Preparation and antifungal activity evaluation of hinokitiol emulsifiable concentrate against Sclerotinia sclerotiorum.

Hinokitiol is a natural broad-spectrum antimicrobial monoterpenoid, which is widely used as an antiseptic in food, cosmetics and other products. In the present study, the toxic actions of hinokitiol to the plant pathogen Sclerotinia sclerotiorum were investigated. The EC50 value for mycelial growth inhibition was 2.63 µg/mL, and there was no positive or negative cross-resistance between hinokitiol and carbendazim. The emulsifiable concentrate of 30% hinokitiol was prepared, which has excellent application prospect in the prevention of sclerotinia and gray mould. Hinokitiol is a promising spray fungicide for stems and leaves rather than seeds and roots.

Antifungal Activity and Putative Mechanism of HWY-289, a Semisynthetic Protoberberine Derivative, against Botrytis cinerea.

The emergence of resistant pathogens has increased the demand for alternative fungicides. The use of natural products as chemical scaffolds is a potential method for developing fungicides. HWY-289, a semisynthetic protoberberine derivative, demonstrated broad-spectrum and potent activities against phytopathogenic fungi, particularly Botrytis cinerea (with EC50 values of 1.34 µg/mL). SEM and TEM imaging indicated that HWY-289 altered the morphology of the mycelium and the internal structure of cells. Transcriptomics revealed that it could break down cellular walls through amino acid sugar and nucleotide sugar metabolism. In addition, it substantially decreased chitinase activity and chitin synthase gene (BcCHSV) expression by 53.03 and 82.18% at 1.5 µg/mL, respectively. Moreover, this impacted the permeability and integrity of cell membranes. Finally, HWY-289 also hindered energy metabolism, resulting in a significant reduction of ATP content, ATPase activities, and key enzyme activities in the TCA cycle. Therefore, HWY-289 may be a potential candidate for the development of plant fungicides.

Targeting SIK3 to modulate hippocampal synaptic plasticity and cognitive function by regulating the transcription of HDAC4 in a mouse model of Alzheimer's disease.

Cognitive deterioration and memory decline associated with the progression of Alzheimer's disease (AD) primarily results from synaptic failure. However, current understanding of the upstream regulatory mechanisms controlling synaptic plasticity remains limited. Salt-inducible kinase 3 (SIK3) is central to the signal pathway and is involved in neuronal regulation of sleep duration in mice. We speculated that the SIK3 cascade signaling pathway might contribute to the pathogenesis of AD. Thus, the present study employed AD transgenic mouse models, Morris Water Maze, virus-mediated gene transfer, electrophysiology, co-immunoprecipitation, western blotting, quantitative polymerase chain reaction, immunofluorescence, ChIP-qPCR, Golgi-Cox staining and dendritic spine analysis to investigate this connection. Our results revealed that SIK3 mRNA/protein expression was significantly reduced in middle-aged AD transgenic mouse models and AD patients. Conditional deletion of SIK3 gene in dorsal hippocampal neurons of 5×FAD mice further accelerated cognitive deterioration and impaired synaptic plasticity. In hippocampal neuronal cultures, SIK3 formed a complex with HDAC4, directly phosphorylated HDAC4 and regulated its nuclear cytoplasmic shuttle. Overexpression of SIK3 could facilitate the expression of synaptic plasticity-related genes by directly repressing mef2c or involving the recruitment of histone deacetylase to promoter regions of target genes through regulation of p-HDAC4, and vice versa. Moreover, up-regulation of SLP-S, the truncated fragment of SIK3, in dorsal hippocampal neurons, restored the synaptic plasticity and alleviates the cognitive impairment in 5×FAD mice. Collectively, these findings revealed a novel and important role of SIK3-HDAC4 regulation of synaptic plasticity and propose a new target for therapeutic approaches of cognitive deficits associated with AD.

The first established microsatellite markers to distinguish Candida orthopsilosis isolates and detection of a nosocomial outbreak in China.

The infection proportion of Candida orthopsilosis, a member of the C. parapsilosis complex, has increased globally in recent years, and nosocomial outbreaks have been reported in several countries. This study aimed to establish microsatellite loci-based typing method that was able to effectively distinguish among C. orthopsilosis isolates. Three reference C. orthopsilosis genome sequences were analyzed to identify repeat loci. DNA sequences containing over eight bi- or more nucleotide repeats were selected. A total of 51 loci were initially identified, and locus-specific primers were designed and tested with 20 epidemiologically unrelated isolates. Four loci with excellent reproducibility, specificity, and resolution for molecular typing purposes were identified, and the combined discriminatory power (DP, based on 20 epidemiologically unrelated isolates) of these four loci was 1.0. Reproducibility was demonstrated by consistently testing three strains each in triplicate, and stability, demonstrated by testing 10 successive passages. Then, we collected 48 C. orthopsilosis non-duplicate clinical isolates from the China Hospital Invasive Fungal Surveillance Net study to compare the DP of the microsatellite-based typing with internal transcribed spacer (ITS) and amplified fragment length polymorphism (AFLP) typing analyses, using ATCC 96139 as a reference strain. These 49 isolates were subdivided into 12 microsatellite types (COMT1-12), six AFLP types, and three ITS types, while all the isolates with the same COMT belonged to consistent AFLP and ITS type, demonstrating the high DP of our microsatellite-type method. According to our results, COMT12 was found to be the predominant type in China, and COMT5 was the second largest and responsible for causing a nosocomial outbreak. This microsatellite-type method is a valuable tool for the differentiation of C. orthopsilosis and could be vital for epidemiological studies to determine strain relatedness and monitor transmission.

Risk Factors and Outcomes of Patients with Carbapenem-Resistant Pseudomonas aeruginosa Bloodstream Infection.

Purpose: The rising incidence of carbapenem-resistant Pseudomonas aeruginosa (PA) bloodstream infection (BSI) has made the selection of antibiotic therapy more difficult and caused high mortality. This study was aimed at exploring the risk factors for carbapenem-resistant Pseudomonas aeruginosa (CRPA) bloodstream infection and identifying the risk factors for the outcomes of patients with PA-BSI. Methods: We performed a retrospective cohort study of patients with PA-BSI in a tertiary hospital from January 2017 to December 2021 in China. Epidemiological, clinical, and microbiological characteristics were described. Risk factors for CRPA-BSI and the outcomes of PA-BSI inpatients were identified, using multivariate logistic regression analysis. Results: A total of 198 PA-BSI inpatients were included. The negative outcome rate was significantly higher in patients infected with CRPA (15/34, 44.12%) than with carbapenem-susceptible Pseudomonas aeruginosa (CSPA) (35/164, 21.34%), and the difference was statistically significant (P=0.005). Multivariate logistic regression analysis showed that previous exposure to carbapenem (OR 3.519, 95% CI 1.359-9.110, P=0.010) was an independent risk factor for CRPA-BSI. In addition, CRPA (OR 1.615, 95% CI 0.626-4.171, P=0.32) was not an independent risk factor for negative outcome among PA-BSI inpatients. Conclusion: Our study showed that previous exposure to carbapenem was an independent risk factor for CRPA-BSI. CRPA was not an independent risk factor for a negative outcome in PA-BSI inpatients.

Design, Synthesis, and Structure-Activity Relationship Studies of Magnolol Derivatives as Antifungal Agents.

Plant pathogenic fungi seriously affect agricultural production and are difficult to control. The discovery of new leads based on natural products is an important way to innovate fungicides. In this study, 30 natural-product-based magnolol derivatives were synthesized and characterized on the basis of NMR and mass spectroscopy. Bioactivity tests on phytopathogenic fungi (Rhizoctonia solani, Fusarium graminearum, Botrytis cinerea, and Sclerotinia sclerotiorum) in vitro of these compounds were performed systematically. The results showed that 11 compounds were active against four kinds of phytopathogenic fungi with EC50 values in the range of 1.40-20.00 µg/mL, especially compound L5 that exhibited excellent antifungal properties against B. cinerea with an EC50 value of 2.86 µg/mL, approximately 2.8-fold more potent than magnolol (EC50 = 8.13 µg/mL). Moreover, compound L6 showed the highest antifungal activity against F. graminearum and Rhophitulus solani with EC50 values of 4.39 and 1.40 µg/mL, respectively, and compound L7 showed good antifungal activity against S. sclerotiorum. Then, an in vivo experiment of compound L5 against B. cinerea was further investigated in vivo using infected tomatoes (curative effect, 50/200 and 36%/100 µg/mL). The physiological and biochemical studies illustrated that the primary action mechanism of compound L5 on B. cinerea might change the mycelium morphology, increase cell membrane permeability, and destroy the function of mitochondria. Furthermore, structure-activity relationship (SAR) studies revealed that hydroxyl groups play a key role in antifungal activity. To sum up, this study provides a reference for understanding the application of magnolol-based antifungal agents in crop protection.

Effects of SHAM on the Sensitivity of Sclerotinia sclerotiorum and Botrytis cinerea to QoI Fungicides.

It is a common practice to add salicylhydroxamic acid (SHAM) into artificial medium in the in vitro sensitivity assay of fungal phytopathogens to the quinone outside inhibitor (QoI) fungicides. The rationale for adding SHAM is to inhibit fungal alternative oxidase, which is presumed to be inhibited by secondary metabolites of plants. Therefore, the ideal characteristics of SHAM should be almost nontoxic to phytopathogens and have no significant effect on control efficacy of fungicides. However, this study showed that the average effective concentration for 50% inhibition (EC50) of mycelial growth values of SHAM were 97.5 and 401.4 µg/ml for Sclerotinia sclerotiorum and Botrytis cinerea, respectively. EC50 values of the three QoI fungicides azoxystrobin, kresoxim-methyl, and trifloxystrobin in the presence of SHAM at 20 and 80 µg/ml for S. sclerotiorum and B. cinerea, respectively, declined by 52.7 to 78.1% compared with those without SHAM. For the dicarboximide fungicide dimethachlone, the average EC50 values in the presence of SHAM declined by 18.2% (P = 0.008) for S. sclerotiorum and 35.9% (P = 0.012) for B. cinerea. Pot experiments showed that SHAM increased control efficacy of the three QoI fungicides against the two pathogens by 43 to 83%. For dimethachlone, SHAM increased control efficacy by 134% for S. sclerotiorum and 86% for B. cinerea. Biochemical studies showed that SHAM significantly inhibited peroxidase activity (P = 0.024) of B. cinerea and esterase activity (P = 0.015) of S. sclerotiorum. The strong inhibitions of SHAM per se on mycelial growth of B. cinerea and S. sclerotiorum and significant influences on the sensitivity of the two pathogens to both the QoI fungicides and dimethachlone as well as inhibitions on peroxidase and esterase indicate that SHAM should not be added in the in vitro assay of sensitivity to the QoI fungicides.

Serotype distribution and antibiotic resistance of Streptococcus pneumoniae isolates from 17 Chinese cities from 2011 to 2016.

BACKGROUND: Streptococcus pneumoniae, the leading pathogen of bacterial infections in infants and the elderly, is responsible for pneumococcal diseases with severe morbidity and mortality. Emergence of drug-resistant strains presented new challenges for treatment and prevention. Vaccination has proven to be an effective means of preventing pneumococcal infection worldwide. Detailed epidemiological information of antibiotic susceptibilities and serotype distribution will be of great help to the management of pneumococcal infections. METHODS: A total of 881 S. pneumoniae isolates were collected from patients at 23 teaching hospitals in 17 different cities from 2011 to 2016. The main specimen types included sputum, blood, broncho-alveolar lavage fluid, pharyngeal swabs, and cerebrospinal fluid. Minimum inhibitory concentrations (MICs) were determined using the agar dilution method. Capsular serotypes were identified using latex agglutination and quellung reaction test. Molecular epidemiology was investigated using multilocus sequence typing. RESULTS: S. pneumoniae isolates were highly resistant to macrolides, tetracycline, and trimethoprim/sulfamethoxazole. The rate of resistance to penicillin was 51.6% (oral breakpoint). However, levofloxacin and moxifloxacin maintained excellent antimicrobial activity and all of the isolated strains were susceptible to vancomycin. Twenty-two serotypes were identified among the 881 isolates. Prevalent serotypes were 19F (25.7%), 19A (14.0%), 15 (6.8%), 6B (3.6%), 6A (3.0%), and 17 (2.8%). The overall vaccine coverage rates for 7- and 13-valent pneumococcal conjugate vaccines were 37.5% and 58.3%, respectively. Vaccine coverage rates in young children and economically underdeveloped regions were higher than those in older adults and developed regions. Vaccine-covered serotypes demonstrated higher resistance compared with uncovered serotypes. Molecular epidemiological typing demonstrated that S. pneumoniae showed significant clonal dissemination and that ST271 (120, 28.3%), ST320 (73, 17.2%) and ST81 (27, 6.6%) were the major STs. CONCLUSIONS: High resistance to clinical routine antibiotics was observed for all 881 S. pneumoniae strains. Drug resistance varied among different serotypes and age groups. Prevalent serotypes among the isolates were 19F, 19A, 15, 6B, 6A, and 17. Community-acquired strains should also be included in future studies to gain a better understanding of the prevalence and resistance of S. pneumoniae in China.

The rapid in vivo evolution of Pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence.

Pseudomonas aeruginosa is an opportunistic pathogen that causes severe airway infections in humans. These infections are usually difficult to treat and associated with high mortality rates. While colonizing the human airways, P. aeruginosa could accumulate genetic mutations that often lead to its better adaptability to the host environment. Understanding these evolutionary traits may provide important clues for the development of effective therapies to treat P. aeruginosa infections. In this study, 25 P. aeruginosa isolates were longitudinally sampled from the airways of four ventilator-associated pneumonia (VAP) patients. Pacbio and Illumina sequencing were used to analyse the in vivo evolutionary trajectories of these isolates. Our analysis showed that positive selection dominantly shaped P. aeruginosa genomes during VAP infections and led to three convergent evolution events, including loss-of-function mutations of lasR and mpl, and a pyoverdine-deficient phenotype. Specifically, lasR encodes one of the major transcriptional regulators in quorum sensing, whereas mpl encodes an enzyme responsible for recycling cell wall peptidoglycan. We also found that P. aeruginosa isolated at late stages of VAP infections produce less elastase and are less virulent in vivo than their earlier isolated counterparts, suggesting the short-term in vivo evolution of P. aeruginosa leads to attenuated virulence.

The effect of MDR1 C3435T polymorphism on the eradication rate of H. pylori infection in PPI-based triple therapy: A meta-analysis.

BACKGROUND: Several studies have reported that multidrug resistance gene 1 (MDR1) C3435T polymorphism was associated with the rate of Helicobacter pylori (H. pylori) eradication in proton pump inhibitor (PPI)-based triple therapy. However, the conclusions were inconsistent. Therefore, this meta-analysis was conducted to evaluate the impact of MDR1 C3435T polymorphism on H. pylori eradication by PPI-based triple therapy. METHODS: Seven eligible studies published up to August 2016 and including 1019 patients were identified by searching the Chinese Biomedical Literature database, Wan fang, PubMed, and the Web of Science electronic databases. Consequently, a meta-analysis was conducted with STATA software, using summary odds ratios (OR) and a 95% confidence interval (CI). RESULTS: Overall, there was no significant difference between MDR1 C3435T polymorphism and the eradication rate of H. pylori in the entire genetic model, irrespective of the PPI used. Furthermore, in Asian populations, the TT genotype decreased H. pylori eradication (TT vs CT+CC: OR=0.411, 95% CI = 0.280-0.602, P = 0.000). In addition, a significantly low eradication rate was observed in a recessive model, in which either lansoprazole (TT vs CT+CC: OR = 0.305, 95% CI = 0.184-0.504, P = 0.000) or omeprazole (TT vs CT+CC: OR = 0.229, 95% CI = 0.069-0.763, P = 0.016) was taken, in a subanalysis of individual PPIs. In the analyses that were stratified by disease type, no significant difference was observed in the peptic ulcer group and the combined diseases subgroup. CONCLUSION: This meta-analysis indicated that the TT genotype of the MDR1 C3435T polymorphism decreased H. pylori eradication in Asian populations and was also associated with a low cure rate of H. pylori in patients taking lansoprazole- and omeprazole-based triple therapies. However, future studies using larger sample sizes are required.

[Expression and affinity purification of Mycobacterium tuberculosis His-LprG-FLAG in HEK293T cells].

OBJECTIVE: To construct a eukaryotic expressing vector of Mycobacterium tuberculosis lipoprotein G (LprG), and express and purify the recombinant protein in HEK293T cells by affinity chromatography. METHODS: The LprG gene was amplified by PCR from the genome of MTB strain H37Rv. The subsequent PCR product and eukaryotic expressing vector pcDNA3.1 were digested by certain restriction enzymes. The recombinant vector, pcDNA3.1-His-LprG-FLAG, was constructed by ligation of target genes and the vector. After identified by enzymes digestion and DNA sequencing analysis, the correct recombinant vector was applied for transfection of HEK293T cells. The expression of His-LprG-FLAG was examined by Western blotting. The target fusion protein successfully expressed in HEK293T cells was purified by Ni(2+) affinity chromatography, and the purification and concentration of the protein was evaluated by SDS-PAGE and Western blotting. RESULTS: The recombinant vector pcDNA3.1-His-LprG-FLAG was successfully constructed, which was identified by double enzyme digestion and DNA sequencing. Western blotting indicated that the fusion protein was expressed in HEK293T cells transfected with the vector, with the molecular mass (Mr) being 27 000. By Ni2+ affinity chromatography, the fusion protein could be purified to a high concentration, as evaluated by SDS-PAGE and Western blotting. CONCLUSION: Fusion protein His-LprG-FLAG has been successfully prepared and expressed in HEK293T cells.

Baseline Sensitivity of Pyraclostrobin and Toxicity of SHAM to Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum is a cosmopolitan plant pathogen notable for its wide host range. The quinone outside inhibitor (QoI) fungicide pyraclostrobin has not been registered for control of S. sclerotiorum in China. In this study, baseline sensitivity of pyraclostrobin was established based on effective concentration for 50% inhibition of mycelial growth (EC50) values of 153 isolates of S. sclerotiorum collected from five provinces of China and toxicity of alternative oxidase inhibitor salicylhydroxamic acid (SHAM) to S. sclerotiorum was determined. Results showed that the frequency distribution of EC50 values of the 153 isolates was unimodal but with a right-hand tail. The mean EC50 value was 0.1027 µg/ml and the range of EC50 values was 0.0124 to 0.6324 µg/ml. Applied as a preventive fungicide in pot experiments, pyraclostrobin at 5, 15, and 45 µg/ml provided control efficacies of 61, 77, and 100%, respectively. There was no positive cross-resistance between pyraclostrobin and carbendazim or dimethachlon. EC50 values for SHAM against four isolates of S. sclerotiorum were 44.4, 51.8, 54.4, and 68.7 µg/ml. SHAM at 20 µg/ml could significantly increase not only the inhibitory effect of pyraclostrobin on mycelial growth on potato dextrose agar media but also the control efficacy in planta. These results indicated that SHAM should not be added into artificial media in in vitro assay of S. sclerotiorum sensitivity to pyraclostrobin. This has broad implications for assay of sensitivity of fungal pathogen to QoI fungicides.

Population dynamics of an Acinetobacter baumannii clonal complex during colonization of patients.

Acinetobacter baumannii has emerged as one of the leading pathogens causing hospital-acquired infection. The success of A. baumannii as a pathogen has to a large extent been attributed to its capacity to remodel its genome. Several major epidemic clonal complexes of A. baumannii spread across different health care facilities around the world, each of which contains a subset of diversified strains. However, little is known about the population dynamics during colonization of A. baumannii within hosts. Here, whole-genome sequencing was used to analyze population dynamics of A. baumannii strains isolated from a group of patients at different time points as well as from different sites of a particular patient. Seven out of nine of the sampled A. baumannii strains belonged to the international clone II (CC92 clonal complex). While the A. baumannii strains were found to be stable in three patients, there was a change of A. baumannii strains in one patient. Comparative genomic analysis revealed that the accessory genome of these strains contained a large set of virulence-encoding genes and these virulence factors might play a role in determining population dynamics. Microscale genome modification has been revealed by analysis of single nucleotide polymorphisms (SNPs) between A. baumannii strains isolated from the same patient. Parallel evolutionary traits have been observed during genome diversification when A. baumannii colonize in different patients. Our study suggested that both antibiotic usage and host environment might impose selective forces that drive the rapid adaptive evolution in colonizing A. baumannii.

Methylenetetrahydrofolate reductase A1298C polymorphism and diabetes risk: evidence from a meta-analysis.

AIM: The relationship between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the susceptibility of diabetes remains inclusive or controversial. For better understanding of the influence of MTHFR A1298C polymorphism on diabetes risk, we performed this meta-analysis. METHODS: All related articles were identified through a search of PubMed, Embase, Chinese Biomedical Literature Database (CBM, Chinese), China National Knowledge Infrastructure (CNKI), and Wangfang Database (Chinese). The relationship between the MTHFR A1298C polymorphism and diabetes susceptibility was conducted by odds ratios (ORs) and 95% confidence intervals. RESULTS: Total of six studies with 897 cases and 852 controls were included in our meta-analysis. Overall, the significance associated was found between MTHFR A1298C polymorphism and the susceptibility of diabetes under recessive model (CC vs. AC/AA: OR=1.70, 95% CI=1.18-2.45, p=0.004). On the subgroup analysis according to ethnicity, the results indicated that MTHFR A1298C polymorphism has a significant association with diabetes in Asian population under dominant model (CC/AC vs. AA: OR=1.31, 95% CI=1.003-1.72, p=0.047). However, there was no association found between MTHFR A1298C polymorphism and diabetes susceptibility in Caucasians. CONCLUSIONS: The results indicated that the MTHFR A1298C polymorphism is a dangerous factor for diabetes, especially for Asians.

Vascular endothelial growth factor +936C/T polymorphism and breast cancer risk: a meta-analysis of 13 case-control studies.

The association between vascular endothelial growth factor (VEGF) +936C/T polymorphism and breast cancer risk has been widely reported, but results were inconsistent. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Eligible articles were identified through search of databases including PubMed, Embase, and Chinese Biomedical Literature Database (CBM). The association between the VEGF +936C/T polymorphism and breast cancer risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). Finally, a total of 13 studies with 6,879 cases and 7,219 controls were included in our meta-analysis. Overall, a significant association was found between VEGF +936C/T polymorphisms and the risk of breast cancer in overall populations under five models (T vs. C: OR = 0.83, 95% CI = 0.73-0.94, P = 0.002; TT vs. CC: OR = 0.74, 95% CI = 0.61-0.91, P = 0.004, Fig. 1a; TC vs. CC: OR = 0.83, 95% CI = 0.71-0.96, P = 0.014; TT vs. CC/CT: OR = 0.77, 95% CI = 0.62-0.94, P = 0.010; TT/TC vs. CC: OR = 0.82, 95% CI = 0.72-0.95, P = 0.006). In the subgroup analysis by ethnicity, there were also significant associations found between VEGF +936C/T polymorphism and breast cancer risk in Asians and Caucasians. In conclusion, the results of our meta-analysis suggest that the VEGF +936C/T polymorphism is significantly associated with breast cancer development and the VEGF 936T allele carriers may be associated with decreased breast cancer risk.

The MMP-1, MMP-2, and MMP-9 gene polymorphisms and susceptibility to bladder cancer: a meta-analysis.

The relationship between matrix metalloproteinase (MMP) polymorphisms and bladder cancer risk has become a hot topic and was studied extensively in recent years, but the results are still controversial. In order to estimate the relationship of MMP polymorphisms and the risk of bladder cancer, we performed this meta-analysis. We conducted a comprehensive search of databases; PubMed, Web of Science, Embase, Chinese Biomedical Literature Database (CBM, Chinese) and Wanfang Database (Chinese) were searched for all case-control studies which mainly study the relationship between MMP-1-1607 1G/2G, MMP-2-1306 C/T, and MMP-9-1562 C/T polymorphisms and the susceptibility of bladder cancer. The association between the MMP polymorphisms and bladder cancer risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). At last, totally five literatures with 1,141 cases and 1,069 controls were contained in the meta-analysis. Among these articles, four articles with 1,103 cases and 1,053 controls were about MMP-1-1607 1G/2G polymorphism and three studies with 839 cases and 775 controls for MMP-2-1306 C/T polymorphism and MMP-9-1562 C/T polymorphism. With regard to MMP-1-1607 1G/2G polymorphism, significant association was found with bladder cancer susceptibility only under recessive model (2G2G vs. 1G2G/1G1G: OR = 1.44, 95% CI = 1.05-1.97, P = 0.022), and as to the MMP-2-1306 C/T polymorphism, significant association was found with bladder cancer susceptibility only under homozygote model (TT vs. CC: OR = 2.10, 95% CI = 1.38-3.10, P = 0), but no associations was found between MMP-9-1562 C/T polymorphism and bladder cancer susceptibility. The results suggest that the MMP-2-1306 C/T and MMP-9-1562 C/T polymorphisms are significantly associated with bladder cancer susceptibility, and no associations were found between MMP-9-1562 C/T polymorphism and bladder cancer susceptibility.

XRCC3 Thr241Met polymorphism and ovarian cancer risk: a meta-analysis.

Genetic polymorphism of X-ray repair crosscomplementing group 3 (XRCC3) Thr241Met has been implicated to alter the risk of ovarian cancer, but the results are controversial. In order to get a more precise result, a meta-analysis was performed. All eligible studies were identified through an extensive search in PubMed, Excerpta Medica Database (Embase), Chinese National Knowledge Infrastructure database, and Chinese Biomedical Literature Database before August 2013. The association between the XRCC3 Thr241Met polymorphism and ovarian cancer risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). Finally, a total of four publications including seven studies with 3,635 cases and 5,473 controls were included in our meta-analysis. Overall, there was no association between XRCC3 Thr241Met polymorphism and risk of ovarian cancer under all five genetic models in overall population (T vs. C: OR = 0.99, 95 % CI = 0.960-1.03, P = 0.752; TT vs. CC: OR = 1.00, 95% CI = 0.91-1.10, P = 0.943; TC vs. TT: OR = 0.97, 95% CI = 0.92-1.04, P = 0.396, Fig. 1; TT vs. TC/CC: OR = 1.00, 95% CI = 0.91-1.12, P = 0.874; TT/TC vs. CC: OR = 0.98, 95% CI = 0.94-1.03, P = 0.486). In the subgroup analysis according to ethnicity, the results suggested that XRCC3 Thr241Met polymorphism was not associated with the risk of ovarian cancer in Caucasians population. No significant association was found between the XRCC3 Thr241 Met polymorphism and the risk of ovarian cancer. Given the limited sample size and ethnicities included in the meta-analysis, further large scaled and well-designed studies are needed to confirm our results.

Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk in Chinese population: a meta-analysis of 22 case-control studies.

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk in the Chinese population has been widely reported, but results were inconsistent. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Eligible articles were identified through search of databases including Medline, PubMed, Web of Science, Embase, Chinese Biomedical Literature Database (CBM, Chinese), China National Knowledge Infrastructure (CNKI, Chinese), and Wangfang Database (Chinese). The association between the MTHFR polymorphism and breast cancer risk was conducted using odds ratios (ORs) and 95 % confidence intervals (95 % CIs). Finally, a total of 22 studies with 6,103 cases and 7,913 controls were included in our meta-analysis: 13 studies with 3,273 cases and 4,419 controls for C677T polymorphism and 9 studies with 2,830 cases and 3,494 controls for A1298C polymorphism. With regard to C677T polymorphism, significant association was found with breast cancer risk under three models (T vs. C: OR = 1.12, 95 % CI = 1.02-1.23, P = 0.015; TT vs. CC: OR = 1.35, 95 % CI = 1.10-1.67, P = 0.005; TT vs. CC/CT: OR = 1.37, 95 % CI = 1.11-1.70, P = 0.004). There was no significant association found between A1298C polymorphism and breast cancer risk under all genetic models (C vs. A: OR = 0.96, 95 % CI = 0.89-1.03, P = 0.268; CC vs. AA: OR = 0.98, 95 % CI = 0.77-1.26, P = 0.899; AC vs. AA: OR = 0.95, 95 % CI = 0.88-1.02, P = 0.174; CC vs. AC/AA: OR = 1.00, 95 % CI = 0.78-1.28, P = 0.996, CC/AC vs. AA: OR = 0.96, 95 % CI = 0.89-1.02, P = 0.196). In summary, during this meta-analysis, we found that MTHFR C677T polymorphism was significantly associated with breast cancer risk in the Chinese population. Meanwhile, MTHFR A1298C polymorphism was not associated with breast cancer risk in the Chinese population.

XPD Asp312Asn and Lys751Gln polymorphisms and breast cancer susceptibility: a meta-analysis.

The association between xeroderma pigmentosum complementation group D (XPD) Asp312Asn and Lys751Gln gene polymorphisms and breast cancer risk has been widely reported, but the results were inconsistent. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. A comprehensive search strategy was conducted towards the electronic databases including Medline, PubMed, Web of Science, Embase, and Chinese Biomedical Literature Database (Chinese). The association between the XPD polymorphism and breast cancer risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of 22 studies with 18,136 cases and 18,351 controls were included in our meta-analysis. Among these, 12 studies with 7,667 cases and 7,480 controls for Asp312Asn polymorphism and 20 studies with 10,469 cases and 10,871 controls for Lys751Gln polymorphism. With regard to Asp312Asn polymorphism, no significantly associated was found with breast cancer risk. However, significant association was found between Lys751Gln polymorphism and breast cancer risk under all genetic models in overall populations (C vs. A-OR = 1.10, 95% CI = 1.04-1.17, P = 0.002; CC vs. AA-OR = 1.17, 95% CI = 1.06-1.30, P = 0.003; AC vs. AA-OR = 1.06, 95% CI = 1.01-1.12, P = 0.032; CC vs. AC/AA-OR = 1.17, 95% CI = 1.04-1.32, P = 0.009; CC/AC vs. AA-OR = 1.07, 95% CI = 1.02-1.12, P = 0.005). In subgroup analysis base on ethnicity, significance was found in Caucasians and mix. The results suggest that XPD Asp312Asn polymorphism was not associated with breast cancer. The XPD Lys751Gln polymorphism significantly increased breast cancer risk, especially for Caucasian and mix.