Tuberculosis (TB) remains one of the biggest infectious killers worldwide. Vaccine is the most satisfactory tool for prevention of TB; however, Bacillus Calmette-Guérin (BCG), the widely used vaccine in clinical for the prevention of TB, has limitations in protective effects. Development of novel TB vaccines is therefore of urgent need. Currently, there are 15 novel TB vaccine candidates in clinical trials, including live-attenuated vaccines, inactivated vaccines, subunit vaccines and viral-vectored vaccines, which open the door for the ultimate target of the End TB Strategy. This review summarizes the latest advances in the development of TB vaccines in global clinical trials, so as to provide insights into TB control.

Objective:To investigate the effect of aspirin on the outcomes in adult patients with ischemic moyamoya disease treated with encephaloduroarteriosynangiosis (EDAS).Methods:Adult patients with ischemic moyamoya disease treated EDAS in the Department of Neurosurgery, the Fifth Medical Center, PLA General Hospital from January 2015 to September 2018 were enrolled retrospectively. The control group only received EDAS treatment, and the aspirin group received EDAS and aspirin antiplatelet treatment. The data of the both groups were analyzed retrospectively and the effective rate of operation, the incidence of perioperative intracerebral hemorrhage, the incidence of recurrent cerebrovascular events at 6 months after operation and the improvement rate of the modified Rankin Scale (mRS) score were compared.Results:A total of 120 adult patients with ischemic moyamoya disease were enrolled, including 60 in the aspirin group and 60 in the control group. EDAS was performed on 107 cerebral hemispheres in both groups. The operative effective rate in the aspirin group was significantly higher than that in the control group (82.24% vs. 65.42%; χ2=7.836, P=0.005). There was no perioperative cerebral hemorrhage event in the aspirin group and the control group. There was no significant difference in the incidence of cerebral infarction within 6 months after operation, but the incidence of transient ischemic attack in the aspirin group was significantly lower than that in the control group (15% vs. 40%; χ2=9.404, P=0.002). In addition, the improvement rate of mRS score in the aspirin group at 6 months after operation was significantly higher than that in the control group (85% vs. 63.33%; χ2=7.350, P=0.007). Conclusions:The combination of EDAS and aspirin can effectively improve the outcomes of adult patients with ischemic moyamoya disease without increasing the risk of perioperative intracerebral hemorrhage.

Objective:To investigate the correlation between RNF213 gene p. R4810K polymorphism and posterior cerebral artery involvement in Chinese children with familial moyamoya disease.Methods:Children with familial moyamoya disease admitted to the Department of Neurosurgery, the Fifth Medical Center of PLA General Hospital from August 2004 to June 2018 were enrolled, and they were divided into posterior cerebral artery involved group and posterior cerebral artery uninvolved group. RNF213 gene p. R4810K single nucleotide polymorphism was detected. Multivariate logistic regression analysis was used to determine the independent risk factors for posterior cerebral artery involvement. Results:A total of 65 children with familial moyamoya disease were enrolled. Their age was 6.98±4.46 years and 37 (56.9%) were male. The first symptom of 55 children (84.6%) was cerebral ischemia, and 37 (56.9%) involved posterior cerebral artery. There were 3 (4.6%) children with p. R4810K AA genotype, 26 (40.0%) with GA genotype, and 36 (55.4%) with GG genotype. The p. R4810K genotype distribution in the posterior cerebral artery involved group was statistically different from that in the uninvolved group (GA+ AA genotype: 56.8% vs. 28.6%; χ2=5.124, P=0.024), and there were no statistical difference in gender, age, first symptom, and genetic pattern. Multivariate logistic regression analysis showed that after adjusting the first onset age and gender, p. R4810K G>A mutation was the only independent risk factor for posterior cerebral artery involvement (odds ratio 3.240, 95% confidence interval 1.082-9.705; P=0.020). Conclusion:The p. R4810K polymorphism of RNF213 gene is associated with posterior cerebral artery involvement in Chinese children with familial moyamoya disease.

Coronavirus disease 2019 (COVID-19), caused by the 2019 novel coronavirus (2019-nCoV), is spreading on a large scale in China. COVID-19 mainly affects the respiratory system and cause symptoms such as severe hypoxemia and high fever. At present, there is no specific treatment drug, and patients' autoimmunity is closely related to disease prognosis. The brain tissue of patients with moyamoya disease is in a state of ischemia and hypoxia for a long time. Hypoxemia and high fever will aggravate the cerebral ischemia and hypoxia in patients with moyamoya disease, and patients with moyamoya disease may also have autoimmune abnormalities. Because people with moyamoya disease are also likely to have COVID-19 and COVID-19 can cause many conditions that may aggravate the symptoms of patients with moyamoya disease, which brings new problems and challenges to the clinical diagnosis and treatment of moyamoya disease. In this article, the diagnosis and treatment process and prevention and control measures of patients with moyamoya disease under the current epidemic situation are thought, and the key issues in the treatment of patients with moyamoya disease after suffering from COVID-19 are sorted out. It is hoped to provide reference for the diagnosis and treatment of moyamoya disease under the COVID-19 epidemic situation.

As the main factor leading to foodborne illnesses, foodborne pathogens have been attached great importance by people. The development of simple, rapid, high-sensitivity and low-cost food-borne pathogen detection methods is of great significance in reducing the incidence of foodborne diseases. Biosensor technology is a new micro-analysis technology developed by multi-disciplinary cross-infiltration. It has the characteristics of high sensitivity and fast analysis speed, and is widely used in the detection of food-borne pathogens. This paper introduces the basic principles of biosensors, summarizes the application of common biosensors in the detection of foodborne pathogens, and prospects for future development.
Biosensing Techniques ; Food Microbiology ; Foodborne Diseases ; Humans

Objective To evaluate recurrence risk factors in postoperative breast cancer patients after 5-year adjuvant endocrine therapy.Methods From Jan 2006 to Dec 2011,a total of 327 patients were enrolled for this study.Kaplan-Meier curves were applied to estimate survival rates and COX's proportional hazards model to identify prognostic variables.Results Among these 327 eligible patients,42 (12.8％) patients suffered from distant metastasis and 34 (10.4％) patients experienced locoregional recurrence after 5-year adjuvant endocrine therapy.Survival analysis showed that patients with histologic grade 3 disease,lymph node metastasis,Ki-67 high expression,high TNM stage and radiotherapy were statistically significant with poorer relapse-free survival (RFS,P =0.000,0.003,0.000,0.003,0.034)and poorer distant metastasis-free survival (DMFS,P =0.000,0.002,0.000,0.002,0.023),respectively.In multivariate analysis,patients with histological grade 3 disease (P =0.002) and more than 3 positive nodes (P =0.032) were risk factors for lower RFS.However,only histological grade 3 (P =0.015) was risk factor for DMFS.Conclusions Late relapse after completion of 5-year adjuvant endocrine therapy was still common,patients with grade 3 disease and more than 3 positive nodes may benefit from extended endocrine therapy.

Objective To investigate the correlations between P53 expression and clinicopathologic factors and prognosis of Luminal breast cancer.Methods From January 2009 to December 2012,a total of 283 patients with Luminal breast cancer in the Shanghai General Hospital Affiliated to Shanghai Jiaotong Univer-sity were included.P53 expressions of them were assayed by immunohistochemistry.Survival analysis was applied using Kaplan-Meier curve and Log-rank test.Single factor analysis and mutiple-factor analysis were applied using Cox proportional hazard regression model.Results The rate of P53 expression was associated with tumor size (χ2 =6.285,P =0.043),lymph node metastasis (χ2 =15.881,P =0.000),histological grade (χ2 =8.132,P =0.043)and Ki-67 (χ2 =6.476,P =0.039),but it was not associated with age (χ2 =0.955,P =0.328),menopausal status (χ2 =3.808,P =0.051),pathological pattern (χ2 =0.847,P =0.655),estrogen receptor (χ2 =1.867,P =0.172),progesterone receptor (χ2 =0.937,P =0.333)and human epidermal growth factor receptor-2 (χ2 =0.110,P =0.741 ).In all the 283 patients,the 5-year relapse-free survival rates for P53-positive group and P53-negative group were 66.7% and 90.7% respectively (χ2 =12.609,P =0.000),while the 5-year overall survival rates were 84.4% and 93.4% respectively (χ2 =4.153,P =0.042),with significant differences.In Cox mutiple-factor analysis,lymph node metastasis (HR =2.484,95%CI:1.393-4.431,χ2 =9.497,P =0.002)and P53 over-expression (HR =3.627,95%CI:1.061-12.401,χ2 =4.220,P =0.040)were independent prognostic factors for the relapse-free survival of patients with Luminal breast cancer,and lymph node metastasis (HR =3.451,95%CI:1.891-6.297,χ2 =16.290,P =0.000)and higher histological grade (HR =2.806,95%CI:1.091-7.219,χ2 =4.582,P =0.032)were independent prognostic factors for overall survival.Conclusion P53 over-expression of patients with Luminal breast cancer is associated with prognostic factors such as lymph node metastasis and histological grade,which indicates the worse prognosis.

Objective To investigate the serum retinol-binding protein 4 (RBP4) level in olanzapinetreated schizophrenia with non-alcoholic fatty liver disease (NAFLD) via a case-control study and to explore its relationship with NAFLD.Methods Schizophrenia receiving olanzapine treatment,with or without NAFLD were enrolled as cases (n=60) or controls (n=60).The serum retinol-binding protein 4,metabolic syndrome component including body mass index (BMI),waist-to-hip ratio (WHR),fasting plasma glucose (FPG),total cholesterol (TG),total glycerin (TC) and blood pressure were assayed.TyG index,CT value ratio of liver and spleen were used for insulin resistance or NAFLD diagnosis and severity assessment respectively.Results The serum level of RBP4 was significantly higher in cases than that in controls ((70± 13)mg/L vs (52±12)mg/L ; t =4.943,P＜0.01) and the same result was showed after influencing factor adjustment thru covariance analysis (F=16.797,P＜0.01).Moreover,cases had significantly higher TyG index,BMI,WHR,FPG,TG and systolic pressure (t=2.383-4.300,P＜0.05-0.01).Cases with severe or moderate NAFLD had significantly elevated serum RBP4 level compared with mild cases((79± 16) mg/L,(72±8) mg/L vs (63t9) mg/L,d =16.2,9.9 ; P＜0.01,0.05).A significantly negative correlation between RBP4 level and the CT value ratio of liver and spleen (r=-0.244,P＜0.05),and a significantly positive correlation between RBP4 level and TyG index,BMI,WHR,TG(r=0.197-0.244,all P＜0.05) were observed.The partial coefficient between RBP4 level and CT value of liver and spleen was significant with influence adjusted(r=-0.453,P＜0.01).Logistic regression showed that serum RBP4 level(β3=0.105,P＜0.01)and TyG index,hyperlipidemia,obesity,central obesity or high blood pressure (β =1.288-9.711,P＜ 0.05-0.01) were closely associated with NAFLD.Conclusion A heighten serum RBP4 level may be one of NAFLD risk factors in schizophrenia treated with olanzapine.

Objective To study the correlation of fecal calprotectin and lactoferrin with intestinal mucosa lesions in Crohn′s disease (CD). Methods Eighty-eight cases of diagnosed CD patients were selected as study group and 35 irritable bowel syndrome (IBS) patients were as controls. Fecal samples of CD patients were collected in one week before colonoscopy examination and of IBS patients were collected of CD patients, CD activity index (CDAI) was calculated at same visit, and CD endoscopic index (CDEI) was calculated in the subsequent endoscopic examination. The level of fecal calprotectin and lactoferrin were tested by ELISA method. Results The median levels of facal calprotectin and lactoferrin in CD patients were 277.16 mg/kg (from 96.85 to 693.57 mg/kg) and 59.68 mg/kg (from 10.75 to 100.58 mg/kg) respectively, which were significantly higher than those of IBS patients (7.6mg/kg, from 5.54 to 32.3 mg/kg and 0.65 mg/kg from 0.23 to 4.34 mg/kg), (Z=-8.301 and -7.986, respectively both P =0.000). There were no significant difference of calprotectin and lactoferrin level between CD patients with colon pathological changes and without colon pathological changes (Z=-0.424 and -0.699,P=0.672 and 0.485, respectively). There was no significant difference of calprotectin and lacoferrin level between remission and active periods in CD patients (Z=-1.491 and -1.075, P=0.136 and 0.283, respectively). The median values of calprotectin and lactoferrin of patients in moderate and severe active period judged under endoscopy were 663.11 mg/kg (from 263.45 to 2015.63 mg/kg) and 105.64 mg/kg (from 56.52 to 187.44) mg/kg respectively, in mild active period were 344.54 mg/kg (from 132.03 to 722.67 mg/kg) and 86.68 mg/kg (from 21.07 to 100.55 mg/kg) accordingly, and in remission period were 133.94 mg/kg (from 60.54 to 583.33 mg/kg) and 45.31 mg/kg (from 7.59 to 48.31 mg/kg, respectively). Both calprotectin and lactoferrin levels were significantly higher in active period than in remission period (χ2=10.63 and 8.18, while, P=0.005 and 0.017, respectively). Conclusions The level of fecal calprotectin and lactoferrin can reflect the pathological changes and severity of the intestinal mucosa.

Objective To evaluate the effect and mechanism of 5-aminosalicylic acid (5-ASA) on bone marrow suppression caused by thiopurines, and to explore the proper dosage of thiopurines when combined with 5-ASA for inflammatory bowel diseases (IBD) patients.MethodsThe clinical data of IBD patients who took thiopurines were retrospectively analyzed. Thiopurine methyltransferase (TPMT) activity and 6-thioguanine nucleotide (6-TGN) concentration were tested.In prospective study, patients firstly treated with azathioprine (AZA) of 50 mg/d for 4 weeks, then combined with 5-ASA of 3 g/d for another 4 weeks.The concentration of 6-TGN in red blood cells (RBC) was analyzed at the end of 4th and 8th week.Results In retrospective study, there were 45 cases in AZA/6-mercaptopurine (MP) combined with 5-ASA group, 94 patients were in AZA/6-MP.alone group.The incidence of bone marrow suppression in these two groups were 46.7％ and 16.0％, respectively.Multivariates regression analysis indicated co-administration of 5-ASA was the only risk factor of increasing bone marrow suppression incidence (OR=3.45,95％ CI 1.31 ～ 9.04).There was no significant difference of TPMT activity between AZA/6-MP combined with 5-ASA group and AZA/6-MP alone group(t=-0.351 ,P=0.734).The 6-TGN concentration was significantly higher in AZA/6-MP combined with 5-ASA group than that of AZA/6-MP alone group (the median concentration was 384.9 pmol/8× 108 RBC and 286.4 pmol/8× 108 RBC,F=29.15,P=0.00).Prospective study was completed in 8 patients.After treated with AZA of 50 mg/d for 4 weeks, the 6-TGN concentration of 7 patients was lower than 230 pmol/8 × 108 RBC.After added with 5-ASA of 3 g/d for another 4weeks, the 6-TGN concentration of 7 patients was over 230 pmol/8 × 108 RBC, three patients of those was even higher than 420 pmol/8 × 108 RBC, and bone marrow suppression occurred in 2 patients.ConclusionsThe incidence of bone marrow suppression increased in Chinese IBD patients treated with recommended routine dossage of AZA/6-MP when conbined with 5-ASA.The mechanism may be related with the increased concentration of 6-TGN in RBC.To reduce the AZA dosage may possibly keep the efficacy while decrease the incidence of bone marrow suppression.