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Abstract Background Malaria is a serious public health concern. Artemisinin and its derivatives are first-line drugs for the treatment of Plasmodium falciparum malaria. In mammals, artemisinin exhibits potent anti-inflammatory and immunoregulatory properties. However, it is unclear whether artemisinin plays a regulatory role in the innate immunity of mosquitoes, thereby affecting the development of Plasmodium in Anopheles when artemisinin and its metabolites enter mosquitoes. This study aims to determine the effect of dihydroartemisinin (DHA), a first-generation semisynthetic derivative of artemisinin, on innate immunity and malaria vector competence of Anopheles stephensi. Methods Anopheles stephensi was fed Plasmodium-infected mice treated with DHA via gavage, Plasmodium-infected blood containing DHA in vitro, or DHA-containing sugar, followed by Plasmodium yoelii infection. The engorged female mosquitoes were separated and dissected 8 and 17 days after infection. Plasmodium oocysts and sporozoites were counted and compared between the control and DHA-treated groups. Additionally, total RNA and proteins were extracted from engorged mosquitoes 24 and 72 h post infection (hpi). Real-time polymerase chain reaction (PCR) and western blotting were performed to detect the transcriptional levels and protein expression of immune molecules in mosquitoes. Finally, the Toll signaling pathway was inhibited via RNA interference and the infection density was analyzed to confirm the role of the Toll signaling pathway in the effect of DHA on the vector competence of mosquitoes. Results DHA treatment via different approaches significantly reduced the number of Plasmodium oocysts and sporozoites in mosquitoes. The transcriptional levels of anti-Plasmodium immune genes (including TEP1, LRIM1, and APL1C), Toll pathway genes (including Tube, MyD88, and Rel1), and the effector defensin 1 were upregulated by DHA treatment at 24 and 72 hpi. TEP1 and Rel1 protein expression was significantly induced under DHA treatment. However, Rel1 knockdown in DHA-treated mosquitoes abrogated DHA-mediated refractoriness to Plasmodium infection. Conclusions DHA treatment effectively inhibited the development of P. yoelii in A. stephensi by upregulating mosquitoes’ Toll signaling pathway, thereby influencing the susceptibility of Anopheles to Plasmodium. Graphical Abstract

Purpose: To investigate the clinical features, radiographic features, treatment strategies, pathological features, and prognosis of orbital cholesterol granuloma (CG). Methods: Twelve patients with orbital CG who were referred to Tianjin Eye Hospital between January 2002 and December 2020 were included in this retrospective case series study. Data collected including patient ophthalmic manifestations, imaging findings, treatment strategies, pathological features, and prognosis were retrospectively reviewed. Results: The patients comprised 10 males and 2 females. The mean age was 34.5 years (standard deviation [SD] = 8.9, median: 36 and range: 16–45 years). Four patients had a history of orbital trauma. The clinical manifestations at the first visit were proptosis (7/12, 58.3%), periorbital or eyelid swelling (6/12, 50%), limitation of eye movement (4/12, 33.3%), ptosis (2/12, 16.7%), and decreased visual acuity (1/12, 8.3%). Computed tomography (CT) showed a nonenhancing, well-circumscribed lesion in the orbit with extensive erosion of the adjacent frontal bone and temporal bone. Magnetic resonance imaging (MRI) showed a nonenhancing mass with intermediate-to-high signal intensity on T1- and T2-weighted images. Ten patients underwent lateral orbitotomy, and two patients underwent supraorbital orbitotomy. All patients had aggressive bone erosion. Histopathologic evaluation of the cyst contents and wall revealed cholesterol clefts, multinucleated giant cells, histiocytes, foamy macrophages, and altered blood pigments. The mean follow-up time of 79.6 months (SD = 49.8, range: 19–193 months). Three patients were lost to follow-up. No postoperative diminution of vision was noted, and no recurrence was observed. Conclusions: CGs can present as superotemporal or temporal orbital lesions. The diagnosis can be established based on CT and MRI. Most of the patients can have no history of orbital trauma.

Abstract The integration of industrial robot application (IRA) into various sectors has catalyzed significant transformations in the labor market, reshaping the dynamics of individual migration decision (IMD). As industries increasingly adopt automation, the implications for workforce distribution and migration patterns become critical areas of study. Based on the conditional logit model and using CMDS data, this paper explores the relationship between IRA and IMD, as well as the heterogeneity effect and influencing mechanism. The findings indicate that IRA reduces the probability of the floating population choosing the city, and the results are robust after considering endogeneity and further robustness test. The impact of IRA on IMD is heterogeneous. Relatively speaking, the floating population with high education levels, health, younger, unmarried, female, agricultural household registration, state-owned enterprises, and non-routine task work does not over-think the impact of IRA during the migration process. In addition, the floating population also considers geographical location, city size, marketization level, wage level, and environmental quality when making migration decisions. the mechanism test shows that IRA attracts or suppresses the floating population through factors such as wage levels, housing price level, difficulty in finding a job, etc., depending on the result of individual utility maximization. These insights reveal the complex interplay between technological advancements in robotics and labor migration, emphasizing the need for comprehensive policy frameworks to manage these transformations effectively.

Abstract Background Metabolic syndrome (MetS) includes a group of metabolic irregularities, including insulin resistance (IR), atherogenic dyslipidemia, central obesity, and hypertension. Consistent evidence supports IR and ongoing low-grade inflammation as the main contributors to MetS pathogenesis. However, the association between the triglyceride-glucose (TyG) index and mortality in people with MetS remains uncertain. The objective of this study was to examine the correlation between the baseline TyG index and all-cause and cardiovascular (CV) mortality in rural Northeast Chinese individuals with MetS. Methods For the Northeast China Rural Cardiovascular Health Study, 3918 participants (mean age, 55 ± 10; 62.4% women) with MetS at baseline were enrolled in 2012–2013 and followed up from 2015 to 2017. The TyG index was calculated using the equation TyG index = ln [fasting TG (mg/dL) × fasting glucose (mg/dL)/2] and subdivided into tertiles [Q1(

Objective To evaluate the effectiveness of machine learning (ML) models in predicting 5-year type 2 diabetes mellitus (T2DM) risk within the Chinese population by retrospectively analyzing annual health checkup records. Methods We included 46,247 patients (32,372 and 13,875 in training and validation sets, respectively) from a national health checkup center database. Univariate and multivariate Cox analyses were performed to identify factors influencing T2DM risk. Extreme Gradient Boosting (XGBoost), support vector machine (SVM), logistic regression (LR), and random forest (RF) models were trained to predict 5-year T2DM risk. Model performances were analyzed using receiver operating characteristic (ROC) curves for discrimination and calibration plots for prediction accuracy. Results Key variables included fasting plasma glucose, age, and sedentary time. The LR model showed good accuracy with respective areas under the ROC (AUCs) of 0.914 and 0.913 in training and validation sets; the RF model exhibited favorable AUCs of 0.998 and 0.838. In calibration analysis, the LR model displayed good fit for low-risk patients; the RF model exhibited satisfactory fit for low- and high-risk patients. Conclusions LR and RF models can effectively predict T2DM risk in the Chinese population. These models may help identify high-risk patients and guide interventions to prevent complications and disabilities.

This paper presents a systematic bibliometric analysis of the artificial intelligence (AI) domain to explore privacy protection research as AI technologies integrate and data privacy concerns rise. Understanding evolutionary patterns and current trends in this research is crucial. Leveraging bibliometric techniques, the authors analyze 8,322 papers from the Web of Science (WoS) database, spanning 1990 to 2023. The analysis highlights IEEE Transactions on Knowledge and Data Engineering and IEEE Access journals as highly influential, the former being an early contributor and the latter emerging as a pivotal source. The study demonstrates substantial disparities in scientific productivity across countries. Specifically, the top 10 countries collectively accounted for 74.8% of the articles, with China and the USA making up nearly half of the total contribution (46.1%). In contrast, regions in Africa and South America exhibited lower scientific production. The evolution of privacy preservation research is reflected, shifting from an algorithm-oriented approach to a focus on data orientation, and subsequently, to privacy solutions centered around Cloud Computing. In recent years, there has been a shift towards embracing Federated Learning and Differential Privacy. The analysis brings to light emerging themes and identifies research gaps, notably a global disparity in research output and a lag in ethical and legal inquiry. It asserts that enhanced interdisciplinary collaboration is imperative to formulate comprehensive privacy solutions for AI. Specifically, the paper imparts invaluable insights that are pivotal for effectively addressing the evolving privacy concerns in the era of AI and big data.

Artemisinin is an endoperoxide sesquiterpene lactone isolated from Artemisia annua and is often used to treat malaria. Artemisinin’s peroxide bridge is the key structure behind its antimalarial action. Scientists have created dihydroartemisinin, artemether, artesunate, and other derivatives preserving artemisinin’s peroxide bridge to increase its clinical utility value. Artemisinin compounds exhibit excellent efficacy, quick action, and minimal toxicity in malaria treatment and have greatly contributed to malaria control. With the wide and unreasonable application of artemisinin-based medicines, malaria parasites have developed artemisinin resistance, making malaria prevention and control increasingly challenging. Artemisinin-resistant Plasmodium strains have been found in many countries and regions. The mechanisms of antimalarials and artemisinin resistance are not well understood, making malaria prevention and control a serious challenge. Understanding the antimalarial and resistance mechanisms of artemisinin drugs helps develop novel antimalarials and guides the rational application of antimalarials to avoid the spread of resistance, which is conducive to malaria control and elimination efforts. This review will discuss the antimalarial mechanisms and resistance status of artemisinin and its derivatives, which will provide a reference for avoiding drug resistance and the research and development of new antimalarial drugs.

Abstract The severity of heat stroke (HS) is associated with intestinal injury, which is generally considered an essential issue for HS. Heat acclimation (HA) is considered the best strategy to protect against HS. In addition, HA has a protective effect on intestinal injuries caused by HS. Considering the essential role of gut microbes in intestinal structure and function, we decided to investigate the potential protective mechanism of HA in reducing intestinal injury caused by HS. HA model was established by male C57BL/6J mice (5–6 weeks old, 17–19 g) were exposed at (34 ± 0.7)°C for 4 weeks to establish an animal HA model. The protective effect of HA on intestinal barrier injury in HS was investigated by 16S rRNA gene sequencing and nontargeted liquid chromatography‐mass spectrometry (LC‐MS) metabolomics. According to the experimental results, HA can change the composition of the gut microbiota, which increases the proportion of lactobacilli, faecal bacteria, and urinobacteria but decreases the proportion of deoxycholic acid. Moreover, HA can reduce liver and kidney injury and systemic inflammation caused by HS and reduce intestinal injury by enhancing the integrity of the intestinal barrier. In addition, HA regulates inflammation by inhibiting NF‐κB signalling and increasing tight junction protein expression in HS mice. HA induces changes in the gut microbiota, which may enhance tight junction protein expression, thereby reducing intestinal inflammation, promoting bile acid metabolism, and ultimately maintaining the integrity of the intestinal barrier. In conclusion, HA induced changes in the gut microbiota. Among the gut microbiota, lactobacilli may play a key role in the potential protective mechanism of HA.

Malaria poses a serious threat to human health. Existing vector-based interventions have shortcomings, such as environmental pollution, strong resistance to chemical insecticides, and the slow effects of biological insecticides. Therefore, the need to develop novel strategies for controlling malaria, such as reducing mosquito vector competence, is escalating. Human defensin 5 (HD5) has broad-spectrum antimicrobial activity. To determine its effect on Plasmodium development in mosquitoes, HD5 was injected into Anopheles stephensi at various time points. The infection density of Plasmodium yoelii in An. stephensi was substantially reduced by HD5 treatment administered 24 h prior to infection or 6, 12, or 24 h post-infection (hpi). We found that HD5 treatment upregulated the expression of the innate immune effectors TEP1, MyD88, and Rel1 at 24 and 72 hpi. Furthermore, the RNA interference of MyD88, a key upstream molecule in the Toll signaling pathway, decreased the HD5-induced resistance of mosquitoes against Plasmodium infection. These results suggest that HD5 microinjection inhibits the development of malaria parasites in An. stephensi by activating the Toll signaling pathway.

Abstract Background The impact of consuming soybean and its products on cardiovascular events (CVEs), cardiovascular mortality, and all-cause mortality remains unclear. This study aimed to examine the prospective association of soybean consumption with CVEs, cardiovascular mortality, and all-cause mortality among the elderly population in rural China. Methods The Northeast China Rural Cardiovascular Health Study included 2477 elderly individuals (mean age 67 ± 6 years, 49.97% men) in the initial phase of the study from 2012 to 2013, with a follow-up period between 2015 and 2017. Soybean consumption was categorized as follows: low-frequency consumption: rare consumption; moderate-frequency consumption: two to three times/week; high-frequency consumption: ≥ four times/week. Cox proportional hazard analysis assessed the potential relationship of soybean consumption with CVEs, cardiovascular mortality, and all-cause mortality. Results The prevalence of soybean and its product consumption was as follows: 38.3% for low-frequency consumption (43.8% for women; 32.8% for men), 49.7% for moderate-frequency consumption (45.8% for women; 53.7% for men), and 11.9% for high-frequency consumption (10.4% for women; 13.5% for men). After adjusting for possible confounders, Cox proportional hazard analysis revealed that the frequency of soybean consumption was an effective predictor of CVEs [Hazard ratio (HR) high (95% CI): 0.555 (0.348, 0.883)], stroke [HR moderate (95% CI): 0.672 (0.494, 0.913); HR high (95% CI): 0.483 (0.276, 0.842)], and all-cause mortality [HR high (95% CI): 0.540 (0.310, 0.942)] in the overall older population. High-frequency consumption of soybean [HR (95% CI): 0.467 (0.225, 0.968)] and moderate-frequency consumption [HR (95% CI): 0.458 (0.270, 0.779)] were associated with stroke events in older men and women, respectively. In addition, high-frequency consumption of soybean [HR (95% CI): 0.437 (0.197, 0.968)] decreased the risk of CVEs in older women. Conclusion Soybean consumption is closely associated with CVEs and all-cause mortality in older individuals residing in rural areas, with a significant gender discrepancy in this relationship. These findings provide new insights into the impact of soybean consumption on cardiovascular well-being in the elderly rural population, thus enhancing our understanding of this field of interest.

Purpose. This study was designed to review the primary sites, clinical manifestations, imaging features, treatments, and outcomes of 36 patients with orbital metastasis in North China. Methods. This was a retrospective review of 36 patients with orbital metastasis at Tianjin Eye Hospital between January 2010 and December 2020 in North China as well as a review of the literature. Results. Thirty-six patients were included in the study; 17 were male, and 19 were female, with an age range of 1–82 years (average 54.9 ± 19.8 years). All the tumours were unilateral. The mean duration from the onset of orbital signs to presentation at the hospital was 2.4 months (range 1–10 months). Breast carcinoma, gastrointestinal tract carcinoma, and lung carcinoma were the most common histological types. Proptosis, ocular pain, and diplopia were the most common clinical manifestations. The superior orbit was the most common quadrant involved. All patients received comprehensive therapy, including surgery, radiotherapy, or chemotherapy. The average follow-up time was 2.45 years (range 7 months to 5.5 years). Ten patients in this study died as a result of disseminated metastasis from the primary tumour. Conclusions. In North China, the most common primary cancer that metastasizes to the orbit is breast cancer, followed by gastrointestinal tract carcinoma and lung cancer. The increasing trend of orbital gastrointestinal tract metastases in North China in recent years is noteworthy. The survival rate of patients with orbital metastasis of neuroblastoma is low.

Abstract Background Mosquito-borne diseases threaten human health, but mosquito control faces various challenges, such as resistance to chemical insecticides. Thus, there is an urgent need for more effective and environment-friendly control agents. Capsaicin can downregulate the mTOR signaling pathway of tumor cells. The TOR signaling pathway can mediate the expression of vitellogenin (Vg) to regulate the fecundity of insects. Whether capsaicin has the potential to inhibit fecundity of mosquitoes by regulating TOR pathway and Vg expression is currently unclear. Methods Anopheles stephensi were fed with blood of mice administered capsaicin by gavage or sugar containing capsaicin followed by a blood feeding with normal mice. Then, the engorged female mosquitoes were tubed individually and underwent oviposition. The eggs and individuals in the subsequent development stages, including larvae, pupae, and emerging adults, were counted and compared between the capsaicin treatment and control groups. Additionally, total RNA and protein were extracted from the engorged mosquitoes at 24 h post blood feeding. Real-time PCR and western blot were performed to detect the transcriptional level and protein expression of the key fecundity-related molecules of mosquitoes. Finally, TOR signaling pathway was inhibited via rapamycin treatment, and changes in fecundity and the key molecule transcription and protein expression levels were examined to verify the role of TOR signaling pathway in the effect of capsaicin on mosquito fecundity. Results The laid and total eggs (laid eggs plus retained eggs) of An. stephensi were significantly reduced by feeding on the blood of capsaicin-treated mice (P

Abstract Background Cardiovascular disease (CVD) brings high mortality and economic burden to patients, especially in rural areas. Simple, low-cost abdominal adiposity measures may help identify individuals with increased CVD risk. It is unclear that which obesity indices is the best to predict CVD in hypertensive people. Methods Northeast China Rural Cardiovascular Health Study (NCRCHS) is a prospective cohort study in a general population in Northeast China. The study examined the cardiovascular health from 2013 to 2015, and follow-up captured the CVD incidence in 2018. Baseline waist-to-height ratio (WHtR), waist circumference (WC), waist-to-hip (WHR)and body mass index (BMI) were calculated and analyzed in relation to the CVD incidence. Results A total of 4244 hypertensive adults without pre-existing CVD at baseline were included in this analysis (age 35–92 years; 2108 men). Over a median follow-up of 4.66 years, a total of 290 CVD cases (6.83%) were documented during the follow-up. Baseline WHtR showed a significant positive association with CVD incidence, even after adjusting for age, sex, diabetes, drinking, smoking, SBP, DBP, Triglyceride, HDL-C, LDL-C, and TC (Hazard Ratios per SD of WHtR ranging from 1.03 to 1.31, p = 0.017). Reclassification and discrimination analyses indicated WHtR addition could improve the conventional model for predicting adverse outcomes within 4 years. Moreover, WHtR predicted the CVD incidence better than other obesity indices (BMI, WC, WHR). Conclusion These findings support a positive association between WHtR and CVD incidence in CVD-free hypertensive adults. WHtR can be used to predict CVD incidence in hypertensive adults.

Considering the risk aversion characteristics of supply chain members, how to effectively design the government subsidy strategy and green supply chain strategy is a realistic and urgent issue. Regarding this, we optimize and compare four three-stage Stackelberg game models between government and a two-echelon green supply chain, namely both manufacturer and retailer risk neutral (BN), manufacturer risk aversion while retailer risk neutral (MA), retailer risk aversion while manufacturer risk neutral (RA) and both manufacturer and retailer risk aversion (BA). The government as the leader decides the subsidy rate of green input cost with the goal of maximizing social welfare; the manufacturer as the first follower makes decisions on product greenness and wholesale price to maximize its own interests; and the retailer as the second follower determines retail prices to maximize its own interests. Employing mathematical reasoning and numerical simulation investigate thoroughly the effects of the government subsidies and the members' risk aversion. Results indicate that an appropriate government subsidy investment has a positive effect on optimal decisions and related benefits. Risk aversion is in favor of improvement of product greenness and social welfare while reduction of retail price. With the increase of manufacturer risk aversion, green subsidy investment rate and retailer expected revenue increase; on the contrary, the wholesale price and manufacturer expected revenue decrease. With the increase of retailer risk aversion, the wholesale price and manufacturer expected revenue increase, while green subsidy investment rate and retailer expected revenue decrease. In the model of BN, product greenness and social welfare are the lowest, while retail price is the highest. BA is opposite to BN. In the model of RA, green subsidy investment rate and retailer expected revenue the lowest, while wholesale price and manufacturer expected revenue the highest. RA is opposite to MA. The government should formulate appropriate subsidy policies to encourage manufacturers to produce green products and raise consumers' green awareness. Enterprises should control their own risk aversion and assess the risk aversion of the other party reasonably.

PurposeThis study aimed to clarify the relationship between liver fibrosis scores (Fibrosis-4, BARD score, and BAAT score) and chronic kidney disease (CKD).MethodsWe collected a range of data from 11,503 subjects (5,326 men and 6,177 women) from the rural regions of Northeastern China. Three liver fibrosis scores (LFSs) including fibrosis-4 (FIB-4), BARD score, and BAAT score were adopted. A logistic regression analysis was used to calculate odds ratios and the 95% confidence interval. A subgroup analysis showed the association between LFSs and CKD under different stratifications. Restricted cubic spline could further explore whether there is a linear relationship between LFSs and CKD. Finally, we used C-statistics, Net Reclassification Index (NRI), and Integrated Discrimination Improvement (IDI) to assess the effect of each LFS on CKD.ResultsThrough the baseline characteristics, we observed that LFSs were higher in the CKD population than in non-CKD. The proportion of participants with CKD also increased with LFSs. In a multivariate logistic regression analysis, the ORs of CKD were 6.71 (4.45–10.13) in FIB-4, 1.88 (1.29–2.75) in the BAAT score, and 1.72 (1.28–2.31) in the BARD score by comparing the high level with the low level in each LFSs. Moreover, after adding LFSs to the original risk prediction model, which consisted of age, sex, drinking, smoking, diabetes, low-density lipoprotein cholesterol, total cholesterol, triglycerides, and mean waist circumference, we found the new models have higher C-statistics. Furthermore, NRI and IDI both indicate LFSs had a positive effect on the model.ConclusionsOur study showed that LFSs are associated with CKD among middle-aged populations in rural areas of northeastern China.

Tongue diagnosis is a unique aspect of traditional Chinese medicine for diagnosing diseases before determining proper means of treatment, but it also has the disadvantage of relying on the subjective experience of medical practitioners and lack objective basis. The purpose of this article is to elucidate tongue-coating microbiota and metabolic differences in primary liver cancer (PLC) patients with thick or greasy tongue coatings. Tongue-coating samples were analyzed in 60 PLC patients (30 PLC with thick or greasy tongue-coating patients and 30 PLC with tongue-coating neither thick nor greasy) and 25 healthy controls (HC) using 16S rRNA gene sequencing technology. As compared to healthy individuals, tongue coatings of patients with PLC had elevated levels of Firmicutes and Actinobacteria. The abundance of Fusobacteria, SR1_Absconditabacteria_, and Spirochaete were higher in tongue coatings of healthy controls compared to samples in patients with PLC. In addition to site-specific differences, higher abundances of Fusobacteria and Actinobacteria were observed in thick or greasy tongue-coating patients as compared to non-thick and greasy tongue-coating patients. The inferred metagenomic pathways enriched in the PLC tongue-coating patients were mainly those involved in replication, recombination, and repair of protein. We also identify a tongue-coating microbiome signature to discriminate HC and PLC, including 15 variables on genus level. The prediction performance of the signature showed well in the training and validation cohorts. This research illustrates specific clinical features and bacterial structures in PLC patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis.

Abstract Background This study aimed to estimate whether metabolic syndrome (MetS) and its components could be used to predict cardiovascular disease (CVD) in a longitudinal analysis in a rural elderly Chinese population. Method At baseline during 2012–2013, a total of 2486 elderly from rural Chinese were enrolled and were followed up during 2015–2017. Stroke and coronary heart disease (CHD) were included in CVD and were diagnosed by clinicians. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF) criteria were used to define MetS separately. Result Hazard ratios adjusting for CHD, stroke and CVD in those with MetS using the NCEP ATP III criteria in females were 1.27 (95 % CI 0.73, 2.21), 1.54 (95 % CI 0.99, 2.40) and 1.45 (95 % CI 1.00, 2.10), respectively; 1.33 (95 % CI 0.77, 2.32), 1.44 (95 % CI 0.92, 2.25) and 1.36 (95 % CI 0.94, 1.97), respectively, with the AHA/NHLBI criteria; and 1.10 (95 % CI 0.89,1.36), 1.62 (95 % CI 1.03, 2.55) and 1.36 (95 % CI 0.93, 1.97), respectively, with the IDF criteria. Additionally, abdominal obesity using the AHA/NHLBI criteria was significantly associated with the incidence of stroke (HR: 1.60; 95 % CI 1.01, 2.52). However, among rural elderly males, neither MetS nor its components predicted new-onset CVD. Conclusions MetS is correlated with high incidence of CVD among rural elderly female, and only using the NCEP ATP III criteria to define MetS could make the incidence of CVD obvious difference. In order to reduce rural elderly CVD, effective measures to prevent, diagnose, and treat MetS should be enacted in a timely manner, especially among females.

ObjectiveThe study aimed to estimate the possible predictors of cardiovascular events (CVEs) in elderly patients with metabolic syndrome (MetS) from rural China. Moreover, we also attempted to find the potential risk factors for newly diagnosed MetS.MethodsThe Northeast China Rural Cardiovascular Health Study (NCRCHS) is a community-based prospective cohort study carried out in rural areas of northeast China. Approximately 1,059 elderly patients with MetS but no cardiovascular diseases and 1,565 elderly patients without MetS at baseline were enrolled in this study. They underwent a physical examination, completed a questionnaire in 2012–2013, and were followed up during 2015–2017. Cox proportional hazard analysis was conducted to assess the possible predictors of newly developed CVEs, and multivariate analysis was used to estimate the risk factors of newly diagnosed MetS.ResultsThe common predictors of newly developed CVEs in both men and women were family history of stroke (HR [hazard ratios] female: 1.696; HR male: 2.504) and soybean consumption (HR female: 0.253; HR male: 0.130). Moreover, minority race (HR: 0.109), systolic blood pressure (SBP) (HR: 1.021), current drinking habits (HR: 2.551), family history of hypertension (HR: 2.297), LDL-C (HR: 1.669), 5,000–20,000 CNY/year annual income (HR: 0.290), and strenuous physical activity (HR: 0.397) were predictors of CVEs only in male elderly patients. For newly diagnosed MetS, body mass index (OR female: 1.212; OR male: 1.207) and fasting blood glucose (OR female: 1.305; OR male: 1.217) were common risk factors in both genders, whereas age (OR:0.958) was a protective factor in men and > 9-h/day sleep duration (OR:0.212) was a protective factor in women. In addition, SBP (OR:1.014) ≥4 times/day, bean consumption (OR:1.955), and uric acid (OR:1.005) increased the risk of MetS in men but not in women.ConclusionOur study identified many effective predictors of CVEs in rural elderly patients with MetS and confirmed the presence of a gender-based discrepancy. Moreover, we also identified additional risk factors, along with the traditional ones, for newly diagnosed MetS in rural elderly patients.

BackgroundThe present study aimed to clarify the effects of four inflammatory indicators (monocyte-to-high-density lipoprotein ratio [MHR], neutrophil-to-lymphocyte ratio [NLR], systematic immune-inflammation index [SII], and systemic inflammation response index [SIRI]) in evaluating the risk of metabolic diseases and cardiovascular disease (CVD), filling the gap of inflammation-metabolism system research in epidemiology.MethodsWe conducted a cross-sectional study and multivariable logistic regression analysis to elucidate the association between inflammatory indicators and metabolic diseases and CVD risk. Metabolic diseases were defined as metabolic disorders (MetDs) or their components, such as metabolic syndrome (MetS), dyslipidemia, and central obesity. We calculated the Framingham risk score (FRS) to evaluate 10-year CVD risk.ResultsOdds ratios for the third vs. the first tertile of MHR were 2.653 (95% confidence interval [CI], 2.142–3.286) for MetD, 2.091 (95% CI, 1.620–2.698) for MetS, 1.547 (95% CI, 1.287–1.859) for dyslipidemia, and 1.515 (95% CI, 1.389–1.652) for central obesity. Odds ratios for the third vs. the first tertile of SIRI were 2.092 (95% CI, 1.622–2.699) for MetD, 3.441 (95% CI, 2.917–4.058) for MetS, 1.417 (95% CI, 1.218–1.649) for dyslipidemia, and 2.080 (95% CI, 1.613–2.683) for central obesity. The odds ratio of a 10-year CVD risk of >30% for the third vs. the first tertile of MHR was 4.607 (95% CI, 2.648–8.017) and 3.397 (95% CI, 1.958–5.849) for SIRI.ConclusionsMHR and SIRI had a significant association with MetD and its components, in which a higher level of MHR or SIRI tended to accompany a higher risk of metabolic diseases. Furthermore, they also correlated with CVD, and the increment of these indicators caused a gradually evaluated risk of 10-year CVD risk.

Objectives The possible predictive effect of echocardiographic aortic root diameter (ARD) on the incidence of cardiovascular events (CVEs) in a large, general population is limited. In addition, there is a lack of data about rural participants. We intend to figure out the possible relationship between ARD and the incidence of CVEs among the general population from rural China.Design Population-based cohort study.Setting Rural areas in Liaoning Province, Northeast China.Participants At baseline, 9810 participants (mean age 53±10, 49.1% male) were enrolled in the Northeast China Rural Cardiovascular Health Study between 2012 and 2017.Main outcome measures Cardiac ultrasonography, lifestyle, medical history, laboratory testing, blood pressure, weight and height. ARD measurement was conducted at the level of the sinuses of Valsalva. Furthermore, the ARD was indexed to height or body surface area.Results During a median follow-up of 4.66 years, 550 non-fatal or fatal CVEs were recorded. Adjusting for blood pressure, age, total cholesterol, fasting blood glucose, estimated glomerular filtration rate, current smoking and drinking, previous cardiovascular diseases and antihypertensive treatment; ARD/height (HR per 1-unit increase=1.781, 95% CI: 1.160 to 2.736, p=0.008) was associated with an increased risk of CVEs in men only. The combination of left ventricular hypertrophy (LVH) and aortic dilation was an independent and powerful predictor for cardiovascular prognosis compared with aortic dilation alone in men but not in women.Conclusions Our study enrols a large sample of rural Chinese residents, and first confirms that ARD/height has a predictive effect on the incidence of CVEs among rural Chinese residents. The combination of LVH and aortic dilation is synergistic, which increases its predictive effect on CVEs in men only, suggesting that aortic dilatation predicts cardiovascular prognosis better than LVH does in men but not in women.

ObjectiveAnti-γ-aminobutyric acid-B receptor (GABABR) encephalitis is a rare type of autoimmune encephalitis. There are only a few, small, published studies regarding prognosis, so prediction of prognosis is of limited accuracy. We identified 37 cases of anti-GABABR encephalitis in China. Here, we present these patients' clinical characteristics and long-term outcomes.MethodsWe collected and retrospectively analyzed the clinical data of 37 patients with anti-GABABR encephalitis from Beijing Fengtai You'anmen Hospital.ResultsThe study cohort comprised 37 patients of anti-GABABR encephalitis of median age 61 years (range: 11–77), 28 of whom were male. The main clinical manifestations were epilepsy (91.9%, 34/37), psychiatric disorders (94.6%, 35/37) and cognitive impairment (97.3%, 36/37). Tumors were identified in 18 (48.6%) patients. First-line immunotherapy was administered to 34 patients, 31 of whom (90.6%) responded favorably. During a median follow-up of 18 months (range: 1–72 months), 21 patients had good outcomes [Modified Ranking Scale (mRS ≤2)], 16 (43.2%) died (mRS 6), and 7 (18.9%) relapsed. Age (P = 0.005), disturbance of consciousness (P = 0.018), admission to the Neurology Intensive Care Unit (P = 0.003), mechanical ventilation (P = 0.009), more numerous clinical manifestations (P = 0.008), comorbid malignancy (P = 0.008), multiple anti-neuronal antibodies (P = 0.029), and hyponatremia (P = 0.023) differed significantly between patients with good outcomes (mRS 0–2) and those with poor outcomes (mRS 3–6).ConclusionMen aged 50–70 years accounted for most of the patients with anti-GABABR encephalitis in our case series. The main clinical manifestations were epilepsy and neuropsychiatric dysfunction. The participants often had concomitant lung cancer, particularly small-cell lung cancer. Patients with lung tumors and/or serious manifestations usually had a poor prognosis with high mortality. Early identification and treatment of tumors improved the poor prognosis to some extent.

ObjectiveCumulative evidence indicates that education plays a major role in predicting cardiovascular risk factors. In this study, we intend to examine the possible relationship between education status and mortality in a large general subject from rural China.MethodsAdult hypertensive subjects (n = 5,227, age = 57.22 ± 10.18 years; 49.1% men) were recruited from general population surveys (Northeast China Rural Cardiovascular Health Study). Their educational status was categorized into two groups as follows: (1) Low education (illiterate or lower than primary school) and (2) medium-high education (higher than primary school). Cardiometabolic comorbidities, related cardiovascular risk factors, and echocardiographic measurements were analyzed in both groups.ResultsLess educated hypertensive subjects had significantly higher prevalence of obesity, diabetes, dyslipidemia, and left ventricular hypertrophy than medium-high educated hypertensive subjects. In the medium-high educated subjects, a significant increase in left ventricular ejection fraction and lower rate of antihypertensive medication was found. Cox proportional hazards analysis indicated that medium-high education was independently associated with all-cause mortality (hazard ratio = 0.76; 95% confidence interval, 0.58, 0.99; P = 0.043) and cardiovascular mortality (hazard ratio = 0.65; 95% confidence interval, 0.44, 0.96; P = 0.028).ConclusionEducation may act as the best predictor of all-cause and cardiovascular mortality in rural hypertensive subjects. This finding suggests that in rural areas, education is likely to represent a cardiovascular specific risk factor and should be evaluated in the strategies of hypertension.

Abstract Background To investigate the combined effect of hypertension and hyperuricemia to the risk of ischemic stroke in a rural Chinese population. Methods The cross-sectional study was conducted from 2012 to 2013 in a rural area of China. After exclusion for missing data, we finally included 11,731 participants into analysis. Results After adjusting for age, current smoking, current drinking, BMI, TG, HDL-C and eGFR, hypertension was significantly associated with ischemic stroke in men (OR: 2.783, 95% CI: 1.793, 4.320) and in women (OR: 4.800, 95% CI: 2.945, 7.822). However, hyperuricemia was significantly associated with ischemic stroke only in women (OR: 1.888, 95% CI: 1.244, 2.864). After full adjustment, participants with both hypertension and hyperuricemia had 8.9 times higher risk than those without them. Finally, the interaction between hypertension and hyperuricemia was statistically significant only in women rather than in men after full adjustment. Conclusions This study demonstrated the positive correlations between hypertension, hyperuricemia and ischemic stroke. Our study also demonstrated the joint effect between hypertension and hyperuricemia towards ischemic stroke only in women, not in men.

The present study examines the roles of parent–child communication and peer attachment in the relationships between marital conflict, family socioeconomic status (SES), and depressive symptoms in migrant children. The present study was a cross-sectional design. A total of 437 children were selected from 2 public schools of migrant children, and they were assessed on measures of marital conflict, family SES, parent–child communication, peer attachment, and depressive symptoms. Results showed that peer attachment moderates the relationships between marital conflict, parent–child communication, and depressive symptoms. That is, for migrant children with high peer attachment, marital conflict influences depressive symptoms directly, but also indirectly through parent–child communication. For migrant children with low peer attachment, marital conflict only exerts a direct influence on depressive symptoms. In addition, parent–child communication mediates the relationship between family SES and depressive symptoms, although the mediating effects were not significant for groups with a high or a low level of peer attachment. Thus, parent–child communication serves as one critical pathway, linking marital conflict, or family SES, with depressive symptoms. Furthermore, peer attachment acts as a buffer against the negative effects of marital conflict on depressive symptoms.

In middle-aged and elderly individuals, the relationship between tea consumption and incident metabolic syndrome (MetS) is still unclear. Therefore, this study intends to figure out the relationship between tea-drinking frequency and MetS in rural middle-aged and older Chinese residents. In the Northeast China Rural Cardiovascular Health Study, 3632 middle-aged or older individuals (mean age 57 ± 8, 55.2% men) without MetS were included at baseline during 2012–2013 and were followed up on between 2015–2017. Participants showing differential tea consumption frequency were divided into the following classes: non-habitual tea drinkers, occasional tea drinkers, 1–2 times/day drinkers, and ≥3 times/day drinkers. Data showed that non-habitual tea drinking was more common among women. The frequency of tea consumption was higher in ethnic groups other than Han and among singles, as well as in concurrent smokers and drinkers and individuals with primary or lower educational status. The increasing tea consumption was in line with baseline elevations in body mass index, systolic and diastolic blood pressure, high-density lipoprotein cholesterol (HDL-C), and AST/ALT ratio. Multivariate logistic regression analysis confirmed that occasional tea drinking increased the incidence of low HDL-C [OR (95% CI): 1.268 (1.015, 1.584)], high waist circumference [OR (95% CI): 1.336 (1.102, 1.621)], and MetS [OR (95% CI): 1.284 (1.050, 1.570)]. In addition, 1–2 times/day tea drinking increased the cumulative incidence of high TG [OR (95% CI): 1.296 (1.040, 1.616)], high waist circumference [OR (95% CI): 1.296 (1.044, 1.609)] and MetS [OR (95% CI): 1.376 (1.030, 1.760)]. We demonstrated that regular tea consumption is correlated with a greater incidence of metabolic disorders and MetS. Our findings may help clarify the contradictory association reported between tea drinking and MetS development in middle-aged and older residents of rural China.

Abstract Background Vector control with Bacillus sphaericus (Bs) is an effective way to block the transmission of malaria. However, in practical application of Bs agents, a sublethal dose effect was often caused by insufficient dosing, and it is little known whether the Bs exposure would affect the surviving mosquitoes’ vector capacity to malaria. Methods A sublethal dose of the Bs 2362 strain was administrated to the early fourth-instar larvae of Anopheles dirus to simulate shortage use of Bs in field circumstance. To determine vector competence, mosquitoes were dissected and the oocysts in the midguts were examined on day 9–11 post-infection with Plasmodium yoelii. Meanwhile, a SYBR quantitative PCR assay was conducted to examine the transcriptional level of the key immune molecules of mosquitoes, and RNA interference was utilized to validate the role of key immune effector molecule TEP1. Results The sublethal dose of Bs treatment significantly reduced susceptibility of An. dirus to P. yoelii, with the decrease of P. yoelii infection intensity and rate. Although there existed a melanization response of adult An. dirus following challenge with P. yoelii, it was not involved in the decrease of vector competence as no significant difference of melanization rates and densities between the control and Bs groups was found. Further studies showed that Bs treatment significantly increased TEP1 expression in the fourth-instar larvae (L4), pupae (Pu), 48 h post-infection (hpi) and 72 hpi (P < 0.001). Further, gene-silencing of TEP1 resulted in disappearance of the Bs impact on vector competence of An. dirus to P. yoelii. Moreover, the transcriptional level of PGRP-LC and Rel2 were significantly elevated by Bs treatment with decreased expression of the negative regulator Caspar at 48 hpi, which implied that the Imd signaling pathway was upregulated by Bs exposure. Conclusions Bs exposure can reduce the vector competence of An. dirus to malaria parasites through upregulating Imd signaling pathway and enhancing the expression of TEP1. The data could not only help us to understand the impact and mechanism of Bs exposure on Anopheles’ vector competence to malaria but also provide us with novel clues for wiping out malaria using vector control.

Abstract Background The present study aims to estimate whether high-density lipoprotein cholesterol (HDL-C) is correlated with cardiovascular events (CVEs) and cardiovascular mortality (CVM) in a large sample of the general population in rural areas of China. Methods Adult participants (n = 10,266, age = 53.79 ± 10.49 years; 46.5% men) were enrolled from the Northeast China Rural Cardiovascular Health Study (NCRCHS). Laboratory testing, blood pressure, weight, height, and questionnaires about socioeconomic status were collected. Results In all, 585 nonfatal or fatal CVEs and 212 cardiovascular deaths were documented during a 4.66-year follow-up. Compared to the reference groups (HDL-C between 1.5 and 1.99 mmol/L), either lower or higher levels of HDL-C were correlated with an increased incidence of CVEs but not CVM [hazard ratio (HR) the lowest = 1.369, 95% confidence interval, 1.007–1.861; HR the highest = 1.044, 0.509–2.231]. Elevated CVM was seen in the lowest HDL-C category (1.840; 1.121–3.021). Conclusions Lower or higher HDL-C was associated with a higher incidence of CVEs but not CVM in the general population of rural China. Perhaps if an appropriate level of HDL-C is maintained, CVEs can be effectively prevented.

Abstract Background We reported a relatively high rate of MetS in rural Northeast residents in 2012–2013. Many strategies like health knowledge propagation and lifestyle modification have been taken to help rural residents decrease metabolic disorders. Hence, we held the present follow-up study in order to figure the changes of metabolic parameters and the possible reasons together with the evaluation of MetS incidence and associated risk factors. Methods A population-based sample of 8147 rural Northeast Chinese residents aged ≥ 35 years at baseline were followed up from 2012–2013 to 2015–2017. MetS was diagnosed following the unify criteria in 2009 using the Asian specific criteria. Results Among residents with MetS at baseline, value of systolic, diastolic blood pressure, total cholesterol, HDL-C decreased while waist circumference increased in both genders in follow-up. Discrepancy of trend in body mass index, LDL-C and estimated GFR existed between male and female. Besides, triglyceride increased, and fast glucose decreased in female only. The alterations of dietary pattern might be accountable for those changes. Among residents without MetS at baseline, the cumulative incidence of newly diagnosed MetS was 24.0% (25.8% for male; 22.3% for female). As the number of metabolic disorders increased at baseline, the incidence of MetS also increased (zero metabolic disorder: 8.3%; one metabolic disorder: 17.1%; two metabolic disorders: 35.4%). In male residents, bad living habits like smoking and drinking were associated with increasing risk of Mets while in female, higher risk of MetS was more likely relevant to dietary pattern. Conclusion Metabolic parameters changes during the past years and seem to be associated with alteration of diet pattern. Incidence of MetS still high among rural Northeast Chinese. The risk factors of higher incidence of MetS show gender discrepancy which make the prophylaxis and control of MetS more effective and directive in rural residents.

Abstract Background The present study aimed to assess the cumulative incidence of major depressive disorder (MDD) among rural Chinese residents. Furthermore, we intended to estimate whether metabolic syndrome (MetS) was associated with MDD by both cross-sectional and prospective analysis. Method Data of 11,675 residents (46.3% men) was used for cross-sectional analysis. The residents were followed up with median 4.66 years. MDD was diagnosed using the Patient Health Questionnaire-9 (PHQ-9). The data of 2796 individuals without any depressive symptoms was used for prospective analysis. Result With median of 4.66 years follow-up, the cumulative incidence of MDD among rural residents was 3.9%. Women had significantly higher cumulative incidence of MDD than men (5.3% for women and 2.9% for men, P

Abstract Background To investigate the influence of hyperhomocysteinemia (HHcy) and metabolic syndrome (MetS) on left ventricular hypertrophy (LVH) in residents in rural Northeast China. Methods We performed a cross-sectional baseline data analysis of 6837 subjects (mean age: 54 ± 10 years) recruited from a rural area of China. Anthropometric indicators were measured according to standard methods. MetS was defined by the modified ATP III criteria. HHcy was defined according to the WHO standard: an Hcy level > 15 μmol/L representing HHcy. Four groups were defined: non-HHcy & non-MetS, HHcy & non-MetS, MetS & non-HHcy and HHcy & MetS. Results The left ventricular mass index for height2.7 (LVMH2.7) in both sexes was significantly higher in the HHcy & MetS group than in the non-HHcy & non-MetS group (females: 51.23 ± 16.34 vs. 40.09 ± 10.55 g-2.7, P

Malaria is still the most widespread parasitic disease and causes the most infections globally. Owing to improvements in sanitary conditions and various intervention measures, including the use of antimalarial drugs, the malaria epidemic in many regions of the world has improved significantly in the past 10 years. However, people living in certain underdeveloped areas are still under threat. Even in some well-controlled areas, the decline in malaria infection rates has stagnated or the rates have rebounded because of the emergence and spread of drug-resistant malaria parasites. Thus, new malaria control methods must be developed. As the spread of the Plasmodium parasite is dependent on the part of its life cycle that occurs in mosquitoes, to eliminate the possibility of malaria infections, transmission-blocking strategies against the mosquito stage should be the first choice. In fact, after the gametocyte enters the mosquito body, it undergoes a series of transformation processes over a short period, thus providing numerous potential blocking targets. Many research groups have carried out studies based on targeting the blocking of transmission during the mosquito phase and have achieved excellent results. Meanwhile, the direct killing of mosquitoes could also significantly reduce the probability of malaria infections. Microorganisms that display complex interactions with Plasmodium, such as Wolbachia and gut flora, have shown observable transmission-blocking potential. These could be used as a biological control strategy and play an important part in blocking the transmission of malaria.

In this paper, we study the long-time dynamics problem of a class of higher-order Kirchhoff coupled systems with nonlinear strong damping. The existence and uniqueness of the solutions of these equations in different spaces are proved by prior estimation and Faedo–Galerkin method; secondly, the family of global attractors of these problems is proved by using the compactness theorem. The results of the Kirchhoff coupled group are promoted through research.

In Alzheimer's disease (AD), amyloid β deposition-induced hippocampal synaptic dysfunction generally begins prior to neuronal degeneration and memory impairment. Lycium barbarum extracts (LBE) have been demonstrated to be neuroprotective in various animal models of neurodegeneration. In this study, we aimed to investigate the effects of LBE on the synapse loss in AD through the avenue of the retina in a triple transgenic mouse model of AD (3xTg-AD). We fed 3xTg-AD mice with low (200 mg/kg) or high (2 g/kg) dose hydrophilic LBE daily for 2 months from the starting age of 4- or 6-month-old. For those started at 6 month age, at 1 month (though not 2 months) after starting treatment, mice given high dose LBE showed a significant increase of a wave and b wave in scotopic ERG. After 2 months of treatment with high dose LBE, calpain-2, calpain-5, and the oxidative RNA marker 8-OHG were downregulated, and presynaptic densities in the inner plexiform layer but not the outer plexiform layer of the retina were significantly increased, suggesting the presynaptic structure of retina was preserved. Our results indicate that LBE feeding may preserve synapse stability in the retina of 3xTg-AD mice, probably by decreasing both oxidative stress and intracellular calcium influx. Thus, LBE might have potential as a neuroprotectant for AD through synapse preservation.

Mallotus oblongifolius (MO), which is rich in polyphenols, is a characteristic tea resource with medicinal value. In this study, a total of 45 polyphenolic components of MO, including narirutin, isoquercitrin, rutin and digallic acid, were identified by UPLC-Q-TOF/MS analysis. In addition, the gastroprotective effect of Mallotus oblongifolius polyphenols (MOP) on ethanol-induced gastric mucosal injury in rats was investigated. The rats received anhydrous ethanol after continuous gavage of MOP or lansoprazole for one week. In addition, the macro- and micro-damage induced by ethanol in the gastric tissue was significantly reduced after MOP pretreatment for one week. Further analysis showed that MOP prevented ethanol-induced acute gastric mucosal injury by increasing the expression of antioxidant enzymes (SOD, CAT, GSH-Px) and decreasing the expression of reactive oxygen species (ROS), lipid oxidation product (MDA) and myeloperoxidase (MPO). Meanwhile, MOP inhibited the phosphorylation of p38/ERK/JNK and promoted the activation of the Nrf2 pathway. These results suggested that MOP may be a promising therapeutic target for the prevention of ethanol-induced gastric mucosal injury by improving oxidative stress, inhibiting the p38/ERK/JNK signaling pathways and activating Nrf2 expression.

Objectives The sensitivity of ECG for detecting left ventricular hypertrophy (LVH) is low. The aim of this study was to explore a better ECG criterion for screening LVH in a large general Chinese population.Design Case–control study.Setting China Medical University in Shenyang, China.Participants All permanent residents in Dawa, Zhangwu and Liaoyang aged 35 years or older were invited. Participants with unqualified data, pacemaker rhythm, frequent premature ventricular beats, Wolff-Parkinson-White syndrome, complete bundle branch block, myocardial infarction or hypertrophic cardiomyopathy were excluded. A total of 10 360 subjects (4630 males) were recruited.Interventions A novel ECG criterion (Northeast China Rural Cardiovascular Health Study (NCRCHS)) composed of different ratios of maximum R wave in lead V5 or V6 (RV5/V6), S wave in lead V3 (SV3) and R wave in lead aVL (RaVL) was proposed and validated using multiple linear regression. Receiver-operating characteristic curves were used to compare the NCRCHS criterion with traditional criteria for LVH detection.Results An optimised model (15*RaVL+8*SV3+7*RV5/V6) was constructed (R2 0.192, p

Piper nigrum Linnaeus is often used as a treatment for chills, stomach diseases, and other ailments. Piperine has many biological functions; however, its mechanism for preventing gastric mucosal damage is still unclear. The objective of this study was to investigate the preventive effects of piperine on ethanol-induced gastric mucosal injury by using GES-1 cells and rats. SOD, CAT, GSH-Px and MDA were effectively regulated in GES-1 cells pre-treated with piperine. Piperine significantly increased SOD, CAT and GSH-Px activities, but decreased the ulcer area, MDA, ROS and MPO levels in the gastric tissues of rats. RT-PCR analysis showed that piperine downregulated the mRNA expression levels of keap1, JNK, ERK and p38, and upregulated the mRNA transcription levels of Nrf2 and HO-1. Western blotting results indicated that piperine could activate the protein expression levels of Nrf2 and HO-1 and inhibit the protein expression levels of keap1, p-JNK, p-ERK and p-p38. In conclusion, piperine suppressed ethanol-induced gastric ulcers in vitro and in vivo via oxidation inhibition and improving gastric-protecting activity by regulating the Nrf2/HO-1 and MAPK signalling pathways.

Piperine, an important natural product, has a good anti-inflammatory effect. However, few researchers have studied its mechanism in these pathways. The objective of this research was to evaluate the molecular mechanism underlying the anti-inflammatory responses of piperine in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The purification and characterization of piperine from Piper nigrum L. were determined by HPLC, UPLC-Q-TOF-MS and 1H NMR. Then, the anti-inflammatory activity was evaluated by a reagent test kit, ELISA kits, RT-PCR and Western blot experiments. The results suggested that piperine (90.65 ± 0.46% purity) at a concentration of 10–20 mg/L attenuated the production of NO and ROS, downregulated the protein and mRNA expression levels of TNF-α, IL-1β and IL-6, and upregulated the protein and mRNA transcription levels of IL-10. Meanwhile, the Western blot results indicated that piperine could inhibit the phosphorylation levels of the ERK, JNK, p38 and p65 proteins. Our findings suggest that piperine is a potential anti-inflammatory substance, whose molecular mechanism may be to regulate the key factors of the NF-κB and MAPK signalling pathways.

Objective: To explore the molecular mechanism of Scutellaria baicalensis Georgi in treating gastric cancer by network pharmacological analysis and molecular docking.Methods: Taking Scutellaria baicalensis Georgi as the object, the active components and corresponding potential drug targets in Scutellaria baicalensis Georgi were obtained from the database of TCM Pharmacological System Analysis Platform (TCMSP). GeneCards/OMIM/DrugBank and other databases were used to collect gastric cancer-related genes, and the obtained genes were intersected with drug targets to obtain the target genes of Scutellaria baicalensis Georgi on gastric cancer. Furthermore, the interaction network of Scutellaria baicalensis Georgi-active ingredients-target-gastric cancer-related genes was constructed. Protein–protein interaction analysis and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on target genes. The PubChem website was used to screen the compounds corresponding to the target genes, and the target protein and 3D structure pdb format files were obtained from the PDB database. Finally, the molecular docking calculation was performed by the AutoDock Vina program. The in vivo cell experiments on the effect of Scutellaria baicalensis on proliferation and migration of gastric cancer cells were used to determine the therapeutic effect of Scutellaria baicalensis on gastric cancer, and the two genes ESR1 and FOS are the key targets of Scutellaria baicalensis on gastric cancer.Results: A total of 10 gastric cancer-related target genes were screened out, and Scutellaria baicalensis Georgi contained 10 active compounds targeting 10 gene sites. There are 30 effective compounds in Scutellaria baicalensis Georgi targeted to treat gastric cancer, and there are 91 corresponding targeting gene sites, involving a total of 10 pathways. The results of molecular docking show that ESR1, FOS, and Scutellaria baicalensis Georgi have good binding free energy and docking fraction. The docking fraction of FOS is −4.200 and the binding free energy is −27.893 kcal/mol. The docking fraction of ESR1 is −5.833 and the binding free energy is −30.001 kcal/mol. The effect of Scutellaria baicalensis Georgi on gastric cancer was verified by in vitro cell experiments and Western blotting.Conclusion:Scutellaria baicalensis Georgi can target and regulate multiple signal pathways by acting on ESR1 and FOS gene loci, thus having a potential therapeutic effect on gastric cancer.

Background: Prolonged heart rate-corrected QT (QTc) interval has been associated with incident cardiovascular diseases (CVD) in general Western populations. However, this association is unclear in Asian population. We aim to estimate the association between QTc interval and incident CVD in a general Chinese population.Methods: We analyzed 8,867 participants age ≥35 years and free of CVD at baseline in the Northeast China Rural Cardiovascular Health Study. A resting 12-lead electrocardiogram was performed on all participants, and QTc interval computed using the Framingham formula. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for associations between QTc interval and incident stroke, coronary heart disease, and combined CVD events.Results: Over a median follow-up of 4.66 years, a total of 439 CVD events occurred (298 stroke cases and 152 CHD cases). After full adjustment, prolonged QTc defined by a sex-specific cutoff was associated with increased risk of developing stroke (HR: 1.82, 95% CI 1.20–2.75, P = 0.004) and combined CVD (HR: 1.52, 95% CI 1.05–2.19, P = 0.026). Spline analyses demonstrated no clear thresholds; when modeled as a linear relationship, each 10 ms increase of QTc interval was associated with an HR of 1.12 (95% CI 1.06–1.19, P < 0.001) for stroke and an HR of 1.10 (95% CI 1.05–1.15, P < 0.001) for combined CVD. Baseline QTc interval was not associated with incident CHD with either modeling strategy.Conclusions: Baseline QTc interval is associated with incident stroke and CVD in adults without prior CVD from a general Chinese population.

Abstract Background Corrected QT (QTc) interval has been correlated with total and CVD mortality. Although much is known about the relation between prolonged QTc interval and clinical outcome, there is no information on the prevalence and specific risk factors of QTc prolongation in general Chinese population. We evaluated the prevalence of prolonged QTc interval and its risk factors in general Chinese population, aiming to fill in the gaps in the literature and provide evidence for potential CVD risk prediction and disease burden estimate in community. Methods A population-based survey was conducted on 11,209 participants over the age of 35 in rural areas of Liaoning Province from 2012 to 2013. Twelve-lead ECGs and automatic analysis were performed on all participants. Logistic regression adjustments were made by using the Bazett’s formula to correlate specific risk factors with prolonged QTc intervals (> 440 ms) for potential confounders. Results The overall prevalence of prolonged QTc interval was 31.6%. The prevalence increased significantly with age (24.1% among those aged 35–44 years; 28.3%, 45–54 years; 35.2%, 55–64 years; 43.4%, ≥65 years, P

Abstract Background To compare the influence of posterior capsule opacification (PCO) morphology and severity on intraocular stray light and visual function with different levels of contrast. Methods Forty-five patients diagnosed with PCO were included in this prospective consecutive case series. The Optical Quality Analysis System II (OQAS II) was adopted to assess the objective visual function including objective scatter index (OSI) and optical quality analysis system values (OVs) with 100, 20, and 9% contrast. RTVue-100 OCT was used to evaluate the PCO morphology and severity. Comparisons among visual function, morphology, and severity between pear type and fibrosis PCO were performed. The correlations among the PCO morphology, severity, OSI, and OVs were also determined. Results There was a significant correlation between increased OSI and decreased visual acuity in PCO patients before laser capsulotomy. The changes of OSI were also correlated with the PCO area for the 3 mm IOL optic region (r = 0.43, p = 0.02). The OSI was significantly higher in pear type PCO when compared with fibrosis PCO (Z = − 4.06, p ≤ 0.001). In addition, the increased OSI in pear type PCO was significantly correlated with the 100% OVs and the 20% OVs but not with the 9% OVs. In fibrosis PCO, OSI was only correlated with the 100% OVs and the 20% OVs pre-YAG. Conclusions OSI and OVs could objectively indicate the visual function impairment in PCO patients. Effects of PCO on light scattering and on objective visual function might be explained by the variations of morphology and severity.

Background: This study intended to use two novel inflammatory indicators: lymphocyte to high-density lipoprotein cholesterol ratio (LHR) and platelet to lymphocyte ratio (PLR), to predict newly diagnosed metabolic syndrome (MetS) among subjects from rural Northeast China.Methods: Adult participants without MetS at baseline (n = 4,980, age = 52.65 ± 10.21 years; 51.9% men) were originated from the Northeast China Rural Cardiovascular Health Study (NCRCHS). LHR (Q1: ≤1.04; Q2: 1.04–1.35; Q3: 1.35–1.79; Q4: ≥1.79) and PLR (Q1: ≤78.50; Q2: 78.50–107.27; Q3: 107.27–140.00; Q4: ≥140.00) were divided in quartile.Results: After 4.66-year follow-up, 1,194 subjects were diagnosed MetS (cumulative incidence 24.0; 25.8% for female and 22.3% for male, P = 0.002). Newly diagnosed MetS had higher value of hemoglobin and platelet count compared to those without MetS. As for LHR, from Q1 to Q4, there were increasing value of waist circumference (WC), serum triglycerides (TG), rates of current smoking and drinking whereas decreasing value of HDL-C. However, for PLR, rates of current smoking and drinking significantly decreased from Q1 to Q4. Similarly, the value of WC and TG showed a decreasing trend. In a logistic regression analysis, after adjusted for possible confounders, LHR [OR (95% CI) Q2: 1.13 (0.86, 1.48); OR (95% CI) Q3: 1.23 (0.94, 1.61); OR (95% CI) Q4: 1.57(1.20, 2.06)] but not PLR was effective predictor of newly diagnosed MetS among rural Chinese.Conclusion: MetS had closed relationship with inflammation among subjects from rural China. As a novel marker of inflammation, LHR but not PLR might be an effective predictor of newly diagnosed MetS and should be widely used in the epidemiological study.

Objective To assess retinal microvascular network impairments in the eyes of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) patients with optical coherence tomography angiography (OCTA). Design Systematic review and meta-analysis. Methods A literature search was conducted in the PubMed and EMBASE databases to identify relevant studies detecting retinal microvascular attenuation among AD, MCI patients and cognitively healthy controls (HCs) by OCTA. Data were extracted by Review Manager V.5.4 and Stata V.14.0. Results Eight investigations were included in this meta-analysis, with 150 AD patients, 195 MCI patients and 226 HCs were eligible for meta-analysis. Evidence based on these studies demonstrated that there was a significantly decreased vessel density (VD) of the Optovue group in superficial capillary plexus (SCP): WMD = -2.26, 95% CI: -3.98 to -0.55, p = 0.01; in deep capillary plexus (DCP): WMD = -3.40, 95% CI: -5.99 to -0.81, p = 0.01, VD of the Zeiss group in SCP:WMD = -0.91, 95% CI: -1.79 to -0.02, p = 0.05 and an enlarged fovea avascular zone (FAZ):WMD = 0.06, 95% CI: 0.01 to 0.11, P = 0.02 in OCTA measurements of MCI patients. Additionally, in OCTA measurements of AD patients, there was a significantly decreased VD in the SCP: WMD = -1.88, 95% CI: -2.7 to -1.07, pConclusion Retinal microvascular alternations could be optimally screened in MCI patients detected by OCTA, which could be a warning sign of relative changes in the MCI before progressing to AD. Retinal microvasculature changes worth further investigation in larger scale clinical trials.

A novel polymer of poloxamer188-b-PCL was synthesized via a ring-opening polymerization. Fourier transform infrared spectroscopy (FTIR), Raman, and 1H nuclear magnetic resonance (1H NMR) spectra were used to study the structures of obtained poloxamer188-b-PCL. The thermo-stability of poloxamer188 -b-PCL was carried out with a thermal gravimetric analyzer (TGA), and cytotoxicity was obtained using the CCK8 method. Cargo-free and curcumin (CUR)-loaded poloxamer188-b-PCL NPs were fabricated via the solvent evaporation method. The morphology, particle size distribution, and stability of cargo-free NPs were studied with a scanning electron microscope (SEM) and laser particle analyzer. The in vitro radioprotection activity of CUR-loaded NPs was performed. FTIR, Raman, and 1H NMR spectra confirmed that poloxamer188-b-PCL was obtained. TGA curves suggested poloxamer188-b-PCL had better thermo-stability than original poloxamer188. Cell tests suggested that the cargo-free NPs had no cytotoxicity. SEM image showed that the cargo-free NPs were spherical with a diameter of 100 nm. Free radical scavenging experiments proved that CUR-loaded NPs had better antioxidant activity than CUR solutions. CUR-loaded NPs could be detected in all tissues, including liver, kidneys and lung. In summary, this work demonstrated a feasibility of developing an injective formulation of CUR and provided a protection agent in caner radiotherapy.

Abstract INTRODUCTION Anopheles stephensi is the main malaria vector in Southeast Asia. Recently, plant-sourced larvicides are attracting great interests. METHODS: The essential oil was extracted from the leaf of Cinnamomum camphora (L.), and a bioassay was conducted to determine the larvicidal efficacy. The chemical composition of the essential oil was determined by GC-MS analysis. RESULTS: The oil showed strong, dose-dependent larvicidal activities. The onset of larvicidal efficiency was rapid. The LC50 and LC95 were determined as 0.146% and 1.057% at 1 h, 0.031% and 0.237% at 12 h, 0.026% and 0.128% at 24 h, respectively. The oil contains 32 compounds. CONCLUSIONS The essential oil of C. camphora leaf has an excellent larvicidal potential for the control of A. stephensi.

Abstract Background Stroke has a high fatality and disability rate, and is one of the main burdens to human health. It is thus very important to identify biomarkers for the development of effective approaches for the prevention and treatment of stroke. Connexin37 is an anti-inflammatory cytokine and is involved in chronic inflammation and atherosclerosis. Recent studies have found that CONNEXIN37 gene variations are associated with atherosclerosis diseases, such as coronary heart disease and stroke, but its association with stroke in distinct human populations remains to be determined. We report here the analysis of the association of the single nucleotide polymorphisms (SNPs) of CONNEXIN37 with ischemic stroke in Han Chinese population. Methods Two SNPs of CONNEXIN37 gene were analyzed in 385 ischemic stroke patients and 362 hypertension control patients using ligase detection reaction (LDR) method. Results Logistic regression analysis demonstrated that, AG and GG genotypes of SNP rs1764390 and CC genotype of rs1764391 of CONNEXIN37 were associated with an increased risk of ischemic stroke, and that G allele of rs1764390 is a risk factor for ischemic stroke. Further, we found that SNP rs1764390 and SNP rs1764391 in CONNEXIN37 were associated with ischemic stroke under additive/dominant model, and recessive/dominant model, respectively. Conclusion Our results indicate that CONNEXIN37 gene polymorphism is an ischemic stroke risk factor in Northern Han Chinese.

Abstract Background Previous researches aiming to estimate the association between metabolic syndrome and depressive symptoms come out with inconsistent results. Besides, most of them are conducted in the developed areas. There is lack of the data from rural China. The aim of this study is to confirm whether gender difference exists among the relationship between MetS, metabolic components and depressive symptoms in the rural Chinese population. Methods A cross-sectional analysis enrolled 11430 subjects’ aged ≥35 from rural Northeast China. Metabolic and anthropometric indicators were measured according to standard methods. Depressive symptoms were defined using the Patient Health Questionnaire-9 (PHQ-9). Results The prevalence of depressive symptoms was 6% among rural Northeast general population and the prevalence of MetS and its components were 39.0% for MetS, 42.9% for abdominal obesity, 67.1% for elevated blood pressure, 47.1% for hyperglycemia, 32.1% for hypertriglyceridemia, 29.5% for low HDL-C. Depressive symptoms were associated with triglyceride component (OR = 1.24, 95%CI: 1.05–1.46, P = 0.01) but not MetS (OR = 1.11, 95%CI: 0.94–1.30, P = 0.23). Moreover, depressive symptoms were associated with triglyceride component (OR = 1.21, 95% CI = 1.00–1.47, P = 0.05) in women only. But once adjusted for menopause status, depressive symptoms were no longer statically associated with triglyceride component (OR = 1.20, 95% CI = 0.99–1.46, P = 0.07). Conclusions Depressive symptoms were associated with triglyceride component but not MetS in rural Chinese population. Routine lipid screening should be recommended among rural depressed residents especially among female.

Objectives. To objectively evaluate posterior capsular opacification (PCO) with RTVue-100 spectral domain-OCT and assess the agreement with the Pentacam system. Methods. Sixty-seven eyes diagnosed with PCO were included. RTVue-100 SD-OCT was used to scan the IOL outline and PCO at horizontal and vertical meridians. PCO was also imaged with a Pentacam and slit-lamp photography system. With RTVue-100 SD-OCT, the PCO area, thickness, density, and objective scores were recorded and used to evaluate the severity of PCO at 3 mm and 5 mm diameter ranges of the IOL optic region. We assessed the correlation of visual acuity, PCO characteristics, and PCO scores. PCO scores acquired from RTVue-100 SD-OCT images were also compared with those from the Pentacam. Differences between pear-type and fibrosis-type PCOs were also compared using RTVue-100 SD-OCT cross-sectional images. Results. The cross-sectional images of PCO acquired with RTVue-100 SD-OCT corresponded well to Pentacam and slit-lamp retroillumination images. IOL-posterior capsular space, area, thickness, and density of the proliferated and accumulated LECs could be clearly visualized and quantified with RTVue-100 SD-OCT. PCO scores were correlated with decreased visual acuity, which was in line with the outcomes using the Pentacam. Differences between the pear-type and fibrosis-type PCO were statistically significant; pear-type PCOs showed a wider and thicker opacification region with lower density compared with fibrosis-type PCOs. Conclusion. RTVue-100 SD-OCT could be a powerful tool in PCO objective evaluation and classification. OCT could be used to visualize the morphology and outline of PCO. Thus, it could discriminate and quantify differences between different types of PCO. PCO scores seem to be a useful factor that could reliably reflect PCO severity.

Background/Aims: We aim to investigate the extent to which depression and quality of life might be associated with decreased glomerular filtration rate (GFR) in a large hypertensive population in rural Northeast China. Methods: A total of 5566 hypertensive participants aged 35 years and older were screened with a stratified cluster multistage sampling scheme in rural areas of Liaoning Province during 2012-2013. Decreased GFR was defined as estimated GFR 2. Results: The overall prevalence of decreased GFR was 3.2%. In the multivariable regression model, participants with moderate or greater depression had a greater risk for having a decreased GFR (OR: 1.739, 95%CI: 1.004 to 3.014) after full adjustment. Every 1-point increase of all the domains in WHOQOL-BREF, except for physical and environment domains, was significantly related to a lower risk for decreased GFR adjusting for age, gender and race. However, after fully adjustment, only social relations remained significant (OR: 0.899, 95%CI: 0.820 to 0.985). Increasing in total scores of WHOQOL-BREF was a protective factor against decreased GFR after fully adjustment. Conclusion: We found that moderate or greater depression and lower quality of life were associated with higher risks for developing decreased GFR.