Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

Liver fibrosis is caused by various factors such as viral infection， alcohol intake， and metabolism-related damage， leading to the replacement of normal tissue by fibrous scars. As a regulatory factor for cell proliferation， insulin-like growth factor 1 （IGF-1） participates in the regulation of cell cycle， the promotion of cell proliferation and differentiation， and the inhibition of cell apoptosis by binding to its receptor insulin-like growth factor-1 receptor （IGF-1R）. Studies have shown that the IGF-1/IGF-1R signaling pathway can regulate the process of liver fibrosis by affecting the senescence and apoptosis of hepatocytes， the activation and proliferation of hepatic stellate cells， and the dysfunction of endothelial cells. In addition， the IGF-1/IGF-1R signaling system can also regulate multiple mechanisms such as DNA damage repair， cell proliferation， lipid metabolism， cell senescence， and oxidative stress， thereby providing new strategies and potential targets for the prevention and treatment of liver fibrosis. This article summarizes the mechanism of action of IGF-1/IGF-1R and its signal transduction system in mediating liver fibrosis by regulating DNA damage repair in different cells， in order to provide a theoretical basis for the treatment of liver fibrosis.

ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction （清肺渗湿汤） combined with western medicine for patients with bronchial asthma of heat wheezing syndrome， and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group， each group with 43 participants. The control group received conventional western medicine， and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group， 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness； secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， asthma control test （ACT） score， pulmonary function indices such as forced expiratory volume in 1 second （FEV₁）， forced vital capacity （FVC）， peak expiratory flow （PEF）， serum inflammatory factor levels including interleukin-4 （IL-4）， tumour necrosis factor-α （TNF-α）， and high-sensitivity C-reactive protein （hs-CRP）， and immune function indices including CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺. All outcome measures were evaluated before and after treatment. Vital signs were monitored， and electrocardiography， blood routine， urine routine， liver function， and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% （39/40）， which was significantly higher than that of the control group （85.0%， 34/40， P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， IL-4， TNF-α， hs-CRP， and CD8⁺ levels， as well as increased ACT scores， CD3⁺， CD4⁺， CD4⁺/CD8⁺， FEV₁， FVC， and PEF levels （P＜0.05 or P＜0.01）. Moreover， the improvements in these indices were more significant in the treatment group than in the control group （P＜0.05 or P＜0.01）. No significant abnormalities in safety indicators were observed in either group， and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms， pulmonary function， and clinical effectiveness， with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.

OBJECTIVE: To investigate the clinical manifestations and genetic etiology of a fetus with Neurodevelopmental disorders with deformed facial features and distal skeletal abnormalities (NEDDFSA). METHODS: Clinical data of a NEDDFSA fetus diagnosed at the Affiliated Women and Children's Hospital Affiliated to Ningbo University in March 2025 was selected as the study subject. Whole-exome sequencing (WES) was carried out on the amniotic fluid and parental peripheral blood samples, and candidate variants was verified by Sanger sequencing. The pathogenicity of candidate variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094). RESULTS: At 30 weeks of gestation, the fetus was found to have microcephaly, short femur and intrauterine growth restriction. WES revealed that the fetus harbored a de novo heterozygous frameshift variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene, which was rated as pathogenic (PM2_Supporting+PS2_Supporting+PVS1). Combined with 25 cases from the literature, the main manifestations of patients have included intellectual disability, growth retardation and cranio-limb skeletal dysplasia, albeit without clear genotype-phenotype correlation. CONCLUSION The de novo variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene probably underlay the NEDDFSA in this fetus. Genetic testing has enabled accurate prenatal diagnosis and provided evidence for genetic counseling and reproductive guidance of this family.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/genetics* ; Transcription Factors/genetics* ; Fetus/abnormalities* ; Exome Sequencing ; Prenatal Diagnosis

Objective To explore the effect and preliminary mechanism of the plant-derived immunostimulatory molecule,ophiopogonin,on enhancing the immune response of a subunit vaccine with the receptor-binding domain(RBD)of coronavirus spike protein as the antigen.Methods CCK-8 assay was used to determine the cytotoxicity of ophiopogonin D'(OPD')on bone marrow-derived dendritic cells(BMDCs).Female Balb/c mice were randomly divided into RBD,RBD/OPD',RBD/Alum,and control groups.The immunization dose was 5 μg of antigen per mouse and 100 μg of adjuvant per mouse,and immunization was carried out according to the intramuscular injection immunization procedure on days 0,21,and 42.The titers of specific IgG and its subtype antibodies were detected by ELISA.The cytokine levels in the supernatant of splenocytes were detected using ELISA.The number of splenocytes secreting IFN-γ was detected by ELISpot.Laser confocal microscopy was employed to observe the uptake of antigen by BMDCs.The phagocytic ability of BMDCs for antigen was quantitatively analyzed by flow cytometry.The mechanism of its enhanced immune effect was preliminarily explored using transcriptomics technology combined with bioinformatics research.Results When the concentration of OPD'was less than 5 μg/mL,the survival rate of BMDCs was 100%.After a single intramuscular injection in mice,except for a slight decrease in body weight,the other biochemical indicators were within corresponding normal ranges.After intramuscular injection immunization of the vaccine,the titers of serum-specific IgG,IgG1,and IgG2a in the RBD/OPD'group were significantly higher than those in the RBD group(P<0.05).Compared with the RBD group,the RBD/OPD'group induced a high-level Th1 cell immune response of IL-1β,TNF-α,and IFN-γ(P<0.01)and had more lymphocytes secreting IFN-γ(P<0.001).Laser confocal microscopy displayed that BMDCs took up more antigens after OPD'treatment,which was further confirmed with flow cytometry in quantitative analysis on antigen uptake rate(P<0.01).Transcriptomics results indicated that there was more significant enrichment of the PPAR signaling pathway in the RBD/OPD'group than the RBD group,suggesting that OPD'may activate the PPAR signaling pathway to exert its adjuvant effect.Conclusion OPD'effectively enhances the immune response of the RBD subunit vaccine,and its action mechanism may be related to the activation of the PPAR signaling pathway.

Objective To prepare tubeimoside Ⅲ nanoemulsion(TBMⅢ-NE)and evaluate its adjuvant effect in vaccines.Methods TBMⅢ-NE was prepared using low-energy emulsification.Dynamic light scattering was used to characterize the particle size and polydispersity index of the obtained TBMⅢ-NE,and transmission electron microscopy(TEM)was employed to observe the morphology.CCK-8 assay was utilized to determine the cytotoxicity of TBMⅢ-NE on bone marrow-derived dendritic cells(BMDCs).The in vitro safety of TBMⅢ-NE was evaluated using a hemolysis assay.The ability of TBMⅢ-NE to promote the phagocytosis of antigens by DC2.4 cells was observed using confocal laser microscopy.After co-incubation of TBMⅢ-NE with BMDCs,the expression levels of CD40,CD86,MHC-Ⅰ,and CCR7 on the surface of BMDCs were detected using flow cytometry,and the levels of cytokines in the supernatant of BMDCs were measured using enzyme-linked immunosorbent assay(ELISA).After female BALB/c mice were immunized with the SARS-CoV-2 antigen RBD in combination with TBMⅢ-NE,ELISA was conducted to determine the serum levels of specific IgG,IgG2a,and IgG1 antibodies.The number of specific IFN-γ-secreting cells in mouse splenocytes was detected using enzyme-linked immunospot(ELISpot)assay.Results The prepared blank nanoemulsion(BNE)and TBMⅢ-NE were in a particle size of 25.46 and 25.89 nm,and a polydispersity index of 0.214 and 0.125,respectively.TEM displayed that TBMⅢ-NE was in uniform sphere and well dispersed.When the TBMⅢ-NE adjuvant was diluted by 400-fold,the survival rate of BMDCs was approximately 86%.Compared with free TBMⅢ,the hemolytic toxicity of TBMⅢ-NE was significantly reduced(P<0.01).TBMⅢ-NE promoted the phagocytosis of antigens by DC2.4 cells and significantly increased the expression of CCR7 on the surface of BMDCs(P<0.05),indicating its potential to promote more dendritic cells to effectively migrate to lymph nodes.TBMⅢ-NE also promoted the expression of IL-6 and IL-1β in the supernatant of BMDCs(P<0.05).When combined with RBD,TBMⅢ-NE significantly increased the levels of specific IgG,IgG2a,and IgG1 antibodies in mouse serum(P<0.01)and promoted the secretion of specific IFN-γ in splenocytes(P<0.01),indicating that TBM Ⅲ-NE could enhance specific cellular immune responses.Conclusion A stable and highly effective TBMⅢ-NE that can induce humoral and cellular immune responses is successfully prepared.

Objective To investigate the interaction between a novel antimicrobial compound,HL-J6,and penicillin-binding protein 1(PBP1)of Staphylococcus aureus.Methods With MRSA252 genomic DNA as the template and PBP1F and PBP1R as primers,the expression plasmid pET30a-pbp1-39-608 was constructed by amplifying the target gene fragment followed by cloning into the Nde I/Xho I restriction sites of the pET30a vector.Then the obtained plasmids were transformed into Escherichia coli for the expression of PBP1-39-608 protein,and the product was purified by affinity chromatography.The inhibitory effect of HL-J6 on the transpeptidase activity of PBP1-39-608 was measured using peptidoglycan side chain backbone peptide,with thiol ester analog S2d as the substrate.The affinity between HL-J6 and PBP1-39-608 was detected using microscale thermophoresis(MST),and the binding interaction was confirmed by cellular thermal shift assay(CETSA).Molecular docking and dynamics simulation were performed using AutoDock Vina and Desmond software,respectively,to elucidate the binding mode of HL-J6 with the PBP1-39-608 protein and the key amino acid residues involved.Results The recombinant plasmid pET30a-pbp1-39-608 was successfully constructed,and PBP1-39-608 protein was produced after induction and purified,yielding a protein with an approximate molecular mass of 65×103.HL-J6 inhibited the transpeptidase activity of PBP1-39-608 in a time-dependent manner(P<0.001).The dissociation constant Kd of the binding between HL-J6 and PBP1-39-608 was 64.92 μmol/L.Molecular docking results showed that HL-J6 bound to the active pocket of PBP1-39-608 by interacting with key residues such as ILE-348,ASN-370,THR-516 and PHE-423,with a binding score of-8.38 kcal/mol(<-5.00 kcal/mol).Dynamics simulation results indicated that the complex became stable after 50 ns.Conclusion HL-J6 effectively inhibits the transpeptidase activity of Staphylococcus aureus PBP1,and shows stable interaction with the protein.

Objective:To analyze the reoperation rate and causes during the early adoption phase of unilateral biportal endoscopy (UBE).Methods:The clinical data of 180 patients who underwent UBE performed by a single surgeon at Beijing Friendship Hospital, Capital Medical University from October 2021 to June 2023 were retrospectively analyzed. Clinical and imaging data of patients who underwent reoperation were collected to analyze the causes of reoperation, and the clinical efficacy of the reoperations was also followed up. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used before and after treatment. Results:A total of 180 patients who underwent UBE were included in this study, of which 6 patients underwent reoperation, and the reoperation rate was 3.33%. Among them, 3 cases occurred in the first 90 surgeries and the other 3 occurred in the subsequent 90 surgeries. The causes of reoperation were as follows: recurrent lumbar disc herniation at the same segment postoperatively in 2 cases, insufficient decompression in 2 cases, disc herniation following isolated decompression in 1 case, and immediate postoperative perianal numbness in 1 case. The time between the initial surgery and reoperation ranged from 0 to 187 days, with an average of 63.3 days. The average follow-up time after reoperation was 18.3 months. The visual analogue scale (VAS) and Oswestry disability index (ODI) scores of the patients at the last follow-up were significantly improved compared with those before operation (VAS score of low back pain: 5.2 ± 1.7 before operation, 1.2 ± 0.8 at the last follow-up, P<0.001; VAS score of leg pain: 7.2 ± 1.5 before operation, 1.2 ± 1.2 at the last follow-up, P<0.001; ODI score: 67.3 ± 5.7 before operation, 20.2 ± 8.2 at the last follow-up, P<0.001). The postoperative modified MacNab scores were generally satisfactory (4 cases were rated as excellent, accounting for 66.7%; 2 cases were rated as good, accounting for 33.3%). Except for one patient who experienced dural injury during open revision surgery, there were no serious complications such as nerve damage. Conclusions:In the early stages of UBE surgery, recurrent lumbar disc herniation and inadequate decompression are the primary reasons for reoperation, typically occurring within the first three months postoperatively. Reoperation does not significantly increase the risk of nerve injury. Enhanced early postoperative follow-up is recommended. For symptomatic patients, a second surgery with thorough decompression can yield satisfactory treatment outcomes.

Objective:To apply bioinformatics methods to screen and analyze differentially expressed genes and biological processes specific to peripheral blood mononuclear cells in postmenopausal women with osteoporosis.Methods:From the Gene Expression Omnibus database, GSE56814, GSE56815, and GSE2208 datasets were screened as the research objects. The limma package in R language was used to screen differentially expressed genes, and the multigene Meta-analysis function in Metascape platform was utilized to perform enrichment analysis of gene ontology and pathway. Protein-protein interaction network construction, module analysis, core gene, and enrichment analysis will be carried out.Results:In the GSE56814 dataset, there were 84 significantly up-regulated genes and 73 significantly down-regulated genes. In the GSE56815 dataset, there were 8 significantly up-regulated genes and 33 significantly down-regulated genes. In the GSE2208 dataset, there were 21 significantly up-regulated genes and 10 significantly down-regulated genes. The multigene Meta-analysis identified 3 modules and 19 core genes in the Metascape platform. The core genes of MCODE1 included STXBP2, EIF2S2, EIF3J, PTPN6, FLNA, HLA- DQA1, CTSD, HSPA6, HLA- DPB1, EIF3E, PLEC. They mainly enriched formation of cytoplasmic translation initiation complex, antigen processing and presentation of exogenous peptide antigen via major histocompatibility complex Ⅱ, cytoplasmic translational initiation, nsp1 from SARS-CoV-2 inhibits translation initiation in the host cell, programmed cell death 1 signaling pathway, allograft rejection reaction. The core genes of MCODE2 included FOS, FOSB, EGR1, EGR2, JUNB. They mainly enriched RNA polymerase Ⅱ-specific, DNA-binding transcription activator activity, cellular response to salt, nerve growth factor-stimulated transcriptional pathways, nuclear kinase and transcription factor activation activation pathways, neurotrophic receptor tyrosine kinase 1 signaling pathway. The core genes of MCODE3 included CEBPA, H2AC6, SPI1. They mainly enriched transcriptional regulation of granulopoiesis. Conclusion:This study obtained a total of 3 modules, 19 core genes, and enriched them in the biological processes related to postmenopausal osteoporosis, providing new ideas and biological targets for exploring its occurrence pathogenesis and drug treatment.

Objective:To analyze the current status of clinical research registration on TCM prevention and treatment of malignant tumors in the Chinese Clinical Trail Registry (ChiCTR); To summarize its characteristics and shortcomings.Methods:Clinical studies on the TCM prevention and treatment for malignant tumors registered from the establishment of ChiCTR database to July 15, 2024 were retrieved. Excel 2019 software was used to sort out the data, including basic research information (registration time, registration number status, registration title, test organizer, research implementation location, etc.), design scheme (disease type, research type, intervention measures, sample size, blind method, etc.), research funding or material sources, as well as other information such as human specimen collection and recruitment of research objects. SPSS 27.0 software was used for frequency statistics.Results:A total of 891 registered studies were included, including 783 interventional studies and 108 observational studies; the areas with a large number of registrations were mainly Shanghai, Beijing, Guangdong Province, etc. ; the research funds mainly came from local finance; a total of 46 tumor diseases were involved in the study, with the largest number of lung cancer (209 items), followed by tumor-related syndromes (155 items), colorectal cancer (148 items), and breast cancer (136 items); the type of research design was mainly random parallel control; the main intervention measures were TCM decoction or herbal decoction pieces (373 items), and the dosage form was mostly decoction (216 items), followed by granules (94 items); single-blind or double-blind design was used in 217 registered trials; 663 registration trials involved the collection of human samples.Conclusions:The number of clinical research registrations on the TCM prevention and treatment for malignant tumors is increasing day by day. The shortcomings such as insufficient standardization of research design and lack of research transparency still exists. In the future, TCM researchers need to strengthen cooperation with international traditional medicine clinical trial registry, giving full play to the leading role of standardization of TCM trials, and using registration as a starting point to improve the quality of clinical research.