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

Functional constipation （FC） is a clinically common functional bowel disorder characterized by a protracted course and associations with various chronic disorders and psychological abnormalities. Although not life-threatening， FC significantly impairs patients' quality of life. FC subtypes include slow-transit constipation （STC）， defecatory disorder （DD）， and normal-transit constipation （NTC）. The pathological mechanisms underlying FC have not been fully elucidated， and overall clinical efficacy remains unsatisfactory. Animal models of FC serve as essential tools for the study of disease mechanisms and the development of novel therapeutics. This article systematically reviews the current state of research on the animal models of FC and identifies that rodents， particularly rats and mice， are the most commonly used species. Dogs and pigs are also employed in complex intervention studies due to their physiological similarities to humans， though their use is limited by housing challenges and ethical considerations. Induction methods vary across different FC subtypes. STC models are primarily established with chemical agents such as loperamide or compound diphenoxylate. DD modeling often involves low-fiber diets combined with methylene blue injection or rectal narrowing. NTC modeling mainly relies on low-fiber dietary interventions. In addition， disease-syndrome combination models based on traditional Chinese medicine （TCM） theory have been developed， encompassing excess patterns such as heat accumulation， cold accumulation， and Qi stagnation， as well as deficiency patterns including Qi deficiency， blood deficiency， Yin deficiency， and Yang deficiency. These are achieved through an approach of disease model + syndrome induction， enabling the integration of mechanisms from both Western and TCM perspectives. Models are evaluated from two aspects： disease and syndrome manifestations （e.g.， colonic transit， secretory function， and TCM syndrome indicators such as mental state and body weight） and disease mechanisms （e.g.， enteric nervous system， interstitial cells of Cajal， smooth muscle cells， gut microbiota， and metabolites）. However， current research still faces challenges such as poor consistency in some models， non-specific interference in mechanism interpretation， insufficient studies on NTC， and lack of TCM tongue and pulse diagnosis in evaluation. Future efforts should focus on optimizing model stability and specificity to provide a more reliable experimental basis for investigating the pathological mechanisms of FC and developing therapeutic agents.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

This study aims to retrospectively analyze the distribution of human papillomavirus (HPV) subtypes and cervical lesion characteristics in female patients at Shenzhen Cancer Hospital. Adopting a retrospective observation research method. Using convenience sampling, the study subjects were selected from women who visited the Shenzhen Hospital of the Chinese Academy of Medical Sciences Cancer Hospital from September 2020 to December 2023.HPV genotyping was performed on cervical exfoliated cells from 6 402 women using rapid nucleic acid hybridization. Additionally, thinprep cytologic test (TCT) was conducted on 845 HPV-positive samples. High-grade squamous intraepithelial lesions (HSIL) were further classified as cervical intraepithelial neoplasia grades 2 or 3 (CIN2/3) through histopathological examination via cervical biopsy or conization. Data were statistically analyzed using χ2 test and two-sided test. The results showed that HPV testing identified 1 205 HPV-positive cases, with an overall positivity rate of 18.8% (1 205/6 402). Among these, the positivity rate for high-risk(HR) HPV was 14.34%(918/6 402), low-risk(LR) HPV was 3.58%(229/6 402), and other HPV types accounted for 0.91% (58/6 402). The most prevalent high-risk HPV subtypes were HPV16, HPV52, HPV39, HPV58, and HPV53, with positivity rates of 3.16% (202/6 402), 2.92% (187/6 402), 1.34% (86/6 402), 1.30%(83/6 402), and 1.05%(67/6 402), respectively. HPV16 had the highest infection rate in cervical malignancies, CIN3, and CIN2/3 groups, with rates of 53.18%(92/173), 47.37%(27/57), and 34.78%(8/23), respectively. Conversely, HPV52 showed the highest infection rate in the atypical squamous cells(ASC), Low-grade squamous intraepithelial lesion(LSIL), and CIN2 groups, at 29.68%(19/64), 23.50%(43/183), and 37.93%(11/29), respectively. Among 845 HPV positive female patients, the pathological diagnosis was squamous cell carcinoma, accounting for 22.13% (187/845), and adenocarcinoma accounting for 1.42%(12/845). HPV infection rates increased with age: 16.39%(97/592) in the ≤30 age group, 14.46%(301/2 082) in the 31-40 group, 17.26%(318/1 842) in the 41-50 group, 23.98%(300/1 251) in the 51-60 group, and 29.76%(189/635) in those over 60. In conclusion,in the female patient population of the Shenzhen Hospital of the Chinese Academy of Medical Sciences Cancer Hospital, HPV16 is associated with cervical cancer and high-grade cervical lesions, while HPV52 is related to low-to moderate-grade cervical lesions. Enhancing HPV screening among adult women is essential for preventing cervical cancer and associated lesions.

Objective To use multiple model integration to predict the potential distribution of suitable areas for Hedysari Radix in China and the main environmental factors affecting its distribution.Methods Based on 119 geographical distribution points obtained from species distribution databases,and incorporating 19 bioclimatic and topographic factors,a species distribution model was constructed using the Biomod2 software package 3.5-1 version ensemble modeling platform,integrating six algorithms including generalized linear model,gradient boosting machine,random forest,and others.Geographic information system spatial analysis methods were used to quantitatively assess the distribution characteristics of suitable habitats of Hedysari Radix under current climate conditions and under future climate scenarios,while identifying the primary environmental drivers of its distribution.Results The ensemble model showed significantly superior predictive performance.TSS value and AUC value were 0.924 and 0.992,respectively.Key environmental factors significantly influencing the distribution of Hedysari Radix included slope,aspect,daily average temperature difference,isothermity,seasonal variation coefficient of temperature,lowest temperature in the coldest month,annual precipitation,driest month precipitation,and seasonal variation coefficient of precipitation.Under current climate conditions,suitable habitats for Hedysari Radix were primarily concentrated in the regions of Longnan and Dingxi in Gansu Province,covering an area of approximately 26.17×104 km2.Under future climate scenarios,suitable habitats will gradually shift toward the northwest into lower temperature zones,with a significant reduction in area.Conclusion The habitat suitability model developed in this study provides a basis for the conservation and sustainable utilization of Hedysari Radix genetic resources,while also offering a methodological reference for ecological adaptability studies of medicinal plants.

Objective:This study aims to investigate the expression of uridine diphosphate-glucose[]pyrophos-phorylase 2(UGP2)in breast cancer(BC)tissues and its oncogenic mechanism,assessing its potential value as a diag-nostic and prognostic biomarker for breast cancer.Methods:(1)Online database analysis was conducted to assess UGP2 mRNA and protein expression levels in breast cancer and explore their correlation with clinical characteristics.Im-munohistochemistry(IHC)was used to verify UGP2 expression in human breast cancer tumor tissues and evaluate its relationship with clinicopathological features.(2)Kaplan-Meier survival analysis and COX regression models were used to analyze the impact of UGP2 expression on breast cancer patient prognosis.(3)Bioinformatics methods were em-ployed to investigate the correlation between UGP2 and tumor immune cell infiltration,and to predict the biological func-tions and associated signaling pathways of UGP2 in breast cancer.Results:(1)The mRNA and protein expression levels of UGP2 were upregulated in breast cancer tissues(both P<0.05),and were negatively correlated with ER-positive and PR-positive status(OR<1,P<0.05),while positively correlated with Ki-67 levels and the triple-negative breast cancer(TNBC)subtype(OR>1,P<0.05).(2)Elevated expression levels of UGP2 were associated with poorer survival rates in breast cancer patients(both P<0.05)and were identified as an independent adverse prognostic factor for breast cancer(HR=1.40,P<0.05).(3)Functional analysis results suggested that UGP2 may promote tumor progression by regulating metabolism,hormone signaling,and the immune microenvironment.Additionally,UGP2 expression was negatively cor-related with NK cell activation status and positively correlated with the inhibitory state.Conclusion:UGP2 expression is elevated in breast cancer tissues and is closely associated with poor patient prognosis.It may promote cancer pro-gression through mechanisms such as metabolic reprogramming and immune suppression.UGP2 shows promise as a potential biomarker and therapeutic target in breast cancer,providing a basis for personalized treatment.

Informal caregivers play an important role in chronic disease management, and their level of caregiver activation directly affects the quality of care and health outcomes of patients with chronic diseases. This article summarizes the concept, assessment tools, current status, influencing factors, and interventions of caregiver activation among informal caregivers of patients with chronic diseases, aiming to provide a reference for research on caregiver activation.

Objective To fabricate nanosilicate functionalized polycaprolactone(PCL/LAP)electrospun membrane and evaluate its role in bone marrow mesenchymal stem cells(BMSCs)-induced bone repairing.Methods The PCL/LAP electrospun membranes were fabricated via electrospinning technology and co-cultured with rat BMSCs.The cytocompatibility of the membranes was evaluated through cytoskeleton staining,live/dead cell staining and CCK-8 assay.The migration capacity of BMSCs was assessed using scratch assay,Transwell migration experiments and expression of migration-related genes(Pdgf and Tgfβ)was evaluated by qRT-PCR.The os-teogenic differentiation and pro-angiogenesis potential were determined by alkaline phosphatase(ALP)staining,alizarin red staining,expression levels of osteogenesis-related genes(Alp,Col1a1,Runx2,Bglap and Bmp2)and angiogenesis-related genes(Angpt1,Fgf2 and Vegfa)along with RUNX2 protein expression.PCL and PCL/LAP electrospun membranes conditioned medium was subsequently used to stimulate vascular endothelial cells(EAhy926).The expression of angiogenesis-associated genes(KDR,ENOS and HIF1A)was quantified by qRT-PCR.Results BMSCs adhered well to the surface of the PCL/LAP membranes,with no significant impact on cell viability(P＞0.05).PCL/LAP membranes not only promoted the proliferation(P＜0.05),migration(P＜0.05),but also enhanced ALP activity and mineralized nodule formation(P＜0.05),increased osteogenic differentiation gene and protein expression(P＜0.05)of BMSCs.Moreover,PCL/LAP promoted the expression of angiogenic genes of BMSCs(P＜0.05),to indirectly regulate angiogenesis-related gene expression in vascular endothelial cells(P＜0.05).Conclusion PCL/LAP electrospun membranes exhibit excellent biocompatibility and can promote proliferation,migration,osteogenic differentiation and BMSC-mediated angiogenic differentiation,showing great potential for bone defect repairing as barrier membrane.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.