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 establish a PTEN gene-downregulated ASD juvenile rat model(VPA-ADV)through combined application of valproic acid(VPA)and PTEN adenovirus(ADV),then to compare the newly constructed animal model with two traditional autistic animal models of VPA and AD,and ultimately to prove the advantages of this model in animal model establishment of acupuncture treatment for ASD.Methods Wista rats at 12.5 days of gestation were randomly divided into 2 groups.VPA rats were given 600 mg/kg of normal saline(NS)intraperito-neally.Weight,eye opening time and tail deformity were recorded.The newborn mice in NS group were randomly divided into three groups(10 rats in each group):normal(NS)group,virus(ADV)group and virus-negative control(ADV-NC)group;VPA group(20 young rats)was randomly divided into 2 groups(10 rats in each group):valproic acid(VPA)group and valproic acid-binding virus interference(VPA+ADV)group.The body weight,tail length,curved tail,geotaxis text time and skeletal deformity of 5 groups of young rats after birth,the neurobehavioral behavior of 21-day-old rats,and the myelin structure of brain tissue under electron microscope were observed,the expression levels of PTEN,PI3K,AKT,GSK3β and MBP were detected by immunohistochemistry,Western blot and q-PCR.Results Compared with the NS group,the VPA group had significantly increased mal-formation rate,slow weight gain,slow tail length growth,and long negative geotaxis reflex time(P＜0.05).Com-pared with the NS group,the weight gain,tail length growth and negative geotaxis reflex time of the three model groups were slower(P＜0.05),and the performance of VPA+ADV model was the most significant.There were significant differences in the time of crossing the central grid,the number of crossing the edge grid,and the time of crossing the edge grid in the open field test between the three groups and the NS group(P＜0.05).In the self-grooming experiment,the number of interactions in VPA-ADV model was the least(P＜0.05),and the number of digging and self-grooming was the most(P＜0.05).In the three-box social experiment,VPA-ADV model had the shortest average number of entries into the social box and the shortest residence time(P＜0.05),the time of find-ing the platform in the water maze experiment was the longest,and the number of times crossing the third quadrant was the least(P＜0.05).The structure of the myelin sheath layer in the corpus callosum was observed by transmis-sion electron microscopy.The structure of the NS group was clear and complete.Compared with the NS group,the myelin structure of the ADV-NC group was similar,and the myelin structure of the three model groups was stratified and broken,and there were pathological changes and myelin damage in the ASD.Among them,the myelin sheath of the VPA-ADV model was thickened,stratified,and severe visible disintegration.The results of immunohisto-chemistry,Western blot and q-PCR showed that the expression of PTEN in VPA+ADV model was down-regulated by about 50％,which was the most obvious.The expression of AKT and MBP increased,and the expression of GSK3β decreased(P＜0.05).However,the results of q-PCR showed that the expression of PI3K-mRNA in the three model groups significantly increased(P＜0.05),and the change of VPA+ADV model was the most signifi-cant.Conclusion The novel PTEN-ASD animal model established by VPA+ADV method is observed to have sig-nificant pathological changes that are typical of the manifestation of ASD myelin dysplasia and is determined to have better results than the two traditional autistic animal models.

By sorting out and analyzing the contents about pulse diagnosis in Tanksuqnameh, it was found that in terms of pulse theory, the book contains academic viewpoints of different periods and doctors about three portions and nine readings pulse method and nutritive qi operation law in Huang Di Nei Jing, the Cunkou pulse-taking method and the Cunguanchi theory in Nan Jing, the Renying and Qikou pulse-taking method and the three-region pulse-taking method in Mai Jing, and the seven superficies-indicating, eight interior-indicating and nine channels pulse of Mai Jue, etc.; in terms of pulse theory interpretation, multiple annotations from famous doctors are cited, and TCM basic theories and knowledge of astronomy and mathematics are applied, combined with the background of ancient Iranian medicine and local medical experience for explanation; in terms of pulse diagnosis techniques, pulse diagnosis techniques such as "three fingers determining three guan", "adjusting finger density", "floating and sinking pulse", "foot back pulse breaking life and death" were recorded in books of Nan Jing, Mai Jue, Lei Zheng Huo Ren Shu, etc.; in terms of influencing pulse factors, the male and female pulse, physical pulse, and four time pulse were recorded. Tanksuqnameh is a universal work of Persian Traditional Chinese Medicine, compiled by the author Rashid-ul-Din based on his research on Chinese culture and medical knowledge, combined with the unique customs, language and culture, and way of thinking in the Middle East region, to reorganize various pulse theories from before the Han Dynasty to the Tang and Song Dynasties in China. The publication of this book indicates that TCM pulse diagnosis had been promoted to the Middle East in the 14th century and provided valuable experience for local medical development. The author's sense of identification and research spirit towards different cultures provide a historical example for achieving cross-cultural communication between TCM and medicine in different regions. The preserved literature from the Tang and Song Dynasties in the book can provide clues for a deeper understanding of ancient pulse theory in TCM, but some details do not explain thoroughly or does not match the current clinical practice. Therefore, attention should be paid to distinguishing in research and application.

A high-altitude environment is characterized by low oxygen levels,low pressure,and low temperatures.Exposure to the plateau environment often causes damage to the body,leading to the occurrence of acute mountain sickness/chronic mountain sickness(AMS/CMS).Research indicates that acute or chronic exposure to the special environment can result in overall organ dysfunctions,such as those in the heart and gastrointestinal tract.The damage to the body caused by exposure to the plateau environment is closely related to acute and chronic hypoxia.Physiological maladjustment or disease is usually accompanied by changes in the structure of the gut microbiota.There have been reports on the correlations between the gut microbiota and bodily harm caused by high-altitude exposure.However,the specific types of bacteria involved and the mechanisms of action are still under investigation.This article reviews the intestinal tissue damage caused by low oxygen levels,immune activation,changes in microbial community structure,and differential metabolic products.The association and underlying mechanisms between bodily harm due to high-altitude exposure and the intestinal microbiota are also explored in hopes of stimulating new lines of thought related to the prevention and treatment of bodily harm caused by exposure to the plateau environment.

Objective:To investigate the efficacy of metagenomic next generation sequencing (mNGS) in the etiological diagnosis of patients with spinal infection, so as to provide reference for timely diagnosis and treatment.Methods:A total of 40 patients with suspected spinal infection admitted to the Department of Infectious Diseases in Henan Provincial People′s Hospital from January 2020 to July 2022 were included. The results of tissue culture, histopathological examination and tissue mNGS detection were analyzed retrospectively. According to the clinical diagnose, the patients were divided into the spinal infection group (28 cases) and the non-spinal infection group (12 cases). The positive rate, sensitivity and specificity of mNGS and tissue culture in the pathogen detection of patients with spinal infection were compared. McNemar test was used for statistical analysis.Results:There were 23 males and 17 females in 40 patients. The positive rate of mNGS was higher than that of tissue culture (75.0%(30/40) vs 12.5%(5/40)), and the difference was statistically significant ( χ2=0.08, P<0.001). Based on clinical diagnostic criteria, the sensitivity of mNGS in the diagnosis of spinal infection was higher than that of tissue culture (82.1% vs 17.9%), with a statistically significant difference ( χ2=0.02, P<0.001), while the specificity compared to the tissue culture (33.3% vs 100.0%), the difference was not statistically significant ( P>0.05). Conclusions:mNGS has a high pathogen detection rate and sensitivity in the etiological diagnosis of patients with spinal infection, which could provide clinical guidance for the diagnosis and treatment of patients with spinal infection.

Objective: To analyze the factors affecting the complication of pulmonary atelectasis among children with tracheobronchial tuberculosis (TBTB), so as to provide the reference for the prevention and treatment of pulmonary atelectasis complicated by TBTB. Methods: Children with TBTB admitted to Department of Paediatrics, Linping Division of the Second Affiliated Hospital of Zhejiang University School of Medicine were selected as the study subjects from October 2018 to March 2023. Subjects's basic information, etiological examination results and laboratory testing results were collected using a self-designed questionnaire, and factors affecting the complication of pulmonary atelectasis among children with TBTB were identified using a multivariable logistic regression model. Results: A total of 120 children with TBTB were included, with the age of 6 months to 12 years. There were 33 children at ages of less than one year (27.50%), 71 girls (59.17%) and 25 children with TBTB and pulmonary atelectasis (20.83%). Multivariable logistic regression analysis identified less than one year of age (OR=1.720, 95%CI: 1.126-3.358), type Ⅵ of TBTB (OR=1.669, 95%CI: 1.101-2.236), high level of C-reactive protein (OR=1.887, 95%CI: 1.088-2.686) and high level of procalcitonin (OR=1.844, 95%CI: 1.034-2.654) as risk factors for the complication of pulmonary atelectasis in children with TBTB. Conclusion Less than one year of age, type Ⅵ of TBTB, high level of C-reactive protein and high level of procalcitonin may increase the risk of pulmonary atelectasis in children with TBTB.

Objective:To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component.Methods:1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis.Results:146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) ( P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS ( P=0.006) , while LDH higher than normal was an independent risk factor for OS ( P=0.031) . Conclusion:FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.

Objective:To observe the expression levels of small ubiquitinated protein specific protease (SENP) 1 and small ubiquitin-related modifier protein (SUMO) 1 in patients with diffuse large B-cell lymphoma (DLBCL), and analyze the clinical value of evaluating prognosis.Methods:The clinical data of 66 patients with DLBCL (DLBCL group) in Inner Mongolia People′s Hospital from February 2017 to October 2020 were retrospectively analyzed, and 60 cases of healthy people in the same period were selected as the healthy control group. The expression levels of SENP1 and SUMO1 were detected by enzyme linked immunosorbent assay (ELISA). The correlation between the expression levels of SENP1, SUMO1 and clinical characteristics was analyzed. The independent risk factors affecting the prognosis were analyzed by Cox multivariate analysis.Results:The SENP1 in DLBCL group was significantly higher than that in healthy control group (50.39 ± 6.86 vs. 7.47 ± 1.32), the SUMO1 in DLBCL group was significantly lower than that in healthy control group (8.84 ± 2.13 vs. 31.49 ± 5.89), and there were statistical differences ( t = 47.640 and 29.210, P<0.01). There were statistical differences in SENP1 and SUMO1 among patients with different clinical stages ( P<0.01). The expression levels of SENP1 and SUMO1 were correlated with clinical stage and international prognostic index (IPI) ( P<0.05), and were not correlated with age, gender, disease site and clinical symptoms ( P>0.05). The 3-year survival rate in patients with high SENP1 expression (30 cases) was significantly lower than that in patients with low SENP1 expression (36 cases), the 3-year survival rate in patients with high SUMO1 expression (38 cases) was significantly higher than that in patients with low SUMO1 expression (28 cases), and there were statistical differences (26.67% vs. 75.00% and 73.68% vs. 39.29%, P<0.05). Cox multivariate regression analysis result showed that clinical stage, IPI, SENP1 and SUMO1 were independent risk factors affecting the prognosis in patients with DLBCL ( HR = 1.352, 1.487, 2.048 and 3.295; 95% CI 1.180 to 1.691, 1.187 to 1.602, 2.536 to 4.023 and 2.752 to 5.325; P<0.05 or <0.01). Conclusions:In patients with DLBCL, SENP1 is highly expressed and SUMO1 is lowly expressed. The expression levels of SENP1 and SUMO1 are closely related to clinical stage and IPI in patients with DLBCL, and they are independent risk factors of the prognosis.

Objective:To investigate the clinical characteristics of patients with aspergillus spondylitis, and to provide reference for timely diagnosis and treatment.Methods:The clinical manifestations, imaging performance, laboratory examination results, diagnosis and treatment outcomes of six patients with confirmed aspergillus spondylitis in Department of Infectious Diseases, Henan Provincial People′s Hospital during April 30, 2015 and May 1, 2020 were retrospectively analyzed.Results:The main manifestations of six patients were fever and neck pain or low back pain. The time from the onset of clinical manifestations to diagnosis was more than two months to 14 months. Spine magnetic resonance imaging (MRI) showed long T1 and T2 signals on vertebral body, high pressure lipid signal, obvious enhanced scan enhancement, and paravertebral abscess formation might be presented. Among the six patients, C-reactive protein increased in four patients, erythrocyte sedimentation rate increased in five patients, β-D-glucan test (G test) increased in three patients, galactomannan antigen test (GM test) increased in four patients. Six patients with aspergillus spondylitis were all confirmed by biopsy of diseased tissue for fungal smear, tissue culture or metagenomics next generation sequencing. After treatment with voriconazole or itraconazole, five patients recovered and one patient was still under treatment.Conclusions:The clinical manifestations and imaging examination of patients with aspergillus spondylitis are nonspecific. Peripheral blood G test and GM test need to be combined for diagnosis. The diagnosis depends on tissue puncture pathology examination, and the metagenomics next generation sequencing is needed if necessary.

The feasibility and safety of intracardiac echocardiography (ICE)-guided catheter ablation for atrial fibrillation (AF) using a minimal/zero-fluoroscopy approach have recently been reported. This approach helps to reduce ionizing radiation exposure and orthopedic complications resulting from using lead aprons. The objectives of this planned prospective, multicenter randomized controlled trial (RCT) (paroxysmal AF (PAF)-ICE trial; ChiCTR2000033624) are to evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF and the impact on occupational hazards among lab staff.Patients will be randomized in a 1:1 ratio to 2 groups: minimal fluoroscopy group ( n = 216) and traditional approach group ( n = 216). In the minimal fluoroscopy group, an ICE catheter will be used for geometry/anatomic construction, transseptal puncture, catheter tracking, and effusion monitoring. Pulmonary vein isolation (PVI) will be performed using an open-irrigated radiofrequency SmartTouch Surround Flow or SmartTouch catheter (Biosense Webster, Diamond Bar, California, USA), and confirmed by a multipolar Lasso or PentaRay catheter (Biosense Webster). In the traditional approach group, an ICE catheter will not be used. Transseptal puncture will be performed under fluoroscopic guidance, with all geometries constructed by mapping the catheters. The primary efficacy endpoint is freedom from AF recurrence (without antiarrhythmic medications) at 12 months after ablation. Other endpoints include duration of lead apron use, measures of intra-procedural efficiency, and peri-procedural complications. This RCT will evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF, also evaluate the benefits to lab staff (regarding reducing occupational hazards) related to this "minimal/zero-fluoroscopy" and "leadless" mode.