X-linked adrenoleukodystrophy(X-ALD) is an inherited progressive neurometabolic disorder caused by mutations in the ATP-binding cassette subfamily D member 1(ABCD1) gene. The encoded ALD protein dysfunction leads to the accumulation of very-long-chain fatty acids(VLCFA). X-ALD is classified according to its clinical characteristics into childhood cerebral ALD, adolescent cerebral ALD, adult cerebral ALD, adrenomyeloneuropathy(AMN), pure adrenocortical insufficiency, and an asymptomatic phenotype, all of which can present with a variety of neurologic manifestations. In this study, we retrospectively analyzed the clinical manifestations, laboratory findings, genetic test results, and follow-up data of four patients with X-ALD, and investigated the clinical features and pathogenicity of the identified gene mutations. All four patients initially presented with adrenocortical insufficiency(Addison′s disease) and received glucocorticoid replacement therapy. Subsequently, all developed neurologic signs and symptoms with rapid progression. The final diagnosis was confirmed based on elevated VLCFA levels, brain magnetic resonance imaging(MRI) findings, and genetic analysis. Notably, a deletion mutation in Exon 10 of the ABCD1 gene was identified in one case for the first time. We report four cases of X-ALD presenting with adrenocortical insufficiency as the initial symptom, and briefly review the relevant literature to analyze the relationship between linical phenotypes and genetic loci, aiming to provide a reference for early diagnosis and treatment of the disease, and to reduce the risk of misdiagnosis and missed diagnosis.

X-linked adrenoleukodystrophy(X-ALD) is an inherited progressive neurometabolic disorder caused by mutations in the ATP-binding cassette subfamily D member 1(ABCD1) gene. The encoded ALD protein dysfunction leads to the accumulation of very-long-chain fatty acids(VLCFA). X-ALD is classified according to its clinical characteristics into childhood cerebral ALD, adolescent cerebral ALD, adult cerebral ALD, adrenomyeloneuropathy(AMN), pure adrenocortical insufficiency, and an asymptomatic phenotype, all of which can present with a variety of neurologic manifestations. In this study, we retrospectively analyzed the clinical manifestations, laboratory findings, genetic test results, and follow-up data of four patients with X-ALD, and investigated the clinical features and pathogenicity of the identified gene mutations. All four patients initially presented with adrenocortical insufficiency(Addison′s disease) and received glucocorticoid replacement therapy. Subsequently, all developed neurologic signs and symptoms with rapid progression. The final diagnosis was confirmed based on elevated VLCFA levels, brain magnetic resonance imaging(MRI) findings, and genetic analysis. Notably, a deletion mutation in Exon 10 of the ABCD1 gene was identified in one case for the first time. We report four cases of X-ALD presenting with adrenocortical insufficiency as the initial symptom, and briefly review the relevant literature to analyze the relationship between linical phenotypes and genetic loci, aiming to provide a reference for early diagnosis and treatment of the disease, and to reduce the risk of misdiagnosis and missed diagnosis.

Objective To formulate the quantitative grip strength training program for application in the postoperative patients with autogenous arteriovenous internal fistula,and to evaluate its effect on the mat-uration and initial use of autogenous arteriovenous internal fistula.Methods A total of 98 patients with ce-phalic venous radial arterial anastomosis internal fistula formation surgery in Shenzhen Hospital of Southern Medical University from September 2021 to November 2022 were selected as the study subjects by the conven-ience sampling method.According to the follow-up time,they were divided into the observation group (n=41) and control group (n=42).The observation group adopted the quantitative grip strength training for function-al exercise of the limb on the side of internal fistula,while the control group adopted the conventional grip training for functional exercise of the limb on the side of internal fistula.In postoperative 8 weeks,the matura-tion rate of internal fistula,natural blood flow amount of internal fistula,internal diameter of cephalic vein,pre-pump pressure used in the initial stage of internal fistula and the incidence rate of internal fistula complica-tions were evaluated in the two groups.Results Compared with the control group,the maturation rate of in-ternal fistula in the observation group was higher (97.6％ vs. 83.3％).The inner diameter of cephalic vein and natural blood flow amount of internal fistula in the observation group were larger than those in the control group[(5.24±0.66)mm vs. (4.63±0.59)mm;(1215.38±562.99)mL/min vs. (955.75±341.94)mL/min],the pre-pump pressure used at the initial stage of internal fistula in the observation group was lower than that in the control group[(119.20±19.83)mmHg vs. (135.74±17.07)mmHg],and the differences were statistically significant (P<0.05).Conclusion The quantitative grip strength training could increase the postoperative maturity rate of patients's internal fistula,and is beneficial to the use in the initial stage of internal fistula.

Objective:To explore the clinical characteristics, therapeutic effect and prognosis of movement disorders in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.Methods:The prospectively collected data of hospitalized 163 patients with anti-NMDAR encephalitis admitted to Xuanwu Hospital, Capital Medical University from June 2012 to October 2019 were analyzed. According to the presence of movement disorders, the patients were divided into movement disorders group (75 cases, 46.0%) and non-movement disorders group (88 cases, 54.0%). Patients were followed up for six months and 12 months after immunotherapy. The clinical manifestations, auxiliary examinations, treatment and prognosis of the two groups were compared.Results:Among 163 patients with anti-NMDAR encephalitis, 91 patients (55.8%) were male and 72 patients (44.2%) were female, with an age of 26(19, 34) years. In the 75 patients of the movement disorders group, 50 patients (66.7%) presented with orofacial dyskinesia, 45 patients (60%) with limb stereotypies, 28 patients (37.3%) with choreoathetosis, nine patients (12.0%) with ballism, seven patients (9.3%) with bradykinesia, five patients (6.7%) with tremor, and 13 patients (17.3%) with status dystonicus. Compared with the non-movement disorders group, the movement disorders group had a higher proportion of ovarian teratoma (14.7% vs 3.4%), modified Rankin Scale score of 3-5 before immunotherapy (76.0% vs 33.0%), abnormal electroencephalogram (89.3% vs 77.3%), increased lumbar puncture pressure (53.3% vs 34.1%), cerebrospinal fluid (CSF) pleocytosis (73.3% vs 51.1%), strong positive NMDAR antibody of CSF (44.0% vs 25.0%), admitting to intensive care unit (60.0% vs 9.1%), treated with intravenous immunoglobulin (80.0% vs 40.9%), plasma exchange (36.0% vs 3.4%), and immunosuppressive therapy (37.2% vs 17.0%); had shorter days from the onset to the beginning of immunotherapy [20(10, 33) d vs 35(15, 77) d]; had longer days from the beginning of immunotherapy to the improvement [34(20, 60) d vs 20(15, 35) d]; and there were significant differences of above items between the two groups ( P<0.05). There was no significant difference in the prognosis and relaps between the two groups at six and 12 months after immunotherapy. Conclusions:Nearly a half of patients with anti-NMDAR encephalitis had movement disorders with multiple phenotypes. The severity of movement disorders was related to the severity of the disease. After active immunotherapy and symptomatic treatment, movement disorders improved with the improvement of primary disease in majority of patients.

Objective:To investigate the blocking effect of non-competitive N-methyl-D-aspartic acid(NMDA) receptor antagonist Memantine on glutamate abnormal signal transmission in immature white matter induced by ischemia in vitro and in vivo. Methods:The oligodendrocyte (OL) precursor oxygen glucose deprivation (OGD) cell models of 2-day-old newborn rats were prepared and divided into the normal control group, the OGD group and the Memantine group.The extracellular glutamate level of the OL precursor was measured by high performance liquid chromatography, while the concentration of intracellular calcium and the apoptosis rate of OL precursor were detected by flow cytometry.The animal models of ischemic periventricular leukomalacia (PVL) were established and divided into the sham group, the PVL group and the Memantine group.The pathological evaluation of white matter was performed under light microscope.The positive OL expression rate of myelin basic protein(MBP) was detected by immunohistoche-mistry.The myelination of white matter was evaluated under electron microscope.Results:Compared with the normal control group in vitro, the OGD group had a higher extracellular glutamate level of the OL precursor [(24.60±2.42) μmol/L vs.(9.49±1.08) μmol/L, t=9.28, P<0.01], a higher intracellular calcium concentration [(32.9±6.9)% vs.(6.9±3.5)%, t=4.41, P<0.01], a higher apoptosis rate of the OL precursor [(24.77±2.05)% vs.(6.65±1.39)%, t=15.01, P<0.01]. After treatment with Memantine, the extracellular glutamate level [(14.70±1.70) μmol/L, t=5.68, P<0.01], the intracellular calcium concentration [(23.1±2.0)%, t=6.13, P<0.01], and the apoptosis rate of the OL precursor [(11.80±2.06)%, t=5.18, P<0.01] decreased significantly.Compared with the sham group in vivo, the white matter of the PVL group showed mild or severe pathological changes, and the PVL group had a lower MBP-positive OL expression rate in the white matter [(5.94±1.37)% vs.(15.40±3.22)%, t=4.63, P<0.01]less myelin sheaths (4.00±1.00 vs.14.67±2.70, t=6.11, P<0.01) and thinner myelin sheaths [(33.83±3.21) nm vs.(79.67±6.45) nm , t=10.43, P<0.01]. After the treatment with Memantine, the number of myelin sheaths (10.30±1.50, t=6.01, P<0.01), the thickness of myelin sheaths [(57.21±4.05) nm, t=7.47, P<0.01], and the pathological changes in the white matter of newborn rats ( Z=88.479, P<0.01) all improved markedly, and the MBP positive OL expression rate in the cerebral white matter [(11.02±1.35)%, t=4.40, P<0.05] also increased significantly. Conclusions:Ischemia-induced abnormal signal transmission of glutamate in immature white matter is the important pathway leading to ischemic PVL.Memantine can effectively block the abnormal signal transmission and thus may probably provide a new approach for the effective prevention and treatment of PVL in premature infants.

Objective:To describe the long-term outcomes of intensive care unit (ICU) survivors of mechanical ventilation, and investigate the views of survivors on ICU rehabilitation clinics.Methods:A single-center cross-sectional descriptive study was designed. ICU survivors of mechanical ventilation admitted to the First Affiliated Hospital of Guangzhou Medical University from January to December 2016 were enrolled. Data were collected from August 2017 to March 2018. The general information questionnaire, Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and ICU rehabilitation clinics questionnaire were used to evaluate ICU survivors social-demographic factors, social and economic outcomes, clinical data, quality of life and the views on ICU rehabilitation clinics.Results:A total of 248 ICU survivors of mechanical ventilation were included in the study, 130 (52.4%) of them were followed up successfully. The mean time from ICU discharge to follow-up day was (19.64±3.20) months. The average age of the survivors was (60.09±15.42) years old, and 55.4% of them were over 60 years old. Among 130 ICU survivors, severe pneumonia was the dominant ICU admission diagnosis (23.1%), followed by surgical operations (cardiac surgery 16.9%, other surgical operations 20.8%), lung transplantation (13.1%), and acute exacerbation of chronic obstructive pulmonary disease (AECOPD, 12.3%), etc. The first APACHEⅡ score after ICU admission was 16.88±7.37, the mechanical ventilation time was (12.52±12.34) days, and the length of ICU stay was (16.71±15.11) days. In terms of social and economic outcomes, the proportion of having full-time or part-time jobs decreased from 32.3% (42/130) before ICU admission to 25.4% (33/130) by the date of follow-up, while the unemployed rate increased from 6.9% (9/130) to 18.5% (24/130). Only 45.1% (23/51) of the ICU survivors returned to the post before ICU admission. 36.2% (47/130) of the ICU survivors reported that they needed care from others, and 86.9% (113/130) reported that their treatment experiences in ICU had an impact on their lives. In terms of quality of life, physiological function dimension, which was 34.62±33.15, scored the lowest and suffered the most. The physical pain dimension and mental health dimension suffered the least, and the scores were 90.19±16.98 and 75.28±15.15, respectively. Furthermore, physical component summary (PCS) score was 61.12±17.09, and mental component summary (MCS) score was 65.97±21.85. In terms of the views of ICU rehabilitation clinics, 68.5% (89/130) of the subjects believed that the establishment of ICU rehabilitation clinics was very helpful or helpful.Conclusions:The long-term outcomes of ICU survivors of mechanical ventilation are not optimistic. Their quality of life is lower than that of general people. It is necessary to set up ICU rehabilitation clinics.

Objective · To compare the efficacy and prognostic factors of HCAG regimen with traditional IA regimen in the treatment of newly diagnosed elderly acute myeloid leukemia (AML) patients. Methods · Forty-one patients with AML (aged 55-71 years) were randomly divided into two groups (Group HCAG and Group IA) between 2014 and 2016 for induction and consolidation therapy. Multivariate analysis was applied to identify prognostic factors for relapse-free survival (RFS). Results · A total of 29 patients (70.7%) achieved complete remission (CR). The estimated 2-year overall survival (OS) was 66.8% in Group HCAG and 75.4% in Group IA (P=0.913). The estimated 2-year RFS was 61.8% in Group HCAG and 49.1% in Group IA (P=0.411). Age remained as the unfavorable prognostic factor, leading to significant differences in OS and RFS. In addition, RFS was influenced by cytogenetic/molecular risk stratification. Conclusion · Although HCAG seemed not to particularly benefit the group, the dose reduction of anthracyclines may be applied in elderly patients with comparable short-time outcome. Furthermore, the introduction of homoharringtonine resulted in an improvement of treatment response for more than 20% compared with CAG regimen.

One unusual human G3P[3] group A rotavirus (RVA) strain M2-102 was identified in stool sample collected from a child with diarrhea in Guangxi Province, China in 2014. It is well known that G3P[3] is a genotype commonly identified in feline and canine RVAs. However, the preliminary phylogenetic analyses of the VP7 and VP4 genes of strain M2-102 indicated that these two genes were closely related to bat RVA strain MYAS33 and simian strain RRV, respectively, whereas both clustered distantly to feline/canine-like RVA strains. In this study, full genome sequencing and molecular analyses were conducted to obtain the true origin of strain M2-102. It was revealed that strain RVA/Human-wt/CHN/M2-102/2014/G3P[3] exhibited a G3-P[3]-I3-R3-C3-M3-A9-N3-T3-E3-H6 genotype constellation for VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5 genes. Phylogenetic analyses revealed that 5 genes (VP7, VP1, VP2, NSP2 and NSP3) from strain M2-102 were closely related to those of bat strain MYAS33 from Yunnan Province which was thought a true bat RVA strain rather than a virus transmitted between species, while another 5 genes (VP4, VP3, NSP1, NSP4 and NSP5) clustered closely with those of simian strain RRV, yet the VP6 gene was closely related to that of human G3P[9] strain AU-1 and AU-1-like RVAs. The epidemiological data indicated that the child infected with M2-102 came from a countryside village, located in Dong Autonomous County of Sanjiang (subtropical hilly wooded area), Liuzhou city in Guangxi Province which might provide natural environment for reassortment events occurring among animal and human RVAs. Therefore, the data suggest that human strain M2-102 might originate from multiple reassortment events among bat, simian and human AU-1-like RVAs, yet it is not clear whether the genomic backbone based on bat MYAS33 (5 genes) and simian RRV (5 genes) like rotaviruses had been obtained through reassortment before being transmitted to the human. This is the first report on whole genome analysis of human G3P[3] RVA from China.
Child, Preschool ; China ; Genome, Viral ; Genomics ; Humans ; Male ; Molecular Sequence Data ; Phylogeny ; Reassortant Viruses ; classification ; genetics ; isolation & purification ; Rotavirus ; classification ; genetics ; isolation & purification ; Rotavirus Infections ; virology ; Viral Proteins ; genetics

Objective To study the liver pathomorphological and serum biochemical changes in Beagle dog with spontaneous hepatocirrhosis and establish the backgroud information of experimental animals for GLP .Methods The ALT, AST,TP,ALB, ALP, TBIL, TC, TG and GGT were detected using an automatic biochemical analyzer , and compared the differences of above index between blank control and diseased animal .The histological changes of the liver were observed by optical microscopy.Results Compared with the blank control ,the ALT,AST,ALP,TBIL and GGT of diseased dogs were increased significantly , and the ALB decreased significantly .Compared with normal dogs , the liver cells had nodular regeneration , arranged irregularly and pseudolobule formation .The pseudolobules were packaged with collagen fibers . Conclusion It is suggested that spontaneous lesions in Beagle dogs should be monitored so as to provide appropriate experimental animal histopathologicalbackgroud information for drug safety evaluation .

Objective To study the relieving cough and reducing phlegm effects and acute toxicity of the Kujyukekuan mixtures. Methods The method used in our study is a cough model induced by the ammonia water , the phenol red test in mice, the mouse pinna swelling model induced by xylene and the maximum tolerant dose experiment. Results In antitussive experiments, R value of Kujyukekuan mixtures at low, medium and high dose of was 112. 26%, 143. 29%, 162. 07%, respectively regarding as ineffective, effective and marked effective;Kujyukekuan mixtures at medium and high doses increased the excretion of phenolsulfonphthalein in the trachea of mice (compared with the normal control group, P<0. 05 or P<0. 01),the results showed good concentration-response relationship;Kujyukekuan mixtures at low, medium and high dose significantly reduced mouse auricle swelling caused by xylene (compared with normal control group, P<0. 01), the results presented a good concentration-response relationship;the MTD of Kujyukekuan mixture was 326. 76 g·kg-1. Conclusion Kujyukekuan mixtures at medium and high doses exert significant eliminating cough and phlegm effects and strong anti-inflammatory property, and has a good security.