Correlation between serum trimethylamine-N-oxide and body fat distribution in middle-aged and older adults: a prospective cohort study.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study. METHODS: Data of 1964 participants (40-75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008-2014 was analyzed. Serum TMAO concentration was quantified by HPLC-MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration. RESULTS: After an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P-trend = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P-trend = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 - 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 - 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results. CONCLUSION: Serum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future. TRIAL REGISTRATION: NCT03179657.

FOXD2-AS1 promotes malignant cell behavior in oral squamous cell carcinoma via the miR-378 g/CRABP2 axis.

BACKGROUND: Oral squamous cell cancer (OSCC) is a prevalent malignancy in oral cavity, accounting for nearly 90% of oral malignancies. It ranks sixth among the most common types of cancer worldwide and is responsible for approximately 145,000 deaths each year. It is widely accepted that noncoding RNAs participate cancer development in competitive regulatory interaction, knowing as competing endogenous RNA (ceRNA) network, whereby long non-coding RNA (lncRNA) function as decoys of microRNAs to regulate gene expression. LncRNA FOXD2-AS1 was reported to exert an oncogenic role in OSCC. Nevertheless, the ceRNA network mediated by FOXD2-AS1 was not investigated yet. This study aimed to explore the effect of FOXD2-AS1 on OSCC cell process and the underlying ceRNA mechanism. METHODS: FOXD2-AS1 expression in OSCC cells were determined via reverse transcription and quantitative polymerase chain reaction. Short hairpin RNA targeting FOXD2-AS1 was transfected into OSCC cells to silence FOXD2-AS1 expression. Then, loss-of-function experiments (n = 3 each assay) were performed to measure cell proliferation, apoptosis, migration, and invasion using colony formation, TdT-mediated dUTP Nick-End Labeling, wound healing and Transwell assays, respectively. RNA binding relation was verified by RNA immunoprecipitation and luciferase reporter assays. Rescue experiments were designed to validate whether FOXD2-AS1 affects cell behavior via the gene cellular retinoic acid binding protein 2 (CRABP2). Statistics were processed by GraphPad Prism 6.0 Software and SPSS software. RESULTS: FOXD2-AS1 was significantly upregulated in Cal27 and SCC9 cells (6.8 and 6.4 folds). In response to FOXD2-AS1 knockout, OSCC cell proliferation, migration and invasion were suppressed (approximately 50% decrease) while OSCC cell apoptosis was enhanced (more than two-fold increase). FOXD2-AS1 interacted with miR-378 g to alter CRABP2 expression. CRABP2 upregulation partly rescued (*p < 0.05, **p < 0.01, ***p < 0.001) the inhibitory impact of FOXD2-AS1 depletion on malignant characteristics of OSCC cells. CONCLUSION: FOXD2-AS1 enhances OSCC malignant cell behaviors by interacting with miR-378 g to regulate CRABP2 expression.

Gene-gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy.

Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene-gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene-gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING_TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene-gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders.

Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m6A-YTHDF2-dependent manner.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 µg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1ß, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1ß. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

Effects and safety of hyaluronic acid gel on intrauterine adhesion and fertility after intrauterine surgery: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

OBJECTIVE: This study aimed to determine the efficacy and safety of hyaluronic acid gel for the prevention of intrauterine adhesions and improved fertility after intrauterine surgery. DATA SOURCES: PubMed, EMBASE, Cochrane Library, Web of science, and ClinicalTrials.gov were searched up to November 1, 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that reported intrauterine adhesion and fertility outcomes among women who used hyaluronic acid after intrauterine surgery. METHODS: The risk of bias was assessed using criteria of the Cochrane Handbook, and the quality of the evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A trial sequential analysis was conducted to assess the outcomes, and Stata 14 was used for sensitivity analyses and publication bias analyses. RESULTS: Data from 16 randomized controlled trials involving 2359 patients were extracted and analyzed. The analysis revealed that hyaluronic acid reduced the incidence of intrauterine adhesion (risk ratio, 0.53; 95% confidence interval, 0.42-0.67; I2=48%) and improve pregnancy rates (risk ratio, 1.24; 95% confidence interval, 1.02-1.50; I2=0%). A subgroup analysis was conducted to evaluate factors that influence the effect of hyaluronic acid on the incidence of intrauterine adhesion. It was found that a small volume of hyaluronic acid reduced the incidence of intrauterine adhesions. Hyaluronic acid exhibited a protective effect among patients who underwent various intrauterine surgeries and who had different gynecologic medical histories. The protective effect was statistically significant after a follow-up of 6 to 12 weeks. The results of the trial sequential analysis indicated that the effect of hyaluronic acid on the incidence of mild intrauterine adhesions, pregnancy rates, live birth rates, and miscarriage rates after intrauterine surgery may be inconclusive and thus further evaluation is required in the form of additional clinical trials. However, the remaining effects were found to be verifiable and did not require more clinical trials for confirmation. CONCLUSION: Hyaluronic acid can safely and effectively reduce the incidence of intrauterine adhesions and may improve fertility outcomes.

The impact of nurses' experiences of hospital violence on resilience: A mediated moderation model.

AIMS: This study aims to investigate the impact of nurses' experiences of hospital violence on resilience, the mediating effect of trust in patients and the moderating effect of organizational trust. BACKGROUND: Despite belonging to the central part of health care worldwide and being the leading provider of medical services, nurses are often subjected to hospital violence, which affects their physical and mental well-being. Trust is a high-order mechanism that encourages positive thinking and personal and professional development. However, research into the impact of trust on resilience concerning nurses' experiences of hospital violence is limited. METHODS: The participants were 2331 nurses working in general hospitals in China. A cross-sectional survey was conducted, and data were collected via questionnaires from July to October 2022 and analysed using SPSS 25.0 and SPSS PROCESS 3.3 macros. This study was prepared and reported according to the STROBE checklist. RESULTS: Mean trust in patients was 48.00 ± 10.86 (12-60), mean organizational trust was 56.19 ± 8.90 (13-65) and mean resilience was 78.63 ± 19.26 (0-100). Nurses' experience of hospital violence had a direct negative effect on resilience (ß = -.096, p = .871), a significant adverse effect on trust in patients (ß = -3.022, p < .001) and a significant positive effect on trust in patients on resilience (ß = 1.464, p < .001). Trusting patients played a mediating role. The significant moderating effect of organizational trust between experience of hospital violence and trust in patients was moderated by a mediating effect index of -0.1867 (95% CI = [-0.3408, -0.0345]). CONCLUSIONS: Nurses' experience of hospital violence exerted a negative effect on resilience, trust in patients had a fully mediated effect and organizational trust had a significant moderating influence in the pathway from nurses' experience of hospital violence to patients' trust-mediated resilience. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study highlights the impact of nurses' experiences of hospital violence on resilience and explores the importance of trust from the nurses' perspective. Measures taken by managers to provide nurses with a safe, trusting and positive work environment can be highly beneficial in enhancing nurse resilience.

Correlation between controlled ovarian stimulation protocols and euploid blastocyst rate in pre-implantation genetic testing for aneuploidy cycles.

BACKGROUND: Several studies have explored which COS protocol yields a higher blastocyst euploidy rate, but findings have been inconsistent. The present study aimed to explore whether controlled ovarian stimulation (COS) protocols was associated with euploid blastocyst rate in pre-implantation genetic testing for aneuploidy (PGT-A) cycles. METHODS: The study was a retrospective study where data were obtained from three reproductive medicine centers. The study included PGT-A cycles with the GnRH-a, GnRH-ant, or PPOS protocols, and the data on patient demographics, protocols, and embryonic outcomes were collected for the PGT-A cycles performed between January 2019 and August 2022. RESULTS: This study included 457 PGT-A cycles from three reproductive medicine centers, with 152, 126, and 179 cycles performed using the PPOS, GnRH-a, and GnRH-ant protocols, respectively. The baseline characteristics of the three groups show no significant differences were observed in female BMI, infertility type, and infertility duration among the PPOS, GnRH-a, and GnRH-ant protocol groups. The study found no significant association between Gn dosage, Gn duration, and blastocyst euploidy. The mean number of euploidy blastocysts in PPOS protocol was significantly lower than that of GnRH-a protocol and GnRH-ant protocol (0.75 ± 0.92 vs. 1.79 ± 1.78 vs. 1.80 ± 1.67). The euploidy rate per biopsy blastocyst (48.4% vs. 49.1% vs. 33.1%), per oocyte retrieved (15.0% vs. 14.7% vs. 10.5%), and per MII oocyte (17.7% vs. 16.4% vs. 11.7%) were significantly higher in the cycles using the GnRH-ant and GnRH-a protocols than that of PPOS protocol group. Regression analyses indicated that, compared with the PPOS protocol, the GnRH-ant protocol was positively associated with the euploid blastocyst rate and the mean number of euploid blastocysts, whereas the GnRH-a protocol showed no such relationship. LIMITATIONS AND REASONS FOR CAUTION: The main limitation of this study was the retrospective design. Although this study also used other tests to account for confounding factors and reduce potential bias, multiple tests have its own weaknesses. CONCLUSIONS: GnRH-ant protocol was the most effective for PGT-A cycles. The findings emphasize the need for personalized treatment strategies, considering patient demographics, and optimizing COS protocols to enhance the chances of successful outcomes in ART procedures.

Higher oxidative balance score decreases risk of stroke in US adults: evidence from a cross-sectional study.

Background: The oxidative balance score (OBS) can be used to represent the overall burden of oxidative stress in an individual. This study aimed to explore the association between the risk of stroke and OBS. Methods and materials: The National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 was used to extract a series of variables for participants who took the stroke questionnaire. The construction of OBS relied on diet and lifestyle components, which included 16 nutrients and 4 lifestyle factors. Weighted multivariable-adjusted logistic regression was performed to investigate the association between stroke risk and OBS. A stratified analysis was also conducted. The dose-response relationship between stroke risk and OBS was elucidated by performing a restricted cubic spline function. Results: A total of 20,680 participants were included for analysis, 768 of whom suffered from stroke. Based on weighted multivariable logistic regression analysis, we discovered that the stroke prevalence decreased by 2% for each OBS unit added [OR: 0.98 (0.97-1.00), P < 0.01]. For the OBS subgroup, we also discovered that higher OBS was related to a reduction in the risk of stroke [Q4 vs. Q1: OR:0.65 (0.46-0.90), P < 0.01]. The prevalence of stroke declined by 3% with every OBS unit added to the diet component [OR: 0.97 (0.96-0.99), P < 0.01]. For the dietary OBS subgroup, higher OBS in diet components was associated with a decrease in the prevalence of stroke [Q4 vs. Q1: OR: 0.65, (0.47-0.91), P < 0.05]. Further stratified analysis showed that every OBS unit raised was associated with a decline in stroke prevalence, which was statistically significant in participants in subgroups of ≥60 years, female, no-diabetes mellitus and no-hypertension. OBS and stroke prevalence were correlated in a linear manner. Conclusion: The study found that a higher OBS was associated with a decrease in stroke prevalence, which could be a significant indicator for evaluating stroke risk.

Mitigating the impact of bisphenol A exposure on mortality: Is diet the key? A cohort study based on NHANES.

Bisphenol A (BPA) is a widespread environmental pollutant linked to detrimental effects on human health and reduced life expectancy following chronic exposure. This prospective cohort study aimed to examine the association between BPA exposure and mortality in American adults and to explore the potential mitigating effects of dietary quality on BPA-related mortality. This study utilized data from 8761 American adults in the 2003-2016 National Health and Nutrition Examination Survey (NHANES). Urinary BPA levels were employed to assess BPA exposure, and dietary quality was evaluated using the Healthy Eating Index-2015 (HEI-2015). All-cause, cardiovascular disease (CVD), and cancer mortality statuses were determined until December 31, 2019, resulting in a cumulative follow-up of 80,564 person-years. The results showed that the highest tertile of urinary BPA levels corresponded to a 36% increase in all-cause mortality and a 62% increase in CVD mortality compared to the lowest tertile. In contrast, the highest tertile of HEI-2015 scores was associated with a 29% reduction in all-cause mortality relative to the lowest tertile. Although no significant interaction was found between HEI-2015 scores and urinary BPA levels concerning mortality, the association between HEI-2015 scores and both all-cause and CVD mortality was statistically significant at low urinary BPA levels. Continuous monitoring of BPA exposure is crucial for evaluating its long-term adverse health effects. Improving dietary quality can lower all-cause mortality and decrease the risk of all-cause and CVD mortality at low BPA exposure levels. However, due to the limited protective effect of dietary quality against BPA exposure, minimizing BPA exposure remains a vital goal.

Associations of serum betaine with blood pressure and hypertension incidence in middle-aged and older adults: a prospective cohort study.

The impact of betaine on the development of hypertension remains unclear, and prospective data are sparse. We aimed to investigate the association of serum betaine with repeated measurements of blood pressure (BP) and hypertension incidence. This study was based on the Guangzhou Nutrition and Health Study (GNHS), a community-based prospective cohort study in China. Baseline serum betaine was measured by high-performance liquid chromatography-tandem mass spectrometry. BP and hypertension status were assessed at the baseline and 3-year intervals. Linear mixed-effects models (LMEMs) were used to analyze the longitudinal association of serum betaine with BP (n = 1996). Cox proportional hazard models were used to evaluate the association of baseline serum betaine with hypertension incidence (n = 1339). LMEMs showed that compared with the lowest quartile group, the higher quartile groups had lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (all P-trend < 0.05). Each standard deviation (16.3 µmol L-1) increase in serum betaine was associated with -0.92 (-1.52, -0.32) mmHg of SBP, -0.49 (-0.84, -0.13) mmHg of DBP and -0.43 (-0.81, -0.05) mmHg of pulse pressure. During a median follow-up of 9.2 years, 371 incident cases of hypertension were identified. Serum betaine was associated with lower risk of hypertension only when comparing the third quartile level with the lowest quartile (HR, 0.74; 95% CI, 0.56-0.99). A nonlinear association between serum betaine and the risk of hypertension was found (P-nonlinear = 0.040). A higher serum betaine level was associated with lower risk of hypertension below 54.5 µmol L-1. Our findings suggested that higher serum betaine was associated with favorable blood pressure in middle-aged and older Chinese adults. Higher concentrations of serum betaine were related to lower hypertension risk in people with relatively low serum betaine concentrations.

Sub-region analysis of DMD gene in cases with idiopathic generalized epilepsy.

Gene sub-region encoded protein domain is the basic unit for protein structure and function. The DMD gene is the largest coding gene in humans, with its phenotype relevant to idiopathic generalized epilepsy. We hypothesized variants clustered in sub-regions of idiopathic generalized epilepsy genes and investigated the relationship between the DMD gene and idiopathic generalized epilepsy. Whole exome sequencing was performed in 106 idiopathic generalized epilepsy individuals. DMD variants were filtered with variant type, allele frequency, in silico prediction, hemizygous or homozygous status in the population, inheritance mode, and domain location. Variants located at the sub-regions were selected by the subRVIS software. The pathogenicity of variants was evaluated by the American College of Medical Genetics and Genomics criteria. Articles on functional studies related to epilepsy for variants clustered protein domains were reviewed. In sub-regions of the DMD gene, two variants were identified in two unrelated cases with juvenile absence epilepsy or juvenile myoclonic epilepsy. The pathogenicity of both variants was uncertain significance. Allele frequency of both variants in probands with idiopathic generalized epilepsy reached statistical significance compared with the population (Fisher's test, p = 2.02 × 10-6, adjusted α = 4.52 × 10-6). The variants clustered in the spectrin domain of dystrophin, which binds to glycoprotein complexes and indirectly affects ion channels contributing to epileptogenesis. Gene sub-region analysis suggests a weak association between the DMD gene and idiopathic generalized epilepsy. Functional analysis of gene sub-region helps infer the pathogenesis of idiopathic generalized epilepsy.

Relationship between advanced maternal age and decline of endometrial receptivity: a systematic review and meta-analysis.

Female fertility decreases with age. A decline in oocyte quality plays a key role in reproductive problems in older women. Whether advanced maternal age (AMA) is associated with a decline in endometrial receptivity (ER) remains controversial. A systematic review and meta-analysis were conducted to evaluate the relationship between AMA and ER. Eighteen eligible studies were included in this meta-analysis. Of the 18 studies, 17, 8, 14, and 9 studies reported the impact of AMA on clinical pregnancy rate (CPR), implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR), respectively. The combined results showed a trend (without significance) toward lower CPR in women with AMA than in younger women. A similar trend of worse outcomes in terms of IR was observed in women with AMA. A significantly higher MR and lower LBR were observed in infertile women with AMA than in younger women. In conclusion, there was a slightly lower IR and CPR without significance; however, significantly increased MR and decreased LBR were observed in women with AMA than in younger women, indicating that AMA is related to the decline of ER. Further prospective cohort studies with a preimplantation genetic testing for aneuploidy model are needed to observe the relationship between AMA and ER and explore the possible mechanisms.

Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial.

PURPOSE: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. METHODS: One hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 µg folic acid, 8 mg vitamin B6, 6.4 µg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. RESULTS: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (ß = -1.680, P = 0.004) and betaine (ß = -1.421, P = 0.020) after 12 weeks of supplementation. CONCLUSIONS: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 .

Association of circadian rhythm with mild cognitive impairment among male pneumoconiosis workers in Hong Kong: a cross-sectional study.

Weakened circadian activity rhythms (CARs) were associated with mild cognitive impairment (MCI) in the general population. However, it remains unclear among pneumoconiosis patients. We aimed to address this knowledge gap. This cross-sectional study comprised 186 male pneumoconiosis patients (71.3 ± 7.8 years) and 208 healthy community men. Actigraphy was used to determine CARs parameters (percent rhythm, amplitude, MESOR, and acrophase). Values below the corresponding medians of the CARs parameters represented weakened CARs. The Cantonese version of Mini-Mental State Examination (CMMSE) was used to assess cognitive function, MCI, and the composite outcome of MCI plus cognitive impairment. Compared with the community referents, pneumoconiosis patients had worse cognition and dampened CARs. Compared with the community referents or pneumoconiosis patients with robust circadian rhythm, pneumoconiosis patients with weakened circadian rhythm were consistently associated with increased risk of MCI and the composite outcome. However, significant association was only observed between MESOR and the composite outcome (adjusted OR = 1.99, 95%: 1.04-3.81). A delayed phase of CARs was insignificantly associated with MCI and the composite outcome. Our findings showed that weakened CARs were associated with worse cognitive function among male pneumoconiosis workers. Intervention in improving CARs may mitigate cognitive deterioration in male pneumoconiosis workers.

Chromosomal polymorphisms have no negative effect on reproductive outcomes after IVF/ICSI-ET/FET.

The present study aimed to explore whether chromosomal polymorphisms (CPs) have negative effects on reproductive outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET)/frozen-thawing embryo transfer (FET)? We conducted a retrospective study consisting of 21,867 assisted reproductive technology treatment cycles, among which, fresh embryo transfer cycles accounted for 10,400, and the rest were FET cycles. According to karyotype of CPs, the former was grouped as: group 1 (male carrier, n = 425), group 2 (female carrier, n = 262), and group 3 (couple without CPs, n = 9713). Accordingly, FET cycles were divided into 3 groups: group 4 (male carrier, n = 298), group 5 (female carrier, n = 311), and group 6 (couple without CPs, n = 10,858). The embryo implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), and early miscarriage rate (EMR) were compared among the groups. In fresh embryo transfer cycles after IVF/ICSI, there were no significant differences in the infertility duration, BMI, basal FSH, no. of oocyte, no. of 2PN, endometrial thickness on trigger day, serum E2, P, and LH level on trigger day (P > 0.05). The female age, no. of 2PN embryo cleavage, top-quality embryo, and no. of embryo transferred were significantly different among groups (P < 0.05). The IR was 38.8%, 36.2%, and 34.0% in groups 1, 2, and 3, respectively. The CPR was 55.1%, 52.3%, and 49.7%, respectively. The LBR was 36.9%, 37.4%, and 36.4%, respectively. The CPR and LBR showed no significant differences among groups. The IR was lower and the EMR was higher in group 3 than those of groups 1 and 2. Binary logistic regression analysis indicated that female age, no. of embryo transferred, EMT, LH, and P on the trigger day were independently factors associated with CPR. Besides, no. of embryo transferred, and EMT on trigger day were associated with LBR, while the CPs was not related with CPR and LBR after IVF/ICSI-ET. In FET cycles, the infertility duration was similar (P > 0.05), but the female age, BMI, no. of embryo transferred were significantly different among groups (P > 0.05). The IR was 24.3%, 23.6% and 22.3% in group 4, 5, and 6, receptivity. The CPR was 31.8%, 30.9%, and 30.0%, the LBR was 23.8%,26.3%, and 23.8%, while the EMR was 12.6%, 13.1%, 14.4%, respectively. The IR, CPR, EMR, and LBR showed no significant differences among groups (P > 0.05). Binary logistic regression analysis indicated that female age, infertility duration, and no. of embryo transferred were independently factors affecting CPR and LBR after FET. The CPs were not associated with CPR and LBR after FET. The results suggested that uniparental carrying of CPs have no effects on the reproductive outcomes after IVF/ICSI-ET/FET. However, it is not clear whether both parents carrying CPs would affect pregnancy outcome.

Serum trimethylamine-N-oxide is associated with incident type 2 diabetes in middle-aged and older adults: a prospective cohort study.

BACKGROUND: The role of trimethylamine-N-oxide (TMAO) in the development of diabetes remains controversial, and prospective data are few. We aimed to investigate the association between serum TMAO and incident type 2 diabetes in middle-aged and older adults. METHODS: This study was based on the Guangzhou Nutrition and Health Study (GNHS), a community-based prospective cohort study in China. A total of 2088 diabetes-free participants aged 40-75 years were included from 2008 to 2010. Incident type 2 diabetes was ascertained during follow-up visits. Baseline serum TMAO was measured by high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for diabetes across tertiles of serum TMAO were calculated using Cox proportional hazard models. Prospective associations of serum TMAO with changes in glycemic traits (fasting glucose, HbA1c, insulin, HOMA-IR) over time were estimated using linear mixed-effects models (LMEMs). RESULTS: We ascertained 254 incident type 2 diabetes cases during a median follow-up of 8.9 years. The median (interquartile range) of serum TMAO was 1.54 (0.86-2.91) µmol/L. From the first to the third tertile of serum TMAO, the multivariable-adjusted HRs for diabetes were 1.00 (reference), 1.17 (95% CI: 0.84-1.61), and 1.42 (95% CI: 1.03-1.96) (P-trend = 0.031). LMEMs showed that the estimated yearly change in fasting glucose was 0.011 (0.001-0.022) mmol/L/y in the highest tertile of serum TMAO, compared with the lowest tertile (P-interaction = 0.044). Serum TMAO was not associated with longitudinal changes in HbA1c, insulin or HOMA-IR. CONCLUSIONS: Our findings suggested that higher serum TMAO was associated with a higher risk of type 2 diabetes and an increase in fasting glucose among middle-aged and older Chinese adults. TRIAL REGISTRATION: NCT03179657. https://clinicaltrials.gov/ct2/show/NCT03179657?term=NCT03179657&draw=2&rank=1.

MiR-223-3p alleviates trigeminal neuropathic pain in the male mouse by targeting MKNK2 and MAPK/ERK signaling.

BACKGROUND: Trigeminal neuralgia (TN) is a neuropathic pain that occurs in branches of the trigeminal nerve. MicroRNAs (miRNAs) have been considered key mediators of neuropathic pain. This study was aimed to elucidate the pathophysiological function and mechanisms of miR-223-3p in mouse models of TN. METHODS: Infraorbital nerve chronic constriction injury (CCI-ION) was applied in male C57BL/6J mice to establish mouse models of TN. Pain responses were assessed utilizing Von Frey method. The expression of miR-223-3p, MKNK2, and MAPK/ERK pathway protein in trigeminal ganglions (TGs) of CCI-ION mice was measured using RT-qPCR and Western blotting. The concentrations of inflammatory cytokines were evaluated using Western blotting. The relationship between miR-223-3p and MKNK2 was tested by a luciferase reporter assay. RESULTS: We found that miR-223-3p was downregulated, while MKNK2 was upregulated in TGs of CCI-ION mice. MiR-223-3p overexpression by an intracerebroventricular injection of Lv-miR-223-3p attenuated trigeminal neuropathic pain in CCI-ION mice, as well as reduced the protein levels of pro-inflammatory cytokines in TGs of CCI-ION mice. MKNK2 was verified to be targeted by miR-223-3p. Additionally, miR-223-3p overexpression decreased the phosphorylation levels of ERK1/2, JNK, and p38 protein in TGs of CCI-ION mice to inhibit MAPK/ERK signaling. CONCLUSIONS: Overall, miR-223-3p attenuates the development of TN by targeting MKNK2 to suppress MAPK/ERK signaling.

Differences in Sleep Patterns and Mental Health Problems During Different Periods of COVID-19 Outbreak Among Community-Dwelling Older Men in Hong Kong.

Objectives: To determine the association of sleep with mental health among Hong Kong community-dwelling older men in the context of the COVID-19 pandemic. Methods: This additional analysis was derived from the community-dwelling men aged >60 recruited during three COVID-19 outbreaks (i.e., pre-outbreak, between the second and third wave, and during the third wave) in Hong Kong from July 2019 to September 2020. Sleep and mental health were measured by Pittsburgh Sleep Quality Index questionnaire and Hospital Anxiety and Depression Scale, respectively. Multivariate logistic regression models were performed for the associations between sleep and mental health after considering the outbreaks' impact. Results: Subjects enrolled between the second and third wave tended to have better sleep but worse mental health. Positive associations between poor sleep and depression (AOR = 3.27, 95% CI: 1.60-7.03) and anxiety (AOR = 2.40, 95% CI: 1.07-5.76) were observed. The period "between second and third wave" was positively associated with depression (AOR = 2.65, 95% CI: 1.22-5.83), showing an additive interaction with poor sleep. Conclusion: The positive association between poor sleep and depression was aggravated by the period "between the second and third wave" among community-dwelling older males in Hong Kong.

Effect of Nebulized Amphotericin B in Critically ill Patients With Respiratory Candida spp. De-colonization: A Retrospective Analysis.

The potential relationship among airway Candida spp. de-colonization, nebulized amphotericin B (NAB), and occurrence of ventilator-associated pneumonia (VAP) in patients who are critically ill has not been fully investigated, especially concerning effects on survival. In this observational, retrospective, cohort study in a 22-bed central intensive care unit, we included patients aged >18 years who required mechanical ventilation (MV) for >48 h, with at least two consecutive positive Candida spp. test results. Patients were categorized into NAB and no NAB (control) groups. Propensity matching at 1:1 was performed according to strict standards, and multiple Cox proportional hazard model and multivariate analyses were performed to evaluate the effects of NAB treatment. Throughout an 8-year study period, 526 patients had received MV and had positive respiratory tract Candida spp. cultures. Of these, we included 275 patients and excluded 251 patients. In total, we successfully matched 110 patients from the two groups (each group, n = 55; total population median age, 64 years; Acute Physiology and Chronic Health Evaluation II [APACHE II] score, 25.5; sequential organ failure assessment score, 9). The Candida spp. de-colonization rate was 69.1% in patients treated with NAB. VAP incidence did not differ significantly between the NAB (10.91%) and control (16.36%) groups (P = 0.405). Pseudomonas aeruginosa-related VAP rates differed significantly between the NAB (10.91%) and control (25.45%) groups (P = 0.048). Five (9.1%) patients in the NAB group died during hospitalization compared with 17 (30.9%) controls (P = 0.014). At 28 days, 9 (16.4%) and 16 (29.1%) deaths occurred in the NAB and control groups, respectively, (P = 0.088). The cumulative 90-day mortality rate differed significantly between the two groups (23.6 vs. 43.6%, P = 0.015). Multivariate logistic regression analyses indicated a decreased 90-day mortality in the NAB group (adjusted odds ratio 0.413; 95% confidence interval 0.210-0.812; P = 0.01). In subgroup analyses, the NAB-associated decreased risk of death at 90 days was consistent across subgroups of patients with a Candida score of 2, younger age (<64 years), a higher APACHE II score (≥25), fewer Candida sites (<2), or MV at admission. NAB treatment contributed to Candida spp. airway de-colonization, was associated with a reduced risk of P. aeruginosa-related VAP, and improved 90-day mortality in patients critically ill with Candida spp. tracheobronchial colonization who had received MV for >2 days. NAB may be an alternative treatment option for critically ill patients with VAP.

Untargeted metabolomics reveal the therapeutic effects of Ermiao wan categorized formulas on rats with hyperuricemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Ermiao wan (2 MW) is one of the most frequently prescription in traditional Chinese medicine (TCM) to treat hyperuricemia. Sanmiao wan (3 MW) and Simiao wan (4 MW), two modified Ermiao wan, also show good clinical effects in the treatment of gout and hyperuricemia. However, their uric acid lowering effects and potential action mechanism still need to be systematically investigated. AIM OF THE STUDY: The aim of present study was to analyze and compare the uric acid-lowering effects of 2 MW, 3 MW and 4 MW in rat with high fructose combined with potassium oxonate (HFCPO)-induced hyperuricemia and their possible mechanisms through plasma metabolomics methods. MATERIALS AND METHODS: HFCPO-induced hyperuricemia rat model was established to evaluate the therapeutic effects of Ermiao wan categorized formulas (ECFs, including 2 MW, 3 MW and 4 MW). Body weight, blood uric acid, creatinine, urine uric acid and urine creatinine levels and histopathological parameters of rats were assessed. Plasma untargeted metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was established to collect the metabolic profiles of rats and explore the metabolic changes that occurred after each ECFs treatment. RESULTS: Oral administration of ECFs could decrease the level of blood uric acid, creatinine and increase the level of urine uric acid and urine creatinine in varying degrees, and alleviated hepatocyte steatosis and atrophy and degeneration of glomerulus, vacuolar degeneration of renal tubular epithelial cells in HFCPO-induced hyperuricemia rats. Plasma untargeted metabolomics analysis showed that significant alterations were observed in metabolic signatures between the HFCPO-induced hyperuricemia group and control group. Thirty five potential biomarkers in rat plasma were identified in the screening by principal component analysis (PCA), partial least squares discrimination analysis (PLS-DA) and orthogonal partial least squares discrimination analysis (OPLS-DA). Differential metabolites related to hyperuricemia, including acylcarnitines and amino acid related metabolites, were further used to indicate relevant pathways in hyperuricemia rats, including tryptophan metabolism, arginine biosynthesis, purine metabolism, arginine and proline metabolism, beta-alanine metabolism, citrate cycle (TCA cycle), glycerophospholipid metabolism and linoleic acid metabolism. 2 MW, 3 MW and 4 MW could invert the pathological process of hyperuricemia to varying degrees through in part regulating the perturbed lipid metabolic pathway. 4 MW were better than 2 MW and 3 MW in the intervention of the disordered tricarboxylic acid metabolism and purine metabolism caused by hyperuricemia. CONCLUSION: In summary, ECFs treatment could effectively alleviate symptoms of hyperuricemia and regulate metabolic disorders in HFCPO-induced hyperuricemia rats.