OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*

Objective: To examine the application value of 3D Slicer software assisted domestic frameless stereotactic robot in biopsy of intracranial lesions. Methods: A retrospective analysis was performed on 80 patients who admitted consecutively and underwent intracerebral lesions biopsy with the domestic frameless stereotactic robot at Department of Neurosurgery, Aerospace Central Hospital from January 2019 to December 2021. There were 36 males and 44 females, with a mean age of (38.5±18.0) years (range: 6 to 71 years). Before surgery only enhanced T1-weighted three-dimensional magnetization prepared gradient echo sequences and diffusion tensor imaging scans were performed. Self-reconstruction of intracranial lesions, cerebral cortex and blood vessels was carried out using 3D Slicer software system after the DICOM format imaging data of 80 patients were collected. These imaging data were merged to the workstation of the domestic frameless stereotactic robot for preoperative surgical planning and the surgical puncture path was designed to avoid blood vessels in the brain functional area, cerebral cortex and sulcus. Results: All frameless stereotactic biopsy were successfully performed. Postoperative pathological diagnosis included 50 cases of diffuse astrocytic and oligodendroglioma, 15 cases of lymphoma, 5 cases of metastatic tumors, 5 cases of inflammatory demyelinating disease, 2 cases of inflammatory granuloma, 1 case of hemangioma, 1 case of acute lymphoblastic leukemia intracranial invasion and 1 case of seminoma. The positive diagnosis rate was 100% (80/80). Postoperative imaging confirmed that the puncture path and target were accurately implemented according to the preoperative planning, and the target error was (1.32±0.44) mm (range: 0.55 to 1.99 mm). One case of puncture-related bleeding occurred at the target after surgery and improved after treatment. Conclusion: The three-dimensional multimodal images reconstructed by the 3D Slicer software before operation could help the surgeons make the preoperative planning and reduce the risk of stereotactic brain biopsy.
Male ; Female ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Brain Neoplasms/pathology* ; Diffusion Tensor Imaging ; Retrospective Studies ; Robotics ; Biopsy ; Software ; Stereotaxic Techniques

Squamosa promoter binding protein-like (SPL) family is a group of important transcription factors involved in the regulation of plant growth and development and the response to environmental stress, but there are few studies in perennial fruit trees such as citrus. In this study, Ziyang Xiangcheng (Citrus junos Sib.ex Tanaka), an important rootstock of Citrus, was used as the material for analysis. Based on plantTFDB transcription factor database and sweet orange genome database, 15 SPL family members were genome-widely identified and cloned from Ziyang Xiangcheng, and named CjSPL1-CjSPL15. Sequence analysis showed that the open reading frame (ORF) length of CjSPLs ranged from 393 bp to 2 865 bp, encoding 130-954 amino acids. Phylogenetic tree divided 15 CjSPLs into 9 subfamilies. Gene structure and conserved domain analysis predicted 20 different conserved motifs and SBP basic domains. Analysis of cis-acting promoter elements predicted 20 different promoter elements, including those related to plant growth and development, abiotic stress and secondary metabolites. The expression patterns of CjSPLs under drought, salt and low temperature stresses were analyzed by real-time fluorescence quantitative PCR (qRT-PCR), and many CjSPLs were significantly up-regulated after stress treatment. This study provides a reference for further study on the function of SPL family transcription factors in citrus and other fruit trees.
Phylogeny ; Transcription Factors/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Multigene Family ; Stress, Physiological

Laminin subunit alpha 4 (LAMA4),a member of the laminin family,is present in the intercellular matrix of adult tissues as a major component of basement membrane.LAMA4 is involved in the adhesion of cells and can bind to corresponding integrins to activate relevant signaling pathways,playing an essential role in the growth,proliferation,and migration of cells.It has been demonstrated that LAMA4 is associated with the occurrence and development of a variety of diseases including tumors,and the expression of LAMA4 can be used as a biomarker of tumor diagnosis and prognosis.This paper summarizes the current research progress in LAMA4 with the focus on the relationship between LAMA4 and diseases,especially tumor,with a view to provide new directions for the future research.
Adult ; Humans ; Laminin ; Extracellular Matrix

This report presented the endemic status of schistosomiasis and analyzed the data collected from the national schistosomiasis prevention and control system and national schistosomiasis surveillance sites in the People’s Republic of China at a national level in 2021. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis in China, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to consolidate the achievements of schistosomiasis elimination, and Sichuan and Jiangsu provinces maintained the criteria of transmission interruption, while Yunnan, Hubei, Anhui, Jiangxi and Hunan provinces maintained the criteria of transmission control by the end of 2021. A total of 451 counties (cites, districts) were found to be endemic for schistosomiasis in China in 2021, with 27 571 endemic villages covering 73 250 600 people at risk of infections. Among the 451 endemic counties (cities, districts), 75.17% (339/451), 22.17% (100/451) and 2.66% (12/451) achieved the criteria of elimination, transmission interruption and transmission control of schistosomiasis, respectively. By the end of 2021, 29 037 cases with advanced schistosomiasis were documented in China. In 2021, 4 405 056 individuals received serological tests and 72 937 were sero-positive. A total of 220 629 individuals received stool examinations and 3 were positive. In 2021, snail survey was performed in 19 291 endemic villages in China and Oncomelania snails were found in 7 026 villages, accounting for 36.42% of all surveyed villages, with 12 villages identified with emerging snail habitats. Snail survey was performed at an area of 686 574.46 hm² and 191 159.91 hm² snail habitats were found, including 1 063.08 hm² emerging snail habitats and 5 113.87 hm² reemerging snail habitats. In 2021, 525 878 bovines were raised in the schistosomiasis endemic areas of China, and 115 437 received serological examinations, with 231 positives detected. Among the 128 719 bovines received stool examinations, no positives were identified. In 2021, there were 19 927 schistosomiasis patients receiving praziquantel chemotherapy, and 729 113 person-time individuals and 256 913 herd-time bovines were given expanded chemotherapy. In 2021, snail control with chemicals was performed in 117 372.74 hm² snail habitats, and the actual area of chemical treatment was 65 640.50 hm², while environmental improvements were performed in snail habitats covering an area of 1 244.25 hm². Data from the national schistosomiasis surveillance sites of China showed that the mean prevalence of Schistosoma japonicum infections were both zero in humans and bovines in 2021, and no S. japonicum infection was detected in snails. The results demonstrate that the overall endemic status of schistosomiasis remained at a low level in China in 2021; however, the progress towards schistosomiasis elimination was slowed and the areas of snail habitats rebounded mildly. Strengthening researches on snail diffusion and control, and improving schistosomiasis surveillance and forecast are recommended to prevent reemerging schistosomiasis.

ObjectiveTo analyze the effective components of Periploca forrestii against rheumatoid arthritis（RA）by targeting tumor necrosis factor （TNF）-α based on network pharmacology and experimental verification. MethodThe preliminary research of the research group found that the alcohol extracts of P. forrestii （CDLF and CQAF） had significant anti-RA activities，and 10 monomers with such activities were identified. The anti-RA activities of active monomers，CDLF， and CQAF were compared by the enzyme-linked immunosorbent assay （ELISA）with interleukin（IL）-6，nitric oxide （NO），IL-1β， and prostaglandin E₂（PGE₂）as indicators. Network pharmacology was employed to analyze the possible molecular mechanism of P. forrestii against RA. The targeting ability of P. forrestii chemical monomers to TNF-α was verified by TNF-α molecular docking，surface plasmon resonance （SPR）， and TNF-α-induced L929 injury model. ResultELISA showed that the anti-RA activities of CDLF and CQAF were significantly stronger than those of identified 10 active monomers. Network pharmacology analysis showed that the core targets of P. forrestii against RA were signal transducer and activator of transcription protein 3 （STAT3），TNF， and IL-6. Gene Ontology（GO） analysis revealed collagen catabolism，inflammatory response，positive regulation of nuclear factor kappa-B（NF-κB） transcription factor activity，and positive regulation of B cell proliferation. Kyoto Encyclopedia of Genes and Genomes （EKGG） pathway enrichment analysis demonstrated TNF signaling pathway，phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway，NF-κB signaling pathway，Toll-like receptor signaling pathway，mitogen-activated protein kinase（MAPK） signaling pathway， etc. Verification experiments by TNF-α molecular docking，SPR， and TNF-α-induced L929 injury model found that CDLF and CQAF had good binding activities and could manifestly antagonize TNF-α. However， the active components separated and identified from CDLF and CQAF did not show the same anti-TNF-α activity. ConclusionThe CDLF and CQAF of P. forrestii may treat RA by targeting TNF-α. The experiments found that the isolated chemical components had weaker binding activity to TNF-α than CDLF and CQAF. Meanwhile，the research group isolated chemical components with a minimum mass fraction of 0.25 ng·g^-1 from P. forrestii， which suggested that the active components generated by binding to TNF-α with anti-RA activities were presumedly trace components .

Objective: To analyze and compare the distribution of the high-risk population of upper gastrointestinal (UGI) cancer and the factors influencing the compliance rate of endoscopic screening in urban China and rural China. Methods: From 2015 to 2017, an epidemiological survey was conducted on residents aged 40-69 in two rural areas (Luoshan county of Henan province, Sheyang county of Jiangsu province) and two urban areas (Changsha city of Hunan province, Harbin city of Heilongjiang province). As a result, high-risk individuals were recommended for endoscopic screening. Chi-square χ(2) test was used to compare the high-risk rate of UGI cancer between urban and rural residents. In addition, the multivariate logistic regression model was used to analyze the factors influencing the compliance rate of endoscopic screening. Results: A total of 48, 310 residents aged 40-69 were enrolled in this study, including 22 870 (47.34%) residents from rural areas and 25 440 (52.66%) residents from urban areas. A total of 23 532 individuals were assessed with a high risk of UGI cancer, with an overall risk rate of 48.71%. A higher proportion of participants with high risk was observed in rural China (56.17%, 12 845/22 870) than in urban China (42.01%, 10 687/25 440). A total of 10 971 high-risk individuals with UGI cancer participated in endoscopic screening, with an overall compliance rate of 46.62% (10 971/23 532), 45.15% (5 799/12 845) in rural China, and 48.40% (5 172/10 687) in urban China. In rural population, the compliance rate of endoscopic screening was higher in those of females, aged 50-69 years, primary school education or above, high income, a family history of UGI cancer, history of gastric and duodenal ulcer, history of reflux esophagitis, and history of superficial gastritis, but lower in smokers (P<0.05). Among the urban population, the compliance rate of endoscopic screening was higher in those aged 40-49 years, uneducated, low income, family history of UGI cancer, history of reflux esophagitis, history of superficial gastritis, but lower in smokers (P<0.05). Conclusions: The proportion of participants with high risk of UGI cancer in rural areas is higher than that of urban areas. The compliance rates of endoscopic screening in urban and rural areas are low, and influencing factors of endoscopic screening exhibit some differences in rural China and urban China.
China/epidemiology* ; Early Detection of Cancer ; Esophagitis, Peptic ; Female ; Gastritis ; Gastrointestinal Neoplasms/epidemiology* ; Humans ; Rural Population ; Urban Population