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Objective:To investigate the clinical phenotype and genetic characteristics of developmental epileptic encephalopathy 18 (DEE18) caused by SZT2 gene variants. Methods:Clinical data of 2 children with SZT2 related DEE18 who visited the Department of Pediatric Neurology, Linyi People′s Hospital in March 2020 and July 2023 were collected. The whole exome sequencing (WES) and Sanger sequencing were applied to verify the child and their parents. SWISS-MODEL software was used to perform protein 3D modeling for the selected SZT2 gene variants. Results:Both of the 2 cases showed severe global developmental delay, epileptic seizures, autism, megacephaly, facial deformity, hypotonia, corpus callosum malformation, persistent cavum septum pellucidum, and slow background activity and focal discharge in video electroencephalography. Case 1 was easy to startle and thin in stature; case 2 had immune deficiency and clustered seizures. WES results showed that case 1 carried a compound heterozygous variant of c.5811G>A (p.W1937X) (paternal) and c.9269delG (p.S3090Ifs *94) (maternal), while case 2 carried a compound heterozygous variant of c.6302A>C(p.H2101P) (paternal) and c.7584dupA (p.E2529Rfs *20) (maternal), the parents of both patients with normal clinical phenotypes. The 4 mutations mentioned above were novel variations that had not yet been reported domestically or internationally. According to the American College of Medical Genetics and Genomics variant classification criteria and guidelines, the p.S3090Ifs *94 variant was interpreted as pathogenic; p.W1937X variant was interpreted as pathogenic; p.E2529Rfs *20 variant was interpreted as likely pathogenic; p.H2101P variant was interpreted as uncertain significance. 3D modeling showed that the variant of p.H2101P resulted in a significant change in the hydrogen bond around the 2 101st amino acid encoded, leading to a decrease in protein stability. The other 3 variants led to early truncation of peptide chain and obvious changes in protein structure. Conclusions:DEE18 caused by SZT2 gene mutation is mainly an autosome recessive genetic disease, and its clinical manifestations include global developmental delay, epileptic seizures, autism, craniofacial malformation, hypotonia, epileptic discharge, corpus callosum malformation, persistent cavum septum pellucidum, shock, small and thin stature, and immune deficiency. Four novel variants related to the SZT2 gene may be the genetic etiology of DEE18 patients in this study.
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Objective:To investigate the clinical phenotype and genetic characteristics of infantile epileptic spasm syndrome caused by BRWD3 gene mutation. Methods:Clinical data of a child with BRWD3 related infantile epileptic spasm syndrome who was admitted to Department of Pediatric Neurology of Linyi People′s Hospital on August 2, 2019 were collected and followed up, whole exome sequencing technology and Sanger sequencing were applied to verify the child and his parents, and the pathogenicity of mutation site was analyzed. The studies till June 2023 were searched with keywords of " BRWD3" in both English and Chinese databases of China National Knowledge Infrastructure, Wanfang, Online Mendelian Inheritance in Man, and PubMed. The clinical phenotype and genetic characteristics of patients with BRWD3 related epilepsy were summarized. Results:The patient was a 4 years and 4 months old boy, with a clinical phenotype including severe global development delay, focal seizures (the onset age was 4 months), epileptic spasm (the onset age was 6 months), autism, megacephaly, high forehead as well as hypsarrhythmia. The whole exome sequencing results showed a de novo and frameshift variation c.4318_4319del(p.Q1441Efs*20)(NM_153252) in the BRWD3 gene, and the variation was interpreted as pathogenic (PVS1+PS2+PM2) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. A total of 7 English literature articles were retrieved reporting 16 cases of BRWD3 gene related epilepsy in children (including 1 case of infantile epileptic spasm syndrome), and there has been no report in China yet. Totally there were 17 cases of BRWD3 gene related epilepsy including this case. All the cases showed X chromosome dominant inheritance, of whom 15 cases showed minor variations, including 7 missense variations, 3 frameshift variations, 3 splicing variations, 2 nonsense variations, and the remaining 2 cases showed large segment deletions. A total of 15 different variants were found. The phenotypes of the 17 patients mainly included epileptic seizures (17/17), intellectual disability (10/17), motor development disorder (7/17), speech impairment (9/17), megacephaly (8/17), facial malformation (8/17), autism (4/17) and hypotonia (4/17). The common seizure types were found to be focal seizures, occasionally epileptic spasm seizures and tonic seizures. Conclusions:BRWD3 gene variation related epilepsy is an X chromosome dominant genetic disease with a wide clinical phenotype spectrum. BRWD3 gene mutation c.4318_4319del(p.Q1441Efs *20) could cause infantile epileptic spasm syndrome, manifested as severe global developmental delay, epileptic spasm, focal seizures, autism, craniofacial malformation and hypsarrhythmia. This research enriches BRWD3 gene mutation spectrum.
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Objective:To analyze the clinical phenotypes and TSC1/TSC2 gene variations in 52 children with tuberous sclerosis complex. Methods:The clinical data of 59 children with tuberous sclerosis complex hospitalized in Linyi People′s Hospital between January 2017 and October 2022 were collected. The analysis of TSC1 and TSC2 gene variations on main family members was performed, and then bioinformatics analysis followed. The positive children were divided into TSC1 gene group and TSC2 gene group, and the difference of clinical characteristics between the two groups was analyzed. Results:Among 59 children, 52 cases were detected TSC1/ TSC2 gene variations (17 cases in the TSC1 gene group and 35 cases in the TSC2 gene group). Of the 52 children, 28 (53.8%) were male, 24 were female (46.2%); 17 (32.7%) were familial cases (10 with TSC1 gene variations and 7 with TSC2 gene variations), 35 (67.3%) were sporadic cases; 46 (88.5%) had hypomelanotic macules, 13 (25.0%) had facial angiofibromas, 5 (9.6%) had shagreen patches, 49 (94.2%) had subependymal nodules/calcifications, 47 (90.4%) had cortical nodules, 2 (3.8%) had subependymal giant cell astrocytomas, 39 (75.0%) had intellectual/developmental disabilities, 49 (94.2%) had epileptic seizures, 8 (15.4%) had cardiac rhabdomyomas, 9 (17.3%) had renal angiomyolipomas, and 4 (7.7%) had retinal hamartomas. Of the 52 children, 49 variations were detected, including 4 large fragment deletion/duplication variations, and 45 point variations; 41 pathogenic variations, 7 likely pathogenic variations, and 1 variation of uncertain significance. In this study, 16 point mutations and 1 large fragment duplication mutation which had not been reported at home and abroad, and 3 high-frequency mutation sites (p.Arg692 *, p.Arg228 *, and p.Arg1200Try) were found. There was a statistically significant difference in the proportion of familial cases [10/17 vs 7/35(20%), χ2=7.838, P=0.005], median onset age of epilepsy [38.0(0.5-134.0) months vs 8.0(0.1-63.0) months, Z=3.506 , P<0.001] and the incidence of developmental retardation/intellectual impairment [8/17 vs 31/35(88.6%), χadj2=8.423, P=0.004] between the TSC1 gene and TSC2 gene groups. Conclusions:Tuberous sclerosis compiex has widespread phenotypes, can affect every body system, especially the skin and nervous system. The pathogenic gene is TSC1/ TSC2. The TSC1 gene group has more familial cases. The TSC2 gene group has an earlier onset age of epilepsy and a higher incidence of developmental retardation/intellectual impairment. In this study, 16 novel point mutations, 1 novel large fragment duplication mutation, and 3 hotspot mutations were identified, expanding the gene variation spectrum of tuberous sclerosis complex.
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Objective To observe the effects of inverse ratio ventilation on respiratory mechanics and postoperative pulmonary com-plications in morbidly obese patients during laparoscopic sleeve gastrectomy Methods A total of 62 morbidly obese patients for a laparo-scopic sleeve gastrectomy were scheduled(18-65 years old,BMI≥35kg/m2 in combination with diabetes,hypertension,hyperlipemia,and other metabolic diseases,or BMI≥40kg/m2,ASA Ⅱ or Ⅲ).Patients were randomly assigned to two groups:inverse ratio ventilation group(IRV)and control group(PVG).Two groups were adjusted with an actual tidal volume(VT)of 7-8ml/kg,and respiratory rates of 12 breaths/min.In the IRV group,the ratio of I∶E was 2∶1;in the control group,the ratio of I∶E was 1∶2.We recorded the indexes of respiratory mechanics and the blood gas at the baseline(T0),5min after anesthesia(T,),15min after pneumoperitoneum(T2),30min after pneumoperitoneum(T3),60min after pneumoperitoneum(T4)and the end of surgery(T5),and the occurrence of pulmonary com-plications on day 1,day 2 after operation was observed,and the cumulative incidence of PPCs at 7 days was counted.Results Compared to the control group,the dynamic lung compliance(Cdyn),mean airway pressure(Pmean),positive end expiratory pressure(PEEP),and the PaO2 at T,-T5 of the inverse ventilation group were increased significantly(P＜0.05),the Ppeak、Pplat at T2-T5 and dynamic lung compliance(VD/VT)at T3-T5 were decreased significantly(P＜0.05),and no difference in the PaCO2 and PETCO2 in the two groups.Grade 1 pulmonary complications occurred in both groups,and there was no difference in the total occurrence of pulmonary com-plications at 7 days.Conclusion Inverse ventilation effectively may improve respiratory mechanics and oxygenation in morbidly obese pa-tients undergoing laparoscopic sleeve gastrectomy.
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@#Objective To explore the clinical effect of hydrocolloid silver-containing dressing combined with Jiedu Shengji ointment in the nursing of venous ulcer wounds of lower limbs.Methods A total of 84 patients with venous ulcer wounds of lower limbs admitted to the wound ostomy clinic of Jiading Central Hospital,Shanghai University of Medicine&Health Sciences from October 2022 to May 2023.Patients were divided into observation group and control group according to the method of single and double days of admission,with 42 cases in each group.The patients in two groups were treated with"three-step dressing change",the patients in control group were treated with conventional external dressing,and the patients in observation group were treated with reticular hydrocolloid silver dressing and Jiedu Shengji ointment for local use.The nursing effects of the two groups were compared.Results The total effective rate of observation group was higher than that of the control group(P<0.05).The wound healing time,treatment time and dressing change times in the observation group were lower than those in control group(P<0.05).The levels of interleukin(IL)-6 and IL-8 in observation group were lower than those in control group(P<0.05).The score of self-conscious pain in observation group was lower than that in control group(P<0.05).The total nursing satisfaction rate of observation group was higher than that of control group(P<0.05).Conclusion"Three-step dressing change"is an effective wound treatment method in the nursing care of patients with deep venous ulcer of lower limbs.It can further accelerate the wound healing process and effect with the local use of reticular hydrocolloid silver-containing dressing and Jiedu Shengji ointment.
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Objective:To summarize the clinical and genetic characteristics of children with epilepsy associated with SCN2A gene variations. Methods:A retrospective study was performed. Eleven children with epilepsy admitted to Department of Pediatric Neurology, Linyi People's Hospital from January 2017 to December 2022 were included; all of them had pathogenic SCN2A gene mutation. Genetic results and clinical data as epileptic seizure type/frequency, intelligence and motor development of these 11 children were collected. Epilepsy-related variations and pathogenesis of SCN2A gene were analyzed, and their correlations with clinical phenotypes in these children were analyzed. Results:Among the 11 patients, 6 had self-limited epilepsy (4 with variation in the intracellular domain and 2 in the transmembrane domain), 1 had febrile convulsion accompanied by childhood absent epilepsy (with variation in the intracellular domain), and 4 had developmental epileptic encephalopathy (2 with variation in the extracellular domain and 2 with variation in the transmembrane domain). SCN2A gene was missense mutation in these 11 children, and the mutation site in 6 children was not reported before. Various forms of video EEG discharge were noted, and 1 child with self-limited epilepsy showed transient multifocal epileptic discharge during frequent seizures. Oxcarbazepine and topiramate were effective for self-limiting epilepsy, and lamotrigine was effective in 1 child with late-onset epileptic encephalopathy. Eleven patients were followed up for (66±32) months; the age ranged from 8 months to 11 years and 6 months at the last follow-up; 10 patients had seizure remission and 1 had uncontrolled seizure. Conclusions:Besides self-limited epilepsy and developmental epileptic encephalopathy, SCN2A gene mutations are also associated with febrile convulsion and childhood absent epilepsy. Phenotypic differences are highly correlated with mutation locations; developmental epileptic encephalopathy associated variants are mostly located in extracellular domains, while self-limited epileptic variants are mostly located in intracellular domains.
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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.
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Humans , Female , Child , Pregnancy , Child, Preschool , Muscle Hypotonia/genetics , Prenatal Diagnosis , Computational Biology , Epileptic Syndromes , FaciesABSTRACT
Objective:To study the application value of nursing management based on self-efficacy theory in the early functional exercise of the affected limb after permanent pacemaker implantation.Methods:This study was a randomized controlled trial. A total of 90 patients who underwent permanent pacemaker implantation in Wuxi Second People′s Hospital (the Affiliated Central Hospital of Jiangnan University) from May 2019 to March 2021 were enrolled. They were divided into observation group and control group with 45 patients each according to random number table. The control group received routine nursing intervention, and the observation group received supplemental management interventions based on self-efficacy theory. The rate of post-operative rehabilitation up to the standard, the scores of the Shoulder Pain and Disability Index (SPADI), Chronic Disease Self-Efficacy Scale (CDSES) and Quality of Life Instrument for Patients with Pacemaker (QLIPP) were compared.Results:The rate of observation group's post-operative rehabilitation up to the standard was 93.33% (42/45), which was higher than that of the control group 77.78% (35/45). The difference was statistically significant ( χ2 =4.41, P<0.05). The pain index of the observation group was (20.27 ± 4.13), (5.25 ± 2.64)points at 1 and 2 weeks after operation, which was significantly lower than (27.06 ± 5.30), (9.35 ± 4.22) points of the control group ( t=6.78, 5.53, both P<0.05). The dysfunction index of the observation group was (15.06 ± 5.96), (7.21 ± 3.68) points, which was significantly lower than (17.75 ± 6.04), (9.03 ± 4.06) points of the control group ( t=2.13, 2.23, both P<0.05). After 2 weeks of operation, the total score of CDSES in the observation group was (4.73 ± 1.68) points, which was higher than (3.67 ± 1.49) points in the control group, and the difference was statistically significant ( t=3.17, P<0.05). The total score of QLIPP in the observation group was (92.78 ± 6.26), (124.40 ± 4.91) points at 2 weeks and 1 month after operation, which was significantly higher than (83.50 ± 7.91), (112.42 ± 5.04) points in the control group ( t=6.17, 9.51, both P<0.05). Conclusions:The application of nursing care based on self-efficacy theory in the patients of early functional exercise of the affected limb after permanent pacemaker implantation can improve rehabilitation compliance, self-efficacy of patients, the function of the affected shoulder joint and the patient′s quality of life.
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Objective:To investigate the clinical characteristics and prognosis of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies.Methods:A total of 216 non-acquired immunodeficiency syndrome (AIDS) related cryptococcal meningitis cases with positive cultures of Cryptococcus, hospitalized at Huashan Hospital, Fudan University during January 2014 and December 2021, were retrospectively included. The serum anti-GM-CSF autoantibodies were detected by enzyme linked immunosorbent assay, and the clinical characteristics and prognosis were compared between patients with and without anti-GM-CSF autoantibodies. Statistical comparisons were mainly performed using the chi-square test or Fisher′s exact test. Cox proportional-hazards model was used to analyze the risk factors associated with prognosis. Results:Among 216 enrolled patients, 23 patients were positive of anti-GM-CSF autoantibodies, with a positive rate of 10.6%. Among 23 patients, seven cases were infected with Cryptococcus gattii, and 16 cases were infected with Cryptococcus neoformans. In the group with positive anti-GM-CSF autoantibodies, 30.4%(7/23) of the patients were infected with Cryptococcus gattii, which was higher than that of 1.6%(3/193) in the group with negative anti-GM-CSF autoantibodies, and the difference was statistically significant ( χ2=38.82, P<0.001). In the group with positive anti-GM-CSF autoantibodies, 30.0% (6/20) had mass lesions with a diameter greater than three centimeters in the lungs, and the one-year all-cause mortality rate was 50.0% (10/20), which were both higher than those of 3.4%(5/145) and 16.1% (29/180) in the negative group, respectively. The differences were both statistically significant (both Fisher′s exact test, P<0.01). Age≥60 years (hazard ratio ( HR)=4.146, P=0.002), predisposing factors ( HR=3.160, P=0.021), epilepsy ( HR=6.129, P=0.002), positive anti-GM-CSF autoantibodies ( HR=2.675, P=0.034), white blood cell count of cerebrospinal fluid (CSF)<100 ×10 6/L ( HR=2.736, P=0.039), the titers of cryptococcal capsular polysaccharide antigen of CSF≥1∶1 280 ( HR=4.361, P=0.009) were independent risk factors for one-year all-cause mortality in patients with cryptococcal meningitis. Conclusions:In non-AIDS related cryptococcal meningitis patients, the positive rate of serum anti-GM-CSF autoantibodies is as high as 10.6%. Patients with anti-GM-CSF autoantibodies could be infected with both Cryptococcus neoformans and Cryptococcus gattii, and they have higher proportion of lung mass lesions than patients with negative anti-GM-CSF autoantibodies. The one-year survival rate decreases significantly in patients with anti-GM-CSF autoantibodies, which is an independent risk factor for the prognosis of cryptococcal meningitis.
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Objective To investigate the functions of the KIFC1 gene in tumor cells and its effect on the proliferation of cervical cancer cells. Methods We designed sgRNAs targeting the KIFC1 gene and constructed a recombinant plasmid based on the pSpCas9 (BB)-2A-GFP vector, which was co-transfected into HeLa cells. We screened monoclonal knockout cell lines through flow cytometry sorting, limited dilution inoculation of cells, and sequencing. RT-qPCR, Western blot, and immunofluorescence were used to detect the transcription and protein expression levels of KIFC1 in knockout cells. Cell phenotypes such as nucleus and microtubule cytoskeleton were observed using phase-contrast microscopy and fluorescence confocal microscopy. Cell proliferation, cell cycle, and apoptosis were analyzed by growth curve plotting, EdU labeling, and acridine orange staining. Results The deletion of the KIFC1 gene resulted in the abnormal phenotypes of HeLa cells, with increased numbers of multinuclei, micronucleus, and disordered microtubules. The cell cycle was disrupted, accompanied with a significant increase in the ratio of late apoptotic cells and a decrease in cell proliferation (all P < 0.05). Conclusion KIFC1 gene deletion affects the assembly of microtubules and cell division in HeLa cells, leading to abnormal nuclear morphology, chromatin elimination, cell cycle arrest, and increased cell apoptosis.
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ObjectiveTo determine the association of dietary diversity and dietary pattern with cognitive function in elderly in community. MethodsA cross-sectional study was conducted to randomly select 143 elderly people over 65 years old in Wangdingdi Community of Tianjin. Self-designed questionnaire was used and then dietary diversity index was calculated. Wechsler Adult Intelligence Scale-Chinese Revised （WAIS-RC） was used to measure intelligence quotient （IQ） to assess cognitive function. Factor analysis and multivariate linear regression model were used to extract dietary patterns and determine the association of dietary diversity index and dietary patterns with cognitive function， respectively. ResultsFactor analysis revealed four dietary patterns， which were meat and cereal dietary pattern， fish and poultry milk dietary pattern， bean vegetable dietary pattern， and egg dietary pattern. Multivariate linear regression showed that egg dietary pattern was significantly associated with performance IQ （P<0.05）， suggesting that egg dietary pattern may have a protective effect on IQ of the elderly. There was no significant association between dietary diversity and cognitive function in the elderly （P>0.05）. ConclusionEgg dietary pattern may protect cognitive function in the elderly. Therefore， the elderly should increase the intake of eggs in daily diet.
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Objective:To explore the association between Toll-like receptor (TLR) gene polymorphism and susceptibility to non-human immunodeficiency virus (HIV)-related cryptococcal meningitis in patients from Fujian Province.Methods:A total of 101 non-HIV patients with cryptococcal meningitis and 270 healthy controls in Huashan Hospital, Fudan University and Cangshan Hospital District, The 900th Hospital of the Joint Logistics Support Force from Fujian Province were prospectively enrolled in this case-control study. Genomic DNA was extracted. Genotyping was performed by multiplex SNaPshot technology on eight TLR single nucleotide polymorphism (SNP) which were reported to be related to cryptococcal meningitis but still lacking validations. The differences of gene polymorphism distributions were compared between all patients and healthy controls, and between patients without predisposing factors and healthy controls. Data were analyzed by chi-square test or Fisher exact test.Results:Except for TLR1 rs5743563, the distributions of allele frequency in seven tested TLR SNPs (TLR1 rs5743604, TLR2 rs3804099, TLR4 rs1927907, TLR6 rs3796508, TLR6 rs5743794, TLR9 rs164637 and TLR9 rs352140) were in Hardy-Weinberg equilibrium. Comparisons between cases and controls found that TLR2 rs3804099 T/T genotype (52.5%(53/101) vs 40.4%(109/270), odds ratio ( OR)=1.63, χ2=4.378, P=0.036) and TLR6 rs5743794 G/G genotype (44.6%(45/101) vs 32.2%(87/270), OR=1.69, χ2=4.877, P=0.027) were correlated with high risks of cryptococcal meningitis, while TLR6 rs3796508 G/G genotype ((83.2%(84/101) vs 92.6%(250/270), OR=0.40, χ2=7.271, P=0.007) and TLR9 rs164637 C/C genotype (96.0%(97/101) vs 100.0%(270/270), Fisher exact test , P=0.005) were found to be protective factors. Seventy out of 101 patients had no predisposing factors. Comparison between patients without predisposing factors and healthy controls also found similar results. TLR6 rs5743794 G/G genotype (52.9%(37/70) vs 32.2%(87/270), OR=2.36, χ2=10.216, P=0.001) was risk factor, while TLR6 rs3796508 G/G genotype (81.4%(57/70) vs 92.6%(250/270), OR=0.35, χ2=7.906, P=0.005) and TLR9 rs164637 C/C genotype (97.1%(68/70) vs 100.0%(270/270), Fisher exact test, P=0.042) were protective factors. Conclusion:TLR gene polymorphism is significantly associated with non-HIV-related cryptococcal meningitis, which indicates that TLR might play an important role in the pathogenesis of cryptococcal meningitis.
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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.
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Humans , Epilepsy/genetics , /genetics , Pedigree , Phenotype , Seizures, Febrile/geneticsABSTRACT
Objective:To investigate the relationship of antinuclear antibody (ANA) status with clinical features and malignancy risk in adult patients with dermatomyositis.Methods:A retrospective analysis was performed to analyze clinical data from 101 inpatients with dermatomyositis in Department of Dermatology, the First Affiliated Hospital of Soochow University from April 2008 to April 2018. These patients were divided into ANA-positive group and ANA-negative group, and differences in myopathy and malignancy risks as well as other clinical features were analyzed between the 2 groups. A 2-year follow-up was undertaken among 92 patients. Chi-square test was used to analyze and compare clinical features between the 2 groups, and a multivariate regression model was used to analyze the relationship of ANA status with amyopathic dermatomyositis and malignancies.Results:Among the 101 patients with dermatomyositis, there were 42 males and 59 females, aged 55.13 ± 14.63 years; 14 patients had amyopathic dermatomyositis, 6 patients had hypomyopathic dermatomyositis, and 81 patients had myopathic dermatomyositis; 42 (41.58%) cases were positive for ANA, and 59 (58.41%) were negative for ANA. Compared with the ANA-negative group, the ANA-positive group showed significantly decreased incidence of cervical erythema (33.33% vs. 59.32%, P=0.010) and shawl sign (14.28% vs. 35.59%, P=0.017) . Twenty-eight (27.72%) patients with dermatomyositis were complicated by malignancies. Malignancies were found in 5 (11.9%) of ANA-positive patients, and in 23 (38.98%) of ANA-negative patients. Univariate analysis showed that ANA-negative patients with dermatomyositis had a higher risk of malignancies compared with ANA-positive patients with dermatomyositis, with an odds ratio of 7.52 (95% CI: 1.62-13.78, P=0.003) . In the multivariate regression model, the absence of ANA ( OR=4.34, 95% CI: 1.37-13.72, P=0.012) and cervical erythema ( OR=3.27, 95% CI: 1.20-8.91, P=0.020) were associated with high incidence of malignancies, while the absence of ANA was not significantly correlated with the occurrence of amyopathic dermatomyositis ( OR=0.99, 95% CI: 0.32-2.99, P=0.980) . Conclusions:ANA-negative adult dermatomyositis patients with cervical erythema had an increased risk of malignancies. Thus, close follow-up and regular tumor screening are necessary in these patients.
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The purpose of this study is to describe the principles in selection and application of antidepressants in patients with depression complicating glaucoma or at high risk of glaucoma. With the aim of providing a partial reference for relevant issues， this paper elaborated a case of major depression after glaucoma surgery receiving 6 weeks of treatment with escitalopram oxalate and sulpiride achieved significant improvement in depressive and psychotic symptoms without triggering or exacerbating glaucoma.
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Objective:To identify problems and demands for antenatal care (ANC) among pregnant women in different trimesters of pregnancy in Shanghai for optimizing ANC service during the epidemic of COVID-19.Method:s Organized by maternal and child health care institute in the 16 districts of Shanghai, a cross sectional study was conducted among pregnant women who came to pregnancy registration in the community health centers or attended ANC in midwifery hospitals from February 7 to February 12, 2020. Consented participating women completed a semi-structured online questionnaire voluntarily. Data was analyzed using frequency,chi-square test and scoring.Result:s A total of 2 002 valid questionnaires were collected from 183 community health centers and 67 midwifery hospitals. About 94.6%(1 894/2 002) of the pregnant women worried about being infected during the COVID-19 epidemic, and 14.7% (294/2 002) demanded for psychological consultation. Time-lapse appointments for ANC were requested by 87.7% (1 756/2 002) of the participants for avoiding presenting themselves in people-density places. Compared with other pregnancy trimesters, pregnant women in the second trimester were more willing to reduce the frequency of ANC (35.2% versus 39.5% versus 48.1%, P<0.01). Compared with multiparas, primiparas were more willing to have online consultation and guidance (49.2% versus 63.8%, P<0.01). Regarding the needs for health knowledge on COVID-19, personal protection against 2019 novel coronavirus (2019-nCoV) was the most concerned for pregnant women, and 71.0% (1 421/2 002) of them preferred to obtain knowledge through health applications, official Weibo and WeChat. Conclusions:Pregnant women in Shanghai critically concern about the risk of 2019-nCoV infections, and highly demand knowledge and measures on prevention and protection from COVID-19. They ask for having time-lapse appointments for ANC and online access to health information and services. Maternal and child care institutes should understand the demands of pregnant women, optimize the means of ANC service, and provide tailored and accessible health education and service for the safety of mother and child.
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Objective@#To identify problems and demands for antenatal care (ANC) among pregnant women in different trimesters of pregnancy in Shanghai for optimizing ANC service during the epidemic of coronavirus disease 2019 (COVID-19).@*Methods@#Organized by Maternal and Child Health Care institute in the 16 districts of Shanghai, a cross sectional study was conducted among pregnant women who came to pregnancy registration in the community health centers or attended ANC in maternity hospitals from February 7 to February 12, 2020. Consented participating women completed a semi-structured online questionnaire voluntarily. Data was analyzed using frequency and scoring, chi-square test.@*Results@#A total of 2 002 valid questionnaires were collected from 183 community health centers and 67 midwifery hospitals. About 94.6% of the pregnant women worried about being infected during the COVID-19 epidemic, and 14.7% demanded for psychological consultation. Appointment ANC services were requested by 87.7% of the participants for avoiding presenting themselves in people-density places. Compared with other pregnancy trimesters, pregnant women in the second trimester were more willing to reduce the frequency of ANC (48.1% VS. 39.5% VS. 35.2%, P<0.01). Compared with multiparas, primiparas were more willing to have online consultation and guidance (63.8% VS. 49.2%, P<0.01). Regarding the needs for health knowledge on COVID-19, personal protection against 2019-nCoV was the most concerned for pregnant women, and 71.0% of them preferred to obtain knowledge through health applications, official Weibo and WeChat.@*Conclusions@#Pregnant women in Shanghai critically concern about the risk of 2019-nCoV infections, and highly demand knowledge and measures on prevention and protection from COVID-19. They ask for having time-lapse appointments for ANC and online access to health information and services. Maternal and Child Care institutes should understand the demands of pregnant women, optimize the means of ANC service, and provide tailored and accessible health education and service for the safety of mother and child.
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Objective To evaluate the efficacy and safety of high-dose fluconazole alone or combined with flucytosine as initial therapy for cryptococcal meningitis(CM)in non-human immunodeficiency virus(HIV)-related patients.Methods Twenty-five non-HIV-infected patients with CM from June 2015 to September 20 18 in Huashan Hospital,Fudan University,who were initially treated with high-dose fluconazole with or without flucytosine for at least seven days were retrospectively reviewed.Clinical features and antifungal(600-800 mg/d)regimens were recorded,clinical responses and drug-related adverse events were evaluated.Mann-Whitney test and Fisher's exact probabilities test were applied to compare variables between groups.Results of the 25 patients enrolled in this study,15 had predisposing factors.Headache(25 cases),fever(21 cases),vomiting(13 cases)and neck stiffness(13 cases)were common manifestations.Abnormalities of cranial computed tomography(CT)scan and/or magnetic resonance imaging(MRI)were found in 22 cases.Nineteen patients were treated with high-dose fluconazole plus flucytosine for initial therapy,and six patients were treated with high-dose fluconazole alone.The course of initial regimens with high-dose fuconazole was 42(29,120)days.At the end of initial therapy,partial response in 20 patients,stable response in three patients and death in two patients were observed,and the overall effective rate was 80％(20/25).In treatment failure group of initial treatment,the proportion of patients with baseline cerebrospinal fuid opening pressure over 300 mmH2 O(1 mmH2O=0.009 8 kPa)and with altered mental status were both significantly higher compared with those in treatment Success group.Fluconazole related adverse drug events were observed including elevated transaminases(one case),gastrointestinal symptoms combined with hypokalemia(two cases),and systemic rash(three cases).Except for three patients with rash reduced the dosage of fluconazole.no other patients were given dosage adjustment.Conclusion High-dose fluconazole alone or combined with flucytosine is effective and safe for the initial therapy of non-HIV-related CM patients.
ABSTRACT
Objective@#To evaluate the efficacy and safety of high-dose fluconazole alone or combined with flucytosine as initial therapy for cryptococcal meningitis (CM) in non-human immunodeficiency virus (HIV)-related patients.@*Methods@#Twenty-five non-HIV-infected patients with CM from June 2015 to September 2018 in Huashan Hospital, Fudan University, who were initially treated with high-dose fluconazole with or without flucytosine for at least seven days were retrospectively reviewed.Clinical features and antifungal (600-800 mg/d) regimens were recorded, clinical responses and drug-related adverse events were evaluated. Mann-Whitney test and Fisher′s exact probabilities test were applied to compare variables between groups.@*Results@#Of the 25 patients enrolled in this study, 15 had predisposing factors. Headache (25 cases), fever (21 cases), vomiting (13 cases) and neck stiffness (13 cases) were common manifestations. Abnormalities of cranial computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were found in 22 cases.Nineteen patients were treated with high-dose fluconazole plus flucytosine for initial therapy, and six patients were treated with high-dose fluconazole alone. The course of initial regimens with high-dose fluconazole was 42 (29, 120) days. At the end of initial therapy, partial response in 20 patients, stable response in three patients and death in two patients were observed, and the overall effective rate was 80%(20/25). In treatment failure group of initial treatment, the proportion of patients with baseline cerebrospinal fluid opening pressure over 300 mmH2O (1 mmH2O=0.009 8 kPa) and with altered mental status were both significantly higher compared with those in treatment success group. Fluconazole related adverse drug events were observed including elevated transaminases (one case), gastrointestinal symptoms combined with hypokalemia (two cases), and systemic rash (three cases). Except for three patients with rash reduced the dosage of fluconazole, no other patients were given dosage adjustment.@*Conclusion@#High-dose fluconazole alone or combined with flucytosine is effective and safe for the initial therapy of non-HIV-related CM patients.
ABSTRACT
Children′s esophageal stenosis is mainly benign stenosis. Esophageal foreign bodies and corrosion are common causes of esophageal stenosis in children requiring emergency management. Endoscop￣ic treatment of esophageal stricture includes endoscopic balloon dilatation,endoscopic radial incision,medical treatement,endoscopic stenting and so on. According to the cause of the stenosis,the nature of the lesion and the morphological structure of the lesion,formulating appropriate endoscopic treatment strategy are important for therapeutic effect and reducing the incidence of complications.