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:This study aims to investigate the predictive performance of serum levels of white blood cell count(WBC),D-dimer(D-D)and N-terminal pro-brain natriuretic peptide(NT-proBNP)for major adverse cardiovascular events(MACE)in elderly patients with acute ST-segment elevation myocardial infarction(ASTE-MI).Methods:A total of 70 elderly patients with ASTEMI treated in Bozhou People's Hospital between April 2020 and May 2023 were prospectively selected as observation group.Incidence of MACE during 1-year follow-up were recorded,another 50 patients with unstable angina pectoris treated in our hospital simultaneously were selected as control group.Serum levels of WBC,D-D and NT-proBNP were compared among above groups.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum WBC,D-D and NT-proBNP for MACE in elderly patients with ASTEMI.A nomogram was established,and calibration curve and deci-sion curve analysis(DCA)were used to evaluate the performance of model.Results:A total of 40 cases(59.70％)experienced MACE during one-year follow-up.Compared to those in control group,patients in observation group had significant higher serum WBC[(11.43±1.98)×109/Lvs.(6.30±1.99)× 109/L],D-D[(0.91±0.20)mg/L vs.(0.47±0.18)mg/L]andNT-proBNP[(192.31±63.19)pg/ml vs.(114.05±22.79)pg/ml](P＜0.001 all).Compared to participants without MACE,those with MACE had significantly higher serum WBC[(13.33±1.90)× 109/L vs.(10.27±0.98)× 109/L],D-D[(1.11±0.25)mg/L vs.(0.87±0.21)mg/L]and NT-proBNP[(238.73±50.22)pg/ml vs.(150.70±39.16)pg/ml](P＜0.001 all).ROC analysis showed that the ar-ea under the curve(AUC)of the combined detection of serum WBC(AUC=0.791,95％CI 0.677～0.879),D-D(AUC=0.767,95％CI 0.650～0.859)and NT-proBNP(AUC=0.733,95％CI 0.614～0.832)was 0.916(95％CI 0.825～0.969),which was significantly higher than those of single detections(Z=2.386,4.953,3.190,P=0.017,0.004,＜0.001).The total score of the nomogram model constructed based on the levels of WBC,D-D and NT-proBNP ranged from 70 to 126 points.The predicted incidence was basically consistent with the actual in-cidence.For the internal verification of the model,the AUC of ROC curve of the training set and the validation set was 0.863 and 0.926 respectively.The DCA curve was located above the critical curve,indicating that the model had a net benefit and good clinical effectiveness.Conclusion:Serum WBC,D-D and NT-proBNP significantly el-evated in elderly patients with ASTEMI.The combined detection of serum WBC,D-D and NT-proBNP levels has good predictive value for MACE in these patients.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

OBJECTIVE To explore the clinical characteristics of the nontuberculous Mycobacteria pulmonary dis-ease(NTMPD)patients with previous pulmonary tuberculosis(PPTB)and analyze the clinical difference from the recurrence of pulmonary tuberculosis.METHODS By means of retrospective survey,the patients who were diag-nosed with NTMPD and recurrent pulmonary tuberculosis in Wuhan Pulmonary Hospital from Mar.2021 to Oct.2023 were recruited as the research subjects,a total of 395 patients with NTMPD were enrolled in the study and were divided into the PPTB-NTMPD group with 92 cases and the NPPTB-NTMPD group with 303 cases according to the history of PPTB.The baseline data,clinical symptoms,imaging findings,underlying diseases,pulmonary diseases,and species of nontuberculous Mycobacteria(NTM)were observed and compared.Totally 92 patients with recurrent pulmonary tuberculosis were randomly screened and assigned as the recurrent pulmonary tuberculo-sis group in a 1:1 ratio by matching the PPTB-NTMPD group with the gender and age.The major clinical charac-teristics were compared between the two groups.The 92 patients with PPTB-NTMPD were divided into the 1-10 years group with 40 cases,the 10-30 years group with 37 cases,and the more than 30 years group with 15 cases according to the interval between the initial diagnosis of pulmonary tuberculosis and the diagnosis of NTMPD.The major clinical characteristics were compared among the groups.RESULTS The age was(64.21±10.71)years old in the PPTB-NTMPD group,(60.26±11.83)years old in the NPPTB-NTMPD group(t=3.020,P=0.003).The proportion of patients with body mass index less than 18.5 kg/m2 was 59.78％in the PPTB-NTMPD group,41.25％in the NPPTB-NTMPD group(x2=6.155,P=0.013);the proportion of patients with cough was 77.17％in the PPTB-NTMPD group,65.68％in the NPPTB-NTMPD group(x2=4.313,P=0.038);the inci-dence of cavitary shadow was 50.00％in the PPTB-NTMPD group,35.31％in the NPPTB-NTMPD group(x2=6.414,P=0.011);the incidence of emphysema and pulmonary bullae was 29.35％in the PPTB-NTMPD group,12.87％in the NPPTB-NTMPD group(x2=13.766,P＜0.001);the incidence of chronic obstructive pulmonary disease(COPD)was 22.83％in the PPTB-NTMPD group,14.19％in the NPPTB-NTMPD group(x2=3.875,P=0.049);the incidence of damaged lung was 9.78％in the PPTB-NTMPD group,2.97％in the NPPTB-NT-MPD group(x2=7.530,P=0.014);there were significant differences.Mycobacterium intracellulare and Myco-bacterium abscessus were the predominant species of NTM in both the PPTB-NTMPD group and the NPPTB-NT-MPD group,there was no significant difference in the distribution of NTM species between the two groups of pa-tients.The incidence of patch shadow of the PPTB-NTMPD group was lower than that of the recurrent pulmonary tuberculosis group(P＜0.05),the incidence of bronchiectatic shadow of the PPTB-NTMPD group was higher than that of the recurrent pulmonary tuberculosis group(P＜0.05).There were significant differences in the age,incidence of pleural thickening and incidence of COPD among the patients with different time intervals between ini-tial diagnosis of pulmonary tuberculosis and the diagnosis of NTMPD in the PPTB-NTMPD group(P＜0.05).CONCLUSIONS The previous pulmonary tuberculosis mainly affect the body mass index less than 18.5 kg/m2 and the post-tuberculosis pulmonary diseases such as cough,pulmonary cavity,emphysema,pulmonary bullae,COPD and damaged lung of the NTMPD patients.The NTMPD patients with previous pulmonary tuberculosis are more likely to have bronchiectasia than the patients with recurrent tuberculosis.It is necessary for the clinicians to attach great importance.

OBJECTIVE To explore the clinical characteristics of the nontuberculous Mycobacteria pulmonary dis-ease(NTMPD)patients with previous pulmonary tuberculosis(PPTB)and analyze the clinical difference from the recurrence of pulmonary tuberculosis.METHODS By means of retrospective survey,the patients who were diag-nosed with NTMPD and recurrent pulmonary tuberculosis in Wuhan Pulmonary Hospital from Mar.2021 to Oct.2023 were recruited as the research subjects,a total of 395 patients with NTMPD were enrolled in the study and were divided into the PPTB-NTMPD group with 92 cases and the NPPTB-NTMPD group with 303 cases according to the history of PPTB.The baseline data,clinical symptoms,imaging findings,underlying diseases,pulmonary diseases,and species of nontuberculous Mycobacteria(NTM)were observed and compared.Totally 92 patients with recurrent pulmonary tuberculosis were randomly screened and assigned as the recurrent pulmonary tuberculo-sis group in a 1:1 ratio by matching the PPTB-NTMPD group with the gender and age.The major clinical charac-teristics were compared between the two groups.The 92 patients with PPTB-NTMPD were divided into the 1-10 years group with 40 cases,the 10-30 years group with 37 cases,and the more than 30 years group with 15 cases according to the interval between the initial diagnosis of pulmonary tuberculosis and the diagnosis of NTMPD.The major clinical characteristics were compared among the groups.RESULTS The age was(64.21±10.71)years old in the PPTB-NTMPD group,(60.26±11.83)years old in the NPPTB-NTMPD group(t=3.020,P=0.003).The proportion of patients with body mass index less than 18.5 kg/m2 was 59.78％in the PPTB-NTMPD group,41.25％in the NPPTB-NTMPD group(x2=6.155,P=0.013);the proportion of patients with cough was 77.17％in the PPTB-NTMPD group,65.68％in the NPPTB-NTMPD group(x2=4.313,P=0.038);the inci-dence of cavitary shadow was 50.00％in the PPTB-NTMPD group,35.31％in the NPPTB-NTMPD group(x2=6.414,P=0.011);the incidence of emphysema and pulmonary bullae was 29.35％in the PPTB-NTMPD group,12.87％in the NPPTB-NTMPD group(x2=13.766,P＜0.001);the incidence of chronic obstructive pulmonary disease(COPD)was 22.83％in the PPTB-NTMPD group,14.19％in the NPPTB-NTMPD group(x2=3.875,P=0.049);the incidence of damaged lung was 9.78％in the PPTB-NTMPD group,2.97％in the NPPTB-NT-MPD group(x2=7.530,P=0.014);there were significant differences.Mycobacterium intracellulare and Myco-bacterium abscessus were the predominant species of NTM in both the PPTB-NTMPD group and the NPPTB-NT-MPD group,there was no significant difference in the distribution of NTM species between the two groups of pa-tients.The incidence of patch shadow of the PPTB-NTMPD group was lower than that of the recurrent pulmonary tuberculosis group(P＜0.05),the incidence of bronchiectatic shadow of the PPTB-NTMPD group was higher than that of the recurrent pulmonary tuberculosis group(P＜0.05).There were significant differences in the age,incidence of pleural thickening and incidence of COPD among the patients with different time intervals between ini-tial diagnosis of pulmonary tuberculosis and the diagnosis of NTMPD in the PPTB-NTMPD group(P＜0.05).CONCLUSIONS The previous pulmonary tuberculosis mainly affect the body mass index less than 18.5 kg/m2 and the post-tuberculosis pulmonary diseases such as cough,pulmonary cavity,emphysema,pulmonary bullae,COPD and damaged lung of the NTMPD patients.The NTMPD patients with previous pulmonary tuberculosis are more likely to have bronchiectasia than the patients with recurrent tuberculosis.It is necessary for the clinicians to attach great importance.

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:This study aims to investigate the predictive performance of serum levels of white blood cell count(WBC),D-dimer(D-D)and N-terminal pro-brain natriuretic peptide(NT-proBNP)for major adverse cardiovascular events(MACE)in elderly patients with acute ST-segment elevation myocardial infarction(ASTE-MI).Methods:A total of 70 elderly patients with ASTEMI treated in Bozhou People's Hospital between April 2020 and May 2023 were prospectively selected as observation group.Incidence of MACE during 1-year follow-up were recorded,another 50 patients with unstable angina pectoris treated in our hospital simultaneously were selected as control group.Serum levels of WBC,D-D and NT-proBNP were compared among above groups.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum WBC,D-D and NT-proBNP for MACE in elderly patients with ASTEMI.A nomogram was established,and calibration curve and deci-sion curve analysis(DCA)were used to evaluate the performance of model.Results:A total of 40 cases(59.70％)experienced MACE during one-year follow-up.Compared to those in control group,patients in observation group had significant higher serum WBC[(11.43±1.98)×109/Lvs.(6.30±1.99)× 109/L],D-D[(0.91±0.20)mg/L vs.(0.47±0.18)mg/L]andNT-proBNP[(192.31±63.19)pg/ml vs.(114.05±22.79)pg/ml](P＜0.001 all).Compared to participants without MACE,those with MACE had significantly higher serum WBC[(13.33±1.90)× 109/L vs.(10.27±0.98)× 109/L],D-D[(1.11±0.25)mg/L vs.(0.87±0.21)mg/L]and NT-proBNP[(238.73±50.22)pg/ml vs.(150.70±39.16)pg/ml](P＜0.001 all).ROC analysis showed that the ar-ea under the curve(AUC)of the combined detection of serum WBC(AUC=0.791,95％CI 0.677～0.879),D-D(AUC=0.767,95％CI 0.650～0.859)and NT-proBNP(AUC=0.733,95％CI 0.614～0.832)was 0.916(95％CI 0.825～0.969),which was significantly higher than those of single detections(Z=2.386,4.953,3.190,P=0.017,0.004,＜0.001).The total score of the nomogram model constructed based on the levels of WBC,D-D and NT-proBNP ranged from 70 to 126 points.The predicted incidence was basically consistent with the actual in-cidence.For the internal verification of the model,the AUC of ROC curve of the training set and the validation set was 0.863 and 0.926 respectively.The DCA curve was located above the critical curve,indicating that the model had a net benefit and good clinical effectiveness.Conclusion:Serum WBC,D-D and NT-proBNP significantly el-evated in elderly patients with ASTEMI.The combined detection of serum WBC,D-D and NT-proBNP levels has good predictive value for MACE in these patients.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

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.