Association between dietary vitamin B1 intake and cognitive function among older adults: a cross-sectional study.

BACKGROUND: This study aims to investigate the relationship between vitamin B1 intake and cognitive function in older adults. METHODS: This cross-sectional observational study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. A total of 2422 participants were included in the analysis, with dietary vitamin B1 intake being determined by averaging two 24-h dietary recalls. Cognitive function was assessed using three cognitive function tests: the Digit Symbol Substitution Test (DSST) for processing speed, the Animal Fluency Test (AFT) for executive function, a Consortium to Establish a Registry for Alzheimer's disease (CERAD) subtest for memory. Test-specific and global cognition z score was created. Multivariate linear regression models were used to explore the association between vitamin B1 and cognitive function. RESULTS: 2422 participants, aged 60 years and older, were included from NHANES across two survey cycles (2011-2014). Higher vitamin B1 intake was associated with higher DSST, AFT scores (P < 0.001) as well as the global cognition z score (P = 0.008). In the fully adjusted model, as compared to the lowest quartile (Q1), the highest quartile (Q4) of vitamin B1 intake was related to higher DSST score (ß = 2.23, 95% CI 0.79 ~ 3.67) and global cognition z sore (ß = 0.09, 95% CI 0.02 ~ 0.16). The association between dietary vitamin B1 intake and cognitive function scores in US adults is linear. There was no detected significant statistical interaction between these variables. CONCLUSIONS: Increased dietary intake of vitamin B1 was associated with better cognitive function in individuals aged over 60.

Ropivacaine inhibits the malignant behavior of lung cancer cells by regulating retinoblastoma-binding protein 4.

Background: Ropivacaine is a local anesthetic commonly used in regional nerve blocks to manage perioperative pain during lung cancer surgery. Recently, the antitumor potential of ropivacaine has received considerable attention. Our previous study showed that ropivacaine treatment inhibits the malignant behavior of lung cancer cells in vitro. However, the potential targets of ropivacaine in lung cancer cells have not yet been fully identified. This study aimed to explore the antitumor effects and mechanisms of action of ropivacaine in lung cancer. Methods: Lung cancer A549 cells were treated with or without 1 mM ropivacaine for 48 h. Quantitative proteomics was performed to identify the differentially expressed proteins (DEPs) triggered by ropivacaine treatment. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and analyze the most significant hub genes. Overexpression plasmids and small interfering RNA were used to modulate the expression of key DEPs in A549 and H1299 cells. MTS, transwell assays, and flow cytometry were performed to determine whether the key DEPs were closely related to the anticancer effect of ropivacaine on the malignant behavior of A549 and H1299 cells. Results: Quantitative proteomic analysis identified 327 DEPs (185 upregulated and 142 downregulated proteins) following ropivacaine treatment. Retinoblastoma-binding protein 4 (RBBP4) was one of the downregulated DEPs and was selected as the hub protein. TCGA database showed that RBBP4 was significantly upregulated in lung cancer and was associated with poor patient prognosis. Inhibition of RBBP4 by siRNA resulted in a significant decrease in the proliferation and invasive capacity of lung cancer cells and the induction of cell cycle arrest. Additionally, the results indicated RBBP4 knockdown enhanced antitumor effect of ropivacaine on A549 and H1299 cells. Conversely, the overexpression of RBBP4 using plasmids reversed the inhibitory effects of ropivacaine. Conclusion: Our data suggest that ropivacaine suppresses lung cancer cell malignancy by downregulating RBBP4 protein expression, which may help clarify the mechanisms underlying the antitumor effects of ropivacaine.

Potential 'anti-cancer' effects of esketamine on proliferation, apoptosis, migration and invasion in esophageal squamous carcinoma cells.

BACKGROUND: Esketamine, an N-methyl-D-aspartate receptor antagonist, is commonly used for anesthesia and analgesia clinically. It was reported to negatively regulate cell proliferation, metastasis and apoptosis in cancer cells, including lung cancer and pancreatic cancer. However, its impact on esophageal squamous cell carcinoma (ESCC) malignance and underlying mechanism remain elusive. This study was aimed to investigate the antitumor effects of esketamine on ESCC in vitro. METHODS: ESCC cell lines (KYSE-30 and KYSE-150) were cultured and treated with different concentrations (0.1, 0.2, 0.4, 0.8, 1, 2 mM) of esketamine. Their proliferation, apoptosis, migration and invasion were assessed with various assays. Furthermore, mass spectrometry-based proteomic analysis and GO/KEGG enrichment analysis were applied to characterize the differentially expressed proteins (DEPs) with or without esketamine treatment. Some key proteins identified from proteomic analysis were further validated with Western blotting and bioinformatics analysis. RESULTS: Esketamine significantly inhibited the proliferation, migration, invasion and promoted apoptosis of the both types of cell lines in a dose- and time-dependent manner. A total of 321 common DEPs, including 97 upregulated and 224 downregulated proteins, were found with HPLC-MS analyses. GO/KEGG enrichment analysis suggested that esketamine affected cell population proliferation, GTPase activity and Apelin signaling pathway. The ERCC6L, AHR and KIF2C protein expression was significantly downregulated in these ESCC cells treated with esketamine compared to the controls and their changes were associated with the suppressive effects of esketamine on ESCC through bioinformatics analysis. CONCLUSIONS: Our work demonstrated that esketamine has potential anti-ESCC properties in vitro but subjected to further in vivo and clinical study.

Nomogram prediction model of postoperative pneumonia in patients with lung cancer: A retrospective cohort study.

Background: The prediction model of postoperative pneumonia (POP) after lung cancer surgery is still scarce. Methods: Retrospective analysis of patients with lung cancer who underwent surgery at The Fourth Hospital of Hebei Medical University from September 2019 to March 2020 was performed. All patients were randomly divided into two groups, training cohort and validation cohort at the ratio of 7:3. The nomogram was formulated based on the results of multivariable logistic regression analysis and clinically important factors associated with POP. Concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, Hosmer-Lemeshow goodness-of-fit test and decision curve analysis (DCA) were used to evaluate the predictive performance of the nomogram. Results: A total of 1252 patients with lung cancer was enrolled, including 877 cases in the training cohort and 375 cases in the validation cohort. POP was found in 201 of 877 patients (22.9%) and 89 of 375 patients (23.7%) in the training and validation cohorts, respectively. The model consisted of six variables, including smoking, diabetes mellitus, history of preoperative chemotherapy, thoracotomy, ASA grade and surgery time. The C-index from AUC was 0.717 (95%CI:0.677-0.758) in the training cohort and 0.726 (95%CI:0.661-0.790) in the validation cohort. The calibration curves showed the model had good agreement. The result of DCA showed that the model had good clinical benefits. Conclusion: This proposed nomogram could predict the risk of POP in patients with lung cancer surgery in advance, which can help clinician make reasonable preventive and treatment measures.

Ultrasound-guided transversus abdominis plane block as an effective anesthetic technique for transverse colostomy in a high-risk elderly patient: A case report.

Ultrasound-guided transversus abdominis plane (TAP) block is considered to be one of most prevalent and effective adjuvant analgesic methods for various abdominal surgeries. However, whether TAP blocks can be used alone as an effective anesthetic technique in minor abdominal operations has rarely been reported. Here we presented a 66-year-old male who had sustained right somatic dysfunction and mild brain dysfunction caused by cerebral infarctions and poorly treated hypertension. The patient received a confine operation of transverse colostomy to alleviate an intestinal obstruction caused by rectal cancer. A 22G needle was advanced in the plane under ultrasound guidance until it reached the TAP. A total of 10 mL 0.375% ropivacaine with 5 mg dexamethasone and 10 µg dexmedetomidine was injected into the TAP. The operation went stably and smoothly without any complaints. After the operation, the patient returned to the care of the surgical recovery staff with patient-controlled intravenous analgesia (PCIA) containing 0.7 mg/kg oxycodone and 2.5 µg/kg dexmedetomidine. During the perioperative period, the elderly patient did not experience apparent or unbearable pain. All these evidences indicated the ultrasound-guided subcostal and lateral TAP block was a simple and effective procedure for transverse colostomy in a high-risk elderly patient.

Learning end-to-end patient representations through self-supervised covariate balancing for causal treatment effect estimation.

A causal effect can be defined as a comparison of outcomes that result from two or more alternative actions, with only one of the action-outcome pairs actually being observed. In healthcare, the gold standard for causal effect measurements is randomized controlled trials (RCTs), in which a target population is explicitly defined and each study sample is randomly assigned to either the treatment or control cohorts. The great potential to derive actionable insights from causal relationships has led to a growing body of machine-learning research applying causal effect estimators to observational data in the fields of healthcare, education, and economics. The primary difference between causal effect studies utilizing observational data and RCTs is that for observational data, the study occurs after the treatment, and therefore we do not have control over the treatment assignment mechanism. This can lead to massive differences in covariate distributions between control and treatment samples, making a comparison of causal effects confounded and unreliable. Classical approaches have sought to solve this problem piecemeal, first by predicting treatment assignment and then treatment effect separately. Recent work extended part of these approaches to a new family of representation-learning algorithms, showing that the upper bound of the expected treatment effect estimation error is determined by two factors: the outcome generalization-error of the representation and the distance between the treated and control distributions induced by the representation. To achieve minimal dissimilarity in learning such distributions, in this work we propose a specific auto-balancing, self-supervised objective. Experiments on real and benchmark datasets revealed that our approach consistently produced less biased estimates than previously published state-of-the-art methods. We demonstrate that the reduction in error can be directly attributed to the ability to learn representations that explicitly reduce such dissimilarity; further, in case of violations of the positivity assumption (frequent in observational data), we show our approach performs significantly better than the previous state of the art. Thus, by learning representations that induce similar distributions of the treated and control cohorts, we present evidence to support the error bound dissimilarity hypothesis as well as providing a new state-of-the-art model for causal effect estimation.

Generating high-fidelity privacy-conscious synthetic patient data for causal effect estimation with multiple treatments.

In the past decade, there has been exponentially growing interest in the use of observational data collected as a part of routine healthcare practice to determine the effect of a treatment with causal inference models. Validation of these models, however, has been a challenge because the ground truth is unknown: only one treatment-outcome pair for each person can be observed. There have been multiple efforts to fill this void using synthetic data where the ground truth can be generated. However, to date, these datasets have been severely limited in their utility either by being modeled after small non-representative patient populations, being dissimilar to real target populations, or only providing known effects for two cohorts (treated vs. control). In this work, we produced a large-scale and realistic synthetic dataset that provides ground truth effects for over 10 hypertension treatments on blood pressure outcomes. The synthetic dataset was created by modeling a nationwide cohort of more than 580, 000 hypertension patient data including each person's multi-year history of diagnoses, medications, and laboratory values. We designed a data generation process by combining an adapted ADS-GAN model for fictitious patient information generation and a neural network for treatment outcome generation. Wasserstein distance of 0.35 demonstrates that our synthetic data follows a nearly identical joint distribution to the patient cohort used to generate the data. Patient privacy was a primary concern for this study; the ϵ-identifiability metric, which estimates the probability of actual patients being identified, is 0.008%, ensuring that our synthetic data cannot be used to identify any actual patients. To demonstrate its usage, we tested the bias in causal effect estimation of four well-established models using this dataset. The approach we used can be readily extended to other types of diseases in the clinical domain, and to datasets in other domains as well.

Learning Causal Effects From Observational Data in Healthcare: A Review and Summary.

Causal inference is a broad field that seeks to build and apply models that learn the effect of interventions on outcomes using many data types. While the field has existed for decades, its potential to impact healthcare outcomes has increased dramatically recently due to both advancements in machine learning and the unprecedented amounts of observational data resulting from electronic capture of patient claims data by medical insurance companies and widespread adoption of electronic health records (EHR) worldwide. However, there are many different schools of learning causality coming from different fields of statistics, some of them strongly conflicting. While the recent advances in machine learning greatly enhanced causal inference from a modeling perspective, it further exacerbated the fractured state in this field. This fractured state has limited research at the intersection of causal inference, modern machine learning, and EHRs that could potentially transform healthcare. In this paper we unify the classical causal inference approaches with new machine learning developments into a straightforward framework based on whether the researcher is most interested in finding the best intervention for an individual, a group of similar people, or an entire population. Through this lens, we then provide a timely review of the applications of causal inference in healthcare from the literature. As expected, we found that applications of causal inference in medicine were mostly limited to just a few technique types and lag behind other domains. In light of this gap, we offer a helpful schematic to guide data scientists and healthcare stakeholders in selecting appropriate causal methods and reviewing the findings generated by them.

Effect of Salt Substitution on Cardiovascular Events and Death.

BACKGROUND: Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain. METHODS: We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia. RESULTS: A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76). CONCLUSIONS: Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).

Protocol for the economic evaluation of the China Salt Substitute and Stroke Study (SSaSS).

INTRODUCTION: Cardiovascular diseases (CVDs) are the leading causes of death and disability worldwide. Reducing dietary salt consumption is a potentially cost-effective way to reduce blood pressure and the burden of CVD. To date, economic evidence has focused on sodium reduction in food industry or processed food with blood pressure as the primary outcome. This study protocol describes the planned within-trial economic evaluation of a low-sodium salt substitute intervention designed to reduce the risk of stroke in China. METHODS AND ANALYSES: The economic evaluation will be conducted alongside the Salt Substitute and Stroke Study: a 5-year large scale, cluster randomised controlled trial. The outcomes of interest are quality of life measured using the EuroQol-5-Dimensions and major adverse cardiovascular events. Costs will be estimated from a healthcare system perspective and will be sought from the routinely collected data available within the New Rural Cooperative Medical Scheme. Cost-effectiveness and cost-utility analyses will be conducted, resulting in the incremental cost-effectiveness ratio expressed as cost per cardiovascular event averted and cost per quality-adjusted life year gained, respectively. ETHICS AND DISSEMINATION: The trial received ethics approval from the University of Sydney Ethics Committee (2013/888) and Peking University Institutional Review Board (IRB00001052-13069). Informed consent was obtained from each study participant. Findings of the economic evaluation will be published in a peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02092090).

Cannabinoid receptor 2 deficiency enhances isoflurane-induced spatial cognitive impairment in adult mice by affecting neuroinflammation, neurogenesis and neuroplasticity.

Isoflurane (Iso) is a commonly used inhalational anesthetic and is associated with the incidence of postoperative cognitive dysfunction (POCD). Cannabinoid receptor 2 (CB2R) was previously reported to have a promising neuroprotective function in cases of POCD, but the specific mechanisms have remained to be fully explored. The aim of the present study was to investigate the effect of CB2R deficiency on spatial cognitive performance in adult mice exposed to Iso. A total of 20 adult CB2R knockout (KO) and 20 wild-type (WT) mice were exposed to Iso (1.4% in oxygen for 4 h) or 100% oxygen. The Morris water maze (MWZ) test was performed 10 days after Iso exposure. Immunofluorescence staining and reverse transcription-quantitative PCR were performed to assess the expression of microglial marker ionized calcium-binding adaptor molecule-1 (Iba1) and the mRNA expression levels of microglial phenotype markers (M1: Interleukin-6, tumor necrosis factor-α, inducible nitric oxide synthase; M2: Chitinase-3 like protein) in the hippocampus. Changes in hippocampal neurogenesis and neuroplasticity were assessed by 5-bromodeoxyuridine (BrdU) immunostaining and Golgi staining. Compared with control mice, WT Iso-exposed mice had impaired spatial performance in the MWZ test. Furthermore, hippocampal Iba1 immunoreactivity and the number of microglial branches were notably increased in Iso-exposed WT mice. This was paralleled by significant upregulation of M1-associated markers and downregulation of M2-associated markers in the hippocampus. An obviously reduced number of BrdU+ neurons and decreased spine density were observed in WT Iso-exposed mice compared with control mice. Of note, CB2R deficiency exacerbated the spatial cognition impairment induced by Iso in the MWZ test. The alterations in the activation, morphology and M1 polarization of microglia, the number of BrdU+ neurons and spine density were more pronounced in CB2R-deficient Iso-exposed KO mice than in WT Iso-exposed mice. These results suggested that CB2R has a crucial role in Iso-induced cognitive impairment, which may be related to changes in hippocampal neuroinflammation, neurogenesis and neuroplasticity.

Feasibility and validity of using death surveillance data and SmartVA for fact and cause of death in clinical trials in rural China: a substudy of the China salt substitute and stroke study (SSaSS).

BACKGROUND: In rural China, mortality surveillance data may be an alternative to primary data collection in clinical trials; SmartVA (verbal autopsy) is also a potential alternative for endpoint adjudication. The feasibility and validity of both need to be assessed. METHODS: We used mortality data from the first 24 months of the China Salt Substitute and Stroke Study (SSaSS) trial and assessed the agreement between (1) mortality surveillance data and face-to-face visits for fact of death; (2) mortality surveillance data and SSaSS adjudication for causes of death; (3) SmartVA and SSaSS adjudication for causes of death; (4) cause-specific mortality fraction of different methods. Face-to-face visits and SSaSS adjudication were taken as reference methods. The agreement was measured by sensitivity, specificity and positive predictive value (PPV) across different 10th Revision of International Statistical Classification of Diseases chapters. RESULTS: One thousand three hundred and sixty-five deaths were included. Mortality surveillance data had 82% sensitivity for fact of death and 81% sensitivity for causes of death, with substantial variances across different disease types and reasonable quality for circulatory death (91% sensitivity and 94% PPV). The sensitivity of SmartVA for causes of death was 61%, with reasonable quality for deaths of external causes of morbidity (90% sensitivity). The leading causes of death from different sources were the same with some variances in the fractions. CONCLUSION: Using mortality surveillance data for fact of death in clinical trials need to account for under-reporting. A face-to-face visit to all participants at the completion of trials may be warranted. Neither mortality surveillance data nor SmartVA provided valid data source for endpoint events.

A cross country comparison for the burden of cardiovascular disease attributable to tobacco exposure in China, Japan, USA and world.

BACKGROUND: Tobacco exposure (TE) is the major contributor for CVD mortality, but few published studies on CVD mortality attributable to TE have analyzed the potential reasons underlying long-term trends in China. Our studysought to find the potential reasons and compared CVD mortality attributable to TE in China, Japan, the United States of America (USA), and the world between 1990 and 2017. METHODS: The mortality data in China, Japan, the USA, and the world were obtained from Global Burden of Disease Study 2017(GBD 2017). Joinpoint regression was used to assess the trend magnitude and directions over time for CVD mortality, while the age-period-cohort method was used to analyzethe temporal trends of CVD mortality according to age, period, and cohort. RESULTS: A significant downward trend was found in the age-standardised mortality rate (ASMR) of CVD attributable to smoking in four regions. China had the smallest decline and the Chinese ASMR became the highest in 2017. All the annual net drifts in the four regions were negative and the local drifts were below zero. The longitudinal age curves of CVD mortality attributable to smoking increased in four regions,with China having the largest increase. The period or cohort RRs indicated a decline, and China had the smallest decline. The researchers further analyzed the IHD and stroke trends, finding that the morality and period or cohort RR of IHD in China was always at a high level. CONCLUSIONS: CVD mortality attributable to TE declined in four regions, and was highest in China. The proportion of IHD mortality attributable to TE was similar to stroke, which significantly changed the traditional cognition of CVD composition, but the control measure was not sufficient for IHD in China.

Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS).

The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up.

Caregiver-Delivered Stroke Rehabilitation in Rural China.

Background and Purpose- Stroke disability is a major health burden in rural China where rehabilitation services are inadequate. We aimed to determine the effectiveness of a novel nurse-led, caregiver-delivered model of stroke rehabilitation in rural China. Methods- A multicenter prospective, randomized open, blinded outcome assessed, controlled trial was conducted in 3 rural county hospitals in China: Zhangwu, Liaoning Province (Northeast); Qingtongxia, Ningxia Hui Autonomous Region (Northwest); and Dianjiang, Chongqing Municipality (Southwest). Adult patients (age 18-79 years) with residual disability (Barthel Index score ≤80/100) after a recent acute stroke were randomized to a new service model or usual care. The new intervention was multifaceted and was based on a task-shifting / training-the-trainers model, supported by a custom-designed smartphone application, where patients and caregivers received evidence-based in-hospital education and stroke rehabilitation training (focus on mobility, self-care, and toileting), delivered by trained nurses before hospital discharge, and 3 postdischarge support telephone calls. Outcome assessments were undertaken before hospital discharge and at 3 and 6 months. Primary outcome was physical functioning (Barthel Index scores) at 6 months, assessed by research staff blind to treatment allocation, adjusted for baseline covariates in an intention-to-treat analysis. Secondary outcomes included measures of mobility, health-related quality of life, mood, and caregiver burden. The study included a process evaluation that assessed intervention fidelity. Results- From November 2014 to December 2016, 246 stroke patients were randomized to intervention (n=118) or control (n=128) groups. There was no statistically significant difference in adjusted 6-month Barthel Index scores between groups (70.1 versus 74.1, mean difference, -4.0 [95% CI, -10.0 to 2.9]), nor any differences across the other outcome measures. Process evaluation interviews revealed that the intervention was desirable and positively accepted by nurses, caregivers, and patients but was considered too complex despite efforts to simplify materials for the rural context. Key strategies identified for future studies included the use of community health workers, smartphone application enhancement, and simpler and more frequent training for nurses, caregivers, and patients. Conclusions- A novel nurse-led, digital supported, caregiver-delivered stroke rehabilitation program did not improve patient physical functioning after stroke in rural China. Further stroke rehabilitation research suitable for resource-poor settings is required, with several components being suggested through stakeholder interviews in our study. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02247921.

CB2 cannabinoid receptor agonist ameliorates novel object recognition but not spatial memory in transgenic APP/PS1 mice.

The cannabinoid receptor 2 (CB2R) has been considered as a potential therapeutic target to ameliorate the neuroinflammation and cognitive impairments of Alzheimer's disease (AD). However, there has been little research on the diverse roles of CB2R in regulating different forms of cognitive abilities and underlying neuroinflammatory mechanisms. Thus, the focus of the present study was to investigate the effects of CB2R activation on cognitive abilities, activation and phenotype conversion of microglia, and dendrite complexity. Results showed that CB2R activation normalized the cortex-dependent novel object recognition memory deficit in a novel object recognition test (P < 0.05) and CB2R activation was ineffective for hippocampus-dependent spatial cognitive dysfunction in the Morris water maze test (P > 0.05). Moreover, activation of CB2R did not affect the formation of plaque in either the cortex or hippocampus (P > 0.05). Interestingly, in the cortex but not in the hippocampus of APP/PS1 mice, there was decreased immunofluorescence intensity of Iba1, M1 to M2 microglial phenotype conversion, and restored dendritic complexity after a long treatment period of CB2R agonist (All P < 0.05). Our results demonstrated that CB2R activation exerts a beneficial role in novel object recognition ability concomitant with region-specific regulation in microglia-mediated neuroinflammation and dendritic complexity in AD-model mice.

Dietary Sodium Reduction Reduces Albuminuria: A Cluster Randomized Trial.

OBJECTIVES: The objective of the study was to assess the impact of sustained dietary salt reduction on albuminuria in nearly 2000 community-dwelling adults. DESIGN AND METHODS: The present study is a prespecified secondary analysis of the China Rural Health Initiative Salt Reduction Study cluster randomized trial undertaken in 120 villages in rural China. Villages were randomized to a sodium reduction program of education and access to reduced-sodium salt substitute or control. Urinary albumin-to-creatinine ratio (uACR) and albuminuria (uACR ≥22.1 or 31.0 mg/g for men and women, respectively) were assessed at 18 months in a stratified random sample of predominantly older individuals living in participating rural villages. RESULTS: A total of 2,566 participants from 119 villages provided 1,903 eligible urine samples. The sodium reduction program reduced sodium intake by an equivalent of 0.82g of salt/day (0.06-1.68 g) (322 [24-661] mg sodium/day). The mean uACR was 8.85 (8.05-9.82) mg/g (1.00 [0.91-1.11] mg/mmol) in intervention participants compared with 10.53 (9.73-11.33) mg/g (1.19 [1.10-1.28] mg/mmol) in control participants (p=0.008). The corresponding odds ratio for albuminuria was 0.67 (0.46-0.99). CONCLUSIONS: Dietary sodium reduction was associated with significantly lower uACR and less albuminuria after 18 months. Whether CKD progression can be slowed by dietary sodium reduction should be a global research priority. CLINICALTRIALS.GOV: NCT01259700.

Association between Serum Copeptin and Stroke in Rural Areas of Northern China: A Matched Case-Control Study.

BACKGROUND: Copeptin has been implicated as an effective prognostic biomarker of stroke outcome; however, few studies have investigated whether copeptin could be used as an etiological factor for stroke or not. The aim of our study was to evaluate the association of serum copeptin with stroke. METHODS: In total, 238 participants including 119 cases (87 ischemic stroke and 32 hemorrhagic stroke) and 119 controls were included in this 1 : 1 matched case-control study. Conditional multivariate logistic regression was conducted to assess the Odds Ratios (ORs) and 95% confidence intervals (CI); restricted cubic spline in logistic regression model was used to evaluate the dose-response association between serum copeptin and total stroke, ischemic stroke, and hemorrhagic stroke. RESULTS: The median serum copeptin was 20.90 pmol/L, 20.90 pmol/L, 6.53 pmol/L, and 8.42 pmol/L for total stroke, ischemic stroke, hemorrhagic stroke, and healthy subjects, respectively. The corresponding ORs (95% CIs) for the highest compared with the lowest quartile were 1.23 (0.62-2.44) for total stroke, 4.01 (1.47-10.96) for ischemic stroke, and 0.13 (0.22-0.69) for hemorrhagic stroke. No nonlinear dose-response relationship was found between serum copeptin and total stroke (P nonlinear = 0.278), ischemic stroke (P nonlinear = 0.362), and hemorrhagic stroke (P nonlinear = 0.314). Compared with the reference copeptin level, a significantly increasing trend was found between serum copeptin and ischemic stroke (P overall = 0.002), and a decreasing trend was found between serum copeptin and hemorrhagic stroke (P overall = 0.007). CONCLUSIONS: Elevated serum copeptin levels were positively associated with ischemic stroke and adversely associated with hemorrhagic stroke. Additional prospective studies with larger sample size are needed to confirm the present findings.

Comparing the combination therapy of ezetimibe and atorvastatin with atorvastatin monotherapy for regulating blood lipids: a systematic review and meta-analyse.

BACKGROUND: Although there were many studies reporting the combination therapy of Ezetimibe and Atorvastatin's efficacy and Atorvastatin monotherapy's, the conclusions were controversial. Therefore, a systematic review and meta analysis of combination therapy and monotherapy were conducted. METHODS: PubMed, Cochrane Library and Embase were searched for studies of the combination therapy of Ezetimibe and Atorvastatin and Atorvastatin monotherapy published up to October 20, 2017. Two investigators assessed the articles for eligibility and evaluated quality.The changed values and the efficacy of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Total Cholesterol (TC) and Triglyceride (TG) indicators were the outcomes. Four doses of the comparisons were included: the combination therapy of Ezetimibe (10 mg) and Atorvastatin (10 mg) (E10 + A10) versus Atorvastatin (20 mg) monotherapy (A20); E10 + A10 vs. A10; E10 + A20 vs. A40; E10 + A40 vs. A80. Review manager software 5.1 was used for quality assessment and Stata version 12.0 software was used for statistical analysis. RESULTS: eventeen studies (11 publications) were included in the meta analysis. Compared with Atorvastatin monotherapy, the overall efficacy of combination therapy of Ezetimibe and Atorvastatin on lowering LDL-C (MD = - 15.38, 95% CI: -16.17 to - 14.60; I2 = 26.2%, n = 17), TC (MD = - 9.51, 95% CI: -10.28 to - 8.74; I2 = 33.7%, n = 17) and TG (MD = - 6.42, 95% CI: -7.78 to - 5.06; I2 = 0%, n = 15) and raising HDL-C (MD = 0.95, 95% CI: 0.34 to 1.57; I2 = 0%, n = 17) was significant. The efficacy of the comparison on HDL-C was largely significant for the different doses. CONCLUSIONS: The overall efficacy and subgroup's efficacy of combination therapy of Ezetimibe and Atorvastatin on lowering LDL-C, TC and TG was significantly better than Atorvastatin monotherapy's. The overall and the E10 + A10/A20 group's effectiveness of combination therapy on rasing HDL-C were significantly.

The Association Between ACE2 Gene Polymorphism and the Stroke Recurrence in Chinese Population.

OBJECTIVES: The angiotensin-converting enzyme 2 (ACE2) is closely associated with cardiovascular disease and cerebrovascular disease. Most studies on ACE2 gene polymorphism focused on its relations with cardiovascular disease, but there was a lack of research on its relations with stroke. Our study aimed to explore the association between 4 single-nucleotidepolymorphisms (SNPs) of ACE2 gene polymorphism and stroke recurrence. DESIGN AND PARTICIPANTS: In our study, the case group included 125 stroke patients with recurrence and the control group included 153 patients without recurrence. Four SNPs (rs2106809, rs2285666, rs879922, and rs2074192) were genotyped by Ligase detection reaction. The association between stroke recurrence and SNPs were analyzed by multivariate logistic regression. RESULTS: We find no association between ACE2 gene polymorphism and stroke recurrence. Haplotype A-G-C may associate with the stoke recurrence of male patients. The recurrence risk of male stroke patients with hypertension history and rs2285666-C allele is 2.82 times as high as that of those without hypertension history but with T allele. Among male stroke patients with hypertension history, the recurrence risk of those with rs2285666-C allele is 2.38 times as high as those with T allele; and the recurrence risk of those with rs2106809-A allele is 2.12 times as high as those with G allele. But those recurrence risks lose their statistical significance after adjustment for other factors. CONCLUSIONS: We find no influence of ACE2 gene polymorphism on stroke recurrence and only find possible interaction between hypertension history and the ACE2 gene in male stroke patients.