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 evaluate the diagnostic efficacy of the Kaiser score for ultrasound(US)BI-RADS 4A lesions and the potential to avoid unnecessary biopsies.Methods Data of patients who underwent breast US and magnetic resonance imaging(MRI)between May 2019 and June 2023 were retrospectively collected,and all cases were confirmed by puncture biopsy or surgical pathology.The diagnostic efficacy of Kaiser score and MRI BI-RADS classification for US BI-RADS 4A lesions was calculated and compared using pathologic findings as the gold standard.Results A total of 119 lesions(74 benign and 45 malignant lesions)were found in the 119 patients.The diagnostic efficacy of the Kaiser score was significantly better than that of the MRI BI-RADS classification(AUC:0.88 vs.0.65,P＜0.000 1).The concordance of the Kaiser score results with the pathologic findings and the inter-observer concordance were better than that of the MRI BI-RADS classification.Unnecessary biopsies could be avoided in 87.8％(65/74)and 33.8％(25/74)of the cases when the Kaiser score and the MRI BI-RADS classification were applied for the diagnosis of US BI-RADS 4A lesions,respectively.Conclusion The Kaiser score can provide a diagnostic basis for risk stratification of US BI-RADS 4A lesions,and its diagnostic efficacy and inter-observer agreement are superior to those of MRI BI-RADS classification.

Objective:To investigate the relationship between serum interacting protein kinase (RIPK)-3 levels and mycoplasma pneumoniae pneumonia (MPP) correlation between disease severity and lung function in children.Methods:A case-control study was conducted. A total of 147 children with MPP admitted to the Children's Hospital Affiliated to Xuzhou Medical University from April 2023 to March 2024 were selected, including 76 cases of mild MPP (mild MPP group) and 71 cases of severe MPP (severe MPP group). Additionally, 36 healthy children who underwent physical examinations during the same period were selected as the healthy control group. The levels of serum RIPK3, C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer of each group were compared, and the correlations between each index and the severity of MPP in children were analyzed. The lung function indicators, including the percentage of peak expiratory flow (PEF% pred) and the percentage of forced expiratory volume in one second (FEV1% pred), were compared between groups, and the correlations between these indicators and the serum RIPK3 levels in children with MPP were analyzed. Measurement data with normal distribution was expressed as " xˉ±s", one-way ANOVA was used on comparison between groups, LSD-t test was used on pairwise comparison.Measurement data with skewed distribution were expressed as M( Q1, Q3). The Kruskal-Wallis H test was used for comparisons among multiple groups, and the Dunn test was used for pairwise comparisons. Counting data was expressed as case(%), χ2 test was used on comparison between groups. The relationships between serum RIPK3, CRP, LDH, D-dimer and the severity of MPP in children were analyzed by Spearman correlation analysis. The relationships between serum RIPK3 levels and PEF% pred, FEV1% pred were analyzed by Pearson correlation analysis. Results:The levels of serum RIPK3, CRP, LDH and D-dimer in children with mild MPP and severe MPP were all higher than those in the healthy control group [(329.67±59.69), (406.77±47.47) ng/L vs. (103.16±15.93) ng/L, (13.49±4.76), (37.76±18.94) mg/L vs. (1.59±0.81) mg/L, (253.12±50.96), (501.96±167.55) U/L vs. (186.06±45.49) U/L, (0.90±0.19), (3.01±1.46) mg/L vs. (0.29±0.12) mg/L], and the levels in the severe MPP group were all higher than those in the mild MPP group (all P < 0.05). The levels of serum RIPK3, CRP, LDH and D-dimer in children with MPP were positively correlated with the severity of the disease (r values were 0.59, 0.76, 0.83, 0.67, all P < 0.001). The levels of PEF% pred and FEV1% pred in children with mild MPP and severe MPP were all lower than those in the healthy control group [(72.65±7.67)%, (59.93±10.17)% vs. (98.54±4.81)%, (73.79±6.56)%, (60.56±10.54)% vs. (98.08±4.65)%], and the levels in the severe MPP group were all lower than those in the mild MPP group (all P < 0.05). The level of serum RIPK3 in children with MPP was negatively correlated with the lung function indicators PEF% pred and FEV1% pred (r values were -0.78, -0.77, all P < 0.001). Conclusions:The serum RIPK3 level in children with MPP is positively correlated with the severity of their condition and negatively correlated with the lung function indicators PEF% pred and FEV1% pred.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Objective: To investigate the effects of "liver-smoothing and spirit-regulating" acupuncture on the intestinal flora, lipopolysaccharide (LPS) and the hippocampal toll-like receptor 4 (TLR4)/ transcription factor (NF)-κB signaling pathway in depressive disorder mouse model, and to explore its underlying mechanisms. Methods: Eighteen male SPF-grade C57BL/6J mice were randomly assigned to the control, model, and acupuncture groups using a random number method, with six mice in each group. The depression disorder model was induced in mice from both the acupuncture and model groups using CUMS. The mice in the acupuncture group were treated with acupuncture at the acupoints of "Baihui" (DU20), "Yintang" (DU29), "Hegu" (LI4), and "Taichong" (LR3) on the 15th day of modeling, with a duration of 20 min per session, once per day, for 2 consecutive weeks. Behavioral differences were assessed using the sucrose preference test, open field test, and forced swim test. Hematoxylin-eosin staining was used to observe pathological changes in the hippocampus and colon. The levels of the inflammatory factors interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and LPS in the hippocampus and colon were measured using Enzyme-linked Immunosorbent Assay. Western blotting was used to detect the expression of TLR4 and NF-κB protein in the hippocampus. Changes in gut microbiota structure and abundance were analyzed by 16 S rDNA sequencing. Results: Compared to the control group, the model group showed reduced sucrose preference rate, time in the center area, and total distance, with an increase in immobility time (P<0.01). Inflammatory pathological changes were observed in the hippocampal CA1 region and colon. The contents of IL-1β, IL-6, TNF-α, and LPS in the hippocampus and colon increased (P<0.01). The protein expression levels of hippocampal TLR4 and NF-κB were increased (P<0.01). The Chao1 index was increased (P<0.01). The relative abundances of Pseudomonadales, Acinetobacter, Moraxellaceae, Solibacillus, Escherichia_shigella, Enterobacteriaceae, Enterobacterales, Dubosiella, and Erysipelottichales were decreased, while the relative abundances of Alloprevotella and gram_negative_bacteriurh_cTPY_13 were increased (P<0.05). The pathways of lipopolysaccharide biosynthesis and pathogenic Escherichia coli infection were upregulated, and the pathway of terpenoid backbone biosynthesis was downregulated (P<0.01). Compared to the model group, the acupuncture group showed increased sucrose preference, time in the center area, and total distance, with a decrease in immobility time (P<0.01). The inflammatory pathological changes in the hippocampal CA1 region and colon were alleviated. The contents of IL-1β, IL-6, TNF-α, and LPS in the hippocampus and colon were reduced(P<0.01). The protein expression levels of hippocampal TLR4 and NF-κB were reduced (P<0.01). The Chao1 index was decreased (P<0.05), and the relative abundances of Dubosiella and Erysipelotrichaceae were increased, while the relative abundance of Rikenellaceae, Alloprevotella, and gram_negative_bacteriuch_cTPY_13 were decreased(P<0.05). The pathways of lipopolysaccharide biosynthesis and pathogenic Escherichia coli infection were significantly downregulated, and the pathway of terpenoid backbone biosynthesis was upregulated (P<0.01). Conclusion " Liver-smoothing and spirit-regulating" acupuncture can improve depressive symptoms in depressive disorder mice, potentially through regulating the LPS and TLR4/NF-κB signaling pathway mediated by intestinal flora, reducing the inflammatory response of the hippocampus, and improving the pathological injury of the hippocampus.

OBJECTIVE: To observe the clinical effect of Tiaoshen Guben holistic therapy of acupuncture and moxibustion (holistic treatment with acupuncture and moxibustion by adjusting the mind and consolidating the root) on comorbidity of depression and insomnia. METHODS: Twenty-four patients with comorbidity of depression and insomnia were included and treated with Tiaoshen Guben holistic therapy of acupuncture and moxibustion. Acupuncture was applied to Baihui (GV20), Guanyuan (CV4), bilateral Neiguan (PC6), etc. The refined moxibustion therapy was delivered at Zhongwan (CV12), Qihai (CV6), bilateral Yongquan (KI1), etc. Subcutaneous embedding therapy with thumb-tack needle was adopted at bilateral Xinshu (BL15), bilateral Pishu (BL20), etc. The intervention was operated once every other day, 3 treatments a week, and for 6 consecutive weeks. Before and after treatment completion, and in 1 month after treatment, Pittsburgh sleep quality index (PSQI) and Hamilton's depression scale (HAMD-17) were adopted to assess sleep quality and depression symptoms in the patients, respectively. Before and after treatment completion, using functional magnetic resonance imaging (fMRI), the functional connectivity (FC) of locus coeruleus (LC) in brain regions was evaluated; and the levels of serum norepinephrine (NE), cortisol (CORT), adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) were detected. RESULTS: Compared with the scores before treatment, PSQI and HAMD-17 scores after treatment completion and in 1 month after treatment were reduced (P<0.01); and strengthened FC was revealed between the right LC and the pars opercularis of the left inferior frontal gyrus, as well as the lateral occipital lobe region. After treatment completion, serum NE was elevated (P<0.01), the levels of CORT, ACTH and CRH were reduced (P<0.01). Before and after treatment completion, the difference in FC between the right LC and the pars opercularis of the left inferior frontal gyrus was negatively correlated with the differences in PSQI score (r = -0.484, P = 0.016) and HAMD-17 score (r = -0.233, P = 0.027). CONCLUSION Tiaoshen Guben holistic therapy of acupuncture and moxibustion can effectively alleviate depression symptoms and improve sleep quality in the patients with comorbidity of depression and insomnia, which is obtained probably through reducing the levels of serum CORT, ACTH and CRH, increasing serum NE, strengthening the FC of the right LC with the pars opercularis of the left inferior frontal gyrus and the lateral occipital lobe region.
Humans ; Moxibustion ; Sleep Initiation and Maintenance Disorders/therapy* ; Male ; Female ; Middle Aged ; Adult ; Acupuncture Therapy ; Depression/complications* ; Aged ; Young Adult ; Acupuncture Points ; Comorbidity

Objective To investigate the relationship between serum phenylacetylglutamine(PAGln),short-chain fatty acids(SCFAs)levels and ventricular remodeling and prognosis in patients with chronic heart failure(CHF).Methods A total of 267 CHF patients treated at Jiulongpo District People's Hospital of Chongqing from January 2019 to December 2022 were selected as the CHF group,and 100 healthy individuals underwent physical examination during the same period were selected as the control group.CHF patients were further divided into a poor prognosis group(n=63)and a good prognosis group(n=204)based on 1-year outcomes.Serum levels of PAGln and SCFAs(acetic acid,propionic acid,butyric acid)were measured using liquid chromatography-tandem mass spectrometry.Echocardiography was used to assess ventricular remode-ling indicators including left ventricular mass index(LVMI),interventricular septal thickness in diastole(IVST),left ventricular posterior wall thickness(LVPWT),and left ventricular end-diastolic diameter(LVEDD).Pearson correlation was used to analyze the associations between serum PAGln,SCFAs levels and LVMI,IVST,LVPWT,LVEDD.Multivariate logistic regression was used to identify risk factors for poor prognosis in CHF patients,and receiver operating characteristic(ROC)curves were used to assess the predic-tive value of PAGln and SCFAs levels.Results Serum PAGln levels were significantly higher in the CHF group than in the control group,while acetic acid,propionic acid,and butyric acid levels were significantly low-er(P＜0.05).LVMI,IVST,LVPWT,and LVEDD were significantly elevated in the CHF group compared to the control group(P＜0.05).Serum PAGln levels were positively correlated with LVMI,IVST,LVPWT,and LVEDD(P＜0.05),while SCFAs levels were negatively correlated with these parameters(P＜0.05).Univa-riate analysis showed that age,duration of CHF,NYHA functional classification,atrial fibrillation,LVEF,NT-proBNP,PAGln,acetic acid,propionic acid,and butyric acid were associated with poor prognosis(P＜0.05).Multivariate analysis identified NYHA class Ⅲ-Ⅳ,atrial fibrillation,elevated NT-proBNP,and elevated PA-Gln as independent risk factors for poor prognosis,while higher LVEF and increased levels of acetic acid,pro-pionic acid,and butyric acid were independent protective factors(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)for the combined prediction using PAGln and SCFAs was 0.881,which was greater than that for PAGln(0.800)or SCFAs(0.789)alone(P＜0.05).Conclusion Elevated serum PAGln and decreased SCFAs levels are closely associated with ventricular remodeling and poor prognosis in CHF pa-tients.The combination of serum PAGln and SCFAs levels has a high predictive value for poor prognosis in CHF.