OBJECTIVE: To explore the clinical features and genetic etiology of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 (MCAHS3) and provide prenatal diagnosis for her parents. METHODS: A female child who had presented at Linyi People's Hospital on 27 July 2022 for recurrent convulsions for over 4 years was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were taken from the child and her parents and subjected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out on amniotic fluid sample at 18 weeks' gestation. Bioinformatic software was used to analyze the pathogenicity of the protein model for the variant loci. RESULTS: The child was a 4-year-old female with frequent seizures, peculiar facial appearance, hypotonia and severe developmental delay. Genetic analysis revealed that she has harbored compound heterozygous variants of the PIGT gene, namely c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q), which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1126del (p.H376Tfs*56) variant was predicted to be pathogenic (PVS1+PM2_Supporting+PM4), and c.1285G>C (p.E429Q) variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PM4). Prenatal diagnosis suggested that the fetus also harbored the same compound heterozygous variants, and the pregnancy was terminated with induced labor. CONCLUSION The c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q) compound heterozygous variants of the PIGT gene probably underlay the MCAHS3 in this patient, and prenatal diagnosis has prevented birth of further affected child in this family.
Humans ; Female ; Child ; Pregnancy ; Child, Preschool ; Muscle Hypotonia/genetics* ; Prenatal Diagnosis ; Computational Biology ; Epileptic Syndromes ; Facies

Objective:To analyze the clinical characteristics of a child with developmental epileptic encephalopathy caused by NR4A2 gene mutation, and to summarize the clinical phenotypes and genotypes to improve the clinician′s understanding of this disease. Methods:The clinical data of a child with developmental epileptic encephalopathy admitted to Linyi People′s Hospital in August 2022 were collected, video electroencephalogram, craniocerebral magnetic resonance imaging and family whole exon sequencing were improved, and the suspected mutation sites were verified by Sanger sequencing. Relevant literature was consulted to summarize the clinical phenotypes and genetic characteristics of nervous system diseases caused by NR4A2 gene. Results:It was found that there was a heterozygous missense mutation at the locus c.866G>A (p.A289H) of NR4A2 gene in the child, which was a de novo mutation, and both parents were wild type. According to the American Society of Medical Genetics and Genomics variation classification, it was assessed as a suspected pathogenic variation. Through literature review, there were 16 related cases reported internationally, with clinical phenotypes including mental retardation/mental retardation, language disorders, seizures, muscle tone changes and different psychological and behavioral problems. Conclusions:The NR4A2 gene is not only associated with dopa responsive disorders, but also with neurological development, intellectual impairment, language development delay, and epilepsy. The mutation of NR42A gene c.866G>A (p.A289H) is the genetic cause of the patient, and the detection of this locus expands the NR4A2 gene spectrum. NR4A2 gene is one of the pathogenic genes of developmental epileptic encephalopathy.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with genetic epilepsy with febrile seizures plus (GEFS+). METHODS: Clinical data of the proband and his family members were collected. Following extraction of genomic DNA, the proband was subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the proband and other family members. RESULTS: The pedigree, including 6 patients with febrile seizures from 3 generations, was diagnosed with typical GEFS+. Among them, 2 had febrile seizures (FS), 1 had febrile seizures plus (FS+), and 3 had febrile seizures with focal seizures. High-throughput sequencing revealed that the proband has carried a heterozygous missense variant of c.4522T>A (p.Tyr1508Asn) of the SCN1A gene. Sanger sequencing confirmed that other five patients and one normal member from the pedigree have also carried the same variant, which yielded a penetrance of 85.7%. CONCLUSION The c.4522T>A (p.Tyr1508Asn) of the SCN1A gene probably underlay the disease in this pedigree. The pattern of inheritance was consistent with autosomal dominant inheritance with incomplete penetrance. Above finding has enriched the variant spectrum of the SCN1A gene.
Epilepsy/genetics* ; Humans ; NAV1.1 Voltage-Gated Sodium Channel/genetics* ; Pedigree ; Phenotype ; Seizures, Febrile/genetics*

Objective: To analyze the extubation indications of tracheotomy patients with severe neuropathy by Meta-analysis in order to determine the effective indication parameters for successful extubation. Methods: The literatures in databases including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Web of Science, PubMed and Cochrane Library were retrieved from their establishment to April 2019. The literatures were case-control studies, cohort studies, randomized controlled trials (RCTs) or surveys related to indication parameters for successful extubation in patients with severe neuropathy. Two researchers identified and extracted literatures and data independently. The quality of literatures was assessed by the Newcastle-Ottawa scale (NOS). Meta-analysis was performed by RevMan 5.3 software. The stability of the results were evaluated by assessing the statistical models (the fixed effects model or the random effects model) and literatures quality (inferior or superior), and by sensitivity analysis. The publication bias of literatures was assessed by funnel plot. Results: Eleven studies involving 1 357 participants were enrolled, and the rate of successful extubation was 46.7%-97.5%. Nine studies defined successful extubation as no need of re-intubation, and other two did not explain. All studies were high quality research, with NOS score of 6-8. Meta-analysis showed that the correlation between the level of consciousness [Glasgow coma score (GCS) ≥ 8 vs. < 8: odds ratio (OR) = 3.34, 95% confidence interval (95%CI) was 2.22-5.03, P < 0.001], the amount of tracheal secretions (less vs. more: OR = 13.07, 95%CI was 5.64-30.32, P < 0.001), cough reflex (with vs. without: OR = 14.33, 95%CI was 6.36-32.28, P < 0.001), swallowing function (good vs. bad: adjusted OR = 18.56, 95%CI was 8.16-42.21, P < 0.001) and successful extubation was statistically significant, and the correlation between the pulmonary infection (with vs. without: adjusted OR = 1.94, 95%CI was 0.87-4.35, P = 0.11), oxygen saturation (≥ 0.95 vs. < 0.95: OR = 2.34, 95%CI was 1.11-4.91, P = 0.12), tolerance of tube plugging (good vs. bad: OR = 2.12, 95%CI was 0.67-6.71, P = 0.20), method of tube drawing (gradually vs. abruptly: OR = 0.99, 95%CI was 0.95-1.04, P = 0.93) and successful extubation was not statistically significant. Sensitivity analysis showed that the results were stable. Funnel plot showed that the studies distributed in both sides of the funnel symmetrically, indicating the publication bias of literatures was small. Conclusion The effective indication of extubation is consciousness level (GCS score ≥ 8), less secretion, cough reflex and good swallowing function.

OBJECTIVE: To analyze the extubation indications of tracheotomy patients with severe neuropathy by Meta-analysis in order to determine the effective indication parameters for successful extubation. METHODS: The literatures in databases including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Web of Science, PubMed and Cochrane Library were retrieved from their establishment to April 2019. The literatures were case-control studies, cohort studies, randomized controlled trials (RCTs) or surveys related to indication parameters for successful extubation in patients with severe neuropathy. Two researchers identified and extracted literatures and data independently. The quality of literatures was assessed by the Newcastle-Ottawa scale (NOS). Meta-analysis was performed by RevMan 5.3 software. The stability of the results were evaluated by assessing the statistical models (the fixed effects model or the random effects model) and literatures quality (inferior or superior), and by sensitivity analysis. The publication bias of literatures was assessed by funnel plot. RESULTS: Eleven studies involving 1 357 participants were enrolled, and the rate of successful extubation was 46.7%-97.5%. Nine studies defined successful extubation as no need of re-intubation, and other two did not explain. All studies were high quality research, with NOS score of 6-8. Meta-analysis showed that the correlation between the level of consciousness [Glasgow coma score (GCS) ≥ 8 vs. < 8: odds ratio (OR) = 3.34, 95% confidence interval (95%CI) was 2.22-5.03, P < 0.001], the amount of tracheal secretions (less vs. more: OR = 13.07, 95%CI was 5.64-30.32, P < 0.001), cough reflex (with vs. without: OR = 14.33, 95%CI was 6.36-32.28, P < 0.001), swallowing function (good vs. bad: adjusted OR = 18.56,95%CI was 8.16-42.21, P < 0.001) and successful extubation was statistically significant, and the correlation between the pulmonary infection (with vs. without: adjusted OR = 1.94, 95%CI was 0.87-4.35, P = 0.11), oxygen saturation (≥ 0.95 vs. < 0.95: OR = 2.34, 95%CI was 1.11-4.91, P = 0.12), tolerance of tube plugging (good vs. bad: OR = 2.12, 95%CI was 0.67-6.71, P = 0.20), method of tube drawing (gradually vs. abruptly: OR = 0.99, 95%CI was 0.95-1.04, P = 0.93) and successful extubation was not statistically significant. Sensitivity analysis showed that the results were stable. Funnel plot showed that the studies distributed in both sides of the funnel symmetrically, indicating the publication bias of literatures was small. CONCLUSIONS The effective indication of extubation is consciousness level (GCS score ≥ 8), less secretion, cough reflex and good swallowing function.
Airway Extubation ; China ; Cohort Studies ; Humans ; Odds Ratio ; Tracheostomy

Objective To explore the clinical features of mitochondrial encephalomyopathy lactic acidosis and strokelike episodes (MELAS) syndrome in fratemal twins brothers.Methods The clinical data,the results of laboratory examinations,electroencephalogram (EEG),imaging,and gene detection,and the process of diagnosis and treatment were retrospectively analyzed the fraternal twin brothers with MELAS syndrome.Results The proband,a 7-year-old male,had intermittent headaches,vomit and twitching at onset.He suffered from exercise intolerance,fatigue,accompanied by short stature and hairy.The fasting blood lactic acid level was increased.Multiple video EEG showed the slowdown of background activity.Head MRI showed recurrent lesions with the characteristics of migration and variation.The point mutation rate of mtDNA A3243G was 34.7％.The diagnosis of MELAS was confirmed.At the same time,his fraternal twin brother was screened and found that his point mutation rate of A3243G was 30.0％.Although there was no clinical symptom at that time,he was onset with convulsion after 3 years.Conclusions Gene detection and family screening are helpful for the early diagnosis of MELAS.The mutation rate of A3243G is very high,which can cause an early onset and serious clinical symptoms.

Objective To summarize the successful application experience of intra-hospital transport of 13 H7N9 avian influenza patients from the general wards to the avian influenza ward. Methods Form the expert group, to determine the design target and principle of the standardized workflow and point out the operation points of standard workflow in intra-hospital transport of each link. Results The standardized workflow included the disposal of the transfer notice, condition assessment, department contact,patient preparation,object preparation,custody transfer personnel preparation,transit guardianship and transfer to the avian influenza ward,a total of eight procedures.Between January 2013 and March 2017,13 cases were successfully transfered.All patients safely arrived avian influenza ward. The process was quick and smooth.Nobody was died or rescued within 1 h after transport. Conclusions The main differences of intra-hospital transport between H7N9 avian influenza patients and general critically ill patients are the transit time control, the particularity of terminal disposal, transshipment arrangement and hospital infection management personnel involved in the whole process.

Objective:To investigate the effect of upregulated and downregulated PSMA7 on the cell cycle and Cyclin D1,CDK4,P16,Rb of RB pathway in A549 cells.Methods:Transfected upregulated pcDNA3.1-PSMA7 vecter and downregulated pGPU6/Hygro-PSMA7-265 vecter into A549 cells,and then tested the effect of PSMA7 on the cell cycle of A549 cells by flow cytometry,and detected the protein level of Cyclin D1,CDK4,P16,Rb by Western blot.Results:Compared with the control group,the cell cycle of the A549 cells did not change significantly,and the expression of Cyclin D1,CDK4 decreased but P16,Rb increased when PSMA7 was upregulated.Compared with the control group,the proportion of phase G0/G1,G2/M of the A549 cells decreased and phase S increased,and the expression of Cyclin D1,CDK4 increased but P16,Rb decreased when PSMA7 was downregulated.There was statistical significance for those results.Conclusion:PSMA7 could affect the expression of Cyclin D1,CDK4,P16,Rb protein level of RB pathway in A549 and promoted the A549 cells into phase S when it′s downregulated.

Objective To summarize and analyze the dynamic change of HBsAg levels in patients with chronic Hepatitis B (CHB) after receiving nucleos(t)ide analogues (NAs) as antiviral treatment.Methods Patients who were performed quantitative Hepatitis B surface antigen(qHBsAg) from July 30, 2012 to December 30,2016 in Peking Union Medical College Hospital were retrospectively enrolled.qHBsAg, HBV DNA, HBeAg were collected and analyzed at baseline and at 192-week follow-up every 24 weeks.qHBsAg and HBeAg were assessed with chemiluminesent microparticle immuno assay(CMIA).HBV DNA was assessed with PCR and COBAS Amplicor.Results 60 patients were included.Patients in HBeAg-positive group had higher HBV DNA than that in HBeAg-negative group (P<0.05)at baseline and the two groups both were under detection limit after 48 weeks.BaselineqHBsAg in HBeAg positive-group and negative-group were (3.43±0.73) log10 IU/mL, (3.08±0.47) log10 IU/mL respectively.qHBsAg in HBeAg-positive group was higher than that in HBeAg negative-group on all follow-ups(P<0.05) except 48weeks.However on 168 weeks and 192 weeks, difference between the two groups was statistically significant(P<0.05).In HBeAg-positive group,quantitative HBeAg dropped significantly during antiviral treatment.Conclusions HBV replication can be suppressed in the process of long-term NAs treatment in CHB patients.However qHBsAg decline is not so obvious, which indicates that HBsAg cleavence is difficult,and long-term NAs therapy is still necessary.

Objective To better understand the infection status of HIV in the patients seeking medical care in Peking Union Medical College Hospital.Methods The HIV detection data of the patients in the hospital from 2003-2014 were collected for a statistical analysis with software SPSS 19.0.Results A total of 715 421 patients were screened,and 1 012 (0.14％) patients were HIV positive,and HIV infection were confirmed in 776 (0.11％) patients by Western Blot testing.The detection rate of HIV infection increased from 0.05％ in 2003 to 0.17％ in 2014 (trend x2=66.83,P=0.000),and the increase during 2012-2014 was obvious.Of the 776 newly diagnosed HIV-infected individuals,631 (81.31％) were men and 145 (18.69％) were women.The percentage of the males infected with HIV increased from 50.00％ to 90.26％ (trend x2=58.41,P=0.000).The median age was 36 years (interquartile range:27-43),and the age group 18-50 years were mostly affected.In the 776 patients infected with HIV,634 (81.70％) were infected through sexual contacts,and the proportion of sexual transmissions increased with year (trend x2=126.38,P=0.000).The proportion of infected men who have sex with men (MSM) increased from 0％ in 2003 to 53.90％ in 2014 (trend X2=11.96,P=0.001),similar to the trend in western countries.The proportion of infected patients who were not married increased from 18.75％ to 42.21％ (trend x2=43.74,P=0.000).The top three source departments of HIV/AIDS cases were internal medicine (51.03％),emergency room (18.30％) and dermatology (13.53％).The proportion of the HIV/AIDS patients from department of gynecology and obstetrics declined from 18.75％ in 2003 to 2.60％ in 2014.No HIV/AIDS patients were detected in department of surgery,department of otorhinolaryngology,department of ophthalmology,department of stomatology and health examination center in 2003,but 14 cases (9.10％),11 cases (7.14％) and 4 cases (2.60％) were detected in these departments respectively in 2014.Conclusion The HIV detection rate increased with year in Peking Union Medical College Hospital,suggesting the necessity of strengthened HIV test in general hospitals.MSM are the population at high risk,to whom more attention should be paid.