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Drug-induced liver injury (DILI) is a common adverse drug reaction leading to the interruption of tuberculosis (TB) therapy. We aimed to identify whether the hepatitis B virus (HBV) infection would increase the risk of DILI during first-line TB treatment. A meta-analysis of cohort studies searched in PubMed, Web of Science and China National Knowledge Infrastructure was conducted. Effect sizes were reported as risk ratios (RRs) and 95% confidence intervals (CIs) and calculated by R software. Sixteen studies with 3960 TB patients were eligible for analysis. The risk of DILI appeared to be higher in TB patients co-infected with HBV (RR 2.66; 95% CI 2.13–3.32) than those without HBV infection. Moreover, patients with positive hepatitis B e antigen (HBeAg) were more likely to develop DILI (RR 3.42; 95% CI 1.95–5.98) compared to those with negative HBeAg (RR 2.30; 95% CI 1.66–3.18). Co-infection with HBV was not associated with a higher rate of anti-TB DILI in latent TB patients (RR 4.48; 95% CI 0.80–24.99). The effect of HBV infection on aggravating anti-TB DILI was independent of study participants, whether they were newly diagnosed with TB or not. Besides, TB and HBV co-infection patients had a longer duration of recovery from DILI compared to non-co-infected patients (SMD 2.26; 95% CI 1.87–2.66). To conclude, the results demonstrate that HBV infection would increase the risk of DILI during TB therapy, especially in patients with positive HBeAg, and close liver function monitoring is needed for TB and HBV co-infection patients.
The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
No studies have reported on how to relieve distress or relax in medical health workers while wearing medical protective equipment in coronavirus disease 2019 (COVID-19) pandemic. The study aimed to establish which relaxation technique, among six, is the most feasible in first-line medical health workers wearing medical protective equipment.
This was a two-step study collecting data with online surveys. Step 1: 15 first-line medical health workers were trained to use six different relaxation techniques and reported the two most feasible techniques while wearing medical protective equipment. Step 2: the most two feasible relaxation techniques revealed by step 1 were quantitatively tested in a sample of 65 medical health workers in terms of efficacy, no space limitation, no time limitation, no body position requirement, no environment limitation to be done, easiness to learn, simplicity, convenience, practicality, and acceptance.
Kegel exercise and autogenic relaxation were the most feasible techniques according to step 1. In step 2, Kegel exercise outperformed autogenic relaxation on all the 10 dimensions among the 65 participants while wearing medical protective equipment (efficacy: 24 v. 15, no space limitation: 30 v. 4, no time limitation: 31 v. 4, no body position requirement: 26 v. 4, no environment limitation: 30 v. 11, easiness to learn: 28 v. 5, simplicity: 29 v. 7, convenience: 29 v. 4, practicality: 30 v. 14, acceptance: 32 v. 6).
Kegel exercise seems a promising self-relaxation technique for first-line medical health workers while wearing medical protective equipment among COVID-19 pandemic.
The aim of this study was to explore the application of the flipped classroom approach in the training of Mass Casualty Triage (MCT) to medical undergraduate students.
In this study, 103 fourth-year medical students were randomly divided into a Flipped Classroom (FC) group (n = 51) and a Traditional Lecture-based Classroom (TLC) group (n = 52). A post-class quiz, simulated field triage (SFT) and feedback questionnaires were performed to assess both groups of students for their learning of the course.
In the post-quiz, the median (IQR) scores achieved by students from the FC and TLC groups were 42(5) and 39(5.5), respectively. Significant differences were found between the two groups. In the SFT, overall triage accuracy was 67.06% for FC, and 64.23% for TLC students. Over-triage and under-triage errors occurred in 18.43% and 14.50% of the FC group, respectively. The TLC group had a similar pattern of 20.77% over-triage and 15.0% under-triage errors. No significant differences were found regarding overall triage accuracy or triage errors between the two groups.
The FC approach could enhance course grades reflected in the post-quiz and improve students’ satisfaction with the class. However, there was no significant difference of competency between the two groups demonstrated in the SFT exercise.
To examine the associations between serum 25-hydroxyvitamin D (25(OH)D) levels and serum liver enzymes in a representative sample of US adults.
The cross-sectional study sample consisted of 24 229 adults with data on serum 25(OH)D levels and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transaminase (GGT) concentrations, in addition to data on other potential confounders. Multivariate logistic regression and linear regression were applied to assess the associations between serum 25(OH)D levels and ALT, AST, ALP and GGT concentrations.
The National Health and Nutrition Examination Survey, 2001–2006.
The cross-sectional study sample consisted of 24 229 adults.
We found a significant association between low serum 25(OH)D levels (<30 nmol/l) and ALP levels in all participants (OR 2·67; 95 % CI 1·98, 3·59; P < 0·001), a confirmed healthy population (OR 3·02; 95 % CI 2·25, 4·07; P < 0·001) and individuals with viral hepatitis (OR 2·87; 95 % CI 1·52, 5·44; P = 0·006) compared with those who had normal 25(OH)D levels (>50 nmol/l). Moreover, in both the logistic regression and linear regression, the associations between 25(OH)D levels and ALP levels were stronger in the subgroups with obesity. No association was present between ALT, AST or GGT levels and serum 25(OH)D levels in this population.
The results of the present study provide epidemiological evidence that vitamin D deficiency is associated with liver ALP levels in humans. This finding suggests a potential adverse effect of low 25(OH)D levels on human liver function. However, the underlying mechanisms still need further investigation.
The Wulian complex is located on the northern margin of the Sulu orogenic belt, and was formed by collision between the North China Craton (NCC) to the north and South China Craton (SCC) to the south. It consists of the metasedimentary Wulian Group, gneissic granite and meta-diorite. The U–Pb analyses for the detrital zircons from the Wulian Group exhibit one predominant age population of 2600–2400 Ma with a peak at c. 2.5 Ga and several secondary age populations of > 3000, 3000–2800, 2800–2600, 2200–2000, 1900–1800, 1500–1300 and 1250–950 Ma; some metamorphic zircons have metamorphic ages of c. 2.7, 2.55–2.45, 2.1–2.0 and 1.95–1.80 Ga, which are consistent with magmatic-metamorphic events in the SCC. Additionally, the Wulian Group was intruded by the gneissic granite and meta-diorite at c. 0.76 Ga, attributed to Neoproterozoic syn-rifting bimodal magmatic activity in the SCC and derived from partial melting of Archaean continental crust and depleted mantle, respectively. The Wulian Group therefore has tectonic affinity to the SCC and was mainly sourced from the SCC. The detrital zircons have positive and negative ϵHf(t) values, indicating that their source rocks were derived from reworking of both ancient and juvenile crustal rocks. The major early Precambrian crustal growth took place during c. 3.4–2.5 Ga with a dominant peak at 2.96 Ga and several secondary peaks at 3.27, 2.74 and 2.52 Ga. The two oldest zircons with ages of 3307 and 3347 Ma record the recycling of ancient continental crust (> 3.35 Ga) and crustal growth prior to c. 3.95 Ga in the SCC.
We study the impact of board reforms implemented in 40 countries worldwide on corporate dividend policy. Using a difference-in-differences analysis, we find that firms pay higher dividends following the reforms. The increase in dividend payouts is more pronounced for firms with weak board governance in the pre-reform period and those in countries with strong external governance mechanisms. Our findings corroborate the dividend outcome model, which postulates that board reforms strengthen the monitoring role of the board and empower outside shareholders to force management to disgorge dividends.
The South Altyn Orogenic Belt (SAOB) is one of the most important orogenic belts in NW China, consisting of the South Altyn Continental Block and the Apa–Mangya Ophiolitic Mélange Belt. However, its Palaeozoic tectonic evolution is still controversial. Here, we present petrological, geochemical, zircon U–Pb and Lu–Hf isotopic data for the Mangya plutons with the aim of establishing the Palaeozoic tectonic evolution. We divide the Early Palaeozoic magmatism in the Apa–Mangya Ophiolitic Mélange Belt into four episodes and propose a plate tectonic model for the formation of these rocks. During 511–494 Ma, the South Altyn Ocean (SAO) was in a spreading stage, and some shoshonite series, I-type granitic rocks were generated. From 484 to 458 Ma, the oceanic crust of the SAO subducted northward, accompanied by large-scale magmatic events resulting in the generation of vast high-K calc-alkaline series, I-type granitic rocks. During 450–433 Ma, the SAO closed, and break-off of the subducted oceanic slab occurred, with the generation of some high-K calc-alkaline series, I–S transitional type granites. The SAOB was in post-orogenic extensional environment from 419 to 404 Ma, and many A-type granites were generated.
Signal-in-space (SIS) continuity and availability are important indicators of performance assessment for Global Navigation Satellite Systems (GNSSs). The BeiDou Navigation Satellite System (BDS) Open Service Performance Standard (BDS-OS-PS-1.0) has been released, and the corresponding public performance indicators have been provided, but the actual SIS performance is uncertain to users. SIS continuity and availability are primarily related to unscheduled outages (failures). Therefore, based on the existing failure classification system and actual operation modes, four types of failure modes are first analysed: long-term failure related to satellite service period, maintenance failure related to satellite manoeuvring, short-term failure associated with random repairable anomalies and equivalent failure corresponding to a combination of the above three types of failures. Second, based on the failure classification and selected precise and broadcast ephemerides from 2015–2016, the Mean Time Between Failure (MTBF) and Mean Time To Repair (MTTR) of each failure type are obtained using appropriate detection methods. Finally, using a corresponding assessment model, the SIS continuity and availability of BeiDou are calculated for individual and equivalent failure cases, and these are compared with the provided index in the BDS Open Service Performance Standard.
Clozapine treatment increases the risk of agranulocytosis, but findings on the epidemiology of agranulocytosis have been inconsistent. This meta-analysis examined the prevalence of agranulocytosis and related death in clozapine-treated patients.
A literature search in the international (PubMed, PsycINFO, and EMBASE) and Chinese (WanFang, Chinese National Knowledge Infrastructure, and Sinomed) databases was conducted. Prevalence estimates of agranulocytosis and related death in clozapine-treated patients were synthesized with the Comprehensive Meta-Analysis program using the random-effects model.
Thirty-six studies with 260 948 clozapine-treated patients published between 1984 and 2018 were included in the meta-analysis. The overall prevalence of agranulocytosis and death caused by agranulocytosis were 0.4% (95% CI 0.3–0.6%) and 0.05% (95% CI 0.03–0.09%), respectively. The prevalence of agranulocytosis was moderated by sample size, study quality, year of publication, and that of data collection.
The prevalence of clozapine-associated agranulocytosis is low. Agranulocytosis-related death appears rare.
Muscle fibre types can transform from slow-twitch (slow myosin heavy chain (MyHC)) to fast-twitch (fast MyHC) or vice versa. Leucine plays a vital effect in the development of skeletal muscle. However, the role of leucine in porcine myofibre type transformation and its mechanism are still unclear. In this study, effects of leucine and microRNA-27a (miR-27a) on the transformation of porcine myofibre type were investigated in vitro. We found that leucine increased slow MyHC protein level and decreased fast MyHC protein level, increased the levels of phospho-protein kinase B (Akt)/Akt and phospho-forkhead box 1 (FoxO1)/FoxO1 and decreased the FoxO1 protein level. However, blocking the Akt/FoxO1 signalling pathway by wortmannin attenuated the role of leucine in porcine myofibre type transformation. Over-expression of miR-27a decreased slow MyHC protein level and increased fast MyHC protein level, whereas inhibition of miR-27a had an opposite effect. We also found that expression of miR-27a was down-regulated following leucine treatment. Moreover, over-expression of miR-27a repressed transformation from fast MyHC to slow MyHC caused by leucine, suggesting that miR-27a is interdicted by leucine and then contributes to porcine muscle fibre type transformation. Our finding provided the first evidence that leucine promotes porcine myofibre type transformation from fast MyHC to slow MyHC via the Akt/FoxO1 signalling pathway and miR-27a.
Heavy metal contamination in the paddy soils of China is a serious concern because of its health risk through transfer in food chains. A field experiment was conducted in 2014–2015 to investigate the long-term effects of different biochar amendments on cadmium (Cd) and arsenic (As) immobilisation in a contaminated paddy field in southern China. Two types of biochar, a rice-straw-derived biochar (RB) and a coconut-by-product-derived biochar (CB), were amended separately to determine their impacts on rice yield and their efficacy in reducing Cd and As in rice. The two-year field experiment showed that biochar amendments significantly improved the rice yields and that CB is superior to RB, especially in the first growth season. Using a large amount of biochar amendment (22.5tha–1) significantly increased soil pH and total organic carbon, and concomitantly decreased the Cd content in rice grains over the four growth seasons, regardless of biochar type and application rate. Arsenic levels in rice were similar to the control, and results from this study suggest that there was a sustainable effect of biochar on Cd sequestration in soil and reduction of Cd accumulation in rice for at least two years. Biochar amendment in soil could be considered as a sustainable, reliable and cost-effective option to remediate heavy metal contamination in paddy fields for long periods.
Northeastern China is a region of high tick abundance, multiple tick-borne pathogens and likely human infections. The spectrum of diseases caused by tick-borne pathogens has not been objectively evaluated in this region for clinical management and for comparison with other regions globally where tick-transmitted diseases are common. Based on clinical symptoms, PCR, indirect immunofluorescent assay and (or) blood smear, we identified and described tick-borne diseases from patients with recent tick bite seen at Mudanjiang Forestry Central Hospital. From May 2010 to September 2011, 42% (75/180) of patients were diagnosed with a specific tick-borne disease, including Lyme borreliosis, tick-borne encephalitis, human granulocytic anaplasmosis, human babesiosis and spotted fever group rickettsiosis. When we compared clinical and laboratory features to identify factors that might discriminate tick-transmitted infections from those lacking that evidence, we revealed that erythema migrans and neurological manifestations were statistically significantly differently presented between those with and without documented aetiologies (P < 0.001, P = 0.003). Twelve patients (6.7%, 12/180) were co-infected with two tick-borne pathogens. We demonstrated the poor ability of clinicians to identify the specific tick-borne disease. In addition, it is necessary to develop specific laboratory assays for optimal diagnosis of tick-borne diseases.
Leucine, one of the branched-chain amino acids, is the only amino acid to regulate protein turnover in skeletal muscle. Leucine not only increases muscle protein synthesis, but also decreases muscle protein degradation. It is well documented that leucine plays a positive role in differentiation of murine muscle cells. However, the role of leucine on porcine myoblast differentiation and its mechanism remains unclear. In this study, porcine myoblasts were induced to differentiate with differentiation medium containing different concentrations of leucine, and wortmannin was used to interdict the activity of protein kinase B (Akt). We found that leucine increased the number of myosin heavy chain-positive cells and creatine kinase activity. Moreover, leucine increased the mRNA and protein levels of myogenin and myogenic determining factor (MyoD). In addition, leucine increased the levels of phosphorylated Akt/Akt and phosphorylated Forkhead box O1 (P-FoxO1)/FoxO1, as well as decreased the protein level of FoxO1. However, wortmannin, a specific repressor of PI3K/Akt signalling pathway, attenuated the positive role of leucine on porcine myoblast differentiation. Our results suggest that leucine promotes porcine myoblast differentiation through the Akt/FoxO1 signalling pathway.
The Wuhan Pre/Post-Natal Twin Birth Registry (WPTBR) is one of the largest twin birth registries with comprehensive medical information in China. It recruits women from the first trimester of pregnancy and their twins from birth. From January 2006 to May 2016, the total number of twins enrolled in WPTBR is 13,869 twin pairs (27,553 individuals). The WPTBR initiated the Wuhan Twin Birth Cohort (WTBC). The WTBC is a prospective cohort study carried out through incorporation of three samples. The first one comprises 6,920 twin pairs, and the second one, 6,949 twin pairs. Both are population-based samples linked to the WPTBR and include pre- and post-natal information from WPTBR. The second sample includes neonatal blood spots as well. Using a hospital-based approach, we recently developed a third sample with a target enrolment of 1,000 twin pairs and their mothers. These twins are invited, via their parents, to participate in a periodic health examination from the first trimester of pregnancy to 18 years. Biological samples are collected initially from the mother, including blood, urine, cord blood, cord, amniotic fluid, placenta, breast milk and meconium, and vaginal secretions, and later from the twins, including meconium, stool, urine, and blood. This article describes the design, recruitment, follow-up, data collection, and measures, as well as ongoing and planned analyses at the WTBC. The WTBC offers a unique opportunity to follow women from prenatal to postnatal, as well as follow-up of their twins. This cohort study will expand the understanding of genetic and environmental influences on pregnancy and twins’ development in China.
Right pulmonary artery–left atrial fistula is a rare congenitalcardiac anomaly, and only a few articles published so far have reported the diagnosis and treatment of right pulmonary artery–left atrial fistula. In this study, we report three cases of successful transcatheter closure or surgical repair of right pulmonary artery–left atrial fistula.
Malaria remains one of the most devastating diseases. Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection resulting in high mortality and morbidity worldwide. Analysis of precise mechanisms of CM in humans is difficult for ethical reasons and animal models of CM have been employed to study malaria pathogenesis. Here, we describe a new experimental cerebral malaria (ECM) model with Plasmodium berghei ANKA infection in KunMing (KM) mice. KM mice developed ECM after blood-stage or sporozoites infection, and the development of ECM in KM mice has a dose-dependent relationship with sporozoites inoculums. Histopathological findings revealed important features associated with ECM, including accumulation of mononuclear cells and red blood cells in brain microvascular, and brain parenchymal haemorrhages. Blood–brain barrier (BBB) examination showed that BBB disruption was present in infected KM mice when displaying clinical signs of CM. In vivo bioluminescent imaging experiment indicated that parasitized red blood cells accumulated in most vital organs including heart, lung, spleen, kidney, liver and brain. The levels of inflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, interleukin (IL)-17, IL-12, IL-6 and IL-10 were all remarkably increased in KM mice infected with P. berghei ANKA. This study indicates that P. berghei ANKA infection in KM mice can be used as ECM model to extend further research on genetic, pharmacological and vaccine studies of CM.