Diagnosis and treatment of tuberculous meningitis / 中华神经科杂志

Tuberculous meningitis (TBM) is one of the most serious and lethal diseases in neurology. The early diagnosis and treatment of TBM still faces severe challenges. Acid-fast staining of cerebrospinal fluid and culture of Mycobacteriumtuberculosis are the "gold standard" for the diagnosis of TBM, but lack sensitivity. With the application of metagenomic next-generation sequencing technology, significant advances have been made in the early diagnosis of TBM. The optimal treatment regimen for TBM remains to be further explored and studied. This article intends to provide an overview of the pathogenesis, pathology, clinical manifestations, diagnosis and treatment advancement of TBM, and provide guidance for clinical practice.

Sialic acid-binding immunoglobulin-like lectin 9 as a potential therapeutic target for chronic obstructive pulmonary disease / 中华医学杂志(英文版)

Chronic obstructive pulmonary disease (COPD) has become the third-leading cause of death worldwide, which is a severe economic burden to the healthcare system. Chronic bronchitis is the most common condition that contributes to COPD, both locally and systemically. Neutrophilic inflammation predominates in the COPD airway wall and lumen. Logically, repression of neutrophilia is an essential fashion to COPD treatment. However, currently available anti-neutrophilic therapies provide little benefit in COPD patients and may have serious side effects. Thus, there is an urgent need to explore an effective and safe anti-neutrophilic approach that might delay progression of the disease. Sialic acid-binding immunoglobulin-like lectin (Siglec)-9 is a member of the Siglec cell surface immunoglobulin family. It is noteworthy that Siglec-9 is highly expressed on human neutrophils and monocytes. Ligation of Siglec-9 by chemical compounds or synthetic ligands induced apoptosis and autophagic-like cell death in human neutrophils. Furthermore, administration of antibody to Siglec-E, mouse functional ortholog of Siglec-9, restrained recruitment and activation of neutrophils in mouse models of airway inflammation in vivo. Given the critical role that neutrophils play in chronic bronchitis and emphysema, targeting Siglec-9 could be beneficial for the treatment of COPD, asthma, fibrosis, and related chronic inflammatory lung diseases.

Association between socioeconomic status and chronic obstructive pulmonary disease in Jiangsu province, China: a population-based study / 中华医学杂志(英文版)

BACKGROUND@#Chronic obstructive pulmonary disease (COPD) is a common public health problem worldwide. Recent studies have reported that socioeconomic status (SES) is related to the incidence of COPD. This study aimed to investigate the association between SES and COPD among adults in Jiangsu province, China, and to determine the possible direct and indirect effects of SES on the morbidity of COPD.@*METHODS@#A cross-sectional study was conducted among adults aged 40 years and above between May and December of 2015 in Jiangsu province, China. Participants were selected using a multistage sampling approach. COPD, the outcome variable, was diagnosed by physicians based on spirometry, respiratory symptoms, and risk factors. Education, occupation, and monthly family average income (FAI) were used to separately indicate SES as the explanatory variable. Mixed-effects logistic regression models were introduced to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for examining the SES-COPD relationship. A pathway analysis was conducted to further explore the pulmonary function impairment of patients with different SES.@*RESULTS@#The mean age of the 2421 participants was 56.63 ± 9.62 years. The prevalence of COPD was 11.8% (95% CI: 10.5%-13.1%) among the overall sample population. After adjustment for age, gender, residence, outdoor and indoor air pollution, body weight status, cigarette smoking, and potential study area-level clustering effects, educational attainment was negatively associated with COPD prevalence in men; white collars were at lower risk (OR: 0.60, 95% CI: 0.43-0.83) of experiencing COPD than blue collars; compared with those within the lower FAI subgroup, participants in the upper (OR: 0.68, 95% CI: 0.49-0.97) tertiles were less likely to experience COPD. Such negative associations between all these three SES indicators and COPD were significant among men only. Education, FAI, and occupation had direct or indirect effects on pulmonary function including post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), FEV1, FVC, and FEV1 percentage of predicted. Education, FAI, and occupation had indirect effects on pulmonary function indices of all participants mainly through smoking status, indoor air pollution, and outdoor air pollution. We also found that occupation could affect post-bronchodilator FEV1/FVC through body mass index.@*CONCLUSIONS@#Education, occupation, and FAI had an adverse relationship with COPD prevalence in Jiangsu province, China. SES has both direct and indirect associations with pulmonary function impairment. SES is of great significance for COPD morbidity. It is important that population-based COPD prevention strategies should be tailored for people with different SES.

Stem cell therapy for chronic obstructive pulmonary disease / 中华医学杂志(英文版)

Chronic obstructive pulmonary disease (COPD), characterized by persistent and not fully reversible airflow restrictions, is currently one of the most widespread chronic lung diseases in the world. The most common symptoms of COPD are cough, expectoration, and exertional dyspnea. Although various strategies have been developed during the last few decades, current medical treatment for COPD only focuses on the relief of symptoms, and the reversal of lung function deterioration and improvement in patient's quality of life are very limited. Consequently, development of novel effective therapeutic strategies for COPD is urgently needed. Stem cells were known to differentiate into a variety of cell types and used to regenerate lung parenchyma and airway structures. Stem cell therapy is a promising therapeutic strategy that has the potential to restore the lung function and improve the quality of life in patients with COPD. This review summarizes the current state of knowledge regarding the clinical research on the treatment of COPD with mesenchymal stem cells (MSCs) and aims to update the understanding of the role of MSCs in COPD treatment, which may be helpful for developing effective therapeutic strategies in clinical settings.

Computed tomography-identified phenotypes of small airway obstructions in chronic obstructive pulmonary disease / 中华医学杂志(英文版)

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characteristic of small airway inflammation, obstruction, and emphysema. It is well known that spirometry alone cannot differentiate each separate component. Computed tomography (CT) is widely used to determine the extent of emphysema and small airway involvement in COPD. Compared with the pulmonary function test, small airway CT phenotypes can accurately reflect disease severity in patients with COPD, which is conducive to improving the prognosis of this disease. CT measurement of central airway morphology has been applied in clinical, epidemiologic, and genetic investigations as an inference of the presence and severity of small airway disease. This review will focus on presenting the current knowledge and methodologies in chest CT that aid in identifying discrete COPD phenotypes.

Clinical analysis of dementia with lewy body / 中国神经精神疾病杂志

Objective To investigate the clinical features,diagnosis,treatment and prognosis of Dementia with Lewy Body (DLB) in order to improve doctors' understanding and experience.Methods Thirteen cases of clinicall diagnosed DLB were analyzed.The clinical manifestations,neurological examination,laboratory tests,treatment and prognosis were analyzed.Results All of 13 patients had fluctuating dementia.Among them,11 were diagnosed with probable DLB,and 2 were diagnosed with possible DLB.There were 8 cases (8/13) with volatility cognitive impairment,8 cases (8/13) with Parkinson's syndrome,8 casess (8/13) with visual hallucinations,13 cases (13/13) with memory loss,4 patients with limb tremor (4/13),5 cases with delirium (5/13),3 cases with increased sleep (3/ 13),1 case with silence (1/13),9 cases with anxiety and depression (9/13),one case with dizziness (1/13),6 cases with abnormal dysplasia (6/13),and one case with abnormal sensitive to diazepam (1/13).The cognitive function fluctuated,the condition deteriorated and two patients died during the follow-up from 6 months and 5 years.Conclusions Lewy body dementia is an irreversible and progressive neurodegenerative disease.Comprehensive understanding of its clinical features is helpful for the early diagnosis and treatment,which may in turn improve the prognosis.

Intervention with flexible bronchoscopy in patiens with respiratory failure caused by tracheal stenosis / 中华急诊医学杂志

Objective To investigate the efficiency and safety of intervention with flexible bronchoscope under general anesthesia by using laryngeal mask in patients with severe tracheal stenosis induced respiratory failure.Methods A total of 16 in-patients with respiratory failure caused by severe tracheal stenosis admitted from September 2009 to March 2012 were retrospectively reviewed.A comprehensive bronchoscopic intervention for the complete patency of airway was successfully performed with various techniques such as cryotherapy,electrocautery,balloon dilatation,and implantation of selfexpanding metal stents under genersl anesthesia by using laryngeal mask.The efficiency of comprehensive bronchoscopic intervention and dyspnea score were evaluated by chest CT scan and bronchoscopic examination before and after the treatment.Data were expressed as ((x-)± s).Paired t test was used for statistical analysis of the data.Results The degrees of tracheal stenosis and dyspnea score before and after intervention were (85.0±8.4)％ vs.(20.9±7.6)％ (P＜0.01) and (3.9±0.3vs.2.4±0.5,P＜ 0.01),respectively.There were no life-threatening complications occurred including massive haemorrhage.Conclusions It is an effective and safe technique to resolve the tracheal stenosis-induced respiratory failure with intervention by using flexible bronchoscope under general anesthesia with laryngeal mask,and it is a promising interventional treatment for clinic application.

Significance of serum and pleural effusion levels of related factors in differential diagnosis of tuberculosis and malignant tumor / 中华传染病杂志

Objective To evaluate the significance of combined detection of leptin (LEP),tumor necrosis factor-α (TNF-α),carcino-embryonic antigen (CEA),C-reactive protein (CRP) and interleukin-6 (IL-6) in both serum and pleural effusion in differential diagnosis of tuberculosis and malignant tumor.Methods LEP,TNF-α,CEA,CRP and IL-6 levels in both pleural fluid and serum samples from 95 cases of pleural effusion (including 54 cases of malignant pleural effusion and 41 cases of tuberculous pleural effusion) were detected by immunoturbidimetry and enzyme linked immunosorbent assay (ELISA),respectively.The data with normal distribution and skewed distribution were analyzed by t test and rank sum test,respectively.Results In patients with tuberculosis and malignant tumor,significant difference was observed in serum LEP [(0.42±0.47) ng/ mL vs (1.80±0.91) ng/mL,t=9.666,P=0.0001],TNF-α [(30.88±24.72) pg/mL vs (59.83±30.93) pg/mL,t=4.917,P=0.0001],CEA [(0.22±0.30) ng/mL vs (5.67±3.60) ng/mL,t=ll.074,P=0.0001] and IL-6 [(146.48±54.90) pg/mL vs (20.51±11.62) pg mL,t=-14.449,P 0.0001] levels.Serum CRP levels of patients with tuberculosis and malignant tumor were comparable [(32.78±22.43) mg/mL vs (37.80±16.74) mg/mL,t =1.249,P=0.215].In pleural effusion of the two groups (tuberculous pleural effusion vs malignant pleural effusion),LEP [(0.69±0.65) ng mL vs (4.33±2.16) ng mL,t 11.711,P 0.0001],TNFα [(20.60±17.80) pg/ mL vs (40.40±20.60) pg/mL,t=4.926,P=0.0001],CEA [(0.10±0.17) ng/mL vs (4.02±2.49) ng/ mL,t=11.537,P=0.0001] and IL-6 [(87.80±48.40) pg/mL vs (9.30±5.50) pg/mL,t =-10.333,P=0.0001] levels were significantly different,while CRP levels [(27.34±17.93) mg mL vs (29.60± 13.40) mg mL,t =0.709,P =0.102] were comparable.Conclusion LEP,TNF-α,and CEA levels in both pleural effusion and serum samples from patients with malignant tumor are higher than those with tuberculosis,while IL 6 levels are quite opposite.Combined detection of these parameters can help the differential diagnosis of tuberculous and malignant pleural effusion.

The construction, expression and immunological activity study of eukaryotic vector expressing cytotoxic T lymphocyte-associated antigen-4 ScFv and hepatitis B virus-S gene / 中华传染病杂志

Objective To construct the eukaryotic vector that expressing hepatitis B virus (HBV) S and the single fragment of variety chain (ScFv) of monoclonal antiboy against cytotoxic Tlymphocyte-associated antigen-4 (CTLA-4) and to analyze the immunological activity of recombinant S-ScFv protein.Methods The oringially constructed pSect2/ScFv4F10 and pSect2/S were double enzyme digested by Sfi I and Hind Ⅲ,respectively.Then the HBV S gene was cloned into the pSect2/ScFv4F10 vector.The pSect2/ScFv4F10 and pSect2/S-ScFv4F10 were expressed in Chinese hamster ovary (CHO) cells,and the expressed proteins were verified through sodium dodecyl sulfatepolyacrylamide gelelectrophoresis(SDS-PAGE)andWesternblotting.Afterultrafiltration concentration and affinity chromatography,the biological affinity of the expressed ScFv4F10 and S-ScFv4F10 proteins were examined by competitive enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) technology.The comparison between groups was done by One-way ANOVA.ResultsThe eukaryotic expression vector of pSect2/S-ScFv4F10was successfully constructed,and relative molecular mass of the expressed protein of S-ScFv4 F10 was about 52 000 that analyzed by SDS-PAGE and Western blotting.With the fixed concentration of 4F10-mAb against CTLA-4,the A570 value of the mixed reaction with purified CTLA-4 antigen gradually increased with the decrease of ScFc fusion protein proportion; when the molar ratio of ScFv,S-ScFv4F10∶4F10=2∶1,the competitiveinhibitionratesagainst 4F10conjugatedantigenwere72.6％and64.5％,respectively.The affinity constants of association kinetics for CTLA-4 mAb,ScFv4F10 and S-ScFv4F10 with CTLA-4 antigen were 7.29 × 108 mol/L,9.52 × 106 mol/L and 2.04 × 106 mol/L,respectively,and the dissociation constants of KD were 1.40 × 10-9 mol/L,1.05 × 10-7 mol/L and 4.91 × 10-7 mol/L,respectively.ConclusionsThe eukaryotic expression vector of pSect2/S-ScFv4F10is successfully constructed,and the recombinant protein of S-ScFv4 F10 has a fairly high affinity with CTLA-4 antigen.

Expression of recombinant protein VP1and its application in developing enzyme-linked immunoassay for Echovirus 30 / 中华临床感染病杂志

Objective To express VP1recombinant protein of Echovirus 30 (ECHO30) in E.coli BL21(DE3) and to develop an enzyme-linked immunoassay (EIA) based on the recombinant antigen for detecting antibodies to ECHO30.Methods The target VP1gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR).The PCR products of the gene were inserted into pET44a vector,and then expressed in E.coli BL21( DE3 ).The purified recombinant protein was used for the development of EIA.Results The molecular weight of the recombinant protein was 95 000,and the antigenicity of which was identified by Western blot and EIA.Conclusion The recombinant protein VP1has been successfully expressed and purified,which can be used as diagnostic antigen.

Effects on HepG2 cells growth of the different domains of genotype 1b hepatitis C virus core proteins / 中华微生物学和免疫学杂志

Objective To study the function of core protein (CORE) of genotype 1b hepatitis C virus (HCV) of different strains (T: derived from tumor tissues; NT: derived from non-tumor tissues; C191: HCV-J6) and different domains (1-172, 1-126, 1-58, 59-126, 127-172 AA) of T CORE in the pathogenesis of HCV infection and to find the therapy target. Methods Different truncated genotype 1b HCV CORE eukaryotic expression plasmids (T, NT, C191) and different domains of T CORE were constructed and transfected to HepG2 cells. Cell apoptosis and necrosis were quantified by flow cytometry. Cell growth curves were observed with real time cell growth instrument. Results COREs from different strains of genotype 1b and different domains of CORE induced cell apoptosis and necrosis, and inhibited HepG2 cell growth at different levels. CORE derived from T induced apoptosis and necrosis and inhibited cell growth higher than that derived NT and C191. N terminal 1-58 AA of CORE derived from T induced cell apoptosis and necrosis and inhibited cell growth higher than any other domains. Conclusion COREs from different strains of genotype 1b HCV and different domains of CORE from the same HCV strain play different roles in their molecular pathogenesis of HCV. Among different domains of CORE, N terminal 1-58 AA might play an important role in its pathogenesis and be one target of gene therapy.

Construction and identification of recombinant adenovirus vector carrying a N-terminal phosphorylation sites-deleted human I?B? mutant gene / 中国病理生理杂志

AIM:To optimize the I?B? mutant(I?B?M)gene derived from human placenta tissue by deleting N-terminal phosphorylation sites of serine 32/36,and to construct and identify its replication-deficient recombinant adenovirus(AdI?B?M).METHODS:The I?B?M gene(203-1 003 bp)was acquired by positional cloning,followed by subcloning it into pShuttle and pGEM-T vectors for further PCR,double digestion,DNA sequencing and homology analysis.Subsequently,the expression unit of pShuttle-I?B?M containing CMV promoter,I?B?M cDNA and poly A signals was inserted into Ad5 vector,after which the resultant recombinant adenovirus AdI?B?M was packaged in 293 cells by cotransfection with lipofectamine.Western blotting analysis and electrophoretic mobility shift assay were utilized to detect the AdI?B?M-mediated expression of I?B?M gene in 293 cells and its suppressive effect on phorbol myristate acetate(PMA)-induced nuclear factor ?B(NF-?B)activation in ECV304 cells,respectively.RESULTS:The relevant nucleotide and amino acid sequence of I?B?M gene was consistent with that of GenBank(accession number M69043).The titer of the prepared AdI?B?M was 4.0?10 12 pfu/L.Moreover,the I?B?M gene was expressed in 293 cells,and potently inhibited the PMA-induced NF-?B activation in ECV304 cells in a dose-dependent manner.CONCLUSION:AdI?B?M is a nonvel vector for both efficient transfer and expression of I?B?M gene as well as specific inhibition of NF-?B activity,providing a promising future for gene therapy of asthma.