A broadly neutralizing human monoclonal antibody against the hemagglutinin of avian influenza virus H7N9 / 中华医学杂志(英文版)

BACKGROUND@#The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.@*METHODS@#H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.@*RESULTS@#The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.@*CONCLUSION@#The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.

Clinical features of corticobasal syndrome and associated chronic pain:analysis of 8 cases / 中华全科医师杂志

Objective:To investigate the clinical features and associated chronic pain in corticobasal syndrome (CBS).Methods:Clinical data of 8 patients diagnosed as probable CBS or possible CBS admitted to Beijing Hospital during January 2010 to June 2020 were retrospectively analyzed. The clinical information included sex, age, course of disease, chief complaint, neurological examination, blood biochemistry, tumor marker, infection and other laboratory tests; the neuropsychological evaluation included Mini-Mental State Examination (MMSE) scale and Hamilton Depression Scale (HAMD); the imaging studies included cranial magnetic resonance imaging (MRI) and/or 18F-Fluorodeoxyglucose positron emission tomography ( 18F-FDG PET). Results:The main clinical manifestations were asymmetrical movement disorders, including rigidity, tremor, myoclonus and abnormalities in posture and gait. Patients showed poor response to levodopa treatment. Among 8 patients, 7 had apraxia, 5 patients had alien hand, and 5 patients had various degrees of cognitive dysfunction. The cranial MRI demonstrated mild cerebral atrophy which was slightly more severe in the contralateral side of the initially affected limb in 7 of the 8 patients. The 18F-FDG PET scan revealed asymmetric decreased metabolism in the frontal, parietal, temporal, and occipital lobe, as well as in basal ganglia, which was more severe in the contralateral side of the initially affected limb in 5 of the 8 patients. Six of the 8 patients were associated with pain, including dystonic pain in 3 patients, neuropathic pain in 1 patient, musculoskeletal pain in 1 patient, and unexplained pain in 1 patient. Pain was the onset symptom in 1 patient and pain was relieved by taking levodopa in another patient. Conclusions:CBS is characterized by asymmetric dyskinesia and cognitive impairment, and often associated with apraxia, cortical sensory deficits, and alien limb. The MRI and PET are helpful for CBS diagnosis. Pain may be one of the common non-motor symptoms in CBS.

Structural changes of gut microbiota in patients with Parkinson's disease / 中华神经科杂志

Objective To investigate the structural changes of gut microbiota in patients with Parkinson's disease ( PD).Methods Twenty-four PD patients and 14 healthy controls from Beijing Hospital in 2015 were recruited in this cross-sectional study.The general clinical information was collected and all subjects were assessed with Parkinson's disease related scales.The gut microbiota status between two groups was analyzed after extracting feces'DNA and carrying out high-throughput sequencing of bacterial 16S rRNA.Results At the phylum level, actinobacteria (0.76%(0.13%, 1.85%) vs 0.14%(0.07%, 0.30%), Z＝2.784, P＜0.01) were significantly increased and bacteroidetes (57.28%(48.75%, 64.95%) vs 63.78%(56.72%, 68.21%), Z＝-4.963, P＜0.01) were significantly decreased in PD patients compared to healthy controls.At the class level, bacilli (0.52%(0.11%, 2.10%) vs 0.13%(0.05%, 0.16%), Z＝2.693, P＜0.01), negativicutes (5.04%(2.93%, 14.02%) vs 2.87%(1.46%, 4.43%), Z＝2.360, P＝0.018), actinobacteria (0.60%(0.10%, 1.59%) vs 0.12%(0.04%, 0.20%), Z＝2.512, P＝0.011 ), gammaproteobacteria ( 1.72%( 0.58%, 5.46%) vs 0.43%(0.24%, 2.19%), Z＝2.179, P＝0.029) were significantly increased in PD patients compared to healthy controls.At the family level, veillonellaceae (3.78%(0.53%, 13.82%) vs 0.49%(0.08%, 3.14%), Z＝2.754, P＜0.01), streptococcaceae (0.33%(0.09%, 0.69%) vs 0.19%(0.14%, 0.24%), Z＝1.770, P＝0.004), enterobacteriaceae (1.04%(0.40%, 4.95%) vs 0.20%(0.10%, 0.45%), Z＝2.784, P＜0.01 ), lactobacillaceae ( 0.079%( 0.014%, 0.575%) vs 0.003%(0.002%, 0.028%), Z＝3.119, P＜0.01), bifidobacteriaceae (0.60%(0.09%, 1.57%) vs 0.11%(0.03%, 0.19%), Z＝2.481, P＝0.012) were significantly increased and pasteurellaceae (0.009%(0.002%, 0.047%) vs 0.110%(0.022%, 0.898%), Z＝-2.545, P＝0.010) were significantly decreased in PD patients compared to healthy controls.Conclusions The structures of gut microbiota in PD patients and healthy controls were significantly different at the levels of phylum , class, and family.All these changes are potentially associated with the development of PD pathology.

Consensus and controversy about the study of mild behavioral impairment and dementia / 中华神经科杂志

Dementia is a clinical syndrome characterized by cognitive impairment and decreased daily activity.In recent years, more and more studies have shown that there are neuropsychiatric syndromes in people with normal cognitive function , thus increasing the risk of dementia.This population has been defined as mild behavioral impairment (MBI).MBI is now considered to be one of the prodromal symptoms of dementia, and there have been some researches and consensus on the definition , diagnosis and screening scale of MBI, but there are still a lot of controversies.For this reason, we systematically reviewed the research progress of MBI , to clarify the evidence on the definition , diagnostic criteria and screening methods of MBI, and to summarize the consensus and controversy of the research on the correlation between MBI and dementia, aiming to draw attention to the applicability and necessity of MBI diagnostic criteria in clinical practice.

Genetic origin of avian influenza A H7N4 virus causing a case of human infection in China , 2018 / 中华微生物学和免疫学杂志

Objective To analyze the molecular characteristics and genetic origin of a novel avian influenza A H7N4 virus casuing a case of human infection in China. Methods Specimens were collected from the patient and chickens and ducks kept by the patient and neighbours and then detected by real-time quantitative PCR. The original specimens and virus isolates were analyzed by next-generation sequencing technology to obtain viral whole-genome sequences. Pairwise sequence alignments and phylogenetic analysis were performed by BLASTs,ClustalX and MEGA 6. 1 softwares. Results In January 2018, a human case infected with avian influenza A H7N4 virus was confirmed. Seven H7N4 viruses were isolated from speci-mens collected from chicken and ducks kept in the patient`s backyard. H7N4 virus was a novel reassortant vi-rus with all eight gene fragments derived from wild waterfowl in Eurasia. HA protein contained a single basic amino acid residue R in cleavage site, suggesting that H7N4 virus was low pathogenic. The receptor-binding sites of HA had QSG at 226-228 residues, which indicated that the virus retained avian-type receptor speci-ficity (SAα2-3Gal). Different from H7N4 viruses in avian, the virus isolated from the patient had substitu-tion at position 627 ( E→K) in PB2 protein, which might increase its adaptation in human host. Conclusion This study reported a case of human infection with a novel reassortant avian influenza A H7N4 virus, which revealed that the traditional backyard breeding models might facilitate cross-species transmission of avian in-fluenza viruses in southern China.

Molecular characteristics of hemagglutinin gene of influenza A (H3N2) virus strains circulating in Jiangsu province, China, 2013-2014 / 中华微生物学和免疫学杂志

Objective To analyze the genetic characteristics and the evolution of the influenza A (H3N2) virus strains circulating in Jiangsu province between 2013 and 2014.Methods This study analyzed thirty-one representative strains of influenza A (H3N2) virus, which were isolated in different regions of Jiangsu province and during different time periods from 2013 to 2014.Results Genetic distances in nucleic acid and amino acid between a strain used for vaccine production (A/Texas/50/2012) and the 31 strains were 0.010 5 and 0.012 4.Similarities between them in nucleic acid and amino acid sequences were 97.9%-99.6% and 97.2%-99.3%.Phylogenetic analysis showed that the hemagglutinin (HA) genes of the 31 strains were divided into three different groups.Three strains isolated in 2013 and three strains isolated in 2014 belonged to Group 1 and Group 2, respectively, while the others belonged to Group 3.Three positive selection sites (237, 366 and 367) in HA protein were observed by REL model.Compared with the strain used for vaccine production, the 31 strains were characterized by amino acid substitutions (N128A/T and P198S/A) in HA protein and all of the mutations located in B-cell epitopes.The total number of mutation sites reached 24.Compared with the A/Texas/50/2012 strain, seven strains presented the glycosylation site 126NWT, and three strains showed disappeared glycosylation sites of 45NSS and 144NNS.Evaluation of vaccine efficacy for A(H3N2) virus strains showed that the vaccine efficacy was not very well.Conclusion The HA gene of A(H3N2) virus had undergone a greater variation and the vaccine efficacy was not very well in Jiangsu province during 2013 to 2014, which made the influenza A(H3N2) virus become the circulating strain.

Effects of hypertriglyceridemic-waist phenotype on cognitive function in patients with type 2 diabetes / 中华老年医学杂志

Objective To investigate the effect of hypertriglyceridemic waist(HTWC)phenotype on cognitive function in patients with type 2 diabetes.Methods According to the standard of plasma triglycerides concentration≥1.7 mmoL/L,waist circumference(WC)≥ 90 cm in men or ≥80 cm in women,304 patients with type 2 diabetes were divided into four groups:normal triglycerides and waist circumference group(group A,n =65),normal waist circumference and hypertriglyceridemia group (group B,n=53),abdominal obesity and normal triglycerides group(group C,n=114),and HTWC group(group D,n =72)for prospective studies.Patients in four groups were surveyed with Mini-mental state examination (MMSE)and Montreal cognitive assessment (MOCA).And changes of cognitive function among the four groups were compared.Results Total score for the MMSE was significantly lower in group D than in group A(27.1±1.9 vs.29.0±1.3,F=2.869,P=0.019).The subscales of attention and calculation(4.0± 1.4 vs.4.6±0.9,F=1.605,P=0.047)and recall(2.2± 0.9 vs.2.6±0.6,F=1.959,P=0.043) were significantly lower in group D than in group A.Total score for the MOCA was significantly lower in group D than in group A(23.4±3.9 vs.25.9±3.6,F =1.975,P=0.031).The subscales of visuospatial and executive(3.5 ± 1.4 vs.4.1 ± 0.9,F=1.537,P =0.048),attention(5.1±1.4 vs.5.7±0.9,F=1.660,P=0.048)and orientation(5.6±1.0 vs.6.0± 0.0,F=2.362,P=0.030)were significantly lower in group D than in group A.Conclusions There is a statistically more significant decline in cognitive function in patients with HTWC phenotype and the effective intervention and treatment are needed.

Effect of type 2 diabetes with hypertension on cognitive function——a study on elderly living in the communities of Beijing / 中华流行病学杂志

Objective To study the effects of type 2 diabetes (T2DM) with hypertension on cognitive function in those community-based elderly who were aged 60 and over,in Beijing.Methods 82 patients with T2DM,142 patients with both T2DM and hypertension and 277 normal controls were investigated in this study.Both methods as:the Montreal Cognitive Assessment (MoCA) and Mini-Mental Status Examination (MMSE) were used to determine cognitive change.Results The total MMSE scores showed significant decrease between T2DM with hypertension and controls [(28.42± 1.52) vs.(28.88± 1.47),P＜0.05].The MoCA score of the total scores [(25.20± 3.91) vs.(26.50 ± 3.29),P＜0.05],sub-scores of visuospatial,executive [(3.60± 1.56) vs.(3.96± 1.18),P＜0.05] and language [(2.10± 0.80) vs.(2.37± 0.80),P＜0.05] significantly decreased in T2DM patients with hypertension and in the normal controls.Data from the Multiple logistic regression analysis showed that older age and less education were risk factors for cognitive impairment.Conclusion T2DM and hypertension damaged the cognitive function of patients.

The study of association between genetic variants in sortilin-related receptor 1 and Alzheimer's disease / 中华老年医学杂志

Objective To investigate the association between gene polymorphism of sortilinrelated receptor 1 (SORL1) and Alzheimer' s disease by detecting a series of single nucleotide polymorphisms (SNPs).Methods The Snapshot method was used to genotypc 6 SNPs (SNP10,19,23,24,25,27) in SORL1 and the distributions of allele and genotype of the 6 SNPs were compared between AD patients and healthy control individuals.Results There were significant differences in the genotype distributions of SNP19,23,24 and 25 between AD patients and control group (all P＜0.01).Subjects with TT genotype in SNP19 had significantly lower risk for AD and was protective for AD (OR=0.089,95％CI:0.011-0.718,P＜0.01).The AT genotype in SNP23 (OR＝3.826,95％CI:1.388～10.544,P＜0.01),CT genotype in SNP24(OR=5.935,95％CI:1.774-19.853,P＜0.01)and CT genotype in SNP25(OR=5.754,95％CI:2.007-16.496,P＜0.01)had higher risks for AD.Conclusions SORL1 gene variants of SNP19,23,24 and 25 might be the important risk factors for late-onset AD.

Association study of interleukin-1 genotypes with Alzheimer′s disease / 中华老年医学杂志

Objective To explore the association of interleukin (IL)-1 genotypes with Alzheimer′s disease (AD). Methods Using polymerase chain reaction and restriction fragment length polymorphism, the IL-1A (-889) and IL-1B (+3953) genotypes in 84 cases of AD and 139 controls were detected and analyzed. Results The frequencies of IL-1A(- 889) C/C, C/T and T/T genotypes were 72.6% and 84.2%, 23.8% and 14.4%, 3.6% and 1.4% in AD cases and controls respectively. The genotypes frequencies of IL-1A (-889) C/C, C/T and T/T in AD cases were similar to that of controls (χ2=4.53, P＞0.05), but the frequencies of IL-1A (-889) T allele were significantly higher in AD cases than in controls (15.5% vs. 8.6%, χ2=4.93, P＜0.05). The frequencies of IL-1B (+3953) C/T genotypes and T allele were also significantly higher in AD cases than in controls (16.7% vs. 6.5%, 8.3% vs. 3.2%, χ2=5.88,5.56, both P＜0.05). Conclusions IL-1 genotypes are associated with AD. IL-1 genotypes may play an important role in the development of AD.

Influence of comfortable nursing on life quality and satisfaction degree of patients with malignant tumor undergoing chemotherapy / 中国实用护理杂志

Objective To explore the role of comfortable nursing in patients with malignant tumor undergoing chemotherapy and the quality of life and satisfaction degree in patients after chemotherapy. Methods 100 patients with malignant tumor undergoing chemotherapy were divided randomly into the observation group and the control group(each had 50 cases). The observation group took the comfortable nursing, the control group was applied with the traditional nursing method, their comfort degree,satisfaction degree and life quality after chemotherapy were observed and compared. Results Comparing the results of two groups of patients, the satisfaction degree of the observation group was significantly higher than the control group, the scores of life quality for the observation group and the control group were (45.2±5.1 ) and (34.1 ±4.6) respectively. Conclusions Comfortable nursing for patients with malignant tumor undergoing chemotherapy may improve their comfort degree, satisfaction degree and life quality, and hence is worthy of being recommended in clinical practice.