OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Hypertrophic cardiomyopathy (HCM) due to a truncating variant of ALPK3 gene. METHODS: A 44-year-old male admitted to Taizhou Hospital of Zhejiang Province on December 29, 2018 was selected as the study subject. Whole-exome sequencing (WES) was carried out, and candidate variant was interpreted by following the guidelines from the American College of Medical Genetics and Genomics (ACMG). For ALPK3 was considered an autosomal recessive gene, the WES results was considered insufficient to explain his phenotype. In April 2023, the proband's WES data were re-analyzed using updated annotation pipelines, and peripheral blood samples were collected from his first-degree relatives (mother and brother) for Sanger sequencing validation. Conservation analysis and protein structural modeling were performed to assess the impact of the variant. Clinical evaluation and genetic counseling were provided to the proband's family members. Relevant literature on ALPK3tv-induced HCM patients were searched in Wanfang Data Knowledge Service Platform, CNKI, and PubMed database using "ALPK3" and "hypertrophic cardiomyopathy" as keywords. Clinical characteristics of HCM patients with heterozygous ALPK3tv variants were summarized and compared with the clinical characteristics of HCM patients with positive sarcomere-associated gene variants (SARC+). This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Ethics No.: K20230314). RESULTS: The proband was a 44-year-old male who was transferred to our institution on December 29, 2018 due to "chest tightness and pain for 6 months, exacerbated for 2 days". Emergency coronary angiography was performed, which led to a preliminary diagnosis of "acute coronary syndrome", and the patient was admitted to the Cardiology Department for treatment. Based on electrocardiogram and echocardiogram findings, the diagnosis was revised as HCM. The patient's condition has stabilized post-coronary angiography, and he was discharged with improved condition. On January 2019, WES was conducted to determine the etiology of the proband's HCM. WES results identified a novel heterozygous c.2156dupC (p.Pro720ThrfsTer53) truncating variant in the ALPK3 gene. At that time, the inheritance pattern could not explain the phenotype. In 2022, a literature indicated that heterozygous ALPK3tv could lead to autosomal dominant HCM. Consequently, in April 2023, the proband's whole-exome data were re-annotated, revealing changes in the transcript and protein versions, with the updated site annotated as ALPK3 (NM_020778.5): c.1550dupC (p.Pro518ThrfsTer53). Sanger sequencing confirmed that the proband's mother and brother also carried this variant. The mother exhibited obstructive HCM, while the brother showed no related phenotype. Bioinformatics analysis demonstrated conservation of this site across multiple species, and the variant has resulted in the loss of a protein domain. Based on ACMG guidelines, the variant was classified as likely pathogenic. Literature review and Bayesian calculation further elevated the pathogenicity rating, indicating that this variant was the cause of HCM in the patient. Literature study revealed distinctions between HCM caused by this variant type and SARC+ HCM. The age of onset among heterozygous ALPK3tv patients was delayed by approximately 10 years compared to SARC+ patients. Both forms of HCM exhibited a male predominance, which was particularly marked in individuals with ALPK3tv. Electrocardiographic left ventricular hypertrophy was more prevalent in heterozygous ALPK3tv patients than in SARC+ patients. The incidence of apical or concentric hypertrophy patterns was higher in heterozygous ALPK3tv patients compared to asymmetric septal hypertrophy, which predominated in SARC+ patients. ALPK3tv patients exhibited lower penetrance and later onset compared to SARC+ patients. A positive correlation between left ventricular wall thickness and age was noted in female patients only. CONCLUSION In this pedigree, the proband has presented with HCM, characterized by echocardiographic evidence of apical left ventricular hypertrophy without significant outflow tract obstruction or extracardiac phenotypes. Although his mother and brother had carried the same heterozygous ALPK3 (NM_020778.5) c.1550dupC (p.Pro518ThrfsTer53), the mother exhibited severe obstructive HCM, while the brother was asymptomatic, suggesting incomplete or age-dependent penetrance within the family. This study has enriched the evidence for the pathogenicity of ALPK3tv among Chinese HCM pedigrees and underscored the importance of periodic literature reviews and genetic re-analysis for unresolved genetic testing results.
Humans ; Male ; Pedigree ; Adult ; Cardiomyopathy, Hypertrophic/genetics* ; Heterozygote ; Asian People/genetics* ; Exome Sequencing ; Mutation ; China ; Female ; East Asian People

As cardiac magnetic resonance imaging technology advances,T1 mapping has emerged as a non-invasive method offering visual and quantitative insights into myocardial fibrosis,edema,and infiltration associated with cardiac dis-eases.The application of T1 mapping in myocardial diseases allows for evaluating both focal and diffuse myocardial fibro-sis,playing a crucial clinical role in the differentiation,treatment,and prognostic risk assessment of diseases.This arti-cle aims to provide a thorough overview of the clinical applications of T1 mapping in patients with cardiomyopathy,summa-rizing the commonly employed scanning techniques and imaging principles.

As cardiac magnetic resonance imaging technology advances,T1 mapping has emerged as a non-invasive method offering visual and quantitative insights into myocardial fibrosis,edema,and infiltration associated with cardiac dis-eases.The application of T1 mapping in myocardial diseases allows for evaluating both focal and diffuse myocardial fibro-sis,playing a crucial clinical role in the differentiation,treatment,and prognostic risk assessment of diseases.This arti-cle aims to provide a thorough overview of the clinical applications of T1 mapping in patients with cardiomyopathy,summa-rizing the commonly employed scanning techniques and imaging principles.

Cardiac magnetic resonance(CMR)has the advantages of being radiation-free,multi-parameter,multi-sequence,and multi-planar,enabling one-stop assessment of cardiac motion and morphologic function,blood flow and per-fusion in patients with coronary artery disease.This article briefly introduces the typical imaging indicators of CMR and highlights the application in the diagnosis,treatment and prognostic assessment of coronary artery disease.

Cardiac magnetic resonance(CMR)has the advantages of being radiation-free,multi-parameter,multi-sequence,and multi-planar,enabling one-stop assessment of cardiac motion and morphologic function,blood flow and per-fusion in patients with coronary artery disease.This article briefly introduces the typical imaging indicators of CMR and highlights the application in the diagnosis,treatment and prognostic assessment of coronary artery disease.

OBJECTIVES: Dysthyroid optic neuropathy (DON) is a class of diseases that makes seriously endanger to the vision of patients with thyroid-associated ophthalmopathy. This study aims to observe the visual function changes in patients with DON, and to evaluate the diagnostic value of indicators diagnosing DON. METHODS: A retrospective study was conducted on 98 eyes of 49 patients with dysthyroid optic neuropathy (DON) who were treated in Xiangya Hospital of Central South University from January 2017 to December 2019. All patients were received the examination of best corrected visual acuity (BCVA), Humphrey visual field, visual evoked potential (VEP), and contrast sensitivity. Ninety-eight eyes were divided into a DON group (45 eyes) and a non-DON group (53 eyes). T-test was used to compare the related indicators between the 2 groups. The sensitivity and specificity of each indicator were analyzed by receiver operating characteristic (ROC) curve. RESULTS: The BCVA and visual field index (VFI) of the DON group were significantly lower than those of the non-DON group (all P<0.05). The mean deviation (MD) and pattern standard deviation (PSD) of the DON group were significantly higher than those of the non-DON group (all P<0.05). The low frequency contrast sensitivity (CSL), medium frequency contrast sensitivity (CSM), and high frequency contrast sensitivity (CSH) of the DON group were significantly lower than those of the non-DON group (all P<0.05), with CSH being particularly prominent. Compared with the non-DON group, at spatial frequencies of 15°, 30°, and 60°, the amplitude of N135 wave was significantly reduced, and the latency of N75 wave, P100 wave, and N135 wave was significantly prolonged in the DON group (all P<0.05); at spatial frequencies of 15° and 30°, the amplitude of P100 wave was significantly reduced in the DON group (P<0.05). The ROC curve analysis results showed that the area under the curve (AUC) of VFI, CSL, CSM, CSH and 15° P100 amplitude diagnosing DON were 0.812, 0.841, 0.880, 0.784, and 0.791, respectively, with CSM possessing the highest sensitivity and specificity. CONCLUSIONS The visual function of patients with DON is decreased. VFI, contrast sensitivity of low, medium, and high frequency, and 15° P100 wave amplitude might be effective indicators for early diagnosis of DON.
Humans ; ROC Curve ; Optic Nerve Diseases/complications* ; Retrospective Studies ; Evoked Potentials, Visual ; Graves Ophthalmopathy

Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems in the world. Pharmaceutical industry is an important part of China's national economy. At present, there are few related studies reported at home and abroad. Objective To investigate the status and influencing factors of WMSDs in chemical pharmaceutical industry. Methods A cross-sectional epidemiological survey was conducted among all workers from three chemical pharmaceutical enterprises in Guangzhou. The Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, symptoms of musculoskeletal disorders, types of work, work organization, and and work postures. Multiple logistic regression method was used to analyze the risk factors of WMSDs in chemical pharmaceutical workers. Results In this study, 563 workers were selected as subjects. The total prevalence rate of WMSDs symptoms in the chemical pharmaceutical workers was 43.9% (247/563), and the leading body part-specific prevalence rate from high to low was 34.3% in the lower back, 24.3% in the upper back, 24.0% in the shoulders, and 23.8% in the neck. The prevalence rate of WMSDs symptoms in multiple body parts (30.0%) was 2.16 times higher than that in single body part (13.9%), and the prevalence rate of WMSDs symptoms in four body parts was the highest (11.4%). The results of multiple logistic regression analysis showed that age ≥50 years (reference age <30 years) (OR=2.140, 95%CI: 1.054-4.345), often or very often (reference never/rarely) long-time head rotating (OR=2.695, 95%CI: 1.753-4.142) and long-time keeping arms above shoulders (OR=1.902, 95%CI: 1.108-3.265) increased the risk of reporting WMSDs symptoms (P<0.05). Regarding education level, workers with high school and technical secondary school (OR=0.333, 95%CI: 0.175-0.636) or college and above (OR=0.413, 95%CI: 0.216-0.790) education had a lower risk of reporting WMSDs symptoms than those with middle school or below (P<0.05). Conclusion The prevalence rate of reporting WMSDs symptoms in chemical pharmaceutical industry is high, the involving body parts are lower back, upper back, shoulders, and neck, and reporting simultaneous occurrence of WMSDs symptoms in multiple body parts is common. The chemical pharmaceutical manufacturers can reduce the risk of WMSDs by strengthening the training on workers' ergonomics knowledge, paying attention to the less educated personnel, protecting the elderly workers, and avoiding awkward work postures, like rotating head for a long time and raising arms over shoulders.

Objective:To retrospectively analyze the clinical characteristics of elderly patients with anti-MDA5 antibody-positive dermatomyositis.Methods:Data of 62 patients with anti-MDA5 antibody-positive dermatomyositis admitted to Second Xiangya Hospital from May 2016 to December 2019 were collected and patients were divided into an elderly group(≥60 years old, 17 cases)and a non-elderly group(<60 years old, 45 cases). The clinical manifestations, laboratory test resuls, treatment and prognosis of the patients in both groups were statistically analyzed.Results:A total of 62 patients with anti-MDA5 antibody-positive dermatomyositis were included in this study, including 17 elderly patients(27.4%)with an average age of(65.5±5.3)years and 45 non-elderly patients(72.6%)with an average age of(46.5±8.4)years.Compared with non-elderly patients, older patients had a shorter disease duration[(1.6±1.0)months vs.(3.7±3.3)months, t=3.883, P<0.001], a higher proportion of patients with exertional dyspnea(15/17 or 88.2% vs.26/45 or 57.8%, χ2=5.11, P=0.024)and with combined positive anti-Ro-52 antibodies(15/17 or 88.2% vs.26/45 or 57.8%, χ2=5.11, P=0.024), and a higher mortality rate[(12/17 or 70.6%) vs.(8/45 or 17.8%, χ2=15.748, P<0.001)]. In contrast, fewer elderly patients than non-elderly patients had the Heliotrope's sign(9/17 or 41.2% vs.38/45 or 57.8%), χ2=5.07, P=0.024). Conclusions:Elderly patients with anti-MDA5 antibody-positive dermatomyositis have a unique clinical phenotype with an acute onset, atypical rashes, severe pulmonary lesions, making treatment difficult, and have a poor prognosis.

After traumatic brain injury(TBI), as an immune signal complex in cytoplasm, the assembly and activation of inflammasomes can induce pyroptosis, trigger extensive inflammations, aggravate brain tissue damage, lead to delayed cell death and progressive neurodegeneration, and cause neurological dysfunction, which plays a key role in the development and prognosis of the disease. After TBI, the mechanism of pyroptosis mediated by inflammasomes and its targeted treatments have become the focus of recent researches. The authors review the research progress in inflammasomes-mediated pyroptosis in terms of related signal pathways, their activation and regulation and application of targeted drugs after TBI, so as to provide references for clinical treatments.

Objective:To evaluate the short-term efficacy and safety of HA280 immunoadsorption (IA) column in idiopathic inflammatory myopathies (IIM).Methods:The clinical data of 72 patients with IIM admitted to the Department of Rheumatology of Xiangya No.2 Hospital of Central South University from January 2015 to March 2018 were analyzed. Of these patients, 22 patients were treated with HA280 immunoadsorption column for three times (the immunoadsorption group) and 50 patients were treated with drugs only (the control group). The changes of clinical symptoms and signs, autoimmune antibodies, myocardial enzyme spectrum, the inflammatory markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and ferritin], immunoglobulin, complement, other biochemical indexes and pulmonary images of the patients were detected and analyzed before and after the treatment. And then the data were analyzed by Chi-square test, samples t testand Wilcoxon rank sum test. Results:Compared with the control group, the symptoms and signs were obviously improved after treatment with HA280 immunoadsorption column. In particular, the clinical improvement rate of non-specific myositis (89%, 16/18) was higher than that of the control group [(58%, 22/38), χ2=5.379, P<0.05]. And the clearance of autoantibody (control group) was grade 39.41 in average, 28.38 in average in the immunoadsorption group( Z=-2.51, P=0.01), myocardial enzyme spectrum [control 717(1 564) U/L, immunoadsorption group 126(432) U/L , Z=3.09, P<0.01], the inflammatory markers such as ESR [the control group was 24(22) mm/1 h, the immunoadsorption group was 10(7) mm/1 h, Z=-3.0, P=0.003] and immunoglobulin G [the control group was 11(5) g/L, the immunoadsorption group was 9(2) g/L, Z=-4.8, P=0.001] and immunoglobulin M [the control group was 0.9(0.4) g/L, the immunoadsorption group was 1.2(0.8) g/L, Z=-2.0, P=0.05]. Moreover, the lung CT scan showed that pulmonary lesions of the patients in the immunoadsorption group (89%, 17/19) was much more improved than the control group [(61%, 27/44), χ2=4.98, P<0.05]. No serious adverse reactions occurred. Conclusion:HA280 immunoadsorption therapy can significantly clear the autoantibodies, decrease muscle enzymes, inflammatory markers and immunoglobulin, improve lung images of some patients in a short time. It has been shown that it is safein patients with IIM. HA280 immunoadsorption therapy could be an effective treatment for IIM.