Background:Remnant cholesterol (RC) has been suggested to be implicated in atherosclerosis. The objective of the study was to evaluate the association between RC and first-ever stroke in the Chinese general population and to investigate whether the association is mediated via hypertension or diabetes. Methods:This study is a retrospective cohort analysis of participants from the China Health and Nutrition Survey. Participants without previous stroke and myocardial infarction in 2009 were enrolled and followed up in 2011 and 2015. Logistic regression analyses were adopted to explore the association of RC with stroke risk. Propensity score methods and doubly robust estimation method were used to ensure the robustness of our findings. Potential mediators were identified by mediation analyses. Results:A total of 7,035 participants were involved, and during 6 years of follow-up, 78 (1.1%) participants experienced a first-ever stroke. Participants with high RC had a significantly higher incidence of stroke (1.4% versus 0.8%; p = 0.007). High RC was associated with 74% higher stroke risk after adjusting for multiple relevant variables (odds ratio [OR], 1.74; 95% CI, 1.06-2.85). The association was consistent in analyses using propensity score methods and doubly robust estimation method. Hypertension showed a significant mediating effect on the association between RC and stroke, while the mediating effect of diabetes was not significant. Conclusion:High RC increased the risk of first-ever stroke in the Chinese general population without previous stroke and myocardial infarction, partially through the pathway of hypertension. RC might be a potential target for the primary prevention of stroke.
Background and objectives:The Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) is mostly common used for assessing the motor symptoms of Parkinson's disease (PD). In remote circumstances, vision-based techniques have many strengths over wearable sensors. However, rigidity (item 3.3) and postural stability (item 3.12) in the MDS-UPDRS III cannot be assessed remotely since participants need to be touched by a trained examiner during testing. We developed the four scoring models of rigidity of the neck, rigidity of the lower extremities, rigidity of the upper extremities, and postural stability based on features extracted from other available and touchless motions.Methods:The red, green, and blue (RGB) computer vision algorithm and machine learning were combined with other available motions from the MDS-UPDRS III evaluation. A total of 104 patients with PD were split into a train set (89 individuals) and a test set (15 individuals). The light gradient boosting machine (LightGBM) multiclassification model was trained. Weighted kappa (k), absolute accuracy (ACC ± 0), and Spearman's correlation coefficient (rho) were used to evaluate the performance of model.Results:For model of rigidity of the upper extremities, k = 0.58 (moderate), ACC ± 0 = 0.73, and rho = 0.64 (moderate). For model of rigidity of the lower extremities, k = 0.66 (substantial), ACC ± 0 = 0.70, and rho = 0.76 (strong). For model of rigidity of the neck, k = 0.60 (moderate), ACC ± 0 = 0.73, and rho = 0.60 (moderate). For model of postural stability, k = 0.66 (substantial), ACC ± 0 = 0.73, and rho = 0.68 (moderate).Conclusion:Our study can be meaningful for remote assessments, especially when people have to maintain social distance, e.g., in situations such as the coronavirus disease-2019 (COVID-19) pandemic.
BackgroundThe prevalence of diabetes mellitus-induced erectile dysfunction (DMED) has recently increased, which has prompted numerous DMED studies. Here, we conduct a bibliometric analysis of relevant literature in the field of DMED and to discuss the research hotspots and future development directions.MethodsThe Web of Science Core Collection database was searched for literature on DMED, and literature characterization including the number of articles, journals, countries/regions, institutions, authors, keywords, and other information was performed using VOS viewer and CiteSpace software. In addition, Pajek software was used for visual map adjustment, and GraphPad Prism was used to generate line graphs.ResultsA total of 804 articles concerning DMED were included in this study. The Journal of Sexual Medicine issued the most documents(92 articles). The United States and China were in the leading position in the field of DMED research, and cross-institutional collaboration on DMED research worldwide needs to be further strengthened. Ryu JK were the authors with the highest number of documents issued (22 articles) while Bivalacqua TJ was the author with the most co-citated(249 co-citated). The keywords analysis shows that the main research hotspots in the field of DMED were mechanism discussions and disease treatment and management.ConclusionsGlobal research on DMED is expected to increase further. The investigation of the mechanism of DMED and the exploration of new therapeutic means and targets are the focus of future research.
BACKGROUND:The causal relationship between obesity-related anthropometric indicators/body composition and erectile dysfunction has not been established in previous observational studies. METHOD:We screened single nucleotide polymorphisms significantly associated with exposure from genome-wide association studies as instrumental variables (p < 5.0 × 10-8 ). The summary statistics for erectile dysfunction were collected from a genome-wide association study with a sample size of 223,805. Exposure and outcome populations included are of European ancestry. We used univariate and multivariate Mendelian randomization (i) to investigate the causal relationship between genetically predicted obesity-related anthropometric indicators/body composition and erectile dysfunction and (ii) to examine the mediating role of coronary artery disease. Mendelian randomization analysis was conducted using an inverse variance weighted method. A series of sensitivity analyses validated the results of the Mendelian randomization analysis. Causal estimates are expressed as odds ratios with 95% confidence intervals. RESULTS:Obesity-related anthropometric indicators/body composition were associated with an increased risk of erectile dysfunction in univariate Mendelian randomization analyses. For the 1-SD increase in body mass index, the odds ratio was 1.841 (95% confidence interval: 1.049-1.355, p = 0.006). For the 1-SD increase in waist circumference and hip circumference, the odds ratios were 1.275 (95% confidence interval: 1.101-1.478, p = 0.001) and 1.156 (95% confidence interval: 1.015-1.317, p = 0.009), respectively. The odds ratio for the 1-SD increase in whole body fat mass was 1.221 (95% confidence interval: 1.047-1.388, p = 0.002). For the 1-SD increase in leg fat percentage (left and right), the odds ratios were 1.256 (95% confidence interval: 1.006-1.567, p = 0.044) and 1.285 (95% confidence interval: 1.027-1.608, p = 0.028), respectively. For the 1-SD increase in leg fat mass (left and right), the odds ratios were 1.308 (95% confidence interval: 1.108-1.544, p = 0.001) and 1.290 (95% confidence interval: 1.091-1.524, p = 0.003), respectively. For the 1-SD increase in arm fat mass (left and right), the odds ratios were 1.269 (95% confidence interval: 1.113-1.447, p < 0.001) and 1.254, respectively. Multivariate Mendelian randomization analysis showed that after adjusting for coronary artery disease, some genetic predispositions to obesity-related anthropometric indicators and body composition were still associated with an increased risk of erectile dysfunction. Significant associations were found for waist circumference-erectile dysfunction (odds ratio: 1.218, 95% confidence interval: 1.036-1.432), leg fat percentage (left)-erectile dysfunction (odds ratio: 1.245, 95% confidence interval: 1.035-1.497), leg fat mass (left)-erectile dysfunction (odds ratio: 1.264, 95% confidence interval: 1.051-1.521), arm fat mass (right)-erectile dysfunction (odds ratio: 1.186, 95% confidence interval: 1.024-1.373), and arm fat mass (left)-erectile dysfunction (odds ratio: 1.17, 95% confidence interval: 1.018-1.360). Meanwhile, coronary artery disease mediated the effects of fat on erectile dysfunction, and the proportion of coronary artery disease-mediated cases ranged from 10% to 22%. CONCLUSION:There is a potential causal relationship between obesity-related anthropometric indicators/body composition and erectile dysfunction. Higher waist circumference, leg fat percentage, and arm fat mass may increase the risk of erectile dysfunction, and coronary artery disease partly mediates this overall effect. Understanding the causal relationship between obesity and erectile dysfunction and the mediating role of coronary artery disease may provide more information for erectile dysfunction intervention and prevention strategies.
Background Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder characterized by recurrent involuntary movements usually triggered by sudden movements. Mutations in the TMEM151A gene were found to be the causative factor of PKD in recent studies. It has also been revealed that loss-of-function is the mechanism by which TMEM151A mutations cause PKD. Methods To investigate the genetic basis of PKD and broaden the clinical spectrum of the TMEM151A mutations, we recruited 181 patients of Chinese origin with movement disorders (MDs), including 39 PRRT2-negative PKD, 3 paroxysmal exercise-induced dyskinesia (PED), 2 paroxysmal non-kinesigenic dyskinesia (PNKD), 127 isolated dystonia, 8 choreas, and 2 myoclonus-dystonia syndromes. Whole-exome sequencing was applied to identify their possible disease-causing mutations. Then, Sanger sequencing was performed for validation and co-segregation analysis. Genetic analysis was also performed on additional family members of patients with TMEM151A mutations. Clinical manifestations of all PKD cases with mutations in TMEM151A reported, so far, were reviewed. Results Two novel variants of the TMEM151A gene (NM_153266.4, NP_694998.1), c.627_643dup (p.A215Gfs*53) and c.627delG (p.L210Wfs*52), were identified in 2 patients with PKD by whole-exome sequencing and further Sanger sequencing. Both variants were inherited by the patients from their respective mothers. No mutation of the TMEM151A gene was found in the other type of movement disorders. In reviewing the clinical presentation of TMEM151A-related PKD, no statistically significant difference in the age of onset, family history, duration of attacks, laterality, and phenotype was found between genders. More male patients received treatment and had a good response. A higher proportion of female patients did not receive any treatment, possibly because they had a milder condition of the disease. Conclusions This study further validated the role of TMEM151A in PKD. Future studies on protein function will be needed to ascertain the pathogenesis of TMEM151A in PKD.
Background:Metabolic abnormalities and body mass index (BMI) are apparent risk factors for recurrent stroke. For the prevention of recurrent stroke, which one is more important remains uncertain. This study aimed to compare metabolic phenotypes and BMI as indicators of recurrent stroke in Chinese hospitalized stroke patients. Methods:In this cross-sectional population-based study, 856 hospitalized stroke patients from the First People's Hospital of Changzhou, the Third Affiliated Hospital of Soochow University, were enrolled. We implemented the standardized questionnaire and biochemical measurements to collect participants' data. Recurrent stroke was defined as new-onset stroke in patients with a definite history of previous stroke. Metabolic phenotypes were categorized based on the Adult Treatment Panel III criteria. Obesity was defined as BMI ≥25 kg/m2. Multivariate logistic regression analyses were used for the association of recurrent stroke with metabolic abnormalities and BMI. Results:Among the hospitalized stroke patients, the prevalence of recurrent stroke was 22.4%. Metabolic abnormalities, rather than BMI, were significantly associated with recurrent stroke. Compared with metabolically healthy patients, metabolically unhealthy patients had a 72% [odds ratio (OR) =1.72, 95% confidence interval (CI): 1.10-2.68] increased risk of recurrent stroke, regardless of BMI and other confounding factors. No statistical association between BMI and recurrent stroke was found. Furthermore, metabolic status significantly improved the risk prediction of recurrent stroke when combined with conventional risk factors (net reclassification index 17.6%, P=0.0047; integrated discrimination improvement 0.7%, P=0.014), whereas BMI did not. Conclusions:Recurrent stroke is likely associated with metabolic abnormalities rather than BMI. For the secondary prevention of stroke, controlling metabolic abnormalities is more crucial than controlling BMI in stroke patients. The longitudinal study and intervention study are warranted in the further.
Objective To evaluate whether the efficacy of Getong Tongluo Capsule ((sic)(sic), GTC, consisted of total flavone ofRadix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract ofGinkgo biloba(EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. Methods This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. Results The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). Conclusion GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667)
Diffusion tensor imaging (DTI) was used to evaluate micro-structural changes and structural connectivity in the TX mice model of Wilson's disease (WD) at 9.4 T. Region of interest (ROI) analysis showed that mean fractional anisotropy (FA) values in the hippocampus, caudate putamen and lateral globus pallidus of the TX mice decreased significantly, relative to those in the control mice. The mean diffusivity (MD) values in these regions showed no significant inter-group differences. The results of fiber tracking demonstrated that structural connectivity of in the brain of TX mice was maintained, indicating that the effects of copper accumulation in these mice were mainly regional.
Purpose: An association between catechol-O-methyltransferase (COMT) 158G/A polymorphism and endometriosis/adenomyosis susceptibility has been reported in the previous studies, but the results were inconsistent. This study was conducted to explore this association in the Chinese population using meta-analysis. Materials and Methods: PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine were searched for all relevant studies published up to December 2015. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations. Results: A total of 7 caseucontrol studies including 782 cases and 700 controls were included in this meta-analysis. Overall, COMT 158G/A polymorphism was found to be significantly associated with endometriosis and adenomyosis risk in the Chinese population (A vs. G, OR = 1.21, 95% CI: 1.02u1.42; AA vs. GG, OR = 1.47, 95% CI: 1.01u2.14; AA vs. GG + GA, OR = 1.42, 95% CI: 0.99u2.03; AA + GA vs. GG, OR = 1.20, 95% CI: 0.97u1.49). In subgroup analyses stratified by ethnicity, source of controls and disease groups, the significant risk was found in Chinese not mentioned the ethnicity, in population-based studies and adenomyosis. Conclusions: COMT 158G/A polymorphism may contribute to the risk of endometriosis and adenomyosis in Chinese, particularly for adenomyosis.
This study aims to explore the role of extra-cellular matrix metalloproteinase inducer (EMMPRIN) in the drug resistance of the pseudomonas aeruginosa (PA). The BALB/c mice were transfected with PA, then the mice were infected with the siRNA of EMMPRIN to silence the EMMPRIN gene. The EMMPRIN mRNA and protein were detected by using RT-PCR and western blot, respectively. In order to examine the function of EMMPRIN in drug resistance of PA, the BALB/c and C57BL/6 mice were treated with EMMPRIN siRNA. The cytokines, EMMPRIN and MMP9 were examined by the RP-PCR and ELISA, respectively, undergoing the silence of EMMPRIN siRNA. Moreover, the western blot assay was also used to test the phosphorylated MAPK in the murine macrophages after silenced by the EMMPRIN siRNA. The EMMPRIN was activated, with lipopolysaccharide stimulation and treated with the MAPK inhibitor, to evaluate whether the MAPK participates in the EMMPRIN-triggered drug resistance. The results indicated that the EMMPRIN expression was elevated in the infected BALB/c at 3 or 5 days post-infection. Silence of EMMPRIN Enhanced the Production of pro-inflammatory cytokines in PA keratitis. Silence of EMMPRIN significantly up-regulated Th1-type cytokines IFN-γ, IL-12, and IL-18, but down-regulated Th2-type cytokines IL-4, IL-5, and IL-10. MMP9 was increased in the cells with rEMMPRIN treatment. EMMPRIN inhibits pro-inflammatory cytokine production via a MAPK signaling pathway. In conclusion, EMMPRIN promotes host resistance against pseudomonas aeruginosa infection via MAPK signaling pathway.
In the present study, we aim to investigate the correlations between polymorphisms in the DEFB1 gene and the susceptibility to chronic respiratory diseases (CRDs). Electronic searches in multiple scientific literature databases (PubMed, EBSCO, Ovid, Springerlink, Wiley, Web of Science, Wanfang database, China National Knowledge Infrastructure database and VIP database) were made to retrieve studies on the associations between DEFB1 gene polymorphisms and CRDs. We used strict inclusion criteria in the present meta-analysis. Data analyses were performed with STATA software (version 12.0; Stata Corp, College Station, TX, USA). Of 76 initially-retrieved articles, 11 were finally incorporated into our meta-analysis, enrolling 1343 patients with CRDs (477 with chronic obstructive pulmonary disease (COPD), 305 with asthma, 286 with cystic fibrosis (CF), 130 with ventilator-associated pneumonia (VAP), 145 with pulmonary tuberculosis, and 1261 healthy controls into our meta-analysis. Our study showed that −44 C/G (rs1800972) and 1654 G/A (rs2738047) in DEFB1 are strongly associated with the increased susceptibility to CRDs. The subgroup analysis on disease types showed that the −44 C/G (rs1800972) in DEFB1 is associated with the susceptibility to COPD, VAP and CF, and the 1654 G/A (rs2738047) associated with the susceptibility to COPD and asthma. Subgroup analyses based on ethnicity indicated that −44 C/G (rs1800972) may confer increased susceptibility to CRDs in Asians but not in Caucasians. Taken together, −44 C/G (rs1800972) and 1654 G/A (rs2738047) are strongly associated with CRD susceptibility, while associations of SNPs −52 G/A (rs1799946) and −20 G/A (rs11362) with CRDs needs further investigation.
OBJECTIVE To explore the law of clinical-diffusion mismatch (CDM) among patients with acute ischemic stroke (AIS) and analyze the relationships between CDM and short-term clinical outcomes. METHODS A prospective study was conducted for 56 patients with AIS admitted into our hospital within 72 hours from March 2011 to March 2012. And brain magnetic resonance imaging (MRI) examinations were completed within one week. All cases were diagnosed with infarction in the area of middle cerebral artery (MCA). The diffusion-weighted imaging (DWI) volume was calculated by semi-automatic method. Also the scores of National Institutes of Health stroke Scale (NIHSS) and modified Rankin Scale (mRS) were scored at baseline, days 7, 15, 30 post-admission respectively. The non-parametric variables were analyzed by Spearman's rank correlation. And the differences for non-parametric variables between CDM and non-CDM groups were analyzed by Mann-Whitney rank-sum test. RESULTS A total of 16/56(28.6%) patients showed CDM. The CDM ratios of the patients undergoing MRI within 72 hours after onset and those beyond 72 hours after onset were 36.3% and 17.4% respectively. Also 50.0% of those with CDM had favorite neurological outcomes. While for the other group without CDM, only 6.7% did so. The differences were significant (P = 0.001). The correlations for all AIS patients between NIHSS scores and DWI volume were strong (rs = 0.721, P = 0.009). Specifically, the correlations for without CDM group (rs = 0.847, P = 0.000) were stronger than those of with CDM group (rs = 0.610, P = 0.012). No significant inter-group differences existed in favorite clinical outcome, mortality case or neurological deterioration. CONCLUSION CDM still occurs within 1 week after onset among patients with AIS. Although no significant differences exist in favorite clinical outcome between patients with CDM and without CDM, the CDM group may improve more in NIHSS scores and have better neurological outcomes.
Objective To discuss the correlation between MRI manifestations and the National Institutes of Health Stroke Scale(NIHSS) or TCM syndrome factors in ischemic stroke of acute stage.Methods The cases of ischemia stroke(n=66) hospitalized by emergency were selected and given MRI examination,NIHSS scoring and TCM syndrome factor scoring.The MRI manifestations were divided into the brain stem group,cerebellar group,lobe group,thalamus group and basal ganglia group according to the focuses,and also divided into the lacunar infarction group,mid-or-small-area group and large-area group according to the infarction size.The correlation between MRI manifestations and NIHSS scores or syndrome factors were compared and analysed.Results In the relation between NIHSS scores and the focuses or size manifested by MRI,only basal ganglia group and lacunar infarction group were rated as mild in NIHSS scoring,and other groups had no significant and statistical difference(P0.05).In the relation between MRI manifestations and syndrome factors,different focuses and size were significantly correlated to various syndrome factors(P0.05).In the lacunar infarction group,mid-or-small-area group and large-area group,wind syndrome,phlegm syndrome and fire-heat syndrome were the most common ones.When infarction size increased,the proportion of qi deficiency syndrome and syndrome of yin deficiency with yang hyperactivity increased too.Conclusion The correlation between syndrome factors and MRI manifestations is more significantly compared that between NIHSS scoring and MRI manifestations.The technology of diffusion weighted imaging(DWI) of MRI can be taken as the index for helping diagnosing TCM syndromes,and it is important in the treatment of acute stroke with Chinese combined with Western medicine.