Pan-genome analysis of the Burkholderia gladioli PV. Cocovenenans reveal the extent of variation in the toxigenic gene cluster.

Burkholderia gladioli has been reported as the pathogen responsible for cases of foodborne illness in many countries. The poisonous bongkrekic acid (BA) produced by B. gladioli was linked to a gene cluster absent in non-pathogenic strains. The whole genome sequence of eight bacteria strains, which were screened from the collected 175 raw food and environmental samples, were assembled and analyzed to detect a significant association of 19 protein-coding genes with the pathogenic status. Except for the common BA synthesis-related gene, several other genes, including the toxin-antitoxin genes, were also absent in the non-pathogenic strains. The bacteria strains with the BA gene cluster were found to form a single cluster in the analysis of all B. gladioli genome assemblies for the variants in the gene cluster. Divergence of this cluster was detected in the analysis for both the flanking sequences and those of the whole genome level, which indicates its complex origin. Genome recombination was found to cause a precise sequence deletion in the gene cluster region, which was found to be predominant in the non-pathogenic strains indicating the possible effect of horizontal gene transfer. Our study provided new information and resources for understanding the evolution and divergence of the B. gladioli species.

MiR-421 inhibition protects H9c2 cells against hypoxia/reoxygenation-induced oxidative stress and apoptosis by targeting Sirt3.

BACKGROUND: MicroRNAs (miRNAs) are involved in myocardial ischemia-reperfusion injury. miRNA-421 (miR-421) plays a significant role in the initiation of apoptosis and myocardial infarction. However, the molecular regulation of miR-421 in myocardial ischemia-reperfusion injury requires further elucidation. METHODS: An in vitro hypoxia/reoxygenation model was established, and the expression levels of miR-421 and Sirtuin-3 (Sirt3) in H9c2 cells were quantified using quantitative real-time polymerase chain reaction. Flow cytometry was employed to measure the effects of miR-421 on myocardial apoptosis induced by hypoxia/reoxygenation. The activity of lactate dehydrogenase and superoxide dismutase and levels of malondialdehyde were measured. The binding sites of miR-421 on Sirt3 were predicted using TargetScan software. A luciferase reporter assay was used to validate the direct targeting of Sirt3 with miR-421. Protein expression levels of Sirt3 and its downstream proteins were evaluated using Western blot analysis. RESULTS: Exposure of H9c2 cells to hypoxia/reoxygenation led to increased apoptosis, levels of malondialdehyde and lactate dehydrogenase, and decreased levels of superoxide dismutase. miR-421 knockdown resulted in decreased apoptosis, levels of lactate dehydrogenase and malondialdehyde, and increased superoxide dismutase levels in H9c2 cells. Hypoxia/reoxygenation significantly decreased the relative expression levels of Sirt3. Down-regulation of Sirt3 resulted from overexpression of miR-421, which directly targeted Sirt3. Knockdown of miR-421 up-regulated Sirt3 expression, inhibited activation of the Jun N-terminal kinase/activator protein 1 pathway and caspase 9/3-dependent cell death. CONCLUSION: The miR-421-Sirt3-Jun N-terminal kinase/activator protein 1 axis is a novel molecular mechanism that accommodates hypoxia/reoxygenation-induced oxidative stress and apoptosis and provides a new direction for the study and treatment of hypoxia/reoxygenation.

Impact of Plaque Calcification and Stent Oversizing on Clinical Outcomes of Atherosclerotic Femoropopliteal Arterial Occlusive Disease Following Stent Angioplasty.

OBJECTIVE: Plaque calcification and stent oversizing are two key factors contributing to in stent restenosis (ISR) following femoropopliteal stent angioplasty. This study aimed to explore a pre-operative quantitative assessment method of plaque calcification and rational parameters of stent oversizing in the femoropopliteal artery. METHODS: A total of 115 patients with atherosclerotic femoropopliteal arterial occlusive disease treated from January 2013 to January 2016 were included retrospectively. Computed tomography angiography (CTA) imaging was performed to analyse calcified plaque parameters (calcified plaque volume [CV], standard CV [SCV], burden of calcified plaque) and stent oversizing parameters at different vessel segments (distal oversizing, maximum oversizing, plaque oversizing). Optimal cut offs for the six parameters were determined by the maximum Youden's index. The relationship between calcified plaque, stent oversizing, and clinical outcomes were assessed by correlation analysis and multivariable Cox regression models. RESULTS: The one year primary patency rate was 77.4%; the rates of ISR, major amputation, target lesion revascularisation, and mortality were 40.9%, 8.7%, 17.4%, and 12.2%, respectively. For all six parameters, patients with values greater than the cut offs had a significantly higher incidence of ISR than those with values below the cut offs. ISR was positively correlated with all six calcification and oversizing parameters. Amputation and mortality were positively correlated with calcification parameters. Multivariable Cox regression analysis demonstrated that all six parameters were independent risk factors for ISR. All calcification parameters were identified as independent risk factors for amputation, while only CV and SCV were independent risk factors for mortality. CONCLUSION: Calcified plaque in the femoropopliteal artery can be quantitatively analysed on pre-operative CTA images. High calcified plaque burden and excessive stent oversizing were associated with unfavourable outcomes following stent angioplasty.

Seasonal and weather variation of sleep and physical activity in 12-14-year-old children.

Background: Understanding variation in physical activity (PA) and sleep is necessary to develop novel intervention strategies targeting adolescents' health behaviors. We examined the extent to which PA and sleep vary by aspects of the physical environment. Participants: We performed a cross-sectional analysis of 669 adolescents in the Project Viva cohort. Methods: We estimated total PA, sleep duration, sleep efficiency, and sleep midpoint timing from wrist accelerometers. We used multivariable linear regression models and generalized estimated equations to assess associations of PA and sleep with season and daily weather conditions obtained from the National Oceanic and Atmospheric Administration archive. Results: Mean age was 12.9 (SD 0.6) years; 51% were female and 68% were white. Mean sleep duration was 466 (SD 42) min per night and total PA was 1,652 (SD 431) counts per min per day. Sleep midpoint time was 41 (95% CI: 27 to 54) min later in summer, 28 (95% CI: -41 to -14) min earlier in spring, and 29 (95% CI: -43 to -15) min earlier in autumn compared to winter. Higher temperature and longer day length both were associated with small reductions of nightly sleep duration. Adolescents were less physically active during winter and on rainy and short sunlight days. There was an inverse U-shaped relationship between PA and mean temperature. Conclusions: Season was associated with large changes in sleep timing, and smaller changes in other sleep and PA measurements. Given the importance of sleep and circadian alignment, future health behavioral interventions may benefit by targeting "season-specific" interventions.

Common variants in DRD2 are associated with sleep duration: the CARe consortium.

Sleep duration is implicated in the etiologies of chronic diseases and premature mortality. However, the genetic basis for sleep duration is poorly defined. We sought to identify novel genetic components influencing sleep duration in a multi-ethnic sample. Meta-analyses were conducted of genetic associations with self-reported, habitual sleep duration from seven Candidate Gene Association Resource (CARe) cohorts of over 25 000 individuals of African, Asian, European and Hispanic American ancestry. All individuals were genotyped for ∼50 000 SNPs from 2000 candidate heart, lung, blood and sleep genes. African-Americans had additional genome-wide genotypes. Four cohorts provided replication. A SNP (rs17601612) in the dopamine D2 receptor gene (DRD2) was significantly associated with sleep duration (P = 9.8 × 10(-7)). Conditional analysis identified a second DRD2 signal with opposite effects on sleep duration. In exploratory analysis, suggestive association was observed for rs17601612 with polysomnographically determined sleep latency (P = 0.002). The lead DRD2 signal was recently identified in a schizophrenia GWAS, and a genetic risk score of 11 additional schizophrenia GWAS loci genotyped on the IBC array was also associated with longer sleep duration (P = 0.03). These findings support a role for DRD2 in influencing sleep duration. Our work motivates future pharmocogenetics research on alerting agents such as caffeine and modafinil that interact with the dopaminergic pathway and further investigation of genetic overlap between sleep and neuro-psychiatric traits.

Impact of continuous positive airway pressure and oxygen on health status in patients with coronary heart disease, cardiovascular risk factors, and obstructive sleep apnea: A Heart Biomarker Evaluation in Apnea Treatment (HEARTBEAT) analysis.

INTRODUCTION: Obstructive sleep apnea (OSA) is associated with impaired health-related quality of life (HRQL). Treatment with continuous positive airway pressure (CPAP) has variable impacts on HRQL, and this may be influenced by patient's tolerance of therapy. The objective is to determine the impact of nocturnal supplemental oxygen (NSO) and CPAP on HRQL compared with healthy lifestyle education (HLSE) in individuals with OSA. METHODS: Patients with coronary heart disease (CHD) or at least 3 major CHD risk factors with apnea-hypopnea index of 15 to 50 events/h were randomized to CPAP, NSO, or HLSE. Health-related quality of life was assessed using the Short-Form 36, and depression was assessed with Patient Health Questionnaire-9 at baseline and 12 weeks. The treatment effect on HRQL change scores through 12 weeks was assessed using multivariable models adjusting for study site, presence of CHD at baseline, race, and baseline HRQL. RESULTS: A total of 318 patients were randomized to 1 of 3 treatment arms with 1:1:1 ratio and 94% completed baseline and follow-up HRQL instruments. Mean Short-Form 36 scores were similar at baseline in all 3 groups ranging from 41.8±12 to 51.6±12 in various domains. In multivariable models, the CPAP group noted a significantly greater improvement than NSO in mental health (+2.33, 95% CI 0.34-4.31, P=.02) and mental composite score (+2.40, 95% CI 0.40-4.41, P=.02). Conversely, the CPAP group noted less improvement than NSO in physical function (-2.68, 95% CI -4.66 to -0.70, P=.008) and physical composite score (-2.17, 95% CI -3.82 to -0.51, P=.01). Compared with HLSE, vitality and Patient Health Questionnaire-9 improved with CPAP but not with NSO. Significant interactions were noted between treatment effects with larger differences in black and sleepy patients. CONCLUSION: These data support the use of CPAP for improving vitality, sleepiness, mental health, social functioning, and depressive symptoms in patients with OSA and established CHD or risk factors. Nocturnal supplemental oxygen may have beneficial effects on perceived physical functioning.

Actigraphic sleep measures and diet quality in the Hispanic Community Health Study/Study of Latinos Sueño ancillary study.

Using a cross-sectional probability sample with actigraphy data and two 24-h dietary recalls, we quantified the association between sleep duration, continuity, variability and timing with the Alternative Healthy Eating Index-2010 diet quality score and its components in 2140 Hispanic Community Health Study/Study of Latinos participants. The Alternative Healthy Eating Index diet quality-2010 score ranges from 0 to 110, with higher scores indicating greater adherence to the dietary guidelines and lower risk from major chronic disease. None of the sleep measures was associated with total caloric intake as assessed using dietary recalls. However, both an increase in sleep duration and sleep efficiency were associated with healthier diet quality. Each standard deviation increase in sleep duration (1.05 h) and sleep efficiency (4.99%) was associated with a 0.30 point increase and 0.28 point increase, respectively, in the total Alternative Healthy Eating Index-2010 score. The component of Alternative Healthy Eating Index-2010 most strongly associated with longer sleep duration was increased nuts and legumes intake. The components of Alternative Healthy Eating Index-2010 most strongly associated with higher sleep efficiency were increased whole fruit intake and decreased sodium intake. Both longer sleep duration and higher sleep efficiency were significantly associated with better diet quality among US Hispanic/Latino adults. The dietary components most strongly associated with sleep duration and sleep efficiency differed, suggesting potentially independent mechanisms by which each aspect of sleep impacts dietary choices. Longitudinal research is needed to understand the directionality of these identified relationships and the generalizability of these data across other ethnic groups.

Post-dredging effect assessment based on sediment chemical quality in urban rivers of Yangzhou.

Deteriorating of urban river environment in Yangzhou is gradually serious in recent years. Treatment measures including pollution source control, sewage interception, and sludge dredging have been carried out in recent years, but urban river environment is still poor. In order to ascertain the causes, post-dredging effects were assessed based on sediment chemical quality in urban rivers of Yangzhou. Results indicate that post-dredging effects are not ideal because of backward dredging technique and incomplete pollution control. Eutrophication degree is still relatively high for most of them and pollution degree of nutrients is total phosphorus (TP) > total nitrogen (TN) > organic matter (OM). Although the pollution of heavy metals is not serious, the major pollution factors Cd and Hg should still be monitored intensively in the sludge dredging for the toxic effect of heavy metals.

Associations between Obstructive Sleep Apnea, Sleep Duration, and Abnormal Fasting Glucose. The Multi-Ethnic Study of Atherosclerosis.

RATIONALE: No data exist as to the role of ethnicity in the associations between obstructive sleep apnea (OSA), sleep duration, and metabolic dysfunction. OBJECTIVES: To examine links between OSA, objectively measured habitual sleep duration, and fasting glucose in U.S. ethnic groups. METHODS: The Multi-Ethnic Study of Atherosclerosis is a multisite community-based study that conducted polysomnography and wrist actigraphy. In 2,151 subjects (1,839 in fully adjusted models), the apnea-hypopnea index was used to classify OSA as none (0-4.9/h), mild (5-14.9/h), or moderate to severe (≥15/h). Actigraphic sleep duration was classified as short (≤5 h/night), intermediate (>5 and <8 h/night), or long (≥8 h/night). Subjects were classified as having normal fasting glucose (<100 mg/dl and no hypoglycemic medication use) or abnormal fasting glucose (≥100 mg/dl and/or hypoglycemic medication use). MEASUREMENTS AND MAIN RESULTS: The sample was 45.8% male, age 68.5 ± 9.2 (mean ± SD) years, and 27.3% African American, 37.2% white, 11.8% Chinese, and 23.8% Hispanic. The prevalence of abnormal fasting glucose was 40.2%. Relative to subjects without apnea, moderate-to-severe OSA was significantly associated with abnormal fasting glucose in African Americans (odds ratio, 2.14; 95% confidence interval, 1.12-4.08) and white participants (odds ratio, 2.85; 95% confidence interval, 1.20-6.75), but not among Chinese or Hispanic subjects, after adjusting for site, age, sex, waist circumference, and sleep duration (P = 0.06 for ethnicity-by-OSA severity interaction). In contrast, sleep duration was not significantly associated with abnormal fasting glucose after considering the influence of OSA. CONCLUSIONS: This large multiethnic study confirmed previous reports of an independent association between OSA and metabolic dysfunction, and suggested that this association may vary by ethnicity.

An integrated genomic approach identifies persistent tumor suppressive effects of transforming growth factor-ß in human breast cancer.

INTRODUCTION: Transforming growth factor-ßs (TGF-ßs) play a dual role in breast cancer, with context-dependent tumor-suppressive or pro-oncogenic effects. TGF-ß antagonists are showing promise in early-phase clinical oncology trials to neutralize the pro-oncogenic effects. However, there is currently no way to determine whether the tumor-suppressive effects of TGF-ß are still active in human breast tumors at the time of surgery and treatment, a situation that could lead to adverse therapeutic responses. METHODS: Using a breast cancer progression model that exemplifies the dual role of TGF-ß, promoter-wide chromatin immunoprecipitation and transcriptomic approaches were applied to identify a core set of TGF-ß-regulated genes that specifically reflect only the tumor-suppressor arm of the pathway. The clinical significance of this signature and the underlying biology were investigated using bioinformatic analyses in clinical breast cancer datasets, and knockdown validation approaches in tumor xenografts. RESULTS: TGF-ß-driven tumor suppression was highly dependent on Smad3, and Smad3 target genes that were specifically enriched for involvement in tumor suppression were identified. Patterns of Smad3 binding reflected the preexisting active chromatin landscape, and target genes were frequently regulated in opposite directions in vitro and in vivo, highlighting the strong contextuality of TGF-ß action. An in vivo-weighted TGF-ß/Smad3 tumor-suppressor signature was associated with good outcome in estrogen receptor-positive breast cancer cohorts. TGF-ß/Smad3 effects on cell proliferation, differentiation and ephrin signaling contributed to the observed tumor suppression. CONCLUSIONS: Tumor-suppressive effects of TGF-ß persist in some breast cancer patients at the time of surgery and affect clinical outcome. Carefully tailored in vitro/in vivo genomic approaches can identify such patients for exclusion from treatment with TGF-ß antagonists.

Integrated genomic analysis defines molecular subgroups in dilated cardiomyopathy and identifies novel biomarkers based on machine learning methods.

Aim: As the most common cardiomyopathy, dilated cardiomyopathy (DCM) often leads to progressive heart failure and sudden cardiac death. This study was designed to investigate the molecular subgroups of DCM. Methods: Three datasets of DCM were downloaded from GEO database (GSE17800, GSE79962 and GSE3585). After log2-transformation and background correction with "limma" package in R software, the three datasets were merged into a metadata cohort. The consensus clustering was conducted by the "Consensus Cluster Plus" package to uncover the molecular subgroups of DCM. Moreover, clinical characteristics of different molecular subgroups were compared in detail. We also adopted Weighted gene co-expression network analysis (WGCNA) analysis based on subgroup-specific signatures of gene expression profiles to further explore the specific gene modules of each molecular subgroup and its biological function. Two machine learning methods of LASSO regression algorithm and SVM-RFE algorithm was used to screen out the genetic biomarkers, of which the discriminative ability of molecular subgroups was evaluated by receiver operating characteristic (ROC) curve. Results: Based on the gene expression profiles, heart tissue samples from patients with DCM were clustered into three molecular subgroups. No statistical difference was found in age, body mass index (BMI) and left ventricular internal diameter at end-diastole (LVIDD) among three molecular subgroups. However, the results of left ventricular ejection fraction (LVEF) statistics showed that patients from subgroup 2 had a worse condition than the other group. We found that some of the gene modules (pink, black and grey) in WGCNA analysis were significantly related to cardiac function, and each molecular subgroup had its specific gene modules functions in modulating occurrence and progression of DCM. LASSO regression algorithm and SVM-RFE algorithm was used to further screen out genetic biomarkers of molecular subgroup 2, including TCEAL4, ISG15, RWDD1, ALG5, MRPL20, JTB and LITAF. The results of ROC curves showed that all of the genetic biomarkers had favorable discriminative effectiveness. Conclusion: Patients from different molecular subgroups have their unique gene expression patterns and different clinical characteristics. More personalized treatment under the guidance of gene expression patterns should be realized.

Association of different obesity patterns with hypertension in US male adults: a cross-sectional study.

Obesity is an important risk factor for hypertension. We aimed to investigate the association between different obesity patterns and hypertension risk in a large male population in the US. Male participants from the National Health and Nutrition Examination Survey (NHANES) (2007-2018) were enrolled in this cross-sectional study. Social demographic information, lifestyle factors, anthropometric measurements and biochemical measurements were collected. Three obesity patterns were classified according to the body mass index (BMI) and waist circumference (WC), including overweight and general obesity, abdominal obesity, and compound obesity. We adopted multivariate logistic regression to investigate the associations between hypertension and different obesity patterns after adjusting for cofounding factors. Subgroup analysis, stratified by age, smoking, drinking and estimated glomerular filtration rate (eGFR), was also conducted to explore the associations between obesity patterns and hypertension risk among different populations. Moreover, the association between WC and hypertension among male individuals was also explored using restricted cubic spline (RCS) analysis. Receiver operating characteristic (ROC) was used to evaluate the discriminatory power of WC for screening hypertension risk. 13,859 male participants from NHANES survey (2007-2018) were enrolled. Comparing with the normal-weight group, the odds ratios (ORs) [95% confidence interval (CI)] for hypertension in individuals with overweight and general obesity, abdominal obesity and compound obesity were 1.41 [1.17-1.70], 1.97 [1.53-2.54] and 3.28 [2.70-3.99], respectively. Subgroup analysis showed that the effect of different obesity patterns on hypertension risk was highly stable among individuals with different clinical conditions. In addition, WC had a positive correlation with the risk of hypertension (OR: 1.43; 95% CI 1.37-1.52; P < 0.001) in fully adjusted multivariate logistic regression model. RCS analysis showed that the association between WC and hypertension risk was in a nonlinear pattern, and WC had a good discriminatory power for hypertension in ROC analysis. Different patterns of obesity have a great impact on the risk of hypertension among male individuals. Increment of WC significantly increased the hypertension risk. More attention should be paid to the prevention of obesity, especially abdominal obesity and compound obesity in male individuals.

Therapeutic Effects of Xianlu Oral Solution on Rats with Oligoasthenozoospermia through Alleviating Apoptosis and Oxidative Stress.

Idiopathic oligoasthenozoospermia (iOAZS) is one of the major causes of male infertility, and the ideal therapies for iOAZS have not been established yet. Traditional Chinese medicine (TCM), including Xianlu oral solution (XL), has been widely used as an adjunct treatment for male infertility in the clinic. However, the underlying mechanisms of XL treatment on iOAZS are still not known. Here, we found that XL treatment has therapeutic effects on ornidazole (ORN)-induced OAZS model rats through the amelioration of testis tissues spermatogenesis and the improvement of sperm concentration and motility. Moreover, XL treatment ameliorated the serum hormone levels, mitochondrial membrane potential, apoptosis status, and oxidative stress status in the testis tissues of iOAZS model rats. These findings identify a potential mechanism underlying the therapeutic effects of Xianlu oral solution on iOAZS, and Xianlu oral solution may be used as a traditional Chinese medicine (TCM) therapy for male infertility caused by iOAZS in clinical practice.

Characteristics and prognosis of primary pulmonary osteosarcoma: a pooled analysis.

BACKGROUND: Primary pulmonary osteosarcoma (PPOS) is an uncommon malignancy originating from the lung with low incidence, and its clinical characteristics and prognosis have not been systematically reported. Therefore, we aimed to recognize the prognostic factors and constructed a survival prediction model for PPOS. METHODS: We collected the data from the Surveillance, Epidemiology, and End Results database and systematic review of previous studies. Demographical and clinical characteristics, radiographic manifestations, treatment modalities, and prognosis were analyzed. A prediction model via nomogram was constructed and then evaluated by the concordance index (C-index) and the receiver operating characteristic (ROC) curve. RESULTS: A total of 49 cases were included for analysis with a median age of 67 years old (range 33-94 years), of which 32 (65.3%) were male. The median size was 6 cm (range 1.8-25 cm), and the median overall survival (OS) was eight months (interquartile range 4.5-12 months) with a 1-year OS rate of 30.8%. Tumor size over 7 cm (hazard ratio [HR] = 2.98; P = 0.018) and those without microscopic findings of osteoid found in the tumors (HR = 2.11; P = 0.048) were referred to a poor OS, while surgery was associated with an improved OS (HR = 0.20; P < 0.001). The C-index of the nomogram prediction model was 0.771, and the area under curve, sensitivity and specificity of the ROC curve were 0.818, 0.848 and 0.800, respectively. CONCLUSIONS: Patients with PPOS had a poor prognosis, and tumor size was mostly prognostic. Surgery seemed to be an effective treatment, and the prediction model with a nomogram in our study could effectively predict the prognosis of patients with PPOS.

The dietary inflammatory index and its association with the prevalence of hypertension: A cross-sectional study.

Aims: We aim to investigate the association of the Dietary Inflammatory Index (DII) with the prevalence of hypertension in a large multiracial population in the United States. Methods: Participants from the National Health and Nutrition Examination Survey (NHANES) (1999-2018) were included in this cross-sectional study. Dietary information was obtained and used to calculate DII. Blood pressures of participants were measured by experienced examiners. The NHANES used the method of "stratified multistage probability sampling," and this study is a weight analysis following the NHANES analytic guidance. Weight logistic regression analysis was adopted to investigate the association of hypertension with DII. Least Absolute Shrinkage and Selection Operator (LASSO) regression was carried out to screen the most important dietary factors associated with the risk of hypertension. Moreover, a nomogram model based on key dietary factors was established; the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic power of the nomogram model for screening hypertension risk. Results: A total of 45,023 participants were included in this study, representing 191 million residents in the United States. Participants with hypertension had an elevated DII compared with those without hypertension. Weight logistic regression showed that an increment of DII was strongly associated with hypertension after adjusting for confounding factors. The nomogram model, based on key dietary factors screened by LASSO regression, showed a favorable discriminatory power with an area under the curve (AUC) of 78.5% (95% CI: 78.5%-79.3%). Results of the sensitivity analysis excluding participants who received any drug treatment were consistent with those in the main analysis. Conclusion: An increment of DII is associated with the risk of hypertension. For better prevention and treatment of hypertension, more attention should be paid to controlling dietary inflammation.

External validation of ABCD series scores for predicting early stroke events following transient ischemic attack in a large nationwide registry.

Introduction: In the context of modern guideline-based strategies, new validations of prognostic scores for predicting early stroke risk are needed. We aimed to compare the validity of the ABCD series scores and assess the incremental values of risk components for predicting in-hospital stroke events in patients with transient ischemic attack (TIA). Patients and methods: We abstracted data from the Chinese Stroke Center Alliance (CSCA), a nationwide registry with 68,433 TIA patients admitted within 7 days of symptom onset from 1476 hospitals. TIA was defined by time-based criteria according to the World Health Organization (WHO). The discrimination of ABCD, ABCD2, ABCD2-I, and ABCD3 scores for predicting in-hospital stroke events was assessed by the area under the receiver-operating characteristics curves (AUC). The incremental predictive values of added risk predictor were determined by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: A total of 29,286 TIA patients were included, of whom 1466 (5.0%) had in-hospital stroke events. Compared with ABCD2-I score (AUC 0.79, 95% confidence interval [CI] 0.77-0.80), ABCD (AUC 0.58, 95% CI 0.57-0.60), ABCD2 (AUC 0.58, 95% CI 0.56-0.59), and ABCD3 (AUC 0.58, 95% CI 0.56-0.60) had lower predictive utility. An incremental value was observed when adding infarction on DWI (IDI = 0.0597, NRI = 1.1036) into ABCD2 score to be ABCD2-I. Conclusion: The traditional scales utilizing medical history (ABCD, ABCD2, and ABCD3 scores) show fair ability for predicting in-hospital stroke events after TIA, but the ABCD2-I score, which adds infarction on DWI, improves the predictive ability.

Lenvatinib plus anti-PD-1 therapy represents a feasible conversion resection strategy for patients with initially unresectable hepatocellular carcinoma: A retrospective study.

Purpose: We aimed to investigate the feasibility of lenvatinib plus anti-PD-1 therapy as a conversion therapy for initially unresectable hepatocellular carcinoma (HCC). Methods: Patients with initially unresectable HCC who received combined lenvatinib and anti-PD-1 antibody between May 2020 and Jan 2022 in Zhongshan Hospital were retrospectively analyzed. Tumor response and resectability were assessed by imaging every two months according to RECIST version 1.1 and modified RECIST (mRECIST) criteria. Results: A total of 107 patients were enrolled. 30 (28%) of them received conversion surgery within 90.5 (range: 53-456) days after the initiation of lenvatinib plus anti-PD-1 therapy. At baseline, the median largest tumor diameter of these 30 patients was 9.2 cm (range: 3.5-15.0 cm), 26 patients had Barcelona Clinic Liver Cancer stage B-C, and 4 had stage A. Prior to surgery, all cases displayed tumor regression and 15 patients achieved objective response. Pathological complete response (pCR) was observed in 10 patients. No severe drug-related adverse events or surgical complications were observed. After a median follow-up of 16.5 months, 28 patients survived and 11 developed tumor recurrence. Survival analysis showed patients achieving tumor response before surgery or pCR had a longer tumor-free survival. Notably, patients with microvascular invasion (MVI) had significantly higher recurrence rate and poorer overall survival than patients without. Conclusions: Lenvatinib combined with anti-PD-1 therapy represents a feasible conversion strategy for patients with initially unresectable HCC. Patients achieving tumor responses are more likely to benefit from conversion resection to access a longer term of tumor-free survival.

[Preparation of rat model of systemic inflammatory response syndrome induced by zymosan].

OBJECTIVE: To establish a model of systemic inflammatory response syndrome (SIRS) in rats. METHODS: SD rats were intraperitoneally injected with different concentrations of zymosan suspension. The general status, temperature, white cell count, tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), interleukin-10 (IL-10) and the pathological changes of main organs were examined. RESULTS: The conditions of rats receiving zymosan doses of 750 mg/kg and 1000 mg/kg were consistent with the criteria of SIRS model; however, the mortality of 1000 mg/kg group was higher than that of 750 mg/kg group. CONCLUSION: The rat model of systemic inflammatory response syndrome has been successfully induced.

Eight Trigrams Boxing Combined with Wenyang Huoxue Recipe Improves Cardiopulmonary Motor Function and the Quality of Life of Patients with Coronary Heart Disease.

OBJECTIVE: To investigate the therapeutic effects of Eight Trigrams Boxing combined with a Wenyang Huoxue recipe on the cardiopulmonary motor function and quality of life in patients with coronary heart disease after an interventional operation (percutaneous coronary intervention [PCI]); further, to provide new clinical evidence and ideas for integrated traditional Chinese and Western medicine in cardiac rehabilitation. METHODS: Sixty patients were selected and successfully underwent PCI in designated hospitals after four weeks, from June 2018 to September 2020. The patients were randomly divided into a treatment group and control group, and both groups were given standard pharmaceuticals after PCI and the Wenyang Huoxue recipe. The treatment group was additionally treated with the Eight Trigrams Boxing Method. The control group was provided with aerobic rehabilitation exercise. The maximum oxygen uptake (VO2max), metabolic equivalent (MET), the results of a 6-min walking test, the Seattle Angina Questionnaire (SAQ) score, SF-36 score, and other indicators were evaluated before and after treatment. The therapeutic effect was evaluated by comparison between the groups and within the groups. RESULTS: The VO2max, MET, 6-min walking distance, SAQ score, and SF-36 score in both groups improved after treatment compared with before treatment. There was no difference between the two groups before treatment. However, after treatment, the VO2max, MET, 6 min walking distance, SAQ score, and SF-36 score in the treatment group were higher compared with the control group. CONCLUSION: A traditional Chinese medicine cardiac rehabilitation program of Eight Trigrams Boxing combined with a Wenyang Huoxue recipe can improve the cardiopulmonary function and quality of life of patients. The therapeutic effect was clear and is worthy of further investigation.