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 clinical efficacy of Traditional Chinese Medicine （TCM）external treatment methods in alleviating skin pruritus caused by eczema through a Meta-analysis. Methods Randomized clinical trials investigating the use of TCM external treatment methods for skin pruritus caused by eczema were searched in databases including China National Knowledge Infrastructure （CNKI）, VIP, Wanfang, Sinomed, PubMed, Embase, LILACS, and Cochrane, up to December 2024. Two reviewers independently screened and entered the statistical data, conducted bias risk assessment by the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0, and performed Meta-analysis using RevMan 5.4.1. Results Ultimately, 14 studies involving 1 788 patients were included. Compared to the control group, TCM external treatment methods （treatment group）showed better improvement in pruritus scores （Z=11.88, P<0.000 01）, better improvement in Eczema Area and Severity Index （EASI） scores （Z=23.15, P<0.000 01）, higher overall clinical efficacy rate （Z=6.21, P<0.000 01）, better improvement in TCM symptoms （Z=5.49, P<0.000 01）, and lower clinical recurrence rate （Z=2.88, P=0.004）. Three of the included studies mentioned adverse reactions, with the treatment group showing lower adverse reactions than the control group. Conclusion The external treatment of TCM was more effective in treating skin pruritus caused by eczema compared to the control group. Given the biases and heterogeneity in the included literature, this conclusion needs to be further substantiated by more large-scale, multi-center, randomized, controlled, and double-blind studies.

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*

ObjectiveTo evaluate the methodological quality and reporting quality of published guidelines/consensuses on traditional Chinese medicine （TCM）/integrated traditional Chinese and Western medicine diagnosis and treatment of nonalcoholic fatty liver disease （NAFLD）， and to provide a basis for formulating guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD in the future. MethodsDatabases including PubMed， Embase， Web of Science， CNKI， Wanfang Data， and CBM and the websites of China Association of Chinese Medicine and China Association of Integrative Medicine were searched for related articles published up to September 1， 2024. Two clinical researchers independently assessed the methodological quality and reporting quality of the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD by using Appraisal of Guidelines for Research and Evaluation Ⅱ （AGREE Ⅱ） and Reporting Items for Practice Guidelines in Healthcare （RIGHT）. ResultsA total of nine guidelines/consensuses were included after literature screening， with four guidelines and five expert consensuses. The scores of different domains assessed by AGREE Ⅱ for the nine guidelines/consensuses were as follows： scope and purpose （47.1%）， stakeholder involvement （41.0%）， rigor of development （21.6%）， clarity of presentation （40.2%）， applicability （19.0%）， and editorial independence （19.6%）. The recommendation level of the articles was B level （recommended after revision） for four articles and C level （not recommended） for five articles. The RIGHT assessment showed high reporting rates for “Basic Information” and “Background”， while other areas needed to be improved. Currently， there was no international standard for the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and the quality of these guidelines/consensuses needed to be enhanced to ensure comprehensiveness and credibility. ConclusionThere is still potential for improving the quality of guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and AGREE Ⅱ and RIGHT checklists should be strictly followed to ensure the fairness， scientific rigor， and transparency of these guidelines/consensuses.

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 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 explore the effect of exenatide on oxidative stress in the hypothalamus of diabetes mice and its potential mechanism.Methods After one week of adaptive feeding,C57BL/6J mice were randomly divided into the CON group(normal chaw diet),the T2DM group(high-fat diet,HFD),and the T2DM+Exe group(HFD+exenatide).After 8 weeks of HFD,mice in the T2DM+Exe group were intraperitoneally injected with exenatide[24 nmol/(kg·d)]for 8 weeks.The weight and glucose and lipid metabolism levels of the mice were measured,and the levels of inflammatory and adipokine factors in mice were detected using the ELISA method.Western Blot was used to detect the expression of melanocortin receptor-4(MC4R)and proopiomelanocor-tin(POMC)in the hypothalamus.Hypothalamic mitochondria were extracted,and the content of mitochondrial reactive oxygen species(ROS)was measured using a flow cytometer.The content of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)in the mitochondria were detected using assay kits.Changes in the ultrastructure of mitochondria were observed using a transmission electron microscope.In vitro experiments,pal-mitic acid(PA)and exenatide were used to treat hypothalamic GT1-7 cells,and short hairpin RNA(shRNA)was used to silence the melanocortin 4 receptor(MC4R),and observe the cellular oxidative stress and lipid deposition.Results Compared with the CON group,the T2DM group mice showed a significant increase in glucose and lipid metabolism indicators,pro-inflammatory factors,and adipose factor levels(P<0.05),the expression of MC4R and POMC proteins in the hypothalamus were decreased(P<0.05),and the mitochondrial ROS and MDA content in the hypothalamus significantly were increased(P<0.05),while SOD and CAT activities were decreased(P<0.05).Mitochondrial morphology was abnormal.After intervention with exenatide,the above indicators were signifi-cantly improved.After inhibiting MC4R expression in vitro experiments,compared with the intervention group with exenatide,the ROS and MDA content was significantly increased(P<0.05),SOD activity was decreased(P<0.05),and lipid deposition occurred in the cells.Conclusions Exenatide exhibits a protective effect on hypotha-lamic oxidative stress injury in diabetic mice,and this mechanism may be associated with the upregulation of MC4R expression.

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.

Objective To explore the effect of exenatide on oxidative stress in the hypothalamus of diabetes mice and its potential mechanism.Methods After one week of adaptive feeding,C57BL/6J mice were randomly divided into the CON group(normal chaw diet),the T2DM group(high-fat diet,HFD),and the T2DM+Exe group(HFD+exenatide).After 8 weeks of HFD,mice in the T2DM+Exe group were intraperitoneally injected with exenatide[24 nmol/(kg·d)]for 8 weeks.The weight and glucose and lipid metabolism levels of the mice were measured,and the levels of inflammatory and adipokine factors in mice were detected using the ELISA method.Western Blot was used to detect the expression of melanocortin receptor-4(MC4R)and proopiomelanocor-tin(POMC)in the hypothalamus.Hypothalamic mitochondria were extracted,and the content of mitochondrial reactive oxygen species(ROS)was measured using a flow cytometer.The content of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)in the mitochondria were detected using assay kits.Changes in the ultrastructure of mitochondria were observed using a transmission electron microscope.In vitro experiments,pal-mitic acid(PA)and exenatide were used to treat hypothalamic GT1-7 cells,and short hairpin RNA(shRNA)was used to silence the melanocortin 4 receptor(MC4R),and observe the cellular oxidative stress and lipid deposition.Results Compared with the CON group,the T2DM group mice showed a significant increase in glucose and lipid metabolism indicators,pro-inflammatory factors,and adipose factor levels(P<0.05),the expression of MC4R and POMC proteins in the hypothalamus were decreased(P<0.05),and the mitochondrial ROS and MDA content in the hypothalamus significantly were increased(P<0.05),while SOD and CAT activities were decreased(P<0.05).Mitochondrial morphology was abnormal.After intervention with exenatide,the above indicators were signifi-cantly improved.After inhibiting MC4R expression in vitro experiments,compared with the intervention group with exenatide,the ROS and MDA content was significantly increased(P<0.05),SOD activity was decreased(P<0.05),and lipid deposition occurred in the cells.Conclusions Exenatide exhibits a protective effect on hypotha-lamic oxidative stress injury in diabetic mice,and this mechanism may be associated with the upregulation of MC4R expression.