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Objectives: To assess whether the extension of the flushing interval will increase risks of complications associated with totally implantable venous access port (TIVAP) in the off-treatment period. Methods: A retrospective single-center observational study was performed. Patients with a TIVAP in the off-treatment period that underwent regular flushing in our clinic were included. Data concerning patients and their TIVAPs were recorded. Patient baseline characteristics and TIVAP-related complications were analyzed. Continuous variables were analyzed by ANOVA or the Kruskal-Wallis H test. To compare the occurrence of TIVAP-related complications, the chi-square test was used; if needed, Fisher’s exact test was used. Results: Totally 607 patients were reviewed, and 563 patients were finally included. Thirteen complications were recorded, including 11 cases of catheter occlusion (1.95%), one case of port cannula rotation (0.18%), and one case of catheter tip malposition (0.18%). No device-related infection or venous thrombosis was recorded. Among these patients, the average flushing interval was 35.27 ± 13.09 days. Patients were divided into three groups according to the flushing interval: every 28 days or less (Group 1, n = 133); every 29–44 days (Group 2, n = 350); and every 45 days or more (Group 3, n = 80). No significant difference in catheter-related complications was found among the three groups (P > 0.05). Conclusions: In the TIVAP off-treatment period, patients without any history of TIVAP-related complications during approximately one year can attempt to prolong the flushing interval to more than 4 weeks; we further suggest that 5–6 weeks may be an appropriate option for these patients.

Abstract Background Abnormally elevated xanthine oxidase (XO) activity has been verified to cause various pathological processes, such as gout, oxidative stress injury and metabolic syndrome. Thus, XO activators may exhibit above potential toxicological properties. Plumbagin (PLB) is an important active compound in traditional Chinese medicine (TCM), while its obvious toxic effects have been reported, including diarrhea, skin rashes and hepatic toxicity. However, the potential toxicity associated with enhancement of XO activity has not been fully illuminated so far. Methods The present study investigated the effect of PLB on XO activity by culturing mouse liver S9 (MLS9), human liver S9 (HLS9), XO monoenzyme system with PLB and xanthine. Then, the molecular docking and biolayer interferometry analysis were adopted to study the binding properties between PLB and XO. Finally, the in vivo acceleration effect also investigated by injected intraperitoneally PLB to KM mice for 3 days. Results PLB could obviously accelerate xanthine oxidation in the above three incubation systems. Both the Vmax values and intrinsic clearance values (CLint, Vmax/Km) of XO in the three incubation systems increased along with elevated PLB concentration. In addition, the molecular docking study and label-free biolayer interferometry assay displayed that PLB was well bound to XO. In addition, the in vivo results showed that PLB (2 and 10 mg/kg) significantly increased serum uric acid levels and enhanced serum XO activity in mice. Conclusion In summary, this study outlines a potential source of toxicity for PLB due to the powerful enhancement of XO activity, which may provide the crucial reminding for the PLB-containing preparation development and clinical application.

Abstract Exosomes are nanosized membrane‐bound extracellular vesicles with the capacity to modify functions and behaviors of recipient cells via transferring unique biological information. Mounting evidence suggests that under developmental conditions, mesenchymal cell‐derived exosomes are capable of mediating intercellular communication between epithelium and mesenchyme during organogenesis of salivary gland, tooth, hair follicle, and kidney, shedding light on potential therapeutic benefits elicited by mesenchymal exosomes in nanomedicine. Representing the most extensively investigated multipotent stem cells, mesenchymal stem cells (MSCs) have been identified and extracted from a wide variety of tissues. Accordingly, exosomes derived from MSCs (MSC‐Exos) can be easily accessed and manipulated as nanoparticles, giving rise to an entirely new therapeutic agents for nanomedicine. MSC‐Exos have presently emerged as efficacious alternatives to MSCs for cell‐free therapeutic strategies in disease contexts of ischemic heart disease, cutaneous wound healing and coronavirus disease 2019. In this review, we first present a critical analysis of research state of exosomes in terms of their biogenesis, molecular composition, isolation and characterization, then summarize current understanding of developmental regulation mediated by mesenchymal cell‐derived exosomes and reparative potential conferred by MSC‐Exos, along with particular emphasis on the underlying mechanisms of action and commentary on the major outstanding issues faced with MSC‐Exos.

Abstract Background This study aims to evaluate the efficacy and safety of the iguratimod (IGU) as monotherapy or combined therapy in patients with rheumatoid arthritis (RA) by using meta-analysis. Methods We searched Medline, EMBASE, Cochrane library, CNKI, Wanfang medical network from initial to 30 June, 2020, for randomized clinical trials (RCTs). Two authors independently screened the studies via reading the title, abstract, and full text. The risk of bias in individual studies was assessed using the Cochrane Risk of Bias tool. STATA 12.0 was used for pooled analysis of all included studies. Results A total of 23 RCTs were included in this analysis. Meta-analysis showed that patients in the IGU monotherapy or combined therapy group had significantly higher ACR20 (OR = 1.97, 95% CI 1.29 to 3.00, P = 0.002), lower DAS28-CRP (SMD = −3.49, 95% CI −5.40 to −1.58, P < 0.001) and DAS28-ESR (SMD = −2.61, 95% CI −3.64 to −1.57, P < 0.001), as well as shorter duration of morning stiffness (SMD = −2.06, 95% CI −2.86 to −1.25, P < 0.001) and lower HAQ score (SMD = −0.91, 95% CI −1.61 to −0.21, P = 0.011), than those received other disease-modifying antirheumatic drugs (DMARDs) monotherapy (primarily comprising methotrexate). For the safety profile, IGU monotherapy had similar risks for gastrointestinal reactions (P = 0.070), leucopenia (P = 0.309), increment in transaminase (P = 0.321), increase of ALT (P = 0.051), and liver damage (P = 0.182) to methotrexate monotherapy, and IGU combined with other DMARDs therapy did not increase the risks of these AEs (P > 0.05). Conclusions Our evidence suggests that IGU is effective and tolerant as monotherapy or combined therapy especially with methotrexate in patients with active RA. IGU may be regarded as a potential alternative to methotrexate, and a preferable choice when combined with other DMARDs for the treatment of RA.

Abstract Background Self-medication is one of the most common forms of inappropriate use of antibiotics. This study aimed to assess the prevalence of self-medication with antibiotics (SMA) in China and evaluate the related factors. Methods A cross-sectional survey was conducted in Wuhan, Hubei, China from July 1, 2019 to July 31, 2019. Participants were recruited in public places to answer a structured questionnaire. The information of participants’ social demographic characteristics, antibiotic knowledge and health beliefs were collected. Binary Logistics regression analysis was used to examine the associated factors of SMA. Results Of the 3206 participants, 10.32% reported SMA in the past 6 months. Participants who with middle or high perceived barriers to seek health care services showed a higher likelihood of SMA (P

Abstract In this study, thin-film composite with embedded polyester screen, cellulose triacetate with a cast nonwoven and cellulose triacetate with embedded polyester screen (CTA-ES) was examined as the intermediate membranes in osmotic microbial fuel cells (OsMFCs). The reactors were fed with actual landfill leachate and the performance was studied in two operation modes: active layer facing draw solution and active layer facing feed solution (AL-FS). The OsMFC with CTA-ES exhibited the best energy generation (maximum power density: 0.44 W m− 2) and pollutant removal efficiency (ammonia nitrogen: 70%, total nitrogen: 74%) in the AL-FS mode, which could be ascribed to the lowest internal resistance (237 Ω) and highest microbial richness. Pseudomonas was the highest proportion of microbial in OsMFCs. The result of this study has demonstrated the potential of OsMFCs for landfill leachate treatment.

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.

Abstract Background Several studies suggested that thrombotic and obstetric antiphospholipid syndromes could be independent identities, but few have systematically compared their clinical characteristics and prognosis. Objective The objective of this study is to identify key differences between thrombotic APS (tAPS) and obstetric APS (oAPS). Methods This single-center, prospective study included consecutive patients with primary antiphospholipid syndrome (APS) receiving treatment at the Peking Union Medical College Hospital during a period from 2013 to 2020. Results Screening of the database yielded a total of 244 women with positive antiphospholipid antibody (aPL). Among the 105 women with primary APS, 39 (37.14%) had isolated tAPS (ItAPS), 44 (41.90%) had isolated oAPS (IoAPS), and 9 (8.57%) had both tAPS and tAPS+oAPS. In comparison to those with IoAPS, patients with ItAPS had older age (41.92 ± 11.97 vs. 33.16 ± 4.22 years, P < 0.01), higher rate of cardiovascular risk (at least one positive of coronary heart disease, hypertension, obesity, diabetes, and hyperlipidemia) (41.03% vs. 6.82%, P < 0.01), and higher frequency of thrombocytopenia (43.59% vs. 20.45%, P < 0.05). Antibody profiles were generally similar among the groups, but isolated anti-β2GPI positivity was more common in patients with IoAPS (52.27% vs. 17.94% for ItAPS, P = 0.01). Triple aPL positivity was more common in patients with both tAPS and oAPS (66.67% vs. 46.15% for ItAPS vs. 25% for IoAPS, P = 0.022). Blood homocysteine was higher in patients with ItAPS (11.20 vs. 9.90 μmol/L for IoAPS, P < 0.05), but there were no differences in inflammatory markers or complements. Recurrence rate of thrombosis was higher in patients with ItAPS (33.33% vs. 2.27% for IoAPS, P ≤ 0.001) with a mean follow-up of 61 months. Conclusion Despite generally similar antibody and biochemical profiles, patients with ItAPS had much higher risk of recurrent thrombosis than IoAPS, supporting distinct mechanisms of pathogenesis.

Infectious bursal disease (IBD) is caused by infectious bursal disease virus (IBDV), which has a genome consisting of two segments of double-stranded linear RNA. IBDVs have been traditionally divided into four phenotypes based on their pathogenicity and antigenicity, including classic, variant, very virulent, and attenuated IBDV. With the emergences of divergent molecular characteristics of novel strains produced by continuous mutations and recombination, it is increasingly difficult to define new IBDV strains using the traditional descriptive classification method. The most common classification scheme for IBDV with segmented genome is based solely on segment A, while the significance of segment B has been largely neglected. In this study, an improved scheme for IBDV genotype classification based on the molecular characteristics of both VP2 (a viral capsid protein encoded by segment A) and VP1 (an RNA-dependent RNA polymerase protein encoded by segment B) was proposed for the first time. In this scheme, IBDV was classified into nine genogroups of A and five genogroups of B, respectively; the genogroup A2 was further divided into four lineages. The commonly used phenotypic classifications of classic, variant, very virulent, and attenuated IBDVs correspond to the A1B1, A2B1, A3B2, and A8B1 genotypes of the proposed classification scheme. The novel variant IBDVs including the strains identified in this study were classified as belonging to genotype A2dB1. The flexibility and versatility of this improved classification scheme will allow the unambiguous identification of existing and emerging IBDV strains, which will greatly facilitate molecular epidemiology studies of IBDV.

BackgroundOrganizational commitment is important for job performance and employee retention. However, studies on the level of organizational commitment and its related factors among emergency physicians in China are scarce. Therefore, this study aimed to identify the factors associated with organizational commitment among emergency physicians in China.MethodsA national cross-sectional study was conducted in 2018 among emergency physicians in China. Data were collected from 10,457 emergency physicians using a standard structured anonymous questionnaire, including demographic characteristics, organizational structure factors and work environment factors. A generalized linear model was used to explore the correlation between the independent variables and organizational commitment.ResultsIn this study, 55.3% of emergency physicians reported a moderate level of organizational commitment. The physicians who were male, younger than 40 years old, had a mid-level title and had a lower average monthly income were more likely to show lower organizational commitment levels. Conversely, the organizational commitment was higher among physicians who perceived that promotion is easy and the number of emergency physicians meet their daily work or had not experienced workplace violence in the last year.ConclusionsThe study showed that organizational commitment among Chinese emergency physicians was moderate and related to gender, age, monthly income, frequency of daily visits, departmental promotion mechanism and workplace violent. Targeted interventions are needed to improve the organizational commitment of emergency physicians in a comprehensive way.

Background: Previous studies had reported that vitamin D receptor (VDR) gene polymorphisms were related to the development of several inflammatory disorders. However, potential links between such variations and the risk of developing a bone infection and underlying mechanisms remain unclear. This study aimed to analyze potential associations between VDR genetic variations and susceptibility to extremity osteomyelitis (OM) in a Chinese Han population and investigate potential mechanisms.Methods: Between January 2016 and August 2020, altogether 398 OM patients and 368 healthy controls were genotyped for six VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), TaqI (rs731236), GATA (rs4516035), and Cdx-2 (rs11568820) by the SNaPshot genotyping method. Then, male C57BL/6 mice were randomly divided into vitamin D–standard, –excess, –deficient, and –rescued groups. One week after making the model surgery, OM occurrence and severity were assessed using the bacterial count and histopathological staining. In vitro, phagocytosis, apoptosis, and bactericidal ability of macrophages were evaluated by overexpression or knockdown of VDR protein.Results: Significant associations were found among rs7975232, rs1544410, and OM development by the recessive model (AA vs. AC + CC, p = 0.037, OR = 0.594), homozygous model (AA vs. CC, p = 0.033, OR = 0.575), and heterozygous model (CT vs. CC, p = 0.049, OR = 0.610), respectively. Patients with the AA genotype of rs7975232 had a relatively higher mean level of vitamin D than those with AC and CC genotypes (22.5 vs. 20.7 vs. 19.0 ng/ml). Similarly, patients with CT genotype of rs1544410 had a relatively higher mean vitamin D level than those with CC genotype (20.94 vs. 19.89 ng/ml). Outcomes of in vivo experiments showed that the femoral bacterial load of vitamin D–deficient mice was highest among different vitamin D dose groups, with the most severe histopathological features of infection, and vitamin D supplementation partly reversed the changes. While in vitro experiment results revealed that active vitamin D promoted phagocytosis and sterilization of macrophages and inhibited apoptosis during infection. Reactive oxygen species (ROS) inhibitor inhibited apoptosis of macrophages induced by bacterial infection. Active vitamin D inhibited excessive ROS production in macrophages via the VDR-Bmi1 signaling pathway.Conclusion: In this Chinese cohort, ApaI and BsmI are associated with a decreased risk of OM development by influencing serological vitamin D level, the latter of which reduced macrophage apoptosis with inhibition of excessive ROS production via the VDR-Bmi1 signaling pathway.

Background and aims:Spinal serum 25-hydroxyvitamin D [25[OH]D] status plays an important role in mediating innate immune responses by acting as a cofactor for induction of antimycobacterial activity and is thus involved in the development of Tuberculosis (TB). Results reported regarding the association of vitamin D with TB remained controversial. We aimed to identify any common association between 25[OH]D status and TB in the Chinese Han population.Methods280 subjects (70 TB patients and 210 matched controls) were recruited. TB cases were diagnosed based on the presence of acid-fast bacilli on smears from sputum and MTB isolation. Healthy controls were randomly selected from four local community-based populations. 25[OH]D was detected by electrochemiluminescence immunoassay (ECLIA) on Roche Elecsys before the initial treatment. Multivariable logistic regression analysis was used to examine the association of Vitamin D with TB.ResultsThere was no significant difference in the serum vitamin D level between total cases and controls, but we found a strong tendency toward a higher serum vitamin D level in male population (P < 0.05) with TB but not in females. High serum vitamin D increased the risk of TB in the Chinese Han population (OR = 1.035, 95%CI: 1.001–1.070, P < 0.05). The serum vitamin D level was significantly decreased with age increasing in cases and controls (all P < 0.001).ConclusionsHigh serum vitamin D may be an independent risk factor for TB in the Chinese Han population.

BackgroundJob satisfaction is recognized as an important factor affecting the performance and quality of medical services of emergency department physicians. However, little is known about the status of job satisfaction among emergency department physicians in China. This study aimed to explore the current level of job satisfaction and its associated factors among emergency department physicians in China.MethodsA nationwide cross-sectional survey was conducted in China from July to August 2018. A total of 10,457 emergency department physicians completed the questionnaire. The structured online questionnaire collected information on socio-demographic characteristics, work-related factors, work-family conflict, and job satisfaction. Student's t-test or ANOVA were used to compare the job satisfaction scores in different characters. The generalized linear model was used to investigate the related factors of job satisfaction among emergency department physicians.ResultsThe respondents' job satisfaction average score was 12.2 ± 3.6, of which 42.01% were satisfied of which the job. The results showed that emergency department physicians over 41 years old, with a higher income and working in central and western regions were positively associated with job satisfaction. In contrast, bachelor degree and above, fixed posts, long years of service, a high frequency of night shift, perceived shortage of physicians, perceived medical errors, and higher work-family conflict scores were negatively correlated with job satisfaction among emergency department physicians.ConclusionJob satisfaction of emergency department physicians in China is low. It is suggested that hospital administrators could improve the job satisfaction of emergency department physicians by establishing an acceptable shift system, ensuring adequate emergency department staffing, increasing their income appropriately and alleviating work-family conflict.

Uniaxial compressive strength (UCS) is a significant parameter in mining engineering and rock engineering. The laboratory rock test is time-consuming and economically costly. Therefore, developing a reliable and accurate UCS prediction model through easily obtained rock parameters is a good way. In this paper, we set five input parameters and compare six hybrid models based on BP neural network and six swarm intelligence optimization algorithms–bird swarm algorithm (BSA), grey wolf optimization (GWO), whale optimization algorithm (WOA), seagull optimization algorithm (SOA), lion swarm optimization (LSO), firefly algorithm (FA) with the accuracy of two single models without optimization–BP neural network and random forest algorithm. Finally, the above eight models were evaluated and compared by root mean square error (RMSE), mean absolute percentage error (MAPE), coefficient of determination (R2), and a10 index to obtain the most suitable prediction model. It is indicated that the best prediction model is the FA-BP model, with a RMSE value of 4.883, a MAPE value of 0.063, and a R2 of 0.985, and an a10 index of 0.967. Furthermore, the normalized mutual information sensitivity analysis shows that point load strength is the most effective parameters on the UCS, respectively.

Abstract Background Congenital heart disease (CHD) is the most common birth defect and has high heritability. Although some susceptibility genes have been identified, the genetic basis underlying the majority of CHD cases is still undefined. Methods A total of 1320 unrelated CHD patients were enrolled in our study. Exome‐wide association analysis between 37 tetralogy of Fallot (TOF) patients and 208 Han Chinese controls from the 1000 Genomes Project was performed to identify the novel candidate gene WD repeat‐containing protein 62 (WDR62). WDR62 variants were searched in another expanded set of 200 TOF patients by Sanger sequencing. Rescue experiments in zebrafish were conducted to observe the effects of WDR62 variants. The roles of WDR62 in heart development were examined in mouse models with Wdr62 deficiency. WDR62 variants were investigated in an additional 1083 CHD patients with similar heart phenotypes to knockout mice by multiplex PCR‐targeting sequencing. The cellular phenotypes of WDR62 deficiency and variants were tested in cardiomyocytes, and the molecular mechanisms were preliminarily explored by RNA‐seq and co‐immunoprecipitation. Results Seven WDR62 coding variants were identified in the 237 TOF patients and all were indicated to be loss of function variants. A total of 25 coding and 22 non‐coding WDR62 variants were identified in 80 (6%) of the 1320 CHD cases sequenced, with a higher proportion of WDR62 variation (8%) found in the ventricular septal defect (VSD) cohort. WDR62 deficiency resulted in a series of heart defects affecting the outflow tract and right ventricle in mouse models, including VSD as the major abnormality. Cell cycle arrest and an increased number of cells with multipolar spindles that inhibited proliferation were observed in cardiomyocytes with variants or knockdown of WDR62. WDR62 deficiency weakened the association between WDR62 and the cell cycle‐regulated kinase AURKA on spindle poles, reduced the phosphorylation of AURKA, and decreased expression of target genes related to cell cycle and spindle assembly shared by WDR62 and AURKA. Conclusions WDR62 was identified as a novel susceptibility gene for CHD with high variant frequency. WDR62 was shown to participate in the cardiac development by affecting spindle assembly and cell cycle pathway in cardiomyocytes.

Recently, atypical infectious bursal disease (IBD) caused by a novel variant infectious bursal disease virus (varIBDV) suddenly appeared in immunized chicken flocks in East Asia and led to serious economic losses. The epizootic varIBDV can partly circumvent the immune protection of the existing vaccines against the persistently circulating very virulent IBDV (vvIBDV), but its mechanism is still unknown. This study proved that the neutralizing titer of vvIBDV antiserum to the epizootic varIBDV reduced by 7.0 log2, and the neutralizing titer of the epizootic varIBDV antiserum to vvIBDV reduced by 3.2 log2. In addition, one monoclonal antibody (MAb) 2-5C-6F had good neutralizing activity against vvIBDV but could not well recognize the epizootic varIBDV. The epitope of the MAb 2-5C-6F was identified, and two mutations of G318D and D323Q of capsid protein VP2 occurred in the epizootic varIBDV compared to vvIBDV. Subsequently, the indirect immunofluorescence assay based on serial mutants of VP2 protein verified that residue mutations 318 and 323 influenced the recognition of the epizootic varIBDV and vvIBDV by the MAb 2-5C-6F, which was further confirmed by the serial rescued mutated virus. The following cross-neutralizing assay directed by MAb showed residue mutations 318 and 323 also affected the neutralization of the virus. Further data also showed that the mutations of residues 318 and 323 of VP2 significantly affected the neutralization of the IBDV by antiserum, which might be deeply involved in the immune circumvention of the epizootic varIBDV in the vaccinated flock. This study is significant for the comprehensive prevention and control of the emerging varIBDV.

BackgroundSmoking remains a major public health issue among Chinese immigrants. Smoking cessation programs that focus on this population are scarce and have a limited population-level impact due to their low reach. Mobile messaging interventions have the potential to reach large audiences and expand smokers’ access to smoking cessation treatment. ObjectiveThis study describes the development of a culturally and linguistically appropriate mobile messaging smoking cessation intervention for Chinese immigrant smokers delivered via WeChat, the most frequently used social media platform among Chinese people globally. MethodsThis study had 2 phases. In phase 1, we developed a mobile message library based on social cognitive theory and the US Clinical Practice Guidelines for Treating Tobacco Use and Dependence. We culturally adapted messages from 2 social cognitive theory-based text messaging smoking cessation programs (SmokefreeTXT and Decídetexto). We also developed new messages targeting smokers who were not ready to quit smoking and novel content addressing Chinese immigrant smokers’ barriers to quitting and common misconceptions related to willpower and nicotine replacement therapy. In phase 2, we conducted in-depth interviews with 20 Chinese immigrant smokers (including 7 women) in New York City between July and August 2021. The interviews explored the participants’ smoking and quitting experiences followed by assessment of the text messages. Participants reviewed 17 text messages (6 educational messages, 3 self-efficacy messages, and 8 skill messages) via WeChat and rated to what extent the messages enhanced their motivation to quit, promoted confidence in quitting, and increased awareness about quitting strategies. The interviews sought feedback on poorly rated messages, explored participant preferences for content, length, and format, discussed their concerns with WeChat cessation intervention, and solicited recommendations for frequency and timing of messages. ResultsOverall, participants reported that the messages enhanced their motivation to quit, offered encouragement, and made them more informed about how to quit. Participants particularly liked the messages about the harms of smoking and strategies for quitting. They reported barriers to applying some of the quitting strategies, including coping with stress and staying abstinent at work. Participants expressed strong interest in the WeChat mobile messaging cessation intervention and commented on its potential to expand their access to smoking cessation treatment. ConclusionsMobile messages are well accepted by Chinese immigrant smokers. Research is needed to assess the feasibility, acceptability, and efficacy of WeChat mobile messaging smoking cessation interventions for promoting abstinence among Chinese immigrant smokers.

ObjectivesPredicting the potential risk factors of high blood pressure (HBP) among children and adolescents is still a knowledge gap. Our study aimed to establish and validate a nomogram-based model for identifying youths at risk of developing HBP.MethodsHBP was defined as systolic blood pressure or diastolic blood pressure above the 95th percentile, using age, gender, and height-specific cut-off points. Penalized regression with Lasso was used to identify the strongest predictors of HBP. Internal validation was conducted by a 5-fold cross-validation and bootstrapping approach. The predictive variables and the advanced nomogram plot were identified by conducting univariate and multivariate logistic regression analyses. A nomogram was constructed by a training group comprised of 239,546 (69.9%) participants and subsequently validated by an external group with 103,190 (30.1%) participants.ResultsOf 342,736 children and adolescents, 55,480 (16.2%) youths were identified with HBP with mean age 11.51 ± 1.45 years and 183,487 were boys (53.5%). Nine significant relevant predictors were identified including: age, gender, weight status, birth weight, breastfeeding, gestational hypertension, family history of obesity and hypertension, and physical activity. Acceptable discrimination [area under the receiver operating characteristic curve (AUC): 0.742 (development group), 0.740 (validation group)] and good calibration (Hosmer and Lemeshow statistics, P > 0.05) were observed in our models. An available web-based nomogram was built online on https://hbpnomogram.shinyapps.io/Dyn_Nomo_HBP/.ConclusionsThis model composed of age, gender, early life factors, family history of the disease, and lifestyle factors may predict the risk of HBP among youths, which has developed a promising nomogram that may aid in more accurately identifying HBP among youths in primary care.

In patients with congenital blindness (CB), the lack of any visual experience may affect brain development resulting in functional, structural, or even psychological changes. Few studies to date have addressed or focused on the synchronicity of regional brain activity in patients with CB. Our study aimed to investigate regional brain activity in patients with CB in a resting state and try to explain the possible causes and effects of any anomalies. Twenty-three CB patients and 23 healthy control (HC) volunteers agreed to undergo resting state functional magnetic resonance imaging (fMRI) scans. After the fMRI data were preprocessed, regional homogeneity (ReHo) analysis was conducted to assess the differences in brain activity synchronicity between the two groups. Receiver operating characteristic (ROC) curve analysis was used to explore whether the brain areas with statistically significant ReHo differences have diagnostic and identification values for CB. All CB patients were also required to complete the Hospital Anxiety and Depression Scale (HADS) to evaluate their anxiety and depression levels. The results showed that in CB patients mean ReHo values were significantly lower than in HCs in the right orbital part of the middle frontal gyrus (MFGorb), bilateral middle occipital gyrus (MOG), and the right dorsolateral superior frontal gyrus (SFGdl), but significantly higher in the left paracentral lobule (PCL), right insula and bilateral thalamus. The ReHo value of MFGorb showed a negative linear correlation with both the anxiety score and the depression score of the HADS. ROC curve analysis revealed that the mean ReHo values which differed significantly between the groups have excellent diagnostic accuracy for CB (especially in the left PCL and right SFGdl regions). Patients with CB show abnormalities of ReHo values in several specific brain regions, suggesting potential regional structural changes, functional reorganization, or even psychological effects in these patients. FMRI ReHo analysis may find use as an objective method to confirm CB for medical or legal purposes.

BackgroundThere is evidence that occupational stress is a risk factor for turnover intentions. However, the structural relationship between occupational stress and turnover intention among emergency physicians has rarely been studied. This study aimed to examine the pathways of occupational stress on turnover intention through job satisfaction and depressive symptoms among emergency physicians in China.MethodsA cross-sectional study was conducted in China from July 2018 to August 2018. Data were collected using a structured questionnaire that included demographic characteristics, occupational stress, job satisfaction, depressive symptoms, and turnover intention. Hierarchical linear regression was performed to explore the related factors of turnover intention. Structural equation modeling was used to examine the pathways from occupational stress to turnover intention.ResultsA total of 10,457 emergency physicians completed the questionnaire. The score of turnover intention was 11.34 (SD = 3.25), and the average item score of turnover intention was 2.84 (SD = 0.81). In structural equation modeling, the occupational stress not only had a direct effect on turnover intention (standardized direct effect = 0.311, bias-corrected 95% confidence interval [0.261, 0.361], P < 0.001), but also had an indirect effect through job satisfaction and depressive symptoms (standardized indirect effect = 0.448, bias-corrected 95% confidence interval [0.412, 0.484], P < 0.001). However, the effect of depressive symptoms on turnover intention was weak (standardized coefficient [β] = 0.08, P < 0.001).ConclusionsJob satisfaction partially mediated the relationship between occupational stress and turnover intention. However, due to the weak effect of depressive symptoms on turnover intention, the mediating role of depressive symptoms between occupational and turnover intention had little practical value. It is recommended that hospital administrators prioritize increasing job satisfaction of emergency physicians to reduce the impact of occupational stress on their turnover intention.

PurposeThe global COVID-19 pandemic impacted the healthcare systems of every nation. The scarcity of medical protective equipment led to impulse buying at the early stages of the COVID-19 outbreak in China which resulted in stockpiling and the increase of prices by retailers and insufficiencies among frontline workers. This situation impacted epidemic control work and market order and is the context from which this paper identifies how the scarcity of medical protective equipment affected Chinese consumers’ impulse buying based on the theories of S-O-R model and bandwagon effect. The research provides insight into the mechanism of mediation (fear of missing out) and moderation (bandwagon) in the relationship between scarcity and impulse buying.Design/Methodology/ApproachThis study uses convenience sampling, surveying 488 Chinese consumers through an online questionnaire. Smart-PLS was used to test the hypotheses.FindingsThe empirical findings demonstrate that scarcity makes consumers fear missing the chance of getting protective medical equipment, leading ultimately to impulse buying. Besides, the scarcity effect on consumers’ impulse buying was found to depend on other consumers’ follow up behaviour in such emergency situations.Research Limitations/ImplicationsThe findings provide managerial and theoretical insight and a point of reference for businesses in the implementation of a scarcity strategy. The findings will also prove useful to the Chinese Risk Response Department as it continuously improves its responses to the risk of consumers’ impulse buying during a pandemic.Originality/ValueThis study consolidates and takes research forward in the areas of impulse buying and consumer behaviour, confirming the mediating effect of fear of missing out and the moderating effect of the bandwagon in the relationship between scarcity and impulse buying.

Abstract. Severe acute respiratory disease coronavirus 2 is currently causing the coronavirus disease 2019 (COVID-19) pandemic, placing extreme strain on the global health system. Vaccination is the main measure for preventing the COVID-19 epidemic, especially for high-risk groups including patients with chronic kidney disease (CKD). However, CKD patients receiving dialysis or kidney transplant may be characterized by decreased renal function and immune disorders, which may have uncertainties in their health. This overview aims to introduce the possible impact of the COVID-19 vaccine on kidney disease and its application in patients with CKD to provide evidence for the COVID-19 vaccine in patients with CKD. The data for this study were collected from PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and the China Knowledge Resource Integrated Database (CNKI). The following keywords were used: “COVID-19”, “COVID-19 vaccine,” and “CKD”. The publication time of the papers was set from the establishment of the databases to September 2021. A total of 47 studies were included, and patients with CKD are a high-risk group for COVID-19 infection and severe illness. Vaccination is a powerful tool for preventing CKD patients from COVID-19. Because of possible side effects, the recurrence or deterioration of kidney disease may occur in CKD patients after vaccination. Although vaccination for patients with CKD remains a problem, with the advantages outweighing the disadvantages, stable CKD patients should complete a vaccination plan, and doctors should be aware of the recurrence or deterioration of kidney disease and close monitoring. Data access statement:. Research data supporting this publication are available from the electronic databases of PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and the China Knowledge Resource Integrated Database (CNKI).

Summary: Background: In the current practice, graft ischaemia and reperfusion injury (IRI) is considered an inevitable component in organ transplantation, contributes to compromised organ quality, inferior graft survival and limitations in organ availability. Among all the donor organs, the heart is most vulnerable to IRI and the tolerated ischaemic time is the shortest. Methods: By combining adapted surgical techniques and normothermic machine perfusion (NMP), we performed the first case of ischaemia-free beating heart transplantation (IFBHT) in man. The donor heart was procured after an in situ NMP circuit was established, then underwent ex situ NMP and implanted under NMP support. The post-transplant graft function was monitored. Findings: The donor heart was procured, preserved, and implanted under a continuously perfused, normothermic, oxygenated, beating state. During ex situ NMP, the donor heart beat with sinus rhythm and adequate ventricular contraction, consumed oxygen and lactate, suggesting a good cardiac function. The dynamic electrocardiogram demonstrated an absence of ischaemic injury of the donor heart during the entire procedure. The echocardiogram showed an immediate graft function with a left ventricle ejection fraction (LVEF) of 70%. The patient was discharged on post-transplantation day 20 and was followed up for 8 months with normal cardiac function and life. Interpretation: This study shows the feasibility of IFBHT procedure, which might be able to completely avoid graft IRI, has thus the potential to improve transplant outcome while increasing organ utilization. Funding: This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial International Cooperation Base of Science and Technology.

BackgroundChinese immigrants bear a high diabetes burden and face significant barriers to accessing diabetes self-management education (DSME) and counseling programs. ObjectiveThe goal of this study was to examine the feasibility and acceptability and to pilot test the potential efficacy of a social media–based DSME intervention among low-income Chinese immigrants with type 2 diabetes (T2D) in New York City. MethodsThis was a single group pretest and posttest study in 30 Chinese immigrants with T2D. The intervention included 24 culturally and linguistically tailored DSME videos, focusing on diabetes education and behavioral counseling techniques. Over 12 weeks, participants received 2 brief videos each week via WeChat, a free social media app popular among Chinese immigrants. Primary outcomes included the feasibility and acceptability of the intervention. Feasibility was evaluated by recruitment processes, retention rates, and the video watch rate. Acceptability was assessed via a satisfaction survey at 3 months. Secondary outcomes, that is, hemoglobin A1c (HbA1c), self-efficacy, dietary intake, and physical activity, were measured at baseline, 3 months, and 6 months. Descriptive statistics and paired 2-sided t tests were used to summarize the baseline characteristics and changes before and after the intervention. ResultsThe sample population (N=30) consisted of mostly females (21/30, 70%) who were married (19/30, 63%), with limited English proficiency (30/30, 100%), and the mean age was 61 (SD 7) years. Most reported an annual household income of

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the GBA1 gene, which produces the glucocerebrosidase (GCase) protein. There are more than 500 mutations reported in GBA1, among which L444P (p.Leu444Pro) and F213I (p.Phe213Ile) are the most common in the Chinese population, while the function of F213I mutation remains elusive. This study aims to establish the GD mouse model of partially humanized Gba1 gene with F213I mutation. In vitro GCase activity assays showed that the product of partially humanized Gba1 gene, in which the mouse exons 5-7 were replace by the corresponding human exons, displayed similar activity with the wild-type mouse Gba1, while the F213I mutation in the humanized Gba1 led to significant decrease in enzyme activity. ES cell targeting was used to establish the mice expressing the partially humanized Gba1-F213I. Gba1F213I/+ mice did not show obviously abnormal phenotypes, but homozygous Gba1F213I/F213I mice died within 24 h after birth, whose epidermal stratum corneum were abnormal from the wild-type. The GCase activity in Gba1F213I/F213I mice greatly decreased. In conclusion, our results showed that the partially humanized GD mouse model with the F213I mutation was developed and homozygous F213I mutation is lethal for newborn mice.

Abstract Background Bainbridge‐Ropers syndrome (BRPS, OMIM #615485) was first identified in 2013 by Bainbridge et al. and is a neurodevelopment disorder characterized by failure to thrive, facial dysmorphism and severe developmental delay. BRPS is caused by heterozygous loss‐of‐function (LOF) variants in the additional sex combs‐like 3 (ASXL3) gene. Due to the limited specific recognizable features and overlapping symptoms with Bohring–Opitz syndrome (BOS, OMIM #612990), clinical diagnosis of BRPS is challenging. Methods In this study, a 2‐year‐8‐month‐old Chinese girl was referred for genetic evaluation of severe developmental delay. The reduced fetal movement was found during the antenatal period and bilateral varus deformity of feet was observed at birth. Whole‐exome sequencing and Sanger sequencing were used to detect and confirm the variant. Results A novel nonsense variant c.1063G>T (p.E355*) in the ASXL3 gene (NM_030632.3) was identified in the proband and the clinical symptoms were compatible with BRPS. The parents were physical and genetic normal and prenatal diagnosis was requested for her pregnant mother with a negative Sanger sequencing result. Conclusion The study revealed a de novo LOF variant in the ASXL3 gene and expanded the mutation spectrum for this clinical condition. By performing a literature review, we summarized genetic results and the clinical phenotypes of all BPRSs reported so far. More cases study may help to elucidate the function of the ASXL3 gene may be critical to understand the genetic aetiology of this syndrome and assist in accurate genetic counselling, informed decision making and prenatal diagnosis.

A sustainable magnetic core-shell nanocatalyst Fe3O4@C@Fe(III) was successfully applied in the synthesis of a series of 2-nitro-2,3-unsaturated O-glycosides with excellent yields (up to 89%) and high stereoselectivity (α:β > 19:1). The substrate ranges are widely applicable, including different kinds of alcohols and even structurally complex acceptors. In addition, phenols could be applied in good yields. Moreover, the catalyst could be easily separated from the reaction by the application of an external magnetic force and reused a minimum of five times without any significant decrease in catalytic performance.

Objective : Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been recommended as the first-line treatment for advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation. This study retrospectively evaluated patients’ survival and related prognostic factors from single-center, real-world data. Methods: From January 2015 to December 2020, patients detected with EGFR mutation showing unresectable clinical stages III to IV advanced lung adenocarcinoma and receiving EGFR-TKIs and radiotherapy (RT) were recruited for the study. The overall survival (OS) and progression-free survival (PFS) were statistically analyzed with SPSS 22.0 software. Results: This study included 238 patients who completed their follow-up by December 30, 2020. The 1-, 2-, 3-year and median OS were 84.4%, 59.7%, 38.7%, and 30.3 months for OS, 57.0%, 28.8%, 15.7%, and 14.1 months for progression-free survival (PFS1), and 78.9%, 71.7%, 33.3%, and 25.0 months for PFS2, respectively. Multivariate analysis showed that, the independent factors for OS are age, clinical stage, the sequence of TKI and CT, and the total treatment response, and total response; the independent factors for progression-free survival 1 are clinical stage and total treatment response; the independent factors for PFS2 are clinical stage, type of TKI, sequence of TKI and CT, and total treatment response. The univariate analysis also showed a significant association between RT duration ( P = 0.041) and dose ( P = 0.026) with PFS1. Conclusion: EGFR-TKIs combined with RT was tolerable and efficient for patients with advanced lung adenocarcinoma. OS and PFS prove CT sequential with TKIs. Better treatment response with CR + PR was associated with a longer duration of OS, PFS1, and PFS2. However, further study is required in a larger sample size to confirm the results.

The two-line rice hybrid “Super 1000” (GX24S × R900) represents a major landmark achievement of breeding for super-hybrid rice in China. However, both male parent R900 and hybrid “Super 1000” have an obvious defect of high susceptibility to rice bacterial blight (BB) and blast. Thus, improving disease resistance and maintaining the original high-yield capacity are essential for the sustainable application of “Super 1000.” In this study, the application of closely linked single-nucleotide polymorphism (SNP) markers for foreground selection of dominant resistance gene loci together with genome-wide SNP markers for the background selection rapidly improved the disease resistance of R900 without disturbing its high-yield capacity. A series of improved R900 lines (iR900, in BC2Fn and BC3Fn generations) were developed to stack resistance genes (Xa23+Pi9, Xa23+Pi1+Pi2/9) by marker-assisted backcrossing and field selection for phenotypes, and further crossed with the female line GX24S to obtain improved hybrid variety Super 1000 (iS1000). The genetic backgrounds of iS1000 and “Super 1000” were profiled by using a 56 K SNP-Chip, and results showed that they shared 98.76% of similarity. Meanwhile, evaluation of the field disease resistance showed that the iR900 lines and iS1000 hybrids possess significantly enhanced resistance to both BB and rice blast. Resistance spectrum assays revealed that the iR900 lines and their derived hybrids exhibited high-level resistance to 28 Xoo strains tested, and enhanced resistance to leaf blast at the seedling stage when infected with 38 Magnaporthe oryzae isolates. Between 2019 and 2020, the multi-location field trials across the middle and lower reaches of the Yangtze River were launched and showed that the iS1000 slightly out-yielded than the original variety. In a large-scale demonstration site (6.73 ha, Yunnan, China), the iS1000 achieved 17.06 t/hm2 of yield in 2019. Moreover, the high similarity was observed in main agronomic traits and grain quality when comparing the improved lines/hybrids to original ones (iR900 vs. R900, iS1000 vs. S1000). This work presented a typical genomics-assisted breeding strategy and practice, which involves in directional introgression and rapid stack of multiple disease resistance genes, endowing the super-high-yield hybrid rice variety with holistic disease resistance but without yield penalty.

Plant-derived agents are powerful bio-pesticides for the eco-friendly control of mosquito vectors and other blood-sucking arthropods. The larval toxicity of beta-carboline alkaloids against the Asian tiger mosquito, Aedes albopictus (Skuse) (Diptera: Culicidae), was investigated under laboratory conditions. The total alkaloid extracts (TAEs) and beta-carboline alkaloids (harmaline, harmine, harmalol, and harman) from Peganum harmala seeds were isolated and tested in this bioassay. All alkaloids were tested either individually or as binary mixtures, using the co-toxicity coefficient (CTC) and Abbott’s formula analysis. The results revealed considerable toxicity of the tested alkaloids against A. albopictus larvae. When all larval instars were exposed to the TAEs at 48 h post-treatment, the mortality of all larval instars varied in a concentration-dependent manner. The second-instar larvae were the most susceptible to different concentrations of TAEs, and the fourth-instar larvae were more tolerant to TAEs than the second-instar larvae. Especially, the third-instar larvae exposed to all alkaloids also showed that all doses resulted in an increased mortality of the third-instar larvae at 48 h post-treatment, and the toxicities of the tested alkaloids in a descending order were TAEs > harmaline > harmine > harmalol, with the LC50 values of 44.54 ± 2.56, 55.51 ± 3.01, 93.67 ± 4.53, and 117.87 ± 5.61 μg/mL at 48 h post-treatment, respectively. In addition, all compounds were also tested individually or in a 1:1 ratio (dose LC25/LC25) as binary mixtures to assess the synergistic toxicity of these binary combinations against the third-instar larvae at 24 and 48 h post-treatment, respectively. The results demonstrated that when tested as a binary mixture, all compounds (especially TAEs, harmaline, and harmine) showed their synergistic effects, exceeding the toxicity of each compound alone. Interestingly, the obtained data further revealed that the TAEs at sublethal doses (LC10 and LC25) could significantly delay the larval development and decrease the pupation and emergence rates of A. albopictus. This phenomenon could be helpful in order to develop more effective control strategies for different notorious vector mosquitoes.

A mattress-type non-influencing sleep apnea monitoring system was designed to detect sleep apnea-hypopnea syndrome (SAHS). The pressure signals generated during sleep on the mattress were collected, and ballistocardiogram (BCG) and respiratory signals were extracted from the original signals. In the experiment, wavelet transform (WT) was used to reduce noise and decompose and reconstruct the signal to eliminate the influence of interference noise, which can directly and accurately separate the BCG signal and respiratory signal. In feature extraction, based on the five features commonly used in SAHS, an innovative respiratory waveform similarity feature was proposed in this work for the first time. In the SAHS detection, the binomial logistic regression was used to determine the sleep apnea symptoms in the signal segment. Simulation and experimental results showed that the device, algorithm, and system designed in this work were effective methods to detect, diagnose, and assist the diagnosis of SAHS.

A sensitive and selective electrochemical dopamine (DA) sensor has been developed using gold nanoparticles decorated marimo-like graphene (Au NP/MG) as a modifier of the glassy carbon electrode (GCE). Marimo-like graphene (MG) was prepared by partial exfoliation on the mesocarbon microbeads (MCMB) through molten KOH intercalation. Characterization via transmission electron microscopy confirmed that the surface of MG is composed of multi-layer graphene nanowalls. The graphene nanowalls structure of MG provided abundant surface area and electroactive sites. Electrochemical properties of Au NP/MG/GCE electrode were investigated by cyclic voltammetry and differential pulse voltammetry techniques. The electrode exhibited high electrochemical activity towards DA oxidation. The oxidation peak current increased linearly in proportion to the DA concentration in a range from 0.02 to 10 μM with a detection limit of 0.016 μM. The detection selectivity was carried out with the presence of 20 μM uric acid in goat serum real samples. This study demonstrated a promising method to fabricate DA sensor-based on MCMB derivatives as electrochemical modifiers.

Largemouth bass ranavirus (LMBV) infects largemouth bass, leading to significant mortality and economic losses. There are no safe and effective drugs against this disease. Oral vaccines that directly target the intestinal mucosal immune system play an important role in resisting pathogens. Herein, the B subunit of Escherichia coli heat-labile enterotoxin (LTB, a mucosal immune adjuvant) and the LMBV main capsid protein (MCP) were expressed using Saccharomyces cerevisiae surface display technology. The yeast-prepared oral vaccines were named EBY100-OMCP and EBY100-LTB-OMCP. The candidate vaccines could resist the acidic intestinal environment. After 7 days of continuous oral immunization, indicators of innate and adaptive immunity were measured on days 1, 7, 14, 21, 28, 35, and 42. High activities of immune enzymes (T-SOD, AKP, ACP, and LZM) in serum and intestinal mucus were detected. IgM in the head kidney was significantly upregulated (EBY100-OMCP group: 3.8-fold; BY100-LTB-OMCP group: 4.3-fold). IgT was upregulated in the intestines (EBY100-OMCP group: 5.6-fold; EBY100-LTB-OMCP group: 6.7-fold). Serum neutralizing antibody titers of the two groups reached 1:85. Oral vaccination protected against LMBV infection. The relative percent survival was 52.1% (EBY100-OMCP) and 66.7% (EBY100-LTB-OMCP). Thus, EBY100-OMCP and EBY100-LTB-OMCP are promising and effective candidate vaccines against LMBV infection.

We targeted high-temperature and highly saline old oil fields, whose environmental conditions could be attributed to the significantly high heterogeneity cause by long-term water flooding. The Huabei Oilfield was chosen as the research object. We developed a hydrophobic functional monomer–polymer with temperature and salt resistance by introducing the temperature-resistant and salt-resistant monomer NVP and a hydrophobic functional monomer into the main chain for copolymerization. We used a crosslinking agent with phenolic resin to prepare a weak gel system that showed temperature and salt resistance and investigated its temperature and salt resistance, infective property, plugging performance, liquid flow ability, micropore throat migration, and plugging characteristics. The results obtained using the infrared spectroscopy technique revealed the successful preparation of the phenolic resin crosslinker. The weak gel exhibited good temperature and salt resistance when the polymer concentration was 2000 mg/L, the cohesion ratio was 1:1.5, the additive concentration was 2000 mg/L, the reservoir temperature was 120 °C, and the injected water salinity was 40,300.86 mg/L. The average viscosity retention rate of the 90-day weak gel reached more than 80% and its microstructure was examined. The coreflow experiment results revealed that the weak gel system was characterized by good infectivity. After plugging the weak gel, the effect on the direction of the liquid flow was evident and the flow rate of the low permeability layer increased to a maximum of 48.63% under conditions of varying permeability levels. A significant improvement in the water absorption profile was achieved. The plugging was carried out through a sand-filling pipe under varying permeability conditions and the pressure measuring points in the sand-filling pipe were sucessfully pressurized. The migration ability of the weak gel was good and the blocking rate was >85%.

This review discusses several research studies that employed comet assay to evaluate the environmental impact of genotoxins in aquatic environments. It focuses on in vivo and in situ studies of aquatic animals. New chemicals are being added each year to the existing burden of toxic substances in the environment. Excessive agricultural and industrial activities adversely affect biodiversity, threatening the survival of species in a particular habitat, as well as posing disease risks to humans. Some of the chemicals, e.g., pesticides and heavy metals, may be genotoxic to the sentinel species and/or to non-target species, causing deleterious effects in somatic or germ cells. Comet assay is a quick, sensitive, and low-cost technique for detecting DNA strand breakage. However, the comet assay has much more to offer than being an assay for testing DNA strand breaks in animal organs. The use of repair enzymes increases the range of DNA lesions that can be detected with the assay. Comparing data from studies that employed different approaches, such as empirical scoring or comet tail lengths, comet assay is one of the challenging techniques to be utilized in environmental studies. The relative amount of DNA in the comet tail indicates DNA break intensity. The assay has been modified to detect various base alterations by including the digestion of nucleoids with a lesion-specific endonuclease. The determination of DNA damage in these indicator species using the comet test would thus offer information on the genotoxic potential of their habitat at an early stage. This would enable intervention techniques to prevent or mitigate adverse health impacts in sentinel animals and humans.

Asparaginase is a critical component of therapy for childhood acute lymphoblastic leukemia (ALL), but it is commonly associated with allergy, which results in morbidity and poorer outcomes. The underlying basis of this allergy is undoubtedly immune-mediated, but the exact components of T-cell immunity have yet to be characterized. We performed longitudinal TCR sequencing of 180 bone marrow samples from 67 children with B-ALL treated as part of the Ma-Spore-ALL-2010 trial, and we evaluated the associations of TCR profile with asparaginase hypersensitivity, with functional validation of asparaginase activity in a separate cohort of 113 children. We found that a more diverse and dynamically changing TCR repertoire was associated with increased risk of clinical hypersensitivity and decreased L-asp activity. Allergic patients had a higher proportion of infrequent clonotypes, as well as a significantly lower degree of shared clonotypes amongst the cohort. Allergic patients also had significantly higher longitudinal variability of clonotypes across timepoints, where a higher dissimilarity between diagnosis and week 5 represented an 8.1-fold increased risk of an allergic event. After an allergy had occurred, there was shaping and convergence of the TCR repertoire towards a common antigen. Understanding the immunological basis of T-cell responses in allergy lays the groundwork for developing predictive biomarkers or strategies to mediate this common toxicity in childhood ALL.

With the increase in heat power density in modern integrating electronics, thermal interface materials (TIM) that can efficiently fill the gaps between the heat source and heat sinks and enhance heat dissipation are urgently needed owing to their high thermal conductivity and excellent mechanical durability. Among all the emerged TIMs, graphene-based TIMs have attracted increasing attention because of the ultrahigh intrinsic thermal conductivity of graphene nanosheets. Despite extensive efforts, developing high-performance graphene-based papers with high through-plane thermal conductivity remains challenging despite their high in-plane thermal conductivity. In this study, a novel strategy for enhancing the through-plane thermal conductivity of graphene papers by in situ depositing AgNWs on graphene sheets (IGAP) was proposed, which could boost the through-plane thermal conductivity of the graphene paper up to 7.48 W m−1 K−1 under packaging conditions. In the TIM performance test under actual and simulated operating conditions, our IGAP exhibits strongly enhanced heat dissipation performance compared to the commercial thermal pads. We envision that our IGAP as a TIM has great potential for boosting the development of next-generation integrating circuit electronics.

Sugar-sweetened beverages (SSBs) consumption has risen significantly, which may lead to various health problems. Studies about the association between SSBs and attention-deficit/hyperactivity disorder (ADHD) in children are rare and inconsistent. We have used the two-stage cluster sampling method to select 6541 students aged 6–12. We further investigated their basic information and SSB intake. Teachers’ questionnaires and parents’ questionnaires were used to evaluating the hyperactive behaviors in children. We examined the associations between SSB consumption and hyperactivity index (HI) by adopting the censored least absolute deviation (CLAD) estimator. Then, we further evaluated the impacts of sex and age on the association between SSB intake and hyperactivity. Children who weekly drank SSB two or more times were associated with 0.05 (0.04, 0.07) and 0.04 (0.02, 0.06) higher scores of ln (HI+1) reported by teachers and parents, respectively, compared to non-consumers children (p for trend < 0.05). A stronger association between SSB intake and hyperactivity occurred in girls and old children. (p for interaction < 0.05). SSB intake has a positive correlation with the risk of hyperactivity in children, and the frequency of SSB consumption and hyperactivity have a dose–response relationship.

Cancer is a serious threat to human health, and chemotherapy for cancer is limited by severe side effects. Curcumin (CUR) is a commonly used natural product for antitumor treatment without safety concerns. However, low bioavailability and poor tumor accumulation are great obstacles for its clinical application. Our previous research has demonstrated that platelet membrane-camouflaged nanoparticles can efficiently ameliorate the in vivo kinetic characteristics and enhance the tumor affinity of payloads. Nevertheless, the antitumor efficiency of this formulation still needs to be thoroughly investigated, and its drug release behavior is limited. Herein, CUR-loaded platelet membrane bioinspired chitosan-modified liposome (PCLP-CUR) was constructed to improve CUR release. PCLP-CUR was shown to have long retention time, improved bioavailability, strong tumor targeting capacity and effective cellular uptake. The incorporation of chitosan enabled PCLP-CUR to release cargoes quickly under mild acidic tumor conditions, leading to more complete drug release and favoring subsequent treatment. Both in vitro and in vivo investigations showed that PCLP-CUR could significantly enhance the anticancer efficacy of CUR with minimal side effects through biomimetic membrane and chitosan modification. In summary, this developed delivery system can provide a promising strategy for tumor-targeting therapy and phytochemical delivery.

Rice blast caused by the filamentous fungus Magnaporthe oryzae, is arguably the most devastating rice disease worldwide. Development of a high-throughput and reliable field blast resistance evaluation system is essential for resistant germplasm screening, resistance genes identification and resistant varieties breeding. However, the occurrence of rice blast in paddy field is easily affected by various factors, particularly lack of sufficient inoculum, which always leads to the non-uniform occurrence and reduced disease severity. Here, we described a procedure for adequately inducing the occurrence of rice seedling blast in paddy field, which involves pretreatment of diseased straw, initiation of seedling blast for the first batch of spreader population, inducing the occurrence of the second batch of spreader population and test materials. This procedure enables uniform and consistent infection, which facilitates efficient and accurate assessment of seedling blast resistance for diverse rice materials.

Abstract Cervical cancer is the second most common cancer in women. Despite advances in cervical cancer therapy, tumor recurrence and metastasis remain the leading causes of mortality. High expression of BMI1 is significantly associated with poor tumor differentiation, high clinical grade, and poor prognosis of cervical cancer, and is an independent prognostic factor in cervical carcinoma. Alantolactone (AL), a sesquiterpene lactone, exhibits potent anti-inflammatory and anticancer activities. In this paper, we investigated the mechanism of AL in reducing the proliferation, migration, and invasion of HeLa and SiHa cervical cancer cells as well as its promotion of mitochondrial damage and autophagy. BMI1 silencing decreased epithelial-mesenchymal transformation-associated proteins and increased autophagy-associated proteins in HeLa cells. These effects were reversed by overexpression of BMI1 in HeLa cells. Thus, BMI1 expression is positively correlated with invasion and negatively correlated with autophagy in HeLa cells. Importantly, AL decreased the weight, volume, and BMI1 expression in HeLa xenograft tumors. Furthermore, the structure of BMI1 and target interaction of AL were virtually screened using the molecular docking program Autodock Vina; AL decreased the expression of N-cadherin, vimentin, and P62 and increased the expression of LC3B and Beclin-1 in xenograft tumors. Finally, expression of BMI1 increased the phosphorylation of STAT3, which is important for cell proliferation, survival, migration, and invasion. Therefore, we suggest that AL plays a pivotal role in inhibiting BMI1 in the tumorigenesis of cervical cancer and is a potential therapeutic agent for cervical cancer.

Mediators of insulin signalling are targets of cullin-RING ubiquitin ligases (CRL) that mediate protein degradation, but the role of protein degradation in insulin signalling is incompletely understood. Here, the authors identified a glucose-responsive CRL4-COP1-ETV5 proteolytic axis that promotes insulin secretion, and is inhibited under hypoglycemia.

Abstract Background Stroke is the second leading cause of death worldwide, and 53.4% of stroke survivors suffer from post-stroke cognitive impairment. Post-stroke cognitive impairment can increase hospitalization rate and cost of care and decrease the quality of life of stroke patients. To date, multiple cognitive rehabilitation interventions have been tested in stroke populations with post-stroke cognitive impairment. However, the most efficacious intervention has not been established. This systematic review aims to compare the efficacy of cognitive rehabilitation interventions for patients with post-stroke cognitive impairment. Methods We will search MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, PubMed, and clinical trial registries to identify eligible randomized clinical trials with no restrictions in the date of publication and language. Studies conducted with patients aged 18 or over, with the presence of cognitive impairment after being diagnosed with stroke will be included. Studies will be restricted to randomized controlled trials comparing a cognitive rehabilitation intervention with another intervention. The primary outcome is any clinical changes in the general or specific cognitive domain (e.g., executive function, attention, memory, or perception). The secondary outcomes that will be collected include adverse effects (e.g., stroke, disability, or mortality) and quality of life. Two independent reviewers will assess articles to identify trials eligible for inclusion. Data extraction and risk of bias assessment of the included studies will also be done independently. Any discrepancies will be solved by discussion, or a third reviewer will be consulted if necessary. A meta-analysis will be carried out if appropriate. Discussion This systematic review for patients with post-stroke cognitive impairment will assess the efficacy of cognitive rehabilitation interventions. And our results will help clinical decision-making and support the development of clinical practice guidelines. Trial registration Systematic review registration: PROSPERO CRD42020173988

Objective: To assess the efficacy and safety of ribavirin and interferon-α (RBV/IFN-α) therapy in COVID-19 patients. Methods: A multicenter, retrospective cohort study of COVID-19 patients admitted to 4 hospitals in Hubei Province, China, from 31 December 2019 to 31 March 2020. Patients were divided into 2 groups according to their exposure to RBV/IFN-α therapy within 48 h of admission. Mixed-effect Cox model and Logistic regression were used to explore the association between early treatments of RBV/IFN-α and primary outcomes. Results: Of 2037 patients included, 1281 received RBV/IFN-α (RBV, IFN-α or RBV combined with IFN-α) treatments and 756 received none of these treatments. In a mixed effect model, RBV/IFN-α therapy was not associated with progression from non-severe into severe type (adjusted hazard ratio (aHR) = 1.09, 95% CI: 0.88−1.36) or with reduction in 30-day mortality (aHR = 0.89, 95% CI: 0.61−1.30). However, it was associated with a higher probability of hospital stay >15 days (adjusted odds ratio (aOR) = 2.11, 95% CI: 1.68−2.64) compared with no RBV/IFN-α therapy. The propensity score-matched cohort and subgroup analysis displayed similar results. Conclusion: RBV/IFN-α therapy was not observed to improve clinical outcomes in COVID-19 patients suggesting that RBV/IFN-α therapy should be avoided in COVID-19 treatment.

Heart failure with preserved ejection fraction (HFpEF) is a global, major health issue for which no effective therapies are available. Here, the authors discover that the interplay between two transcription factors, Xbp1s and FoxO1, is critical for metabolic adaptation and lipid handling in HFpEF-stressed cardiomyocytes.

Li et al. show that dexamethasone and lactoferrin induced polymorphonuclear myeloid-derived suppressor cells relieve inflammatory conditions in mouse models with minimal effect on tumour growth. This work demonstrates promise for combating inflammatory adverse events during anti-cancer treatments.

Introduction: The infiltration pattern of endometriosis is one of the most important pathophysiological features of this lesion. Recent studies indicate the infiltrating nature of endometriosis is associated with a lesion’s genetic characteristics. However, related research regarding abdominal wall endometriosis (AWE) is limited. The aim of this study is to investigate whether AWE lesions with different infiltrating depth have different clinical and pathological features. Material and methods: A retrospective review of all cases of surgically excised AWE from 2001 to 2018 was performed from the records at Dalian Medical University and its affiliated hospitals. Descriptive data were collected and analyzed. Hematoxylin-eosin stained (H&E) slides were re-evaluated by pathologists for the density of ectopic endometrial glands (DOG). Results: Ninety-one cases were included in this study. Cases were divided into three types according to the depth of infiltration of the lesion: the fascia type (38 cases), the muscle type (40 cases) and the peritonieum type (13 cases). The primary analysis showed that mass size (P = 0.009), serum CA125 levels (P = 0.04) and operation time (P = 0.02) were significantly different among the three groups. Analysis showed that the diameter of the lesion was positively correlated with the infiltrating depth of the lesion, as well as the level of serum CA125 and the operation time. Even for lesions larger than 3 cm, serum CA125 levels and operation time still showed positive correlation with the lesion diameter (P = 0.02 and P < 0.01, respectively). Further histological research indicated that ectopic endometrial glands in deep lesions were more active and had higher density compared to masses in the superficial layers. Conclusion: This study suggests the three types of AWEs have different clinical and pathological features. When a lesion infiltrates deep into the abdominal wall, it has a larger size, is associated with increased serum CA125 levels, and needs longer time for surgical excision. The different infiltrating ability of AWEs is associated with different activities of ectopic endometrial glands.

Preoperative diagnosis of fracture-related infection (FRI) is difficult for patients without obvious signs of infection. However, specific profiles of gut microbiota may be used as a potential diagnostic tool for FRI as suggested by a previous study. The fecal microbiome was compared between 20 FRI patients (FRI group), 18 fracture healed patients (FH group), and 12 healthy controls (HC group) included after collection of fecal samples and evaluation. The α and β diversity indices were used to characterize the fecal microbiome. Dysbiosis indexes were constructed based on the characteristic high-dimensional biomarkers identified in the fecal microbiota from the three groups by linear discriminant analysis and generalized linear model analysis to quantify the dysbiosis of fecal microbiota. The effectiveness of α and β diversity indices and dysbiosis indexes was assessed in distinguishing the fecal microbiome among the three groups. The influences of serum inflammatory factors on gut microbiota were also addressed. The α diversity indices were significantly different between the three groups, the highest in HC group and the lowest in FRI group (P < 0.05). The β diversity indices showed significant phylogenetic dissimilarity of gut microbiome composition among the three groups (P < 0.001). The dysbiosis indexes were significantly higher in FRI group than in FH and HC groups (P < 0.001). The area under Receiver operating characteristic curve showed the characteristics of gut microbiota and the gut microbiota was found as effective in distinguishing the three groups. The dysbiosis in the FRI patients was associated with systemic inflammatory factors. In addition, significant differences in the gut microbiota were not observed between the FRI patients versus without sinus tract or pus before operation. Since FRI patients, with or without sinus tract or pus, have a characteristic profile of gut microbiota, their gut microbiota may be used as an auxiliary diagnostic tool for suspected FRI.

BackgroundData on burden of peripheral artery disease (PAD) and its attributable risk factors are valuable for policymaking. We aimed to estimate the burden and risk factors for PAD from 1990 to 2019.MethodsWe extracted the data on prevalence, incidence, death, years lived with disability (YLDs), and years of life lost (YLLs) from the Global Burden of Disease Study 2019 to measure PAD burden. Moreover, the attributable burden to PAD risk factors was also estimated.ResultsGlobally, in 2019, 113,443,017 people lived with PAD and 10,504,092 new cases occurred, resulting in 74,063 deaths, 500,893 YLDs, and 1,035,487 YLLs. The absolute numbers of PAD prevalent and incident cases significantly increased between 1990 and 2019, contrasting with the decline trends in age-standardized prevalence and incidence rates. However, no statistically significant changes were detected in the global age-standardized death or YLL rates. The burden of PAD and its temporal trends varied significantly by location, gender, age group, and social-demographic status. Among all potentially modifiable risk factors, age-standardized PAD deaths worldwide were primarily attributable to high fasting plasma glucose, followed by high systolic blood pressure, tobacco, kidney dysfunction, diet high in sodium, and lead exposure.ConclusionPAD remained a serious public health problem worldwide. More strategies aimed at implementing cost-effective interventions and addressing modifiable risk factors should be carried out, especially in regions with high or increasing burden.