylene-induced ear swelling model in mice.

Humans ; Consanguinity ; Exome Sequencing ; Mutation/genetics* ; Sequence Analysis, DNA ; Ciliary Motility Disorders ; Axonemal Dyneins/genetics*

Objective: To investigate the prospective effects of intake of each food group on the development of lung function of pupils,so as to provide theoretical basis for promoting the healthy development of lung function and preventing chronic respiratory diseases in Chinese children. Methods: A cluster stratified sampling method was used to select a total of 893 pupils in grades 2-5 from Chengdu in November 2021. Dietary data of respondents were collected using a food frequency questionnaire within the past year,then the food group intake was categorized into T1, T2 and T3 from low to high by the trichotomous method, and anthropometric measurements including lung capacity were obtained in 2022. Logistic regression models and test for trend were used to analyze the prospective effects of intake of each food group on lung function development of pupils. Results: Among male students, consumption of vegetables [118.6(50.5, 188.2)g/d] and milk and dairy products [200.0(73.3, 250.0)g/d] were higher in the excellent lung capacity group than in the non excellent lung capacity group [90.0(37.1, 192.9), and 178.6(35.7, 250.0)g/d],with statistically significant differences ( Z =-1.98, -2.24); among girls, the group with excellent lung capacity consumed less staple food [391.1(273.6, 511.4)g/d] than the group with non excellent lung capacity [407.4(309.5, 594.3)g/d], and the group with excellent lung capacity consumed more aquatic products [31.2(14.6, 69.8)g/d] and milk and dairy products [215.0(107.1, 250.1) g/d ] than that of the non excellent lung capacity [19.4(10.7, 58.3), 114.3(35.7, 250.0)g/d] ( Z =-2.01, -3.33, -5.10)( P < 0.05 ). After adjusting for energy, body mass index Z score(BMI Z ), mother s education level, averge family income monthly, whether presence of smokers in the living environment, and whether participation in physical activities during the past week, among male students, T3 group of vegetable intake ( OR =0.48, 95% CI = 0.27-0.86), T2 group of bean and soy product intake ( OR = 0.52 , 95% CI =0.27-0.96)，T2 and T3 groups of milk and dairy products intake (T2： OR =0.54, 95% CI =0.31-0.93; T3： OR = 0.52 , 95% CI =0.30-0.90) were negatively associated with non excellent lung capacity ( P <0.05). Among girls, T3 group of aquatic product intake( OR =0.52, 95% CI =0.28-0.97), T2 and T3 groups of milk and dairy product (T2: OR =0.44, 95% CI =0.25- 0.76 ;T3: OR =0.33, 95% CI =0.19-0.59) were negatively associated with nonexcellent lung capacity, whereas the T2 group of red meat intake ( OR =2.51, 95% CI =1.37-4.67) was positively associated with non excellent lung capacity. Non excellent lung capacity was found to be negatively associated with vegetable and milk and dairy product intake in boys by test for trend; in girls, milk and dairy products intake was negatively associated with non excellent lung capacity, whereas red meat intake was positively associated with non excellent lung capacity ( t =-1.13，-0.44；-3.03，1.95, P trend <0.05). Conclusions Milk and dariy products intakes reduce the risk of non excellent lung capacity in pupils, vegetables intakes reduce the risk of non excellent lung capacity in boys, and the intake of red meat increases the risk of non excellent lung capacity in girls. Promoting rational food choices is necessary for children to improve healthy lung development.

MicroRNA(miRNA)is a kind of small non-coding single stranded RNA that can participate in multiple biological processes.It also plays an important role in regulating the immune function of the body.Immune thrombocytopenia(ITP)is an autoim-mune disease,whose cause and deterioration are closely related to miRNA regulates immune function of CD4+T cells subsets.In ITP patients,different expression of miRNA can affect the immune function of CD4+T cells subsets,which causes not only unbalanced ex-pression of Th1/Th2,Th17/Treg and excessive differentiation of TFH,but also abnormal cytokine secretion furthermore.This paper summarizes the unbalanced mechanism of miRNA regulating immune function of CD4+T cells subsets in ITP,so as to provide inspira-tion for exploring the immunology and immunotherapy of ITP.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.