Differential Sampling of AC Waveforms Based on a Commercial Digital-to-Analog Converter for Reference.

This paper introduces an innovative differential sampling technique for calibrating AC waveforms, leveraging a commercially available 16-bit digital-to-analog converter (DAC) as the reference standard. The novelty of this approach lies in its enhanced stability over traditional direct sampling methods, especially as the frequency of the AC waveform increases. Notably, this technique provides a cost-effective sampler alternative to the differential sampling methods that rely on a programmable Josephson voltage standard (PJVS). A critical aspect of this methodology is the precise measurement of the DAC's output voltage, for which a static measurement strategy is adopted to utilize the exceptional linearity and transfer accuracy of the Keysight 3458A (Santa Rosa, CA, USA) in its standard DCV mode. The differential sampling method has demonstrated good accuracy, achieving a near 1 µV/V agreement with a pulse-driven AC Josephson voltage standard (ACJVS) across a 40 Hz to 200 Hz frequency range. The method attained an expanded uncertainty (k = 2) of 1 part in 106 while measuring a 0.707107 VRMS sine wave at 50 Hz, showcasing its efficacy in precise AC waveform calibration.

Effectiveness of exercise-based cardiac rehabilitation for patients with left ventricular assist device: A systematic review and meta-analysis.

PURPOSE: Exercise-based cardiac rehabilitation (EBCR) improves functional capacity in heart failure (HF). However, data on the effect of EBCR in patients with advanced HF and left ventricular assist devices (LVADs) are limited. This meta-analysis aimed to evaluate the impact of EBCR on the functional ability of LVAD patients by comparing the corresponding outcome indicators between the EBCR and ST groups. METHODS: PubMed, Embase, Clinical Trials, and Cochrane Library databases were searched for studies assessing and comparing the effects of EBCR and standard therapy (ST) in patients following LVAD implantation. Using pre-defined criteria, appropriate studies were identified and selected. Data from selected studies were extracted in a standardized fashion, and a meta-analysis was performed using a fixed-effects model. The protocol was registered on INPLASY (202340073). RESULTS: In total, 12 trials involving 477 patients were identified. The mean age of the participants was 52.9 years, and 78.6% were male. The initiation of EBCR varied from LVAD implantation during the index hospitalization to 11 months post-LVAD implantation. The median rehabilitation period ranged from 2 weeks to 18 months. EBCR was associated with improved peak oxygen uptake (VO2) in all trials. Quantitative analysis was performed in six randomized studies involving 214 patients (EBCR: n = 130, ST: n = 84). EBCR was associated with a significantly high peak VO2 (weighted mean difference [WMD] = 1.64 mL/kg/min; 95% confidence interval [CI], 0.20-3.08; p = .03). Similarly, 6-min walk distance (6MWD) showed significantly greater improvement in the EBCR group than in the ST group (WMD = 34.54 m; 95% CI, 12.47-56.42; p = .002) in 266 patients (EBCR, n = 140; ST, n = 126). Heterogeneity was low among the included trials. None of the included studies reported serious adverse events related to EBCR, indicating the safety of EBCR after LVAD implantation. CONCLUSION: This study demonstrated that EBCR following LVAD implantation is associated with greater improvement in functional capacity compared with ST as reflected by the improved peak VO2 and 6MWD values. Considering the small number of patients in this analysis, further research on the clinical impact of EBCR in LVAD patients is warranted.

Adolescent male rats show altered gut microbiota composition associated with depressive-like behavior after chronic unpredictable mild stress: Differences from adult rats.

Accumulating evidence reveals the metabolism and neurotransmitter systems are different in major depressive disorder (MDD) between adolescent and adult patients; however, much is still unknown from the gut microbiome perspective. To minimize confounding factors such as geographical location, ethnicity, diet, and drugs, we investigated the gut microbial differences between adolescent and adult male Sprague-Dawley rats. We exposed the adolescent rats to chronic unpredictable mild stress (CUMS) for 3 weeks and assessed their behavior using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). We collected and sequenced fecal samples after the behavioral tests and compared them with our previous data on adult rats. Both adolescent and adult CUMS rats exhibited reduced sucrose preference in SPT, reduced total distance in OFT, and increased immobility time in FST. Moreover, compared to their respective controls, the adolescent CUMS rats had distinct amplicon sequence variants (ASVs) mainly in the Muribaculaceae family, Bacteroidetes phylum, while the adult CUMS rats had those in the Lachnospiraceae family, Firmicutes phylum. In the adolescent group, the Muribaculaceae negatively correlated with FST and positively correlated with SPT and OFT. In the adult group, the different genera in the Lachnospiraceae showed opposite correlations with FST. Furthermore, the adolescent CUMS rats showed disrupted microbial functions, such as "Xenobiotics biodegradation and metabolism" and "Immune system", while the adult CUMS rats did not. These results confirmed the gut microbiota differences between adolescent and adult rats after CUMS modeling and provided new insight into the age-related influence on depression models.

Paliperidone Palmitate versus Risperidone Long-Acting Injectable in Patients with Schizophrenia: A Meta-Analysis of Efficacy and Safety.

Purpose: The aim of this study was to assess the efficacy and safety of paliperidone palmitate (PP) treatment compared with risperidone long-acting injectable (LAI) treatments for patients with schizophrenia. Patients and Methods: Data mining was conducted in April 2022 across PubMed, Web of Science, Embase, the Cochrane Library, ClinicalTrials.gov, and PsycINFO. All published randomized controlled trials (RCTs) that assessed the effect of PP treatment for patients with schizophrenia when compared with the risperidone-LAIAs group were included. Relevant data were extracted and synthesized narratively. Results were expressed as standardized mean differences (SMDs) or risk ratios (RRs), with 95% confidence intervals (CIs). Results: Four RCTs with 2451 patients met all the inclusion and exclusion criteria. Efficacy analyses showed no significant statistical differences in Positive and Negative Syndrome Scale (PANSS) total score changes at the endpoint (SMD = 0.10, P = 0.19), or in response rates (RR = 0.93; P = 0.40). Regarding the safety outcomes, PP treatment showed significantly increased risks of discontinuation rates for any reason (35.7% vs 30.4%; RR = 1.19; 95% CI, 1.03 to 1.39; P = 0.02) and nonsignificantly increased risks of total treatment emergent adverse events (TEAEs) (66.6% vs.64.8%; RR = 1.01; 95% CI, 0.94 to 1.09; P = 0.78) compared with the risperidone-LAIAs-treated group. Furthermore, PP may significantly increase total discontinuation rates compared with risperidone-LAIAs. Conclusion: Our meta-analysis did not find a more beneficial effect of PP compared to risperidone-LAIAs treatments for schizophrenia. Clinicians should interpret and translate our data with caution, as the meta-analysis was based on a limited number of randomized controlled trials and patients.

Safety and Effectiveness of a Sequential Suture and Plug Vascular Closure Devices Technique for Large-Bore Access Closure after Percutaneous Endovascular Aneurysm Repair.

PURPOSE: To evaluate the safety and effectiveness of sequential sutures and plugged vascular closure devices (VCDs) for large-bore access closure during percutaneous access endovascular aneurysm repair (PEVAR). MATERIALS AND METHODS: Data on 16 patients who underwent PEVAR at the authors' center from January 2022 to May 2022 were retrospectively reviewed. The median age was 72 years (interquartile range [IQR], 59-75 years), with a male-to-female ratio of 3:1. All patients received sequential suture and plug VCDs using dual Exoseal after 1 Proglide for access closure. Success was defined as the ability to achieve complete hemostasis and was confirmed by ultrasonography. The patients were followed up for access-related adverse events at 30 and 90 days after the procedure, and the severity was graded according to the Society of Interventional Radiology (SIR) classification. RESULTS: Overall, 24 access sites were included. The median sheath size was 21 F (IQR, 18-23 F). The median hemostasis time was 11.0 minutes (IQR, 9.3-13.0 minutes), the median procedural time was 133.5 minutes (IQR, 102.5-151.0 minutes), and the median length of stay was 5 days (IQR, 4.0-6.8 days). The success rate was 95.8%, and a pseudoaneurysm (SIR Grade 2) developed in 1 patient, which was treated by a percutaneous injection of thrombin. No other access-related adverse events occurred, and the total adverse event rate was 4.2%. CONCLUSIONS: Placement of sequential suture and plug VCDs using 1 Proglide and dual Exoseal is a safe and effective method and may be an option for access closure during PEVAR.

The clinical value of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and D-dimer-to-fibrinogen ratio for predicting pneumonia and poor outcomes in patients with acute intracerebral hemorrhage.

Background: This study aimed to investigate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and D-dimer-to-fibrinogen ratio (DFR) as predictors of pneumonia and poor outcomes in patients with acute intracerebral hemorrhage (ICH). Methods: We retrospectively examined patients with acute ICH treated in our institution from May 2018 to July 2020. Patient characteristics, laboratory testing data, radiologic imaging data, and 90-day outcomes were recorded and analyzed. Results: Among the 329 patients included for analysis, 183 (55.6%) developed pneumonia. Systolic blood pressure, initial hematoma volume, D-dimer concentration, NLR, PLR, DFR, and white blood cell, platelet, neutrophil, and lymphocyte counts at admission were significantly higher in patients who developed pneumonia than in those who did not; however, the Glasgow coma scale (GCS) score at admission was significantly lower in pneumonia patients compared with non-pneumonia patients (all P <0.05). Multivariate logistic regression showed that the NLR and PLR were independent predictors of pneumonia, and the NLR and DFR were independent predictors of poor 90-day outcomes (modified Rankin scale score 4-6). Conclusion: The NLR and PLR were independent predictors of pneumonia and the NLR and DFR were independent predictors of poor 90-day outcomes. The NLR, PLR, and DFR can provide prognostic information about acute ICH patients.

Neurotransmitter and Related Metabolic Profiling in the Nucleus Accumbens of Chronic Unpredictable Mild Stress-Induced Anhedonia-Like Rats.

Major depressive disorder (MDD) is a serious mental disorder that affects many people. The neurotransmitter deficiency hypothesis has been the crux of much research on the treatment of depression. Anhedonia, as a core symptom, was closely associated with altered levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and diverse types of glutamate (Glu) receptors in the nucleus accumbens (NAc). However, there were no reports showing how Glu changed in the NAc, and there were other unreported molecules involved in modulating stress-induced anhedonia. Thus, we investigated changes in neurotransmitters and their related metabolites in GABAergic, serotonergic and catecholaminergic pathways in the NAc of a rat model of chronic unpredictable mild stress- (CUMS-) induced anhedonia-like behavior. Then, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to detect target neurotransmitters and related metabolites in the NAc. Finally, the Western blot was used to assess the expression of key enzymes and receptors. Here, we found that the 5-HT level in anhedonia-susceptible (Sus) rats was increased while the Glu level decreased. DA did not show a significant change among CUMS rats. Correspondingly, we detected a reduction in monoamine oxidase-A (MAOA) and Glu receptor 1 levels in anhedonia-Sus rats while Glu receptor 2 (GluR2) and NMDA2B levels were increased in anhedonia-resilient (Res) rats. We also found that the levels of glutamine (Gln), kynurenic acid (Kya), histamine (HA), L-phenylalanine (L-Phe), and tyramine (Tyra) were changed after CUMS. These alterations in neurotransmitters may serve as a new insight into understanding the development of anhedonia-like behavior in depression.

Distribution and possible sources of atmospheric microplastic deposition in a valley basin city (Lanzhou, China).

The deposition is an important process of microplastics transporting from atmosphere to water and soil. But the spatial and temporal distribution of microplastics in urban atmospheric deposition and its influencing factors are poorly understood. The current study investigated the possible sources, spatial and temporal distribution, and potential ecological risk of microplastics in deposition from the valley basin of Lanzhou city during the COVID-19 pandemic (from February to August, 2020). The deposition flux of microplastics was 353.83 n m-2 d-1. Most plastic samples were small sized (50～500 µm) and transparent. The dominant chemical composition and shapes were PET, fragments and fibers, respectively. A modified method was conducted to identify the sources of microplastics, and the local sources were suggested as the main possible sources. The distribution of microplastics investigated through the inverse distance weight interpolation showed spatial variation and temporal differentiation which was dominated by the human activity. The rainfall also affected the temporal distribution. The preliminary assessment indicated higher potential ecological risk of microplastics in deposition. This study suggested the dominant effect of human activity on the source and distribution of atmospheric microplastic deposition in city.

Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway.

BACKGROUND: The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms. METHODS: A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. Behaviors tests were carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), measurement of MDA, SOD, GSH, GSH-PX, T-AOC and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. EX527, a Sirt1 inhibitor and ML385, a Nrf2 inhibitor were injected intraperitoneally 30 min before EDA injection daily. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi (Gpx4)-EGFP infusion. RESULTS: The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. In addition, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage, energy metabolism and pro-inflammatory cytokines activation in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. EX527 abolished the antidepressant effect of EDA as well as the protein levels of Nrf2, HO-1 and Gpx4. Similarly, ML385 reversed the antidepressant and anxiolytic effects of EDA via decreased expressions of HO-1 and Gpx4. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors. CONCLUSION: These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect.

A two-year measurement of methane and nitrous oxide emissions from freshwater aquaculture ponds: Affected by aquaculture species, stocking and water management.

Aquaculture ponds are of increasing worldwide concerns as critical sources of atmospheric methane (CH4) and nitrous oxide (N2O), but little is known about these gases emissions as affected by aquaculture species, stocking and water management in aquaculture ponds. Here, a two-year study was carried out to quantify CH4 and N2O emissions from freshwater crab and fish aquaculture ponds in subtropical China. We further explored how the microbial functional genes [CH4: mcrA and pmoA; N2O: archaeal and bacterial amoA (AOA + AOB), nirS, nirK, nosZ] may drive CH4 and N2O release in the crab aquaculture pond typically undergoing flooding-to-drainage alteration. Over the two-year period, annual CH4 and N2O fluxes averaged 0.95 mg m-2 h-1 and 20.94 µg m-2 h-1 in the fish aquaculture, and 0.78 mg m-2 h-1and 28.48 µg m-2 h-1 in the crab aquaculture, respectively. The direct N2O emission factors were estimated to be 0.77% and 0.36% of the total N input by feed or 1.59 g N2O-N kg-1 and 1.06 g N2O-N kg-1 aquaculture yield in the crab and fish ponds, respectively. Among three functional stocking areas, CH4 and N2O emissions were consistently the highest at the feeding area (FA) in the both aquaculture ponds, followed by at the undisturbed area (UA) and aerated area (AA). The shift in sediment soil moisture from waterlogging to drainage conditions significantly increased the abundance of AOB relative to AOA and pmoA, decreased those of denitrifying functional genes (nirS, nirK, nosZ) and mcrA, while did not alter the functional group ratio of nirS + nirK relative to nosZ. Our results highlight that a better understanding of CH4 and N2O emissions from aquaculture ponds requires taking into consideration of data sourced from more diverse aquaculture systems with different management patterns. In addition, a deep analysis of the microbial processes that drive CH4 and N2O production and consumption from aquaculture ponds remains to be addressed in future studies.

To explore the therapeutic effect of Kangfuxiaomi shuan II on cervicitis in rats.

PURPOSE: The rat cervicitis model was established with 20% phenol glue to explore the therapeutic effect of Kangfuxiaomi shuan II on rat cervicitis and its mechanism. METHODS: After modeling, the rats were treated with Shuangzuotai suppository (37.84 mg/kg), Kangfuxiaoyan shuan (205.6 mg/kg) and Kangfuxiaomi shuan II (40, 80, 160 mg/kg). The histopathological changes and injury degree of cervix in rats were evaluated by vulvar inflammation score and organ index. The therapeutic effect of Kangfuxiaomi shuan II on cervicitis was evaluated by detecting the levels of copper-protein (CP), C-reactive protein (CRP), Rat interleukin 6 (IL-6), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and epidermal growth factor (EGF), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cervical tissue. RESULTS: Compared with the model group, the vulvar inflammation score and cervical index of rats in other groups decreased significantly (P<0.01). Kangfuxiaomi shuan II could significantly reduce the levels of CP, CRP, and MDA in serum of rats with cervicitis, and significantly increase the activity of SOD in serum of rats with cervicitis (P<0.01). The levels of EGF and iNOS in cervical tissue of rats also increased in different degrees, while the level of COX-2 decreased significantly (P<0.01), which significantly improved the pathological degree of vulvar inflammation in rats with cervicitis. CONCLUSIONS: Kangfuxiaomi shuan II has a certain therapeutic effect on cervicitis in rats, and its mechanism may be related to the regulation of inflammatory cytokine network and immunity.

Metro and elderly health in Hong Kong: protocol for a natural experiment study in a high-density city.

INTRODUCTION: Public transport accessible to older people may offer a transformative solution to achieving healthy ageing. However, the evidence to support such transport infrastructure modifications is unclear. Previous studies on public transport use and elderly health were mostly observational studies using cross-sectional data. Few studies have examined the before-and-after effects of a new metro, for example, to see if it leads to improved elderly health. METHODS AND ANALYSIS: We use a new metro line in Hong Kong as a natural experiment to examine the impact of the metro-led public transport intervention on elderly health. In Hong Kong, more than 90% of daily travels are made by public transport. The public transport modifications consist of the new metro line with eight stations and changes in the walking environment and bus services around the stations. We will look at the before-and-after differences in public transport use and health outcomes between elderly participants living in treatment neighbourhoods (400 m walking buffered areas of the new metro stations) and in control groups (living in comparable areas but unaffected by the new metro). Questionnaire-based baseline data were collected in 2019 before the COVID-19 pandemic, while some qualitative interviews are ongoing. Amid the pandemic, we conducted a quick telephone-based survey of COVID-19's potential impact on public transport use behaviours of our elderly cohort in September 2020. Note there is no lockdown in Hong Kong until the writing of the paper (January 2021). After the new metro opens, we will conduct a follow-up survey, tentatively in late 2022. We aim to investigate if the new metro and the associated changes in the built environment have any effects on public transport use behaviours, physical activity and wider health outcomes among the elderly (eg, social inclusion, quality of life, subjective well-being). ETHICS AND DISSEMINATION: The Human Research Ethics Committee of the University of Hong Kong reviewed and approved the study procedures and materials (reference number: EA1710040). Results will be communicated through scientific papers and research reports.

Effect of main family caregiver's anxiety and depression on mortality of patients with moderate-severe stroke.

Anxiety and depression are common mental illness in stroke caregivers, resulting in significant stress to the emotion health of caregivers. Caregivers' emotion can seriously affect the recovery rate of stroke patient, therefore, how to control and affect the caregivers' anxiety and depression is of great importance. Here three multiple centers observation and validation study were performed to screen out the risk factors for development of anxiety and depression in main family caregiver, and the effect of anxiety and depression of family caregivers on 6-month mortality of patients with moderate-severe stroke. The severity of the stroke, the duration of care time and the medical payment associated with increased risk of anxiety and depression. Anxiety and depression of main family caregivers are associated with increased risk 6-month mortality of patients with moderate-severe stroke. Therefore, the support provided to the family caregivers might have positive effect on prognosis of the patients with stroke.

To explore the therapeutic effect of Kangfuxiaomi shuan II on cervicitis in rats

ABSTRACT Purpose: The rat cervicitis model was established with 20% phenol glue to explore the therapeutic effect of Kangfuxiaomi shuan II on rat cervicitis and its mechanism. Methods: After modeling, the rats were treated with Shuangzuotai suppository (37.84 mg/kg), Kangfuxiaoyan shuan (205.6 mg/kg) and Kangfuxiaomi shuan II (40, 80, 160 mg/kg). The histopathological changes and injury degree of cervix in rats were evaluated by vulvar inflammation score and organ index. The therapeutic effect of Kangfuxiaomi shuan II on cervicitis was evaluated by detecting the levels of copper-protein (CP), C-reactive protein (CRP), Rat interleukin 6 (IL-6), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and epidermal growth factor (EGF), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cervical tissue. Results: Compared with the model group, the vulvar inflammation score and cervical index of rats in other groups decreased significantly (P<0.01). Kangfuxiaomi shuan II could significantly reduce the levels of CP, CRP, and MDA in serum of rats with cervicitis, and significantly increase the activity of SOD in serum of rats with cervicitis (P<0.01). The levels of EGF and iNOS in cervical tissue of rats also increased in different degrees, while the level of COX-2 decreased significantly (P<0.01), which significantly improved the pathological degree of vulvar inflammation in rats with cervicitis. Conclusions: Kangfuxiaomi shuan II has a certain therapeutic effect on cervicitis in rats, and its mechanism may be related to the regulation of inflammatory cytokine network and immunity.

miR-103a-3p alleviates oxidative stress, apoptosis, and immune disorder in oxygen-glucose deprivation-treated BV2 microglial cells and rats with cerebral ischemia-reperfusion injury by targeting high mobility group box 1.

BACKGROUND: Cerebral ischemia-reperfusion injury (CI/R) is among the most common diseases affecting the central nervous system. Due to the poor efficacy and adverse side effects of the drugs used to treat CI/R in clinical trials, a new treatment strategy is urgently needed. In this study, we aimed to investigate whether miR-103a-3p alleviates CI/R in vivo and vitro and to explore the relevant mechanisms. METHODS: BV2 microglial cells underwent oxygen-glucose deprivation (OGD) treatment to imitate the pathophysiology of CI/R in vitro. A middle cerebral artery occlusion (MCAO) rat model was established to imitate the pathophysiology of CI/R in vivo. The expression levels of miR-103a-3p and HMGB1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, enzyme-linked immunosorbent assay (ELISA), and hematoxylin and eosin (H&E) and Nissl staining were used to evaluated apoptosis, oxidative stress, inflammatory response, and histopathology, respectively. RESULTS: OGD-stimulated BV2 microglial cells and brain tissues with CI/R had low expression of miR-103a-3p but high expression of high mobility group box 1 (HMGB1). As expected, miR-103a-3p and HMGB1 had a targeting relationship. Overexpression of HMGB1 enhanced the the levels of interleukin (IL)-1 beta, tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA), but reduced the content of superoxide dismutase (SOD), IL-4, and IL-10, in vitro. Moreover, high expression of HMGB1 aggravated the brain injury of the model rats, and increased the secretion of inflammatory factors, exacerbated oxidative stress, and further induced tissue apoptosis in the brain tissue. Importantly, these effects of HMGB1 overexpression were partly reversed by miR-103a-3p overexpression on HMGB1 interference. CONCLUSIONS: HMGB1 is targeted by miR-103a-3p, which may be a new strategy in the treatment of CI/R.

New metro system and active travel: A natural experiment.

BACKGROUND: We used the first metro system in a developing city as a natural experiment to investigate the causal inference in the new metro's impact on modal shift and active travel. MATERIAL AND METHODS: The treatment group was formed by residents from neighbourhoods located within the 800-m walking distance to new metro stations. The first control group was formed by residents lived 1.6 km away from and outside of walking distance to the nearest station, and the second was 5 km away and outside of cycling distance. The groups were determined by local transit-oriented planning practice and empirical studies on active travel. Of the 5627 participants who had finished a baseline travel behaviour survey before new metro launched, 1770 returned and completed the follow-up survey a year after the metro's operation, which consists of 833 cohort participants in the treatment group and 937 in the two types of control groups. We used a difference-in-difference method to make before and after comparisons of travel behaviour changes between treatment and control groups. RESULTS: Our longitudinal data analyses revealed diverse travel behaviour changes. In general, people who used to take bus have adopted metro. The average metro usage was 30.9 (28.8-33.3) minutes daily for work trips and 16.6 (14.9-18.7) minutes daily for non-work trips. Walking time decreased 19.7 minutes at most (p < 0.001), and cycling decreased 22.1 minutes daily (p < 0.001). Car and e-bike usages remained largely unchanged before and after new metro, without difference between treatment and control groups. CONCLUSION: The natural experiment study provided the first empirical evidence in a developing city context on causal inference in new metro's impact on active travel. A new metro does not necessarily promote active travel increase or car use reduction, calling for caution in making general assumptions about the effects of urban rail transit investments. We suggest local urban and transport planning knowledge could be useful in designing and explaining the complex natural experiments in transport and health.

Efficacy and Acceptability of Cariprazine in Acute Exacerbation of Schizophrenia: Meta-Analysis of Randomized Placebo-Controlled Trials.

PURPOSE: The purpose of this study was to assess the efficacy and acceptability of cariprazine treatment in acute exacerbation of schizophrenia. METHODS: This review included randomized controlled trials of patients with acute exacerbation of schizophrenia in relation to efficacy and acceptability. The efficacy outcomes were assessed by pooling standardized mean differences (SMDs) calculated from the difference in the reduction in the mean of the Positive and Negative Syndrome Scale (PANSS) total score, PANSS positive and negative scores, and response rate. The primary acceptability outcomes were determined by pooling the risk ratios (RRs) of discontinuation for any reason, the incidence of serious adverse events, and treatment emergent events. FINDINGS: Four randomized controlled trials consisting of 1843 patients met all inclusion and exclusion criteria. Efficacy analysis showed significant positive effects in relation to cariprazine therapy (SMD: -0.37, P < 0.00001 for PANSS total score change; SMD: -0.32, P < 0.00001 for PANSS positive score change; SMD: -0.32, P < 0.0001 for PANSS negative score change; RR, 1.41; 95% confidence interval [CI], 1.19-1.67; P < 0.0001 for response rate). For primary acceptability outcomes, less patients taking cariprazine discontinued treatment for any reason compared with patients receiving placebo (RR, 0.90; 95% CI, 0.78-1.04; P = 0.16). Significantly less patients on cariprazine had serious adverse events during the double-blind treatment period compared with patients taking placebo (RR, 0.55; 95% CI, 0.34-0.89; P = 0.01). Significantly more patients on cariprazine had treatment emergent events compared with those receiving placebo (RR, 1.10; 95% CI, 1.03-1.18; P = 0.006). IMPLICATIONS: Results suggest that cariprazine may be an effective and acceptable treatment for schizophrenia and future research is warranted.

ox-LDL induces endothelial dysfunction by promoting Arp2/3 complex expression.

Oxidized low-density lipoproteins (ox-LDL) play a critical role in endothelial injury including cytoskeleton reorganization, which is closely related to actin-related protein 2/3 (Arp2/3) complex. The aim of this study was to investigate the role of Arp2/3 complex in ox-LDL-induced endothelial dysfunction. In this study, we found that Arp2 and Arp3 expression was increased under atherosclerotic conditions both in ApoE-/- mice and in ox-LDL-stimulated human coronary artery endothelial cells (HCAECs). Arp2/3 complex inhibitor CK666 significantly reduced ox-LDL-induced ROS generation and cytoskeleton reorganization, and increased NO release in HCAECs. Pretreatment with LOX-1- but not CD36-blocking antibody markedly decreased ox-LDL-induced Arp2 and Arp3 expression. Moreover, Rac-1 siRNA remarkably suppressed ox-LDL-stimulated Arp2 and Arp3 expression. Additionally, CK666 reduced endothelial nitric oxide synthase (eNOS) expression and atherosclerotic lesions in ApoE-/- mice. Collectively, ox-LDL induces endothelial dysfunction by activating LOX-1/Rac-1 signaling and upregulating Arp2/3 complex expression.