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

This article reports a case of a male patient with anti-N-methyl-D-aspartate receptor （NMDAR） encephalitis comorbid with early-onset Alzheimer's disease （AD）. The patient presented with depression， hallucinations and delusions syndrome， and cognitive impairment， and was admitted to a psychiatric hospital. Through multidisciplinary consultation， the diagnosis was confirmed based on positive biological and pathological biomarkers. The patient's symptoms improved after receiving a therapeutic regimen comprising high-dose glucocorticoid therapy and psychiatric-related treatments. Based on relevant current research findings domestically and internationally， this article reviews the pathogenesis and clinical manifestations of early-onset AD and anti-NMDAR encephalitis， in order to enhance the discrimination ability of psychiatric specialists for such patients and improve the diagnosis and treatment level. ［Funded by Medical Research Project of Chengdu City （number， 2024403）］

ObjectiveTo develop an assessment tool for apraxia of speech (AOS) of Chinese Putonghua speakers and test its reliability and validity. MethodsThe Chinese Apraxia of Speech Assessment and Diagnostic Tool (CAADT) was developed based on the Apraxia of Speech Rating Scale 3.5, combined with the linguistic characteristics of Chinese and clinical experience. The tool consistsed of eleven items across three sections: articulation, prosody and alternating motion rates. Six experts evaluated the content validity. From November, 2024 to May, 2025, 51 patients with post-stroke AOS (experimental group) and ten patients with post-stroke aphasia without AOS (control group) were recruited from Anhui Wannan Rehabilitation Hospital (the Fifth People's Hospital of Wuhu), and tested with CAADT. Reliability was assessed using Cronbach's α coefficient, Kendall's coefficient of concordance W and Pearson correlation coefficient. Validity was evaluated using the content validity index (CVI) and Spearman correlation coefficient. Discriminative effect was analyzed using the receiver operating characteristic (ROC) curve. ResultsThe Cronbach's α coefficients for the articulation and prosody sections and the total scale were all > 0.9, while it was 0.454 for the alternating motion rates. Inter-rater reliability was good (W ≥ 0.598, P < 0.001). Test-retest reliability showed high positive correlations for the three sections and the total score between the two assessments (r ≥ 0.84, P < 0.001). The scale-level CVI was 0.95, and the item-level CVI ≥ 0.83. The Spearman correlation coefficients among the sections ranged from 0.30 to 0.70. ROC analysis revealed an area under the curve of 0.953, with a cut-off value of 11, yielding a sensitivity of 0.92 and a specificity of 0.90. ConclusionCAADT demonstrates good reliability, validity and discriminative effect, which can be used for clinical assessment and auxiliary diagnosis of Chinese Putonghua speaking patients with post-stroke AOS.

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective:To explore potential categories of disease progression fear and self-management ability in patients with maintenance hemodialysis (MHD) and their influencing factors.Methods:Convenience sampling was used to select MHD patients in the Blood Purification Center of the Affiliated Nantong Hospital of Nanjing University of Chinese Medicine, the Affiliated Suzhou Hospital of Nanjing University Medical School, and the Affiliated Huaian First People's Hospital of Nanjing Medical University from November 2022 to May 2023 as study subjects. General Information Questionnaire, Fear of Progression Questionnaire-short form (FoP-Q-SF), Hemodialysis Self-management Instrument (HDSMI), and Perceived Social Support Scale (PSSS) were used to conduct the survey. Mplus 8.7 software was applied to conduct latent profile analysis, and multiple Logistic regression was used to explore the factors influencing the disease progression fear and self-management ability of different MHD patients.Results:A total of 380 questionnaires were distributed, and 364 valid questionnaires were recovered, with an effective recovery rate of 95.79%. The mean scores of FoP-Q-SF and HDSMI in 364 MHD patients were (2.53±0.84) and (2.81±0.54), respectively. MHD patients' fear of disease progression and self-management ability were manifested in three different potential categories, named high fear-general self-management (59.34%, 216/364), moderate fear-low self-management (24.45%, 89/364), and low fear-good self-management (16.21%, 59/364). Multiple Logistic regression showed that age, education level, marital status, comorbidities, duration on dialysis, and social support were influencing factors in the potential categories of fear of disease progression and self-management ability in MHD patients, and the difference was statistically significant ( P<0.05) . Conclusions:Healthcare professionals should give appropriate interventions to MHD patients with different types of fear of progression and self-management ability in order to reduce patients' fear of disease progression and improve their self-management ability.

Objective:To explore the trajectories of kinesiophobia in initial hemodialysis patients and their influencing factors.Methods:A convenience sampling method was used to recruit patients undergoing their first hemodialysis treatment at Hemodialysis Center, the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from June to December 2023. Baseline data were collected using a general information questionnaire, the Tampa Scale for Kinesiophobia (TSK), the Dialysis Patient Symptom Burden Index (DFSSBI), the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), the Multidimensional Fatigue Inventory (MFI-20), and the Pittsburgh Sleep Quality Index (PSQI). The TSK was used to measure kinesiophobia levels at 1, 3, and 6 months post-dialysis. Data were analyzed using a latent class growth mixture model, univariate analysis, and multinomial Logistic regression.Results:A total of 251 patients were surveyed, and 239 completed follow-ups. Three latent classes of kinesiophobia trajectories were identified: persistently high kinesiophobia group (32.22%, 77/239), moderate kinesiophobia-declining group (28.45%, 68/239), and persistently low kinesiophobia group (39.33%, 94/239). Multinomial Logistic regression analysis indicated that age, marital status, presence of sleep disorders, history of falls in the past year, symptom burden, fear of disease progression, and fatigue significantly influenced kinesiophobia trajectory classes ( P<0.05) . Conclusions:Kinesiophobia in initial hemodialysis patients exhibits distinct trajectories. Healthcare professionals should implement targeted interventions based on the influencing factors of kinesiophobia trajectory development.

Objective To retrospectively study the characteristics and short-term outcomes of patients with decompensated liver cirrhosis accompanied by diastolic cardiac dysfunction,and to inform the clinical diagnosis and treatment of decompensated liver cirrhosis.Methods We retrospectively analyzed the clinical data of patients with liver cirrhosis and diastolic heart dysfunction admitted to Nanfang Hospital of Southern Medical University from April 1,2019 to July 31,2023.The patients were divided into compensated cirrhosis group(n=37)and decompensated cirrhosis group(n=226),and those with decompensated cirrhosis were further divided into subgroups of patients with heart dysfunction(n=84)and patients without heart dysfunction(n=142).We compared two groups using the independent samples t-test and Mann-Whitney U test for continuous data in normal distribution and data in skewed distribution,respectively;compared multiple groups using the Kruskal-Wallis H test,with subsequent paired comparisons using the Wilcoxon test;compared categorical data between two groups using the chi-square test or corrected chi-square test;identified the factors affecting patient survival using a Logistic regression model;and plotted Kaplan-Meier survival curves,with inter-group comparisons using the log-rank test.Results A total of 263 eligible patients were ultimately included,among whom 226 patients were diagnosed with decompensated liver cirrhosis(84 patients with diastolic dysfunction).Between the diastolic dysfunction group and non-diastolic dysfunction group,significant differences were detected in age(t=-4.566,P<0.05),activated partial thromboplastin time(Z=-3.026,P<0.05),prothrombin time(Z=-2.450,P<0.05),international normalized ratio(Z=2.779,P<0.05),and the proportion of moderate esophageal varices(χ2=4.273,P<0.05).During hospitalization,35 patients experienced new or aggravated ascites(18 with cardiac dysfunction and 17 without cardiac dysfunction),6 patients experienced new gastroesophageal variceal bleeding,and 9 patients experienced new or aggravated hepatic encephalopathy(3 with cardiac dysfunction and 6 without cardiac dysfunction).Jaundice was the most common decompensation event upon admission,and electrophysiological abnormalities were the most common electrocardiogram findings upon admission.During the 90-day follow-up period,30 individuals(12 with cardiac dysfunction and 18 without cardia dysfunction)died.The logistic regression analysis showed that age(odds ratio[OR]=1.075,95%confidence interval[CI]:1.033-1.119,P<0.001),N-terminal pro-B-type natriuretic peptide(NT-proBNP,OR=0.996,95%CI:0.992-0.999,P=0.016),and mild/moderate ascites(OR=0.270,95%CI:0.092-0.789,P=0.017)were independent predictive factors for cirrhotic cardiomyopathy.Conclusion Timely attention should be paid to elderly patients with decompensated liver cirrhosis and diastolic heart dysfunction who have a decline in NT-proBNP and mild to moderate ascites.Symptomatic treatment such as diuretics may improve diastolic heart dysfunction.

The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl₂+I/R group), lung I/R + high-dose ZnCl₂ group (HZnCl₂+I/R group), lung I/R + medium-dose ZnCl₂ group (MZnCl₂+I/R group) and TPEN+MZnCl₂+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn²⁺ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl₂+I/R group and HZnCl₂+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn²⁺ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn²⁺ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl₂ on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl₂ can improve lung I/R injury in rats.
Animals ; Reperfusion Injury/pathology* ; Male ; Rats, Sprague-Dawley ; Rats ; Chlorides/administration & dosage* ; Lung/pathology* ; Zinc Compounds/administration & dosage* ; Apoptosis/drug effects* ; Caspase 3/metabolism* ; Cation Transport Proteins/metabolism*