Network meta-analysis of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults.

OBJECTIVE: To compare the outcomes associated with the use of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults. METHODS: We searched eight electronic databases from database inception to July 11, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the treatment of chronic constipation. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of the evidence was assessed using the Confidence in Network Meta-Analysis framework. The analysis was conducted using R version 4.3.0. RESULTS: Out of the 37 RCTs, a total of 21 different types of interventions were reported, involving 3,903 patients. This NMA demonstrated that both prebiotics and synbiotics resulted in an increase in frequency of stool movements per week. Compared to placebo, lactulose (Mean difference [MD] = 3.39, 95% Confdence interval [CI] [1.13, 5.65], moderate certainty), mix2 (consisting of Lactulose and Bacillus coagulans) (MD = 3.63, 95% CI [1.37, 5.89], moderate certainty), mix6 (consisting of Lactulose and Bifidobacterium coagulans) (MD = 4.30, 95% CI [1.04, 7.54], low certainty), and mix7 (consisting of Lactulose, Bifidobacterium subtilis, and Enterococcus faecium) (MD = 4.58, 95% CI [1.35, 7.78], moderate certainty) exhibited a significant effect. Notably, mix7 demonstrated the highest probability of being the most effective intervention (94.8%). Furthermore, when compared to L. plantarum, four probiotics and two synbiotics showed significant advantages in the Patient Assessment of Constipation Symptoms (PAC-SYM) score. L. reuteri (MD = -13.74, 95% CI [-22.20, -4.66], very low certainty) exhibited a significant effect in improving the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. In terms of safety, there were no statistically significant differences between the intervention and control groups in all adverse event analyses. CONCLUSIONS: Moderate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the number of weekly stool movements in patients with constipation. The use of L. paracasei showed improvements in PAC-SYM scores, while L. reuteri demonstrated enhancements in PAC-QoL scores.

Extended endoscopic endonasal approach to the chiasmatic cistern: An anatomical study of the arachnoid.

This paper studied the arachnoid of the chiasmatic cistern (CC) and the methods for increasing the exposure of the CC from an endoscopic perspective. Eight anatomical specimens with vascular injection were used for endoscopic endonasal dissection. The anatomical characteristics of the CC were studied and documented, and anatomical measurements were collected. The CC is an unpaired five-walled arachnoid cistern located between the optic nerve, optic chiasm, and the diaphragma sellae. The average exposed area of the CC before the anterior intercavernous sinus (AICS) was transected was 66.67 ± 33.76 mm2 . After the AICS was transected and the pituitary gland (PG) was mobilized, the average exposed area of the CC was 95.90 ± 45.48 mm2 . The CC has five walls and a complex neurovascular structure. It is located in a critical anatomical position. The transection of the AICS and mobilization of the PG or the selective sacrifice of the descending branch of the superior hypophyseal artery can improve the operative field.

Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: systematic review and network meta-analysis of randomised trials.

OBJECTIVE: To compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches. METHODS: We searched four electronic databases from database inception to August 31, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the acute treatment of migraine. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of evidence using the CINeMA approach. We conducted frequentist network meta-analyses (NMA) to summarise the evidence. Data were analyzed using R-4.3.1. RESULTS: A total of 18 eligible studies including 10 different types of interventions with 22,429 migraine patients were included. NMA results showed that compared to ubrogepant (25 mg and 50 mg) and zavegepant, lasmiditan (100 mg and 200 mg) exhibits an elevated probability of achieving pain relief within a 2-hour interval. Similarly, relative to zavegepant, rimegepant (75 mg) and ubrogepant (50 mg and 100 mg) demonstrate an enhanced likelihood of sustaining pain relief over a 24-hour period. Furthermore, in contrast to ubrogepant (25 mg) and lasmiditan (50 mg), rimegepant (75 mg) presents a heightened probability of achieving freedom from photophobia within 2 h. Regarding safety, lasmiditan carries the highest risk of adverse events, which are associated with an increased incidence of adverse effects, including dizziness, somnolence, asthenia, paresthesia, and fatigue. CONCLUSIONS: In this NMA, a spectrum of evidence ranging from very low to high levels underscores the favorable efficacy and tolerability of rimegepant 75 mg and ubrogepant 100 mg, positioning them as potential candidates for the acute management of migraine. Concurrently, lasmiditan (100 mg and 200 mg) exhibits notable efficacy, albeit accompanied by an increased susceptibility to adverse events. These findings should still be approached with caution, primarily due to the intrinsic limitations associated with indirect comparisons.

The relationship of publication language, study population, risk of bias, and treatment effects in acupuncture related systematic reviews: a meta-epidemiologic study.

BACKGROUND: There are debates in acupuncture related systematic reviews and meta-analyses on whether searching Chinese databases to get more Chinese-language studies may increase the risk of bias and overestimate the effect size, and whether the treatment effects of acupuncture differ between Chinese and non-Chinese populations. METHODS: In this meta-epidemiological study, we searched the Cochrane library from its inception until December 2021, and identified systematic reviews and meta-analyses with acupuncture as one of the interventions. Paired reviewers independently screened the reviews and extracted the information. We repeated the meta-analysis of the selected outcomes to separately pool the results of Chinese- and non-Chinese-language acupuncture studies and presented the pooled estimates as odds ratios (OR) with 95% confidence interval (CI). We calculated the Ratio of ORs (ROR) by dividing the OR of the Chinese-language trials by the OR of the non-Chinese-language trials, and the ROR by dividing the OR of trials addressing Chinese population by the OR of trials addressing non-Chinese population. We explored whether the impact of a high risk of bias on the effect size differed between studies published in Chinese- and in non-Chinese-language, and whether the treatment effects of acupuncture differed between Chinese and non-Chinese population. RESULTS: We identified 84 Cochrane acupuncture reviews involving 33 Cochrane groups, of which 31 reviews (37%) searched Chinese databases. Searching versus not searching Chinese databases significantly increased the contribution of Chinese-language literature both to the total number of included trials (54% vs. 15%) and the sample size (40% vs. 15%). When compared with non-Chinese-language trials, Chinese-language trials were associated with a larger effect size (pooled ROR 0.51, 95% CI 0.29 to 0.91). We also observed a higher risk of bias in Chinese-language trials in blinding of participants and personnel (97% vs. 51%) and blinding of outcome assessment (93% vs. 47%). The higher risk of bias was associated with a larger effect estimate in both Chinese-language (allocation concealment: high/unclear risk vs. low risk, ROR 0.43, 95% CI 0.21 to 0.87) and non-Chinese-language studies (blinding of participants and personnel: high/unclear risk vs. low risk, ROR 0.41, 95% CI 0.23 to 0.74). However, we found no evidence that the higher risk of bias would increase the effect size of acupuncture in Chinese-language studies more often than in non-Chinese-language studies (the confidence intervals of all ROR in the high-risk group included 1, Table 3). We further found acupuncture appeared to be more effective in Chinese than in non-Chinese population (Table 4). CONCLUSIONS: The findings of this study suggest the higher risk of bias may lead to an overestimation of the treatment effects of acupuncture but would not increase the treatment effects in Chinese-language studies more often than in other language studies. The difference in treatment effects of acupuncture was probably associated with differences in population characteristics. TRIAL REGISTRATION: We registered our protocol on the Open Science Framework (OSF) ( https://doi.org/10.17605/OSF.IO/PZ6XR ).

Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a potentially life-threatening condition in which a clot can migrate from the deep veins, most commonly in the leg, to the lungs. Conventional treatment of PE used unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, and vitamin K antagonists (VKAs). Recently, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors. DOACs have characteristics that may be favourable to conventional treatment, including oral administration, a predictable effect, no need for frequent monitoring or re-dosing, and few known drug interactions. This review reports the efficacy and safety of these drugs in the long-term treatment of PE (minimum duration of three months). This is an update of a Cochrane Review first published in 2015.  OBJECTIVES: To assess the efficacy and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of PE. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials registers to 2 March 2022. We checked the reference lists of relevant articles for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which people with a PE confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with a conventional anticoagulant or compared with each other for the long-term treatment of PE (minimum duration three months). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent PE, recurrent venous thromboembolism (VTE), and deep vein thrombosis (DVT). Secondary outcomes were all-cause mortality, major bleeding, and health-related quality of life. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified five additional RCTs with 1484 participants for this update. Together with the previously included trials, we have included ten RCTs with a total of 13,073 participants. Two studies investigated an oral DTI (dabigatran) and eight studies investigated oral factor Xa inhibitors (three rivaroxaban, three apixaban, and two edoxaban). The studies were of good methodological quality overall.  Meta-analysis showed no clear difference in the efficacy and safety of oral DTI compared with conventional anticoagulation in preventing recurrent PE (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.50 to 2.04; 2 studies, 1602 participants; moderate-certainty evidence), recurrent VTE (OR 0.93, 95% CI 0.52 to 1.66; 2 studies, 1602 participants; moderate-certainty evidence), DVT (OR 0.79, 95% CI 0.29 to 2.13; 2 studies, 1602 participants; moderate-certainty evidence), and major bleeding (OR 0.50, 95% CI 0.15 to 1.68; 2 studies, 1527 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for imprecision due to the low number of events. There was also no clear difference between the oral factor Xa inhibitors and conventional anticoagulation in the prevention of recurrent PE (OR 0.92, 95% CI 0.66 to 1.29; 3 studies, 8186 participants; moderate-certainty evidence), recurrent VTE (OR 0.83, 95% CI 0.66 to 1.03; 8 studies, 11,416 participants; moderate-certainty evidence), DVT (OR 0.77, 95% CI 0.48 to 1.25; 2 studies, 8151 participants; moderate-certainty evidence), all-cause mortality (OR 1.16, 95% CI 0.79 to 1.70; 1 study, 4817 participants; moderate-certainty evidence) and major bleeding (OR 0.71, 95% CI 0.36 to 1.41; 8 studies, 11,447 participants; low-certainty evidence); the heterogeneity for major bleeding was significant (I2 = 79%). We downgraded the certainty of the evidence to moderate and low because of imprecision due to the low number of events and inconsistency due to clinical heterogeneity. None of the included studies measured health-related quality of life. AUTHORS' CONCLUSIONS: Available evidence shows there is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent PE, recurrent VTE, DVT, all-cause mortality, and major bleeding. The certainty of evidence was moderate or low. Future large clinical trials are required to identify if individual drugs differ in effectiveness and bleeding risk, and to explore effect differences in subgroups, including people with cancer and obesity.

Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review.  OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence).   For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence).  AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortality. DOACs reduced the rate of major bleeding compared to conventional anticoagulation. The certainty of evidence was moderate or high.

Cystathionine beta-Synthase in hypoxia and ischemia/reperfusion: A current overview.

Besides its presence in the liver, brain, pancreas, and kidney, Cystathionine beta-Synthase (CBS) is also found in many other tissues, where it acts through regulation of hydrogen sulfide (H2S) generation and homocysteine (Hcy) metabolism, to interact with other molecules during hypoxia and ischemia/reperfusion (I/R). Despite all the advances accumulated in decades of research on CBS, there are still controversies, and the role of CBS in many tissues during hypoxia and I/R is still unclear. Herein, we overviewed the expression level, the role, and the mechanism through which CBS interacts with other molecules during hypoxia and I/R processes in tissues of humans and other organisms. CBS appeared to be deregulated under hypoxia and I/R, after which it mostly conduces the reparation in the concerned tissue after damage; however, it has been described that CBS could also play pathological effects (exacerbating the damage). From all findings, it emerges that variations in CBS expression in these conditions depend on the organism, tissue, or subcellular localization, CBS could play both protective and pathological effects; and artificially controlling CBS expression may help to provide novel strategies for treatment or prevention of hypoxia and I/R -related injury.

Relationship between antidepressive agents and incidence risk of breast cancer: systematic review and meta-analysis.

Purpose: This study aimed to review the association between antidepressive agent (AD) use and the incidence risk of breast cancer. Methods: CBM, WOS, Embase, PubMed and Cochrane Library were systematically searched in July 2019. The methodological quality of the studies was assessed through the Newcastle-Ottawa Scale. Results: We included 19 studies from six countries or regions with relationships between breast cancer and ADs. Subgroup analysis showed no significant association in nested case-control or case-control studies; however, cohort studies revealed a significant association (odds ratio = 1.11; 95% CI: 1.04-1.17). Conclusions: This meta-analysis indicates that breast cancer was not associated with the use of ADs when considering all types of studies, but an association was observed if we considered cohort studies.

Air pollution and metabolic syndrome risk: Evidence from nine observational studies.

BACKGROUND AND AIMS: Globally, the number of metabolic syndrome (MetS) cases has increased substantially over time. However, the association between air pollution (AP) and MetS risk has been contradictory in observational studies. This is the first reported meta-analysis quantitatively exploring the aforementioned association. METHODS: We searched PubMed, Embase, and Web of Science database entries up to September 14, 2020, and searches were updated up to December 6, 2020 to identify eligible articles on the AP-MetS risk association. No language restriction was imposed. Random-effects models were applied to estimate summary and subgroup effect sizes with 95% confidence intervals (CIs). PROSPERO registration number: CRD42020210431. RESULTS: Eight articles (nine studies) were eligible for the meta-analysis. Increased MetS prevalence was not found to be associated with particulate matter less than 1 µm (PM1), 2.5 µm (PM2.5), and 10 µm (PM10) in diameter or nitrogen dioxide (NO2), and the summary effect sizes were 1.33 (95% CI: 0.95-1.85), 1.34 (95% CI: 0.96-1.89), 1.18 (95% CI: 0.98-1.19), and 1.28 (95% CI: 0.89-1.82), respectively, based on cross-sectional studies. The summary results indicated no association between each 10 µg/m3 increase in PM2.5 and MetS incidence (effect size 2.78 [95% CI: 0.70-11.02]), based on cohort studies. Subgroup analysis demonstrated that MetS incidence in older men increased dramatically by 992% with each 10 µg/m3 increase in PM2.5. CONCLUSIONS: The evidence presented here suggests that although exposure to PM1, PM2.5, PM10, or NO2 was not found to have a significant association with the occurrence of MetS, the statistical significance of the relationship between exposure to PM1, PM2.5, or PM10 and MetS prevalence was approximately borderline. More studies on AP-MetS risk association in low-/middle-income countries, as well as on the association between other air pollutants and MetS risk, are warranted. A sufficient number of high-quality studies is required to perform a meaningful meta-analysis of the relationship between air pollutants and MetS.

Association between alcohol intake, mild cognitive impairment and progression to dementia: a dose-response meta-analysis.

BACKGROUND: Mild cognitive impairment (MCI) is a cognitive state falling between normal aging and dementia. The relation between alcohol intake and risk of MCI as well as progression to dementia in people with MCI (PDM) remained unclear. OBJECTIVE: To synthesize available evidence and clarify the relation between alcohol intake and risk of MCI as well as PDM. METHOD: We searched electronic databases consisting of PubMed, EMBASE, Cochrane Library, and China Biology Medicine disc (CBM) from inception to October 1, 2019. Prospective studies reporting at least three levels of alcohol exposure were included. Categorical meta-analysis was used for quantitative synthesis of the relation between light, moderate and heavy alcohol intake with risk of MCI and PDM. Restricted cubic spline and fixed-effects dose-response models were used for dose-response analysis. RESULT: Six cohort studies including 4244 individuals were finally included. We observed an unstable linear relation between alcohol intake (drinks/week) and risk of MCI (P linear = 0.0396). It suggested that a one-drink increment per week of alcohol intake was associated with an increased risk of 3.8% for MCI (RR, 1.038; 95% CI 1.002-1.075). Heavy alcohol intake (> 14 drinks/week) was associated with higher risk of PDM (RR = 1.76; 95% CI 1.10-2.82). And we found a nonlinear relation between alcohol intake and risk of PDM. Drinking more than 16 drinks/week (P nonlinear = 0.0038, HR = 1.42; 95% CI 1.00-2.02), or 27.5 g/day (P nonlinear = 0.0047, HR = 1.46; 95% CI 1.00-2.11) would elevate the risk of PDM. CONCLUSION: There was a nonlinear dose-response relation between alcohol intake and risk of PDM. Excessive alcohol intake would elevate the risk of PDM.

The CnB1 p.D102A variant is linked to dilated cardiomyopathy via impaired Calcineurin activity.

BACKGROUND: The role of calcineurin (protein phosphatase 2B (PP2B)) in the pathogenesis of human dilated cardiomyopathy (DCM) has not been fully elucidated. We determined the potential involvement of calcineurin in the pathogenesis of DCM caused by mutations in CnB1, a subunit of calcineurin. METHODS: By whole-exome sequencing, we identified a new CnB1 variant in a Han Chinese proband with cardiomyopathy from a 3-generation family with 2 normal individuals and 3 individuals with familial dilated cardiomyopathy. The potential pathogenic variant was validated by Sanger sequencing. We performed functional and mechanistic experiments in a CnB1-knockin (KI) mouse model and at the cellular level. RESULTS: We detected a rare heterozygous CnB1 variant (p.D102A) in a proband with dilated cardiomyopathy. This variant was localized to the EF hand 3 region of CnB1, where no variants have been previously reported. KI mice harboring the p.D102A variant exhibited decreased cardiac function and cardiac dilatation. Immunoblotting, RT-PCR and immunofluorescence results showed decreased cardiomyocyte size and heart failure-related protein expression. A calcineurin activity assay demonstrated decreased calcineurin activity in the KI mice, accompanied by the decreased ability of CnB1 to bind CnA. CONCLUSIONS: CnB1 p.D102A is a disease-associated variant that confers susceptibility to cardiac dilatation. This variant is associated with impaired calcineurin activity and a subsequent decrease in the ability of CnB1 to bind CnA.

Different fuel regulation in two types of myofiber results in different antioxidant strategies in Daurian ground squirrels (Spermophilus dauricus) during hibernation.

We previously showed that different skeletal muscles in Daurian ground squirrels (Spermophilus dauricus) possess different antioxidant strategies during hibernation; however, the reason for these varied strategies remains unclear. To clarify this issue, we studied REDD1, FOXO4, PGC-1α, FOXO1, and atrogin-1 proteins to determine the potential cause of the different antioxidant strategies in Daurian ground squirrels during hibernation, and to clarify whether different strategies affect atrophy-related signals. Results showed that the soleus (SOL) muscle experienced intracellular hypoxia during interbout arousal, but no oxidative stress. This may be due to increased PGC-1α expression enhancing antioxidant capacity in the SOL under hypoxic conditions. Extensor digitorum longus (EDL) muscle showed no change in oxidative stress, hypoxia, or antioxidant capacity during hibernation. The FOXO1 and PGC-1α results strongly suggested differentially regulated fuel metabolism in the SOL and EDL muscles during hibernation, i.e., enhanced lipid oxidation and maintained anaerobic glycolysis, respectively. Atrogin-1 expression did not increase during hibernation in either the SOL or EDL, indicating that protein synthesis was not inhibited by atrogin-1. Thus, our results suggest that different fuel regulation may be one mechanism related to antioxidant defense strategy formation in different kinds of skeletal muscle fibers of Daurian ground squirrels during hibernation.

Maternal preconception and first trimester exposure to PM10 and the risk of oral clefts in offspring: a population-based, case-control study.

BACKGROUND: Current literature describes limited and controversial evidence on the associations between maternal preconception and first trimester exposure to particulate matter with a diameter ≤10 µm (PM10) and the risk of oral cleft (OC). METHODS: We conducted a case-control study involving 3086 OC cases and 7950 controls, registered in the Maternal and Child Health Certificate Registry in Liaoning Province between 2010 and 2015. PM10 concentrations were obtained from the Environment Protection Bureau. The exposure windows included the 3 months before pregnancy, the first trimester and the individual months. Unconditional logistic regression model was performed to estimate the OR and 95% CI for the association between PM10 exposure and the risk of OC, cleft lip only (CLO), cleft palate only (CPO), and cleft lip and palate (CLP). RESULTS: Maternal PM10 exposure was positively associated with an increased risk for OC during the 3 months preconception (per 10 µg/m3 increment: OR=1.04, 95% CI 1.01 to 1.07; highest vs lowest quartile: OR=1.23, 95% CI 1.04 to 1.45) and the first trimester (per 10 µg/m3 increment: OR=1.05, 95% CI 1.02 to 1.08; highest vs lowest quartile: OR=1.37, 95% CI 1.15 to 1.64). Analyses based on individual months presented similar positive associations, particularly in the second month of pregnancy (OR=1.77, 95% CI 1.51 to 2.09) for highest versus lowest quartile. In the subtype analysis, stronger associations were observed for CLO, whereas there was negligible evidence for CPO and CLP. Sensitivity analyses using propensity score matching generated similar findings. CONCLUSIONS: Our study provides evidence that PM10 exposure during the 3 months preconception and the first trimester increases the risk of OC.

Higher Levels of High-Sensitivity C-Reactive Protein Is Positively Associated with the Incidence of Hyperuricemia in Chinese Population: A Report from the China Health and Retirement Longitudinal Study.

PURPOSE: The aim of the present cohort study was to explore the longitudinal association between high-sensitivity C-reactive protein (CRP) and hyperuricemia in Chinese population. Furthermore, we conducted subgroup analyses to explore this association according to age, sex, and body mass index. METHODS: A total of 5,419 healthy participants were enrolled in the final cohort analysis. The high-sensitivity CRP level was measured by immunoturbidimetric assay. Hyperuricemia was defined as serum uric acid ≥7.0 mg/dL (416 µmol/L) in men and ≥6.0 mg/dL (357 µmol/L) in women. Multivariate logistic regression was used to analyze the association. RESULTS: During the 4 years follow-up, 474 participants developed hyperuricemia. Compared with participants in the lowest tertile of high-sensitivity CRP, the multivariate-adjusted odds ratio (OR) (95% confidence interval [CI]) for incident hyperuricemia in the highest tertile was 1.36 (1.02, 1.82). In the subgroup analyses, high-sensitivity CRP was positively associated with the incidence of hyperuricemia after multivariate adjustments (P for trend = 0.04) in women. Compared with the women in the lowest tertile of high-sensitivity CRP, the multivariate-adjusted OR (95% CI) in the highest tertile was 1.69 (1.10, 2.66). No statistically significant association was found in other subgroups. CONCLUSIONS: The findings of this prospective cohort study suggest that higher level of high-sensitivity CRP is an independent risk factor for hyperuricemia in Chinese, especially in women.

The Role of miR-210 in the Biological System: A Current Overview.

BACKGROUND: MicroRNAs (miRNAs) represent a group of non-coding RNAs measuring 19-23 nucleotides in length and are recognized as powerful molecules that regulate gene expression in eukaryotic cells. miRNAs stimulate the post-transcriptional regulation of gene expression via direct or indirect mechanisms. SUMMARY: miR-210 is highly upregulated in cells under hypoxia, thereby revealing its significance to cell endurance. Induction of this mRNA expression is an important feature of the cellular low-oxygen response and the most consistent and vigorous target of HIF. Key Message: miR-210 is involved in many cellular functions under the effect of HIF-1α, including the cell cycle, DNA repair, immunity and inflammation, angiogenesis, metabolism, and macrophage regulation. It also plays an important regulatory role in T-cell differentiation and stimulation.

Health research capacity of professional and technical personnel in a first-class tertiary hospital in northwest China: multilevel repeated measurement, 2013-2017, a pilot study.

OBJECTIVES: To explore the health research capacity (HRC) and factors associated with professional and technical personnel (PTP) in a first-class tertiary hospital in northwest China. METHODS: We collected the repeated measurement data from a first-class tertiary hospital in northwest China between 2013 and 2017. HRC of PTP was assessed by a comprehensive evaluation system and measured by research capacity score (RCS). The participants were divided into research group (RCS >0) and comparison group (RCS = 0); participants of the comparison group were selected by two-stage stratified random sampling. Multilevel model for repeated measures was used to investigate the potential factors associated with HRC. RESULTS: A total of 924 PTP were included (308 in the research group and 616 in the comparison group). This study found consistent growth in RCS and associated 95% CIs for the hospital during 2013 and 2017. The linear multilevel model showed PTP with a doctorate degree had higher RCS than those with a master's degree (ß, 1.74; P <0.001), bachelor's degree (ß, 2.02; P <0.001) and others without a degree (ß, 2.32; P <0.001). Furthermore, the PTP with intermediate (ß, 0.13; P = 0.015), vice-high (ß, 0.27; P = 0.001) and senior (ß, 0.63; P <0.001) professional titles had higher RCS than those with junior positions. Compared with PTP in the administration, those in paediatrics had higher RCS (ß, 0.28; P = 0.047) though similar to PTP in other departments. PTP with an administrative position had a higher RCS than those in non-administrative positions (ß, 0.26; P <0.001). The RCS increased with the research fund (ß, 0.15; P <0.001). However, no associations were found between RCS and sex, age, ethnic, graduate school or technical type. CONCLUSIONS: HRC with associated variation of PTP for the hospital in northwest China increasingly improved and degree, professional title, administrative position, and research fund were related to HRC of PTP. Multi-central prospective studies are needed to clarify the potential relationship of related factors and HRC of PTP.

The effect of bladder catheterization on the incidence of urinary tract infection in laboring women with epidural analgesia: a meta-analysis of randomized controlled trials.

INTRODUCTION AND HYPOTHESIS: There is conflicting evidence on whether intermittent catheterization (IC) is less associated with urinary tract infection (UTI) and more likely to prevent urinary retention than continuous catheterization (CC). We aimed to compare the effect of IC with that of CC on the incidence of postpartum UTI, urinary retention and hemorrhage in laboring women with epidural analgesia. METHODS: Electronic searches were performed in PubMed, EMBASE and Cochrane Library from their inception to October 2018. We selected RCTs comparing IC with CC in laboring women with epidural analgesia. A meta-analysis was performed using the RevMan software, and a random-effects model was used to pool the effect size. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence. RESULTS: Six RCTs (N = 850) were included in this review. The meta-analyses indicated that there was no significant difference between the IC and CC group in the incidence of postpartum UTI (RR = 1.25, 95% CI: 0.91 to 1.71, P = 0.16), postpartum urinary retention (RR = 0.76, 95% CI: 0.21 to 2.77, P = 0.68) and postpartum hemorrhage (RR = 1.72, 95% CI: 0.60 to 4.95, P = 0.31). GRADE assessment results showed that the quality of evidence was low. CONCLUSIONS: Based on the available evidence, there is no measurable difference in rates of UTI between CC and IC, not that neither stragety decreases UTI, since the included trials do not address this.

Quercetin protects against intestinal barrier disruption and inflammation in acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition.

OBJECTIVE: To investigate the effects of quercetin on intestinal barrier disruption and inflammation in acute necrotizing pancreatitis (ANP) in rats, and its possible mechanism. METHODS: ANP was established by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, and quercetin (50 mg/kg × 3) was administered by intraperitoneal injection prior to and after ANP induction. Pancreatitis was assessed by pancreatic histopathology, plasma amylase, pancreatic myeloperoxidase (MPO) activity, IL-1ß, TNFα and IL-6 levels. Injury of the distal ileum was assessed by histological evaluation. The ultrastructural changes of ileal epithelial cells were examined by transmission electron microscope (TEM). Intestinal barrier function was estimated by plasma diamine oxidase (DAO), d-lactate, endotoxin; and intestinal tight junction proteins including zonula occludens-1 (ZO-1), claudin 1, occludin; and bacterial translocation. Intestinal inflammation was determined by IL-1ß, TNFα and IL-17 A expression. TLR4, MyD88, pp38 MAPK, and endoplasmic reticulum stress (ERS)-related molecules (Bip, p-IRE1α, sXBP1, p-eIF2α, ATF6) were measured by immunohistochemistry and WB. RESULTS: Quercetin intervention attenuated pancreatic and ileal pathological damages in ANP (P < 0.05), ameliorated intestinal barrier disruption and inflammation (P < 0.05). Meantime, QE significantly suppressed intestinal TLR4/MyD88/p38 MAPK pathway and ERS activation. CONCLUSIONS: Quercetin plays a protective role against intestinal barrier disruption and inflammation in ANP, probably partly by inhibiting TLR4/MyD88/p38 MAPK and ERS activation.

Membranous subaortic stenosis coexisting with hypertrophic cardiomyopathy: A case report.

Subaortic stenosis (SAS) is a congenital heart disease, and its association with hypertrophic cardiomyopathy is very rare and clinically underappreciated. We report here a case of a 45-year-old female who was admitted to our hospital with chest tightness and shortness of breath. Both transthoracic and transesophageal echocardiography revealed asymmetric left ventricular hypertrophy and a membrane-like echo below the level of the aortic valve. This patient was diagnosed with membranous SAS with hypertrophic cardiomyopathy. Screening of her immediate family members revealed that her son also had hypertrophic cardiomyopathy. The patient chose conservative treatments and has been closely followed-up after discharge.

Fast fabrication of NiO@graphene composites for supercapacitor electrodes: Combination of reduction and deposition.

Graphene-based inorganic composites have been attracting more and more attention since the attachment of inorganic nanoparticles instead of conducting polymeric materials to graphene sheets turns out higher capacitances and good capacity retention. Here we report a fast fabrication method to prepare NiO@graphene composite modified electrodes for supercapacitors. By this method, preparation of electrochemical active materials of NiO/graphene and modification of the electrode can be simultaneously performed, which is achieved separately by traditional method. Moreover, the problem of poor adhesion of active materials on the surface of the electrode can be well solved. The NiO particles introduced to the films exhibit pseudocapacitive behavior arising from the reversible Faradaic transitions of Ni(II)/Ni(III) and greatly improve the capacitance of the electrodes. With the increase in NiO content, highly reduced graphene can be obtained during cyclic voltammetry sweeping, leading to the increase in the electrode capacitance. The highest specific capacitance of the constructed electrodes can reach 1258 F/g at a current density of 5 A/g.