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

Objective To explore the application effect of the dual-track nursing intervention model in the treatment process of children with lobar pneumonia.Methods A total of 186 children with lobar pneumonia were selected and randomly divided into control group and intervention group u-sing a double-blind method,with 93 cases in each group.The control group received conventional nursing intervention,while the intervention group implemented the dual-track nursing intervention model on the basis of conventional nursing.This model included the establishment and training of nurs-ing teams,personalized nursing plans,health education,and psychological support.Outside the hos-pital,it emphasized family support,regular follow-up guidance,and community-based collaborative ed-ucation.Both groups received a 3-week intervention.The improvement times of clinical symptoms,hos-pital stay,pulmonary function indicators before and after nursing,treatment compliance,and family members' satisfaction with nursing were compared and analyzed between the two groups.Results The fever resolution time[(3.89±0.96)d],cough relief time[(6.21±1.34)d],disappearance time of pulmonary rales[(7.89±1.56)d],and hospital stay duration[(9.45±1.89)d]in the intervention group were all shorter than those in the control group[(5.23±1.14),(7.45±1.67),(9.32±2.01),and(11.28±2.35)d,respectively],with statistically significant differences(P＜0.05).After nursing,the forced expiratory volume in one second(FEV1)[(1.51±0.22)L],forced vital capacity(FVC)[(1.75±0.25)L],and FEV1/FVC[(94.12±5.65)％]in the intervention group were all higher than those in the control group[(1.42±0.15)L,(1.66±0.22)L,and(85.73±8.41)％,respectively],with statistically significant differences(P＜0.05).The scores for exami-nation cooperation[(23.91±3.82)points],nursing cooperation[(24.19±4.03)points],standardized medication use[(24.26±3.94)points],and rational diet[(23.77±3.62)points]in the intervention group were higher than those in the control group[(20.16±3.53),(19.64±3.46),(23.05±3.68),and(18.85±3.41)points,respectively],with statistically significant differences(P＜0.05).The satisfaction rate of family members with nursing work in the intervention group was higher than that in the control group,with a statistically significant difference(98.92％versus 89.25％,P＜0.05).Conclusion The dual-track nursing intervention model has a signifi-cant application effect in children with lobar pneumonia.It can accelerate their recovery process,improve treatment compliance,promote pulmonary function improvement,and enhance family mem-bers' satisfaction.

Objective To explore the biological functions of pyroptosis-related genes in pneumonic plague using bioinformatics methods,and to evaluate their potential applicability as diagnostic markers.Methods The pneumonic plague-related dataset GSE220123 was retrieved from the Gene Expression Omnibus(GEO)database and screened for differentially expressed pyroptosis-related genes(DE-PRGs).The functions of DE-PRGs were studied via Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and immune infiltration analysis.The hub genes were identified via protein-protein interaction(PPI)network analysis,and further screened for key genes with sustained high expression characteristics based on differential expression analysis.The relative expression levels of the key genes were verified using the reverse transcription real-time quantitative PCR(qPCR)method.Results A total of 17 DE-PRGs were screened,and PPI network analysis revealed 7 Hub genes.Among them,Casp4 continued to be up-regulated during the course of pneumonic plague.The results of reverse transcription qPCR were consistent with the those of bioinformatic analyses.Conclusion DE-PRGs play a crucial role in the immune response of pneumonic plague,especially Casp4,which has significant applications as a diagnostic biomarker and potential therapeutic target for pneumonic plague.

Objective:To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis.Methods:The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software.Results:Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP.Conclusion:The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.

Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Lipids,including fats(triglycerides)and lipoids(phospholipids and sterols),not only serve as an energy source for the body but also play a pivotal role throughout the reproductive process,particularly in the establishment and maintenance of early pregnancy.This encompasses the regulate of early embryonic development and uterine tolerance,and the facilitation of embryo implantation.Given the diversity of lipids,this review focuses on extensively studied lipid mediators such as polyunsaturated fatty acids,endocannabinoids,prostaglandins,lysophosphatidic acid,sphingolipids and steroid hormones.It systematically elaborates on the regulatory effects of fatty acid,phospholipid,and cholesterol metabolism on the formation of endometrial receptivity and embryo implantation,as well as the potential underlying mechanisms.The review aims to provide new insights and feasible intervention approaches for predicting and improving the outcomes of natural pregnancy and/or assisted reproductive technology.

Brother of regulator of imprinted sites (BORIS), also known as CCCTC binding factor-like (CTCFL), is a relatively newly discovered cancer-testis antigen. Drug development related to BORIS has been carried out in multiple directions, including small molecules, small RNA molecules, polypeptides, vaccines, and cellular therapies. Due to its unique ability to interfere with the higher-order spatial structure of the genome, BORIS may represent a new class of drug targets. Here we systematically review the molecular biology research results related to BORIS, including the diversity of its gene products, the multipartite interactions mediated by BORIS, the subsequent impact on signaling pathways, and current drug development strategies, in order to gain a better understanding of the molecular mechanisms of BORIS in both upstream and downstream regulation networks and to identify potential research directions for further breakthroughs.

Objective:To carry out cytogenetic and molecular genetic analysis for two infertile patients carrying rare small supernumerary marker chromosomes (sSMC).Methods:Two infertile patients who received reproductive and genetic counseling at CITIC Xiangya Reproductive and Genetic Hospital on October 31, 2018 and May 10, 2021, respectively were selected as the study subjects. The origin of sSMCs was determined by conventional G banding, fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq). Microdissection combined with high-throughput whole genome sequencing (MicroSeq) was carried out to determine the fragment size and genomic information of their sSMCs. Results:For patient 1, G-banded karyotyping and FISH revealed that he has a karyotype of mos47, XY, del(16)(p10p12), + mar[65]/46, XY, del(16)(p10p12)[6]/48, XY, del(16)(p10p12), + 2mar[3].ish mar(Tel 16p-, Tel 16q-, CEP 16-, WCP 16+ ). CNV analysis has yielded a result of arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25]. MicroSeq revealed that his sSMC has contained the region of chromosome 16 between 24979733 and 34023115 (GRCh37). For patient 2, karyotyping and reverse FISH revealed that she has a karyotype of mos 47, XX, + mar[37]/46, XX[23].rev ish CEN5, and CNV analysis has yielded a result of seq[GRCh37]dup(5)(p12q11.2)chr5: g(45120001_56000000)dup[0.8]. MicroSeq results revealed that her sSMC has contained the region of chromosome 5 between 45132364 and 55967870(GRCh37). After genetic counseling, both couples had opted in vitro fertilization (IVF) treatment and preimplantation genetic testing (PGT). Conclusion:For individuals harboring sSMCs, it is vital to delineate the origin and structural characteristics of the sSMCs for their genetic counseling and reproductive guidance. Preimplantation genetic testing after microdissection combined with high-throughput whole genome sequencing (MicroSeq-PGT) can provide an alternative treatment for carrier couples with a high genetic risk.

Tissue regeneration is an important engineering method for the treatment of oral soft and hard tissue defects.Growth factors,as one of the three elements of tissue regeneration,are a necessary condition for tissue regeneration.Concentrated growth factor(CGF)is a new generation of blood extract prepared by changing the centrifugal speed on the basis of the preparation of platelet-rich plasma(PRP)and platelet-rich fibrin(PRF).It contains abundant growth factors and a fibrin matrix with a three-dimensional network structure,being capable of activating angiogenesis and promoting tissue regeneration and healing.CGF has been widely used in the repair and regeneration of oral soft and hard tissues.This paper introduces the preparation and composition of CGF and reviews the application of CGF in oral implantation and the regeneration of oral bone tissue,periodontal tissue,and dental pulp tissue.
Platelet-Rich Plasma/metabolism* ; Platelet-Rich Fibrin ; Cell Proliferation ; Bone and Bones ; Intercellular Signaling Peptides and Proteins/metabolism* ; Bone Regeneration

There are inconsistencies in treatment outcomes, measurement instruments, and criteria for assessing clinical effectiveness in studies related to distal radius fractures (DRF), resulting in potential biases and failing to provide high-quality clinical evidence. To address these challenges, international researchers have reached a consensus on developing the core outcome indicator set for distal radius fractures(COS-DRF). However, it's important to note that the existing COS-DRF framework could not reflect the unique characteristics of Traditional Chinese Medicine (TCM) treatment. Currently, there are no established standards for treatment outcomes and measurement instruments specific to TCM clinical research, nor has a COS-DRF been established for TCM clinical studies in China. In light of these gaps, our research team aims to construct a core set of treatment outcomes for TCM clinical research on distal radius fractures. This involves compiling a comprehensive list of treatment outcomes and measurement instruments, initially derived from a thorough literature review and expert consensus, which will then undergo further refinement and updates based on real-world clinical experiences, incorporating feedback from 2 to 3 rounds of expert consensus or Delphi questionnaire surveys. Our goal is to establish a COS-DRF or CMS-DRF that aligns with the principles and practices of TCM, and provide high-quality evidence for clinical practice.
Humans ; China ; Consensus ; East Asian People ; Outcome Assessment, Health Care ; Wrist Fractures/therapy* ; Medicine, Chinese Traditional ; Review Literature as Topic ; Fracture Fixation/standards*