OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

ObjectiveProtein-protein interactions (PPIs) are fundamental to the execution of biological functions within living cells. However, traditional biochemical methods, such as co-immunoprecipitation (Co-IP), often fail to capture transient, weak, or membrane-associated interactions due to the stringent detergent requirements for cell lysis. Proximity labeling (PL) has emerged in recent years as a transformative technology for mapping the proteomes of specific subcellular compartments and identifying dynamic interactomes in situ. Golgi protein 73 (GP73, also known as GOLPH2), a resident type II Golgi transmembrane protein, is a well-recognized clinical biomarker for liver diseases, including hepatocellular carcinoma (HCC). Despite its clinical significance, the comprehensive physiological and pathological functions of GP73 remain partially understood. This study aims to establish an APEX2-mediated proximity labeling system specifically targeting GP73 to map its interactome in a living cellular environment, thereby providing new insights into its molecular roles and regulatory mechanisms. MethodsTo achieve spatial specificity, we first constructed a stable cell line expressing a fusion protein consisting of GP73 and the engineered soybean peroxidase APEX2. The localization of the GP73-APEX2 fusion protein was validated to ensure it correctly targeted the Golgi apparatus. The proximity labeling reaction was initiated by incubating the cells with biotin-phenol (BP) for 30 min, followed by a brief (1 min) treatment with1 mmol/L hydrogen peroxide (H₂O₂). This catalytic reaction converts BP into highly reactive, short-lived biotin-phenoxyl radicals that covalently attach to endogenous proteins within a small labeling radius of the GP73-APEX2 enzyme. Subsequently, the cells were quenched, and biotinylated proteins were enriched using high-affinity streptavidin-coated magnetic beads. The captured “neighbor” proteins were subjected to on-bead digestion and analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for high-throughput identification. Rigorous bioinformatics analysis, including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction network mapping, was performed to interpret the biological significance of the identified candidates. ResultsOur results demonstrate the successful establishment of a robust and sensitive APEX2-based proximity labeling system for GP73. We identified a total of 95 high-confidence interacting proteins that were significantly enriched in the GP73 proximity proteome compared to control groups. Bioinformatics analysis revealed that these interactors were predominantly associated with biological processes such as vesicular transport, protein localization, and, most notably, molecular functions related to “ribosome binding” and “translation regulation”. This suggested an unexpected role for the Golgi-resident GP73 in the cellular translation machinery. To validate these findings, we performed targeted biochemical assays which confirmed a direct interaction between GP73 and the subunits of the eukaryotic translation initiation factor 3 (eIF3) complex, specifically EIF3G and EIF3I. Furthermore, functional validation using the surface sensing of translation (SUnSET) assay—a non-radioactive method to monitor protein synthesis—revealed that the overexpression of GP73 significantly promoted global protein translation levels in the cell, whereas its depletion or inhibition resulted in reduced translation efficiency. ConclusionThis study successfully utilized APEX2-mediated proximity labeling to provide the first systematic map of GP73 interactome in living cells. Our findings uncover a novel, unconventional function of GP73 as a regulator of cellular protein translation, likely mediated through its interaction with the eIF3 complex. This discovery significantly broadens our understanding of the biological roles of GP73 beyond its traditional function in the Golgi apparatus and suggests that it may act as a bridge between Golgi-related trafficking and the protein synthesis machinery. Furthermore, the technical framework established in this study provides a valuable template for investigating other complex organelle-associated protein networks and resolving transient macromolecular interactions in various physiological and pathological contexts.

Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

Diabetic retinopathy (DR) is one of the most prevalent and vision-threatening microvascular complications of diabetes mellitus, yet its pathogenesis extends far beyond vascular injury alone. As the retina is among the most energy-demanding tissues in the body, its neurons, glial cells, pigment epithelial cells, pericytes, and endothelial cells are highly dependent on mitochondrial oxidative phosphorylation to maintain visual signal transduction, ionic homeostasis, and neurovascular integrity. This review summarizes current evidence indicating that mitochondrial dysfunction is not merely a downstream consequence of chronic hyperglycemia, but a central pathogenic hub that initiates, amplifies, and perpetuates retinal neurovascular degeneration in DR. Persistent hyperglycemia activates multiple abnormal metabolic pathways, including the polyol pathway, hexosamine pathway, protein kinase C signaling, advanced glycation end-product formation, and angiotensin II-related responses. Although these pathways differ mechanistically, they converge on excessive reactive oxygen species (ROS) generation, antioxidant depletion, and mitochondrial injury. Under diabetic stress, electron transport chain overload promotes mitochondrial ROS leakage, damages mitochondrial DNA, disrupts membrane potential, and impairs the transcription of key respiratory chain components. In parallel, mitochondrial quality-control systems become progressively compromised. The balance between fusion and fission shifts toward pathological fragmentation through reduced MFN1/2 and OPA1 activity and enhanced DRP1-mediated fission. Mitochondrial biogenesis is suppressed through inhibition of the AMPK/SIRT1/PGC-1α/NRF1/TFAM axis, while mitophagy changes from an early compensatory response to a later state of autophagic flux blockade and accumulation of dysfunctional mitochondria. Importantly, damaged mitochondria serve as signal amplifiers linking metabolic stress to inflammation and programmed cell death. Mitochondrial ROS, oxidized mitochondrial DNA, calcium overload, cardiolipin exposure, and membrane permeabilization activate interrelated death pathways, including intrinsic apoptosis, ferroptosis, and pyroptosis. Cytochrome C and apoptosis-inducing factor promote caspase-dependent and caspase-independent apoptosis; iron dyshomeostasis, glutathione depletion, GPX4 dysfunction, and lipid peroxidation drive ferroptosis; and mitochondrial danger signals activate the NLRP3 inflammasome and gasdermin-dependent pyroptosis. These pathways jointly damage the retinal neurovascular unit and contribute to pericyte loss, endothelial barrier breakdown, Müller cell dysfunction, retinal ganglion cell apoptosis, retinal pigment epithelial injury, and photoreceptor degeneration. This review also emphasizes the role of epigenetic regulation in stabilizing mitochondrial pathology. DNA methylation, histone modifications, and non-coding RNAs interact to silence mitochondrial protective genes, alter antioxidant responses, and maintain the “metabolic memory” of DR even after glycemic normalization. Therefore, mitochondrial dysfunction should be understood as a dynamic, multidimensional network rather than a single pathological event. Current clinical approaches, such as laser photocoagulation, intravitreal anti-VEGF therapy, and vitrectomy, mainly target advanced vascular lesions and are limited by invasiveness, incomplete responsiveness, recurrence, and potential adverse effects. Therapeutically, strategies targeting mitochondrial ROS, restoring mitochondrial dynamics, enhancing biogenesis, regulating mitophagy, inhibiting inflammasome activation, correcting epigenetic abnormalities, and improving targeted delivery systems show promising potential. However, major translational barriers remain, including retinal cell heterogeneity, stage-specific mitochondrial responses, insufficient organelle-specific drug delivery, and long-term safety concerns. A deeper understanding of mitochondrial regulatory networks may support earlier, more precise, and multi-target interventions for preventing or slowing DR progression.

Sichuan Province is a hilly schistosomiasis-endemic province in China with the highest endemicity and largest coverage. During the period of more than 70 years of integrated control, there are five distinct phases of schistosomiasis control in Sichuan Province, including baseline investigation, Oncomelania hupensis snail control, chemotherapy for both humans and livestock, management of source of Schistosoma japonicum infections, and sustained control and intensified surveillance and early warning, and a package of key interventions are implemented, including environmental modification, snail control with chemical treatment, large-scale chemotherapy for humans and livestock, management of source of S. japonicum infections, intensified integrated control, establishment of an early warning and surveillance system. As a result, schistosomiasis has been eliminated across all 63 disease-endemic counties (cities, districts) in Sichuan Province by June 2025. Government-led multi-sectoral collaborations, science and technology-supported precision control strategies, and a sustainable control model tailored to the ecological and socio-economic conditions in endemic regions are essential to achieving the target of schistosomiasis elimination in Sichuan Province.

This paper systematically analyzes schistosomiasis transmission risks during the elimination stage and reviews the evolution of the schistosomiasis surveillance system in China from a One Health perspective, with a special emphasis on schistosomiasis surveillance and response practices during the elimination stage from a One Health perspective. These practices include precise screening of human schistosomiasis under low-endemicity conditions, systematic monitoring of schistosomiasis in domestic and wild animals, ecological management of Oncomelania snails, and information-coordinated responses. Nevertheless, the current surveillance and response system for schistosomiasis suffers from challenges of insufficient cross-sectoral coordination and complex external environments, which constrain precise schistosomiasis surveillance and response in China. Therefore, it is urgently necessary to integrate coordination mechanisms, empower the surveillance system with technological innovation, improve capacity building, and actively promote diverse social participation in the One Health framework, so as to consolidate current schistosomiasis control achievements and achieve the target for schistosomiasis elimination across China, which may provide a replicable technical model for global zoonoses control.

ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

Objective To observe the clinical and CT findings of hepatic perivascular epithelioid cell tumor(PEComa)compared with liver cancer and liver adenoma.Methods Thirty patients with hepatic PEComa,31 patients with liver cancer and 31 patients with liver adenoma were retrospectively enrolled.Compared with liver cancer and liver adenoma,the clinical and CT findings of hepatic PEComa were observed.Results Significant differences of patients' gender,age and symptoms,also of the proportion of hepatitis,cirrhosis and positive alpha fetoprotein(AFP)were found between hepatic PEComa group and liver cancer group(all P＜0.05),while of patients' gender and age were found between hepatic PEComa group and liver adenoma group(both P＜0.05).Significant differences of the proportion of fat and malformed blood vessels,enhancement mode,as well as contrast enhancement ratio CER of arterial and venous phases were noticed between hepatic PEComa group and liver cancer group(all P＜0.05),while of the proportion of fat,capsule and malformed blood vessels,as well as enhancement mode and CER of arterial and venous phases were noticed between hepatic PEComa group and liver adenoma group(all P＜0.05).Conclusion Compared with liver cancer and liver adenoma,hepatic PEComa was mostly benign and more common in women,with somewhat characteristic CT findings being helpful to differential diagnosis.

Objective To compare the differences of baseline characteristics of patients with myelodysplastic syndrome(MDS)who achieved platelet(PLT)response after arsenic-containing TCM compounds combined with Western medicine treatment.Methods Totally 72 MDS patients were selected from 12 outpatient departments and wards,such as Xiyuan Hospital,China Academy of Chinese Medical Sciences,Dongfang Hospital,Beijing University of Chinese Medicine from October 2021 to October 2024.Among them,45 patients received arsenic-containing TCM compounds combined with Western medicine treatment,27 patients received Western medicine treatment.The blood routine[white blood cell(WBC)count,hemoglobin,PLT,neutrophil count],TCM syndrome scores,safety indicators,and adverse events were observed before and after three courses of treatment.The efficacy of all patients was evaluated,and the baseline characteristics of patients who achieved PLT response in the arsenic-containing TCM compounds group and the Western medicine treatment group were compared.Results Comparing the differences of baseline characteristics of the two groups,it was found that the patients who achieved PLT response in the arsenic-containing TCM compounds group were compared with those in the Western medicine treatment group:Age<60 years old(P=0.038),longer disease duration(P=0.012),lower WBC(P=0.017),lower reticulocyte percentage(P=0.037),lower blood urea nitrogen(P=0.046),lower high-density lipoprotein cholesterol(P=0.014),and lower N-terminal pro-B-type natriuretic peptide(P=0.034),abnormal electrocardiogram(P=0.013),high blasts(P=0.009),grade 0 reticular fiber staining(P<0.01),normal chromosome karyotype(P<0.01),gene mutation(P<0.01)and high TCM syndrome scores(P=0.013)were found.Conclusion Arsenic-containing TCM compounds consisting of Qinghuang Powder and Bushen Jianpi Decoction combined with Western medicine is used to treat MDS.Patients with age<60 years old,long disease duration,low WBC count,low reticulocyte percentage,low blood urea nitrogen,low high-density lipoprotein cholesterol,low N-terminal pro-B-type natriuretic peptide,abnormal electrocardiogram,high blasts,grade 0 reticular fiber staining,normal chromosome karyotype,gene mutation and high TCM syndrome score are more likely to obtain PLT response.

Objective:To construct an evaluation indicator system for accessories of patient monitor,so as to provide a basis for clinical management,equipment procurement,and technical improvement for accessories of medical monitor.Methods:The initial selection indicators of corresponding accessories of three types of monitoring of medical monitors,including electrocardiogram(ECG),blood oxygen saturation(SpO2)and non-invasive blood pressure(NIBP),were determined through literature research,expert consultation,and actual investigation.The Delphi method was adopted to conduct two rounds of questionnaire consultation for experts from clinical medicine,biomedical engineering and other fields in medical institutions included Sichuan Provincial People's Hospital,The Affiliated Hospital of Southwest Medical University and Medical Institute of Chengdu Institute of Metrology Verification and Testing.The evaluation indicators were screened and optimized,and the Analytic Hierarchy Process(AHP)was used to calculate the weights of each indicator.The consistency test was conducted to verify the rationality of the evaluation indicator system.Results:The evaluation indicator system for accessories of medical monitor included three first-level indicators:clinical value,cost value,and management value.The number of second-level indicators about ECG,SpO2 and NIBP of evaluation indicator system were respectively 10,9 and 8,and the number of third-level indicators of that were respectively 20,19,and 14.In the first-level indicators,the clinical value had the highest weight,with 72.49%for ECG,70.88%for SpO2 and 70.32%for NIBP.In the second-level indicators,the accuracy(28.70%for ECG,38.13%for SpO2 and 43.03%for NIBP)and safety(27.47%for ECG,26.48%for SpO2 and 23.06%for NIBP)were the core indicators.The weights of cost value and management value were between 14.62%and 17.41%,and between 12.27%and 12.89%,respectively.Conclusion:The evaluation indicator system for accessories of medical monitor integrates multi-dimensional expert opinions and quantitative analysis,highlights the priority principle for clinical performance.It can provide theoretical support for optimizing selection about accessory for medical institutions,and improving quality of monitoring,and promoting standardized management in the industry.