Sidong Chen

Dose–Risk and Duration–Risk Relationships between Aspirin and Colorectal Cancer: A Meta-Analysis of Published Cohort Studies

Background In previous meta-analyses, aspirin use has been associated with reduced risk of colorectal cancer. However, uncertainty remains on the exact dose–risk and duration–risk relationships. Methods We identified studies by searching several English and Chinese electronic databases and reviewing relevant articles. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression. Subgroup analyses were conducted to explore possible heterogeneity among studies. Potential heterogeneity was calculated as Q statistic and I 2 value. Publication bias was evaluated using funnel plots and quantified by the Begg’s and Egger’s test. Results Twelve studies were included in this meta-analysis. An inverse association between aspirin use and colorectal cancer was observed in both the overall group (RR = 0.74, 95% CI 0.64–0.83 for aspirin dose; RR = 0.80, 95% CI 0.75–0.85 for frequency of aspirin use; RR = 0.75, 95% CI 0.68–0.81 for years of aspirin use) and subgroups stratified by sex and cancer site. The dose-response meta-analysis showed that there was a 20% statistically significant decreased risk of colorectal cancer for 325 mg aspirin per day increment, 18% decreased risk for 7 times aspirin per week increment and 18% decreased risk for 10 years aspirin increment. Conclusion Long-term (>5 years), low-dose (75–325 mg per day) and regular aspirin use (2–7 times per week) can effectively reduce the risk of colorectal cancer.

The Efficacy and Safety of Linezolid and Glycopeptides in the Treatment of Staphylococcus aureus Infections

To assess the effectiveness and safety of linezolid in comparison with glycopeptides (vancomycin and teicoplanin) for the treatment of Staphylococcus aureus infections, we conducted a meta-analysis of relevant randomized controlled trials. A thorough search of Pubmed and other databases was performed. Thirteen trials on 3863 clinically assessed patients were included. Linezolid was slightly more effective than glycopeptides in the intent-to-treat population (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01–1.10), was more effective in clinically assessed patients (OR 95% CI: 1.38, 1.17–1.64) and in all microbiologically assessed patients (OR 95% CI: 1.38, 1.15–1.65). Linezolid was associated with better treatment in skin and soft-tissue infections (SSTIs) patients (OR 95% CI: 1.61, 1.22–2.12), but not in bacteraemia (OR 95% CI: 1.24, 0.78–1.97) or pneumonia (OR 95% CI: 1.25, 0.97–1.60) patients. No difference of mortality between linezolid and glycopeptides was seen in the pooled trials (OR 95% CI: 0.98, 0.83–1.15). While linezolid was associated with more haematological (OR 95% CI: 2.23, 1.07–4.65) and gastrointestinal events (OR 95% CI: 2.34, 1.53–3.59), a significantly fewer events of skin adverse effects (OR 95% CI: 0.27, 0.16–0.46) and nephrotoxicity (OR 95% CI: 0.45, 0.28–0.72) were recorded in linezolid. Based on the analysis of the pooled data of randomized control trials, linezolid should be a better choice for treatment of patients with S. aureus infections, especially in SSTIs patients than glycopeptides. However, when physicians choose to use linezolid, risk of haematological and gastrointestinal events should be taken into account according to the characteristics of the specific patient populations.

XRCC1 Arg399Gln polymorphism confers risk of breast cancer in American population: a meta-analysis of 10846 cases and 11723 controls.

Background In the X-ray repair cross-complementing group 1 (XRCC1) gene, a polymorphism, Arg399Gln (rs25487), has been shown to change neoconservative amino acid and thus result in alternation of DNA repair capacity. Numerous studies have investigated the association between Arg399Gln and breast cancer risk in the American population, but yielding inconsistent results. This study aimed to clarify the role of this polymorphism in susceptibility to breast cancer. Methods Literatures were searched in multiple databases including PubMed, Springer Link, Ovid, EBSCO and ScienceDirect databases up to April 2013. A comprehensive meta-analysis was conducted to estimate the overall odds ratio (OR), by integrating data from 18 case control studies of 10846 cases and 11723 controls in the American population. Results Overall, significant association was observed between the Arg399Gln polymorphism and breast cancer risk under the random-effects model (OR for dominant model = 1.12, 95% CI: 1.02–1.24, P heterogeneity = 0.003; OR for additive model = 1.07, 95% CI: 1.01–1.14, P heterogeneity = 0.017). Further sensitivity analysis supported the robust stability of this current result by showing similar ORs before and after removal of a single study. Conclusions This meta-analysis suggests that the XRCC1 Arg399Gln polymorphism may significantly contribute to susceptibility of breast cancer in the American population.

Construction and characterization of an anti‐asialoglycoprotein receptor single‐chain variable‐fragment‐targeted melittin

Antibody–therapeutic agent conjugation to be delivered specifically to tumor cells is required for many target‐based therapeutic strategies. In the present study, a recombinant immunotoxin was constructed by which melittin was fused to an anti‐asialoglycoprotein receptor (ASGPR) single‐chain variable fragment antibody (C1), and targeting ability and cytolytic efficacy of the fusion protein were studied. Our results suggested that the recombinant 29.4 kDa protein C1M was expressed in Escherichia coli as a soluble style. Binding of C1M to the surface of hepatocellular carcinoma (HCC) cells was confirmed by both immunohistochemistry and flow cytometry assays. C1M kept the hemolytic activity of melittin and exhibited cytolytic capacity to HepG2 cells at a concentration of 1.5 µg/mL, under which erythrocytes would not be lysed. The effects were greatly inhibited by coadministration with asialoorosomucoid, a natural ligand for ASGPR. These results suggested that C1M conferred targeting and ASGPR‐specific cytotoxicity to HCC cells. This work makes it possible to further investigate its antihepatoma efficacy in vivo.

Livestock-associated methicillin and multidrug resistant S. aureus in humans is associated with occupational pig contact, not pet contact.

This study aimed to explore the association of livestock-associated S. aureus with occupational pig contact and pet contact. In this cross-sectional study, 1,422 participants (including 244 pig workers, 200 pet-owning workers and 978 control workers) responded to a questionnaire and provided a nasal swab for S. aureus analysis. Resulting isolates were tested for antibiotic susceptibility, the immune evasion cluster (IEC) genes, and multilocus sequence type. Compared with controls, the pig workers demonstrated a greater prevalence of multidrug-resistant S. aureus (MDRSA) [prevalence ratio (PR) = 3.38; 95% CI: 2.07–5.53] and methicillin-resistant S. aureus (MRSA) (PR = 7.42; 95% CI: 3.71–14.83), but the prevalence of MDRSA and MRSA was similar in pet-owning workers and controls. There was a positive relation of frequency of pig contact with prevalence of MDRSA and MRSA carriage. Only pig workers carried MDRSA CC9 (16 isolates) and MRSA CC9 (16 isolates), and all of these isolates were tetracycline resistant and absent of IEC genes. These findings suggest that livestock-associated MRSA and MDRSA(CC9, IEC-negative, tetracycline-resistant) in humans is associated with occupational pig contact, not pet contact, and support growing concern about antibiotics use in pig farms and raising questions about the potential for occupational exposure to opportunistic S. aureus.

Second-hand smoke exposure in different types of venues: before and after the implementation of smoke-free legislation in Guangzhou, China

Objectives Smoke-free legislation was implemented in Guangzhou on 1 September 2010. However, the smoke-free policy did not cover all indoor areas and smoking rooms can be set in some public places. This study aimed to assess changes in self-reported second-hand smoke (SHS) exposure in different types of venues and in homes, in order to evaluate the effectiveness of smoke-free legislation. Methods/design A repeated cross-sectional survey of representative participants was conducted in Guangzhou before and after the smoke-free legislation. Logistic regression models were used to examine the effectiveness of smoke-free legislation. Main outcome measures Self-reported exposure to SHS,antitobacco advertisements and tobacco advertisements. Participants A total of 4900 participants before the ban and 5135 participants after the ban were selected using a multistage stratified design. Results In full smoking ban places, overall self-reported SHS exposure has declined significantly from 58.8% to 50.3% (p<0.05) with greater drops in cultural venues, government offices and commercial venues. The smoke-free policy did not alter SHS exposure in smokers’ homes (39.6% in 2009 vs 40.0% in 2011; p=0.454). Although a slight decrease in SHS exposure was observed in smoking rooms in hotels, workplaces, restaurants, cafes/bars/nightclubs and amusement parks, SHS continued to be high in those areas. The implementation of smoke-free legislation was accompanied by an increase in antitobacco advertisements. Conclusions SHS exposure declines more significantly in full smoking ban places than in partial smoking ban places. The smoke-free policy in public places does not lead to more SHS exposure in homes. Therefore, it is recommended that Guangzhou should implement a 100% smoke-free policy in all public places and workplaces in the future.

Variants in the 5′-upstream region of GPC5 confer risk of lung cancer in never smokers

BACKGROUND A recent genome-wide study (GWAS) has identified GPC5 as a promising susceptibility gene for Lung cancer in never smokers (LCINS). However, the most significant single nucleotide polymorphism (SNP) in this GWAS, rs2352028, has yielded controversial results. The aim of this study was to clarify the relationship between rs2352028 and LCINS. Considering that rs2352028 might be largely marker-SNP correlated to causative variants, two predicted functional SNPs, rs3759452 and rs7322083, were additionally investigated in this study. METHODS A hospital based case-control study including 298 cases and 599 controls in a never-smoking Chinese Han population was conducted, and then a meta-analysis combining our data and published data was performed to verify the findings. RESULTS The SNP rs3759452, predicted to potentially change transcription factor binding site of GPC5, was significantly associated with LCINS risk (odds ratio for dominant model=1.55, 95% confidence interval=1.14-2.12). Nevertheless, no significant evidence was showed for rs2352028, both in our case-control study and the meta-analysis including 13 studies of 2342 LCINS cases and 13,398 never-smoking controls. Further subgroup meta-analysis according to population ethnicity and cancer histology also reported no significant association of rs2352028. CONCLUSIONS The association conferring rs3759452 further supports the value of GPC5 in susceptibility to LCINS. Nevertheless, comprehensive analyses are warranted to dissect the functional mechanism underpinning rs3759452.

Dose–response relations between second-hand smoke exposure and depressive symptoms among middle-aged women

A growing body of evidence indicates a strong association between smoking and depression. However, little is known about the possible effects of second-hand smoke (SHS) exposure on depression. This study aimed to examine the potential dose-response relation between SHS exposure and depressive symptoms among non-smoking middle-aged women. A cross-sectional survey was conducted using a stratified three-stage sampling method. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression Scale with a cut-off point of 16. Self-reported SHS exposure was defined as non-smokers׳ inhalation of the smoke exhaled from smokers on at least one day a week. The multivariable logistic regression analysis was completed with adjustment for potential confounders. Among 1280 middle-aged women, 19.4% were classified as having depressive symptoms. There was a 104% increased odds of depressive symptoms corresponding to SHS exposure in general (OR=2.04, 95% CI 1.48-2.79) using no exposure as reference. There were significant positive relations between SHS exposure in general and depressive symptoms in a dose-response manner. These significant trends were observed consistently whether SHS exposure occurred in homes or workplaces. Our findings suggest that long-term and regular SHS exposure is associated with a significant, dose-dependent increase in risk of depressive symptoms.

Multiple Sexual Partners as a Potential Independent Risk Factor for Cervical Cancer: a Meta-analysis of Epidemiological Studies

Its known that having multiple sexual partners is one of the risk factors of human papillomavirus (HPV) infection which is a major cause of cervical cancer. However, it is not clear whether the number of sexual partners is an independent risk factor for cervical cancer. We identified relevant studies by searching the databases of MEDLINE, PubMed and ScienceDirect published in English from January 1980 to January 2014. We analyzed those studies by combining the study-specific odds ratios (ORs) using random-effects models. Forty-one studies were included in this meta-analysis. We observed that the number of sexual partners was associated with the occurrence of non-malignant cervical disease (OR=1.82, 95%CI 1.63-2.00) and invasive cervical carcinoma (OR=1.77, 95%CI 1.50-2.05). Subgroup analyses revealed that the association remained significant after controlling for HPV infection (OR=1.52, 95%CI 1.21-1.83 for non-malignant disease; OR=1.53, 95%CI 1.30- 1.76 for invasive cervical carcinoma). We found that there was a non-linear relation of the number of sexual partners with both non-malignant cervical disease and invasive cervical carcinoma. The risk of both malignant and non-malignant disease is relatively stable in women with more than 4-7 sexual partners. Furthermore, the frequency-risk of disease remained significant after controlling for HPV infection.The study suggested that having multiple sexual partners, with or without HPV infection, is a potential risk factor of cervical cancer.

Three single nucleotide variants of the HDAC gene are associated with type 2 diabetes mellitus in a Chinese population: a community-based case-control study.

OBJECTIVES There are no data regarding the possible role of the single nucleotide polymorphism (SNP) of class I histone deacetylases (HDACs) in type 2 diabetes mellitus (DM). We designed this study to examine whether polymorphisms of HDACs can be implicated in that disease. METHODS A community-based, case-control study was conducted, with a total of 568 subjects (284 patients and 284 controls) enrolled. Four polymorphisms of HDAC1 (rs1741981) and HDAC3 (rs11741808, rs2547547, rs2530223) were examined by the use of TaqMan technology. RESULTS We found a significant association with risk of type 2 DM for three SNPs of HDAC3, including rs11741808 [odds ratio (OR)=0.53, 95% confidence interval (CI): 0.35-0.81], rs2547547 [OR=1.72, 95% CI: 1.13-2.64], and rs2530223 [OR=1.39; 95% CI: 1.01-1.91]. Subgroup analysis showed that BMI≥23kg/m(2), high triglyceride and high blood pressure, together with the rs11741808AG genotype, were associated with a significantly decreased risk for type 2 DM, with ORs of 0.50 (95% CI: 0.27-0.91), 0.38 (95% CI: 0.20-0.71) and 0.43 (95% CI: 0.24-0.76) compared with the AA genotype, respectively. In a population with normal total cholesterol, the AG genotype yielded a significantly decreased risk of type 2 DM risk, with an OR of 0.42 (95% CI: 0.25-0.70) when compared with the persons of the AA genotype. For rs2547547, in a population with normal total cholesterol and triglyceride, the AG genotype was associated with a significantly increased risk of type 2 DM, with ORs of 1.92 (95% CI: 1.17-3.15) and 2.24 (95% CI: 1.28-3.94) when compared with the population carrying the AA genotype. CONCLUSIONS The results suggest that variants of HDAC3 contribute to an increased prevalence of type 2 DM in the Chinese Han population.