[Guidelines for diagnosis and treatment of glucocorticoid-induced osteoporosis].

Glucocorticoid-induced osteoporosis (GIOP) is a skeletal disease characterized by decreased bone strength and increased fracture risk associated with long-term glucocorticoid use. GIOP is the most common secondary osteoporosis that critically affects the quality of life of patients. Currently, the incidence of GIOP in China remains high, with insufficient awareness and lack of prevention and treatment norms. Therefore, the Chinese Rheumatology Association has established this standard based on domestic and international experience, with the aim of raising awareness of prevention and treatment among clinicians, guiding the standardized diagnosis and treatment of this disease, and improving the overall prognosis of patients with GIOP.

[Research and reflection on the diversified method system of multi-stages and multi-scenarios surveillance and early warning of infectious diseases].

With the outbreak of infectious diseases, more and more attention has been paid to surveillance and early warning work. Timely and accurate monitoring data is the basis of infectious diseases prevention and control. Effective early warning methods for infectious diseases can improve the timeliness and sensitivity of early warning work. This paper briefly introduces the intelligent early warning model of infectious diseases, summarizes the emerging surveillance and early warning methods of infectious diseases, and seeks the possibility of diversified surveillance and early warning in different epidemic stages and different outbreak scenarios of infectious diseases. This paper puts forward the idea of constructing a diversified method system of infectious diseases surveillance and early warning based on multi-stages and multi-scenarios and discusses the future development trend of infectious diseases surveillance and early warning, in order to provide reference for improving the construction level of infectious diseases surveillance and early warning system in China.

[Animal study on left bundle branch current of injury and anatomic location of leads in His-purkinje conduction system pacing].

Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.

[Epidemiological characteristics of infectious diseases of group A, B and C among Chinese students' population].

OBJECTIVE: To analyze the secular trend, ranking change, age- and regional- characteristics of leading infectious diseases among Chinese students population aged 6 to 22 years from 2008 to 2017. METHODS: Data were drawn from the national surveillance from 2008 to 2017, and the participants were students aged from 6 to 22 years who were diagnosed with notifiable infectious diseases. A total of 40 infectious diseases were classified into three groups based on national notifiable infectious diseases classification of A, B and C. The morbidity and mortality rates from infectious diseases were calculated using the numbers of students published by the ministry of education as the denominator. The age- and province-specific infectious diseases with the highest incidence were selected as the leading infectious diseases for analysis. RESULTS: From 2008 to 2017, the incidence rate, the number of cases and the number of deaths of infectious diseases among the boys aged 6-22 years in China were higher than that of the girls, and the overall trend was downward during the study period. The incidence rates in the boys and girls decreased from 2008 to 2015 with decrease of 43.4% and 40.1%, respectively. However, by 2017, the increase rate rebounded with the increases of 47.1% and 53.8%. The rebound trend was mainly caused by the increase of group C of infectious diseases. During the past decade, the top leading three diseases of groups A and B of infectious diseases were viral hepatitis, tuberculosis and dysentery in 2018, respectively, which changed to tuberculosis, scarlet fever and viral hepatitis in 2017. The top leading three infectious diseases in terms of mortality were rabies, tuberculosis, and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) in 2008, which were transformed into HIV/AIDS, rabies, and tuberculosis in 2017. There was no significantly obvious change in the incidence and mortality order of group C of infectious diseases during the decade. In the analysis of age groups and regions, the leading infectious diseases in groups A and B transferred from viral hepatitis to scarlet fever and tuberculosis, while in group C, mumps and infectious diarrhoea almost always dominated the leading infectious diseases. But in recent years, influenza and hand-foot-and-mouth disease increased significantly in the eastern region. CONCLUSION: During the past decade, China has got remarkable achievements in the prevention and control of children infectious disease. However, the change patterns and characteristics of notifiable infectious diseases among children and adolescents show the urgent need for prevention and control of respiratory tract infectious diseases, HIV/AIDS and other sexually transmitted diseases as well as new emerging infectious diseases in China in the future. This study provides important basis for policy making of Chinese national school-based infectious disease prevention and control mechanism.

[Study on warfarin medication checklist for improving patient compliance].

This study explored whether clinical pharmacists can improve patients' medication compliance with the use of warfarin medication checklist and the correlation between them. A total of 147 inpatients discharged from Shanghai Tongren Hospital with warfarin from July 2018 to September 2019 were randomly divided into the control group and the intervention group by random number table, including 75 in the control group and 72 in the intervention group. There were no statistically significant differences in gender, age, marital status, drinking history, smoking history, department distribution, type of thromboembolic disease, comorbidity and combined medication between the two groups (P>0.05). The control group received routine warfarin medication education at discharge, while the intervention group received clinical pharmacist's assessment of bleeding risk and targeted medication education using warfarin medication checklist at discharge. The monitoring time and value of the international normalized ratio (INR) between the two groups during hospitalization and within 6 months after discharge were recorded, as well as warfarin-related adverse events. The Morisky Medication Adherence Scale was used to evaluate the medication compliance of patients in the two groups. Spearman correlation analysis was used to study the relationship between warfarin compliance and variables in the warfarin medication checklist. The intervention group had better follow-up regularity than the control group (χ²=34.3, P<0.001), and the medication compliance in the intervention group was better than that in the control group (χ²=38.6, P<0.001). There were significant correlations between warfarin compliance and duration of warfarin therapy (R=-0.275, P=0.027), number of comorbidities (R=-0.335, P=0.004), bleeding risk (R=-0.433, P<0.001). In conclusion, using warfarin medication checklist can improve patients' medication compliance. Patients' medication compliance was significantly negatively correlated with duration of warfarin therapy, number of comorbidities and bleeding risk. Clinical pharmaceutical care can improve the medication compliance of patients with warfarin, so as to improve the medication results, which may be helpful for the drug treatment of patients with chronic diseases.

[The impact of occupational aluminum exposure on workers' overall cognitive function and various cognitive fields].

Objective: To evaluate the effects of occupational aluminum exposure on workers' overall cognitive function and cognitive fields. Methods: From July to August 2019, using the method of cluster sampling, 101 and 117 workers were selected from the electrolytic aluminum workshop of an aluminum plant in a region and the maintenance workshop of a plant in the same region. The venous blood of the subjects was collected, the plasma was extracted, and the blood aluminum concentration was measured by ICP-MS. According to the blood aluminum concentration and type of work, 93 workers who were lower than the median blood aluminum concentration and in the maintenance workshop of a factory were divided into low aluminum exposure group, and 85 workers who were higher than the median blood aluminum concentration and in the electrolytic aluminum workshop of an aluminum factory were divided into high aluminum exposure group. The basic information of the respondents, was collected through the employee physical examination form. The overall cognitive function of workers was evaluated by Beijing Montreal Cognitive Assessment Scale (MoCA) . Multiple linear regression analysis and logistic regression analysis were used for multiple statistical analysis. Results: Compared with the low aluminum exposure group (25.42±1.808) , the total score of MoCA in the high aluminum exposure group (23.84±2.919) was significantly lower, and the scores of visual space, executive function, abstract and delayed recall were significantly lower (P<0.05) . Linear regression analysis showed that the total score of MoCA, visual space and executive function, naming and delayed recall were negatively correlated with blood aluminum concentration (ß=-0.018、-0.008、-0.003、-0.008, P<0.05) .MOCA total score, visual space and executive function, attention, language, abstraction, orientation were positively correlated with educational level (ß=0.853、0.310、0.216、0.171、0.412、0.122, P<0.05) . Logistic regression analysis showed that adjusting for age, smoking, drinking and education, blood aluminum was a risk factor for mild cognitive impairment (OR=1.017, P<0.05) ; Education level was the protective factor of mild cognitive impairment (OR=0.419, P<0.05) . Conclusion: Occupational aluminum exposure can affect the overall cognitive function of workers, and occupational aluminum exposure increases the risk of MCI.

[Effects of occupational exposure to aluminum on verbal function of workers].

Objective: To explore the effect of occupational aluminum (Al) exposure on workers' overall cognitive level and speech function. Methods: In July 2019, by using cluster sampling method, the group of 232 exposed to Al from an Al plant in Shanxi Province were selected as the exposed group, and the group of 228 not exposed to Al were selected as the control group. The blood Al concentration was determined by inductively coupled plasma mass spectrometry (ICP-MAS) . The exposed group was divided into high exposure group and low exposure group according to the median (M) concentration of Al in serum. The general cognitive function and speech function were evaluated with the Montreal Cognitive Assessment Scale (MoCA) , and the differences in the general cognitive function and speech function between the groups were compared, and non-conditional logistic regression was used to analyze the possible influencing factors of mild cognitive impairment (MCI) . Results: There were significant differences in age, working age, education and drinking status between Al exposed group and control group (P<0.05) . The total MoCA score, animal naming tese (ANT) score and category fluency repetition (CFT) score in Al exposure group were lower than control group and the differences were statistically significant (P<0.05) . The full rate of ANT was lower than that of CFT in Al exposure group (P<0.05) . The total MoCA score, ANT score and CFT score in the high exposure group were significantly lower than those in the control group (P<0.05) . The score of MoCA, ANT and CFT in high exposure group were lower than those in low exposure group between the level of serum aluminum>60 µg/L group and ≤60 µg/L group (P<0.05) . Logistic regression analysis showed that working age, serun Al concentration, ANT score, CFT score and SR score were the possible influencing factors of MCI in occupational Al exposure workers (P<0.05) . Conclusion: Occupational Al exposure can lead to impaired speech function of workers, the higher the ANT score, CFT score and SR score, the lower working age and serum Al concentration, the lower risk of MCI.

A mathematical model for HIV prevention and control among men who have sex with men in China.

In recent years, men who have sex with men (MSM) constitute a major group of HIV transmission in China. High primary drug-resistance (PDR) rate in MSM also represents a serious challenge for the Chinese antiretroviral therapy (ART) program. To assess the efficiency of ART in controlling HIV/AIDS infection among MSM, we developed a compartmental model for the annually reported HIV/AIDS MSM from 2007 to 2019 in the Zhejiang Province of China. R0 was 2.3946 (95% CI (2.2961-2.4881)). We predict that 90% of diagnosed HIV/AIDS individuals will have received treatment till 2020, while the proportion of the diagnosed remains as low as 40%. Even when the proportion of the diagnosed reaches 90%, R0 is still larger than the level of AIDS epidemic elimination. ART can effectively control the spread of HIV, even in the presence of drug resistance. The 90-90-90 strategy alone may not eliminate the HIV epidemic in Chinese MSM. Behavioural and biologic interventions are the most effective interventions to control the HIV/AIDS epidemic among MSM.

Objective response of first-line chemotherapy of triple-negative breast cancer translates into survival benefit: an analysis in an independent, prospective clinical trial and a real-world setting.

This study sought to assess whether the objective response (OR, including complete response and partial response) of first-line chemotherapy can predict overall survival (OS) for patients with metastatic triple-negative breast cancer (mTNBC) in both clinical trial and a real-world setting. The survival predictable parameters were assessed in two independent cohorts, the training cohort of 236 patients as part of a phase 3 trial (CBCSG006, Trial registration number NCT0128762) and the validation cohort of 360 patients from the real-world setting. Univariable and multivariable Cox proportional hazard models were applied to explore associations with progression-free survival and OS in the training cohort and then in the validation cohort. OR (OR vs non-OR, HR, 0.438, p<0.001) together with Eastern Cooperative Oncology Group (ECOG) performance status, disease-free survival, number of metastatic organ sites and platinum-based chemotherapy used as first-line chemotherapy were observed to be independent prognostic factors for progression-free survival (PFS), and OR (OR vs non-OR, HR, 0.602, p=0.002) together with ECOG score, disease-free survival, number of metastatic organ sites and previous anthracycline and/or taxane treatment were observed to be independent predictive factors for OS in the training cohort. These predictors were confirmed in the validation cohort. For OR and non-OR group, median OS was 23.72 and 13.83 months in the training cohort (HR, 0.637, p=0.002), and 21.95 and 13.80 months in the validation cohort (HR, 0.608, p<0.001), respectively. By adding OR in the OS predictors, the concordance index (C-index) improved from 0.622 to 0.645 in the training cohort and 0.653 to 0.675 in the validation cohort. PFS and OS of mTNBC can be predicted by OR status with any regimen of first-line chemotherapy in an independent prospective clinical trial and a real-world setting. Therefore, TNBC, not like other subtypes of breast cancer, may be in need of combination chemotherapy or intense chemotherapy to achieve a high response rate for survival.

[Effect of Dendrobium nobile Lindl. alkaloids on myocardial lipid metabolism during cardiopulmonary bypass ischemia-reperfusion in dogs].

Objective: To explore the effects and mechanisms of Dendrobium nobile Lindl. alkaloids (DNLA) on myocardial lipid metabolism during ischemia-reperfusion in dogs undergoing cardiopulmonary bypass (CPB). Methods: Twenty-four healthy hybrid dogs, half male and half female, were randomly divided into sham group, model group, solvent control group and treatment group (DNLA, 6 mg/kg) (n=6), all of which were established with CPB. Except for the sham group, the aorta of the other groups was occluded for 60 min and then reopened. The uptake rate of free fatty acids, the concentration of long-chain acyl coenzyme A (LCACoA), mRNA and protein expression of fatty acid translocase enzyme/CD36 (FAT/CD36) in myocardial tissue and the cardiac function indexes were measured at 4 time points: before cardiopulmonary bypass (T1), 15 min (T2), 60 min (T3), and 90 min (T4) after reperfusion in each group. Results: Before CPB, there were no statistically significant differences in the uptake rate of free fatty acids, the concentration of LCACoA and mRNA expression of FAT/CD36 in myocardial tissue in each group (P>0.05). After the opening of the aorta, the above indexes in model group [(35.8±4.7)%, (8.55±1.51) nmol/g, 3.23±0.68] and treatment group [(27.4±2.7)%, (6.10±1.38) nmol/g, 2.20±0.56] were higher than those in sham group [(19.6±3.9)%, (4.16±0.81)nmol/g, 1.19±0.52], which were the highest at T2, and then gradually decreased (all P<0.05). Compared with the model group, the increase of above indicators in the treatment group was significantly lower at T2 (all P<0.05). Before CPB, there was no statistically significant differences in cardiac function indexes [left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and±dp/dtmax] among the groups (P>0.05). After the aorta was opened, the above indexes in model group [(76.5±9.1) mmHg, (31.1±2.9) mmHg, (1.2±0.4) mmHg/ms, (-0.9±0.1) mmHg/ms] and treatment group [(92.9±8.7) mmHg, (25.3±3.6) mmHg, (1.8±0.4) mmHg/ms, (-1.3±0.1) mmHg/ms] were lower than those in sham group [(165.5±12.9) mmHg, (6.5±0.5) mmHg, (3.3±0.6) mmHg/ms, (-2.9±0.3) mmHg/ms] (all P<0.05), but the impairment degree of cardiac function indicators in treatment group was significantly lower than that those in model group (all P<0.05). Conclusion: During CPB in dogs, DNLA can inhibit the abnormal expression of FAT/CD36, decrease the uptake of free fatty acids, and reduce the abnormal accumulation of LCACoA in myocardium,thereby alleviating the myocardial injury after ischemia-reperfusion.

[Analysis of epidemiological characteristics of report cases of rotavirus diarrhea in children under 5 years old in China, 2005-2018].

Objective: To analyze the epidemiological characteristics of rotavirus in children under 5 years old in China (excluding China Hong Kong, Macau and Taiwan data, the same below) from 2005 to 2018. Method: Data on other infectious diarrhea in the country from 2005 to 2018 were downloaded from the National Notifiable Disease Report System was to build a database for report cases of rotavirus diarrhea in children under 5 years of age, and descriptive epidemiological methods were used to analyze the data. Result: In 2005-2018, a total of 820 588 cases of rotavirus infection in children under 5 years old were reported nationwide, with male 500 944 cases, and with an average annual incidence of 63.7/100 000. The reported incidence showed a fluctuating upward trend increased from 8.4/100 000 to 178.1/100 000. The number of reporting provinces increased from 17 to 30. The reported incidence showed a peak of season from November to following February. The reported cases of rotavirus diarrhea in children under 5 months of age was 13.1%(107 845 cases), and the high-incidence age ranged from 6 months to 2 years old, accounting for 70.3% (576 874 cases), with a peak of 11-13 months (163 947 cases). The top three provinces (cities) reporting the incidence rate were Zhejiang (535.2/100 000), Guangdong (334.3/100 000) and Beijing (317.3/100 000), the provinces with the low reported case rates were Shanxi (0.9/100 000), Heilongjiang (1.6/100 000) and Liaoning (2.5/100 000), but there was no case reported in Tibet; The report cases of south region (745 526 cases) were 9.9 times north region (74 935 cases).The cases of rotavirus infection and other diarrhea pathogens were detected simultaneously accounted for 1.8% (15 030 cases) and mainly were positive for rotavirus and adenovirus (90.1%, 13 544 cases). Conclusion: The rate of rotavirus infection in children has increased rapidly since the age of 6 months, and 84.4% of the reported cases were infants before the age of 2 years.

[Pilot surveillance and evaluation of influenza-like illness based on automatic computer analysis of electronic medical record in sentinel hospital].

Objective: To compare the accuracy of influenza-like illness (ILI) surveillance by automatic computer analysis based on electronic medical records and by doctor's report. Methods: A total of 3 542 patients who presented to Yichang Central Hospital fever clinic, respiratory department or emergency department between April to October 2019 with an ICD-10 code for acute respiratory illness (J00-J22) and complete electronic medical information of ILI related syndromes were drawn as the study sample. Taking the classification of the study sample according to the ILI case definition by influenza surveillance professionals as the gold standard, draw the receiver operating characteristic (ROC) curve and calculate sensitivity, specificity, diagnostic consistency to compared the accuracy of ILI surveillance by automatic computer analysis and by doctor's report. Results: Median age of 3 542 cases was 30 (24, 38) years old; 1 179 cases (33.29%) compliance with the case definition, ILI reported by doctors was 1 306 cases (36.87%), and computer automatic identification ILI were 1 150 cases (32.47%); 1 391 (39.27%) cases were men. The results of automatic computer analysis and doctor report consistency of kappa values with gold standard judgment were 0.97 and 0.66 respectively; area under the ROC curve was 0.98 and 0.84, respectively. And the sensitivity and specificity of automatic computer analysis were higher than that of doctor's report (all P values were <0.001), the sensitivity was 96.95% and 82.27%, and the specificity was 99.70% and 85.78%, respectively. Conclusion: The automatic computer analysis based on electronic medical records can identified ILI cases with good sensitivity and specificity in ILI case surveillance.

[Current situation and related policies on the implementation and promotion of influenza vaccination among health care workers].

Health care workers have higher risk of influenza infection because of their occupational exposure to infected patients. Infection of the health care workers may not only result in the increasing risk of the nosocomial infection and family transmission, but also disrupt the health services due to absence from work. Health care workers were recommended as a priority group of influenza vaccinationin more than 40 countries and regions in the world. In recent years, domestic surveys show that the influenza vaccine coverage among health care workers was low. This paper outlines the current status and related policies of influenza vaccination among health care workers in China and global. Additionally, we analyzed and discussed the proper immunization strategy of influenza vaccine for medical staff in China.

[The mortality burden of influenza in China: a systematic review].

Objective: To systematically review the mortality burden study of influenza in mainland China. Method: "influenza", "flu", "H1N1", "pandemic", "mortality", "death", "fatality", "burden", "China" and "Chinese" were used as keywords, and a systematic literature search was conducted to identify articles in three English databases (PubMed, Web of Science and Embase) and three Chinese database (CNKI, WanFang and VIP) during 1990-2018 (excluding Hong Kong, Macao and Taiwan). The language of literature was restricted to Chinese and English. The inclusion criteria were human-oriented researches with method based on population, and research indexes included mortality and excess mortality. The exclusion criteria were non-primary research materials, predictive research and research on the burden of avian influenza related deaths. A total of 17 literatures were included, and the basic information to descriptive characteristics, methodology of modeling and the corresponding results were extracted. Results: All the 17 studies adopted indirect statistical models, with 14 of which adopted the regression model, and all the research index was excess mortality. All causes (16 studies), respiratory and circulatory diseases (14 studies) and pneumonia and influenza (10 studies) were the main causes of death associated with influenza. Influenza associated mortality burden in the elderly was higher, with the lowest excess mortality rates of all causes, respiratory and circulatory diseases, pneumonia and influenza being 49.57, 30.80 and 0.69 per 100 000 people, and the highest rates being 228.16, 170.20 and 30.35 per 100 000 people, respectively. In the non-elderly, the corresponding lowest rates were -0.27, -0.08 and 0.04 per 100 000 people respectively, and the highest rates were 3.63, 2.6 and 0.91 per 100 000 people, respectively. The influenza-related excess mortality was higher in the north, with a minimum of 7.8 per 100 000 and a maximum of 18.0 per 100 000, and slightly lower in the south, with a minimum of 6.11 per 100 000 and a maximum of 18.7 per 100 000. There were also differences in deaths caused by different influenza virus subtypes, with influenza A(H3N2) and influenza B virus possibly posing a heavier mortality burden. Conclusions: Studies on influenza mortality burden is mainly based on indirect model and urban level in China. The mortality burden of influenza in the elderly, the northern and subtype A(H3N2) and B were more severe.

[Platelet derived growth factor-BB regulates phenotype transformation of pulmonary artery smooth muscle cells via SIRT3 affecting glycolytic pathway].

Objective: To investigate whether platelet-derived growth factor-BB (PDGF-BB) can regulate phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) via SIRT3 affecting glycolytic pathway. Methods: The PASMCs were isolated from Sprague Dawley rats. PASMCs were divided into 3 groups by using 2-deoxyglucose (2-DG), an inhibitor of the glycolytic pathway: normal control group, PDGF-BB group(30 ng/ml) and PDGF-BB (30 ng/ml)+2-DG (10 mmol/L) group. In lentivirus-mediated overexpression assay, cells were divided into control group, PDGF-BB group(30 ng/ml), PDGF-BB+deacetylase sirtuin-3 (SIRT3) overexpression group and PDGF-BB+empty vector group. The expression levels of phenotype related index such as α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), calponin, vimentin were detected by qRT-PCR and Western blot. Meanwhile, the expression of α-SMA was detected by cellular immunofluorescence staining. EDU staining was used to detect the proliferation of PASMCs. The expression of SIRT3 was detected by Western blot. The expressions of glucose transporter 1 and aerobic glycolytic enzymes were detected by qRT-PCR and Western blot in lentivirus-mediated overexpression assay. Results: (1) PDGF-BB affects PASMCs phenotypic transformation through glycolytic pathway: compared with normal control group, PDGF-BB significantly decreased the expressions of contractile phenotype markers such as α-SMA, SM-MHC, calponin mRNA and protein (all P<0.05), but it increased the expressions of the synthetic phenotype marker vimentin mRNA and protein (both P<0.05). Cellular immunofluorescence assay showed that PDGF-BB significantly decreased the number of α-SMA positive cells, while 2-DG reversed the process. (2) PDGF-BB promoted cell proliferation through glycolytic pathway: the proliferation of PASMCs was significantly higher in PDGF-BB group than in control group (P<0.05), and which could be significantly reduced by 2-DG (P<0.05). (3) PDGF-BB inhibited the expression of SIRT3 protein in PASMCs: the expression of SIRT3 protein in PDGF-BB group was lower than that in control group (P<0.05). (4) PDGF-BB affected glycolytic pathway through SIRT3:compared with the control group, PDGF-BB significantly increased the expression levels of glucose transporter 1 (Glut1), hexokinase 2 (HK2) and 6-phosphfructo-2-kinase 3 (PFKFB3) mRNA (all P<0.05), which was reserved by over-expression of SIRT3. There were no significant difference in mRNA expression levels between PDGF-BB group and PDGF-BB+empty vector group (P>0.05).Compared with the control group, PDGF-BB significantly increased the expression levels of Glut1, HK2 and PFKFB3 protein(all P<0.05), which was reserved by over-expression of SIRT3. There were no significant differences in protein expression levels between PDGF-BB group and PDGF-BB+empty vector group (all P>0.05). Conclusion: PDGF-BB regulates phenotypic transformation of PASMCs via SIRT3 affecting glycolytic pathway.

Biomarker assessment of the CBCSG006 trial: a randomized phase III trial of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer.

Background: CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods: Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results: Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46-9.00] months for GP arm and 6.07 (95% CI 5.32-6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions: GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration: ClinicalTrials.gov, NCT01287624.

Perspectives on novel vaccine development.

Vaccination is a common routine for prevention and control of human and animal diseases by inducing antibody responses and cell-mediated immunity in the body. Through vaccinations, smallpox and some other diseases have been eradicated in the past few years. The use of a patho- gen itself or a subunit domain of a protein antigen as immunogens lays the basis for traditional vaccine development. But there are more and more newly emerged pathogens which have expe- rienced antigenic drift or shift under antibody selective pressures, rendering vaccine-induced im- munity ineffective. In addition, vaccine development has been hampered due to problems includ- ing difficulties in isolation and culture of certain pathogens and the antibody-dependent enhancement of viral infection (ADE). How to induce strong antibody responses, especially neu- tralizing antibody responses, and robust cell-mediated immune responses is tricky. Here we re- view the progress in vaccine development from traditional vaccine design to reverse vaccinology and structural vaccinology and present with some helpful perspectives on developing novel vaccines.

[Macrophage colony stimulating factor enhances non-small cell lung cancer invasion and metastasis by promoting macrophage M2 polarization].

Objective: To investigate the key cytokine which polarizes M2 macrophages and promotes invasion and metastasis in non-small cell lung cancer (NSCLC). Methods: After co-culture with A549 cells in vitro, the proportion of CD14(+) CD163(+) M2 macrophages in monocytes and macrophage colony stimulating factor (M-CSF) levels in culture supernatant were detected by flow cytometry, ELISA assay and real-time qPCR, respectively. The effects of CD14(+) CD163(+) M2 macrophages on invasion of A549 cells and angiogenesis of HUVEC cells were measured by transwell assay and tubule formation assay, respectively. The clinical and prognostic significance of M-CSF expression in NSCLC was further analyzed. Results: The percentage of CD14(+) CD163(+) M2 macrophages in monocytes and the concentration of M-CSF in the supernatant followed by co-culture was (12.03±0.46)% and (299.80±73.76)pg/ml, respectively, which were significantly higher than those in control group [(2.80±1.04)% and (43.07±11.22)pg/ml, respectively, P< 0.05]. Human recombinant M-CSF promoted M2 polarization of macrophages in vitro. M2 macrophages enhanced the invasion of A549 cells (66 cells/field vs. 26 cells/field) and the angiogenesis of HUVEC cells (22 tubes/field vs. 8 tubes/field). The mRNA expression of M-CSF in stage Ⅰ-Ⅱ patients (16.23±4.83) was significantly lower than that in stage Ⅲ-Ⅳ (53.84±16.08; P<0.05). M-CSF levels were associated with poorer overall survival and disease-free survival in NSCLC patients (P<0.05). Conclusions: Tumor-derived M-CSF can induce CD14(+) CD163(+) M2 polarization of macrophages, which can further promote the metastasis and angiogenesis of NSCLC. M-CSF could be used as a potential therapeutic target of NSCLC.

[The prevalence and related factors of HBV infection among adults in Mianyang].

Objective: To analyze the prevalence and related factors of HBV infection among people aged 18 years old and above in Mianyang city. Methods: A total of 260 950 residents, living in Mianyang city more than 6 months, aging 18 years old and above were employed by multi-stage random sampling method from November 2014 to September 2015. Questionnaire survey was conducted on participants using a self-designed questionnaire, including general demographic characteristics, family history of Hepatitis B, history of Hepatitis B vaccination and history of present illness, etc. 5ml blood was collected from all participants, and the blood samples were detected for HBsAg by enzyme-linked immunosorbent assay (ELISA). The multivariate unconditional logistic regression was performed to identify the related factors of positive HBsAg. Results: Among the 260 950 subjects, 113 184 were males (43.37%), 147 766 were females (56.63%), and the average age was (47.68±17.36) years old. The positive rate of HBsAg was 6.10%(15 822 cases). Subjects who were 25-34 years old (OR=1.23), 35-44 years old (OR=1.26), 45-54 years old (OR=1.23), and 55-64 years old (OR=1.34) were more likely to be HBsAg positive,65 years and older (OR=0.88) were less likely to be, compared with subjects aging 18-24 years old; males were more likely to be HBsAg positive compared with females (OR=1.35); people living in Fucheng district were more likely to be HBsAg positive compared with who living in Jiangyou district(OR=1.91); married people were more likely to be HBsAg positive compared with unmarried ones (OR=1.36); medical staff were less likely to be HBsAg positive compared with non-medical staff (OR=0.61); subjects with a surgery history were more likely to HBsAg positive compared with who without (OR=1.13); subjects with trauma history were more likely to HBsAg positive compared with who without (OR=1.13); people with history of Hepatitis B were more likely to HBsAg positive compared with who without (OR=4.21); people with Hepatitis B vaccination history were less likely to be HBsAg positive compared with who without (OR=0.48); all the P values above were less than 0.05. Conclusion: The positive rate of HBsAg among adults in Mianyang city was very high, and we should pay more attention to people aging between 25 and 64 years old, male, medical staff, with surgery history, trauma history, and a family history of Hepatitis B and Hepatitis B vaccination history.