Genetic Variants, Serum 25-Hydroxyvitamin D Levels, and Sarcopenia: A Mendelian Randomization Analysis.

Importance: Vitamin D deficiency is commonly associated with sarcopenia; however, the latest International Clinical Practice Guidelines for Sarcopenia do not recommend vitamin D supplementation for sarcopenia owing to a lack of an apparent therapeutic effect on the indices of sarcopenia among participants with replete vitamin D concentration (ie, 25-hydroxyvitamin D [25(OH)D] level >20 ng/mL) from randomized clinical trials. While there is consensus in all vitamin D guidelines that serum levels of 25(OH)D less than 10 ng/mL should be corrected, approximately 30% of the world population's 25(OH)D levels range from 10 to 20 ng/mL, and it remains unclear whether such suboptimal levels can maintain optimal health, including sarcopenia risk. Objective: To investigate the association of serum 25(OH)D level, especially suboptimal levels, with sarcopenia risk. Design, Setting, and Participants: This genome-wide genetic association study was performed from August 2022 to February 2023 among the 295 489 unrelated European participants from the UK Biobank (2006-2010). Nonlinear and standard mendelian randomization analyses were used to examine the association of serum 25(OH)D concentration with sarcopenia risk. Exposures: A weighted genetic risk score using 35 unrelated single-nucleotide variants from the UK Biobank and weights from the SUNLIGHT Consortium was selected as an instrumental variable for serum 25(OH)D concentration. Main Outcomes and Measures: The primary outcome was sarcopenia, and the secondary outcomes consisted of grip strength, appendicular lean mass index, and gait speed. Results: The final genetic analyses included 295 489 participants (mean [SD] age, 56.3 [8.1] years; 139 216 female [52.9%]). There was an L-shaped association between genetically predicted serum 25(OH)D concentration and sarcopenia risk. The risk of sarcopenia decreased rapidly as 25(OH)D concentration increased until 20 ng/mL and then leveled off. The odds ratio of sarcopenia for serum 25(OH)D level of 10 vs 20 ng/mL was 1.74 (95% CI, 1.17-2.59). Similar patterns were also observed when the association between serum 25(OH)D concentration and risks of each of the sarcopenia indices were evaluated. Conclusions and Relevance: In this mendelian randomization genetic association study of adults in the UK Biobank, the findings supported a nonlinear association between suboptimal 25(OH)D levels and sarcopenia risk. Randomized clinical trials among participants with suboptimal 25(OH)D levels are required to verify the potential causality.

Intra-Articular Magnesium Plus Bupivacaine Is the Most Effective and Safe Postoperative Analgesic Option Following Knee Arthroscopy: A Network Meta-analysis.

PURPOSE: To evaluate the comparative efficacy and safety of single-dose intra-articular injection of commonly used analgesics after knee arthroscopy. METHODS: A systematic literature review was done to search for randomized controlled trials (RCTs) published from database inception to October 1, 2020, that compared analgesics (i.e., morphine, bupivacaine, ropivacaine, and magnesium alone or in combination) with placebo or each other after knee arthroscopy. The primary outcomes were postoperative pain intensity at 2 hours and 24 hours. Secondary outcomes included the time to first analgesic request, number of patients requiring supplementary analgesics and side effects. We estimated summary standardized mean differences (SMDs) or odds ratios with 95% credible intervals (95% CrIs) using Bayesian network meta-analysis with random effects. RESULTS: In total, 78 randomized controlled trials comprising 4,425 participants were included. Compared with placebo, magnesium plus bupivacaine was most likely to be effective in relieving pain at both 2-hour (SMD = -3.81, 95% CrI -5.28 to -2.35) and 24-hour after surgery (SMD = -2.81, 95% CrI: -4.29 to -1.30). Following was morphine plus bupivacaine (2-hour: SMD = -2.19, 95% CrI -3.05 to -1.31; 24-hour: SMD = -1.44, 95% CrI -2.14 to -0.73) and bupivacaine alone (2-hour: SMD = -1.66, 95% CrI -2.33 to -0.98; 24-hour: SMD = -0.67, 95% CrI -1.22 to -0.07); ropivacaine alone and magnesium alone were not effective on pain relief. The interval time to first analgesic request was significantly extended compared with placebo except for ropivacaine alone and magnesium alone. The number of patients requiring supplementary analgesics was reduced in all groups except ropivacaine alone. No statistically significant difference was found between any studied analgesics or placebo with regard to side effects. CONCLUSIONS: Of 6 common postoperative intra-articular analgesics, magnesium plus bupivacaine provides the most effective pain relief without increasing short-term side effects after knee arthroscopy. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies.

Puerarin from Pueraria lobata alleviates the symptoms of irritable bowel syndrome-diarrhea.

As a functional bowel disorder, irritable bowel syndrome (IBS), especially IBS-diarrhea (IBS-D), affects approximately 9-20% of the population worldwide. Classical treatments for IBS usually result in some side effects and intestinal microbial disorders, which inhibit the clinical effects. Natural edible medicines with beneficial effects and few side effects have received more attention in recent years. Puerarin is the main active ingredient in pueraria and has been used in China to treat splenasthenic diarrhea and as a natural food in folk medicine for hundreds of years. However, there have been no reports of using puerarin in the treatment of IBS-D, and the underlying mechanism is also still unclear. In this study, a comprehensive model that could reflect the symptoms of IBS-D was established by combining neonatal maternal separation (NMS) and adult colonic acetic acid stimulation (ACAAS) in rats. The results showed that puerarin could reverse the abdominal pain and diarrhea in IBS-D rats. The therapeutic effect was realized by regulating the richness of the gut microbiota to maintain the stabilization of the intestinal micro-ecology. Furthermore, the possible mechanism might be related to the activity of the hypothalamic-pituitary-adrenal (HPA) axis by the suppressed expression of corticotropin-releasing hormone receptor (CRF) 1. At the same time, intestinal function was improved by enhancing the proliferation of colonic epithelial cells by upregulating the expression of p-ERK/ERK and by repairing the colonic mucus barrier by upregulating occludin expression. All these results suggest that puerarin could exert excellent therapeutic effects on IBS-D.

Selenium and bone health: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Bone health affects the ability of human body to stay active, and its degradation can cause considerable morbidity and mortality. The factors related to bone health play an important role in preventing osteoporosis and its adverse consequences. However, the risk factors for osteoporosis have not been fully elucidated. Deficiency in the trace element selenium may be one of the risk factors for the development of osteoporosis. Previous studies have investigated the effects of selenium on osteoporosis; however, the results are inconclusive. Therefore, the present study aimed to systematically examine the existing literature on the associations between dietary or serum selenium and bone mineral density (BMD), osteoporosis or osteoporotic fractures, and to quantify such associations through meta-analysis. METHODS AND ANALYSIS: PubMed, Embase and Cochrane Library will be searched using a specified search strategy to identify relevant studies up to October 2019. Both interventional and observational studies in humans will be included. The outcomes will include BMD and the prevalence or incidence of osteoporosis and osteoporotic fractures. For dietary or serum selenium and BMD, osteoporosis or osteoporotic fractures pooled analyses, estimates will be expressed as the mean difference, and the pooled OR, relative risk, HR or beta coefficient, and corresponding 95% CIs. Heterogeneity of the studies and publication bias will be investigated accordingly. To assess the quality and the risk of bias of the included studies, the Newcastle-Ottawa Quality Scale or the Cochrane risk of bias assessment tool will be used where appropriate. ETHICS AND DISSEMINATION: Since no private and confidential patient data will be included in the reporting, approval from an ethics committee is not required. The results will be published in a peer-reviewed journal. The study raises no ethical issues. PROSPERO REGISTRATION NUMBER: CRD42019147188.

Comparative efficacy and safety of intra-articular analgesics after knee arthroscopy: a Bayesian network meta-analysis protocol.

INTRODUCTION: Most of the patients who received arthroscopic knee surgery will suffer moderate to severe pain, which can delay the rehabilitation process and increase the risk of postoperative complications. Therefore, seeking a safe and effective postoperative analgesia is necessary for promoting the application of arthroscopic surgery. This protocol aims to detail a planned systematic review and meta-analysis on the comparative efficacy and safety of single-dose intra-articular injection of analgesics for pain relief after knee arthroscopy. METHOD AND ANALYSIS: PubMed, Embase, Web of Science and Cochrane Library will be searched from inception to 1 June 2020 to retrieve randomised controlled trials (RCTs) that compared the commonly used single-dose intra-articular analgesics (ie, morphine; bupivacaine (including levobupivacaine); ropivacaine and magnesium alone or in combination) with placebo or between each other for postoperative pain relief among patients who had received knee arthroscopy. The primary outcome is pain intensity at 2-hour and 24-hour postoperatively; the secondary outcomes include side effects (eg, knee effusion, nausea, vomiting and flushing), the number of patients requiring supplementary analgesia and the time to first analgesic request. The methodological quality of the included RCTs will be assessed based on the Cochrane risk of bias table. The Bayesian network meta-analysis will be conducted using WinBUGS V.1.4.3. ETHICS AND DISSEMINATION: Since no private or confidential patient data will be contained in the reporting, approval from an ethics committee is not required. Our study raises no ethical issue, and the results will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019130876.

CPF impedes cell cycle re-entry of quiescent lung cancer cells through transcriptional suppression of FACT and c-MYC.

Blockade of cell cycle re-entry in quiescent cancer cells is a strategy to prevent cancer progression and recurrence. We investigated the action and mode of action of CPF mixture (Coptis chinensis, Pinellia ternata and Fructus trichosanthis) in impeding a proliferative switch in quiescent lung cancer cells. The results indicated that CPF impeded cell cycle re-entry in quiescent lung cancer cells by reduction of FACT and c-MYC mRNA and protein levels, with concomitant decrease in H3K4 tri-methylation and RNA polymerase II occupancy at FACT and c-MYC promoter regions. Animals implanted with quiescent cancer cells that had been exposed to CPF had reduced tumour volume/weight. Thus, CPF suppresses proliferative switching through transcriptional suppression of FACT and the c-MYC, providing a new insight into therapeutic target and intervention method in impeding cancer recurrence.

Association Between Dietary Selenium Intake and the Prevalence of Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study.

Objective: The aim was to examine the association between dietary selenium intake and nonalcoholic fatty liver disease (NAFLD) in a large group of middle-aged and elderly Chinese persons.Method: The data included in this analysis were from a population-based study, the Xiangya Hospital Health Management Center Study. NAFLD was diagnosed by (1) imaging or histological evidence of hepatic steatosis; (2) absence of specific etiologies of NAFLD; and (3) no heavy consumption of alcohol. Dietary selenium intake was assessed using a validated semi-quantitative food frequency questionnaire. The association between dietary selenium intake and the prevalence of NAFLD was evaluated using logistic and spline regression in a cross-sectional study of 5436 subjects.Results: The prevalence of NAFLD was 36.8%. Compared with the lowest quintile, the energy-adjusted odds ratios for NAFLD were 1.27 (95% confidence interval [CI], 1.07-1.52), 1.30 (95% CI, 1.09-1.55), and 1.58 (95% CI, 1.33-1.89) for the third, fourth, and fifth quintiles of selenium intake, respectively, and there was a positive dose-response relationship (r = 0.88, p for trend = 0.008). Similar results were observed for men and women separately. The findings were not materially altered by adjustment for potential confounders (i.e., age, gender, body mass index, smoking status, diabetes, hypertension, activity level, nutritional supplements, energy intake, fat intake, fiber intake, cholesterol and saturated fatty acid intake).Conclusions: In this middle-aged and elderly population, subjects with higher dietary selenium intake, even below the recommended nutrient intake in China, had higher prevalence of NAFLD in a dose-response relationship manner.

Association between dietary selenium intake and the prevalence of osteoporosis: a cross-sectional study.

OBJECTIVE: To examine the correlation between dietary selenium (Se) intake and the prevalence of osteoporosis (OP) in the general middle-aged and older population in China. METHODS: Data for analyses were collected from a population based cross-sectional study performed at the Xiangya Hospital Health Management Centre. Dietary Se intake was evaluated using a validated semi-quantitative food frequency questionnaire. OP was diagnosed on the basis of bone mineral density scans using a compact radiographic absorptiometry system. The correlation between dietary Se intake and the prevalence of OP was primarily examined by multivariable logistic regression. RESULTS: This cross-sectional study included a total of 6267 subjects (mean age: 52.2 ± 7.4 years; 42% women), and the prevalence of OP among the included subjects was 9.6% (2.3% in men and 19.7% in women). Compared with the lowest quartile, the energy intake, age, gender and body mass index (BMI)-adjusted odds ratios of OP were 0.72 (95% confidence interval [CI] 0.55-0.94), 0.72 (95% CI 0.51-1.01) and 0.47 (95% CI 0.31-0.73) for the second, third and fourth quartiles of dietary Se intake, respectively (P for trend = 0.001). The results remained consistent in male and female subjects. Adjustment for additional potential confounders (i.e., smoking status, drinking status, physical activity level, nutritional supplements, diabetes, hypertension, fibre intake, and calcium intake) did not cause substantial changes to the results. CONCLUSIONS: In the middle-aged and older humans, participants with lower levels of dietary Se intake have a higher prevalence of OP in a dose-response manner.

Efficacy and safety of the pulsed electromagnetic field in osteoarthritis: a meta-analysis.

OBJECTIVE: To investigate the efficacy and safety of the pulsed electromagnetic field (PEMF) therapy in treating osteoarthritis (OA). DESIGN: Meta-analysis. DATA SOURCES: PubMed, Embase, the Cochrane Library and Web of Science were searched through 13 October 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials compared the efficacy of PEMF therapy with sham control in patients with OA. DATA EXTRACTION AND SYNTHESIS: Pain, function, adverse effects and characteristics of participants were extracted. RevMan V.5.2 was used to perform statistical analyses. RESULTS: Twelve trials were included, among which ten trials involved knee OA, two involved cervical OA and one involved hand OA. The PEMF group showed more significant pain alleviation than the sham group in knee OA (standardised mean differences (SMD)=-0.54, 95% CI -1.04 to -0.04, p=0.03) and hand OA (SMD=-2.85, 95% CI -3.65 to -2.04, p<0.00001), but not in cervical OA. Similarly, comparing with the sham-control treatment, significant function improvement was observed in the PEMF group in both knee and hand OA patients (SMD=-0.34, 95% CI -0.53 to -0.14, p=0.0006, and SMD=-1.49, 95% CI -2.12 to -0.86, p<0.00001, respectively), but not in patients with cervical OA. Sensitivity analyses suggested that the exposure duration <=30 min per session exhibited better effects compared with the exposure duration >30 min per session. Three trials reported adverse events, and the combined results showed that there was no significant difference between PEMF and the sham group. CONCLUSIONS: PEMF could alleviate pain and improve physical function for patients with knee and hand OA, but not for patients with cervical OA. Meanwhile, a short PEMF treatment duration (within 30 min) may achieve more favourable efficacy. However, given the limited number of study available in hand and cervical OA, the implication of this conclusion should be cautious for hand and cervical OA.

Association between Dietary Magnesium Intake and Hyperuricemia.

OBJECTIVE: To examine the cross-sectional associations between dietary magnesium (Mg) intake and hyperuricemia (HU). METHODS: 5168 subjects were included in this study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Hyperuricemia (HU) was defined as uric acid ≥ 416 µmol/L for male population and ≥ 360 µmol/L for female. A multivariable logistic analysis model was applied to test the associations after adjusting a number of potential confounding factors. RESULTS: The relative odds of the overall prevalence of HU were decreased by 0.57 times in the fourth quintile of Mg intake (OR 0.57, 95% CI 0.35-0.94) and 0.55 times in the fifth quintile (OR 0.55, 95% CI 0.30-1.01) comparing with the lowest quintile, and P for trend was 0.091. The results of multivariable linear regression also suggested a significant inverse association between serum uric acid and Mg intake (ß = -0.028, P = 0.022). For male, the relative odds of HU were decreased by 0.62 times in the third quintile of Mg intake (OR 0.62, 95% CI 0.40-0.97), 0.40 times in the fourth quintile (OR 0.40, 95% CI 0.23-0.72) and 0.35 times in the fifth quintile (OR 0.35, 95% CI 0.17-0.71) comparing with the lowest quintile, and P for trend was 0.006. Multivariable adjusted inverse association was also existed between serum uric acid and Mg intake in male population (ß = -0.061, P = 0.002). However, no significant association was observed between dietary Mg intake and HU for female. CONCLUSIONS: The findings of this cross-sectional study indicated that dietary Mg intake is inversely associated with HU, independent of some major confounding factors. In addition, this association remains valid for the male subgroup, but not for the female subgroup. LEVEL OF EVIDENCE: LevelIII, cross-sectional study.

Association between low dietary zinc and hyperuricaemia in middle-aged and older males in China: a cross-sectional study.

OBJECTIVE: To examine the associations between dietary zinc intake and hyperuricaemia. DESIGN: Cross-sectional study. SETTING: This study was conducted in a health examination centre of China. PARTICIPANTS: A total of 5168 middle-aged and older participants (aged 40 years or above) (2697 men and 2471 women) were included. OUTCOME MEASURES: Dietary zinc intake was assessed using a validated semiquantitative food frequency questionnaire. Hyperuricaemia was defined as uric acid ≥416 µmol/L for males and ≥360 µmol/L for females. RESULTS: For males, the prevalence of hyperuricaemia was 22.9%. After adjusting for age, body mass index (BMI) and energy intake, the ORs were 0.68 (95% CI 0.45 to 0.92) in the second quintile, 0.63 (95% CI 0.45 to 0.89) in the third quintile, 0.68 (95% CI 0.46 to 1.00) in the fourth quintile and 0.55 (95% CI 0.35 to 0.87) in the fifth quintile comparing the lowest quintile of Zn intake, respectively (p for trend=0.03). In the multivariable adjusted model, the relative odds of hyperuricaemia were significantly decreased by 0.71 times in the second quintile of zinc intake (OR 0.71, 95% CI 0.52 to 0.98), 0.64 times in the third quintile (OR 0.65, 95% CI 0.44 to 0.94) and 0.55 times in the fifth quintile (OR 0.56, 95% CI 0.32 to 0.97) compared with those in the lowest quintile, and p for trend was 0.064. For females, the prevalence of hyperuricaemia was 10.0%, and unadjusted, minimally adjusted as well as multivariable adjusted ORs all suggested no significant association between dietary zinc intake and hyperuricaemia. CONCLUSIONS: The findings of this cross-sectional study indicated that dietary zinc intake was inversely associated with hyperuricaemia in middle-aged and older males, but not in females. The association was significant after considering the influence of age, BMI and energy intake, and after that, minimum adjustment remained independent of further confounding factors such as vitamin C intake, alcohol drinking status and nutrient supplementation.

Molecular cloning and identification of a putative PKC epsilon cDNA from Limulus polyphemus brain.

The protein kinase C (PKC) family of enzymes is broadly distributed and has been implicated in a diverse array of cellular functions. Recent evidence supporting PKC involvement in the regulation of the Limulus choline cotransporter prompted us to clone PKC from a Limulus central nervous system (CNS) cDNA library. An Aplysia californica calcium independent PKC (Apl II) cDNA probe was used to screen the library and 5' RACE SMART PCR was used to obtain the full-length sequence. The resulting cDNA, which included 5' and 3' nontranslation regions, was 4675 bp. Analysis of the encoded peptide sequence using the Swiss-prot database revealed at least 58% identity to PKC epsilon. A commercial polyclonal antibody against PKC epsilon was used in Western blots to positively label a 30 kDa protein from Limulus CNS and the expressed fusion protein of the encoded sequence. These data support the presence of a newly identified PKC-like homolog in Limulus which likely represents a PKC epsilon equivalent.