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Typhoon catastrophes can seriously threaten national and regional security and development. How to quantitatively portray the spatiotemporal characteristics and the causes of typhoon catastrophe losses will be an important subject of scientific research in terms of disaster risk reduction. In this study, the overall characteristics, spatial patterns, and main influencing factors of the losses caused by retired typhoons landing in mainland China from 2009 to 2019 were investigated, through the usage of improved typhoon disaster index (G-index), spatial autocorrelation, and cold/hotspots analysis methods. The results showed that 18 retired typhoons affected 17 provinces in China from 2009 to 2019, among which the areas affected by minor, moderate, severe, and extremely severe disasters accounted for 38.02%, 44.16%, 13.84%, and 4.32%, respectively. The disaster has strong spatial clustering, and the hotspots based on the G index are the key areas to be concerned about prevention and mitigation against typhoon mega-disasters. Furthermore, the effects of exposed population, maximum wind speed, and maximum accumulative process precipitation on typhoon disaster losses were positively correlated, while the effects of exposed GDP (Gross Domestic Product) on disaster losses are weakly negatively correlated. This study identified the hotspots of typhoon catastrophes and underlined the efforts to formulate effective disaster risk reduction and build resilience.

Vitiligo is a skin depigmentation disorder. GATA3 expression is downregulated in vitiligo patients, and its role and regulatory mechanism in vitiligo are unclear. GATA3 and HMGB1 levels were detected by qRT-PCR in peripheral blood cells of vitiligo patients and healthy controls, as well as H

Hyperuricemia (HUA) is a common chronic metabolic disease that can cause renal failure and even death in severe cases. Berberine (BBR) is an isoquinoline alkaloid derived from Phellodendri Cortex with strong antioxidant, anti-inflammatory, and anti-apoptotic properties. The purpose of this study was to investigate the protective effects of berberine (BBR) against uric acid (UA)-induced HK-2 cells and unravel their regulatory potential mechanisms. The CCK8 assay was carried out to detect cell viability. The expression levels of inflammatory factors interleukin-1β (IL-1β) and interleukin-18 (IL-18) and Lactate dehydrogenase (LDH) were measured using Enzyme-linked immunosorbent assays (ELISA). The expression of the apoptosis-related protein (cleaved-Caspase3, cleaved-Caspase9, BAX, BCL-2) was detected by western blot. The effects of BBR on the activities of the NOD-like receptor family pyrin domain containing 3 (NLRP3) and the expression of the downstream genes were determined by RT-PCR and western blot in HK-2 cells. From the data, BBR significantly reversed the up-regulation of inflammatory factors (IL-1β, IL-18) and LDH. Furthermore, BBR down-regulated protein expression of pro-apoptotic proteins BAX, cleaved caspase3 (cl-Caspase3), cleaved caspase9 (cl-Caspase9), and enhanced the expression of antiapoptotic protein BCL-2. Simultaneously, BBR inhibited the activated NLPR3 and reduced the mRNA levels of NLRP3, Caspase1, IL-18, and IL-1β. Also, BBR attenuated the expression of NLRP3 pathway-related proteins (NLRP3, ASC, Caspase1, cleaved-Caspase1, IL-18, IL-1β, and GSDMD). Furthermore, specific NLRP3-siRNA efficiently blocked UA-induced the level of inflammatory factors (IL-1β, IL-18) and LDH and further inhibited activated NLRP3 pathway. Collectively, our results suggested that BBR can alleviate cell injury induced by UA. The underlying unctionary mechanism may be through the NLRP3 signaling pathway.

The peroxisome proliferator-activated receptor (PPARδ) agonists are reported to improve insulin sensitivity, reduce glucose levels, and alleviate dysfunctional lipid metabolism in animal models of type 2 diabetes mellitus. However, the underlying mechanisms remain incompletely understood. Metabolism plays an essential role in the biological system. Monitoring of metabolic changes in response to disease conditions or drug treatment is critical for better understanding of the pathophysiological mechanisms. In this study, metabolic profiling analysis by gas chromatography-mass spectrometry integrated with targeted analysis by liquid chromatography-mass spectrometry was carried out in plasma samples of db/db diabetic mice after six-week treatment of PPARδ agonist GW501516. GW501516 treatment significantly altered levels of metabolites, such as branched-chain amino acids (BCAAs), BCAA metabolites (3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid), long-chain fatty acids, uric acid and ketone bodies (3-hydroxybutyric acid and 2-hydroxybutyric acid) which are all associated with the impaired systemic insulin sensitivity. The present results indicate the beneficial effect of PPARδ agonist in alleviating insulin resistance of diabetic mice by favorably modulating metabolic profile, thus providing valuable information in understanding the therapeutic potential of PPARδ agonists in correcting metabolic dysfunction in diabetes.

Background To inform policy and implementation that can enhance prevention and improve tuberculosis (TB) care cascade outcomes, this review aimed to summarize the impact of various interventions on care cascade outcomes for active TB. Methods and findings In this systematic review and meta-analysis, we retrieved English articles with comparator arms (like randomized controlled trials (RCTs) and before and after intervention studies) that evaluated TB interventions published from January 1970 to September 30, 2022, from Embase, CINAHL, PubMed, and the Cochrane library. Commentaries, qualitative studies, conference abstracts, studies without standard of care comparator arms, and studies that did not report quantitative results for TB care cascade outcomes were excluded. Data from studies with similar comparator arms were pooled in a random effects model, and outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) and number of studies (k). The quality of evidence was appraised using GRADE, and the study was registered on PROSPERO (CRD42018103331). Of 21,548 deduplicated studies, 144 eligible studies were included. Of 144 studies, 128 were from low/middle-income countries, 84 were RCTs, and 25 integrated TB and HIV care. Counselling and education was significantly associated with testing (OR = 8.82, 95% CI:1.71 to 45.43; I2 = 99.9%, k = 7), diagnosis (OR = 1.44, 95% CI:1.08 to 1.92; I2 = 97.6%, k = 9), linkage to care (OR = 3.10, 95% CI = 1.97 to 4.86; I2 = 0%, k = 1), cure (OR = 2.08, 95% CI:1.11 to 3.88; I2 = 76.7%, k = 4), treatment completion (OR = 1.48, 95% CI: 1.07 to 2.03; I2 = 73.1%, k = 8), and treatment success (OR = 3.24, 95% CI: 1.88 to 5.55; I2 = 75.9%, k = 5) outcomes compared to standard-of-care. Incentives, multisector collaborations, and community-based interventions were associated with at least three TB care cascade outcomes; digital interventions and mixed interventions were associated with an increased likelihood of two cascade outcomes each. These findings remained salient when studies were limited to RCTs only. Also, our study does not cover the entire care cascade as we did not measure gaps in pre-testing, pretreatment, and post-treatment outcomes (like loss to follow-up and TB recurrence). Conclusions Among TB interventions, education and counseling, incentives, community-based interventions, and mixed interventions were associated with multiple active TB care cascade outcomes. However, cost-effectiveness and local-setting contexts should be considered when choosing such strategies due to their high heterogeneity.

Typhoon disasters cause billions of dollars in losses each year, and many countries around the world are adversely affected by these events. Presently, the determinant powers of both natural and socioeconomic factors on disaster losses (such as the house collapse rate following a typhoon), as well as their interaction effects, remain unclear. In this study, the GeoDetector method was used to quantify the impacts of natural and socioeconomic factors and their interactions on the house collapse rate caused by Super Typhoon Lekima in 2019; and then detect the dominant factor, involving in the spatial pattern of house collapses was identified by the local indicators of spatial association (LISA) method. This study found that in addition to natural factors, socioeconomic factors also played a non-negligible role in the house collapse rate caused by Super Typhoon Lekima. The dominant factor was maximum precipitation, and the statistical value of q was 0.39. Next in importance were the elevation and maximum wind speed. Among the interactive effects of 14 influencing factors, the interaction between maximum precipitation and the ratio of four-six floor buildings was the largest (q = 0.74). In southeastern Zhejiang and northern Shandong, highly concentrated areas of ​collapsed houses were found. The results of the study can be used to develop more specific policies aimed at safety improvements and successful property protection.

Defective mitophagy and mitochondrial dysfunction have been linked to aging and Alzheimer's disease (AD). β2-Adrenergic receptor (ADRB2) is critical for mitochondrial and cognitive function. However, researchers have not clearly determined whether ADRB2 activation ameliorates defective mitophagy and cognitive deficits in individuals with AD. Here, we observed that the activation of ADRB2 by clenbuterol (Clen, ADRB2 agonist, 2 mg/kg/day) ameliorated amyloid-β-induced (Aβ1-42 bilateral intracerebral infusion, 2 μl, 5 μg/μl) memory deficits. Activation of ADRB2 also attenuated Aβ-induced mitochondrial dysfunction, as revealed by increased ATP levels, mitochondrial membrane potential (MMP/Δψm) and complex I activity. Further studies revealed that ADRB2 activation restored mitophagy deficits, as revealed by the increased light chain 3 (LC3)-II/LC3-I ratio, Atg5 levels, and Atg7 levels and decreased p62 levels, along with the upregulation of PTEN-induced putative kinase 1 (PINK1), Parkin and NAD

Typhoons are an environmental threat that mainly affects coastal regions worldwide. The interactive effects of natural and socioeconomic factors on the losses caused by typhoon disasters need further examination. In this study, GeoDetector was used to quantify the determinant powers of natural and socioeconomic factors and their interactive effects on the rate of house collapse in Guangdong and Guangxi Provinces of southeast China caused by Typhoon Mangkhut in 2018. We further identify the dominant factors that influenced the disaster losses. The local indicators of spatial association method was then introduced to explain the spatial heterogeneity of the disaster losses under the influence of the dominant factor. The results indicate that both natural and socioeconomic factors significantly affected the house collapse rate. The maximum precipitation was the dominant factor, with a q value of 0.21, followed by slope and elevation, with q values of 0.17 and 0.13, respectively. Population density and per capita gross domestic product had q values of 0.15 and 0.13, respectively. Among all of the interactive effects of the influencing factors, the interactive effect of elevation and the ratio of brick-wood houses had the greatest influence (q = 0.63) on the house collapse rate. These results can contribute to the formulation of more specific safety and property protection policies.

ObjectivesThis study aimed to determine the variation in the interval between the onset of symptoms and clinical presentation, and its associated factors among symptomatic individuals with gonorrhoea.DesignA cross-sectional study was conducted between 1 June and 30 July 2017.Setting129 sexually transmitted disease clinics from 21 cities of Guangdong, China.ParticipantsUsing convenience sampling method to recruit symptomatic individuals with gonorrhoea over 18 years old.Outcome measureTime to clinical presentation.ResultsAmong 1664 participants, the median age was 29 (24–36) years old, and the majority were male (92.5%) and married (52.9%). The median time to clinical presentation was 3 (2–6) days. About 471 (28.3%) patients had sexual contact while symptomatic. After adjusting for covariates, participants who were female (aβ=0.44, 95% CI: 0.22 to 0.80), from east Guangdong region (aβ=0.44, 95% CI: 0.22 to 0.80) and had the absence of dysuria (aβ=0.26, 95% CI: 0.06 to 0.46) had increased time to clinical presentation. Participants who had commercial sex in the past 6 months (aβ=−0.11, 95% CI: −0.21 to –0.01) had decreased time to clinical presentation. Participants who were female (adjusted odds ratio (aOR)=1.66, 95% CI: 1.08 to 2.50) and delayed in seeking healthcare more than 7 days (aOR=46.71, 95% CI: 24.27 to 89.93) were more likely to have sexual contact while symptomatic.ConclusionThe time to clinical presentation for individuals with symptomatic gonorrhoea is variable and a high proportion of participants continued to have sexual behaviour while symptomatic. Strategies to increase health literacy may help to minimise the sequelae of gonorrhoea and reduce onward transmission.

In the new situation of modernization, there is an influx of diverse social thinking. At the same time, coupled with the influence of COVID-19, which has swept the world, the ideological and psychological space of college students has been greatly impacted. In this context, the ideological and psychological health of college students is an important value for the education of college students. To be specific, as an important place for cultivating college students, colleges and universities should pay attention to students’ thoughts and ideas from their hearts. In addition, colleges and universities should give full play to the role of educational psychology in colleges and universities and actively promote the synergistic development of all educational sectors in schools, so as to promote the realization of the goal of education in the new era. In recent years, a series of mental health problems such as anxiety, depression, low self-esteem, and interpersonal sensitivity have become frequent among college students, and some have even developed suicidal ideation. This has a very serious negative impact on individuals, families, and society. Therefore, if the mental health problems of college students can be detected early, the relevant school departments and counselors can provide timely and targeted help to such students. At the same time, these at-risk students can receive early treatment, thus reducing the harm. As a result, it is quite valuable to find an effective method to identify students with mental health problems. Traditionally, researchers have used questionnaires to survey students about their mental health. However, this approach has the disadvantage of being easily concealed and inefficient. In recent years, researchers have begun to use weblogs to identify students with mental health problems, but this approach still has shortcomings. First of all, they still use questionnaires to obtain labels. In addition, students’ psychological activities may not only be reflected in their online behavior but also in their other daily behaviors. Big data in higher education plays a crucial role in analyzing and identifying students with psychological abnormalities. As a result, this research mainly extracts the behavioral characteristics of students by cleaning and transforming a large amount of disorganized student school data based on the educational data collected from school cards, academic affairs systems, access control systems, and related business systems. What is more, this study further analyzes the differences in behavioral characteristics between normal and abnormal students through hypothesis testing and finally establishes a model to identify abnormal students and evaluate the results.

Idiopathic pulmonary fibrosis (IPF) is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function. Chronic inflammation has been demonstrated to be the pathological basis of fibrosis. Emerging studies have revealed that most interleukin-17 (IL-17) isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity. Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes, including the initiation and exacerbation of IPF. Here, we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.

The lack of biomarkers greatly limits the diagnosis and treatment of major depressive disorder (MDD). Endogenous L-carnitine (LC) and its derivative acetyl-L-carnitine (ALC) play antidepressant roles by improving brain energy metabolism, regulating neurotransmitters and neural plasticity. The levels of ALC in people and rodents with depression are significantly reduced. It is necessary to determine whether serum LC and ALC might be used as novel biomarkers for the diagnosis of MDD. Here, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the concentration of LC and ALC in the serum of healthy controls and patients with MDD; among the latter, in patients who were responsive (effective group) and non-responsive (ineffective group) after 2 weeks of treatment. The diagnostic value of serum LC and ALC for MDD was assessed. Compared with healthy controls, the serum LC and ALC concentrations in patients with MDD were significantly decreased (P < 0.001). Pearson correlation analysis shows that the HDRS-24 score was negatively associated with serum ALC (r = −0.325, P = 0.007). Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.801 with 83.1% sensitivity and 66.3% specificity for LC, and an AUC of 0.898 with 88.8% sensitivity and 76.4% specificity for ALC, differentiating patients with MDD from healthy controls. Furthermore, the concentration of LC and ALC in patients with depression was significantly increased in the effective treatment group, and no significant change was observed in the ineffective treatment group. These results suggest that serum LC and ALC may be novel biomarkers for the diagnosis of MDD.

Background Fascin is crucial for cancer cell filopodium formation and tumor metastasis, and is functionally regulated by post‐translational modifications. However, whether and how Fascin is regulated by acetylation remains unclear. This study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor metastasis. Methods Immunoprecipitation and glutathione‐S‐transferase pull‐down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP‐associated factor (PCAF), and immunofluorescence was used to investigate their colocalization. An in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry. A specific antibody against acetylated Fascin was generated and used to detect the PCAF‐mediated Fascin acetylation in esophageal squamous cell carcinoma (ESCC) cells using Western blotting by overexpressing and knocking down PCAF expression. An in vitro cell migration assay was performed, and a xenograft model was established to study in vivo tumor metastasis. Live‐cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium formation. The clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using immunohistochemistry. Results Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471 (K471) by PCAF. Using the specific anti‐AcK471‐Fascin antibody, Fascin was found to be acetylated in ESCC cells, and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF knockdown. Functionally, Fascin‐K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis, whereas Fascin‐K471 deacetylation exhibited a potent oncogenic function. Moreover, Fascin‐K471 acetylation reduced filopodial length and density, and lifespan of ESCC cells, while its deacetylation produced the opposite effect. In the filipodium shaft, K471‐acetylated Fascin displayed rapid dynamic exchange, suggesting that it remained in its monomeric form owing to its weakened actin‐bundling activity. Clinically, high levels of AcK471‐Fascin in ESCC tissues were strongly associated with prolonged overall survival and disease‐free survival of ESCC patients. Conclusions Fascin interacts directly with PCAF and is acetylated at lysine 471 in ESCC cells. Fascin‐K471 acetylation suppressed ESCC cell migration and tumor metastasis by reducing filopodium formation through the impairment of its actin‐bundling activity.

Background: Acute lung injury (ALI) is a complicated and severe lung disease, which is often characterized by acute inflammation. Poliumoside (POL), acteoside (ACT) and forsythiaside B (FTB) are phenylethanoid glycosides (PGs) with strong antioxidant, anti-inflammatory, and anti-apoptotic properties, which are extracted from Callicarpa kwangtungensis Chun (CK). The aim of this study was to investigate the protective effects of POL, ACT, and FTB against TNF-α-induced damage using an ALI cell model and explore their potential mechanisms.Methods and Results: MTT method was used to measure cell viability. Flow cytometry was used for detecting the apoptosis rate. Reactive oxygen species (ROS) activity was determined using fluorescence microscope. The expression of mRNA in apoptosis-related genes (Caspase 3, Caspase 8, and Caspase 9) were tested by qPCR. The effects of POL, ACT, FTB on the activities of nuclear factor erythroid-2 related factor 2 (Nrf2), nuclear factor kappa-B (NF-κB) and the expression of their downstream genes were assessed by western blotting and RT-PCR in A549 cells. In the current study, POL, ACT, and FTB dose-dependently attenuated TNF-α-induced IL-1β, IL-6 and IL-8 production, cell apoptosis, the expression of apoptosis-related genes (Caspase 3, Caspase 8, and Caspase 9) and ROS activity. POL, ACT, and FTB not only increased in the mRNA levels of antioxidative enzymes NADPH quinone oxidoreductase (NQO1), glutamate cysteine ligase catalytic subunit (GCLC), heme oxygenase (HO-1), but also decreased the mRNA levels of IL-1β, IL-6 and IL-8. Furthermore, they upregulated the expression of Keap1 and enhanced the activation of Nrf2, while decreased the expression of phosphor-IκBα (p-IκBα) and nuclear p65. In addition, no significant changes were observed in anti-inflammatory and antioxidant effects of POL, ACT, FTB following Nrf2 and NF-κB p65 knockdown.Conclusion: Our study revealed that POL, ACT, and FTB alleviated oxidative damage and lung inflammation of TNF-α-induced ALI cell model through regulating the Nrf2 and NF-κB pathways.

Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.

Ulcerative colitis (UC), an inflammatory disease, is widely thought to be associated with colonic barrier damage and inflammatory response. With the destruction of the colonic barrier, lipopolysaccharide (LPS) enters the liver through the portal vein and causes liver injury. Liver injury in turn exacerbates UC to form a vicious cycle, so the treatment of liver injury cannot be ignored. Andrographolide (Andro) has a protective effect against colitis and liver injury, but with low bioavailability. Andrographolide sodium bisulfite (ASB), a water-soluble sulfonate of Andro, has better bioavailability, whether it has a better curative effect against UC and liver injury is rarely reported. Hence, we investigated the protective effect and potential mechanism of ASB against dextran sulfate sodium (DSS)-induced UC and liver injury in mice. The results showed that treatment with ASB significantly relieved the clinical symptoms of UC and liver injury by reducing disease activity index, inhibiting gut-derived LPS leakage, and improving colonic and hepatic injury, and its curative effect was better than Andro. Moreover, ASB effectively decreased the YAP-mediated colonic inflammation and TLR4/MyD88/NF-κB-mediated pro-inflammatory factor release in the liver. Both colonic and hepatic inflammation were associated with macrophage proinflammatory polarization, but they were significantly inhibited by ASB. ASB showed good safety in the treatment of UC and liver injury and has no nephrotoxicity as previously described. In conclusion, ASB has an effective protective effect on DSS-induced UC and liver injury, mainly by suppressing macrophage proinflammatory polarization from the gut-liver axis.

Typhoon disasters have caused casualties, property loss, and other negative impacts to social and economic development. Vulnerability is an important component of typhoon risk. However, little is known about the contributions of vulnerability factors and their interaction effects on typhoon-induced losses at a fine scale. Focusing on the vulnerability measures of Typhoon Hato in 2017 and Typhoon Mangkhut in 2018, this study aims to quantify the contribution and interactive effects of physical and socioeconomic factors on vulnerability based on the GeoDetector method and determine the factors that account for most of the change in vulnerability. The results show that from Typhoon Hato in 2017 to Typhoon Mangkhut in 2018, the vulnerability of the economy and houses decrease on average. Rain intensity and wind intensity are the dominant factors of disaster loss for Typhoon Hato and Typhoon Mangkhut, respectively. Vegetation cover and landform explain vulnerability better than average slope in most instances. For different loss types, the dominant socioeconomic vulnerability factor is different. For both typhoons, emergency transfer has a higher determining power (q) ranking for the population vulnerability, while the percentage of the GDP made up of primary industry have higher q ranking for economic vulnerability. The dominant interaction effects between two vulnerability factors differ depending on the typhoon and loss type but show a nonlinear enhancement effect in most cases. Moreover, changes in the maximum 4-hour accumulated rainfall account for most of the change in vulnerability between Hato and Mangkhut. Overall, the results can be conducive to understanding the complexity of vulnerability to typhoons and provide a reference for possible indicators for vulnerability assessment models, and determining the reasons for changes in vulnerability can be constructive to the formulation of specific policies for disaster prevention and mitigation.

Acute lung injury (ALI), hallmarked with alveolar epithelial barrier impairment and pulmonary edema induced by acute inflammation, presents a severe health burden to the public, due to the limited available interventions. Oxyberberine (OBB), having improved anti-inflammatory activity and safety, is a representative component with various activities derived from berberine, whereas its role against ALI with alveolar epithelial barrier injury remains uncertain. To investigate the influence and underlying mechanisms of OBB on ALI, we induced acute inflammation in mice and A549 cells by using lipopolysaccharide (LPS). Changes in alveolar permeability were assessed by analyzing lung histopathology, measuring the dry/wet weight ratio of the lungs, and altering proinflammatory cytokines and neutrophils levels in the bronchoalveolar lavage fluid (BALF). Parameters of pulmonary permeability were assessed through ELISA, western blotting, quantitative real-time PCR, and immunofluorescence analysis. U46619, the agonist of RhoA/ROCK, was employed to further investigate the mechanism of OBB on ALI. Unexpectedly, we found OBB mitigated lung impairment, pulmonary edema, inflammatory reactions in BALF and lung tissue, reduction in ZO-1, and addition of connexin-43. Besides, OBB markedly reduced the expression of RhoA in association with its downstream factors, which are linked to the intercellular junctions and permeability both in vivo and in vitro. Nevertheless, U46619 abolished the benefits obtained from OBB in A549 cells. In conclusion, these outcomes indicated that OBB exerted RhoA/ROCK inhibitor-like effect to moderate alveolar epithelial barrier impairment and permeability, ultimately preventing ALI progression.

Background Typhoons greatly threaten human life and property, especially in China. Therefore, it is important to make effective policy decisions to minimize losses associated with typhoons. Methods In this study, the GeoDetector method was used to quantify the determinant powers of natural and socioeconomic factors, and their interactions, on the population casualty rate of super typhoon Lekima. The local indicator of spatial association (LISA) method was followed to explore the spatial pattern of the population casualty rate under the influence of the identified dominant factors. Results Both natural and socioeconomic factors were found to have significantly impacted the population casualty rate due to super typhoon Lekima. Among the selected factors, maximum precipitation was dominant factor (q = 0.56), followed by maximum wind speed (q = 0.45). In addition, number of health technicians (q = 0.35) and number of health beds (q = 0.27) have a strong influence on the population casualty rate. Among the interactive effects of 12 influencing factors, the combined effects of maximum precipitation and ratio of brick-wood houses, the maximum precipitation and ratio of steel-concrete houses, maximum precipitation and number of health technicians were highest (q = 0.72). Furthermore, high-risk areas with very high casualty rates were concentrated in the southeastern part of Zhejiang and northern Shandong Provinces, while lower-risk areas were mainly distributed in northern Liaoning and eastern Jiangsu provinces. Conclusions These results contribute to the development of more specific policies aimed at safety and successful property protection according to the regional differences during typhoons.

MicroRNA (miR)‑29b is a key tumor regulator. It can inhibit tumor cell proliferation, induce apoptosis, suppress tumor invasion and migration, thus delaying tumor progression. Our previous studies revealed an increased level of miR‑29b in hepatoma 22 (H22) cells in ascites tumor‑bearing mice. The present study investigated the effect of miR‑29b on proliferation and apoptosis of hepatocellular carcinoma ascites H22 cells and its association with the transforming growth factor‑β1 (TGF‑β1) signaling pathway and p53‑mediated apoptotic pathway. Briefly, H22 cells were transfected with miR‑29b‑3p (hereinafter referred to as miR‑29b) mimic or miR‑29b inhibitor. MTS cell proliferation assay and flow cytometry were used to analyze cell viability and apoptosis. The expression change of the TGF‑β1 signaling pathway and p53‑mediated apoptotic pathway were detected by reverse transcription‑quantitative PCR, western blotting and immunofluorescence. Furthermore, cells were treated with exogenous TGF‑β1 and TGF‑β1 small interfering RNA to evaluate the crosstalk between TGF‑β1 and p53 under miR‑29b regulation. The overexpression of miR‑29b decreased cell viability, increased cell apoptosis, activated the TGF‑β1 signaling pathway and p53‑mediated apoptotic pathway. Conversely, these effects were reversed by the miR‑29b inhibitor. Moreover, the effect of miR‑29b mimic was further increased after treating cells with exogenous TGF‑β1. The activation of the TGF‑β1 signaling pathway and p53‑mediated apoptotic pathway induced by miR‑29b overexpression were reversed by TGF‑β1 inhibition. In summary, these data indicated that miR‑29b has an important role in proliferation and apoptosis of H22 cells by regulating the TGF‑β1 signaling pathway, the p53‑dependent apoptotic pathway, and the crosstalk between TGF‑β1 and p53.

Background: The reviews on the risk factors with ARDS and the worse outcomes concluded lacking robust data of risk factors to prevent COVID-19 and identified an urgent need for large sample and high-quality research in this area, as well as the features of the ARDS.Methods: This retrospective cohort study included 333 COVID-19 inpatients at two hospitals in Hubei of China in 2020. The COVID-19-related ARDS was diagnosed according to the Berlin criteria. The outcomes were ARDS development and the intubation or in-hospital death. The cox proportional hazard ratio (HR) models were employed to determine the significant risk factors. Results: The median number of days from symptom onset to ARDS diagnosis was 11.0 (IQR, 8.0–13.0). Up to 84.1% COVID-19-related ARDS patients demonstrated multiple organ injuries. The mortality rates were 41.9% and 85.7% in moderate and severe ARDS. The survival patients on invasive mechanical ventilation (IMV) had been intubated earlier since ARDS diagnosis than those who had not survived (5.5 median days, IQR 4.0-7.0 days versus 11.5 median days, IQR 6.0-14.0 days, P < 0.001). Males and all abnormal laboratory indices associated with the higher risk of ARDS (P0.05). The sensitivity analyses found that lymphocyte count of < 1000 per mm3 at hospital admission were still significantly associated with developing ARDS when adjusting for age and male gender (HR, 4.10; 95% CI, 2.40-7.10), and oxygenation index (OI) ratio < 150 were more likely to predict the intubation/death after age adjustment (HR, 2.50; 95% CI, 1.17-5.30). Conclusion: The SARS-CoV-2-caused ARDS was not the typical ARDS according to Berlin criteria. The alive patients with IMV had been intubated earlier since ARDS diagnosis than those who had not survived. We identified male gender and abnormal laboratory indices associated with the ARDS but were not linked with the intubation/death. Sensitivity analysis concluded lymphocyte count of < 1000 per mm3 could predict ARDS while OI ratio less than 150 could predict intubation/death.

Background: More evidence in understanding the heterogeneity of COVID-19-associated acute respiratory distress syndrome (ARDS) and in improving strategy to increase the survival from the critical patients intubated is always needed. The study aimed to comprehensively explore the features of COVID-19-associated ARDS and the features and outcomes between the early and late intubation groups. Methods: This retrospective cohort included 65 adult COVID-19 inpatients with ARDS at two hospitals in Hubei, China. The ARDS in these patients was diagnosed according to the Berlin criteria. We defined intubation within 7 days of ARDS diagnosis as ‘early’ intubation and that performed from the eighth day as ‘late’ intubation based on literatures. The outcomes were invasive mechanical ventilation and in-hospital death. The log-binomial regression models were used to explore the risk factors and the Kaplan-Meier statistic was used to estimate the risk of mortality. Results: The median number of days from symptom onset to ARDS diagnosis was 11.0 (IQR, 8.0–13.0). Up to 84.1% COVID-19-related ARDS patients demonstrated multiple organ injuries. The mortality rates were 41.9% and 85.7% in moderate and severe ARDS. The early intubation and the late intubation had the differences in days from symptom onset/hospital admission/ARDS diagnosis to intubation (P = 0.023, P = 0.011, P < 0.001). Compared with the early-intubation group, the late-intubation group showed less severity at admission (median oxygenation index 159.0 95% CI 134.0-203.0 vs. 133.9 95% CI 98.3-183.2), but required more aggressive therapies (ICU 80% vs. 70%, CRRT 50% vs. 10%, prone-position 50% vs. 30%, and ECMO 50% vs. 10%) and had higher risk to die at hospital (RR, 3.18; 95% CI 1.98-5.12). Conclusion: The ARDS caused by COVID-19 was not typical ARDS due to prolonged onset time, multiple organ injuries, and higher mortalities. The late-intubation group showed less severity at admission but higher risk of in-hospital death than the early-intubation group.

A simple, rapid, and selective ultra-performance liquid chromatography-tandem mass spectrometry method for determination of l-carnitine (LC) and acetyl-l-carnitine (ALC) in human serum was developed. Acetyl-l-carnitine-d3 (ALC-d3 ) was selected as internal standard (IS). After protein precipitation with acetonitrile-water (1 mL, 2:1, v/v), the analytes and IS were separated on a 2.5-μm XSelect HSS T3 C18 column by gradient elution with methanol-water (containing 0.01% ammonia water) as the mobile phase at a flow rate of 0.2 mL/min. Analytes were detected with multiple reaction monitoring using a positive scan mode with electrospray ionization. Good linearity (R2 > 0.999) was observed in the concentration range for LC and ALC. The inter- and intra-day values of relative error were -10.4% to 10.0% with CVs less than 9.84%. The average recoveries of the two analytes were 91.29%-98.23%. Blood samples containing LC and ALC were stable under various storage conditions. Normal, haemolytic, and hyperlipidaemic serum had no significant effect on the quantification of LC and ALC. This method was successfully applied to study the concentrations of endogenous LC and ALC in the serum of patients with first-episode depression.

In view of the damage of the emergency road network in earthquake-stricken areas to different degrees, considering the fact that the supply of relief materials in the early stage of the earthquake is in short supply, and considering whether the victims feel fair about the emergency relief materials, a two-objective nonlinear programming model with both fairness and timeliness is constructed in the early stage of the earthquake. In this model, the objective is to maximize the sum of the psychological satisfaction function values of the victims, and to minimize the sum of the time for the delivery of relief materials to the affected points. Based on this model, the distribution scheme of relief materials from multiple relief points to multiple affected points is selected. Based on the NSGA - II improved a multi-objective optimization algorithm to solve the model. Finally, some examples are designed with some disaster points in lushan earthquake as the background, and the reliability and effectiveness of the model and algorithm are proved by data experiment.

Background As a prevalent type of cryptogenic fibrotic disease with high mortality, idiopathic pulmonary fibrosis (IPF) still lacks effective therapeutic drugs. The compounds extracted from buds and flowers of Chrysanthemum indicum Linné with supercritical-carbon dioxide fluid (CISCFE) has been confirmed to have antioxidant, anti-inflammatory, and lung-protective effects. This paper aimed to clarify whether CISCFE could treat IPF induced by bleomycin (BLM) and elucidate the related mechanisms. Methods Rats (Sprague-Dawley, male) were separated into the following groups: normal, model, pirfenidone (50 mg/kg), CISCFE-L, −M, and -H (240, 360, and 480 mg/kg/d, i.g., respectively, for 4 weeks). Rats were given BLM (5 mg/kg) via intratracheal installation to establish the IPF model. A549 and MRC-5 cells were stimulated by Wnt-1 to establish a cell model and then treated with CISCFE. Haematoxylin-eosin (H&E) and Masson staining were employed to observe lesions in the lung tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) were performed to observe changes in genes and proteins connected with the Wnt/β-catenin pathway. Results CISCFE inhibited the proliferation of MRC-5 cells (IC50: 2.723 ± 0.488 μg/mL) and A549 cells (IC50: 2.235 ± 0.229 μg/mL). In rats, A549 cells, and MRC-5 cells, BLM and Wnt-1 obviously induced the protein expression of α-smooth muscle actin (α-SMA), vimentin, type I collagen (collagen-I), and Nu-β-catenin. The mRNA levels of matrix metalloproteinase-3 (MMP-3) and − 9 (MMP-9), two enzymes that degrade and reshape the extracellular matrix (ECM) were also increased while those of tissue inhibitor of metalloproteinase 1 (TIMP-1) were decreased. However, CISCFE reversed the effects of BLM and Wnt-1 on the expression pattern of these proteins and genes. Conclusion These findings showed that CISCFE could inhibit IPF development by activating the Wnt/β-catenin pathway and may serve as a treatment for IPF after further investigation.

The typhoon knowledge graph can correlate various kinds of information in the typhoon data, conduct overall and related analysis, and finally provide effective assistance for typhoon prevention and post-disaster protection. The data of typhoon landing in China from 2000 to 2015 were selected to build a typhoon knowledge graph based on Neo4j graph database platform. The typhoon knowledge graph can be used to understand the occurrence of historical typhoons and obtain the distribution of typhoon data in time and space.

Background Men who have sex with men (MSM) bear a high burden of syphilis infection. Expanding syphilis testing to improve timely diagnosis and treatment is critical to improve syphilis control. However, syphilis testing rates remain low among MSM, particularly in low- and middle-income countries. We describe the protocol for a randomised controlled trial (RCT) to assess whether provision of syphilis self-testing services can increase the uptake of syphilis testing among MSM in China. Methods Four hundred forty-four high-risk MSM will be recruited online and randomized in a 1:1:1 ratio to (1) standard syphilis self-testing arm; (2) a self-testing arm program enhanced with crowdsourcing and a lottery-based incentive, and (3) a standard of care (control). Self-testing services include a free syphilis self-test kit through the mail at monthly intervals. Participants in the lottery incentive arm will additionally receive health promotion materials generated from an open crowdsourcing contest and be given a lottery draw with a 10% chance to win 100 RMB (approximately 15 US Dollars) upon confirmed completion of syphilis testing. Syphilis self-test kits have step-by-step instructions and an instructional video. This is a non-blinded, open-label, parallel RCT. Participants in each arm will be followed-up at three and 6 months through WeChat (a social media app like Facebook messenger). Confirmation of syphilis self-test use will be determined by requiring participants to submit a photo of the used test kit to study staff via secure data messaging. Both self-testing and facility-based testing will be ascertained by sending a secure photographic image of the completed kit through an existing digital platform. The primary outcome is the proportion of participants who tested for syphilis in the past 3 months. Discussion Findings from this study will provide much needed insight on the impact of syphilis self-testing on promoting routine syphilis screening among MSM. The findings will also contribute to our understanding of the safety, effectiveness and acceptability of syphilis self-testing. These findings will have important implications for self-testing policy, both in China and internationally. Trial registration ChiCTR1900022409 (10 April, 2019).

Moxifloxacin (MFX) shows goodA formulation ofSignificantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference.MFX showed limited efficacy against

Background: The evidence on the impact of HIV on COVID-19 is insufficient and inconsistent. This study synthesized the risk of SARS-CoV-2 infection, severe COVID-19 symptoms and COVID-19 related mortality among people living with HIV (PLWH). Methods: We conducted a systematic review and meta-analysis by searching PubMed, medRxiv and Cochrane between December 1st , 2019 to September 18th, 2020 for original studies, published in English, on HIV-SARS-CoV-2 co-infected patients. We extracted individual-level data from case reports/series and summarized patients’ characteristics and clinical outcomes. Studies were assessed for bias using NOS. Risk of SARS-CoV-2 infection, severe COVID-19 and mortality were pooled at 95% CI. Risk ratio was used to compare the risk between PLWH and patients without HIV. Findings: We identified 2,464 articles and included 61 of them. The pooled SARS-CoV-2 infection rate among PLWH was 1·5% (95% CI 0·7%- 3·2%) and there was a higher infection rate compared to people without HIV (RR 1·17, 95% CI 1·13- 1·21). The pooled rate of severe COVID-19 symptoms was 23·8% (95% CI, 14·7%- 36·1%) for PLWH, comparable to people without HIV (RR 1·32, 95% CI, 0·76-2·30). The pooled fatality rate among PLWH was 9·4% (95% CI 5·4%-15·8%). The crude RR between PLWH and patients without HIV is comparable (RR 1·02, 95% CI 0·90-1·16) but an increased COVID-19 mortality risk among PLWH was observed after adjust for potential confounders (adjusted RR 2·07, 95% CI 1·73%- 2·47%). Interpretation: Local health system should strengthen COVID-19 prevention and treatment among PLWH, and sustain the HIV care continuum for PLWH. Funding: This work was supported by the National Key Research and Development Program of China (2017YFE0103800), NIMH (R34MH109359 and R34MH119963), National Science and Technology Major Project (2018ZX10101-001-001-003), and the National Nature Science Foundation of China (81903371). Declaration of Interests: The authors had no conflict of interest to disclose.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. Histone deacetylase inhibitors (HDACIs) have been demonstrated as an emerging class of anticancer drugs for a range of haematological and solid tumours. However, the effect of HDACIs has not yet been investigated on ESCC cells. In this study, HDACIs were initially considered to have anticancer activity for ESCC, due to the high expression of HDAC genes in ESCC cell lines by analysing expression data of 27 ESCC cell lines from the Broad-Novartis Cancer Cell Line Encyclopedia. Next, we used five ESCC cell lines and one normal immortalized esophageal epithelial cell line to screen three HDACIs, panobinostat (LBH589), vorinostat (SAHA), and trichostatin A (TSA), for the ability to inhibit growth. Here, we report that LBH589 more effectively suppressed cell proliferation of ESCC cell lines, in a dose-dependent manner, than TSA and SAHA, as well as had lower toxicity against the SHEE normal immortalized esophageal epithelial cell line. Further experiments indicated that LBH589 treatment significantly inhibited TP53 (mutated TP53) expression, both at the mRNA and protein level, and simultaneously increased p21 and decreased cyclin D1 expression. Taken together, we propose that LBH589 inhibits ESCC cell proliferation mainly through inducing cell cycle arrest by increasing p21 and decreasing cyclin D1 in a p53-independent manner. SIGNIFICANCE OF THE STUDY: In this study, the antitumor activity of HDACIs LBH589, SAHA, and TSA on ESCC was characterized, with LBH589 displaying the most potent anti-proliferative activity while not harming normal immortalized esophageal epithelial cells. Furthermore, we propose that LBH589 exerts its anti-proliferative effect by inducing cell cycle arrest. The ability to specifically target cancer cells indicates therapeutic potential for use of LBH589 in the treatment of ESCC.

BACKGROUND: Despite the abundance of measures to assess medication adherence by persons suffering schizophrenia, few studies have evaluated their concordance and validity against a reference standard in resource-poor community settings. We explored the concordance and validity of several measures to assess antipsychotic medication adherence in a resource-poor community. METHOD: Based on a random sample of 278 villagers diagnosed with schizophrenia from Liuyang, Hunan Province, China, we used a concordance correlation coefficient (r(c)) and Kappa statistic to assess agreement among pill counts, refill records, clinician rating, Drug Attitude Inventory (DAI), and the Brief Adherence Rating Scale (BARS). The validity of various measures was evaluated by their concordance and sensitivity/specificity to home-based unannounced pill count (UPC) as the reference standard. RESULTS: The estimated proportion of adherent patients according to all measures (41%~88%) was substantially higher than identified by UPC (35%). Concordance between any two measures was poor (r(c) /Kappa mostly < 0.30). Validity of various measures also was poor against the UPC (r(c)

Pogostone (PO), a major component of Pogostemon cablin, displays potent protective effects against lipopolysaccharide-induced acute lung injury (ALI) in mice. This study aimed to investigate the protective effect of PO on TNF-α-induced cell injury in human alveolar epithelial cells in vitro and its underlying mechanism. The cell viability was measured using the MTS method. The cell apoptosis was determined using flow cytometry. The activities of reactive oxygen species (ROS) were detected using a fluorescence microscope. The pro-inflammatory cytokines and antioxidant genes were assessed using reverse transcription-polymerase chain reaction. The protein expression of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκBα), and nuclear factor-kappa B (NF-κB) p65 was analyzed using the Western blot analysis. PO alleviated cell apoptosis and inhibited ROS production. It alleviated TNF-α-induced cell injury, suppressed the levels of inflammatory cytokines [interleukin (IL)-6, IL-1β, and IL-8], and enhanced the expression of antioxidant genes (quinine oxidoreductase 1, glutamate cysteine ligase catalytic subunit, heme oxygenase-1). It increased the expression of Keap1 and promoted the activation of Nrf2. However, the phosphorylation of IκBα and the nuclear expression of NF-κB p65 decreased. The anti-inflammatory and antioxidant effects of PO were abrogated following Nrf2 and NF-κB p65 knockdown. The results indicated a protective effect of PO against TNF-α-induced cell injury in A549 cells by modulating the balance between Nrf2 and NF-κB p65 signaling pathways. They verified PO as a promising anti-inflammatory adjuvant drug for treating ALI.

Atherogenesis is a chronic inflammatory process that involves complex interactions between endothelial dysfunction, lipid deposition and vascular smooth-muscle cell (VSMC) proliferation. However, the molecular mechanism is still unclear. We found that a pro-atherosclerotic factor (oxLDL) induced the expression of Krüppel-like factor 5 (KLF5), which in turn increased miR-29a expression levels. The increased miR-29a was retained within HASMCs and down-regulated Fbw7/CDC4 expression by targeting the 3´UTR of Fbw7/CDC4, subsequently increasing KLF5 stability by reducing the Fbw7/CDC4-dependent ubiquitination of KLF5, forming a positive feedback loop to enhance VSMC proliferation and promote atherogenesis. These results indicate a potentially important role for the oxLDL-activated feedback mechanism in VSMC proliferation and atherogenesis. Suppression of miR-29a may be an effective way to attenuate atherosclerosis. In conclusion, our data are the first to reveal that the regulatory crosstalk between KLF5, miR-29a, and Fbw7/CDC4 cooperatively promotes atherosclerotic development.

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are most widely used as effective anti-inflammatory agents. However, their clinical application brings about inevasible gastrointestinal side effects. Pogostemon cablin is a traditional herbal medicine used for the treatment of gastrointestinal diseases in China. One of its representative components, the tricyclic triterpenoid β-patchoulone (β-PAE) has demonstrated great anti-inflammatory activity and gastroprotective effect against ethanol-induced gastric injury, but its protective effect against gastric ulcer induced by indomethacin is still unknown. Purpose To assess the protective effect of β-PAE against ulcer produced by indomethacin and reveal the underlying pharmacological mechanism. Study design We used an indomethacin-induced gastric ulcer model of rats in vivo. Methods Gastroprotective activity of β-PAE (10, 20, 40 mg/kg, i.g.) was estimated via indomethacin-induced gastric ulcer model in rats. Histopathological and histochemical assessment of ulcerated tissues were performed. Protein and mRNA expression were determined by Elisa, Western blotting and qRT-PCR. Results β-PAE could inhibit ulcer formation. Histopathological and histochemical assessment macroscopically demonstrated that β-PAE alleviates indomethacin-induced gastric ulceration in dose-dependent manner. After administration of β-PAE, elevated tumor necrosis factor -α level was significantly decreased and the phosphorylation of JNK and IκB was markedly inhibited. β-PAE suppressed the levels of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule and monocyte chemoattractant protein 1, as well as myeloperoxidase. Meanwhile, β-PAE increased cyclooxygenase enzyme activities (COX-1 and COX-2) to enhance the production of prostaglandin E2. Proangiogenic protein, vascular endothelial growth factor and its receptor fms-like tyrosine kinase-1 mRNA expression were promoted while anti-angiogenic protein, endostatin-1 and its receptor ETAR mRNA expression were decreased. Conclusion β-PAE may provide gastroprotection in indomethacin-induced gastric ulcer in rats by reducing inflammatory response and improving angiogenesis.

Fish generally perform routine swimming behaviors during food digestion; thus, changes in swimming performance and adjustments to spontaneous behavior resulting from digestion can have important ecological significance for wild fishes. The effects of feeding on metabolism, spontaneous activity, fast-start escape movement, and critical swimming speed (U crit) were investigated in five cyprinids with different habitat preferences, specifically the Chinese crucian carp (Carassius auratus), common carp (Cyprinus carpio), black carp (Mylopharyngodon piceus), Chinese bream (Parabramis pekinensis), and qingbo (Spinibarbus sinensis). Generally, species in still water exhibited increased feeding metabolism, whereas species in flowing water showed higher spontaneous activity and locomotion performance. Digestion had no significant effects on either spontaneous activity or fast-start escape movement in the five cyprinids. These results could be due to the small meal sizes (approximately 2% body mass) and active foraging modes of cyprinids. The changes in aerobic swimming performance due to feeding were more complex. No effect of digestion on U crit was observed in crucian carp (still water, high feeding metabolism, and low U crit), common carp (widely distributed, high feeding metabolism, and high U crit), and qingbo (flowing water, low feeding metabolism, and high U crit), but digestion resulted in a significant decrease in the U crit of Chinese bream (moderate feeding metabolism but high U crit) and black carp (moderate feeding metabolism and low U crit), suggesting no connection between postprandial U crit changes and feeding metabolism (or between U crit and preferred habitat). The maximum metabolic rate (MMR) of common carp and crucian carp increased after feeding, whereas the corresponding values for the other three cyprinids remained the same. The oxygen uptake capacity appears to meet the oxygen demand of both aerobic swimming and digestion in common carp and crucian carp, whereas qingbo sacrifices digestion for locomotion, and black carp and Chinese bream sacrifice locomotion for digestion under postprandial swimming conditions. The locomotion-priority mode of qingbo is adaptive to its active foraging mode in the demanding swimming habitat of rapidly flowing water, whereas the high respiratory capacities of postprandial crucian carp and common carp and hence the maintenance of their aerobic swimming performances might be a by-product of natural selection for hypoxia tolerance rather than for swimming speed.

Statin combined with ezetimibe demonstrates significant benefit in lowering low density lipid cholesterol (LDL-C) and cardiovascular events abroad, but whether intermediate intensity statins combined with ezetimibe is superior to high-intensity statin monotherapy in Chinese people is unknown.A total of 125 patients were randomly assigned to a intermediate intensity rosuvastatin group (rosuvastatin 10mg/d, n=42), high-dose rosuvastatin group (rosuvastatin 20mg/d, n=41) or combination therapy group (ezetimibe 10mg/d and rosuvastatin 10mg/d, n=42) with a 12-week follow-up. The primary end point was the proportion of patients who achieved the 2011 ESC/EAS LDL-C goal70mg/dL (1.8mmol/L) at week 12. Secondary end points included changes from baseline in lipids, the occurrence of all cardiovascular events, high-sensitivity C-reactive protein and safety markers.The combination therapy group in the primary end point was significantly higher than rosuvastatin (20mg) and rosuvastatin (10mg) at week 12 (81.0% vs 68.3% vs 33.3%, P0.001). And the similar change was observed in reducing LDL-C levels at week 12 (67.28% vs 52.80% vs 43.89%, P0.001). The incidence of drug-related adverse events was much higher in the rosuvastatin 20mg group than the rosuvastatin 10mg group and the combination therapy group (17.0% vs 2.4% vs 4.8%, P0.05).The combination of rosuvastatin 10mg/ezetimibe 10mg was an effectively alternative therapy superior to rosuvastatin 20mg or 10mg with a greater effect on lowering LDL-C and a lower incidence of drug-related adverse events in Chinese patients.

Background The number of Chinese migrants in Sub-Saharan Africa (SSA) is increasing, which is part of the south-south migration. The healthcare seeking challenges for Chinese migrants in Africa are different from local people and other global migrants. The aim of this study is to explore utilization of local health services and barriers to health services access among Chinese migrants in Kenya. Methods Thirteen in-depth interviews (IDIs) and six focus group discussions (FGDs) were conducted among Chinese migrants (n = 32) and healthcare-related stakeholders (n = 3) in Nairobi and Kisumu, Kenya. Data was collected, transcribed, translated, and analyzed for themes. Results Chinese migrants in Kenya preferred self-treatment by taking medicines from China. When ailments did not improve, they then sought care at clinics providing Traditional Chinese Medicine (TCM) or received treatment at Kenyan private healthcare facilities. Returning to China for care was also an option depending on the perceived severity of disease. The main supply-side barriers to local healthcare utilization by Chinese migrants were language and lack of health insurance. The main demand-side barriers included ignorance of available healthcare services and distrust of local medical care. Conclusions Providing information on quality healthcare services in Kenya, which includes Chinese language translation assistance, may improve utilization of local healthcare facilities by Chinese migrants in the country.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible interstitial lung disease, with no effective cure. Polydatin is a resveratrol glucoside with strong antioxidant, anti-inflammatory and anti-apoptotic properties, which is used for treating health-related disorders such as cardiac disabilities, various types of carcinoma, hepatitis and hepatic fibrosis. The present study aimed to investigate the protective effect of polydatin against bleomycin-induced IPF and the possible underlying mechanism. A549 cells were treated with transforming growth factor-β1 (TGF-β1) and polydatin to observe phenotypic transformation and the related gene expression was detected. Sprague-Dawley rats were divided into seven groups and intratracheally infused with bleomycin to establish a pulmonary fibrosis model (the sham control group received saline). The rats were given pirfenidone (50 mg/kg), resveratrol (40 mg/kg) and polydatin (10, 40 and 160 mg/kg) for 28 days. The results demonstrated that polydatin had low toxicity to A549 cells and inhibited TGF-β1-induced phenotypic transformation as determined by MTS assay or observed using a light microscope. It also decreased the gene expression levels of α-smooth muscle actin and collagen I and increased the gene expression levels of epithelial cell cadherin in vitro and in vivo by reverse transcription-quantitative PCR. Furthermore, polydatin ameliorated the pathological damage and fiber production in lung tissues found by hematoxylin and eosin staining and Masson trichrome staining. Polydatin administration markedly reduced the levels of hydroxyproline, tumor necrosis factor-α, interleukin (IL)-6, IL-13, myeloperoxidase and malondialdehyde and promoted total superoxide dismutase activity in lung tissues as determined using ELISA kits or biochemical reagent kits. It inhibited TGF-β1 expression and phosphorylation of Smad 2 and 3 and ERK-1 and -2 in vivo as determined by western blot assays. These results suggest that polydatin protects against IPF via its anti-inflammatory, antioxidant and antifibrotic activities, and the mechanism may be associated with its regulatory effect on the TGF-β pathway.

Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) caused by gram-positive bacteria threatens human life because effective treatments and medicines is unavailable. Protostemonine (PSN), an active alkaloid mainly isolated from the roots of Stemona sesslifolia, has anti-inflammatory effects on asthma and gram-negative bacteria-induced ALI. Here, we found that PSN exhibits anti-inflammatory effects and alleviates heat-killed methicillin-resistant Staphylococcus aureus (HKMRSA)-induced pneumonia. PSN treatment significantly attenuated HKMRSA-induced pathological injury, pulmonary neutrophil infiltration, tissue permeability and the production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in murine ALI model. In addition, PSN decreased the content of TNF-α, IL-1β, IL-6 and the expression of iNOS, as well as the production of NO in HKMRSA-induced bone marrow derived macrophages (BMDMs). Furthermore, treatment with PSN suppressed the activation of MAPKs (e.g. p38 MAPK, JNK and ERK) and NF-κB. Collectively, our results suggest that PSN ameliorates gram-positive bacteria-induced ALI in mice by inhibition of the MAPK and NF-κB signaling pathways, and our studies suggest that PSN might be a novel candidate for treating ALI/ARDS.

Background Chlamydia trachomatis (CT) infection is considered to be related to adverse pregnancy outcomes, but we are still not sure whether prenatal screening and treatment of CT infection can prevent these. We conducted a pilot study to investigate the feasibility and acceptability of prenatal CT screening and treatment in China, in order to collect preliminary data for a RCT. Methods We recruited pregnant women at a gestational age between 12–14 weeks in a hospital in Guangzhou, China in April and May of 2018. All participants were screened for CT using Nucleic Acid Amplification Testing at the registry. Chlamydia-positive patients were provided one dose of azithromycin for treatment, and they were re-tested one-month after the treatment. We followed up every participant until delivery or end of pregnancy. We included nine adverse pregnancy outcomes (preterm birth (PTB), smaller than gestational age (SGA), birth defect, infant death, etc.). Results Of 453 women reached, 306 agreed for the screening and provided urine samples for testing. 302 (98.7%) of the collected samples were valid for testing, and 283 (92.5%) of questionnaires were obtained, but one was withdrew before delivery. Finally, we included 282 participants in this analysis whose mean age was 30.46 year (SD: 3.88). 14(5%) women were CT-positive at the registry. Eleven cases received treatment and three refused. All treated women was re-tested as negative after treatment. In treatment group (N=11), neither adverse pregnancy outcomes nor side effect of treatment was observed. In the non-treatment group (N=3), one still birth was found. Among 268CT-negative pregnant women, we observed 13 PTBs, 20 SGAs and 1 heart birth defect. Conclusion It is feasible and acceptable to conduct CT screening study among pregnant women. Although the sample size is limited, the study provided useful information for planning a RCT aimed to evaluate the efficacy of the testing and treatment strategy. Disclosure No significant relationships.

BackgroundSyphilis self-testing may help expand syphilis testing among men who have sex with men (MSM). China has rapidly scaled up human immunodeficiency virus (HIV) self-testing, creating an opportunity for integrated syphilis self-testing. However, there is a limited literature on implementing syphilis self-testing.MethodsA cross-sectional online survey was conducted among Chinese MSM in 2018. Participants completed a survey instrument including sociodemographic characteristics, sexual behaviors, syphilis self-testing, and HIV self-testing history. Multivariable logistic regression was conducted to identify correlates of syphilis self-testing. We also recorded potential harms associated with syphilis self-testing.ResultsSix hundred ninety-nine MSM from 89 cities in 21 provinces in China completed the study. A total of 361/699 (51.7%) men tested for syphilis, of whom 174/699 (24.9%) men used syphilis self-testing. Among 174 who had self-tested, 90 (51.7%) reported that the self-test was their first syphilis test and 161 (92.5%) reported that they undertook syphilis self-testing together with HIV self-testing. After adjusting for covariates, syphilis self-testing was correlated with disclosure of sexual orientation to family or friends (adjusted odds ratio [aOR], 1.90; 95% confidence interval [CI], 1.32–2.73), reporting 2–5 male sexual partners (aOR, 1.81; 95% CI, 1.04–3.16), HIV self-testing (aOR, 39.90; 95% CI, 17.00–93.61), and never tested for syphilis in the hospital (aOR, 2.96; 95% CI, 1.86–4.72). Self-reported harms associated with syphilis self-testing were minimal.ConclusionsScaling up syphilis self-testing could complement facility-based testing in China among MSM. Self-testing may increase first-time testing and has limited harms. Our findings suggest that syphilis self-testing could be integrated into HIV self-testing services.

BackgroundIndividuals with risk-loving attitudes may be more likely to participate in high-risk sex and gambling. We investigated whether a lottery-based financial incentive to have a negative syphilis test may attract Chinese men who have sex with men (MSM) who practised risky sexual behaviours.MethodsIn July 2018, a national online cross-sectional survey was conducted in China. We collected information on willingness to participate in a lottery-based financial incentive where men were eligible if they tested negative for syphilis, and the minimum prize that would attract them to participate. We used a validated risk attitude scale which asked about the willingness to take risks in six domains, ranging from 0 (avoids taking risk) to 10 (fully prepared to take risks). To avoid multicollinearity, we used principal components analysis to create a ‘risk attitude index’. Bivariable and multivariable logistic regression explored factors associated with willingness to test negative for syphilis.Results699 MSM enrolled with a median age of 26 years (IQR: 23–30). 70% self-identified as gay and 52% reported ever testing for syphilis. 64% stated they were likely or very likely to test for syphilis linked with a lottery-based incentive. The median desired amount for the lottery had an expected value of ¥10 (US$1.50, IQR: ¥5–¥30). Men who had greater odds of willingness to participate in the lottery-based incentive were those scoring highest on the risk attitude index (adjusted OR (AOR) 2.6, 95% CI 1.5 to 4.3), those reporting more than one sexual partner in the last 3 months (AOR 1.7, 95% CI 1.2 to 2.4), those who had not used condoms during their last sex (AOR 1.5, 95% CI 1.0 to 2.2) and those who ever had group sex (AOR 1.5, 95% CI 1.0 to 2.2).ConclusionChinese MSM with higher risk attitudes and who reported riskier sexual behaviours indicated greater interest in the concept of a lottery-based incentive for syphilis testing. A lottery-based incentive may be a promising strategy for promoting condom use among risk-loving men.

Background Schizophrenia is a leading cause of disability, and a shift from facility- to community-based care has been proposed to meet the resource challenges of mental healthcare in low- and middle-income countries. We hypothesized that the addition of mobile texting would improve schizophrenia care in a resource-poor community setting compared with a community-based free-medicine program alone. Methods and findings In this 2-arm randomized controlled trial, 278 community-dwelling villagers (patient participants) were randomly selected from people with schizophrenia from 9 townships of Hunan, China, and were randomized 1:1 into 2 groups. The program participants were recruited between May 1, 2015, and August 31, 2015, and the intervention and follow-up took place between December 15, 2015, and July 1, 2016. Baseline characteristics of the 2 groups were similar. The patients were on average 46 years of age, had 7 years of education, had a duration of schizophrenia of 18 years with minimal to mild symptoms and nearly one-fifth loss of functioning, and were mostly living with family (95%) and had low incomes. Both the intervention and the control groups received a nationwide community-based mental health program that provided free antipsychotic medications. The patient participants in the intervention group also received LEAN (Lay health supporters, E-platform, Award, and iNtegration), a program that featured recruitment of a lay health supporter and text messages for medication reminders, health education, monitoring of early signs of relapses, and facilitated linkage to primary healthcare. The primary outcome was medication adherence (proportion of dosages taken) assessed by 2 unannounced home-based pill counts 30 days apart at the 6-month endpoint. The secondary and other outcomes included patient symptoms, functioning, relapses, re-hospitalizations, death for any reason, wandering away without notifying anyone, violence against others, damaging goods, and suicide. Intent-to-treat analysis was used. Missing data were handled with multiple imputations. In total, 271 out of 278 patient participants were successfully followed up for outcome assessment. Medication adherence was 0.48 in the control group and 0.61 in the intervention group (adjusted mean difference [AMD] 0.12 [95% CI 0.03 to 0.22]; p = 0.013; effect size 0.38). Among secondary and other outcomes we noted substantial reduction in the risk of relapse (26 [21.7%] of 120 interventional participants versus 40 [34.2%] of 117 controls; relative risk 0.63 [95% CI 0.42 to 0.97]; number needed to treat [NNT] 8.0) and re-hospitalization (9 [7.3%] of 123 interventional participants versus 25 [20.5%] of 122 controls; relative risk 0.36 [95% CI 0.17 to 0.73]; NNT 7.6). The program showed no statistical difference in all other outcomes. During the course of the program, 2 participants in the intervention group and 1 in the control group died. The limitations of the study include its lack of a full economic analysis, lack of individual tailoring of the text messages, the relatively short 6-month follow-up, and the generalizability constraint of the Chinese context. Conclusions The addition of texting to patients and their lay health supporters in a resource-poor community setting was more effective than a free-medicine program alone in improving medication adherence and reducing relapses and re-hospitalizations. Future studies may test the effectiveness of customization of the texting to individual patients. Trial registration Chinese Clinical Trial Registry ChiCTR-ICR-15006053., Wenjie Gong and colleagues show that mobile messaging can increase medication adherence and reduce relapses in schizophrenia patients in rural China., Author summary Why was this study done? Schizophrenia is a leading cause of disability, but in low- and middle-income countries (LMICs) the treatment gap remains high, and even when treatment is available, adherence to antipsychotics is low. Mobile text messaging has been shown to be useful to strengthen community- and family-based care in resource-poor settings due to its availability, reliability, and ease of use. However, there has been no clear evidence that texting improves treatment adherence, symptoms, and functioning in people with schizophrenia. What did the researchers do and find? We developed an intervention called LEAN, involving the recruitment of lay health supporters; an electronic platform with mobile texting for medication reminders, health education, and monitoring; the awarding of token gifts for positive behavioral improvement, and integration of the texting with the health system. In this 2-arm randomized controlled trial, the control group received a free antipsychotic medication program (the 686 Program) while the intervention group received the 686 Program plus LEAN. We found significant improvement in medication adherence (0.48 in the control group versus 0.61 in the intervention group) and a substantial reduction in the risks of relapse and re-hospitalization with the intervention. What do these findings mean? LEAN demonstrated a 27% improvement in adherence, which is larger than the 15%–18% range reported in other text message interventions. Two unique features may have contributed to the relative superiority of LEAN: active engagement of lay health supporters and the use of texting to connect the entire treatment team from patients to lay health supporters to village doctors to psychiatrists, all in support of the patient. Texting effectively addressed the low adherence at marginal cost, and LEAN’s experiences may be useful for other LMICs with resource constraints. However, an adaptation of LEAN should fully consider some implementation details including keeping the program simple and integrated into routine care, maintaining low cost, and choosing existing texting platforms if available.

Cisplatin remains the standard first-line chemotherapeutic agent in the treatment of many types of cancers, but its clinical application is hindered by its severe nephrotoxicity. Previous studies reported that scutellarin enhanced the anti-cancer activity of cisplatin in lung cancer cells, with no confirmation on cisplatin-induced renal damage. Here, we investigated the nephroprotective effect of scutellarin on cisplatin-induced renal injury and its underlying mechanisms. Renal function, histological change, inflammation, apoptosis, autophagy and involved pathways were investigated. Pretreatment with scutellarin prevented cisplatin-induced decline of renal function including BUN, CRE, and histological damage. Scutellarin also reduced renal inflammation by suppressing the levels of pro-inflammatory cytokine, TNF-α and IL-6. Similarly, scutellarin administration inhibited apoptosis triggered by cisplatin through reducing the expressions of Cleaved caspase-3, Cleaved PARP, p53, and the ratio of Bax/Bcl-2. Moreover, scutellarin prevented cisplatin-induced inhibition of autophagy via enhancing LC3-II/LC3-I and Atg7, and inhibition of p62. Of note, the activations of JNK, ERK, p38 and stat3 induced by cisplatin were strikingly attenuated in scutellarin-treated mice. Thus, these results provide compelling evidence that scutellarin is a novel nephroprotectant against cisplatin-induced renal toxicity.