A case of dilated cardiomyopathy caused by FHL2 gene variant and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and genetic features of a child with dilated cardiomyopathy (DCM).@*METHODS@#Clinical data of the child who had presented at the Zhengzhou Children's Hospital on April 28, 2020 was collected. Trio-whole exome sequencing (trio-WES) was carried out for the child and her parents, and candidate variants were validated by Sanger sequencing. "FHL2" was taken as the key word to retrieve related literature from January 1, 1997 to October 31, 2021 in the PubMed database and was also searched in the ClinVar database as a supplement to analyze the correlation between genetic variants and clinical features.@*RESULTS@#The patient was a 5-month-old female infant presented with left ventricular enlargement and reduced systolic function. A heterozygous missense variant c.391C>T (p.Arg131Cys) in FHL2 gene was identified through trio-WES. The same variant was not detected in either of her parents. A total of 10 patients with FHL2 gene variants have been reported in the literature, 6 of them had presented with DCM, 2 with hypertrophic cardiomyopathy (HCM), and 2 with sudden unexplained death (SUD). Phenotypic analysis revealed that patients with variants in the LIM 3 domain presented hypertrophic cardiomyopathy and those with variants of the LIM 0~2 and LIM 4 domains had mainly presented DCM. The c.391C>T (p.Arg131Cys) has been identified in a child with DCM, though it has not been validated among the patient's family members. Based on the guidelines of the American College of Medical Genetics and Genomics, the c.391C>T(p.Arg131Cys) variant was re-classified as likely pathogenic (PS2+PM2_Supporting+PP3+PP5).@*CONCLUSION@#The heterozygous missense variant of c.391C>T (p.Arg131Cys) in the FHL2 gene probably predisposed to the DCM in this child, which has highlighted the importance of WES in the clinical diagnosis and genetic counseling.

Genetic analysis of a child with restricted cardiomyopathy and phenylketonuria and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and genetic characteristics of a child with restricted cardiomyopathy (RCM) and phenylketonuria (PKU), and summarize the clinical characteristics and genetic diversity of RCM in children through a literature review.@*METHODS@#A child with RCM in conjunct with PKU who was admitted to the Children's Hospital Affiliated to Zhengzhou University in June 2020 due to edema of eyelids and lower limbs for 1 year and aggravation for over 1 month was selected as the study subject. Relevant clinical data were collected. Peripheral blood samples of the child and his parents were collected for whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing and bioinformatic analysis. Childhood, TNNI3 gene and restricted cardiomyopathy were used as the keywords to search the Wanfang data knowledge service platform, Chinese Journal Full-text database and PubMed database, and the search period was limited to from the time of establishment till August 2022. Clinical manifestations and characteristics of the TNNI3 gene variants were summarized.@*RESULTS@#The child, a 2-year-old-and-4-month-old male, had normal intelligence, facial features and normal hair and skin color, but his motor and physical development was delayed, in addition with edema of bilateral eyelids and lower limbs. The results of WES and Sanger sequencing revealed that he has harbored compound heterozygous variants of the PAH gene, namely c.331C>T (p.R111X) and c.940C>A (p.P341T), which were inherited from his father and mother, respectively. In addition, he has also harbored a de novo heterozygous variant of c.508C>T (p.R170W) of the TNNI3 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the TNNI3: c.508C>T (p.R170W) was classified as a pathogenic variant (PS2+PS4+PM2_Supporting+PM5), PAH: c.331C>T (p.R111X) as a pathogenic variant (PVS1+PM2_Supporting+PM3+PP4), and c.940C>A (p.P341T) as a likely pathogenic variant (PM2_Supporting+PM3+PM5+PP4). In total 30 children with RCM caused by TNNI3 gene variants were retrieved, with a male-to-female ratio of 1 : 1.55 and manifestations including heart failure, sinus rhythm, bi-atrial enlargement, ST-T wave change, ventricular restricted filling, and decreased ventricular diastolic function. In total 16 variants of the TNNI3 gene were identified, among which c.575G>A was the most common, and all cases had conformed to an autosomal dominant inheritance.@*CONCLUSION@#Phenylalanine hydroxylase deficiency and RCM are rare diseases with complex clinical manifestations. The PAH: c.331C>T (p.R111X)/c.940C>A (p.P341T) and TNNI3: c.508C>T (p.R170W) variants probably underlay the RCM and PKU in this child.

Clinical and genetic analysis of five children with Catecholaminergic polymorphic ventricular tachycardia due to variants of RYR2 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of five children with Catecholaminergic polymorphic ventricular tachycardia (CPVT).@*METHODS@#Five children with clinical manifestations consistent with CPVT admitted to the Department of Cardiology of Children's Hospital Affiliated to Zhengzhou University from November 2019 to November 2021 were selected as the study subjects. Their clinical data were collected. Potential variants were detected by whole exome sequencing, and Sanger sequencing was used to verify the candidate variants. All patients were treated with β-blocker propranolol and followed up.@*RESULTS@#All patients had developed the disease during exercise and presented with syncope as the initial clinical manifestation. Electrocardiogram showed sinus bradycardia. The first onset age of the 5 patients were (10.4 ± 2.19) years, and the time of delayed diagnosis was (1.6 ± 2.19) years. All of the children were found to harbor de novo heterozygous missense variants of the RYR2 gene, including c.6916G>A (p.V2306I), c.527G>C (p.R176P), c.12271G>A (p.A4091T), c.506G>T (p.R169L) and c.6817G>A (p.G2273R). Among these, c.527G>C (p.R176P) and c.6817G>A (p.G2273R) were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.527G>C (p.R176P) was classified as a pathogenic variant (PS2+PM1+PM2_Supporting+PM5+PP3+PP4), and the c.6817G>A (p.G2273R) was classified as a likely pathogenic variant (PS2+PM2_Supporting+PP3+PP4). The symptoms of all children were significantly improved with the propranolol treatment, and none has developed syncope during the follow up.@*CONCLUSION@#Discovery of the c.527G>C (p.R176P) and c.6817G>A (p.G2273R) variants has expanded the mutational spectrum of the RYR2 gene. Genetic testing of CPVT patients can clarify the cause of the disease and provide a reference for their genetic counseling.

Delay on detection, and diagnosis of pulmonary tuberculosis and the influencing factors in Inner Mongolia students during 2011-2022 / 中国学校卫生

Objective@#To analyze the delay on detection, care seeking, diagnosis and treatment of tuberculosis among students in Inner Mongolia Autonomous Region (Inner Mongolia) from 2011 to 2022 and its influencing factors, so as to provide support for the prevention and treatment of tuberculosis among students.@*Methods@#The general demographic indicators of students with tuberculosis in Inner Mongolia from January 1, 2011 to December 31, 2022 were collected from the infectious disease monitoring (new) module of the China Disease Prevention and Control Information System. General characteristics and trend of four types of delayed pulmonary tuberculosis patients in students were analyzed. The influencing factors were analyzed using univariate and multivariate Logistic regressions.@*Results@#From 2011 to 2022, there were 6 032 cases of pulmonary tuberculosis among students in Inner Mongolia. The rates of delayed detection, delayed care seeking, delayed diagnosis, and delayed treatment were 51.71%, 64.01%, 7.82 %, and 2.30%, respectively. The results of multivariate Logistic regression analysis showed that tracking ( OR =1.51) in the patient source,league level diagnosis ( OR =3.16) in the diagnostic institution level,and county level diagnosis ( OR =2.41) were positively associated with delayed discovery ( P <0.05). At the level of diagnostic unit, league city level diagnosis ( OR =2.69), and county level diagnosis ( OR =3.67) associated with more delayed care seeking ( P <0.05). Referral ( OR =1.58) and follow up ( OR =2.55), floating population ( OR =2.05), further consultation with a doctor ( OR =2.11), and no results in imaging manifestations ( OR =2.19) were positively associated with delayed diagnosis( P <0.05). The factors contributing to delayed treatment were referral ( OR =1.84), follow up ( OR =4.91), active screening ( OR =5.46), and floating population( OR =1.95)( P <0.05).@*Conclusions@#From 2011 to 2022, the delay on detection and care seeking for tuberculosis patients among students in Inner Mongolia is at a relatively high level, while the delay in diagnosis and treatment is at a relatively low level but shows an increasing trend. It is necessary to focus on the factors associated with delays in identification, diagnosis and treatment in tuberculosis outbreak in the context of school to prevent or reduce school tuberculosis outbreak.

Expression and Clinical Significance of m6A Methylatransferase ZC3H13 in Gastric Cancer Tissues and Serum / 肿瘤防治研究

Objective To investigate the expression of m6A methylatransferase ZC3H13 in tissues and peripheral blood of patients with gastric cancer and its application value in gastric cancer. Methods UALCAN and GEPIA databases were used to analyze the expression difference of ZC3H13 in gastric cancer and adjacent normal tissues at transcription level; GEPIA and Kaplan-Meier Plotter databases were used to analyze the correlation between ZC3H13 expression level and OS of gastric cancer patients.ELISA was used to determine the concentration of ZC3H13 in 80 newly-diagnosed gastric cancer patients and 50 healthy controls, and to analyze its relation with clinicopathological data; IHC method was used to detect the expression level of ZC3H13 in 74 cases of cancer tissues and 40 cases of unpaired paracancerous tissues, and to analyze its relation with clinicopathological data. Results The expression of ZC3H13 in gastric cancer tissues was significantly higher than that in adjacent gastric tissues (P < 0.05).The positive rate of ZC3H13 protein in gastric cancer tissues was significantly higher than that in adjacent normal tissues (74.3%vs.52.5%, P < 0.05).Serum ZC3H13 concentration in gastric cancer group was significantly higher than that in healthy control group (P < 0.05).The expression level of ZC3H13 in gastric cancer tissues and peripheral blood was related to gender, differentiation degree, clinical stage and infiltration depth of gastric cancer (P < 0.05).Multivariate analysis showed that ZC3H13 expression was not an independent risk factor for poor prognosis of gastric cancer patients (P > 0.05).The AUC was 0.826(P < 0.05), indicating good diagnostic value.The critical value of serum ZC3H13 protein concentration was 4.87 ng/ml, and the sensitivity and specificity of ZC3H13 in the diagnosis of gastric cancer were 98.8% and 50.0%. Conclusion ZC3H13 is highly-expressed in gastric cancer tissues, and the concentration of ZC3H13 protein in peripheral blood is also significantly increased.ZC3H13 may play an important role in the occurrence and development of gastric cancer, and has certain clinical diagnostic value for gastric cancer.

Identification of variants in TNNI3 gene in two children with restrictive cardiomyopathy / 中华医学遗传学杂志

OBJECTIVE@#To identify the pathogenesis in two patients of restrictive cardiomyopathy (RCM) using high-throughput sequencing.@*METHODS@#Peripheral blood samples from the two patients and their parents were collected and genomic DNAs were extracted to conduct targeted next generation sequencing or whole exome sequencing. Bioinformation analysis was performed to identify the pathogenic variants in genes associated with cardiomyopathy, which were further validated by Sanger sequencing.@*RESULTS@#By high throughput sequencing, we detected a de novo heterozygous variant c.549+1G>T in TNNI3 gene in patient 1. The variant has not been reported previously and was predicted to be pathogenic in line with American College of Medical Genetics and Genomics (ACMG) guidelines (PVS1+PS2+PM2). Another heterozygous variant c.433C>T (p.Arg145Trp) in TNNI3 gene was identified in patient 2 and his father. The variant had been reported as pathogenic variant in Clinvar and HGMD databases; based on ACMG guidelines, the variant was predicted to be likely pathogenic (PS3+PM1+PP3).@*CONCLUSION@#TNNI3 variants may be the causative gene responsible for restrictive cardiomyopathy in the two patients. High throughput sequencing results provide bases for the diagnosis of restrictive cardiomyopathy.

A recombinant adenovirus vector expressing human IFN-λ1 inhibits the growth of orthotopic gastric cancer and its possible mechanism / 中华微生物学和免疫学杂志

Objective To investigate the inhibitory effects of a recombinant adenovirus vector ex-pressing human IFN-λ1 ( r-Ad-hIFN-λ1) on the growth of orthotopic gastric cancer and to analyze its possi-ble mechanism in a nude mice model of orthotopic human gastric carcinoma .Methods Orthotopic trans-plantation was performed to establish the nude mice model of orthotopic gastric cancer .Thirty mice were ran-domly divided into three groups including PBS control group , Ad-Lac Z empty vector group and r-Ad-hIFN-λ1 experiment group .The mice in each group were given the corresponding interventions once a week for three times.The sizes of tumor were detected by using B-mode ultrasound at different time points to draw growth curves .The expression of IFN-λ1 at mRNA level in skeletal muscle tissues was analyzed by RT-PCR.Western blot assay and immunohistochemical staining were used to detect IFN-λ1 protein in gastric tumor samples .The apoptosis of cells in paraffin-embedded tumor tissues was detected by TUNEL .The per-centages of natural killer ( NK) cells in spleen tissues were analyzed by flow cytometry .Results Compared with control group and empty vector group , the mice in r-Ad-hIFN-λ1 experiment group showed the smallest tumor size [(331.25±6.00) mm3, (322.92±5.92) mm3 vs (248.39±7.60) mm3; P<0.05].hIFN-λ1 was transfected into skeletal muscle successfully and expressed in gastric cancer tissue .Highly expressed hIFN-λ1 was observed in cytoplasm of tumor cells from experiment group by immunohistochemical staining . The apoptotic index of tumor tissues for experiment group was 0.700±0.059 which was significant different from that of control group (0.271±0.026, P<0.05) and empty vector group (0.333±0.028, P<0.05). The percentage of NK cells in spleens from mice in experiment group [(26.49±1.89)%] was significantly higher than that of control group [(13.94 ±1.31)%, P<0.05)] and empty vector group [(19.12 ±1.69)%, P<0.05)].Conclusion Transfection of r-Ad-hIFN-λ1 and expression of hIFN-λin skeletal muscle could significantly inhibit the growth of gastric cancer by inducing tumor cells ′apoptosis and enhan-cing NK cells.

Clinical study of postoperative three-dimensional conformal radiotherapy concurrent with paclitaxel and TS-1 chemotherapy in the treatment of advanced gastric carcinoma / 中国医师进修杂志

Objective To investigate the clinical efficacy of postoperative three-dimensional conformal radiotherapy concurrent with paclitaxel +TS-1 chemotherapy in the treatment of advanced gastric carcinoma.Methods A total of 60 patients with advanced gastric carcinoma were randomly divided into treatment group and control group.In treatment group,30 patients received simultaneous three-dimensional conformal radiations therapy combined with paclitaxel +TS-1 chemotherapy.In control group,30 patients received paclitaxel +TS-1 chemotherapy.The long term survival rate,local recurrence rate and side reactions were observed in two groups.Results The 1,2-year survival rate in treatment group [93.1％ (27/29),75.9 ％ (22/29)] and control group [72.4 ％ (21/29),48.3 ％ (14/29)] had significant difference (P ＜ 0.05).The 1,2-year local recurrence rate in treatment group [6.9％ (2/29),13.8％ (4/29)] and control group [31.0％ (9/29),44.8 ％ (13/29)] had significant difference (P ＜ 0.05 or ＜ 0.01).The side reactions in two groups were mainly manifested as leukopenia,thrombocytopenia,anemia,nausea,vomiting,liver function damage and oral mucositis.The incidence rate of nausea,vomiting in treatment group was significantly higher than that in control group [83.3％ (25/30) vs.53.3％ (16/30)] (P =0.012).Conclusions Postoperative threedimensional conformal radiotherapy concurrent with paclitaxel +TS-1 chemotherapy in the treatment of advanced gastric carcinoma may improve the long-term survival rate,lower local recurrence rate.But the adverse reactions are increased.

Observation of the effect of three-dimensional conformal radiation dose fractionation treatment of advanced non-small cell lung cancer / 中国基层医药

Objective To explore the effect of three-dimensional conformal radiation dose fractionation treatment of advanced non-small cell lung cancer(NSCLC).Methods 75 NSCLC patients were treated with hypofractionated 3DCRT( observation group),while 73 cases were treated with conventional fractionated radiotherapy (control group).The efficacy and adverse reactions were observed;Survival after treatment were followed up in 1,2,3 years.Lung function was detected before and after radiotherapy treatment,including FVC,FEV1 and CLCO.Results The total effective cases of control group were 47 cases patients ( 64.4％ ),observation group's was 60 cases ( 80.0％ ),total effective rate had statistically significant difference ( x2 =4.50,P ＜ 0.05 ).Survival of control group after treatment in 1,2,3year were 50.7％,24.7％,8.2％,the median survival was 13 months,observation group's were 73.3％,45.3％,20.0％,and 19 months.The survival of these two groups was statistically different (x2 =8.07,6,94,4.22,all P ＜ 0.05 ).The patients blood system side effects of observation group were significantly lower than the control group ( x2 =4.73,P ＜0.05 ) ;acute radiation pneumonia,esophagitis of these two groups had no significant difference in the incidence( P ＞ 0.05 ).Conclusion Hypofractionated 3DCRT treatment of advanced NSCLC had good effect,and its adverse reactions was low,and it was worthy of clinical application.

Electrogenerated chemiluminescence sensor for the determination of metoclopramide using ordered mesoporous carbon for immobilizing tris(2, 2'-bipyridyl) ruthenium / 药物分析学报

A novel electrogenerated chemiluminescence (ECL) sensor for the determination of metoclopramide was developed by employing ruthenium complex as an ECL signal producer and an ordered mesoporous carbon (OMC) material as modified material. The ECL sensor was fabricated by adsorption ruthenium complex into a mixture of OMC and Nafion, which showed good electrochemical and ECL behaviors. It was found that the ECL intensity of the sensor fabricated was greatly enhanced in the presence of metoclopramide. Based on this finding, a highly sensitive and reproducible ECL method was developed for the determination of metoclopramide. The result showed that the ECL intensity was linear with the concentration of metoclopramide in the range from 1.0×10-10 to 5.0×10-7M and the detection limit was 3×10-11M. The ECL sensor exhibited a long-term stability and a fine reproducibility with relative standard deviation of 1.0 % for 1.0×10-10M metoclopramide in 18 continuous determinations. The developed method has been applied to the determination of metoclopramide in tablet samples with satisfactory results.