Decreased hospital-acquired respiratory infections among older inpatients during the COVID-19 pandemic: a retrospective observational study in a general hospital in China.

BACKGROUND: To mitigate hospital-acquired transmission of coronavirus disease 2019 (COVID-19), various prevention and control measures have been strictly implemented in medical institutions. These stringent measures can potentially reduce the incidence of hospital-acquired respiratory infections. This study aimed to assess if there were changes in the prevalence of hospital-acquired respiratory infections during a period of national attention focused on COVID-19 prevention. METHODS: A retrospective analysis of the clinical data from adult patients with hospital-acquired respiratory infections admitted between October and December 2019 and during the same period in 2020 was performed. All patients were referred from a general hospital in Beijing China and COVID-19 patients were not treated at the hospital. Hospital-acquired respiratory infections were diagnosed based on the criteria of the Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN). A comparison of the incidence and mortality rate of hospital-acquired respiratory infections between the two selected time periods was conducted. Additionally, multivariate logistics regression analysis was used to identify mortality-associated risk factors. RESULTS: This study included 2,211 patients from October to December 2019 (pre-COVID-19 pandemic) and 2,921 patients from October to December 2020 (during the COVID-19 pandemic). The incidence of hospital-acquired respiratory infections in 2019 and 2020 was 4.7% and 2.9%, respectively, with odds ratio (OR): 0.61, 95% confidence interval (CI): 0.46-0.81, and P = 0.001. In-hospital mortality of hospital-acquired respiratory infections in 2019 and 2020 was 30.5% and 38.4%, respectively, with OR: 1.42, 95%CI: 0.78-2.59, and P = 0.25. Multivariate logistics regression analysis revealed that a history of previous malignancy (OR: 2.50, 95%CI: 1.16-5.35, P = 0.02), was associated with in-hospital mortality. CONCLUSIONS: The incidence of hospital-acquired respiratory infections was significantly decreased following the implementation of various prevention and control measures during the COVID-19 pandemic. A history of previous malignancy was associated with higher in-hospital mortality in older inpatients with hospital-acquired respiratory infections.

Short-term effect of particulate matter on lung function and impulse oscillometry system (IOS) parameters of chronic obstructive pulmonary disease (COPD) in Beijing, China.

OBJECTIVE: This study aimed to evaluate the associations between particulate matter (PM), lung function and Impulse Oscillometry System (IOS) parameters in chronic obstructive pulmonary disease (COPD) patients and identity effects between different regions in Beijing, China. METHODS: In this retrospective study, we recruited 1348 outpatients who visited hospitals between January 2016 and December 2019. Ambient air pollutant data were obtained from the central monitoring stations nearest the participants' residential addresses. We analyzed the effect of particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) exposure on lung function and IOS parameters using a multiple linear regression model, adjusting for sex, smoking history, education level, age, body mass index (BMI), mean temperature, and relative humidity . RESULTS: The results showed a relationship between PM2.5, lung function and IOS parameters. An increase of 10 µg/m3 in PM2.5 was associated with a decline of 2.083% (95% CI: -3.047 to - 1.103) in forced expiratory volume in one second /predict (FEV1%pred), a decline of 193 ml/s (95% CI: -258 to - 43) in peak expiratory flow (PEF), a decline of 0.932% (95% CI: -1.518 to - 0.342) in maximal mid-expiratory flow (MMEF); an increase of 0.732 Hz (95% CI: 0.313 to 1.148) in resonant frequency (Fres), an increase of 36 kpa/(ml/s) (95% CI: 14 to 57) in impedance at 5 Hz (Z5) and an increase of 31 kpa/(ml/s) (95% CI: 2 to 54) in respiratory impedance at 5 Hz (R5). Compared to patients in the central district, those in the southern district had lower FEV1/FVC, FEV1%pred, PEF, FEF75%, MMEF, X5, and higher Fres, Z5 and R5 (p < 0.05). CONCLUSION: Short-term exposure to PM2.5 was associated with reductions in lung function indices and an increase in IOS results in patients with COPD. The heavier the PM2.5, the more severe of COPD.

The relationship between frailty and community-acquired pneumonia in older patients.

PURPOSES: To explore the relationship between frailty and community-acquired pneumonia (CAP) in older patients. METHODS: A prospective observational study included 109 older patients(≥ 65 years) hospitalized with CAP in respiratory department of Fuxing hospital, Capital Medical University from June 2018 to December 2020. Frailty scores(Frail Scale, range 0-5) and pneumonia severity CURB-65 scale(mild = 1, modest = 2, and severe ≥ 3) were measured. We extracted clinical variables including white blood cell(WBC), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein(CRP), hemoglobin, and albumin. Charlson Comorbidity Index(CCI) was calculated as well. The correlations between the variables and frailty scores were investigated, respectively. After adjusting for covariates, binomial logistic regression analysis was used to assess independent effect of frailty scores on the outcome(discharge or death/progression) in older CAP patients. RESULTS: The subjects had a median age 87(interquartile range,8.5) years, 60.6% male, 45.9% pre-frail, and 32.1% frail. There were positive correlations between frailty scores and CURB-65 scale (p = 0.000, r = 0.542), CCI(p = 0.000, r = 0.359) and NLR(p = 0.005, r = 0.268). Negative correlations were observed between frailty scores and hemoglobin (p = 0.002, r = - 0.298), albumin (p = 0.000, r = - 0.465). In multivariable logistic regression analysis, the factors associated with discharge or death/progression of CAP were frailty scores (OR = 1.623, p = 0.037), NLR (OR = 1.086, p = 0.008) and albumin (OR = 0.869, p = 0.034). CONCLUSIONS: Frailty is correlated with CURB-65 scale, CCI and hemoglobin, and albumin in older patients with CAP. Frailty is also a correlate of increased risk for death or progression in these older people.

Role of diet in stroke incidence: an umbrella review of meta-analyses of prospective observational studies.

BACKGROUND: Stroke is one of the major challenges for the global healthcare system, which makes it necessary to explore the relationship between various modifiable factors and stroke risk. Recently, numerous meta-analyses of prospective observational studies have reported that dietary factors played a key role in the occurrence of stroke. However, the conclusions of previous studies have remained controversial and unclear. Accordingly, we conducted an umbrella review synthesizing and recalculating available evidence to assess the certainty of the associations between dietary factors and stroke. METHODS: Relevant meta-analyses examining the associations between dietary factors and stroke were searched in PubMed and Embase databases up to September 1, 2021. For each eligible meta-analysis, two independent reviewers appraised the methodologic quality using the AMSTAR 2 criteria and estimated the summary effect size, 95% confidence intervals, 95% prediction intervals, heterogeneity between studies, and small-study effects. Moreover, we further assessed the associations between dietary factors and ischemic stroke as well as hemorrhagic stroke. Lastly, a set of pre-specified criteria was applied to qualitatively evaluate the epidemiological credibility of each dietary factor. RESULTS: Overall, our umbrella review included 122 qualified meta-analyses for qualitative synthesis, involving 71 dietary factors related to food groups, foods, macronutrients, and micronutrients. Using the AMSTAR 2 criteria, 5 studies were assessed as high quality, 4 studies as moderate quality, and 113 studies as low or critically low quality. We identified 34 dietary factors associated with stroke occurrence, 25 dietary factors related to ischemic stroke, and 11 factors related to hemorrhagic stroke. Among them, high/moderate certainty epidemiological evidence demonstrated an inverse association between intake of fruits (RR: 0.90) and vegetables (RR: 0.92) and stroke incidence, but a detrimental association between red meat (RR: 1.12), especially processed red meat consumption (RR:1.17), and stroke incidence. Besides, the evidence of high/moderate certainty suggested that the intake of processed meat, fruits, coffee, tea, magnesium, and dietary fiber was associated with ischemic stroke risk, while consumption of tea, fruits, and vegetables was relevant to hemorrhagic stroke susceptibility. CONCLUSIONS: Our study has reported that several dietary factors have a significant impact on stroke risk and offered a new insight into the relationship between dietary modification and stroke occurrence. Our results may provide an effective strategy for stroke prevention.

Association of GWAS-susceptibility loci with ischemic stroke recurrence in a Han Chinese population.

BACKGROUND: Recently, genome-wide association studies (GWAS) have found many new susceptible genetic variants for ischemic stroke (IS) occurrence. However,the roles of GWAS-susceptibility loci in stroke prognosis are just beginning. The present study aimed to examine whether these GWAS-linked loci polymorphisms are associated with ischemic stroke recurrence in a Chinese population. METHODS: We genotyped six single nucleotide polymorphisms (SNPs) (9p21: rs2383207 and rs4977574; 12p13: rs12425791 and rs11833579; PDE4D: rs966221; and ALOX5AP: rs1050391) in four GWAS-reported ischemic stroke risk genes in 657 patients. RESULTS: The risk of recurrent stroke was significantly associated with PDE4D rs966221 in the dominant model (p = 0.027)and recessive model (p = 0.027). Furthermore, Kaplan-Meier analyses indicated no significant difference in the rate of recurrent stroke among the three genotypes of other five SNPs. Cox regression analysis showed that the GA + GG genotype within the rs966221 polymorphism had a 1.399-fold risk for stoke recurrence (95% confidence interval = 1.038-1.886; p = 0.027). Stratified analysis revealed that the increased recurrence risk of PDE4D rs966221 was more prominent in the large artery atherosclerosis (LAA) subgroup. CONCLUSIONS: The reults of the present study demonstrate that PDE4D rs966221 may be a valuable biomarker for predicting the recurrent risks of patient with the LAA-IS and adds to our knowledge of the genetic basis of recurrent stroke risk.

Genetic polymorphisms in lncRNAs predict recurrence of ischemic stroke.

Genetic polymorphisms in long non-coding RNAs (lncRNAs) are considered as potential genetic biomarkers for the prediction of human complex diseases such as ischemic stroke (IS). However, so far, no reports have focused on the relationship of lncRNA polymorphisms with IS onset and prognosis. In our study, eight potential functional polymorphisms of four well-known lncRNAs (H19 rs2107425 and rs2251375, MALAT1 rs4102217 and rs3200401, MEG3 rs11160608 and rs4081134, SENCR rs4526784 and rs555172) were genotyped in 657 ischemic stroke patients. Then, the association between lncRNA polymorphisms and IS onset and recurrence were investigated. These lncRNA variants were not associated with age onset of IS. However, we observed that MEG3 rs4081134 AA genotype was statistically related with a reduced risk of stroke recurrence, particularly for patients with large-artery atherosclerotic stroke. Also, the decreased risk was more prominent in elders, non-smokers, non-drinkers and hypertensive patients. Furthermore, the variant genotype AA of rs4081134 was an independent predictor for IS recurrence using the multivariate Cox regression model. Our findings indicated that MEG3 rs4081134 can serve as a useful biomarker and potential therapeutic target in IS recurrence. More researches are needed to verify our results and explore the underlying molecular mechanisms.

Association between microRNA binding site polymorphisms in immunoinflammatory genes and recurrence risk of ischemic stroke.

MicroRNA binding site polymorphisms in immunoinflammatory genes have been implicated as candidate biomarkers for prediction of complex human diseases. However, the roles of microRNA binding site polymorphisms in stroke onset and prognosis remain unclear. Thus, for the first time, five potential functional polymorphisms in immunoinflammatory genes (CXCR2 rs1126579, TLR4 rs11536889, ADIPOR2 rs12342, MMP-2 rs7201 and MMP-9 rs1056628) were genotyped in 657 patients with ischemic stroke. These five polymorphisms were not related with age onset of ischemic stroke. However, we found that ADIPOR2 rs12342 was significantly associated with a decreased recurrence risk, especially for the patients with small-vessel disease. Moreover, by using multivariate Cox regression, the variant genotype GG/GA of rs12342 was observed as an independent protective factor for stroke recurrence, even after Bonferroni correction. In addition, after the addition of rs12342 in the model with clinical factors, the new model showed the improved discriminatory ability to predict stroke recurrence. In short, our results suggested that ADIPOR2 rs12342 may be a novel genetic biomarker and therapeutic target for ischemic stroke recurrence. Further studies are required to replicate our findings and clarify the potential biological mechanism.

Using the anterior capsule of the hip joint to protect the tensor fascia lata muscle during direct anterior total hip arthroplasty: a randomized prospective trial.

BACKGROUND: The direct anterior approach for total hip arthroplasty (THA) has specific advantages, but injury to the tensor fasciae lata muscle (TFLM) remains a concern. This injury in part negates some of the advantages of the intermuscular approach, because injury of the muscle fibers of the TFLM can lead to less satisfactory clinical results. Thus, in this study, we propose an intraoperative method to protect the TFLM and demonstrate its feasibility. METHODS: Fifty-six patients undergoing THA by the direct anterior approach were divided randomly into two groups. In group A, the TFLM was protected by an autogenous tissue "pad" created from the anterior capsule of the joint which protect the TFLM from direct contact with the retractors. In group B, the operation was carried out with no protection of the TFLM except the attempt by the surgeons to consciously avoid injury of the TFLM. We evaluated magnitude of changes in the muscle cross-sectional area (MSCA) and fatty atrophy (FA) by magnetic resonance imaging. The differences in blood hemoglobin and serum levels of myoglobin, lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were compared at different time, postoperatively. The Harris hip score, postoperative drainage volume and visual analogue scores (VAS) were compared between the two groups. RESULTS: LDH, CPK and myoglobin in group B were significantly higher than group A at 8, 24, and 48 h after the surgery. (p < 0.05) Compared to the group A, the decrease of hemoglobin in group B displayed significantly at 24 and 48 h after surgery. (P < 0.05) The significantly increased MSCA and FA of TFLM were demonstrated in group B. The PDV and VAS in group B were significantly higher than group A. (P < 0.05) The Harris score in group A was significantly higher than group B (P < 0.05) one month after surgery, but there was no significant difference six months later. CONCLUSIONS: Using the anterior capsule of the hip joint as an autogenous, protective capsular tissue pad to limit the trauma to the TFLM during a direct anterior approach to THA is an effective method to protect the TFLM and improve the clinical effect. TRIAL REGISTRATION: ChiCTR: ChiCTR1900025173. Retrospectively registered August 15, 2019.

Genetic variants in migraine: a field synopsis and systematic re-analysis of meta-analyses.

OBJECTIVE: Numerous genetic variants from meta-analyses of observational studies and GWAS were reported to be associated with migraine susceptibility. However, due to the random errors in meta-analyses, the noteworthiness of the results showing statistically significant remains doubtful. Thus, we performed this field synopsis and re-analysis study to evaluate the noteworthiness using a Bayesian approach in hope of finding true associations. METHODS: Relevant meta-analyses from observational studies and GWAS examining correlation between all genetic variants and migraine risk were included in our study by a PubMed search. Identification of noteworthy associations were analyzed by false-positive rate probability (FPRP) and Bayesian false discovery probability (BFDP). Using noteworthy variants, GO enrichment analysis were conducted through DAVID online tool. Then, the PPI network and hub genes were performed using STRING database and CytoHubba software. RESULTS: As for 8 significant genetic variants from observational studies, none of which showed noteworthy at prior probability of 0.001. Out of 47 significant genetic variants in GWAS, 36 were noteworthy at prior probability of 0.000001 via FPRP or BFDP. We further found the pathways "positive regulation of cytosolic calcium ion concentration" and "inositol phosphate-mediated signaling" and hub genes including MEF2D, TSPAN2, PHACTR1, TRPM8 and PRDM16 related to migraine susceptibility. CONCLUSION: Herein, we have identified several noteworthy variants for migraine susceptibility in this field synopsis. We hope these data would help identify novel genetic biomarkers and potential therapeutic target for migraine.

Association between 12p13 Polymorphisms and Ischemic Stroke in Asian Populations: New Evidence from a Case-Control Study and a Meta-Analysis.

A genome-wide association study first reported the association between ischemic stroke risk and two polymorphisms on chromosome 12p13: rs12425791 and rs11833579. Since then, a series of studies have investigated the association of these two polymorphisms with stroke risk, but the results were inconsistent even in Asian populations. Thus, we carried out a case-control study to uncover the potential relationship, and then conducted a meta-analysis to further address the issue. 540 ischemic stroke patients and 540 unrelated controls were enrolled in the case-control study. Genotyping was accomplished by polymerase chain reaction-ligation detection reaction. The meta-analysis was conducted by combining our study with previous published data. In our case-control study, the significant association was observed between ischemic stroke and rs12425791 (AG vs. GG: OR = 1.32, P < 0.05) but not rs11833579. When pooled with previous studies, the significant relationship of rs12425791 with ischemic stroke was found (A vs. G: OR = 1.07, P < 0.05; AA + AG vs. GG: OR = 1.10, P < 0.05) in Asian populations, as well as in subgroup analysis. A correlation approaching significance was identified between ischemic stroke risk and rs11833579 (AA + AG vs. GG: OR = 1.06, P = 0.05). New evidence from this case-control study and meta-analysis indicates that 12p13 rs12425791/rs11833579 polymorphisms are associated with ischemic stroke susceptibility in Asian populations.

Association of miR-122, miR-124 miR-126 and miR-143 gene polymorphisms with ischemic stroke in the northern Chinese Han population.

Objectives: Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes can have diverse functional consequence by affecting the processing and target selection of miRNA. Recent evidence indicates that miRNA play important roles in the pathogenesis of atherosclerosis, which is a major cause of ischemic stroke (IS). The aim of this study was to clarify whether genetic variations in four miRNA genes (miR-143 rs4705342, miR-122 rs17669, miR-126 rs4636297, and miR-124 rs531564) contribute to IS susceptibility. Methods: A case-control study was used to explore miRNA genetic polymorphisms in 567 IS patients and 552 control subjects that were frequency matched by age and gender. We genotyped four SNPs using polymerase chain reaction/ligation detection reaction. Results: The miR-126 gene rs4636297 polymorphism was associated with decreased small vessel stroke risk (GA vs. GG: odds ratio (OR) = 0.62, p = .015; GA + AA vs. GG: OR = 0.637, p = .018; A vs. G: OR = 0.696, p = .033). Using logistic regression analysis, this significant association remained after adjusting for confounding risk factors (adjusted OR = 0.626, 95% confidence interval (CI) = 0.426-0.921). However, the three other miRNA (miR-143 rs4705342, miR-122 rs17669, and miR-124 r531564) were not associated with IS risk under allele or genotype, nor in different inheritance models. In addition, there were no significant associations with stroke subtypes for these three miRNA SNPs. Conclusion: Our study suggests that the miR-126 gene rs4636297 polymorphism may play an important role in the pathogenesis of small vessel occlusive stroke in the northern Chinese Han population.

Association between CLU gene rs11136000 polymorphism and Alzheimer's disease: an updated meta-analysis.

Large-scale genome-wide association studies (GWAS) identified that the single nucleotide polymorphism rs11136000 in Clusterin (CLU) gene was associated with risk of Alzheimer's disease (AD) in Caucasian ancestry. However, recent studies reported either a weak association or no association between rs11136000 polymorphism and AD in Asian populations. Therefore, we performed a meta-analysis to explore whether rs11136000 polymorphism is associated with susceptibility to AD in Asian populations. A total of 17 articles including 26 studies with 19,829 cases and 30,900 controls, which were identified by searching PubMed, MEDLINE, and AlzGene up to Nov 2016, were collected for this meta-analysis. The significant association between rs11136000 and AD in the pooled population was found under all the models. In subgroup analysis, we identified significant association in Asian population under the additive mode (OR = 0.90, 95% CI = 0.85-0.96) but not in the recessive model (OR = 0.80, 95% CI = 0.53-1.21) and the dominant model (OR = 0.94, 95% CI = 0.86-1.03). Our analysis further supports previous findings that the rs11136000 polymorphism C allele is associated with AD susceptibility. To our knowledge, this is the new largest meta-analysis to access to the association of CLU rs11136000 polymorphism with AD risk.

An updated analysis with 45,078 subjects confirms the association between SNCA rs11931074 and Parkinson's disease.

Large-scale genome-wide association study (GWAS) has identified that the alpha-synuclein (SNCA) rs11931074 polymorphism is associated with Parkinson's disease (PD) susceptibility in individuals of Japanese descent. Subsequently, a number of replication studies have been performed in Asian and Caucasian populations. However, the results remain controversial due to the relatively small sample sizes and genetic heterogeneity. Here, to overcome the limitations of individual studies, we reevaluated this association with data from 33 independent studies involving 15,368 patients and 29,710 control samples identified by searching PubMed and EMBase databases. Odds ratios (OR) with 95% confidence interval (CI) were applied to assess the association between SNCA rs11931074 polymorphism and PD. Heterogeneity, sensitivity analysis, and publication bias were conducted to measure the robustness of our findings. Using allele, recessive, dominant, and additive models, we did not reveal significant heterogeneity among 33 studies. Significant association of the SNCA rs11931074 polymorphism with PD was observed (T vs. G: OR = 1.36, 95% CI = 1.31-1.42; TT vs. TG + GG: OR = 1.58, 95% CI = 1.46-1.72; TT + TG vs. GG: OR = 1.44, 95% CI = 1.35-1.55; TT vs. GG: OR = 1.87, 95% CI = 1.68-2.09) in the pooled populations. Furthermore, subgroup analyses accounting for ethnicity found similar significant results in both Asian and Caucasian populations. In conclusion, our meta-analysis further indicates that the SNCA rs11931074 polymorphism contributes to PD susceptibility. We believe that our findings will be very useful for future genetic studies on PD.

SOX10 induced Nestin expression regulates cancer stem cell properties of TNBC cells.

The mechanisms modulating the cancer stem cell (CSC) properties of triple negative breast cancer (TNBC) cells were not fully understood. In this study, we performed data mining in Breast Cancer Gene-Expression Miner v4.0 and found that TNBC tumors had significantly higher NES mRNA expression than other breast cancer subtypes. Pooled data suggested that NES mRNA expression is associated worse metastatic relapse (MR) free survival and also worse any event (AE) free survival in TNBC patients. Following data mining in multiple big data databases confirmed a positive correlation between SOX10 mRNA expression and NES mRNA expression in breast cancer tissues. In addition, the expression of SOX10 mRNA is significantly higher in TNBC tissues than in other breast cancer subtypes. SOX10 overexpression resulted in Nestin upregulation at both mRNA and protein levels. Bioinformatic analysis predicted a SOX10 binding site in NES promoter and the following dual luciferase assay verified the binding site. Functionally, SOX10 overexpression substantially increased CSC properties of TNBC cells, while SOX10 knockdown decreased the CSC properties, in terms of CD24-/CD44+ cell ratio and tumorsphere-forming capabilities. Enforced Nestin expression partly counteracted the effect of SOX10 knockdown on reducing the CSC properties. Based on these findings, we infer that SOX10 regulates cancer stem cell properties of TNBC cells via inducing Nestin expression.

Serum miR-152, miR-148a, miR-148b, and miR-21 as novel biomarkers in non-small cell lung cancer screening.

Lung cancer, predominantly by non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths over the world. Late diagnosis is one of important reasons for high mortality rate in lung cancer. Current diagnostic approaches have disadvantages such as low accuracy, high cost, invasive procedure, etc. MicroRNAs were previously proposed as promising novel biomarkers in cancer screening. In this study, we evaluated the predictive power of four candidate miRNAs in NSCLC detection. Our study involved 152 NSCLC patients and 300 healthy controls. Blood samples were obtained from the total 452 subjects. After miRNA extraction from serum, the expression of miRNAs in cases and controls were quantified by qRT-PCR and normalized to the level of U6 small RNA. Statistical analyses were performed to compare miRNA levels between cases and controls. Stratified analyses were employed to compare miRNA levels in NSCLC patients with different clinical characteristics. Serum miR-148a, miR-148b, and miR-152 were significantly downregulated in NSCLC patients. However, overexpression of serum miR-21 was observed in NSCLC patients. The combination of four candidate miRNAs exhibited the highest predictive accuracy in NSCLC screening compared with individual miRNAs (AUC = 0.97). Low level of miRNA-148/152 members may associate with advanced stage, large tumor size, malignant cell differentiation, and metastasis. High expression of miR-21 was possibly correlated with large size tumor and advanced cancer stage. Our results showed the dysregulation of miR-148/152 family and miR-21 in NSCLC patients. Hence, the four candidate miRNAs have great potential to serve as promising novel biomarkers in NSCLC screening. Further large-scale studies are needed to validate our results.

Association of MTHFR C677T with total homocysteine plasma levels and susceptibility to Parkinson's disease: a meta-analysis.

The C677T single-nucleotide polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR) may elevate homocysteine (Hcy) levels and increase the risk of Parkinson's disease (PD); however, results are conflicting. Our aim was to resolve contradictions in the literature and to determine whether MTHFR C677T has a significant role in regulating Hcy levels and/or is a significant risk factor for PD. MEDLINE, EMBASE, the Cochrane Library, China Biological Medicine Database and Google Scholar were searched until May 2014. Strict selection and exclusion criteria were determined, and odds ratios (ORs)/weighted mean differences (WMDs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed using STATA 12.0. Fifteen studies that together assessed 2690 PD cases and 8465 controls were included. Meta-analysis showed that no significant difference in the distribution of MTHFR C677T between PD cases and controls was found. While stratifying for ethnicity, significant association was revealed in Europeans (T vs. C, OR = 1.17, 95 % CIs 1.04-1.31) but not in Asians. Significant association between the T allele and increased Hcy levels was found in PD cases and controls; Hcy levels were higher in PD cases and controls carrying the MTHFR T677 allele than in non-carriers (TT vs. CC, PD WMD = 6.50, 95 % CIs 6.20-6.80; controls WMD = 4.52, 95 % CIs 4.24-4.80). Other within-group comparisons showed similar results. This meta-analysis suggests that MTHFR C667T may confer PD susceptibility in Europeans. The T allele may be an independent risk factor for elevated Hcy levels in PD patients.

Idiopathic hypertrophic craniocervical pachymeningitis.

PURPOSE: Hypertrophic craniocervical pachymeningitis (HCP) is a rare disease causing chronic inflammatory hypertrophy of the cranial and spinal dura mater. To increase awareness of this condition, we report the details of a case here. METHODS: We reviewed the case of a 78-year-old man presenting with a rare case of HCP and summarized the clinical features, laboratory evaluations and treatment of the case. RESULTS: In this case, the HCP involved the intracranial dura and high cervical regions, manifesting as lower cranial nerve palsies, headache, and neck pain, developing over 7 months. Magnetic resonance imaging revealed thickening of the dura in the craniocervical region with peripheral enhancement. Steroid therapy was commenced and the symptoms improved rapidly. CONCLUSIONS: HCP can be diagnosed by MRI and laboratory investigations. In this case corticosteroid treatment was effective, although care must be taken when slowly reducing the dose. This case highlights HCP as a cause of progressive cerebellomedullar and cervical spinal cord symptoms.

Association of ATP-Binding Cassette Transporter G1 Polymorphisms with Risk of Ischemic Stroke in the Chinese Han Population.

BACKGROUND: The adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1), a member of the superfamily of ATP-binding cassette transporters, is involved in the transport of cholesterol and phospholipids in macrophages. As such, ABCG1 plays a crucial role in the development of atherosclerosis in humans. In this study, we investigate the association between ABCG1 polymorphisms and the risk of developing ischemic stroke in a Chinese Han population. METHODS: This case-control study included 389 ischemic stroke patients and 380 healthy subjects. ABCG1 rs1378577 and rs57137919 polymorphisms were analyzed by a polymerase chain reaction-ligation detection reaction. RESULTS: We found that the genotypic distribution and allelic frequency of these polymorphisms were similar in patients and controls. In a subgroup with hypertriglyceridemia (144 patients and 115 controls), the frequency of rs1378577 GG genotype and G allele as well as rs57137919 AA genotype was lower in the patient group compared with that in the control group (P = .018, P = .035, and P = .023, respectively). Logistic regression analysis revealed a reduced risk of ischemic stroke in a recessive model for both rs1378577 and rs57137919. Subtype analyses demonstrated that rs1378577 TG and GG genotypes and the G allele were associated with reduced risk of atherothrombotic stroke (P = .030, P = .006, and P = .004, respectively), even after adjusting for confounding factors in a dominant model. CONCLUSIONS: Data from the present study demonstrate that ABCG1 polymorphisms are associated with reduced risk of developing ischemic stroke in hypertriglyceridemic population and atherothrombotic stroke in this cohort of Chinese Han population.

Association of p16 gene methylation with prostate cancer risk: a meta-analysis.

PURPOSE: The tumor suppressor gene p16 is frequently silenced and inactivated by hypermethylation in human cancers, including prostate cancer. However, the association between the methylation status of p16 and prostate cancer risk remains ambiguous. This study aimed to assess the association of p16 methylation with prostate cancer risk by a comprehensive metaanalysis. METHODS: Relevant studies were identified by searching PubMed, Embase and Web of Science databases before October 2014 with no restrictions. The strength of the association between p16 methylation and prostate cancer risk was assessed by combined odds ratio (OR) and 95 % confidence interval (CI). The between-study heterogeneity and the contributions of single studies to the final results were tested by chi-square-based Q test and sensitivity analyses, respectively. Publication bias was evaluated by funnel plots. RESULTS: A total of 1,296 samples from 12 independent studies were enrolled in the present metaanalysis. Overall, a significant association was observed between p16 methylation and prostate cancer risk (OR=3.06; 95% CI:1.34- 6.98;p=0.008). Stratified analyses by ethnic groups further revealed that prostate cancer risk was increased for individuals carrying the methylated p16 compared with those with unmethylated p16 in Caucasian populations (OR=2.51;95% CI:1.01-6.26;p=0.047) and Asian populations (OR=9.50;95% CI:1.78-50.61;p=0.008). CONCLUSIONS: This study identified a strong association of p16 methylation with prostate cancer risk and suggested that p16 methylation might be a potential biomarker for prostate cancer.

miR-146a and miR-196a2 polymorphisms in patients with ischemic stroke in the northern Chinese Han population.

MicroRNAs are endogenous non-coding RNAs about 22 nucleotides in length that can repress the expression of proteins by binding to the 3'-untranslated regions of target messenger RNAs. We hypothesized that polymorphisms in miR-146a and miR-196a2 are associated with risk of ischemic stroke in the northern Chinese Han population. In a case-control study of 368 ischemic stroke patients and 381 control subjects that were frequency matched by age and gender, we genotyped two single nucleotide polymorphisms (rs11614913 in miR-196a2 and rs2910164 in miR-146a) using polymerase chain reaction-ligation detection reaction. The frequencies of the rs2910164 CC genotype and C allele within miR-146a were not significantly different in patients with ischemic stroke compared with those in the healthy control group. In subgroup meta-analysis, rs2910164 in miR-146a and large-artery atherosclerosis, rather than small-vessel disease, showed the significant association under the dominant model (CC vs CG+GG, OR 1.694; 95 % CI 1.199-2.395 p = 0.003). After adjusting for confounding risk factors of ischemic stroke by logistic regression analysis, this significant correlation remained. In addition, the distributions of the miR-196a2 genotypes and alleles were not statistically different between ischemic stroke and healthy groups. We also did not find any significant association from stroke subtypes. The CC genotype and C allele of rs2910164 within miR-146a are associated with an increased incidence of large-artery atherosclerotic stroke in the northern Chinese Han population. This study indicates that miR-146a (rs2910164) might contribute to ischemic stroke susceptibility in the northern Chinese Han population.