Potential treatment with Chinese and Western medicine targeting NSP14 of SARS-CoV-2 / 药物分析学报

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious global health threat.This raises an urgent need for the devel-opment of effective drugs against the deadly disease.SARS-CoV-2 non-structural protein 14 (NSP14)carrying RNA cap guanine N7-methyltransferase and 3'-5'exoribonuclease activities could be a potential drug target for intervention.NSP14 of SARS-CoV-2 shares 98.7％ of similarity with the one (PDB 5NFY) of acute respiratory syndrome (SARS) by ClustalW.Then,the SARS-CoV-2 NSP14 structures were modelled by Modeller 9.18 using SARS NSP14 (PDB 5NFY) as template for virtual screening.Based on the docking score from AutoDock Vina1.1.2,18 small molecule drugs were selected for further evaluation.Based on the 5 ns MD simulation trajectory,binding free energy (AG) was calculated by MM/GBSA method.The calculated binding free energies of Saquinavir,Hypericin,Baicalein and Bromocriptine for the N-terminus of the homology model were-37.2711 ± 3.2160,-30.1746 ± 3.1914,-23.8953 ± 4.4800,and-34.1350 ± 4.3683 kcal/mol,respectively,while the calculated binding free energies were-60.2757 ± 4.7708,-30.9955 ± 2.9975,-46.3099 ± 3.5689,and-59.8104 ± 3.5389 kcal/mol,respectively,when binding to the C-terminus.Thus,the compounds including Saquinavir,Hypericin,Baicalein and Bromocriptine could bind to the N-terminus and C-terminus of the homology model of the SARS-CoV-2 NSP14,providing a candidate drug against SARS-CoV-2 for further study.

Different distributions of nerve demyelination in chronic acquired multifocal polyneuropathies / 中华医学杂志(英文版)

BACKGROUND@#Multifocal motor neuropathy (MMN), Lewis-Sumner syndrome (LSS), and many chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) are representative of acquired multifocal polyneuropathy and are characterized by conduction block (CB). This retrospective study aimed to investigate the demyelinating distribution and the selective vulnerability of MMN, LSS, and CIDP with CB (CIDP-CB) in nerves.@*METHODS@#Fifteen LSS subjects (107 nerves), 24 MMN subjects (176 nerves), and 17 CIDP-CB subjects (110 nerves) were included. Their clinical information was recorded, blood and cerebrospinal fluid tests were conducted, and nerve conductions of the median, ulnar, radial, peroneal, and tibial nerves were evaluated. CB, temporal dispersion, distal motor latency (DML), and F-wave latency were recorded, and nerve conduction velocity, terminal latency index, and modified F-wave ratio were calculated.@*RESULTS@#CB was more likely to occur around the elbow in CIDP-CB than in MMN (78.6% vs. 6.8%, P < 0.01) but less likely to occur between the wrist and the elbow than in LSS (10.7% vs. 39.3%, P < 0.05). Tibial nerve CB was most frequently observed in MMN (47.4%, P < 0.05). CIDP-CB was characterized by a prolonged DML in all nerves, and slow motor nerve velocity of the upper limb was significant when CB nerves were excluded (P < 0.05).@*CONCLUSIONS@#We report the different distributions of segmental and diffuse demyelination of the ulnar and tibial nerves in LSS, MMN, and CIDP-CB. These distinct distributions could help in differentiating among these conditions.

Correlation between blood-brain barrier permeability and physical disability in patients with neuromyelitis optica spectrum disorders / 上海交通大学学报（医学版）

Objective· To explore association between blood-brain barrier (BBB) permeability and physical disability in patients with neuromyelitis optica spectrum disorders (NMOSD).Methods· Clinical data of 105 patients with NMOSD was retrospectively analyzed in Department of Neurology at Changhai Hospital,Second Military Medical University and Renji Hospital,Shanghai Jiao Tong University School of Medicine from June 2009 to June 2016.According to the difference between the expanded disability status scale (EDSS) scores when discharged from hospital and when admitted to hospital,NMOSD patients were divided into disability-reduction group and disability-exacerbation group,and their clinical characteristics were compared between the two groups,then association between BBB permeability and physical disability was analyzed.Results · Between the disabilityreduction group and the disability-exacerbation group,there was no significant difference in gender,age,disease duration,inducing factor,clinical symptoms,and medication (all P＞0.05),and the abnormal rates of thoracic spinal cord in clinical examination were statistically different (P=0.023).There was no significant difference in biochemical data between the two groups (P＞0.05),and a statistically significant difference was observed in the rate of cerebrospinal/serum albumin ratio (QALB) in the cerebrospinal fluid examination (P=0.042).The percentages of exacerbation of disability in the QALB normal and high groups were 27.60％ (16/58) and 46.80％ (22/47),respectively,and there was a statistically significant difference between the two groups (x2=4.150,P=0.042).BBB permeability was positively correlated with physical disability (r=0.299,P=0.042).Conclnsion · The higher the BBB permeability of NMOSD patients on admission is,the higher the degree of physical disability is.The difference in BBB permeability provides key clues to the investigation of the immunological mechanisms of physical disability in NMOSD patients.

Role of B lymphocytes in pathogenesis of neuromyelitis optica spectrum disorder / 上海交通大学学报（医学版）

The neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of central nervous system autoimmune diseases caused by humoralmediated immunity.NMOSD is characterized by specific expression of aquaporin-4 (AQP-4) antibody and involvement of optic nerve and spinal cord.However,the expression level of AQP-4 antibody is not directly proportional to disease activity and recurrence rate,suggesting that multiple mechanisms have been involved in mediating the process of disease.Many evidences of clinical and basic experiments indicated that B lymphocytes play an important role in the pathogenesis of NMOSD.This paper mainly summarized the role of B lymphocytes in the pathogenesis of NMOSD,including aspects of antigen presentation,humoral immunity,regulatory B cell effect and B cell immune tolerance.

Associations of MRI-lesions and clinical features with disability in Chinese patients with multiple sclerosis

Objective: To analyze associations of MRI-lesions and clinical features with disability in patients with multiple sclerosis (MS) in Shanghai, China. Methods: We studied patients with MS, identified from a survey in Shanghai, whose sites of lesions in the CNS was based on the MRI examinations. Associations between MRI-lesions, various clinical variables and the severity of disability were analyzed with univariate and multivariate logistic regression analysis. Results: There were 210 patients in this study. The disability of the patients with lesions confined to the spinal cord was significantly more severe than those with lesions in the brain (p < 0.008). Current age (OR: 1.041, 95% CI: 1.007~1.077), MS duration (OR: 1.082, 95% CI: 1.011~1.159) and MRI-lesions in the spinal cord (OR: 2.441, 95% CI: 1.039~5.737) were significantly associated with severity of disability on multivariate logistic regression analysis. Conclusion: MRI-lesions in the spinal cord, older age, a longer MS duration were significantly associated with a more severe disability in this MS study in Shanghai China.

A cohort study on the relationship between cerebrovascular hemodynamic changing and risk of stroke / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the role of cerebrovascular hemodynamic indexes (CVHI) changing in stroke and to provide reference for stroke prevention and risk factor study.</p><p><b>METHODS</b>From 2003 to 2004, participants aged 40 years and above in two communities in Fengxian district were recruited by cluster sampling. Risk factors of stroke and CVHI were investigated and checked during baseline investigation. A total of 10 565 individuals completed the survey and met the inclusion criterion. After baseline investigation, the cohort was followed up for stroke occurrence. Relative risk (RR) of CVHI and common risk factors were estimated by cohort study design.</p><p><b>RESULTS</b>Age of the cohort was (56.2 ± 11.4) years. 4444 (42.1%) were males and 6121 (57.9%) were females. Total follow-up duration was 67 885.7 person-years. A total of 195 stroke cases occurred and incidence density of stroke was 287.2 per 100 000 person-years. Stroke incidence in exposure groups of hypertension, heart disease and alcohol drinking was 3.47% (108/3118), 2.96% (21/710) and 2.50% (47/1882), respectively. The incidence in corresponding non-exposure group was 1.17% (87/7448), 1.77% (174/9855) and 1.70% (148/8683) respectively. There was significant difference between 2 groups (χ(2) value was 62.72, 4.56 and 4.94, respectively, P < 0.05). Stroke incidence in CVHI score < 25, 25 - 49, 50 - 74 and ≥ 75 groups was 9.12% (59/647), 5.68% (44/775), 2.52% (39/1545) and 0.72% (53/7403)(χ(2)trend = 273.57, P < 0.05), respectively. Incidence of stroke in 40 - 49, 50 - 59, 60 - 69, ≥ 70 years age group was 0.22% (8/3565), 1.28% (43/3357), 2.71% (50/1848) and 5.88% (94/1600) (χ(2)trend = 181.48, P < 0.05), respectively. Multiple Cox regression analysis indicated that RR (95%CI) value of hypertension and cigarette smoking was 1.40(1.02 - 1.92) and 1.59(1.19 - 2.12), respectively when comparing with non-exposure group. RR (95%CI) value in CVHI score < 25, 25 - 49 and 50 - 74 points group were 6.15 (4.08 - 9.26), 4.55 (2.98 - 6.96) and 2.68 (1.75 - 4.09), respectively when comparing with the score ≥ 75 points group. RR (95%CI) value in age 50 - 59, 60 - 69 and ≥ 70 years group was 4.61 (2.16 - 9.82), 7.81 (3.67 - 16.60) and 13.49(6.44 - 28.24), respectively when comparing with below 40 years group.</p><p><b>CONCLUSION</b>CVHI score is the strong independent predictive factor and hypertension, cigarette smoking and age are the independent risk factors of stroke.</p>

Clinical and genetic study of spinocerebellar ataxia type 7 in East Asian population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Spinocerebellar ataxia type 7 (SCA7) is known as an autosomal dominant cerebellar ataxia; patients with genetically confirmed diagnoses of SCA7 have increased rapidly in recent years. However, SCA7 is a rare subtype of SCA, and most data available about SCA7 are those of white people. The aim of the present study was to systematically review the prevalence and clinical and genetic aspects of SCA7 patients in East Asian population.</p><p><b>METHODS</b>A search for publications on SCA7 was performed by using the "PubMed" database with the published language limited in English. Publications mainly focusing on the prevalence of SCA7 in patients with SCA and the clinical and genetic features of SCA7 patients were fully reviewed and analyzed.</p><p><b>RESULTS</b>The prevalence of SCA7 in SCA patients ranged from 0 to 7.7%, which was similar to those reported previously. The clinical manifestations were typically present at the 30's of its victims (median, 29 years; interquartile range (IQR), 19.5-36.5 years), and the symptoms appeared 15 years ((15.17+/-4.22) years) earlier on average in the offspring than in the parents. Gait ataxia and visual impairment were both found in all patients of whom the clinical features were described. Mutant SCA7 alleles contained 40-100 CAG repeats, with a median of 47 repeats (IQR, 44.5-50.0); and the offspring had 13 more repeats on average compared with their parents (12.62+/-19.03). A strong negative correlation was found between CAG repeat size and the onset age of patients (r=-0.739, P=0.000). In addition, no significant difference was found in CAG repeat sizes between patients with visual impairment as the initial symptom and those with gait disturbance as their initial symptom (P=0.476).</p><p><b>CONCLUSIONS</b>The prevalence of SCA7 in SCA patients, the age at onset and CAG repeats of SCA7 patients in East Asia are consistent with those of white people. However, larger population study is needed to assess the correlation between the CAG repeat size and initial symptoms of SCA7 patients in East Asia.</p>

Preliminary clinical and genetic study of a family with ophthalmoplegia,dysphagia and facial weakness / 中华神经科杂志

Objective To investigate the features of familiar facial palsy,ophthalmoplegia and dysphagia characterized by autosomal dominant inheritance in a family and to discuss the classification and pathogenesis of the disease.Methods Clinical,electrophysiological,pathological examinations were performed and blood samples were obtained from 5 patients and 26 family members.PCR protocol was used to identify a certain gene. Results In the 5 patients receiving physical examination,all had ptosis,external ophthalmoplegia,facial paralysis,dyphagia,hoarseness,decreased pharyngeal reflex;4 had amyotrophy of muscle of tongue,temporal nuscle,masseter and muscles of distal lower limbs;3 had proximal limb asthenia and distal limbs amyotrophy.Compared to those of oculopharyngeal muscular dystrophy(OPMD)with similar symptoms and signs,both electrophysiological manifestation and pathological findings of the family members supported the diagnosis of muscular dystrophy,but the(GCG)6(GCA)3GCG in the first exon of PABPN1 mutated neither in normal family members nor in patients.Conclusions This family presents clinical manifestations somewhat resembling to those of OPMD and distinctive to other disorders,but has a totally different genetic background from OPMD.It may be a new subtype of muscular dystrophy.

Clinical and gene study on one pedigree of hereditary spinocerebellar ataxia type 7 / 中华神经科杂志

Objective To summarize the clinical characteristics and make genetic diagnosis in the patients with hereditary spinocerebellar ataxia type 7 (SCA7).Methods Pedigree analysis and clinical examination were performed in one family with SCA7 by clinical findings,of which retinal morphology and visual electrophysiology were available on part numbers.The polymorphic cytosine adenine guanine (CAG) repeats in the encode region of SCA7 gene were detected by combining polymerase chain reaction with deoxyribonucleic acide (DNA) sequencing on 19 familial numbers and 12 controls.Results 6 patients were identified,who manifesting cerebellar ataxia,decreased visual acuity and colour vision defect,as was pigmentary retinopathy on fundoscopy;The 6 patients had not only extinction of the electroretinogram (ERG) but also remarkably reduced amplitudes of oscillatory potentials and flash-visual evoked potentials. On normal alleles CAG repeat size ranges from 8 to 25 repeats,wherease on mutated alleles of the 6 numbers it ranges from 50 to 97 repeats.The 6 numbers were diagnosised as SCA7 patients.One asymptomatic individual of this family,who displayed a normal allele with 18 CAG repeats and another containing abnormal expantion of 56 repeats,was diagnosised as a asymptomatic carrier whose age maybe still below the age of onset.Conclusion The clinical manifestations of SCA7 are heterogeneous,and the detection of CAG repeats can provide an effective way for the gene diagnosis and the prediction of asymptomatic patients.

Isolation and Identification of Antimicrobial Activity of Symbiotic and Epiphyte Microorganisms on Marine Organisms / 微生物学通报

The 125 strains of the symbiotic and epiphyte microorganisms were isolated from marine organisms (Sea cucumber, Sea urchin, Sea anemone, Sea actinia, Ulra, Sargassum, Undaria). Among them,21 strains of bacteria,8 strains of actinomycetes and 2 strains of fungi have shown to have antagonistic activity on bacterial or fungal growth. In the 21 strains of bacteria, 7 strains belong to Bacillus sp., 11 strains belong to Vibro sp., and 3 strains belong to Pseudomonas sp.. In the 8 strains of actinomycetes, 5 strains belong to Streptomyces sp., 3 strains belong to Micromonospora sp.. 2 strains of fungi belong to Penicillum sp..

A incidência de cesáreas e a remuneraçäo da assistência ao parto / Incidence of cesarean section and the remuneration of the assistance to delivery

Estuda-se a incidência de cesáreas no total de partos ocorridos nos hospitais de Ribeiräo Preto (SP) antes e depois da instituiçäo da equiparaçäo da remuneraçäo ao parto por via baixa e cesariano pela Previdência Social. Esta medida da Previdência Social näo alterou a tendência à elevaçäo da incidência de cesáreas no período do estudo (1978-1981). Observou-se a existência de um gradiente na taxa de cesáreas, sendo mais baixa a incidência média de cesáreas entre as pacientes näo-pagantes e a mais elevada nas pacientes particulares, ficando a incidência de cesáreas entre as pacientes previdenciárias em uma posicäo intermediária. Atribui-se este gradiente a diferenças na modalidade de assistência segundo a classe social das pacientes

A incidência de cesáreas e a remuneraçäo da assistência ao parto / The occurrence of cesarean sections and the remuneration of labor assistance

Os autores estudam a incidência de cesáreas no total de partos ocorridos nos hospitais de Ribeiräo Preto (SP), antes e depois da instituiçäo da equiparaçäo da remuneraçäo ao parto por via baixa e por cesariana pela Previdência Social. Esta medida da Previdência Social näo alterou a tendência à elevaçäo da incidência de cesáreas no período do estudo (1978-1981). Observou-se a existência de um gradiente na taxa de cesáreas, sendo mais baixa a incidência média de cesáreas entre as pacientes näo-pagantes e a mais elevada nas pacientes particulares, ficando a incidência de cesáreas entre as pacientes previdenciárias em uma posiçäo intermediária. Atribuiu-se este gradiente a diferenças na modalidade de assistência, segundo a classe social das pacientes