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

In response to the high risk of recurrence and metastasis after breast cancer surgery， this paper proposes a six-dimensional integrated preventive and therapeutic model， namely the "disease-syndrome-constitution-trend-strategy-efficacy" framework， including disease identification， syndrome differentiation， constitution differentiation， trend assessment， strategy implementation， and effect evaluation. This model builds upon the traditional three-dimensional approach of disease identification， syndrome differentiation and constitution differentiation， and introduces "trend" to dynamically capture the evolving tendencies of disease progression and the transformation of syndrome and constitution， thereby operationalizing the concept of "treating before disease onset". The "strategy" dimension enables the organic integration and individualized regulation of TCM and western medical interventions， while the "efficacy" dimension establishes a multidimensional evaluation system integrating TCM and western medicine to assess the efficacy of the "strategy"， so as to promote the systematic， dynamic， and precise development of treating before disease onset in TCM.

Objective:To observe the intervention effect of personalized nutrition program combined with rehabilitation training in stroke rehabilitation patients.Methods:86 stroke rehabilitation patients who were admitted to our hospital from January 2023 to June 2024 were prospectively selected,they were divided into control group and study group according to the random number table method,with 43 cases in each group,the control group received rehabilitation training,while the study group received personalized nutrition program combine with rehabilitation training.Simple Fugl Meyer motor function(FMA)score,immune function indicators[immunoglobulin(Ig)A,IgG,complement C3,IgM,complement C4],National Institutes of Health Stroke Scale(NIHSS),nutritional status indicators[albumin(ALB),prealbumin(PA),total protein(TP),hemoglobin(HB)],Stroke Specific Quality of Life Scale(SS-QOL),Barthel Index(BI)score were compared between the two groups.Results:NIHSS score in the study group at 8 weeks after intervention was lower than that in the control group,and SS-QOL score,BI score,FMA score,IgM,IgA,IgG,complement C3,complement C4,ALB,HB,TP and PA were higher than those in the control group(P＜0.05).Conclusion:Personalized nutrition program combined with rehabilitation training in stroke rehabilitation patients,can reduce neurological damage,improve limb motor function,enhance nutritional status,immunity,and quality of life.

Objective:To explore the potential mechanism of action of Xian Fang Huo Ming Yin modified formula(XFHMY)in the treatment of medication-related osteonecrosis of the jaw(MRONJ)through bioinformatics analysis and in vitro and in vivo experiments.Methods:Firstly,the efficacy of XFHMY was evaluated by establishing a mice model of MRONJ induced by zoledronic acid(ZOL);Subsequently,the potential molecular mechanism of XFHMY in the treatment of MRONJ was predicted by using network pharmacology;Lastly,the network pharmacology prediction results were collectively validated through MC3T3-E1 cell proliferation and differentiation experiments,Western blot analysis,and immunohistochemical staining of mouse maxillary bone tissue.Results:Animal experiments showed that,compared to the model group,the XFHMY group exhibited significantly improved wound healing in the tooth extraction socket(P＜0.001),a significant reduction in bone volume fraction and empty lacunae rate in the maxilla(P＜0.0001,P＜0.001),and a significant increase in trabecular separation and osteoclast number(P＜0.01,P＜0.05).Network pharmacology analysis identified 59 common targets,with both GO and KEGG analyses indicating the Wnt/β-catenin signaling pathway as a crucial mechanism for XFHMY in treating MRONJ.Ten key active components,including quercetin,luteolin,and fisetin,were screened,and these compounds demonstrated strong binding affinity with CTNNB1,a core target of this pathway.In vitro experiments revealed that XFHMY(0.25,0.5,1,2,4 mg/mL)promoted MC3T3-E1 cell proliferation(P＜0.0001)and activated the Wnt/β-catenin pathway by upregulating β-catenin and Runx2 protein expression,thereby reversing ZOL-induced inhibition of MC3T3-E1 cell proliferation and differentiation while enhancing both processes.Immunohistochemical analysis of mouse maxillae showed that,compared to the model group,the XFHMY group had significantly increased β-catenin and Runx2 protein expression(P＜0.05,P＜0.01),consistent with the in vitro findings.Conclusion:XFHMY promotes the proliferation and differentiation of osteoblasts through activating the Wnt/β-catenin signaling pathway,which in turn attenuates MRONJ.The novel pharmacological mechanism proposed in this study provides a theoretical basis for the clinical application of XFHMY.

Excessive ionizing radiation can disrupt the molecular structures of organisms,leading to health issues such as acute radiation syndrome and cancer,posing serious threats to human health.The development of radioprotective drugs holds significant importance for mitigating ionizing radiation damage and safeguarding public health,yet its research process faces multidimensional ethical challenges.This paper systematically explores the ethical issues involved in the full lifecycle of radioprotective drug development,focusing on the ethical particularities of animal experimentation,ethical dilemmas in human trials,data privacy and security risks,as well as challenges in managing conflicts of interest.Targeted solutions are proposed,including strengthening ethical review mechanisms,promoting interdisciplinary collaboration,constructing data security management systems,and establishing conflict-of-interest mediation mechanisms.These comprehensive measures aim to build a scientifically rigorous ethical framework for radioprotective drug research,fostering sustainable development in this field.

Radiation prevention and treatment drugs are a rapidly developing field.Radiation prevention and treatment drugs can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds,which are widely used in medical,scientific research and other fields.This paper reviews the classification of radiation prevention and treatment drugs,which can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds.At the same time,its mechanism of action and clinical application are elaborated in detail,and the risk assessment is carried out from the aspects of effectiveness,safety and drug interaction.Finally,the risk reduction strategies are summarized from the aspects of clinical medication specification and monitoring,continuous drug safety research,improvement of emergency reserve and support capacity and construction of full-cycle regulatory system,so as to provide reference for the rational application and further research of radiation prevention and treatment drugs.

Objective To investigate the impact of various health education intervention strategies on the proper use of personal respiratory protective equipment (RPE) among workers exposed to dust. Methods Dust-exposed workers were recruited from 60 selected enterprises in Guangdong Province using cluster random sampling method. They were randomly allocated to the control, low-intensity intervention, and high-intensity intervention groups, with 358, 346, and 371 workers in each group, respectively. Workers in the control group received no designed intervention. Workers in the low-intensity intervention group received traditional plus mobile health education on the proper use of RPE. Workers in the high-intensity intervention group received all components of the low-intensity intervention, supplemented with peer education. The intervention lasted for six months. RPE usage was compared among the three groups of workers before and after the intervention. Results Workers in the control, low-intensity intervention, and high-intensity intervention groups showed higher rates of both RPE wearing and correct RPE wearing after the intervention than before it within their respective groups (RPE wearing rate: 94.1% vs 99.2%, 95.7% vs 100.0%, 94.6% vs 100.0%, all P<0.01; correct RPE wearing rate: 66.8% vs 91.1%, 67.3% vs 95.7%, 66.6% vs 96.5%, all P<0.01). Post-intervention correct RPE wearing rates were highest in the high-intensity intervention group, followed by the low-intensity intervention group, and the control group, with the percentage of 96.50%, 95.66% and 91.06%, respectively (P<0.01). Binary logistic regression analysis result showed that different intervention strategies affected the correct use of personal RPE among dust-exposed workers after adjusting for gender, age, and other confounding factors (P<0.05). Compared with the control group, the rates of correct RPE use increased in the low-intensity intervention group and the high-intensity intervention group (odd ratio was 2.14 and 3.01; 95% confidence interval was 1.12 - 4.10 and 1.53 - 5.91, respectively). Conclusion The implementation of traditional plus mobile health education interventions on the proper use of RPE can promote correct RPE utilization among dust-exposed workers, and integrating peer education further enhances the intervention effectiveness.

AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P＜0.05,P＜0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.

Objective:To investigate the mechanism of improving liver injury by enhancing the abundance of Akkermansia mu-ciniphila(AKK bacteria)with hepatocyte-specific Yap1 knockout during PD-1 monoclonal antibody treatment.Methods:Hepatocyte-specific Yap1 knockout mice(genotype Yap1Flox/Flox;albumin-Cre,labeled as Yap1LKO)and control mice(genotype Yap1Flox/Flox,labeled Yap1Flox),aristolocholic acidⅠ(AAⅠ)and CCl4 were used to induce liver injury,Yap1LKO mice and Yap1Flox mice were randomly di-vided into control group and PD-1 monoclonal antibody group.After the intervention,real-time PCR detected changes in the abun-dance of AKK bacteria in the fecal microbial DNA of mice,16S rRNA gene sequencing further analyzes intestinal flora changes,the livers of mice were made into wax blocks for HE staining to observe the histopathological changes of the liver.Results:Yap1Flox mice exhibited balloon-like edema degeneration of hepatocytes and infiltration of inflammatory factors in the manifold area,compared with Yap1Flox mice,Yap1LKO mice had reduced the abundance of AKK bacteria in the intestine,fibrosis of the liver,and the degree of dam-age was more serious;PD-1 monoclonal antibody treatment alone did not increase the abundance of AKK bacteria in the intestines of mice,and fibrosis appeared in the liver;however,the abundance of intestinal AKK bacteria in Yap1LKO mice treated with PD-1 mono-clonal antibody increased,the ratio(F/B value)of Firmicutes to Bacteroides at the phylum level decreased,and the morphology of he-patocytes returned to normal and the degree of liver damage decreased.Conclusion:In AAⅠ and CCl4 induced liver injury mice,he-patocyte-specific Yap1 knockout reduced the abundance of AKK bacteria in the intestine,and the degree of liver injury was more se-vere than that in Yap1Flox mice.When treated with PD-1 monoclonal antibody,hepatocyte-specific Yap1 knockout could increase the abundance of AKK bacteria in the intestine,change the composition of intestinal flora,maintain intestinal homeostasis and ameliorate liver injury.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.