Lipids, lipid-modifying drug target genes and migraine: a Mendelian randomization study.

INTRODUCTION: Migraine, a prevalent headache disorder with unclear mechanisms and limited treatments, may be influenced by dyslipidemia and genetic factors. Statins and emerging lipid-modifying agents show potential but lack evidence for migraine management. Mendelian Randomization analysis offers insights into causal relationships and therapeutic targets. This study aims to explore genetically predicted lipid traits, drug targets, and their association with migraine risk. METHOD: We conducted Mendelian randomization (MR) analyses utilizing genetic variants associated with lipid traits and variants in genes encoding the protein targets of various classes of lipid-lowering drugs. The specific drug classes investigated included HMGCR, PCSK9, NPC1L1, ABCG5/ABCG8, LDLR, LPL, ANGPTL3, APOB, CETP, and APOC3. To determine the effects on migraine risk, we meta-analyzed MR estimates for regional variants using data from two large sample sets. The genetic variants were weighted based on their associations with specific lipid traits, such as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Apolipoprotein A1, and Apolipoprotein B. To obtain association weights, we utilized data from lipid genetics consortia. For lipid-modifying drug targets that exhibited suggestive significance, we further employed expression quantitative trait locus (eQTL) data. Additionally, we performed colocalization analysis to assess genetic confounding. RESULT: The use of genetic proxies for HMGCR inhibition demonstrated a significant association with a decreased risk of migraine in the FinnGen dataset (OR = 0.64, 95% CI: 0.46-0.88, p = 0.0006) and a nearly significant association in the Choquet dataset (OR = 0.78, 95% CI: 0.60-1.01, p = 0.06). When pooling the estimates, the overall effect size showed a reduced risk of migraine (OR = 0.73, 95% CI: 0.60-0.89, p = 0.0016). Similarly, genetic mimicry of LPL enhancement was associated with a lower risk of migraine in the FinnGen dataset (OR = 0.82, 95% CI: 0.69-0.96, p = 0.01) and the Choquet dataset (OR = 0.91, 95% CI: 0.83-0.99, p = 0.03). Pooling the estimates showed a consistent effect size (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002). Sensitivity analyses yielded no statistically significant evidence of bias arising from pleiotropy or genetic confounding. CONCLUSION: In the study, it was observed that among the 10 lipid-lowering drug targets investigated, LPL and HMGCR showed significant associations with migraine risk. These findings indicate that LPL and HMGCR have the potential to serve as candidate drug targets for the treatment or prevention of migraines.

The Effect of Ketamine on Acute and Chronic Wound Pain in Patients Undergoing Breast Surgery: A Meta-Analysis and Systematic Review.

INTRODUCTION: Perioperative use of ketamine has been discussed widely in many kinds of surgery. The aim of our study was to evaluate the short-term and long-term benefits and safety of ketamine after breast surgery. METHOD: We performed a quantitative systematic review. We included randomized controlled trials that compared intravenous administration of ketamine to a placebo control group, or compared bupivacaine in combination with ketamine to bupivacaine alone in thoracic paravertebral blocks or pectoral blocks among patients undergoing breast surgery. The primary outcome was postoperative pain intensity. Secondary outcomes included cumulative opioid consumption during the 0- to 24-hour postoperative period, the effect on postmastectomy pain syndrome, the effect on postoperative depression, and the adverse events associated with the use of ketamine. RESULTS: Thirteen randomized controlled trials with 1,182 patients were included for analysis. Compared with placebo, intravenous ketamine was effective in reducing wound pain intensity during the first 6 hours after surgery (weighted mean difference [WMD] -0.83; 95% confidence interval [CI] -1.65, -0.01; P = 0.048) and during the first 24 hours after surgery (WMD -0.65; 95% CI -0.95, -0.35; P < 0.001), and in decreasing opioid consumption (WMD -4.14; 95% CI -8.00, -0.29; P = 0.035) during the first 24 hours after surgery, without increasing the risks for gastrointestinal and central nervous system adverse events. Adding ketamine to bupivacaine in thoracic paravertebral blocks was also effective in reducing postoperative wound pain during the first 6 hours after surgery (WMD -0.59; 95% CI, -1.06, -0.12; P = 0.014) and during the first 24 hours after surgery (WMD -0.90; 95% CI -1.27, -0.53; P < 0.001), and in decreasing opioid consumption (WMD - 4.59; 95% CI -5.76, -3.42; P < 0.001) during the first 24 hours after surgery. Perioperative use of ketamine was associated with improved postoperative depression symptoms (standardized mean difference -0.80; 95% CI - 1.34, -0.27; P = 0.003) and less incidence of postmastectomy pain syndrome (relative risk 0.79; 95% CI 0.63, 0.99; P = 0.043). CONCLUSION: Ketamine is an effective and safe multimodal analgesic in patients undergoing breast surgery, administered both intravenously and when added to bupivacaine in paravertebral blocks. In addition, ketamine showed a long-term benefit for preventing postoperative depression and postmastectomy pain syndrome.

A randomized controlled trial to evaluate the impact of a geo-specific poster compared to a general poster for effecting change in perceived threat and intention to avoid drowning 'hotspots' among children of migrant workers: evidence from Ningbo, China.

BACKGROUND: Drowning among children of migrant workers is a major, though neglected public health issue in China. METHODS: A randomised controlled trial was used to examine the potential impact of viewing a preventive health poster with/without geo-located drowning events on perceptions of drowning risk among Chinese migrant children. A total of 752 children from three schools in Jiangbei district were selected by multi-stage sampling and randomly assigned to the intervention (n = 380) or control (n = 372). Multilevel models were used to analyse changes in responses to the following questions after viewing the assigned poster for 10 min: (1) "Do you believe that drowning is a serious health problem in Ningbo city?"; (2) "Do you believe that there are lots of drowning-risk waters around you?"; (3) "Do you believe that the likelihood of your accessing a drowning-risk water is great?"; and (4) "Would you intend to avoid accessing to those drowning-risk waters when being exposed?" RESULTS: At baseline there were no significant differences between the intervention and control groups in perceptions of drowning risk or covariates. Following the intervention, participants that viewed the geo-specific poster were more likely to respond more favourably to the first three questions (p < 0.001) than those who viewed the standard poster. However, there was no substantive difference between the geo-specific or standard poster in terms of changing intentions to avoid drowning hotspots (p = 0.214). CONCLUSIONS: Use of 'geo-located' information added value to the effectiveness of a drowning prevention poster for enhancing awareness of drowning hotspots among children of migrant workers. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-16008979 (Retrospectively registered) (The date of trial registration: Aug 5, 2016, the date of enrolment of the first participant: Nov 10, 2015).

Mortality among drowning rescuers in China, 2013: a review of 225 rescue incidents from the press.

BACKGROUND: Drowning is common worldwide. Rescue efforts attempted by untrained bystanders often lead to the death of the primary drowning victim (PDV), the rescuer or both. Our study aimed to inform prevention by identifying risk factors in rescuer drowning. METHODS: Data on drowning rescue incidents reported online in mainland China, 2013, were reviewed. Information on the drowning incidents, PDVs and rescuers were retrieved for analysis. RESULTS: A total of 225 rescue incidents were identified, of which 14 were victim-rescuer drowning incidents (VRDIs) (6.2%). A person-to-person rescue by swimming to PDVs was the most commonly used method (58.9%). Resuscitation was given immediately to 35.5% of PDVs after rescue. The mortality rate of the rescuers (13.3%) was similar to that of the PDVs (11.5%) (χ(2) = 0.5, p =0.49). Being an adult (OR = 0.2, 95% CI: 0.1-0.5) and other than the first rescuer (OR = 0.4, 95% CI: 0.2-0.9) decreased the risk of rescuers drowning. CONCLUSIONS: Most of the currently employed life-saving methods are dangerous and even potentially life threatening. The idea of "rescuers' safety first" should be embraced, especially with teenage and child rescuers, who should never be encouraged to rescue others without first guaranteeing their own safety. Promotion of basic rescue skills should be implemented in the general public.

EPIDEMIOLOGY AND RISK FACTORS FOR NONFATAL DROWNING IN THE MIGRANT CHILDREN.

The purpose of this study was to determine the incidence and potential risk factors for nonfatal drowning among migrant workers' children in China. We conducted a cross-sectional survey of students from third to ninth grade at five Migrant Workers' Children schools in Ningbo, China in 2014. General information and a history of nonfatal drowning was obtained from self-reported questionnaires by migrant students. A multivariate logistic regression model was used to identify potential risk factors. A total 3,859 students were included in the current study. Of these, 13.4% had experienced a nonfatal drowning accident (15.2% for males, 11.2% for females). Most nonfatal drowning occurred in natural water settings. Diving into unknown water without adult supervision had the greatest association with history of nonfatal drowning [odds ratio (OR) = 1.97; 95% confidential interval (CI): 1.31-2.95], followed by fishing in water (OR = 1.50; 95% CI: 1.05-2.14), swimming or playing in water (OR = 1.47; 95% CI: 1.02-2.12), and trying to rescue peers in the water if they were drowning (OR = 1.31; 95% CI: 1.04-1.64). There were factors associated with a lower risk of drowing: having a parent accompany the child to school (OR = 0.69; 95% CI: 0.51-0.93),understanding the the danger of swimming alone (OR = 0.69; 95% CI: 0.48-0.99) and having a knowledge about water safety (OR = 0.98; 95% CI: 0.98-0.99). The study population was at inceased risk for nonfatal drowning. Preventive measures, such as improved water-safety knowledge, decreasing risky water-related activities and better supervision of children need to be developed and tested to decrease the risk of nonfatal drowning among the study population.

Ensemble effects of high entropy alloy for boosting alkaline water splitting coupled with urea oxidation.

FeCoNiMoRu/CNFs exhibits a small potential of 1.43 V vs. RHE (100 mA cm-2) and superior stability for 90 h toward urea electro-oxidation (UOR). In situ electrochemical Raman results strongly demonstrate the ensemble effects of the various metal sites on improving the UOR activity by co-stabilizing the important intermediates. This work will open new directions in the application of high-entropy alloys for small molecule oxidation reactions.

Effectiveness and safety of Shenmai injection in treatment of shock: A Meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of Shenmai injection for shock. METHODS: Randomized controlled trials (RCTs) that evaluated the therapeutic effect of Shenmai injection on shock (including septic shock, cardiogenic shock, hypovolemic shock, neurogenic shock and anaphylactic shock) were included in this analysis. The major electronic databases were searched until May 2015. The methodological quality of the trials was assessed according to the Cochrane Handbook. Review Manager 5.3 and Stata 12.0 software were applied for data analysis. RESULTS: Thirty RCTs involving 2038 participants were included. The methodological quality of the trials was generally passable. The combined use of Shenmai injection and conventional medicine was significantly more effective at managing shock compared to conventional medicine alone in the outcomes of total effective rate [risk ratio (RR) 1.25, 95% confidence interval (CI) 1.18 to 1.31] and mortality rate [risk difference (RD) -0.10, 95% CI -0.17 to -0.02]. Likewise, improvements were observed in other metrics. Three trials reported adverse events, but no trial reported serious adverse effects. CONCLUSION: Our results indicated the potential effectiveness of Shenmai injection combined with conventional medicine treatment for shock. However, further rigorously designed trials are needed to collect and weigh up all the evidence for the use of Shenmai injection.

Demographic Factors Associated With Leading Causes of Injury Mortality in Ningbo, China: 2004-2013.

Injuries have emerged as a crucial public health concern in China. Data were obtained from the death registry system in Ningbo during 2004-2013. Mortality rates resulting from all injuries and the 6 most common types of injuries were analyzed to identify time trends using linear regression models on both the absolute scale and log scale. A decreased male to female ratio and increasing age were observed among the total injury deaths. The annual all-injury mortality rates declined considerably during the observation period. Injury mortality rates for motor vehicle traffic crashes, drowning, and suicide all showed a deceasing trend; however, only mortality from falls showed an increasing trend. There was a sharp increasing trend among females, with a disproportionate number of falls. The injury patterns in Ningbo are mostly comparable to those in high-income countries. Appropriate preventive strategies should be urgently tailored to control this aggressive evolution in older individuals and females.

Prevalence of macro- and microvascular complications in patients with type 2 diabetes and kidney disease with or without albuminuria in a single Chinese Diabetes Centre.

OBJECTIVE: To investigate the relationship between diabetic retinopathy, neuropathy and low ankle-brachial index in mild-to-moderate chronic kidney disease of type 2 diabetic patients. METHODS: We enrolled 875 type 2 diabetic patients who were divided into two phenotypes (with or without albuminuria) and stratified into three groups (stage 1 with estimated glomerular filtration rate ⩾ 90 mL/min/1.73 m(2), stage 2 with estimated glomerular filtration rate of 60-89, stage 3 with estimated glomerular filtration rate of 30-59). The prevalence of diabetic retinopathy, neuropathy and low ankle-brachial index was compared and the risk factors of renal impairment were determined. RESULTS: Among chronic kidney disease stages, the prevalence of diabetic retinopathy increased from 42.5%, 56.6% to 66.7% in albuminuric subjects and from 29.4%, 33.0% to 50.0% with no significant trend in normoalbuminuric subjects (p = 0.005, 0.007 and 0.399 compared with albuminuric subjects in each stage). There was a significantly increased prevalence of low ankle-brachial index (17.5%, 22.6% and 44.4%) in normoalbuminuric subjects but no significant trend in albuminuric subjects. Diabetic retinopathy (odds ratio = 2.474, 95% confidence interval = 1.009-6.068) was an independent risk factor of declining kidney function in albuminuric patients. CONCLUSION: The prevalence of diabetic retinopathy was graded according to the estimated glomerular filtration rate declining in albuminuric patients while the prevalence of low ankle-brachial index was gradually increased in normoalbuminuric patients, indicating the diverse underlying mechanisms of mild to moderate chronic kidney disease between these two phenotypes.

The dynamics of hypertension prevalence, awareness, treatment, control and associated factors in Chinese adults: results from CHNS 1991-2011.

OBJECTIVES: To analyze the trends in blood pressure (BP), and the prevalence, awareness, treatment and control of hypertension and associated factors in Chinese adults from 1991 to 2011. METHODS: On the basis of the longitudinal data of China Health and Nutrition Survey, 75 526 records of 24 410 adults were selected according to the eligibility criteria. The age-standardized levels of SBP, DBP, prevalence, awareness, treatment and control of hypertension were calculated by sex and age group within each year. Generalized estimating equation was employed to investigate the associations between demographic factors and status of hypertension, awareness, treatment and control. RESULTS: From 1991 to 2011, the BP level elevated (SBP 120.0-124.5 mmHg, DBP 76.7-79.3 mmHg) and the prevalence of hypertension increased from 23.4 to 28.6%. The increasing levels of BP and hypertension prevalence were more apparent among men and older patients. The rates of hypertension awareness, treatment and control also increased while kept at low levels. Factors such as age, sex, smoking habit, drinking habit, household income, health insurance, BMI, residential region, marital status, educational level and nationality were significantly associated with the status of hypertension, awareness, treatment and control. CONCLUSION: The BP level and hypertension prevalence have increased among Chinese adults in recent years. However, levels of hypertension awareness, treatment and control were quite low. To reduce the disease burden of the hypertension, improvements in health education programs, detection and treatment strategies are warranted.

Ureteroscopic lithotripsy in Trendelenburg position for proximal ureteral calculi: a prospective, randomized, comparative study.

PURPOSE: We conducted a prospective, randomized, comparative study to compare the clinical outcome between the Trendelenburg position ureteroscopic lithotripsy (tURSL) and the conventional position ureteroscopic lithotripsy (cURSL) for the management of single proximal ureteral stone. METHODS: From January 2012 to September 2013, consecutive patients with single proximal ureteral calculi less than 2 cm and planned for ureteroscopic lithotripsy at our institution were enrolled in this study. The eligible patients were randomized into cURSL group and tURSL group according to sequence of random numbers generated by computer. In tURSL group, patients were turned into a Trendelenburg lithotomy position with head down 30° while the conventional lithotomy position was applied in cURSL group. URSL was performed using a 6/7.5F semi-rigid ureteroscope with holmium laser. When retropulsion occurred, the stones fragments were followed by semi-rigid ureteroscope up to the renal collecting system. The Olympus P5 flexible ureteroscope was used if there was any suspicion of stone migration into lower calices or incomplete stone fragmentation by semi-rigid ureteroscope. Patients' demographics between the two groups, perioperative course, clinical outcome and complication rates were compared. Data were analyzed using Chi-square test, Fisher's exact test or Student's t test. Binary logistic regression analysis was applied to estimate the effects of surgical position and stone size on stone migration. RESULTS: A total of 355 cases were finally analyzed in this study (176 in cURSL group and 179 in tURSL group). The mean operative time was significantly prolonged in cURSL group than in tURSL group, while the stone-free rate (SFR) at 4 weeks was significantly higher in tURSL group. A statistically significant difference was found in stone migration rate between the two groups (26.7 vs. 43.6 %, P = 0.001). In the stone migration subsetting, less stones fragments were found to migrate into lower calices in tURSL stone migration subgroup (P = 0.000). Also, the flexible ureteroscope utilization as well as the operative time was significantly decreased in tURSL stone migration subgroup (25.5 vs. 72.3 %, P = 0.000), (44.96 ± 11.0 min vs. 59.17 ± 9.2 min, P = 0.000) with higher SFR after retrograde intrarenal surgery (RIRS) (96.2 vs. 74.5 %, P = 0.000). CONCLUSION: The tURSL was safe and highly efficacious for the management of proximal ureteral calculus, especially in nonobese patient. Even with important stone migration risk, it rendered higher SFR and less operative time compared with cURSL. Moreover, less utilization of flexible ureteroscope and decreased deflection time in tURSL could potentially reduce the medical cost.

Incidences, types, and influencing factors of snow disaster-associated injuries in Ningbo, China, 2008.

OBJECTIVE: The incidence, types, and influencing factors of injuries due to snow-ice disasters are essential for public health preparedness. This study was designed to assess such factors of injuries during the 22-day snowstorm in Ningbo, Zhejiang Province, China, in 2008. METHODS: A multistage cluster probability sampling method was applied to select the study population in urban, rural, and mountainous areas. Data including sociodemographic characteristics, frequency, and types of injuries during the snowstorm between January 20 and February 10, 2008, were obtained by face-to-face interviews using a structured questionnaire and by checking the participants' medical records. Univariate and multivariate regression analyses were used to determine the factors significantly associated with the risk of injuries. RESULTS: A total of 3169 residents of 1416 families took part in this survey. In 581 residents, 602 injuries were identified. Incidences of frostbite, falling injury, and traffic accident-related injury were 12.78%, 5.30%, and 0.50%, respectively. Injury occurred more frequently in women than in men (odds ratio [OR], 1.42; 95% CI, 1.19-1.70). Frostbite occurred more frequently in women than in men (adjusted OR, 1.86; 95% CI, 1.43-2.41) and more frequently in urban areas than in other areas (adjusted OR, 1.65; 95% CI, 1.24-2.20). Travel by bus or car, wearing a scarf, wearing gloves, wearing a raincoat, reducing outdoor activity, and performing regular physical exercise were independent protective factors of frostbite, with an adjusted OR (95% CI) of 0.35 (0.20-0.61), 0.45 (0.33-0.62), 0.35 (0.26-0.48), 0.45 (0.33-0.61), 0.36 (0.27-0.48), and 0.18 (0.13-0.24), respectively. Falling injury occurred more often in mountainous areas than in other areas (adjusted OR, 1.74; 95% CI, 1.27-2.42). Age 45 years or older, working outside more than 15 days, and wearing a raincoat were independent risk factors of falling injury, with an adjusted OR (95% CI) of 2.30 (1.60-3.32), 1.92 (1.36-2.72), and 2.21 (1.56-3.11), respectively. Falling and traffic accident-related injuries were mainly due to slippery roads. CONCLUSIONS: Frostbite and falling injury were the major injuries caused by an unprecedented snow-ice disaster. Keeping warm and maintaining regular physical exercise appeared to reduce frostbite risk. Public health intervention also reduced the risk of falling and traffic accident-related injuries.

Electrochromatic carbon nanotube/polydiacetylene nanocomposite fibres.

Chromatic materials such as polydiacetylene change colour in response to a wide variety of environmental stimuli, including changes in temperature, pH and chemical or mechanical stress, and have been extensively explored as sensing devices. Here, we report the facile synthesis of carbon nanotube/polydiacetylene nanocomposite fibres that rapidly and reversibly respond to electrical current, with the resulting colour change being readily observable with the naked eye. These composite fibres also chromatically respond to a broad spectrum of other stimulations. For example, they exhibit rapid and reversible stress-induced chromatism with negligible elongation. These electrochromatic nanocomposite fibres could have various applications in sensing.