Elevated Hsp90-beta contributes to differential diagnosis of pleural effusion caused by lung cancer and correlates with malignant biological behavior of lung cancer.

BACKGROUND: Hsp90-beta has been investigated to be correlated with the occurrence and development of tumor. The intention of this research was to test the level of Hsp90-beta in malignant pleural effusion (MPE) of patients with lung cancer and disclose the clinical significance of Hsp90-beta as a potential tumor marker for differential diagnosis of pleural effusion caused by lung cancer. METHODS: The level of Hsp90-beta was determined using enzyme-linked immunosorbent assay. Calculations of the Hsp90-beta threshold, the sensitivity and specificity for distinguishing MPE from benign pleural effusion were performed using receiver operator characteristic curve. RESULTS: The level of Hsp90-beta in MPE of lung cancer patients was higher than that in control individuals (P < 0.05) and increased MPE Hsp90-beta was correlated with the pathological differentiation, tumor size and lymphatic metastasis (P < 0.05). The cutoff value of Hsp90-beta produced by receiver operator characteristic curve for distinguishing lung cancer from control individuals were 1.659 ng/mL and the sensitivity and specificity were 93.46 and 79%. CONCLUSIONS: Increased Hsp90-beta in MPE was correlated with malignant biological behavior of lung cancer patients, indicating that the level of Hsp90-beta could be a tool of referential value for differential diagnosis of pleural effusion caused by lung cancer.

Increased stathmin in serum as a potential tumor marker for lung adenocarcinoma.

BACKGROUND: Stathmin has been found to be involved in malignant tumors; the aim of this study was to investigate the relationship between serum stathmin and clinico-pathological features of lung cancer. METHODS: In three lung cancer cell lines, stathmin expression and its secretion level in the supernatant were examined by Western blot and enzyme-linked immunosorbent assay (ELISA). Expression of stathmin was examined by immunohistochemistry in 48 lung cancer tissues, and serum stathmin expression level was examined by ELISA in 96 patients with lung cancer and 82 normal individuals. Sensitivity and specificity of serum stathmin were determined by receiver operator characteristic curve (ROC). RESULTS: In the three cell lines and their supernatant, stathmin levels were higher than those in 16 HBE cell line. Lung cancer tissues expressed higher level stathmin more frequently than normal lung tissue (P < 0.05). Serum stathmin level was significantly higher in the patients with lung cancer than in normal individuals (P < 0.001). Increased stathmin level in cancer tissue and serum were significantly associated with adenocarcinoma histology, lymph node metastasis and advanced stage. The threshold level of serum stathmin for distinguishing lung cancer from normal individuals was 1.86 ng/ml. The sensitivity and specificity were 93.7% and 91.5%, respectively. CONCLUSIONS: Measurement of serum stathmin level could be a potential biomarker for lung cancer, especically those of adenocarcinoma, with lymph node metastasis and at advanced clinical stages.

Thoracic perfusion of recombinant human endostatin (Endostar) combined with chemotherapeutic agents versus chemotherapeutic agents alone for treating malignant pleural effusions: a systematic evaluation and meta-analysis.

BACKGROUND: Endostar is a new endogenous angiogenic inhibitor with implicated anti-tumor activity. This study was to investigate whether thoracic perfusion of Endostar could be used to control malignant pleural effusions (MPE). METHODS: We searched the databases of MEDLINE, Web of Science, EMBASE, Goggle, Cochrance Library and CNKI to select the studies regarding the efficacy of Endostar to treat MPE. A total of 13 randomised controlled trials (RCTs) with 1066 patients were included. RESULTS: The overall response rate (ORR) (P < 0.001; odds ratio = 3.58) and disease control rate (DCR) (P < 0.001; odds ratio = 2.97) of Endostar combined with chemotherapeutic agents were significantly higher than those of chemotherapeutic agents alone. In addition, Endostar combined treatment remarkably promoted quality of life (QOL) of patients (P < 0.001; odds ratio = 3.04) compared with that of chemotherapeutic agents alone. Moreover, Endostar combined treatment did not have an impact on the incidence of adverse reactions (AEs) (P < 0.05). CONCLUSIONS: The efficacy of Endostar combined chemotherapeutic agents was superior to chemotherapeutic agents alone through thoracic perfusion in treating MPE, which indicated that Endostar could be an effective agent for controlling MPE.

Increased serum amyloid A as potential diagnostic marker for lung cancer: a meta-analysis based on nine studies.

BACKGROUND: Previous studies have disclosed that serum amyloid A (SAA) is likely involved in the lung cancer pathogenesis and progression. We performed a systematic evaluation and meta-analysis to disclose the correlation between the expression of SAA and lung cancer and to evaluate its value for lung cancer diagnosis. METHODS: We searched the relevant articles from the databases of Medline, Embase, Cochrance Library and Web of Science and calculated the standardized mean difference (SMD) with 95 % confidence interval (CI) to assess the expression difference of SAA between lung cancer and normal patients. Moreover, we counted the positive rate, sensitivity and specificity and drew a summary receiver operating characteristic curve (SROC) to evaluate the diagnostic value of SAA for lung cancer. RESULTS: A total of nine studies with 1392 individuals were included in this analysis. The results showed an increased SAA was correlated with the incidence of lung cancer (P < 0.001), especially with the lung squamous cell carcinoma (LSCC) (p = 0.012). The overall sensitivity and specificity of SAA for discerning lung cancer was 0.59 (95 % CI: 0.54-0.63) and 0.92 (95 % CI: 0.88-0.95), respectively. The area under the SROC curve was 0.9066 (SE = 0.0437). CONCLUSIONS: Increased SAA in lung cancer was intimately correlated with the development and progression of lung cancer. A higher specificity of SAA suggested that it should be a significant biomarker for discerning lung cancer from normal individuals, especially for LSCC (p = 0.012).

Thoracic perfusion of matrine as an adjuvant treatment improves the control of the malignant pleural effusions.

BACKGROUND: Many studies have investigated the efficacy and safety of matrine in treating malignant pleural effusion by thoracic perfusion. This study is an analytic value of available evidence. METHODS: Twelve studies were analyzed in this study. Pooled odds ratios and hazard ratio with 95 % confidence intervals were calculated using the fixed effects model. RESULTS: Overall response rate of matrine combined with other medications in treating malignant pleural effusion (MPE) was significantly higher than those of other medications alone (p < 0.05). Time to pleural effusion relief and quality of life were improved after the treatment of matrine combined with other medications (p < 0.05). Moreover, matrine combined with other medications had a lower incidence of adverse reactions (p < 0.05). CONCLUSIONS: Matrine combined with other medications improves the control of the malignant pleural effusions and decreases the incidence of adverse reactions.

Spatial-temporal Distribution and Influencing Factors of Late Diagnosis of HIV/AIDS Based on Bayes Spatial-temporal Model / 中山大学学报(医学科学版)

ObjectivesTo analyze the spatial and temporal clustering characteristics and related influencing factors of late diagnosis of HIV/AIDS in Lanzhou， to identify its high-risk areas and time trends in Lanzhou， and to provide a theoretical basis for developing targeted HIV/AIDS prevention and control strategies in Lanzhou. MethodsThe subjects of this study were adult HIV/AIDS cases reported in Lanzhou City between 2011 and 2018. Data used in the study were sourced from the Lanzhou Center for Disease Control and Prevention and the Lanzhou Statistical Yearbook. To analyze the spatial distribution characteristics and influencing factors of the relative risk （RR） of late HIV/AIDS diagnosis， Bayes spatial-temporal model was used. ResultsA total of 1984 new HIV/AIDS cases were reported in Lanzhou from 2011 to 2018， with an mean age of 37.51 years and predominantly male （91.8%）. The number of late diagnosis cases was 982， with an mean age of 39.67 years and a predominance of males （91.8%）. Late diagnosis was more common in older individuals and women with HIV/AIDS. Chengguan District （51.1%）， Anning District （50.3%） and Yuzhong County （51.9%） had an above-average proportion of late diagnosis of HIV/AIDS. The proportion of late diagnosis cases in Lanzhou showed a fluctuating upward trend from 2011 to 2018. The results of Bayes spatial-temporal model showed that the risk of late HIV/AIDS diagnosis in Lanzhou had fluctuated from 2011 to 2015， and then increased rapidly after 2015 ［RR （95% credibility interval， 95%CI） increased from 1.01 （0.84， 1.23） to 1.11 （0.77， 1.97）］； the trends of risk of late diagnosis in Honggu district and three counties were similar to the overall trend in Lanzhou city， while the risk of late diagnosis in Chengguan District and Qilihe District showed a decreasing trend. The regions with the RR for late diagnosis greater than 1 included Yongdeng County （RR=1.07， 95% CI： 0.55， 1.96）， Xigu District （RR=1.04， 95% CI： 0.67， 1.49）， Chengguan District （RR=2.41， 95% CI： 0.85， 6.16）， and Qilihe District （RR=2.03， 95% CI： 1.10， 3.27）. Besides， the heatmap analysis showed that Chengguan District and Qilihe District were the hot spots. The influencing factors analysis showed that the higher GDP per capita （RR=0.65， 95% CI： 0.35， 0.90） and the larger proportion of males with HIV/AIDS cases （RR=0.53， 95% CI： 0.19， 0.92） could lead to the lower the relative risk of late HIV/AIDS diagnosis. However， the higher the population density （RR=1.35， 95% CI： 1.01， 1.81） caused the higher the risk of late diagnosis. ConclusionOur study shows the risk of late diagnosis of HIV/AIDS in Lanzhou was on the rise， and there are significant regional differences. GDP per capita， the proportion of males in HIV/AIDS cases and population density are influencing factors in the late diagnosis of HIV/AIDS. Therefore， for regions with a high risk of late diagnosis or related risk factors， targeted HIV screening and prevention services should be given priority in order to reduce the proportion and risk of late diagnosis of HIV/AIDS.

Increased level of annexin A1 in bronchoalveolar lavage fluid as a potential diagnostic indicator for lung cancer.

BACKGROUND: Annexin A1 has been implicated in various tumor types, but few studies have investigated its involvement in lung cancer. The purpose of this investigation was to quantify the annexin A1 level in bronchoalveolar lavage fluid (BALF) and analyze its usefulness in lung cancer diagnosis. METHODS: Annexin A1 expression was measured by immunohistochemistry and enzyme immunoassay. The sensitivity and specificity of annexin A1 for distinguishing lung cancer were determined by receiver operator characteristic (ROC) curves. RESULTS: Tumor tissues, BALF and serum of patients with lung cancer contained higher levels of annexin A1 than those of the control group of patients with benign lung diseases. Moreover, an increased level of BALF annexin A1 was closely correlated with lymphatic invasion and malignant progression of lung cancer. The sensitivity and specificity of BALF annexin A1 for distinguishing lung cancer were 94.2% and 90.2%, respectively. CONCLUSIONS: Increased annexin A1 in BALF was correlated with lymphatic invasion and malignant progression of lung cancer, suggesting that it could be an indicator for discerning lung cancer and predicting outcome.

Stathmin overexpression is associated with growth, invasion and metastasis of lung adenocarcinoma.

Stathmin has been investigated as a tumor biomarker because it appear to be associated with tumorigenesis; however, the effect of stathmin in lung adenocarcinoma (LAC) remains poorly understood. The purpose of this study was to examine the expression of stathmin in lung adenocarcinoma, and to disclose the relationship between them. The expression of stathmin was examined by RT-PCR, IHC and Western blot. Furthermore, small interfering RNA (shRNA)-mediated silencing of stathmin was employed in LAC cells to investigate cell proliferation, invasion and apoptosis. In this study, we showed that overexpression of stathmin was significantly associated with poorly differentiated, lymph node metastasis and advance TNM stages of lung adenocarcinoma. And silencing of stathmin expression inhibited the proliferation, migration and invasion of lung adenocarcinoma PC-9 cells, and retarded the growth of PC-9 cells xenografts in nude mice. Additionally, the anticarcinogenic efficacy of stathmin silencing might be involved in P38 and MMP2 signaling pathways. In conclusion, these results showed that stathmin expression was significantly up-regulated in LAC, which may act as a biomarker for LAC. Furthermore, silence of stathmin inhibiting LAC cell growth indicated that stathmin may be a promising molecular target for LAC therapy.

Evaluation of efficacy and safety for recombinant human adenovirus-p53 in the control of the malignant pleural effusions via thoracic perfusion.

A certain number of studies have showed that p53 gene transfer has an anti-tumor activity in vitro and in vivo. This study was to evaluate the efficacy and safety of thoracic perfusion of recombinant human adenovirus p53 (rAd-p53, Gendicine) for controlling malignant pleural effusion (MPE). We searched for the relevant studies from the database of MEDLINE, Web of Science, EMBASE, Cochrance Library and CNKI to collect the trials concerning the efficacy and safety of rAd-p53 to treat MPE. Fourteen randomised controlled trials (RCTs) with 879 patients were involved in this analysis. The rAd-p53 combined with chemotherapeutic agents significantly improved the overall response rate (ORR) (P < 0.001; odds ratio = 3.73) and disease control rate (DCR) (P < 0.001; odds ratio = 2.32) of patients with MPE as well as the quality of life (QOL) of patients (P < 0.001; odds ratio = 4.27), compared with that of chemotherapeutic agents alone. In addition, the participation of rAd-p53 did not have an obvious impact on the most of incidence of adverse reactions (AEs) (P < 0.05) except the fever (P < 0.001). However, the fever was self-limited and could be tolerated well. The application of rAd-p53 through thoracic perfusion for treating MPE had a better efficacy and safety, which could be a potential choice for controlling MPE.

Efficacy and safety of icotinib in treating non-small cell lung cancer: a systematic evaluation and meta-analysis based on 15 studies.

Icotinib is a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that developed and used in China; this work was to evaluate its efficacy and safety in treating non-small cell lung cancer (NSCLC). Clinical studies evaluating the efficacy and safety of icotinib in treating NSCLC were identified from the databases of Medline, Web of Science, Embase and Cochrance Library. Pooled efficacy and safety of icotinib were calculated through a series of predefined search strategies. A total of 15 studies with 2,304 patients were involved in this study. The overall response rate (ORR) and disease control rate (DCR) of icotinib were 40.99% (95% CI: 33.77% to 48.22%) and 77.16% (95% CI: 51.43% to 82.31%). The pooled progression-free survival (PFS) and overall survival (OS) were 7.34 months (95% CI: 5.60 to 9.07) and 14.98 months (95% CI: 9.78 to 20.18). Patients with EGFR mutations exhibited better ORR (OR = 3.67, p < 0.001), DCR (OR = 1.39, p = 0.001) and PFS (11.0 ± 0.76 vs. 1.97 ± 0.82 months). Moreover, patients with rash had a higher ORR (OR = 2.14, p = 0.001) than those without rash. The common adverse effects (AEs) included skin rash (31.4%), diarrhea (14.2%), pruritus (6.7%) and hepatic toxicity (3.8%) and most of them were well tolerated. In conclusion, Icotinib is an effective and well tolerated regimen for Chinese patients with advanced NSCLC. Further randomized trials with large population are required to provide stronger evidence for icotinib in treating NSCLC.

Overexpression of stathmin promotes metastasis and growth of malignant solid tumors: a systemic review and meta-analysis.

Stathmin has been investigated to be involved in development and progress of malignant tumors. This study was to clarify the relationship between expression of stathmin and tumors and assess its clinical significance. We identified 25 studies with a total of 3,571 individuals from the electronic bibliographic databases and strictly evaluated the quality and heterogeneity of included studies. We analysed the relationship between expression of stathmin and clinical characteristics by the fixed-effects and random-effects of meta-analysis and constructed a summary receiver-operator characteristic curve to estimate the test characteristics. The results showed that patients with cancer displayed a higher stathmin expression than those of non-cancer individuals (OR, 0.31), and overexpression of stathmin correlated with tumor cell differentiation (OR, 0.73), lymph node invasion (OR, 0.80) and high TNM stage (OR, 0.67). The pooled sensitivity of stathmin for distinguishing malignant tumors was 0.73 and the specificity was 0.77. The maximum balance joint for sensitivity and specificity (the Q-value) was 0.7566 and the area under the curve (AUC) was 0.8234. In conclusion, these results showed that overexpression of stathmin intimately correlated with malignant behavior of tumors, suggesting it could be a risk factor of malignant tumors. Stathmin had great sensitivity and specificity indicated it should be a significant molecular biomarker for malignant tumors.

Evaluation of estimation of prevalence ratio using bayesian log-binomial regression model / 中华流行病学杂志

To evaluate the estimation of prevalence ratio (PR) by using bayesian log-binomial regression model and its application,we estimated the PR of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea in their infants by using bayesian log-binomial regression model in Openbugs software.The results showed that caregivers' recognition of infant's risk signs of diarrhea was associated significantly with a 13％ increase of medical care-seeking.Meanwhile,we compared the differences in PR's point estimation and its interval estimation of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea and convergence of three models (model 1:not adjusting for the covariates;model 2:adjusting for duration of caregivers' education,model 3:adjusting for distance between village and township and child month-age based on model 2) between bayesian log-binomial regression model and conventional log-binomial regression model.The results showed that all three bayesian log-binomial regression models were convergence and the estimated PRs were 1.130(95％CI:1.005-1.265),1.128(95％CI:1.001-1.264)and 1.132(95％CI:1.004-1.267),respectively.Conventional log-binomial regression model 1 and model 2 were convergence and their PRs were 1.130(95％ CI:1.055-1.206) and 1.126(95％ CI:1.051-1.203),respectively,but the model 3 was misconvergence,so COPY method was used to estimate PR,which was 1.125 (95％CI:1.051-1.200).In addition,the point estimation and interval estimation of PRs from three bayesian log-binomial regression models differed slightly from those of PRs from conventional log-binomial regression model,but they had a good consistency in estimating PR.Therefore,bayesian log-binomial regression model can effectively estimate PR with less misconvergence and have more advantages in application compared with conventional log-binomial regression model.

Evaluation of estimation of prevalence ratio using bayesian log-binomial regression model / 中华流行病学杂志

To evaluate the estimation of prevalence ratio (PR) by using bayesian log-binomial regression model and its application,we estimated the PR of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea in their infants by using bayesian log-binomial regression model in Openbugs software.The results showed that caregivers' recognition of infant's risk signs of diarrhea was associated significantly with a 13％ increase of medical care-seeking.Meanwhile,we compared the differences in PR's point estimation and its interval estimation of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea and convergence of three models (model 1:not adjusting for the covariates;model 2:adjusting for duration of caregivers' education,model 3:adjusting for distance between village and township and child month-age based on model 2) between bayesian log-binomial regression model and conventional log-binomial regression model.The results showed that all three bayesian log-binomial regression models were convergence and the estimated PRs were 1.130(95％CI:1.005-1.265),1.128(95％CI:1.001-1.264)and 1.132(95％CI:1.004-1.267),respectively.Conventional log-binomial regression model 1 and model 2 were convergence and their PRs were 1.130(95％ CI:1.055-1.206) and 1.126(95％ CI:1.051-1.203),respectively,but the model 3 was misconvergence,so COPY method was used to estimate PR,which was 1.125 (95％CI:1.051-1.200).In addition,the point estimation and interval estimation of PRs from three bayesian log-binomial regression models differed slightly from those of PRs from conventional log-binomial regression model,but they had a good consistency in estimating PR.Therefore,bayesian log-binomial regression model can effectively estimate PR with less misconvergence and have more advantages in application compared with conventional log-binomial regression model.

Relationship between prevalence of Kashin-Beck disease and ecological environment in Gansu Province / 中华地方病学杂志

Objective To explore the relationship between prevalence of Kashin-Beck disease (KBD) and ecological environment, and to broaden the perspective of KBD etiology. Methods In 37 counties of KBD areas in Gansu Province, information about the ecological environment and implementation situation of control measures (altitude, temperature, rainfall, evapo ration, frost free period, annual sunshine hours, population density, per capita income, the proportion of staple food, returning farmland to forest, to forestry and replant crops) and X-ray detection rate of KBD of 7-12-year-old children in 2012 - 2014 was collected. Using four quantile regression method, the regression model was introduced to analyze the 11 ecological factors which related to the pathogenesis of KBD. The effect of three points on X-ray detection rate of KBD was estimated. Results The X-ray detection rate of KBD was independent of altitude, temperature, evaporation, population density, per capita income and cash crops, and was dependent of rainfall, frost free period, annual sunshine hours, the staple food purchase ratio, and returning farmland to forest and grassland. No matter where in any place numbered, the higher rainfall (measure value:0.003 3 to 0.006 4), the longer frost free period (measure value: 0.029 2 to 0.043 8), the longer annual sunshine hours (measure value:0.001 6 to 0.001 8), and the higher staple food purchase ratio (measure value:0.019 7 to 0.027 6), the higher risk of X-ray detection rate of KBD; the higher returning farmland to forest and to grassland, the lower risk of X-ray detection rate of KBD (measure value: - 0.037 2 to - 0.013 3). Conclusion The X-ray detection rate of KBD is closely related to local ecological environment.