Assessment of causal effects of physical activity on the risk of osteoarthritis: a two-sample Mendelian randomization study.

BACKGROUND: Growing evidence supports an association between physical activity (PA) and the risk of osteoarthritis (OA), but this may be influenced by confounding and reverse causality. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to reveal the causal relationship between PA and OA. METHODS: MR was performed to explore the causation of PA and OA with genetic variants as instrumental variables. The genetic variants were derived from the summary statistics of a large genome-wide association study meta-analysis based on the European population (n = 661,399), including self-reported leisure screen time (LST) and moderate-to-vigorous physical activity (MVPA), and Arthritis Research UK Osteoarthritis Genetics Consortium cohorts (417,596, 393,873 and 403,124 for overall, hip and knee OA, respectively). The major MR analysis used in this work was the inverse variance weighted (IVW) approach, and sensitivity, pleiotropy, and heterogeneity studies were performed to evaluate the validity of the findings. RESULTS: IVW estimates indicated that LST had a risk effect on overall OA (odds ratio (OR) = 1.309, 95% confidence interval (CI): 1.198-1.430, P = 2.330 × 10-9), hip OA (OR = 1.132, 95% CI: 1.009-1.269, P = 0.034) and knee OA (OR = 1.435. 95% CI: 1.286-1.602, P = 1.225 × 10-10). In contrast, no causal relationship was found between MVPA and OA (overall OA: OR = 0.895, 95% CI: 0.664-1.205, P = 0.465; hip OA: OR = 1.189, 95% CI: 0.792-1.786, P = 0.404; knee OA: OR = 0.707, 95% CI: 0.490 -1.021, P = 0.064). In addition, we observed significant heterogeneity in instrumental variables, but no horizontal pleiotropy was detected. CONCLUSIONS: Recent findings demonstrated a protective impact of reducing LST on OA, independent of MVPA. This provides valuable insights into the role of physical activity in OA and offers lifestyle recommendations, such as reducing recreational sedentary behaviors and promoting appropriate exercise, for individuals at risk of OA.

Assessment of New Strategies to Improve the Performance of Antimicrobial Peptides.

In this research, we constructed a novel engineered tripeptide modified with lipoic acid (LA-RWR), followed by crosslinking of lipoic acid to form nanoparticles (c-LA-RWR). LA-RWR was also modified with phenethylamine (PEA) on the C-terminus to achieve better antibacterial activities. The as-prepared c-LA-RWR and LA-RWR-PEA were effective against E.coli, S.aureus, C.albicans, and methicillin-resistant Staphylococcus aureus, with minimum inhibitory concentration values ranging from 2 to 16 µg/mL, which greatly improved the performance of LA-RWR. Similar antibacterial activities were demonstrated in anti-biofilm activity; there was no matter on the biofilm that was already established or forming. Moreover, c-LA-RWR/LA-RWR-PEA remarkably induced cytoplasmic membrane depolarization and outer membrane permeabilization, resulting in varying degrees of damage to the bacterial morphology, which were consistent with the results obtained via electron microscopy. Thus, our results show that c-LA-RWR/LA-RWR-PEA exhibited excellent efficacy against a variety of microorganisms with good biosafety, providing new strategies by which to improve the performance of antimicrobial peptides.

Research on cost accounting of enterprise carbon emission (in China).

Enterprises in China face two major challenges about their existence and energy supply at present. One is the difficulty in providing enough energy at an acceptable and reasonable price; the other is a severe environmental issue caused by over-consumption of energy. The government and relevant enterprises, therefore, mainly focus on carbon emission reduction, and the cost accounting of carbon emission, an essential prerequisite, and object of carbon emission reduction, should be further attention. The carbon emission cost is divided into internal cost and external cost, combined with the extended accounting model and cost calculation. This can comprehensively measure and reflect the two costs of the life cycle of the product, provide more relevant data and information support for the deepening and development of the circular economy, and provide an effective cost information basis and guide enterprise managers for scientific decision-making and governance.

Does renewable energy electricity and economic complexity index help to achieve carbon neutrality target of top exporting countries?

Despite extensive studies into international trade and CO2 pollution, a panel of only top exporting economies was not considered. As the current research is an endeavor to address the gap by exploring the impact of economic complexity index (ECI) and renewable energy electricity (RELC) on consumption-based carbon emissions (CCO2) in the presences of exports, imports, and gross domestic product (GDP) in the top exporting countries from 1990 to 2019. The results confirm a relationship between consumption-based carbon emissions, economic complexity index, renewable energy electricity, exports, imports, and economic growth in both the short-run and long run. Empirical evidence for cross-sectional auto-regressive distributed lags (CS-ARDL) estimates, confirms that economic complexity index imports and GDP are positively associated and have significant adverse short-run and long-run impacts on consumption-based carbon emission. Whereas, export and renewable energy electricity significantly reduce carbon emissions. To achieve carbon neutrality target, policymakers should make economic complexity reforms, import green products, and promote investments in sustainable sources.

Improved trends of lung cancer mortality-to-incidence ratios in countries with high healthcare expenditure.

BACKGROUND: Lung cancer stage has a significant impact on prognosis, and early detection of lung cancer relies on screenings. Despite the strong relationship between screening and lung cancer staging, the role of healthcare expenditure in lung cancer outcomes remains unknown. The aim of this study was to evaluate the relationship between economic status and clinical outcomes in lung cancer. METHODS: Data were obtained from GLOBOCAN and the World Health Organization. Mortality-to-incidence ratios (MIRs) and their change over time, calculated as the difference between the MIRs of 2012 and 2018 (δMIR), were used to evaluate their correlation to expenditures on healthcare and human development index (HDI) disparities via Spearman's rank correlation coefficient. RESULTS: Regions such as North America have relatively high crude incidence rates but low MIR values. Furthermore, countries with lower crude incidence rates spent less on healthcare. The results show significant negative associations between HDI, current health expenditure (CHE) per capita, CHE as a percentage of gross domestic product (CHE/GDP), and MIR. As for MIR and δMIR, countries with favorable MIRs also showed improving MIRs based on δMIR. CONCLUSIONS: HDI, CHE per capita, CHE/GDP, and development status play noticeable roles in the prognosis of lung cancer, leading to large disparities in clinical outcomes.

Power Analysis and Sample Size Determination for Crossover Trials with Application to Bioequivalence Assessment of Topical Ophthalmic Drugs Using Serial Sampling Pharmacokinetic Data.

OBJECTIVE: To develop methods for determining a suitable sample size for bioequivalence assessment of generic topical ophthalmic drugs using crossover design with serial sampling schemes. METHODS: The power functions of the Fieller-type confidence interval and the asymptotic confidence interval in crossover designs with serial-sampling data are here derived. Simulation studies were conducted to evaluate the derived power functions. RESULTS: Simulation studies show that two power functions can provide precise power estimates when normality assumptions are satisfied and yield conservative estimates of power in cases when data are log-normally distributed. The intra-correlation showed a positive correlation with the power of the bioequivalence test. When the expected ratio of the AUCs was less than or equal to 1, the power of the Fieller-type confidence interval was larger than the asymptotic confidence interval. If the expected ratio of the AUCs was larger than 1, the asymptotic confidence interval had greater power. Sample size can be calculated through numerical iteration with the derived power functions. CONCLUSION: The Fieller-type power function and the asymptotic power function can be used to determine sample sizes of crossover trials for bioequivalence assessment of topical ophthalmic drugs.

Unfavorable Mortality-To-Incidence Ratio of Lung Cancer Is Associated with Health Care Disparity.

The mortality-to-incidence ratio (MIR) is associated with the clinical outcome of cancer treatment. For several cancers, countries with relatively good health care systems have favorable MIRs. However, the association between lung cancer MIR and health care expenditures or rankings has not been evaluated. We used linear regression to analyze the correlation between lung cancer MIRs and the total expenditures on health/gross domestic product (e/GDP) and the World Health Organization (WHO) rankings. We included 57 countries, for which data of adequate quality were available, and we found high rates of incidence and mortality but low MIRs in more developed regions. Among the continents, North America had the highest rates of incidence and mortality, whereas the highest MIRs were in Africa, Asia, Latin America, and the Caribbean. Globally, favorable MIRs correlated with high e/GDP and good WHO ranking (regression coefficient, -0.014 and 0.001; p = 0.004, and p = 0.014, respectively). In conclusion, the MIR for lung cancer in different countries varies with the expenditure on health care and health system rankings.

Association of Methylation Signals With Incident Coronary Heart Disease in an Epigenome-Wide Assessment of Circulating Tumor Necrosis Factor α.

Importance: Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine with manifold consequences for mammalian pathophysiology, including cardiovascular disease. A deeper understanding of TNF-α biology may enhance treatment precision. Objective: To conduct an epigenome-wide analysis of blood-derived DNA methylation and TNF-α levels and to assess the clinical relevance of findings. Design, Setting, and Participants: This meta-analysis assessed epigenome-wide associations in circulating TNF-α concentrations from 5 cohort studies and 1 interventional trial, with replication in 3 additional cohort studies. Follow-up analyses investigated associations of identified methylation loci with gene expression and incident coronary heart disease; this meta-analysis included 11 461 participants who experienced 1895 coronary events. Exposures: Circulating TNF-α concentration. Main Outcomes and Measures: DNA methylation at approximately 450 000 loci, neighboring DNA sequence variation, gene expression, and incident coronary heart disease. Results: The discovery cohort included 4794 participants, and the replication study included 816 participants (overall mean [SD] age, 60.7 [8.5] years). In the discovery stage, circulating TNF-α levels were associated with methylation of 7 cytosine-phosphate-guanine (CpG) sites, 3 of which were located in or near DTX3L-PARP9 at cg00959259 (ß [SE] = -0.01 [0.003]; P = 7.36 × 10-8), cg08122652 (ß [SE] = -0.008 [0.002]; P = 2.24 × 10-7), and cg22930808(ß [SE] = -0.01 [0.002]; P = 6.92 × 10-8); NLRC5 at cg16411857 (ß [SE] = -0.01 [0.002]; P = 2.14 × 10-13) and cg07839457 (ß [SE] = -0.02 [0.003]; P = 6.31 × 10-10); or ABO, at cg13683939 (ß [SE] = 0.04 [0.008]; P = 1.42 × 10-7) and cg24267699 (ß [SE] = -0.009 [0.002]; P = 1.67 × 10-7), after accounting for multiple testing. Of these, negative associations between TNF-α concentration and methylation of 2 loci in NLRC5 and 1 in DTX3L-14 PARP9 were replicated. Replicated TNF-α-linked CpG sites were associated with 9% to 19% decreased risk of incident coronary heart disease per 10% higher methylation per CpG site (cg16411857: hazard ratio [HR], 0.86; 95% CI, 0.78-1.95; P = .003; cg07839457: HR, 0.89; 95% CI, 0.80-0.94; P = 3.1 × 10-5; cg00959259: HR, 0.91; 95% CI, 0.84-0.97; P = .002; cg08122652: HR, 0.81; 95% CI, 0.74-0.89; P = 2.0 × 10-5). Conclusions and Relevance: We identified and replicated novel epigenetic correlates of circulating TNF-α concentration in blood samples and linked these loci to coronary heart disease risk, opening opportunities for validation and therapeutic applications.

Prospective Randomized Study of Ultrasound-Guided Foam Sclerotherapy Combined with Great Saphenous Vein High Ligation in the Treatment of Severe Lower Extremity Varicosis.

BACKGROUND: To evaluate the effect of ultrasound-guided foam sclerotherapy (UGFS) in a single session combined with great saphenous vein (GSV) high ligation for severe lower extremity varicosis classified as C4-C6, compared with GSV stripping plus multistab avulsion or transilluminated powered phlebectomy (TIPP). METHODS: From January 2012 to December 2014, 177 patients with primary GSV insufficiency, classified as C4-C6, were randomized into the UGFS group or the control group. The UGFS group was managed by GSV high ligation and foam sclerotherapy in one session under the surveillance of ultrasonography, whereas the control group received GSV high ligation and stripping combined with multistab avulsion or TIPP. The patients were followed up at 1, 6, and 12 months after treatment. Outcome assessments included reflux recurrence rate, procedure-related adverse events, hemodynamic parameters, revised Venous Clinical Severity Score (VCSS), and Aberdeen Varicose Vein Questionnaire (AVVQ) score. The medical cost and operating time of the 2 groups were also compared. RESULTS: In total, 73 patients received UGFS, whereas 90 patients underwent traditional surgery. Sixty-five patients in the UGFS group (89.0%) and 74 patients in the control group (82.2%) completed the follow-up. At the end of 12 months, the cumulative reflux recurrence rate was 13.8% in the UGFS group and 13.5% in the control group (P = 0.955). In the UGFS and control groups, minor complications (27.7% vs. 21.6%, P = 0.406) and major complications (3.1% vs. 2.7%, P = 0.895) were not significantly different. Compared with baseline values, obvious improvements of the venous filling index, VCSS, and AVVQ scores after treatment were confirmed in both groups (P < 0.001). The average operating and recovery times were much shorter (38.3 vs. 81.2 min, 5.4 vs. 9.6 days, P < 0.001, respectively), and the average hospital cost was much lower ($853 vs. $1,575, P < 0.001) in the UGFS group than in the control group. The patient satisfaction rate reached 92.3% in the UGFS group and 89.2% in the control group 12 months after operation (P = 0.270). CONCLUSIONS: Our outcomes indicated that UGFS combined with GSV high ligation was safe and effective for severe lower extremity varicosis.

Effects of physical exercise on health-related quality of life and blood lipids in perimenopausal women: a randomized placebo-controlled trial.

OBJECTIVE: This study aims to evaluate the treatment effects of physical exercise on menopausal symptoms in middle-aged female medical staff experiencing perimenopausal syndrome. METHODS: A total of 157 female medical staff aged 40 to 55 years and with a Kupperman index score of 15 points or higher were randomized 1:1 into an intervention group (n = 78) or a control group (n = 79). Women in the intervention group were asked to perform aerobic physical exercise (walking with strides) three times a week or more, whereas those in the control group continued as normal. Measurements were taken at baseline and on weeks 4, 8, and 12, with total Kupperman index score, scores on individual elements of the scale, weight, and waist circumference recorded. In addition, fasting blood glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were recorded at baseline and on week 12. The effects of physical exercise therapy on perimenopausal syndrome were evaluated by comparing changes in these parameters between the control group and the intervention group. RESULTS: Fifty-four and 57 women completed all three follow-ups in the intervention and control groups, respectively. On week 12, the mean (SD) change in total Kupperman index score (-9.23 [6.23]) from baseline to week 12; the mean (SD) changes in individual scores for paresthesia (-1.08 [1.51]), insomnia (-1.00 [1.46]), irritability (-1.00 [1.34]), joint or muscle pain (-0.75 [0.74]), fatigue (-0.56 [0.75]), headache (-0.54 [0.75]), formication (-0.38 [0.66]), and sexual life (-0.62 [1.71]); and the mean (SD) changes in total cholesterol (-0.76 [0.63] mmol/L) and triglycerides (-0.20 [0.50] mmol/L) were significantly higher in the intervention group than in the control group (P < 0.05). In the intervention group, total Kupperman index score, weight, body mass index, waist circumference, triglycerides, and total cholesterol were significantly lower on week 12 compared with baseline (P < 0.05). CONCLUSIONS: Physical exercise can substantially reduce menopausal symptoms and improve blood lipid status and body weight.

Population impact of a high cardiovascular risk management program delivered by village doctors in rural China: design and rationale of a large, cluster-randomized controlled trial.

BACKGROUND: The high-risk strategy has been proven effective in preventing cardiovascular disease; however, the population benefits from these interventions remain unknown. This study aims to assess, at the population level, the effects of an evidence-based high cardiovascular risk management program delivered by village doctors in rural China. METHODS: The study will employ a cluster-randomized controlled trial in which a total of 120 villages in five northern provinces of China, will be assigned to either intervention (60 villages) or control (60 villages). Village doctors in intervention villages will be trained to implement a simple evidence-based management program designed to identify, treat and follow-up as many as possible individuals at high-risk of cardiovascular disease in the village. The intervention will also include performance feedback as well as a performance-based incentive payment scheme and will last for 2 years. We will draw two different (independent) random samples, before and after the intervention, 20 men aged≥50 years and 20 women aged≥60 years from each village in each sample and a total of 9,600 participants from 2 samples to measure the study outcomes at the population level. The primary outcome will be the pre-post difference in mean systolic blood pressure, analyzed with a generalized estimating equations extension of linear regression model to account for cluster effect. Secondary outcomes will include monthly clinic visits, provision of lifestyle advice, use of antihypertensive medications and use of aspirin. Process and economic evaluations will also be conducted. DISCUSSION: This trial will be the first implementation trial in the world to evaluate the population impact of the high-risk strategy in prevention and control of cardiovascular disease. The results are expected to provide important information (effectiveness, cost-effectiveness, feasibility and acceptability) to guide policy making for rural China as well as other resource-limited countries. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT01259700). Date of initial registration is December 13, 2010.

Comparison between hospital-based and community-based services for the special health care needs of children with developmental delays.

BACKGROUND: Recognizing special health care needs (SHCN) is obligatory for children with developmental delay (DD). The purpose of this study was to compare hospital-based and community-based services for the SHCN of children with DD. METHODS: We collected 114 children with DD. An expert-designed questionnaire was used to measure the SHCN of children in either hospital-based or community-based services. The questionnaire included the children's characteristics, family ecology and SHCN, which encompassed four categories, team assessment and counseling, rehabilitation, complementary and alternative treatment, and home care. We compared the differences and needs between the two health care services. RESULTS: More children with DD in hospital-based services had disabled certificates, catastrophic illness certificates and multiple caregivers than community based services. More children with DD in community-based services had severe-disabled certificates than those in hospital-based services (p < 0.001). Children in hospital-based services had more SHCN for some items of team assessment and counseling, rehabilitation, and complementary and alternative treatment than those in community-based services (p < 0.05). The need for home care was not significantly different between the two services except for nutrition counseling (p = 0.048). CONCLUSION: SHCN in multiple aspects imply the necessity for team assessment and counseling, rehabilitation, complementary and alternative treatments and nutrition counseling in approaching children with DD in hospital-based services.

[Impact of hypocaloric and hypo-nitrogen parenteral nutrition on clinical outcome in postoperative patients: a multi-center randomized controlled trial of 120 cases].

OBJECTIVE: To evaluate the impact of hypocaloric and hypo-nitrogen parenteral nutrition (PN) on infective complication rate, postoperative hospital stay and treatment cost in postoperative period. METHODS: 120 patients with gastrointestinal tumors with the Nutrition Risk Screening (NRS) score of 3 or 4 undergoing radical gastrectomy in 5 hospitals were randomly assigned into 2 equal groups: control group, receiving PN with 30 (28 - 32) kcal x kg(-1) x d(-1) and nitrogen 0.20 (0.19 - 0.21) g x kg(-1) x d(-1) in regular "3 liter bag", and study group receiving calorie of 18 (range 16 - 20) kcal x kg(-1) x d(-1) and nitrogen of 0.10 (0.09 - 0.11) g x kg(-1) x d(-1) with triple chamber bag. PN support was infused continuously for at least six postoperative days through peripheral vein or peripherally inserted central catheter. The differences between these two groups in blood glucose level, infectious complication, phlebitis, systemic inflammatory response syndrome (SIRS), and duration of hospital stay after operation, and treatment cost. All data were evaluated by both intention to treat (ITT) analysis and per protocol (PP) analysis. RESULTS: There were no significant differences in the clinical baseline and operative types between the two groups. ITT analysis showed that the occurrence of hyperglycemia in postoperative period in the control group was 43.3%, significantly much higher than that in the study group (6.6%, P = 0.000). The infectious complication rate of the study group was 3.3%, significantly lower than that of the control group (16.6%, P = 0.0149), the phlebitis rate of the study group was 0.0%, significantly lower than that of the control group (18.3%, P = 0.0005). The SIRS rate of the study group was 25.0%, significantly lower than that of the control group (45.0%, P = 0.0216). PP analysis showed that the postoperative duration of hospital stay of the control group was 14.1 days +/- 5.8 days, significantly longer than that of the study group (12.4 days +/- 4.0 days, P = 0.047), the total PN cost of the study group was 3411.6 +/- 181.1 Yuan RMB, significantly higher than that of the control group (2945 +/- 162 Yuan RMB, P = 0.000); but the total post-operative cost of treatment of the control group was 13156 +/- 3282 Yuan RMB, significantly higher than that of the study group (11 642 +/- 3019 Yuan RMB, P = 0.010); and the time for compounding of the study group was 5.0 min +/- 1.7 min, significantly shorter than that of the control group (15.4 min +/- 3.7 min, P = 0.000). CONCLUSION: Hypocaloric and hypo-nitrogen PN in postoperative days 1 - 6 in patients with scores 3 or 4 decreases the rates of hyperglycemia, infectious complications, phlebitis, and SIRS, shortens the postoperative hospital stay, and lowers the cost of treatment comparing with conventional PN. The use of triple chamber bag shortens the compounding time of PN.

[Safety assessment in radomized controlled clinical trials].

OBJECTIVE: To introduce some methods of safety assessment in randomized controlled clinical trials. METHODS: Recent advances and current parctice in normalized safety assessment were reviewed and relevant data analyzed. RESTULTS: The statistical issues including analysis and presentation of adverse events data and laboratory data were involved and summed up. CONCLUSION: With the progressive development of randomized controlled clinical trials in China, the methods introduced in this paper are sure to prove of consultative value for the safety assessment.