OBJECTIVE To explore the efficacy and safe ty of Tripterygium wilfordii polyglycoside combined with finerenone in the treatment of diabetic nephropathy （DN）. METHODS This study selected 104 DN patients admitted to the Nephrology Department of Handan Central Hospital from January 2023 to May 2024 as the subjects and randomly assigned them into the control group （52 cases） and the combination group （52 cases）. All patients received basic treatment such as lipid-lowering and blood glucose control. On this basis， patients in the control group received finerenone， while those in the combination group received a combination therapy of T. wilfordii polyglycoside and finerenone. Both groups underwent treatment for a duration of three months. The two groups were compared in terms of clinical efficacy， renal function indicators [24-hour urine protein excretion （24 h UPE）， urinary albumin-to-creatinine ratio （UACR）， urinary albumin excretion rate （UAER） ] ， inflammatory factors [high mobility group box 1 protein （HMGB1）， interleukin-6 （IL-6）， nuclear factor-κB （NF-κB）， high-sensitivity C reactive protein （hs-CRP） ] ， and oxidative stress indicators [total antioxidant capacity （T-AOC）， superoxide dismutase （SOD）， advanced oxidation protein products （AOPP）， malondialdehyde （MDA） ] before and after treatment. Additionally， the occurrence of adverse drug reactions was recorded. RESULTS In terms of efficacy， the total effective rate of patients in the combination group was higher than that of the control group （ P ＜0.05）. After treatment， the levels of 24-h UPE， UACR， UAER， HMGB1， IL-6， NF-κB， hs-CRP， AOPP and MDA in the two groups were significantly lower than those in the same group before treatment； the levels of T-AOC and SOD in the two groups were significantly higher than those in the same group before treatment， with the combination group showing superior changes in the above indicators compared to the control group at the corresponding time point （ P ＜0.05）. In terms of safety， there was no statistical significance in the total incidence of adverse drug reactions between the two groups （ P ＞0.05）. CONCLUSIONS Compared to finerenone monotherapy， the combination therapy of T. wilfordii polyglycoside and finerenone demonstrates significant efficacy in treating DN. It effectively reduces proteinuria levels， alleviates inflammatory reaction， mitigates oxidative stress， and does not increase the risk of adverse reactions.

Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

Objective To evaluate the cost-utility of risdiplam in the treatment of pediatric spinal muscular atrophy （SMA） and analyze changes in patients’ out-of-pocket economic burden under the medical insurance scenarios. Methods A Markov model was developed from the healthcare system perspective to compare the long-term costs and quality-adjusted life years （QALYs） of risdiplam treatment versus conventional therapy. The incremental cost-utility ratio （ICUR） was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the robustness of the model. On this basis, health insurance scenarios were simulated to evaluate patients’ individual economic burden. Results Base-case analysis showed that risdiplam treatment generated additional health benefits but substantially increased medical costs. The resulting ICUR did not demonstrate a clear cost-utility advantage under the current willingness-to-pay threshold. Sensitivity analyses indicated that the model results were relatively robust, with drug costs and key utility parameters being the main drivers of economic outcomes. Health insurance scenario analysis demonstrated that increasing reimbursement levels and reducing patient copayment rates could significantly alleviate patients’ financial burden. Conclusion Risdiplam for pediatric SMA faces economic challenges under the current health insurance payment framework in China. However, optimizing health insurance reimbursement policies and developing multi-tiered healthcare security mechanisms may improve its affordability and accessibility.

Objective To evaluate the feasibility of establishing canine rectovaginal fistula ani-mal model using magnetic surgery techniques.Methods Ten female Beagle dogs were randomly di-vided into study group(n=5)and control group(n=5).The study group underwent rectovaginal fistula modeling using magnetic surgery technology,while the control group was subjected to sharp puncture of the rectovaginal septum followed by indwelling rubber tube placement to establish the model.Surgical procedure duration and postoperative adverse events were recorded in both groups.Two weeks later,the magnets and rubber tubes were removed.The formation of rectovaginal fistulas in the animals of two groups was observed,and the success rates of model construction of two groups were statistically analyzed.Results Both groups successfully completed the preparation of the recto-vaginal fistula models.The operative time in both groups was less than 2 minutes.No adverse events such as magnet detachment were observed in the study group during the postoperative period.In the control group,the rubber tube dislodged on day 6 post-surgery in one dog,leading to spontaneous healing of the fistula.Two weeks after surgery,the magnets and rubber tubes were removed.Naked-eye observation showed that the rectovaginal fistula formed well in the experimental dogs of the study group,while the rectovaginal fistula formed well in 4 experimental dogs in the control group.The success rate of model construction in the study group was 100％,and was 80％in the control group.Conclusion The construction of a canine rectovaginal fistula model by magnetosurgical techniques has the advantages of simple operation and high success rate.Magnetosurgical techniques may serve as an ideal animal model for constructing and studying the histopathological changes and treatment methods of rectovaginal fistulas.

Objective:To evaluate alterations in dopaminergic neurons, cortical metabolism, and functional connectivity networks in patients with early-onset Parkinson′s disease (EOPD) using multimodal neuroimaging.Methods:In this prospective cross-sectional study, 26 patients with EOPD and 16 healthy controls (HC group) were recruited from the PLA General Hospital between April and November 2023. All participants underwent integrated 11C-β-CFT PET/MR, 18F-FDG PET/CT brain imaging and resting-state functional MRI. Clinical assessments were conducted using the Unified Parkinson′s Disease Rating Scale and Hoehn-Yahr staging. Cognitive status was evaluated using the Mini-Mental State Examination and Montreal Cognitive Assessment. Standardized uptake value ratios for both 11C-β-CFT and 18F-FDG PET images were calculated using cerebellar gray matter as the reference region. Voxel-wise two-sample t-tests were performed to identify regions with significant group differences in tracer uptake. Seed regions showing altered 11C-β-CFT or 18F-FDG uptake were used to compute seed-based functional connectivity (FC) with all other brain voxels, and group differences in FC were assessed. Correlations between imaging metrics and clinical scales were evaluated using Pearson or Spearman analyses as appropriate. Results:Compared with HC group, EOPD group showed significantly reduced 11C-β-CFT uptake in the bilateral putamen, globus pallidus, and left temporal pole ( P<0.05), and decreased 18F-FDG uptake in the right superior frontal gyrus and anterior cingulate cortex ( P<0.05). Relative to HC group, EOPD group exhibited markedly lower FC between the right putamen and the left gyrus rectus as well as the right parahippocampal gyrus; the right superior frontal gyrus and the left gyrus rectus; the anterior cingulate cortex and the olfactory area of the frontal lobe, the left gyrus rectus, and the right superior parietal gyrus; the left temporal pole and the left orbitofrontal cortex as well as the left olfactory area ( P<0.05). Correlation analyses revealed no statistically significant associations between altered FC values and clinical scale scores in the EOPD group. Conclusions:Patients with EOPD demonstrate impaired nigrostriatal dopaminergic function, regional cortical hypometabolism, and aberrant functional connectivity across multiple brain networks.

Objective:To investigate the expression characteristics and clinical significance of FOXC1 in colon cancer,and decipher its mo-lecular mechanism in regulating tumor cell proliferation and apoptosis.Methods:The GEPIA database was employed to analyze the expres-sion of FOXC1 and its correlation with prognosis in colon cancer.Differential expression of FOXC1 was detected by qRT-PCR and Western blot in colon cancer cells(HCT116 and SW620)and normal colon epithelial cells(NCM460),and stable FOXC1-knockdown(sh-FOXC1)cell lines were established.Western blot,flow cytometry,CCK-8,and plate colony formation assays were performed to analyze the effects of FOXC1 knockdown on cell proliferation,cell cycle,and apoptosis.Furthermore,the downstream signaling pathway was verified using Rap1 overexpression rescue experiments.Results:FOXC1 mRNA expression was significantly higher in colon cancer tissues than in normal tissues(P<0.001).FOXC1 overexpression was nearing significance in relation to tumor staging(P=0.053),and patients with high FOXC1 expression had a shorter overall survival(Log-rank P=0.013).After FOXC1 knockdown,the expression of CyclinD1 and Bcl-2 decreased,whereas the ex-pression of Bax increased(P<0.01).The proportion of cells in the G0/G1 phase increased,while the proportion of cells in the S phase de-creased(P<0.001),and the cell proliferation activity and number of colonies formed decreased(P<0.001).Mechanistic studies demonstrated that after FOXC1 knockdown,Rap1 expression was reduced,while the expression of Rap1GAP increased(P<0.05).After restoration of Rap1 expression in FOXC1-knockdown cells,the downregulation of CyclinD1 and Bcl-2 expression and the increase in Bax expression were re-versed(P<0.05),the S phase ratio was increased(P<0.05),and cell proliferation activity and colony formation abilities were also re-scued.Conclusion:FOXC1 promotes colon cancer progression by facilitating Rap1 expression and downregulating Rap1GAP.Targeted inter-vention of the FOXC1-Rap1 signaling axis may emerge as a potential therapeutic strategy.

Objective To analyze the current status and emerging technology trends in domestic medical drainage tube patents,so as to explore possible factors for low patent conversion rates.Methods Patents associated with"drainage tube","medical drainage tube","surgical drainage tube"and related terms were retrieved from the National Intellectual Property Administration Database and the Innojoy Patent Search Engine,covering the period from 2010 to 2020.Screening and visual analysis were conducted using Excel and SPSS 27.0.Results A total of 2 895 relevant patents were identified,comprising 2 489 utility model patents,367 invention patents and 39 design patents.The number of patent applications demonstrated a year-on-year growth trend,with a higher concentration in eastern coastal regions and provinces housing numerous top-tier hospitals and medical institutions.Approximately 49.26％of the patents filed by individuals were affiliated with hospitals,universities,or enterprises.Innovation hotspots included the design,functionality,performance,and safety aspects of drainage tubes and probes.Of the patents,72.61％were invalid,and 61.73％had a survival period of three years or less.Only 5.15％were commercially utilized through transfers,pledges,or licensing.Conclusion Domestic patent applications for medical drainage tubes have seen rapid growth,with a focus on enhancing tube structures such as sleeves,balloons,drainage holes,and threaded designs.However,the unsatisfactory situation of patent conversion and operation have been mainly limited by factors such as weak core technology of patents,insufficient awareness of achievements conversion,poor operation of patent conversion mechanism,insufficient market promotion,and insufficient integration of industry,academia,and research.To address this issue,enhancing intellectual property protection,revitalizing valid patents,and expanding transformation channels would benefit patients and facilitate hospitals'high-quality development,injecting new vitality into the health industry.

Objective:To investigate the prevalence and risk factors of overweight and obesity among Chinese children aged 3-18 years from 11 provinces, antonomous regions, or municipalities.Methods:This national cross-sectional community health survey utilized a multistage stratified cluster-random sampling method to recruit 193 997 nationally representative participants from 11 provinces, autonomous regions, or municipalities between January 2017 and December 2019. All participants underwent physical examinations, and their caregivers completed questionnaires assessing participants′ dietary, lifestyle, familial, and perinatal information. Multilevel multinomial logistic regression models were employed to identify the potential risk factors.Results:The cohort comprised 193 997 children (102 178 boys, 91 819 girls),aged (10±4) years. Overall prevalence rates were 30 574(15.8%)overweight children and 17 217(8.9%) obesity children. Boys exhibited higher overweight and obesity rates than girls (17.0% (17 368/102 178) vs. 14.4% (13 206/102 178), 11.3% (11 553/91 819) vs. 6.2% (5 664/91 819), χ2=249.12,1 578.69,both P<0.001). The detection rates of obesity in Tanner stage 2 and 3 were the highest in boys and girls, with 13.4%(2 231/16 665) and 8.6%(880/10 221) respectively. Risk factors for obesity included parental overweight (paternal OR=2.34 and maternal OR=2.29), annual household income of 100 000-200 000 yuan (compared with<100 000 yuan, OR=1.04), higher paternal education (compared with below high school,high school and a college education OR=1.09,1.14), birth weight >4.0 kg (≤5 and>5 years old OR=1.74, 1.44,respectively), and western food consumption≥1 time/month (compared with<1, 1-2, 3-4,>4 times/month OR=1.36, 1.30, 1.67(≤5 years), 1.19, 1.16, 1.15 (>5 years), respectively) (all P<0.05). Conversely, coarse grain intake≥1 times/week (compared with<1 times/week, every day, 3-4, 1-2 times/week OR=0.74, 0.80, 0.71 (≤5 years), 0.75, 0.87, 0.90(>5 years), respectively, all P<0.05) was associated with reduced obesity risk. Conclusions:Obesity epidemiology in children demonstrates significant heterogeneity across age, gender, geographic regions, and pubertal stages. It is necessary to establish a personalized prevention and control strategy.

Objective:To analyze the pathogenicity and clinical phenotype associated with a newly identified heterozygous variant in the ZEB1 gene that causes posterior pleomorphic corneal dystrophy (PPCD). Methods:A pedigree study was conducted.Clinical data of four people in 2 generations from one family with PPCD who visited Henan Eye Hospital in October 2023 were collected, including 3 patients. Relevant ophthalmic examinations were performed.Best corrected visual acuity, slit lamp microscopy, intraocular pressure, Pentacam corneal topography, Corvis ST corneal biomechanics analyzer, corneal endothelial microscopy, swept-source anterior segment coherence optical tomography (CASIA), laser scanning confocal microscopy, and ultra-wide-field fundus photography were performed to examine clinical phenotypes.Peripheral venous blood samples were collected from family members to extract genomic DNA, and whole exome sequencing was performed.Sanger sequencing and pedigree co-segregation analysis were carried out.Conservation analysis was performed using GERP+ + and Clustal Omega software, and the pathogenicity of the variant was assessed according to American College of Medical Genetics and Genomics (ACMG) guidelines.This study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]).All subjects or guardian signed informed consent.Results:This family conformed to autosomal dominant inheritance.Under a slit-lamp microscope, corneal endothelial vesicular lesions in both eyes could be seen in the proband, her father and her brother.Under a laser scanning confocal microscope, endothelial cells were missing at the lesions, and some were crater-like changes, and some lesions were circular or elliptical vesicular, and no other systemic abnormalities were observed.The ocular and physical examination of the proband's mother showed no abnormalities.Genetic testing results showed that the proband, her father and her brother all carried the ZEB1c.790G>A (p.Gly264Arg) heterozygous variant, but her mother did not carry the variantion.Sanger sequencing verified that this variantion was co-segregated within the family.The variantion is a newly discovered missense mutation that had not been reported in the Thousand Genomes Project, Genome Aggregation Database, and ExAC database.The prediction results of the variant by MutationTaster, SIFT, PROVEAN, VESST3, DANN, FATHMM-MKL, CADD, fitCons and other software were harmful, and GERP+ +, Weblogo, Clustal Omega analysis showed that the amino acids affected by the variant were highly conservative.According to the ACMG Guidelines, this variation was possible pathogenic.Conclusions:The identification of the missense mutation c. 790G>A (p.Gly264Arg) in the ZEB1 gene within this PPCD family provides new insights into the genetic basis of PPCD and the variant may be the pathogenic variant of in this family.

Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.
Animals ; Mice ; Histone-Lysine N-Methyltransferase/biosynthesis* ; Histones/genetics* ; Nuclear Transfer Techniques ; Female ; Gene Expression Regulation, Developmental ; Promoter Regions, Genetic ; Epigenesis, Genetic ; Embryo, Mammalian/metabolism*