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

Objectives:To analyze the cardiac involvement of patients with Fabry disease(FD)in Anhui region.Methods:This retrospective analysis included 48 previously and currently diagnosed FD patients(25 males)in Anhui region,overall patient and gender specific cardiac involvement was analyzed.Results:The median age of FD patients is 28.0(19.0,46.0)years.The cardiac manifestations of patients with FD were most commonly characterized by palpitations/arrhythmias(13/42 cases)and exertional dyspnea(11/42 cases),electrocardiographic changes were most commonly characterized by T-wave inversion(22/42 cases),ST-segment depression(16/42 cases),and left ventricular hypervoltage(18/42 cases),cardiac structural and functional changes were most common in papillary muscle hypertrophy(29/36 cases),bilateral sign(22/37 cases)and left ventricular hypertrophy(21/46 cases),as well as reduced left ventricular global longitudinal strain(26/39 cases).Neuropathic pain(28/43 cases)was the most common extracardiac manifestation of FD patients.FD patients of different gender differed in age at diagnosis(P=0.018),alpha galactosidase A activity(P<0.001),globotriaosylsphingosine(lyso-GL3)levels(P<0.001),enzyme replacement therapy rate(P=0.043),dyshidrosis(P<0.01),and the incidence of angiokeratoma(P=0.004).Correlation analysis showed that genotype was not correlated with enzyme activity or Lyso-GL-3 levels,whereas the Sokolow-Lyon index was positively correlated with Lyso-GL-3 levels(ρ=0.423,P=0.008),and the Sokolow-Lyon indices(septal thickness:ρ=0.562,P<0.001;left ventricle posterior wall thickness:ρ=0.569,P<0.001)and QRS duration(septal thickness:ρ=0.543,P<0.001;left ventricle posterior wall thickness:ρ=0.557,P<0.001)were positively correlated with left ventricular wall thickness.Conclusions:Cardiac involvement in patients with FD in the Anhui region is characterised by palpitations or arrhythmias,accompanied by nonspecific electrocardiographic changes.Echocardiography frequently reveals papillary muscle hypertrophy.The manifestation of cardiac involvement in patients of different genders is similar.

Objective:To evaluate the value of peripheral blood systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), D-dimer, and albumin (ALB) alone or their combination in the diagnosis of early-onset colorectal cancer (EOCRC).Methods:From January 1, 2023 to November 30, 2024, 104 patients with EOCRC (EOCRC group) hospitalized at Renmin Hospital of Wuhan University were enrolled. During the same period, by simple random sampling method, 104 patients with benign colorectal polyps (benign polyp group) and 104 healthy individuals for health examinations (healthy control group) from outpatient department were enrolled. The peripheral blood parameters (including neutrophil count, lymphocyte count, CEA, and others) and pathological characteristics of EOCRC (including TNM stage, tumor differentiation grade, and depth of invasion) were collected. The relationship between peripheral blood parameters and EOCRC pathological features were analyzed. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) was calculated to evaluate the diagnostic value. Multivariate logistic regression analysis was performed to analyze the peripheral blood parameters which independently correlated with EOCRC and a combined diagnostic model was established. Simple random sampling method was used to divide the subjects in the negative control group (healthy control group + benign polyp group) and positive group (EOCRC group) into a training set (218 cases) and a validation set (94 cases) at a ratio of 7∶3, and the diagnostic performance of the combined diagnostic model in the training and validation sets was assessed. Hosmer-Lemeshow test and calibration curve were used to evaluate the fit and consistency of the model. Independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test were used for statistical analysis. Results:EOCRC group had the highest levels of SII(744.03 (473.01, 1 246.28), 437.77 (342.28, 607.47), 497.31 (385.76, 721.63)×10 9/L), NLR(2.42 (1.76, 3.94), 1.96 (1.54, 2.52), 1.91 (1.55, 2.75)), CEA (3.58 (1.96, 20.85), 1.31 (0.95, 1.93), 1.21 (0.76, 2.11) μg/L) and D-dimer (0.36 (0.20, 0.90), 0.19 (0.12, 0.28), 0.18 (0.12, 0.30) mg/L), and the lowest levels of LMR(3.51±1.56, 4.38±1.37, 4.72±1.84) and ALB(42.40 (39.90, 44.70), 44.57 (42.83, 46.25), 44.95 (43.10, 46.58) g/L) than benign polyp group and healthy control group, and the differences were statistically significant ( H=31.18, 16.21, 76.72 and 47.72, F=15.40, H=34.19; all P<0.001). In EOCRC patients, there were statistically significant differences in SII and LMR between patients with different tumor invasion depth ( Z=-2.48, t=2.31; both P<0.05), in CEA between patients with different TNM stage, with or without lymph node metastasis and distant metastasis( Z=-2.68, -2.50 and -2.65; all P<0.05), in D-dimer between patients with different TNM stage, differentiation grade, invasion depth, and with or without lymph node metastasis and distant metastasis ( Z=-2.50, -2.60, -2.06, -2.14 and -3.33; all P<0.05), and in ALB between patients with or without distant metastasis ( Z=-2.52, P=0.012).The AUC of combination of SII, NLR, LMR, CEA, D-dimer, and ALB in differential diagnosis of the healthy control group and the EOCRC group was 0.914 (95% confidence interval (95% CI): 0.870 to 0.958, P<0.001), and the AUC of the combination in differential diagnosis of the benign polyp group and the EOCRC group was 0.904 (95% CI: 0.857 to 0.950, P<0.001). The results of multivariate logistic regression analysis revealed that SII, NLR, LMR, CEA, and ALB were all independently correlated with EOCRC (all P<0.05). The diagnostic model for EOCRC was established by the combination of SII, NLR, LMR, CEA, and ALB, and the AUC of the model in the training set and validation set was 0.911 and 0.883, respectively. The Hosmer-Lemeshow goodness-of-fit test indicated good model fit ( P=0.437). Calibration curve analysis showed strong consistency between predicted probabilities and actual probabilities, and the mean absolute error was 0.015. Conclusions:SII, NLR, LMR, CEA, D-dimer, and ALB all demonstrate diagnostic value in the diagnosis of EOCRC. The combined diagnostic model based on SII, NLR, LMR, CEA, and ALB demonstrates excellent diagnostic performance, which may serve as an adjunctive diagnostic approach for EOCRC.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective:To systematically evaluate the fairness of traditional Chinese medicine (TCM) healthcare resource allocation at the prefecture-level in China using the healthcare resource agglomeration degree (HRAD) method, so as to provide empirical evidence for optimizing resource distribution.Methods:Data on TCM healthcare resources (including the number of TCM institutions, public TCM hospitals, TCM hospital beds, and TCM healthcare technicians) were collected from 333 prefecture-level regions in 2023. The HRAD method was employed to assess fairness in geographic allocation (HRAD i) and population-based allocation (HRAD i/PAD i). A multi-indicator comprehensive evaluation was conducted using the entropy weight method to determine weighting coefficients. Results:Significant disparities were observed in the geographic agglomeration of TCM resources (HRAD i) in China. Resource-rich regions (HRAD i>5) were primarily concentrated in eastern and some central-western provinces, while resource-scarce regions (HRAD i<1) were mainly distributed in western, northeastern, and parts of central and eastern provinces. Analysis of population-based fairness (HRAD i/PAD i) revealed that most prefecture-level cities nationwide had ratios<1, with only 8 provinces having more cities with ratios>1 than<1. The comprehensive evaluation showed that top-ranked cities in the east (e.g., Hangzhou, Dongying, Shenzhen), central region (e.g., Taiyuan, Zhengzhou), and west (e.g., Hainan Prefecture, Alxa League) were predominantly core cities or sparsely populated areas. Conclusions:China′s prefecture-level TCM healthcare resource allocation exhibits significant geographic and population-based inequities, with excessive concentration in provincial capitals and developed cities. Urgent strategies are needed to optimize resource allocation, enhance fairness and accessibility, including promoting the decentralization of high-quality resources, strengthening regional collaborative support, enhancing talent attraction in underdeveloped areas, and leveraging information technology to improve efficiency.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To summarize clinical characteristics and prognosis of immune checkpoint inhibitor (ICI) -related Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN) .Methods:A retrospective analysis was conducted on patients diagnosed with ICI-related SJS/TEN in Zhongda Hospital, Southeast University from January 2018 to October 2023. Data on clinical manifestations, laboratory examinations, treatment and prognosis of the patients were analyzed.Results:A total of 9 patients were diagnosed with ICI-related SJS/TEN, including 8 males and 1 female, with the onset age ranging from 58 to 77 (67.56 ± 7.33) years. ICI were applied to all the 9 patients before onset of SJS/TEN. The latent period was 6 - 261 d, and the median duration was 76 d. All the patients presented with erythema as initial lesions, 3 cases with target lesions, 6 with blisters, and 5 cases with a positive Nikolsky's sign. Oral mucosal damage occurred in 7 cases, eye damage occurred in 6 cases, and urogenital damage occurred in 6 cases. All the 9 cases were treated with systematic glucocorticoids, 7 cases with intravenous immunoglobulin and 7 cases with antibiotics. Eight cases recovered and 1 case died. Among 6 patients followed for an average of 6.92 months, none achieved complete or partial remission, 3 died and 3 experienced disease progression.Conclusions:ICI-related SJS/TEN occurred with a relatively long latent period, and all the cases presented with erythema initially, with mucosal damage present in most of the cases. Management required discontinuation of ICI, and most patients recovered with corticosteroids and intravenous immunoglobulin, however, the prognosis for the primary malignancy remained poor.

Objective:To explore the morphological characteristics of the corpus callosum (CC) in patients with unilateral medial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS), and their correlation with hippocampal volume and clinical indicators.Methods:This was a cross-sectional study. Clinical (age of onset, disease duration, seizure frequency, seizure duration, etc.) and imaging data of 44 patients mTLE with unilateral HS confirmed by postoperative pathology and 42 healthy controls (HCs) recruited at West China Hospital of Sichuan University from June 2017 to May 2023 were analyzed retrospectively. Among the 44 patients, 19 had left-sided HS and 25 had right-sided HS. All subjects underwent high-resolution 3D T 1WI. Hippocampal volumes were obtained using FreeSurfer. ART was used to measure the morphological parameters of the CC for each participant, including total CC area, volume, perimeter, length, thickness, circularity, and the area of seven CC subregions defined by Witelson: rostrum, genu, body, anterior midbody, posterior midbody, isthmus and splenium. Differences in these metrics between two or three groups were compared using independent samples t-test or one-way ANOVA. Pearson or Spearman correlation analysis was used to observe the correlation between morphological features of the CC and hippocampal volume and other clinical indicators in patients with mTLE with unilateral HS. Results:Compared with HCs, patients with mTLE with unilateral HS had significantly reduced total CC area, CC circularity, as well as the area and thickness of the genu, anterior midbody, posterior midbody, isthmus, splenium, and the area of the rostrum ( P<0.05). Significant differences were observed in the total area, circularity, and subregional areas (genu, rostrum, anterior midbody, posterior midbody, splenium), as well as thickness (genu, anterior midbody, posterior midbody, isthmus) of the CC among mTLE with left-sided HS, mTLE with right-sided HS, and HCs ( P<0.05). When compared to HCs, the total area of the CC, circularity and the areas of the genu, rostrum, anterior midbody, posterior midbody, and splenium, and the thicknesses of the genu, anterior midbody, posterior midbody, and isthmus of the CC were significantly reduced in patients with mTLE with right-sided HS ( P<0.05), and the thicknesses of the midbody and isthmus of the CC were significantly reduced in patients with mTLE with left-sided HS compared to HCs ( P<0.05), and the two-by-two comparison of the rest of the indicators did not show statistically significant differences ( P>0.05). Correlation analysis showed that some morphological abnormalities in the CC in mTLE with unilateral HS patients were significantly correlated with age of onset, disease duration, seizure frequency, seizure duration, and hippocampal volume. Conclusions:mTLE with unilateral HS patients can exhibit morphological abnormalities in the CC, particularly in those with right-sided lesions. These abnormalities are significantly associated with seizure-related factors and hippocampal atrophy.

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies