Recent studies on dilated cardiomyopathy caused by TTN mutations in children / 中国当代儿科杂志

The mutations of TTN gene that encodes titin are the most common mutation type among the genetic causes of dilated cardiomyopathy (DCM). This article reviews the worldwide studies on potential molecular pathogenesis (transcription, post-translational modification, etc.), clinical phenotypes, and gene therapies of pediatric DCM caused by TTN mutations, with the hope of providing a reference for the precision treatment of pediatric DCM caused by TTN mutations.

Phenotype and genotype characteristics of children with cardiomyopathy associated with MYH7 gene mutation: a retrospective analysis / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical phenotype and genotype characteristics of children withcardiomyopathy (CM) associated with MYH7 gene mutation.@*METHODS@#A retrospective analysis was conducted on the medical data of five children with CM caused by MYH7 gene mutation who were diagnosed and treated in the Department of Cardiology, Hebei Children's Hospital.@*RESULTS@#Among the five children with CM, there were three girls and two boys, all of whom carried MYH7 gene mutation. Seven mutation sites were identified, among which five were not reported before. Among the five children, there were three children with hypertrophic cardiomyopathy, one child with dilated cardiomyopathy, and one child with noncompaction cardiomyopathy. The age ranged from 6 to 156 months at the initial diagnosis. At the initial diagnosis, two children had the manifestations of heart failure such as cough, shortness of breath, poor feeding, and cyanosis of lips, as well as delayed development; one child had palpitation, blackness, and syncope; one child had fever, runny nose, and abnormal liver function; all five children had a reduction in activity endurance. All five children received pharmacotherapy for improving cardiac function and survived after follow-up for 7-24 months.@*CONCLUSIONS@#The age of onset varies in children with CM caused by MYH7 gene mutation, and most children lack specific clinical manifestations at the initial diagnosis and may have the phenotype of hypertrophic cardiomyopathy, dilated cardiomyopathy or noncompaction cardiomyopathy. The children receiving early genetic diagnosis and pharmacological intervention result in a favorable short-term prognosis.

Recent research on childhood hypertrophic cardiomyopathy caused by MYH7 gene mutations / 中国当代儿科杂志

Hypertrophic cardiomyopathy (HCM) is the most common monogenic inherited myocardial disease in children, and mutations in sarcomere genes (such as MYH7 and MYBPC3) are the most common genetic etiology of HCM, among which mutations in the MYH7 gene are the most common and account for 30%-50%. MYH7 gene mutations have the characteristics of being affected by environmental factors, coexisting with multiple genetic variations, and age-dependent penetrance, which leads to different or overlapping clinical phenotypes in children, including various cardiomyopathies and skeletal myopathies. At present, the pathogenesis, course, and prognosis of HCM caused by MYH7 gene mutations in children remain unclear. This article summarizes the possible pathogenesis, clinical phenotype, and treatment of HCM caused by MYH7 gene mutations, in order to facilitate the accurate prognostic evaluation and individualized management and treatment of the children with this disorder.

Clinical and genetic characteristics of children with primary dilated cardiomyopathy / 中国当代儿科杂志

OBJECTIVES@#To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM).@*METHODS@#A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data.@*RESULTS@#Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05).@*CONCLUSIONS@#There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.

One-step multiplex nested real-time RT-PCR assay for 2019-nCoV and Influenza A/B viruses detection / 中华检验医学杂志

Objective:To develop a single-tube one-step multiplex nested real-time reverse transcription polymerase chain reaction (RT-PCR) assay for the simultaneous detection of 2019-nCoV, influenza A virus, influenza B virus and internal-control with human-derived gene.Methods:This study included 30 positive specimens for 2019-nCoV nucleic acid detection and 336 screening specimens collected from the arrivals at Guangzhou Baiyun Airport between February 2020 and February 2022. Sixty-four positive specimens of other respiratory pathogens were also collected from the arrivals at Guangzhou Baiyun Airport during the three-year period before the occurrence of COVID19 outbreak in 2020, and 7 positive viral strains of respiratory pathogens were provided by collaborative laboratories. In order to establish a set of multiplex nested real-time RT-PCR assay, a group of primers and probe combinations for a multiplex nested real-time RT-PCR was designed and screened according to a selection of nucleotide conserved regions of the ORF and N genes of 2019-nCoV and the M gene of influenza A and B viruses, while nested amplification primers and probe for the internal-control with human-derived gene were introduced. Then the prepared pseudovirus-positive quality control and sample discs were applied to evaluate the sensitivity and specificity. Clinical specimens were performed to validate the applicability of the method.Results:The results show that the established one-step multiplex nested real-time RT-PCR assay can specifically detect 2019-nCoV and influenza A and B viruses, with the limit-of-detection of about 125 copies/ml for 2019-nCoV and about 250 copies/ml for influenza A and B viruses. Totally 101 positive samples of various respiratory pathogens were detected, showing that the detection sensitivities of 2019-nCoV and influenza A and B viruses were 96.67%, 92.86% and 96.15%, respectively, with the specificity of 100%. No false-positive detection was found in the applied detection of more than 300 clinical samples.Conclusions:A one-step multiplex nested real-time RT-PCR assay for 2019-nCoV, influenza A and B viruses and human-derived gene internal-control was developed. The assay has good sensitivity and specificity and can be used for rapid screening of 2019-nCoV and influenza A and B viruses in high-volume samples.

Molecular epidemiology of HFMD-associated pathogen coxsackievirus A4 in Fujian Province, 2011-2014 / 中国人兽共患病学报

To analyze the epidemiology,genetic variation and genetic evolution of coxsackievirus A4 (CVA4) in patients with hand,foot and mouth disease in Fujian,the virus isolates were molecular typed and amplified the whole VP1 region by RT-PCR,then the genetic variation and evolution were studied.The results showed that 33 CVA4 cases (8.1％) were confirmed from the 407 non-EV71 non-CVA16 HFMD cases in Fujian Province during 2011 and 2014,accounting for 31 cases in 2012 and 2 cases in 2014.Compared with common characteristics of the HFMD epidemic,no specificity in the distribution of CVA4 cases was found between gender and age groups.Sequence analysis of VP1 nucleotide sequences of Fujian CVA4 isolates showed that the nucleotide and amino acid sequences similarity were 92.6 ％-100 ％ and 95.7 ％-100 ％ respectively,low similarity with the prototype (83.7％-85.4％,96.1％-99.0％) and abroad isolates (82.1％-89.1％,90.4％-99.6％) both in nucleotide and amino acid sequences,high similarity with domestic isolates both in nucleotide and amino acid sequences,with the similarity of 87.9％ 99.2 ％ and 96.1％-100 ％.The results from phylogenetic tree showed that the genetic distance between Fujian CVA4 isolates and the prototype and abroad strains was far,and the genetic distance was close to domestic isolates in China.The distribution of the phylogenetic trees of Fujian CVA4 strains showed multiple branches.Therefore,CVA4 is the major HFMD associated-pathogen other than EV71,CVA 16,CVA6,and CVA10 in Fujian Province from 2011 to 2014.CVA4 strains from Fujian Province is co-circulating and co-evolving with other domestic isolates.There is existence of multiple closely related CVA4 transmission chains in various regions of Fujian.

Molecular epidemiology of HFMD-associated pathogen coxsackievirus A4 in Fujian Province, 2011-2014 / 中国人兽共患病学报

To analyze the epidemiology,genetic variation and genetic evolution of coxsackievirus A4 (CVA4) in patients with hand,foot and mouth disease in Fujian,the virus isolates were molecular typed and amplified the whole VP1 region by RT-PCR,then the genetic variation and evolution were studied.The results showed that 33 CVA4 cases (8.1％) were confirmed from the 407 non-EV71 non-CVA16 HFMD cases in Fujian Province during 2011 and 2014,accounting for 31 cases in 2012 and 2 cases in 2014.Compared with common characteristics of the HFMD epidemic,no specificity in the distribution of CVA4 cases was found between gender and age groups.Sequence analysis of VP1 nucleotide sequences of Fujian CVA4 isolates showed that the nucleotide and amino acid sequences similarity were 92.6 ％-100 ％ and 95.7 ％-100 ％ respectively,low similarity with the prototype (83.7％-85.4％,96.1％-99.0％) and abroad isolates (82.1％-89.1％,90.4％-99.6％) both in nucleotide and amino acid sequences,high similarity with domestic isolates both in nucleotide and amino acid sequences,with the similarity of 87.9％ 99.2 ％ and 96.1％-100 ％.The results from phylogenetic tree showed that the genetic distance between Fujian CVA4 isolates and the prototype and abroad strains was far,and the genetic distance was close to domestic isolates in China.The distribution of the phylogenetic trees of Fujian CVA4 strains showed multiple branches.Therefore,CVA4 is the major HFMD associated-pathogen other than EV71,CVA 16,CVA6,and CVA10 in Fujian Province from 2011 to 2014.CVA4 strains from Fujian Province is co-circulating and co-evolving with other domestic isolates.There is existence of multiple closely related CVA4 transmission chains in various regions of Fujian.

Laboratory diagnosis of the first imported case of Zika virus infection from Suriname into Guangdong,China / 中国人兽共患病学报

We detected Zika virus (ZIKV) in a febrile case returning from Suriname and entry China from Guangzhou Baiyun International Airport Port.Serum and saliva samples were collected from a suspected case returning from Suriname.We detected ZIKV RNA using real-time fluorescence RT-PCR methods by both in-house reagent and commercial detection kits.RT-PCR detection was carried out with saliva sample and sequence analysis was performed.Phylogenetic tree was constructed to analyze the source of imported cases.Real-time fluorescent RT-PCR result showed that saliva was detected ZIKV RNA positive while for serum was weakly positive.A specific 1 500 bp fragment in size was amplified with saliva sample by RT-PCR.Sequence analysis showed 99％ homologous to the corresponding sequence of Brazil ZIKV (GenBank No.KX197250).Phylogenetic tree indicated it was located on African lineage.According to the epidemiological investigation results,clinical manifestations and nucleic acid detection of case,the suspected case was confirmed to infect Zika virus,being the first case from Suriname into Guangdong Province.

Laboratory detection on severe acute respiratory syndrome / 中华检验医学杂志

Objective To provide scientific evidence to identify and confirm severe acute respiratory syndrome (SARS) by laboratory detection.Methods Multiple clinical specimens were collected serially and systematically from the 4 suspected SARS patients, which occurred between Dec.2003 to Jan.2004 in Guangdong Province. The samples were tested by serologic and molecular methods.Results IgM or IgG antibodies against SARS-CoV were detectable after 6—8 days of the onset in four patients. The four-fold or greater rising in antibodies was clearly detected in three of the four patients, while the fourth patient’s seroconversion was from negative to positive. The results analysed by enzyme-linked immunosorbent assay( ELISA), immunoflourescence assay (IFA), and neutralization test were highly correlated. SARS-CoV RNA was just detected in 3 throat swab specimens from case 1 by real-time PCR. M, N and S genes were amplified by reverse transcriptase polymerase chain reaction (RT-PCR) from the positive samples. Sequencing results showed that they were SARS-CoV gene segments, and most closely matched SARS-CoV gene sequences were isolated from civet cats in Guangdong Province. Nevertheless, SARS-CoV was not isolated from any samples of the 4 patients.Conclusion Based on these results, the 4 reported cases were laboratorily confirmed as SARS cases.

Study on spotted fever group Rickettsiae in Guangdong province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the existence of spotted fever group Rickettsiae (SFGR) in Guangdong province.</p><p><b>METHODS</b>Sera were tested to find the SFGR in population and host animals. The target samples were screened by polymerase chain reaction (PCR), and Rickettsiae was isolated with embryonated hen eggs and identified by serological tests.</p><p><b>RESULTS</b>Eight hundred and sixty people in natural condition and 321 of mice were determined. The mean positive rate of healthy population was 3.84%. To compare results among elected places, Fisher's exact test was applied. The difference was suggestive (P < 0.01), and there was no significant difference between mountain and plain areas. There was also no significant difference between mountain and plain areas (P > 0.05). Positive rate of mice was 4.67%, with Rattus fulvescens, Rattus edwardsi, Bandicota indica 11.59%, 12.90%, 3.13% respectively. It was the first time that SFGR antibodies in Rattus fulvescens, Rattus edwardsi, Bandicota indica were reported. A total number of 321 mice spleens and 394 ticks from the surface of mice body were collected. Two strains of SFGR, GDFK58-2000 and GDFK59-2000, were isolated in the ticks from the body surface of 2 Rattus fulvescens. They were identified as Rickettsia sibirica by serological tests. Five hundred thirty-three bp OmpA gene fragments of the two strains were cloned and sequenced. Compared with other relevant strains in Genbank, the rates of homology of nucleotide sequences of GDFK58-2000 and GDFK59-2000 and other Rickettsia sibirica strains were from 99.6% to 100%, and the homology of amino acid speculated was 100%.</p><p><b>CONCLUSION</b>It has been proved that epidemic areas of north Asia tick-transmitted SFGR, did exist in Guangdong province confirmed by hostanimals, transmission vectors and aetiology.</p>