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 investigate the effect of miR-142-3p on the apoptosis of rat pancreatic exocrine cell line AR42J by regulating Hmgb1.Methods AR42J cells were divided into blank group(blank),acute pancreatitis model group(AP,100 nmol/L cerulein for 24 h),and then transfected with miR-142-3p mimics,mimics NC,miR-142-3p inhibitor and inhibitor NC,respectively.The cells in the model group were recorded as miR-142-3p mimics group,mimics NC group,miR-142-3p inhibitor group and inhibitor NC.The expression of miR-142-3p in cells was detected by RT-qPCR.The protein expressions of HMGB1,caspase-3,Bax and Bcl-2 were detected by Western blot.Hoechst staining was used to determine cell apoptosis.The apoptosis rate of cells was detected by flow cytometry.The targeting relationship between miR-142-3p and Hmgb1 was determined by dual luciferase reporter gene assay.Results Compared with blank control group,the expression level of miR-142-3p in the AP group was significantly down-regulated(P＜0.01),the expression level of HMGB1 and caspase-3 proteins was up-regulated(P＜0.05),the expression level of Bax protein was significantly up-regulated(P＜0.01),the expression level of Bcl-2 protein was significantly decreased(P＜0.01)and the apoptosis rate increased significantly(P＜0.01).Compared with the mimics NC group,the level of miR-142-3p in the miR-142-3p mimics group was significantly up-regulated(P＜0.01),the expression of HMGB,caspase-3 and Bax proteins was significantly down-regulated(P＜0.01),the expression of Bcl-2 protein was up-regulated(P＜0.05),and the apoptosis rate decreased signifi-cantly(P＜0.01).Compared with inhibitor NC group,the expression level of miR-142-3p in miR-142-3p inhibitor group was down-regulated(P＜0.05),the expression levels of HMGB1,caspase-3 and Bax proteins were signifi-cantly up-regulated(P＜0.01),the expression level of Bcl-2 protein was decreased(P＜0.05)and the apoptosis rate increased significantly(P＜0.01).The dual luciferase reporter gene assay showed that Hmgb1 was the target gene of miR-142-3p.Conclusions 1)The expression of miR-142-3p was low in the model group.2)miR-142-3p can inhibit the apoptosis of AR42J cells by inhibiting the expression of Hmgb1.

Objective:To explore the application effect of cardiac respiratory arrest scenario simulation exercise combined with four-step disk method in the teaching practice of standardized nurses in the department of anesthesiology, and to provide teaching plan and reference for the training of core competence of standardized nurses.Methods:A randomized controlled study was conducted to select 127 standardized trained nurses in rotation anesthesia and intoxication department of West China Hospital, Sichuan University from July 2020 to December 2023 by cluster sampling method. A total of 64 first-year standardized training nurses from three batches of rotation anesthesiology department from July 2020 to December 2021 were selected as the control group, and the conventional teaching method was applied to their teaching practice. A total of 63 first-year standardized training nurses from three batches of rotation anesthesiology department in 2022 and from July to December 2023 were selected as the observation group. On the basis of routine teaching, the cardio-respiratory arrest scenario simulation exercise combined with four-step review method was implemented to carry out teaching practice. One week before leaving the course, the theoretical test scores, skill operation scores (6 operations including anesthesia machine, intravenous induration needle infusion, open sputum aspiration, defibrillation apparatus, simple respiratory sac ventilation and single cardiopulmonary resuscitation), post competency scores and teaching satisfaction scores of the two groups of standardized training nurses were assessed and compared.Results:The control group included 11 males and 53 females, aged (23.25 ± 0.78) years. In the observation group, there were 12 males and 51 females, aged (23.29 ± 0.81) years. The average score of skill operation in the observation group was (93.54 ± 0.92) points, which was higher than that in the control group (91.02 ± 1.08) points, and the difference between the two groups was statistically significant ( t=-14.10, P<0.01). The total theoretical score of the observation group (81.32 ± 3.84) points was higher than that of the control group (61.86 ± 2.05) points, and the difference between the two groups was statistically significant ( t=-35.69, P<0.01). The scores of self-evaluation of post competence and other evaluation and teaching satisfaction of the observation group were (95.81 ± 2.69), (94.22 ± 2.57) and (96.81 ± 2.75) points, which were higher than those of the control group (88.47 ± 5.56), (91.64 ± 3.10) and (91.52 ± 3.50) points. The differences between the two groups were statistically significant ( t=-9.49, -5.10, -9.47, all P<0.01). Conclusions:The application of heart-respiratory arrest scenario simulation and GRAI repetition method in the teaching practice of standardized nurses can improve the theoretical mastery level of standardized nurses and their operational performance, enhance their post competency, improve their teaching satisfaction, enhance their self-confidence and self-awakening ability, improve their learning enthusiasm, and their theoretical connection with practice level. To promote the improvement of teaching program and teaching quality, it is worth applying and popularizing in teaching practice.

Objective:To explore the application effect of cardiac respiratory arrest scenario simulation exercise combined with four-step disk method in the teaching practice of standardized nurses in the department of anesthesiology, and to provide teaching plan and reference for the training of core competence of standardized nurses.Methods:A randomized controlled study was conducted to select 127 standardized trained nurses in rotation anesthesia and intoxication department of West China Hospital, Sichuan University from July 2020 to December 2023 by cluster sampling method. A total of 64 first-year standardized training nurses from three batches of rotation anesthesiology department from July 2020 to December 2021 were selected as the control group, and the conventional teaching method was applied to their teaching practice. A total of 63 first-year standardized training nurses from three batches of rotation anesthesiology department in 2022 and from July to December 2023 were selected as the observation group. On the basis of routine teaching, the cardio-respiratory arrest scenario simulation exercise combined with four-step review method was implemented to carry out teaching practice. One week before leaving the course, the theoretical test scores, skill operation scores (6 operations including anesthesia machine, intravenous induration needle infusion, open sputum aspiration, defibrillation apparatus, simple respiratory sac ventilation and single cardiopulmonary resuscitation), post competency scores and teaching satisfaction scores of the two groups of standardized training nurses were assessed and compared.Results:The control group included 11 males and 53 females, aged (23.25 ± 0.78) years. In the observation group, there were 12 males and 51 females, aged (23.29 ± 0.81) years. The average score of skill operation in the observation group was (93.54 ± 0.92) points, which was higher than that in the control group (91.02 ± 1.08) points, and the difference between the two groups was statistically significant ( t=-14.10, P<0.01). The total theoretical score of the observation group (81.32 ± 3.84) points was higher than that of the control group (61.86 ± 2.05) points, and the difference between the two groups was statistically significant ( t=-35.69, P<0.01). The scores of self-evaluation of post competence and other evaluation and teaching satisfaction of the observation group were (95.81 ± 2.69), (94.22 ± 2.57) and (96.81 ± 2.75) points, which were higher than those of the control group (88.47 ± 5.56), (91.64 ± 3.10) and (91.52 ± 3.50) points. The differences between the two groups were statistically significant ( t=-9.49, -5.10, -9.47, all P<0.01). Conclusions:The application of heart-respiratory arrest scenario simulation and GRAI repetition method in the teaching practice of standardized nurses can improve the theoretical mastery level of standardized nurses and their operational performance, enhance their post competency, improve their teaching satisfaction, enhance their self-confidence and self-awakening ability, improve their learning enthusiasm, and their theoretical connection with practice level. To promote the improvement of teaching program and teaching quality, it is worth applying and popularizing in teaching practice.

OBJECTIVEThe aim of this study was to survey the influence of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) repression to receptor activator of nuclear factor-kappaB ligand (RANKL) expression of human periodontal ligament fibroblasts (HPDLFs) under the stimulation of lipopolysaccharide (LPS).

METHODSThe level of RANKL in HPDLFs stimulated by 100 ng x mL(-1), 1 microg x mL(-1) and 10 microg x mL(-1) Escherichia coli (E. coli) LPS after 6, 12, 24 and 48 h was detected by enzyme linked immunosorbent assay (ELISA). The level of RANKL in HPDLFs stimulated by 1 microg x mL(-1) E. coli LPS after pretreatment with different titre anti-TLR2+anti-TLR4, anti-TLR2 and anti-TLR4 antibody were observed respectively.

RESULTSRANKL was detected at 6 h after stimulation with LPS, and the levels of these cytokine were highest at 24 h, and then gradually decreased. The regularity of each LPS concentration was approximately similar. After pretreatment with anti-TLR2+anti-TLR4, anti-TLR2 and anti-TLR4 antibody, the level of RANKL was significantly decreased under the stimulation of 1 microg x mL(-1) LPS (P<0.05). In the three groups, the expression of RANKL was significantly different (P<0.05). The level of RANKL in anti-TLR2+anti-TLR4 antibody pretreatment group was the lowest, the level in anti-TLR4 antibody pretreatment group was higher, and the level in anti-TLR2 antibody pretreatment group was the highest.

CONCLUSIONTLR2 and TLR4 participate in the process of RANKL expres-in HPDLFs induced by LPS. Anti-TLR4 antibody has better inhibition effect to RANKL expression of HPDLFs stimulated by LPS than anti-TLR2.

Escherichia coli ; Fibroblasts ; Humans ; Lipopolysaccharides ; Periodontal Ligament ; RANK Ligand ; Toll-Like Receptor 2 ; Toll-Like Receptor 4

OBJECTIVE: A method based on dubious condition of information entropy was introduced and applied to discuss a complexity problem in the analysis of correlation between traditional Chinese medicine (TCM) syndrome and season. METHODS: Eight hundred and seventy one cases of chronic virus hepatitis B (hepatitis B) with TCM clinical data were analyzed by information entropy method. RESULTS: It was found that hepatitis B with Yin deficiency of liver and kidney happened more often in summer than in other seasons. CONCLUSION: It is inferred that the difference of seasons may influence the variation of TCM syndromes.