OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

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

Objective:To explore the relationship between the health literacy of employees and smoking, drinking, diet and exercise, and provide scientific basis for health education and targeted intervention.Methods:From February to July 2019, a cluster random sampling method was adopted to select enterprise employees in Shihezi City to conduct a questionnaire survey. Self-made questionnaires and "National Resident Health Literacy Monitoring Questionnaire" were used to assess the social demographics, health literacy, and Health-related behaviors were investigated, and 1053 valid questionnaires were collected. Logistic regression model was used to analyze the relationship between health literacy and the three dimensions with smoking, drinking, diet and exercise.Results:Total score of health literacy of enterprise employees is (42.06±11.03) points and the employee health literacy rate of Shihezi City in 2019 is 19.47%. Univariate analysis showed that non-smokers had higher health literacy and three-dimensional health literacy availability than smokers ( P<0.01) ; fewer drinkers had higher health literacy availability than overdrinkers ( P<0.05) ; balanced diet health literacy availability The health literacy availability rates in the three dimensions were higher than those in the unbalanced diet ( P<0.01) . In the logistic regression analysis, healthy lifestyle and behavioral literacy were independently related to smoking behavior ( OR=1.571, P<0.05) ; the presence of health literacy and the three dimensions of health literacy were not statistically related to alcohol consumption ( P>0.05) ; there is a statistical correlation between health literacy, healthy lifestyles, behaviors, and health skills and regular exercise among employees ( OR=1.829、2.503、1.395, P<0.05) ; employees with health literacy and three dimensions of health literacy are more likely to have a balanced diet ( P<0.01) . Conclusion:There is a correlation between the health literacy of enterprise employees and diet and exercise. The improvement of health literacy level is an important way to interfere with unhealthy behaviors.

Objective:To explore the relationship between the health literacy of employees and smoking, drinking, diet and exercise, and provide scientific basis for health education and targeted intervention.Methods:From February to July 2019, a cluster random sampling method was adopted to select enterprise employees in Shihezi City to conduct a questionnaire survey. Self-made questionnaires and "National Resident Health Literacy Monitoring Questionnaire" were used to assess the social demographics, health literacy, and Health-related behaviors were investigated, and 1053 valid questionnaires were collected. Logistic regression model was used to analyze the relationship between health literacy and the three dimensions with smoking, drinking, diet and exercise.Results:Total score of health literacy of enterprise employees is (42.06±11.03) points and the employee health literacy rate of Shihezi City in 2019 is 19.47%. Univariate analysis showed that non-smokers had higher health literacy and three-dimensional health literacy availability than smokers ( P<0.01) ; fewer drinkers had higher health literacy availability than overdrinkers ( P<0.05) ; balanced diet health literacy availability The health literacy availability rates in the three dimensions were higher than those in the unbalanced diet ( P<0.01) . In the logistic regression analysis, healthy lifestyle and behavioral literacy were independently related to smoking behavior ( OR=1.571, P<0.05) ; the presence of health literacy and the three dimensions of health literacy were not statistically related to alcohol consumption ( P>0.05) ; there is a statistical correlation between health literacy, healthy lifestyles, behaviors, and health skills and regular exercise among employees ( OR=1.829、2.503、1.395, P<0.05) ; employees with health literacy and three dimensions of health literacy are more likely to have a balanced diet ( P<0.01) . Conclusion:There is a correlation between the health literacy of enterprise employees and diet and exercise. The improvement of health literacy level is an important way to interfere with unhealthy behaviors.

BACKGROUND:Cytokines and neurotrophic factors secreted from human umbilical cord blood-derived mesenchymal stem cells secrete have neuroprotective effects on cerebral ischemia-reperfusion injury, but there are few reports about intranasal administration of human umbilical cord blood-derived mesenchymal stem cellconditioned medium in the treatment of stroke.
OBJECTIVE:To investigate the protective effects of intranasal administration of human umbilical cord-derived mesenchymal stem cells-conditioned medium on neurologic function of rats with cerebral ischemia-reperfusion injury.
METHODS:Adult rats were subjected to 2 hours of right middle cerebral artery occlusion and the human umbilical cord-derived mesenchymal stem cells were isolated from the postpartum human cord. We made the conditioned medium of human umbilical cord-derived mesenchymal stem cells. Ischemic rats were randomized and assigned to three groups and were treated by intranasal routine starting 24 hours after middle cerebral artery occlusion with:(1) saline for control group;(2) Dulbecco’s modified Eagle’s medium/Ham’s nutrient mixture F-12 medium for medium control group;(3) conditioned medium treatment group (10mL/kg) daily for 14 days. Behavioral tests (foot fault test, and modified Neurological Severity Score) were performed before and at 1, 7, 14 days after middle cerebral artery occlusion.
RESULTS AND CONCLUSION:There was no difference in the behavioral tests among the three groups at postoperatively 1 day (P>0.05). Compared to the control and medium control group rats, respectively, rats in the conditioned medium group significantly improved functional outcome after stroke in days 7 and 14 (P<0.05). There was also no significant difference in functional tests between the control group and medium control group in days 7 and 14 (P>0.05). These results suggest that human umbilical cord-derived mesenchymal stem cells-conditioned medium via intranasal administration can significantly improve neurologic functional outcome after cerebral ischemia-reperfusion injury.