The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy.

Intervertebral disc degeneration (IVDD) is an aging disease that results in a low quality of life and heavy socioeconomic burden. The mitochondrial unfolded protein response (UPRmt) take part in various aging-related diseases. Our research intents to explore the role and underlying mechanism of UPRmt in IVDD. Nucleus pulposus (NP) cells were exposed to IL-1ß and nicotinamide riboside (NR) served as UPRmt inducer to treat NP cells. Detection of ATP, NAD + and NADH were used to determine the function of mitochondria. MRI, Safranin O-fast green and Immunohistochemical examination were used to determine the degree of IVDD in vivo. In this study, we discovered that UPRmt was increased markedly in the NP cells of human IVDD tissues than in healthy controls. In vitro, UPRmt and mitophagy levels were promoted in NP cells treated with IL-1ß. Upregulation of UPRmt by NR and Atf5 overexpression inhibited NP cell apoptosis and further improved mitophagy. Silencing of Pink1 reversed the protective effects of NR and inhibited mitophagy induced by the UPRmt. In vivo, NR might attenuate the degree of IDD by activating the UPRmt in rats. In summary, the UPRmt was involved in IVDD by regulating Pink1-induced mitophagy. Mitophagy induced by the UPRmt might be a latent treated target for IVDD.

Effects of typical marine environmental factors on the bioluminescence intensity of individual Noctiluca scintillans.

Red Noctiluca scintillans (RNS) is one of the major red tide species and dominant bioluminescent plankton in the global offshore. Bioluminescence offers a number of applications for ocean environment assessments such as interval waves study, fish stocks evaluation and underwater target detection making it of significant interest in forecasting bioluminescence occurrence and intensity. RNS is susceptible to changes in marine environmental factors. However, the effects of marine environmental factors on the bioluminescent intensity (BLI, photon s-1) of individual RNS cells (IRNSC) is poorly known. In this study, the effects of temperature, salinity and nutrients on the BLI were studied by field and laboratory culture experiments. In the field experiments, bulk BLI was measured by an underwater bioluminescence assessment tool at various temperature, salinity and nutrient concentrations. To exclude the contribution by other bioluminescent planktons, an identification method of IRNSC was first developed using the features of the bioluminescence flash kinetics (BFK) curve of RNS to identify and extract BLI emitted by an individual RNS cell. To decouple the effects of each environmental factor, laboratory culture experiments were conducted to examine the effects of a single factor on the BLI of IRNSC. The field experiments showed that BLI of IRNSC negatively correlated with temperature (3-27°C) and salinity (30-35‰). The logarithmic BLI can be well fitted using a linear equation with temperature or salinity with Pearson correlation coefficients of -0.95 and -0.80, respectively. The fitting function with salinity was verified by the laboratory culture experiment. On the other hand, no significant correlation was observed between BLI of IRNSC and nutrients. These relationships could be used in the RNS bioluminescence prediction model to improve the prediction accuracy of bioluminescent intensity and spatial distribution.

Effect of China's long-term care insurance on health outcomes of older disabled people: role of institutional care.

Since the public long-term care insurance (LTCI) system was piloted in Chengdu, China, in October 2017, there has been considerable growth of LTC institutions in China. This study aimed to evaluate the health value effect of LTCI in older patients with severe disabilities in an LTC institution. This prospective study was based on data from 985 severe disability patients with or without LTCI from October 2017 to May 2021 in the Eighth People's Hospital, Chengdu, China. The Cox proportional hazard model estimated LTCI's health value, including survival probability and risk of pneumonia/pressure ulcers. Subgroup analysis was performed for sex, age, Charlson Comorbidity Index (CCI), and the number of drugs. In the analysis, 519 and 466 patients in LTCI and non-LTCI groups were included, respectively. In adjusted Cox analyses, the LTCI group had a significantly elevated survival rate compared with the non-LTCI groups at 12 months (P < .001, hazard ratio (HR) = 1.758, 95% confidence interval (CI) 1.300-2.376). At 40 months, the adjusted survival rate was 62.6% in the LTCI group, which was significantly higher (53.7%; P = .003, HR = 1.438, 95% CI 1.131-1.831). The subgroups of patients aged 60 to 79 years (interaction P = .007) and with CCI ≥ 3 (interaction P = .026) were more significantly associated with survival improvement than those aged >80 years and with CCI< 3. The LTCI group was also at lower risk for hospital-acquired pneumonia (P = .016, HR 0.622, 95% CI 0.422-0.917) and pressure ulcers (P = .008, HR 0.695, 95% CI 0.376-0.862). The improved survival of LTCI remained stable in sensitivity analyses. For older patients with severe disabilities, in a LTC institution, LTCI significantly improved their health profile and longevity after a year, suggesting the large role and development potentiality of institution care in the LTCI system of China.

Plantamajoside attenuates cardiac fibrosis via inhibiting AGEs activated-RAGE/autophagy/EndMT pathway.

Advanced glycation end products (AGEs) have been identified to transduce fibrogenic signals via inducing the activation of their receptor (RAGE)-mediated pathway. Recently, disrupting AGE-RAGE interaction has become a promising therapeutic strategy for chronic heart failure (CHF). Endothelial-to-mesenchymal transition (EndMT) is close to the cardiac fibrosis pathological process. Our previous studies have demonstrated that knockout RAGE suppressed the autophagy-mediated EndMT, and thus alleviated cardiac fibrosis. Plantamajoside (PMS) is the major bioactive compound of Plantago Asiatica, and its activity of anti-fibrosis has been documented in many reports. However, its effect on CHF and the underlying mechanism remains elusive. Thus, we tried to elucidate the protective role of PMS in CHF from the viewpoint of the AGEs/RAGE/autophagy/EndMT axis. Herein, PMS was found to attenuate cardiac fibrosis and dysfunction, suppress EndMT, reduce autophagy levels and serum levels of AGEs, yet did not affect the expression of RAGE in CHF mice. Mechanically, PMS possibly binds to the V-domain of RAGE, which is similar to the interaction between AGEs and RAGE. Importantly, this competitive binding disturbed AGEs-induced the RAGE-autophagy-EndMT pathway in vitro. Collectively, our results indicated that PMS might exert an anti-cardiac fibrosis effect by specifically binding RAGE to suppress the AGEs-activated RAGE/autophagy/EndMT pathway.

The mediating effect of psychological empowerment on the relationship between work environment and clinical decision-making among midwives: a multicentre cross-sectional study.

BACKGROUND: Clinical decision-making is considered an essential behaviour in clinical practice. However, no research has been done to examine the associations among midwives' clinical decision-making, work environment and psychological empowerment. Thus, this study aimed to determine the influence of work environment on midwives' clinical decision-making and confirm the mediating role of psychological empowerment. METHOD: This study was designed as a multicentre cross-sectional study, and included 602 registered midwives from 25 public hospitals in China. A sociodemographic questionnaire, Work Environment Scale, Psychological Empowerment Scale and Clinical decision-making Scale were applied. A structural equation model was conducted to estimate the hypothesis model of the clinical decision-making among midwives and explore the potential mediating mechanism of midwives' clinical decision-making. This model was employed maximum likelihood estimation method and bootstrapping to examine the statistical significance. RESULTS: The mean score of clinical decision-making among midwives was 143.03 ± 14.22, at an intermediate level. The data of this hypothesis model fitted well, and the results showed that work environment positively affected psychological empowerment, which in turn positively affected clinical decision-making; psychological empowerment partly mediated the relationship between work environment and clinical decision-making among midwives. CONCLUSIONS: Midwives' clinical decision-making could be promoted directly or indirectly by providing a healthy work environment and improving psychological empowerment. It is essential for hospital managers to pay attention to the assessment of the midwives' work environment and actively improve it, such as establishing a supportive, fair and just workplace, and maintaining effective communication with midwives. Furthermore, managers can also promote midwives' clinical decision-making behaviour by enhancing their psychological empowerment via enhancing job autonomy.

[Cangxi Tongbi Capsules promote chondrocyte autophagy by regulating circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit development of knee osteoarthritis].

To investigate the mechanism by which Cangxi Tongbi Capsules promote chondrocyte autophagy to inhibit knee osteoarthritis(KOA) progression by regulating the circRNA＿0008365/miR-1271/p38 mitogen-activated protein kinase(MAPK) pathway. The cell and animal models of KOA were established and intervened with Cangxi Tongbi Capsules, si-circRNA＿0008365, si-NC, and Cangxi Tongbi Capsules combined with si-circRNA＿0008365. Flow cytometry and transmission electron microscopy were employed to determine the level of apoptosis and observe autophagosomes, respectively. Western blot was employed to reveal the changes in the protein levels of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ, Beclin-1, selective autophagy junction protein p62/sequestosome 1, collagen Ⅱ, a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS-5), and p38 MAPK. The mRNA levels of circRNA＿0008365, miR-1271, collagen Ⅱ, and ADAMTS-5 were determined by qRT-PCR. Hematoxylin-eosin staining was employed to reveal the pathological changes of the cartilage tissue of the knee, and enzyme-linked immunosorbent assay to measure the levels of interleukin-1ß(IL-1ß) and tumor necrosis factor-alpha(TNF-α). The chondrocytes treated with IL-1ß showed down-regulated expression of circRNA＿0008365, up-regulated expression of miR-1271 and p38 MAPK, lowered autophagy level, increased apoptosis rate, and accelerated catabolism of extracellular matrix. The intervention with Cangxi Tongbi Capsules up-regulated the expression of circRNA＿0008365, down-regulated the expression of miR-1271 and p38 MAPK, increased the autophagy level, decreased the apoptosis rate, and weakened the catabolism of extracellular matrix. However, the effect of Cangxi Tongbi Capsules was suppressed after interfering with circRNA＿0008365. The in vivo experiments showed that Cangxi Tongbi Capsules dose-dependently inhibited the p38 MAPK pathway, enhanced chondrocyte autophagy, and mitigated articular cartilage damage and inflammatory response, thereby inhibiting the progression of KOA in rats. This study indicated that Cangxi Tongbi Capsules promoted chondrocyte autophagy by regulating the circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit the development of KOA.

[A new xanthone from hulls of Garcinia mangostana and its cytotoxic activity].

Eight compounds were isolated from ethyl acetate fraction of 80% ethanol extract of the hulls of Garcinia mangostana by silica gel, Sephadex LH-20 column chromatography, as well as prep-HPLC methods. By HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the eight compounds were identified as 16-en mangostenone E(1), α-mangostin(2), 1,7-dihydroxy-2-(3-methy-lbut-2-enyl)-3-methoxyxanthone(3), cratoxyxanthone(4), 2,6-dimethoxy-para-benzoquinone(5), methyl orselinate(6), ficusol(7), and 4-(4-carboxy-2-methoxyphenoxy)-3,5-dimethoxybenzoic acid(8). Compound 1 was a new xanthone, and compound 4 was a xanthone dimer, compound 5 was a naphthoquinone. All compounds were isolated from this plant for the first time except compounds 2 and 3. Cytotoxic bioassay suggested that compounds 1, 2 and 4 possessed moderate cytotoxicity, suppressing HeLa cell line with IC_(50) va-lues of 24.3, 35.5 and 17.1 µmol·L~(-1), respectively. Compound 4 also could suppress K562 cells with an IC_(50) value of 39.8 µmol·L~(-1).

The VLPFC versus the DLPFC in Downregulating Social Pain Using Reappraisal and Distraction Strategies.

The dorsolateral prefrontal cortex (DLPFC) and ventrolateral PFC (VLPFC) are both crucial structures involved in voluntary emotional regulation. However, it remains unclear whether the functions of these two cortical regions that are involved in emotional regulation, which are usually active in non-social situations, could be generalized to the regulation of social pain as well. This study employed transcranial magnetic stimulation (TMS) to examine the causal relationship between the DLPFC/VLPFC and the emotional regulation of social pain via distraction and reappraisal. Ninety human participants (45 males and 45 females) initially underwent either active (DLPFC/VLPFC, n = 30/30) or sham (vertex, n = 30) TMS sessions. Participants were then instructed to use both distraction and reappraisal strategies to downregulate any negative emotions evoked by social exclusion pictures. Convergent results of the subjective emotional rating and electrophysiological indices demonstrated that: (1) both the DLPFC and VLPFC highly facilitate the downregulation of affective responses caused by social exclusion, revealing a causal role of these lateral PFCs in voluntary emotional regulation of both non-social and social pain; and (2) these two cortical regions showed relative functional specificity for distraction (DLPFC) and reappraisal (VLPFC) strategies, which helps to refine the cortical targeting of therapeutic protocols. In addition, the TMS effect was sustainable for at least 1 h, showcasing the potential feasibility of using this method in clinical practice. Together, these findings provide cognitive and neural evidence for the targeting of the VLPFC and/or the DLPFC to improve emotional regulation abilities, especially in social contexts.SIGNIFICANCE STATEMENT This study aimed to examine the role of the dorsolateral prefrontal cortex (DLPFC) and ventrolateral PFC (VLPFC) in emotional regulation, particularly in response to social pain through the use of distraction and reappraisal strategies, as this is a relatively underexplored area of inquiry. This study makes a significant contribution to the literature because our results provide novel empirical information on the role of these cortical structures in the processing of negative emotions elicited within certain social contexts. As such, our findings have potential clinical implications, paving the way for future clinicians to be able to accurately target specific brain regions among patients struggling with impaired social cognition abilities, including those diagnosed with posttraumatic stress disorder, autism spectrum disorder, social anxiety disorder, and depression.

Differentiating the abnormalities of social and monetary reward processing associated with depressive symptoms.

BACKGROUND: Reward dysfunction is a major dimension of depressive symptomatology, but it remains obscure if that dysfunction varies across different reward types. In this study, we focus on the abnormalities in anticipatory/consummatory processing of monetary and social reward associated with depressive symptoms. METHODS: Forty participants with depressive symptoms and forty normal controls completed the monetary incentive delay (MID) and social incentive delay (SID) tasks with event-related potential (ERP) recording. RESULTS: In the SID but not the MID task, both the behavioral hit rate and the ERP component contingent negative variation (CNV; indicating reward anticipation) were sensitive to the interaction between the grouping factor and reward magnitude; that is, the depressive group showed a lower hit rate and a smaller CNV to large-magnitude (but not small-magnitude) social reward cues compared to the control group. Further, these two indexes were correlated with each other. Meanwhile, the ERP components feedback-related negativity and P3 (indicating reward consumption) were sensitive to the main effect of depression across the MID and SID tasks, though this effect was more prominent in the SID task. CONCLUSIONS: Overall, we suggest that depressive symptoms are associated with deficits in both the reward anticipation and reward consumption stages, particularly for social rewards. These findings have a potential to characterize the profile of functional impairment that comprises and maintains depression.

Altered motivation of effortful decision-making for self and others in subthreshold depression.

BACKGROUND: Amotivation is a typical feature in major depressive disorders and refers to individuals exhibiting reduced willingness to exert effort for rewards. However, the motivation pattern when deciding whether to exert effort for self versus others in people with depression remains unclear. METHODS: We conducted a functional magnetic resonance imaging study and employed an adapted Effort-Expenditure for Rewards Task in subthreshold depressive (SD) participants (n = 33) and healthy controls (HC) (n = 32). This required participants to choose between a fixed low-effort/low-reward and a variable high-effort/high-reward option, and then immediately exert effort to obtain corresponding rewards for themselves or for unfamiliar people. RESULTS: Compared with the HC group, the SD group showed blunted activity in the left dorsal anterior cingulate cortex/dorsomedial prefrontal cortex, bilateral anterior insula (AI), and right putamen-left dorsolateral prefrontal cortex functional connectivity when choosing to exert effort for themselves. Additionally, the SD group exhibited increased willingness and greater activation in the bilateral AI when choosing to exert effort for others. Furthermore, these brain activations and functional connectivity were positively related to self-reported motivation. CONCLUSIONS: These findings show altered motivation during effort-based decision-making in individuals with the mild depressive state, particularly with higher motivation for others. Thus, this suggests that motivational behaviors and prefrontal-striatal circuitry are altered in individuals with SD, which can be utilized to discover treatment targets and develop strategies to address mental illness caused by motivation disorders.

Probiotics for preventing acute upper respiratory tract infections.

BACKGROUND: Probiotics are live micro-organisms that may give a beneficial physiological effect when administered in adequate amounts. Some trials show that probiotic strains can prevent respiratory infections. Even though our previously published review showed the benefits of probiotics for acute upper respiratory tract infections (URTIs), several new studies have been published. This is an update of a review first published in 2011 and updated in 2015. OBJECTIVES: To assess the effectiveness and safety of probiotics (any specified strain or dose), compared with placebo or no treatment, in the prevention of acute URTIs in people of all ages, at risk of acute URTIs. SEARCH METHODS: We searched CENTRAL (2022, Issue 6), MEDLINE (1950 to May week 2, 2022), Embase (1974 to 10 May 2022), Web of Science (1900 to 10 May 2022), the Chinese Biomedical Literature Database, which includes the China Biological Medicine Database (from 1978 to 10 May 2022), the Chinese Medicine Popular Science Literature Database (from 2000 to 10 May 2022), and the Master's Degree Dissertation of Beijing Union Medical College Database (from 1981 to 10 May 2022). We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials on 10 May 2022. SELECTION CRITERIA: We included individual randomised controlled trials (RCTs) and cluster-RCTs comparing probiotics with placebo or no treatment to prevent acute URTIs. The participants were children, adults, or the elderly in the community, care facilities, schools, or hospitals. Our main outcomes were the number of participants diagnosed with URTIs (at least one event and at least three events), the incidence rate (number of cases/person year) of acute URTIs, and the mean duration of an episode of URTIs. Our secondary outcomes were the number of participants who were absent from childcare centre, school, or work due to acute URTIs; the number of participants who used prescribed antibiotics for acute URTIs; and the number of participants who experienced at least one adverse event from probiotics. We excluded studies if they did not specify acute respiratory infections as 'upper'; studies with more than 50% of participants vaccinated against influenza or other acute URTIs within the last 12 months; and studies with significantly different proportions of vaccinated participants between the probiotics arm and the placebo or no treatment arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of trials and extracted data using standard Cochrane methodological procedures. We analysed both intention-to-treat and per-protocol data and used a random-effects model. We expressed results as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, both with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 23 individual RCTs and one cluster-RCT. As one of the individual RCTs did not report outcomes in a usable way, we could only meta-analyse data from 23 trials, involving a total of 6950 participants including children (aged from one month to 11 years old), adults (mean age 37.3), and older people (mean age 84.6 years). One trial reported 22.5% flu-vaccine participants within the last 12 months, and 25.4% flu-vaccine participants during the intervention. Probiotics were more likely to be given with milk-based food in children; administered in powder form in adults; and given with milk-based food or in capsules in the elderly. Most of the studies used one or two strains (e.g. Lactobacillus plantarum HEAL9, Lactobacillus paracasei (8700:2 or N1115)) and 109 or 1011 colony-forming units (CFU)/day of probiotics for more than three months. We found that probiotics may reduce the number of participants diagnosed with URTIs (at least one event) (RR 0.76, 95% CI 0.67 to 0.87; P < 0.001; 16 studies, 4798 participants; low-certainty evidence); likely reduce the number of participants diagnosed with URTIs (at least three events) (RR 0.59, 95% CI 0.38 to 0.91; P = 0.02; 4 studies, 763 participants; moderate-certainty evidence); may reduce the incidence rate (number of cases/person year) of URTIs (rate ratio 0.82, 95% CI 0.73 to 0.92, P = 0.001; 12 studies, 4364 participants; low-certainty evidence); may reduce the mean duration of an episode of acute URTIs (MD -1.22 days, 95% CI -2.12 to -0.33; P = 0.007; 6 studies, 2406 participants; low-certainty evidence); likely reduce the number of participants who used prescribed antibiotics for acute URTIs (RR 0.58, 95% CI 0.42 to 0.81; P = 0.001; 6 studies, 1548 participants; moderate-certainty evidence); and may not increase the number of participants who experienced at least one adverse event (RR 1.02, 95% CI 0.90 to 1.15; P = 0.79; 8 studies, 2456 participants; low-certainty evidence). Evidence showing a decrease in the number of people absent from childcare centre, school, or work due to acute URTIs with probiotics is very uncertain (RR 0.14, 95% CI 0.03 to 0.59; 1 study, 80 participants; very low-certainty evidence). Adverse events from probiotics were minor, and most commonly gastrointestinal symptoms, such as vomiting, flatulence, diarrhoea, and bowel pain.  AUTHORS' CONCLUSIONS: Overall, we found that probiotics were better than placebo or no treatment in preventing acute URTIs.

Association of sleep duration with sarcopenic obesity in multi-ethnic older adults: findings from the WCHAT Study.

OBJECTIVE: Sarcopenic obesity is a prevalent geriatric syndrome, characterized by concurrence of sarcopenia and obesity. Sleep duration is linked to both obesity and sarcopenia. However, little was known regarding the association of sleep duration with sarcopenic obesity. In this study, we aimed to examine the association of sleep duration with sarcopenic obesity in multi-ethnic community-dwelling older adults. METHODS: Sarcopenia was defined according to the criteria established by Asian Working Group for Sarcopenia (AWGS) 2019. Obesity was defined as body fat percentage above the 60th percentile specified by sex. Sarcopenic obesity was defined as concurrence of obesity and sarcopenia. Sleep duration was collected by a self-reported questionnaire and was further divided into 5 groups: "<6 h", "6-7 h", "7-8 h", "8-9 h" (reference group) and "≥9 h" (long sleep). Logistic regressions were adopted to examine the association. RESULTS: 2256 multi-ethnic adults aged 60 and over from the West China Health and Aging Trend (WCHAT) study were involved for present study. Overall, 6.25% of the participants were classified as sarcopenic obesity. In the fully adjusted model, long sleep duration (≥ 9 h) was significantly associated with sarcopenic obesity compared with reference group (OR = 1.81, 95%CI = 1.10-2.98, P = 0.019). However, in subgroup analysis, this association can only be observed in male (OR 1.98, 95% CI = 1.02-3.87, P = 0.043) not in female (OR = 1.83, 95%CI = 0.85-3.94, P = 0.118). Regarding ethnic difference, Han older adults with long sleep duration (≥ 9 h) presented increased risk of sarcopenic obesity while ethnic minorities did not. CONCLUSION: This study disclosed that long sleep duration significantly increased the risk of sarcopenic obesity among older adults. And our findings highlight the critical role of assessing sleep duration to identify individuals at risk of sarcopenic obesity.

Thrombolytic therapy for pulmonary embolism.

BACKGROUND: Thrombolytic therapy is usually reserved for people with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve blood clots more rapidly than heparin and may reduce the death rate associated with PE. However, there are still concerns about the possible risk of adverse effects of thrombolytic therapy, such as major or minor haemorrhage. This is the fourth update of the Cochrane review first published in 2006. OBJECTIVES: To assess the effects of thrombolytic therapy for acute pulmonary embolism. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 August 2020. We undertook reference checking to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared thrombolytic therapy followed by heparin versus heparin alone, heparin plus placebo, or surgical intervention for people with acute PE (massive/submassive). We did not include trials comparing two different thrombolytic agents or different doses of the same thrombolytic drug. DATA COLLECTION AND ANALYSIS: Two review authors (ZZ, QH) assessed the eligibility and risk of bias of trials and extracted data. We calculated effect estimates using the odds ratio (OR) with a 95% confidence interval (CI) or the mean difference (MD) with a 95% CI. The primary outcomes of interest were death, recurrence of PE and haemorrhagic events. We assessed the certainty of the evidence using GRADE criteria. MAIN RESULTS: We identified three new studies for inclusion in this update. We included 21 trials in the review, with a total of 2401 participants. No studies compared thrombolytics versus surgical intervention. We were not able to include one study in the meta-analysis because it provided no extractable data. Most studies carried a high or unclear risk of bias related to randomisation and blinding. Meta-analysis showed that, compared to control (heparin alone or heparin plus placebo), thrombolytics plus heparin probably reduce both the odds of death (OR 0.58, 95% CI 0.38 to 0.88; 19 studies, 2319 participants; low-certainty evidence), and recurrence of PE (OR 0.54, 95% CI 0.32 to 0.91; 12 studies, 2050 participants; low-certainty evidence). Effects on mortality weakened when six studies at high risk of bias were excluded from analysis (OR 0.71, 95% CI 0.45 to 1.13; 13 studies, 2046 participants) and in the analysis of submassive PE participants (OR 0.61, 95% CI 0.37 to 1.02; 1993 participants). Effects on recurrence of PE also weakened after removing one study at high risk of bias for sensitivity analysis (OR 0.60, 95% CI 0.35 to 1.04; 11 studies, 1949 participants). We downgraded the certainty of evidence to low because of 'Risk of bias' concerns. Major haemorrhagic events were probably more common in the thrombolytics group than in the control group (OR 2.84, 95% CI 1.92 to 4.20; 15 studies, 2101 participants; moderate-certainty evidence), as were minor haemorrhagic events (OR 2.97, 95% CI 1.66 to 5.30; 13 studies,1757 participants; low-certainty evidence). We downgraded the certainty of the evidence to moderate or low because of 'Risk of bias' concerns and inconsistency. Haemorrhagic stroke may occur more often in the thrombolytics group than in the control group (OR 7.59, 95% CI 1.38 to 41.72; 2 studies, 1091 participants). Limited data indicated that thrombolytics may benefit haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment, echocardiograms, pulmonary hypertension, coagulation parameters, composite clinical outcomes, need for escalation and survival time to a greater extent than heparin alone. However, the heterogeneity of the studies and the small number of participants involved warrant caution when interpreting results. The length of hospital stay was shorter in the thrombolytics group than in the control group (mean difference (MD) -1.40 days, 95% CI -2.69 to -0.11; 5 studies, 368 participants). Haemodynamic decompensation may occur less in the thrombolytics group than in the control group (OR 0.36, 95% CI 0.20 to 0.66; 3 studies, 1157 participants). Quality of life was similar between the two treatment groups. None of the included studies provided data on post-thrombotic syndrome or on cost comparison. AUTHORS' CONCLUSIONS: Low-certainty evidence suggests that thrombolytics may reduce death following acute pulmonary embolism compared with heparin (the effectiveness was mainly driven by one trial with massive PE). Thrombolytic therapy may be helpful in reducing the recurrence of pulmonary emboli but may cause more major and minor haemorrhagic events, including haemorrhagic stroke. More studies of high methodological quality are needed to assess safety and cost effectiveness of thrombolytic therapy for people with pulmonary embolism.

MeCP2 inhibits proliferation and migration of breast cancer via suppression of epithelial-mesenchymal transition.

Methyl-CpG-binding protein 2 (MeCP2) is an important epigenetic regulator for normal neuronal maturation and brain glial cell function. Additionally, MeCP2 is also involved in a variety of cancers, such as breast, prostate, lung, liver and colorectal. However, whether MeCP2 contributes to the progression of breast cancer remains unknown. In the present study, we investigated the role of MeCP2 in cell proliferation, migration and invasion in vitro. We found that knockdown of MeCP2 inhibited expression of epithelial-mesenchymal transition (EMT)-related markers in breast cancer cell lines. In conclusion, our study suggests that MeCP2 inhibits proliferation and invasion through suppression of the EMT pathway in breast cancer.

Porous Cobalt Metal-Organic Frameworks as Active Elements in Battery-Supercapacitor Hybrid Devices.

With the trigonal linker 4,4',4″-s-triazine-2,4,6-triyltribenzoic acid as a building block, porous cobalt metal-organic frameworks (named as PCN) have been successfully prepared and directly utilized as active materials in alkaline battery-type devices. For comparison, their carbon-supported hybrids (CNFs/PCN) have also been employed as battery-type electrodes. We found that the pristine PCN displayed a better performance than the CNFs/PCN composite electrode in electrochemical cells. To further investigate their electrochemical performances, alkaline battery-supercapacitor hybrid (BSH) devices with these materials as positive electrodes and activated carbon (AC) as the negative electrode were fabricated. The results indicate that the PCN//AC BSH devices delivered a maximum energy density of 16.0 Wh kg-1 at a power density of 749 W kg-1 within the voltage range of 0-1.5 V, which are much higher than those of CNFs/PCN//AC devices (12.4 Wh kg-1 at 753 W kg-1).

May Measurement Month 2018: an analysis of blood pressure screening results from China.

To further improve awareness, treatment, and control of hypertension, the May Measurement Month (MMM) campaign continued in 2018 in China. Study subjects were adults aged 18 years or more, ideally those who had not their blood pressure (BP) measured for at least a year. Blood pressure was measured three times consecutively with a 1-min interval in the sitting position, using automated BP monitors in 288 342 participants and transmitted to a central database by a smartphone app. Questionnaire data were collected with the same app. After imputation, the overall proportion of hypertension was 29.8%. Of those with hypertension, the rates of awareness, treatment, and control were 62.3%, 57.3%, and 35.9%, respectively. In analysis based on linear regression models, both systolic and diastolic BP were higher with cigarette smoking, alcohol intake, and overweight and obesity. Our study results suggest that hypertension management is improving in comparison with the data in MMM 2017 and the nationwide survey in 2012-15, and several known lifestyle factors are key to hypertension management.

CT-guided minimally-invasive penile fracture repair.

We present the case of a 28 year old patient with an incomplete tear of the tunica albuginea occurred after having sexual intercourse in the female superior position. The diagnostic assessment was performed first clinically, then with CT, owing to its high resolution, allowed to exactly detect the tear location leading to precise preoperative planning. After adequate diagnosis through imaging and proper planning, the patient was performed a selective minimally invasive surgical approach to repair the lesion. The patient had good erection with no angular deformity or plaque formation after a 3-month follow-up.

[Prevalence of Sarcopenia and Associated Factors in Community-dwelling Elderly Populations in Chengdu China].

OBJECTIVE: To determine the prevalence of sarcopenia in community-dwelling elderly populations in Chengdu and its associated risk factors. METHODS: A total of 947 community dwelling residents aged ≥60 yr. in Chengdu participated in this study. Their appendicular skeletal muscle mass was measured through bioelectrical impedance analyses. Sarcopenia was defined using the diagnostic algorithm recommended by the Asia Working Group (AWGS) for Sarcopenia. Data in relation to the demographic characteristics, chronic diseases and life style of the participants were obtained through a questionnaire survey, which included the 15-item geriatric depression scale (GDS-15) and the mini nutritional assessment (MNA). RESULTS: Overall, 10.5% of the elderly participants were identified with sarcopenia: 8.4% in men and 12.5% in women. The prevalence of sarcopenia increased with age: 2.3% in the 60-64 yr., 5.6% in the 65-74 yr., 19.7% in the ≥75 yr.. Age [odds ratio (OR)=1.109, 95% confldence interval (CI):1.054-1.168], smoking (OR=3.482, 95%CI:1.356-8.938) and Malnorishment (OR=5.598, 95%CI:2.677-11.709) are significant predictors of sarcopenia after adjustment for potential confounders. CONCLUSION: Approximately 10% community-dwelling elderly in Chengdu have sarcopenis. Age, smoking, malnutrition are risk factors of sarcopenia.

Multi-stimuli-responsive supramolecular gel constructed by pillar[5]arene-based pseudorotaxanes for efficient detection and separation of multi-analytes in aqueous solution.

Here, a novel pseudorotaxanes-type crosslinker of a supramolecular polymer network (WP5-PN) has been constructed from a host water-soluble pillar[5]arene (WP5) and a guest naphthalene dimethylamine derivative (PN) via a stepwise process involving multiple non-covalent interactions. The obtained supramolecular polymers were able to transform into a supramolecular polymer gel (WP5-PN-G) and show AIE properties in DMSO-H2O binary solution. Interestingly, due to the dynamic and reversible nature of non-covalent interactions, the resultant supramolecular polymer gels exhibited external stimuli-responsiveness to different parameters, such as temperature, acid-base, competitive guest and mechanical stress. Moreover, WP5-PN-G showed fluorescent response for Fe3+ and Cu2+, while its xerogel showed excellent recyclable separation properties for these metal ions with adsorption rates up to 98.07% and 95.38%, respectively. Moreover, by rational introduction of these metal ions into the WP5-PN-G, corresponding metal ion coordinated metallogels, such as WP5-PN-FeG and WP5-PN-CuG were obtained. These metallogels could selectively and sensitively sense F- and CN-, respectively. The detection limits of these metallogels for F- and CN- were about 1 × 10-8 M. The WP5-PN-G has potential applications in multi-analytes detection and separation as well as fluorescent display materials.