Development of a prognostic signature for immune-associated genes in bladder cancer and exploring potential drug findings.

BACKGROUND: Bladder cancer, predominantly affecting men, is a prevalent malignancy of the urinary system. Although platinum-based chemotherapy has demonstrated certain enhancements in overall survival when compared to surgery alone, the efficacy of treatments is impeded by the unfavorable side effects of conventional chemotherapy medications. Nonetheless, immunotherapy exhibits potential in the treatment of bladder cancer. METHODS: To create an immune-associated prognostic signature for bladder cancer, bioinformatics analyses were performed utilizing The Cancer Genome Atlas (TCGA) database in this study. By identifying differential gene expressions between the high-risk and low-risk groups, a potential therapeutic drug was predicted using the Connectivity Map database. Subsequently, the impact of this drug on the growth of T24 cells was validated through MTT assay and 3D cell culture techniques. RESULTS: The signature included 1 immune-associated LncRNA (NR2F1-AS1) and 16 immune-associated mRNAs (DEFB133, RBP7, PDGFRA, CGB3, PDGFD, SCG2, ADCYAP1R1, OPRL1, PGR, PSMD1, TANK, PRDX1, ADIPOR2, S100A8, AHNAK, EGFR). Based on the assessment of risk scores, the patients were classified into cohorts of low-risk and high-risk individuals. The cohort with low risk demonstrated a considerably higher likelihood of survival in comparison to the group with high risk. Furthermore, variations in immune infiltration were noted among the two categories. Cephaeline, a possible medication, was discovered by analyzing variations in gene expression. It exhibited promise in suppressing the viability and growth of T24 bladder cancer cells. CONCLUSION: The novel predictive pattern allows for efficient categorization of patients with bladder cancer, enabling focused and rigorous treatment for those expected to have a worse prognosis. The discovery of a possible curative medication establishes a basis for forthcoming immunotherapy trials in bladder cancer.

The associations of secondhand smoke exposure with neurodevelopmental disorders and critical time window identification: A systematic review and meta-analysis.

BACKGROUND: Secondhand smoke (SHS) exposure was harmful for brain development. However, the association between SHS exposure and NDDs diagnosis were unclear. OBJECTIVES: To evaluate associations between SHS exposure and NDDs diagnosis, identify critical time windows, and summarize the strength of evidence. METHODS: To investigate the associations of SHS exposure and the development of NDDs, we searched Ovid, EMBASE, Web of Science, Cochrane Library, and PubMed for all the relevant studies up to 31 March 2023. The risk estimates and standardized mean differences (SMD) for the individuals with any NDDs who were exposed to SHS exposure compared with those unexposed or low-exposed. RESULTS: The results showed that a total of 31,098 citations were identified, of which 54 studies were included. We identified significant associations between SHS exposure and the risks of NDDs including specific types of NDDs like attention deficit hyperactivity disorder (ADHD) and learning disabilities (LD) despite the observed heterogeneity for NDDs and ADHD. We also observed a significant association between cotinine exposure and ADHD. However, inconsistent ratings between the two quality-of-evidence methods for all the meta-analyses indicated the current evidence of the associations and the potential exposure window remained inconclusive. DISCUSSION: Our findings suggested that SHS exposure was associated with a higher risk of developing ADHD and LD, with inconclusive quality-of-evidence. In addition, period-specific associations remained unclear based on current evidence.

Relationship between body composition and pulmonary function in the general population-a cross-sectional study in Ningxia.

Studies considering the relationship between non-obesity-related body composition and lung function are few; therefore, this study aimed to explore these correlations and effects. This cross-sectional study conducted in rural Qingtongxia City and Pingluo County, Ningxia, China, included 776 participants aged 30-75 years. Body composition and lung function were measured using direct segmental multifrequency bioelectrical impedance analysis and a digital spirometer, respectively. Their correlation was assessed using partial correlation analysis, controlling for age and smoking status, and the body composition effect on lung function was analyzed using binomial logistic regression analysis. The body components total body water content, protein content, mineral content, muscle mass, fat-free mass (FFM), skeletal muscle mass, basal metabolic volume, and chest circumference (CC) positively correlated with pulmonary function (forced vital capacity and forced expiratory volume in one second) in both sexes. Neck circumference and hip circumference positively correlated with pulmonary function in women. Additionally, lung function declines more slowly in women (odds ratio [OR] = 0.66, 95% confidence interval [CI] = 0.44-0.98, p = 0.04); CC (OR = 0.92, 95% CI = 0.86-0.98, p = 0.01) increased as a protective factor for decreased lung function. Increased waist circumference (OR = 1.04, 95% CI = 1.00-1.09, p = 0.04) was a risk factor for reduced lung function. FFM contains body composition indicators positively correlating with lung function, excluding fat-related body composition. Abdominal obesity increases the risk of decreased lung function.

Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression.

BACKGROUND: Corosolic acid is a pentacyclic triterpene acid with hypoglycemic, anti-inflammatory, and anti-cancer effects. However, its potential targets in hepatocellular carcinoma (HCC) are unknown, hindering clinical utilization. METHODS: Differentially expressed proteins of the Bel-7404 cell line were identified with tandem mass tag analysis and differentially expressed genes (DEGs) of an HCC TCGA dataset using bioinformatics. Gene functions and pathways were inferred using the DAVID database. Online databases were used to establish P4HA2 expression in HCC (GEPIA2) and its relationship with patient survival (UALCAN and The Human Protein Atlas), the association between P4HA2 expression and immune cell infiltration (TIMER2), and DNA methylation of the P4HA2 gene (MethSurv). Cell proliferation, cell cycle, and cell death were assessed with PI and SYTOX-Green staining, CCK-8, and colony formation assays. Protein expression levels were detected by Western blotting. RESULTS: A total of 44 differentially expressed proteins and 4498 DEGs were identified. Four genes whose proteins were also found in the differential protein profile but with opposing expressions were selected as candidate targets. The candidate gene prolyl 4-hydroxylase subunit alpha 2 (P4HA2) was recognized as the only potential target due to its high expression in public datasets, association with poor patient survival, and relation to immune cell infiltration in HCC tissues. Moreover, the DNA methylation status in 4 CpG islands of the P4HA2 gene correlated with a poor prognosis. Furthermore, corosolic acid treatment inhibited the proliferation of HCC cell lines Bel-7404 and HepG2 in a dose-dependent manner, caused G2/M phase cell cycle arrest, and promoted cell death. In addition, the treatment reduced P4HA2 protein levels. CONCLUSION: Our results indicate that P4HA2 is a potential target of corosolic acid. Thus, they contribute to understanding molecular changes in HCC after corosolic acid treatment and facilitate finding new treatment regimens.

Chinese medicinal herbs for reducing endocrine therapy-induced side effects in patients with hormone receptor-positive breast cancer: a systematic review and meta-analysis.

CONTEXT: Chinese medicinal herbs (CMH) have been considered a potentially efficacious approach for patients with breast cancer that experience adverse effects from endocrine treatment. OBJECTIVE: To investigate the impact of CMH on endocrine therapy-induced side effects in patients with hormone receptor-positive (HR+) breast cancer. METHODS: Ten databases (e.g., PubMed, Web of Science, Cochrane Library, China National Knowledge Information Database and other databases) were searched up to 20 May 2022. The search terms included Chinese herb, breast cancer, endocrine therapy, clinical trial and their mesh terms. The study selection and data extraction were performed by two independent reviewers. The risk of bias was evaluated using the Cochrane risk of bias method. RESULTS: A total of 31 studies with 2288 patients were included. There were significant improvements in bone mineral density (BMD) [lumbar BMD (MD 0.08, 95% CI 0.07 to 0.09, p < 0.00001) and femoral neck BMD (MD 0.08, 95% CI 0.07 to 0.10, p < 0.00001)] and bone gal protein (BGP) (MD 0.24, 95% CI 0.17 to 0.31, p < 0.00001), with a significant reduction in triglycerides (MD -0.53, 95% CI -1.00 to -0.07, p < 0.05) and no effect on estradiol levels (MD 0.90, 95% CI -0.31 to 2.12, p = 0.15). CONCLUSIONS: CMH combined with complementary therapy can moderately reduce endocrine therapy-induced side effects, including bone loss and dyslipidemia in patients with HR + breast cancer, revealing the potential role of CMH in treating (HR+) breast cancer. More high-quality RCTs are warranted to further validate the effectiveness and safety of CMH.

Pre-conceptional and prenatal exposure to secondhand smoke and autism spectrum disorder: a national multi-center study in China.

BACKGROUND: Despite extensive research evaluating the association between prenatal exposure to secondhand smoke (SHS) and the development of autism spectrum disorders (ASD), no study has investigated the association by considering the pre-conceptional period. This study aimed to investigate the associations of pre-conceptional and prenatal SHS exposure and the development of ASD among toddlers. METHODS: In this cross-sectional study, parents of 6049 toddlers aged 16-30 months were recruited from 7 tertiary hospitals, 21 communities, and 7 kindergartens located in seven cities in six provinces from five geographical regions of China. We analyzed the associations of SHS exposure and the odds of ASD among toddlers in different exposure windows (pre-conceptional and/or prenatal periods). Data were analyzed from November 2021 to January 2022. RESULTS: Among the 6049 toddlers included in the analysis [22.7 (4.1) months; 44.8% girls], 71 were identified and diagnosed with ASD. Compared with the unexposed toddlers, toddlers with pre-conceptional SHS exposure had higher odds of ASD (OR 2.30, 95% CI 1.36-3.84), while we observed a non-significantly positive association regarding prenatal SHS exposure. When considering both pre-conceptional and prenatal periods, toddlers who were continuously exposed to SHS during these two periods had higher odds than those without SHS exposure (OR 2.32, 95% CI 1.24-4.14). CONCLUSION: We reported positive SHS-ASD associations when exposed during the pre-conceptional period and continuously exposed during pre-conceptional and prenatal periods, emphasizing the critical window of pre-conception for targeted intervention on smoking.

EEG-based grading of immune effector cell-associated neurotoxicity syndrome.

CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals. We conducted a retrospective observational study of 120 CAR-T cell therapy patients who had received EEG monitoring. We determined a daily ICANS grade for each patient through chart review. We used visually assessed EEG features and machine learning techniques to develop the Visual EEG-Immune Effector Cell Associated Neurotoxicity Syndrome (VE-ICANS) score and assessed the association between VE-ICANS and ICANS. We also used it to determine the significance and relative importance of the EEG features. We developed the Visual EEG-ICANS (VE-ICANS) grading scale, a grading scale with a physiological basis that has a strong correlation to ICANS severity (R = 0.58 [0.47-0.66]) and excellent discrimination measured via area under the receiver operator curve (AUC = 0.91 for ICANS ≥ 2). This scale shows promise as a biomarker for ICANS which could help to improve clinical care through greater accuracy in assessing ICANS severity.

Association between paternal age at childbirth and autism spectrum disorder in offspring. / çˆ¶äº²ç”Ÿè‚²å¹´é¾„ä¸Žå„¿ç«¥å­¤ç‹¬ç—‡è°±ç³»éšœç¢çš„ç›¸å ³æ€§.

OBJECTIVES: To study the association between paternal age at childbirth and the risk of autism spectrum disorder (ASD) in offspring. METHODS: In this cross-sectional study, 71 children with ASD who were diagnosed in the Department of Child Healthcare in six hospitals in Guangzhou, Foshan, Beijing, Wuhan, Hangzhou, and Chongqing of China from August 2016 to March 2017 were enrolled as subjects, and 284 typically developing children matched for age, sex, and maternal age at childbirth with the ASD children served as controls. A self-design questionnaire was used to collect the data on social demography, maternal pregnancy, and delivery. The association between paternal age at childbirth and the development of ASD in offspring was evaluated by the logistic regression analysis. RESULTS: After control for demographic factors and pregnancy- and delivery-related factors, the logistic regression analysis showed that a relatively high paternal age at childbirth was significantly associated with the increased risk of ASD in offspring (OR=1.12, 95%CI: 1.02-1.23, P<0.05). After grouping based on the paternal age, the logistic regression analysis showed that paternal age at childbirth of ≥40 years was significantly associated with the risk of ASD in offspring (before adjustment: OR=7.08, 95%CI: 1.77-28.32, P<0.05; after adjustment: OR=8.50, 95%CI: 1.71-42.25, P<0.05). CONCLUSIONS: High paternal age at childbirth is significantly associated with the increased risk of ASD in offspring, and paternal age at childbirth ≥40 years may be the high-risk age group for ASD in offspring.

Serum IGF-1 levels are associated with sarcopenia in elderly men but not in elderly women.

BACKGROUND: Sarcopenia is an age-associated decline in muscle mass that negatively affects the metabolic rate, strength, and function of the body and ultimately leads to a decrease in quality of life. Insulin-like growth factor 1 (IGF-1) is a modulator of muscle mass and muscle function. There is evidence that IGF-1 is related to the appendicular skeletal muscle mass index (ASMI) and grip strength. The aim of this study was to explore the relationship between serum IGF-1 levels and sarcopenia in older people. METHODS: In this cross-sectional survey of 984 people older than 60 years old, we used the 2019 criteria of the Asian Working Group for Sarcopenia (AWGS) to define sarcopenia. We collected demographic variables, measured ASMI and grip strength, and detected serum IGF-1 data. The levels of serum IGF-1 were separated into quintiles (Q1-Q5). RESULTS: Adjusted for age, education level, smoking, number of diseases and BMI, the multivariable linear regression analysis revealed that serum IGF-1 levels were related to ASMI in elderly men (coefficient = 0.03, 95% CI = 0.02-0.05, P < 0.001) but were not related to their grip strength. There was no significant relationship between serum IGF-1 levels and ASMI or grip strength in elderly women. The multivariable log-binomial regression analysis showed that higher serum IGF-1 levels were associated with a lower prevalence of sarcopenia in elderly men (prevalence ratio (PR) = 0.99, 95% CI = 0.98-1.00, P < 0.05) but not in elderly women. CONCLUSION: Serum IGF-1 levels were highly correlated with sarcopenia in older men. Further studies are needed to further explore the possible reasons for the observed difference between genders. Serum IGF-1 might predict sarcopenia prevalence in elderly men.

Noninvasive Detection of Hippocampal Epileptiform Activity on Scalp Electroencephalogram.

Importance: The hippocampus is a highly epileptogenic brain region, yet over 90% of hippocampal epileptiform activity (HEA) cannot be identified on scalp electroencephalogram (EEG) by human experts. Currently, detection of HEA requires intracranial electrodes, which limits our understanding of the role of HEA in brain diseases. Objective: To develop and validate a machine learning algorithm that accurately detects HEA from a standard scalp EEG, without the need for intracranial electrodes. Design, Setting, and Participants: In this diagnostic study, conducted from 2008 to 2021, EEG data were used from patients with temporal lobe epilepsy (TLE) and healthy controls (HCs) to train and validate a deep neural network, HEAnet, to detect HEA on scalp EEG. Participants were evaluated at tertiary-level epilepsy centers at 2 academic hospitals: Massachusetts General Hospital (MGH) or Brigham and Women's Hospital (BWH). Included in the study were patients aged 12 to 78 years with a clinical diagnosis of TLE and HCs without epilepsy. Patients with TLE and HCs with a history of intracranial surgery were excluded from the study. Exposures: Simultaneous intracranial EEG and/or scalp EEG. Main Outcomes and Measures: Performance was assessed using cross-validated areas under the receiver operating characteristic curve (AUC ROC) and precision-recall curve (AUC PR) and additional clinically relevant metrics. Results: HEAnet was trained and validated using data sets that were derived from a convenience sample of 141 eligible participants (97 with TLE and 44 HCs without epilepsy) whose retrospective EEG data were readily available. Data set 1 included the simultaneous scalp EEG and intracranial electrode recordings of 51 patients with TLE (mean [SD] age, 40.7 [15.9] years; 30 men [59%]) at MGH. An automatically generated training data set with 972 095 positive HEA examples was created, in addition to a held-out expert-annotated testing data set with 22 762 positive HEA examples. HEAnet's performance was validated on 2 independent scalp EEG data sets: (1) data set 2 (at MGH; 24 patients with TLE and 20 HCs; mean [SD] age, 42.3 [16.2] years; 17 men [39%]) and (2) data set 3 (at BWH; 22 patients with TLE and 24 HCs; mean [SD] age, 43.0 [14.4] years; 20 men [43%]). For single-event detection of HEA on data set 1, HEAnet achieved a mean (SD) AUC ROC of 0.89 (0.01) and a mean (SD) AUC PR of 0.39 (0.03). On external validation with data sets 2 and 3, HEAnet accurately distinguished TLE from HC (AUC ROC of 0.88 and 0.95, respectively) and predicted epilepsy lateralization with 100% and 92% accuracy, respectively. HEAnet tracked dynamic changes in HEA in response to seizure medication adjustments and performed comparably with human experts in diagnosing TLE from 1-hour scalp EEG recordings, diagnosing TLE in several individuals that experts missed. Without reducing specificity, addition of HEAnet to human expert EEG review increased sensitivity for diagnosing TLE in humans from 50% to 58% to 63% to 67%. Conclusions and Relevance: Results of this diagnostic study suggest that HEAnet provides a novel, noninvasive, quantitative, and clinically relevant biomarker of hippocampal hyperexcitability in humans.

Prognostic value of hypothyroidism in patients undergoing intensity-modulated radiation therapy for nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to investigate the effect of hypothyroidism and thyroxine replacement therapy on the prognosis of nasopharyngeal carcinoma (NPC) patients. METHODS: The clinical data of 284 NPC patients, who received intensity-modulated radiation therapy (IMRT) between January 2011 and December 2016, were retrospectively analyzed. RESULTS: Hypothyroidism occurred in 38% of patients. Patients with hypothyroidism had significantly better disease-free survival (DFS) (p = 0.002) and relapse-free survival (RFS) (p = 0.008). Multivariate analysis showed that hypothyroidism was a positive independent prognostic factor (DFS and RFS). Among the patients with hypothyroidism, thyroxine replacement therapy did not yield inferior survival (DFS, RFS, all p > 0.05). CONCLUSIONS: The NPC patients with complete response are at risk of hypothyroidism, which is attributable to escalating dose. These patients experienced clinical hypothyroidism could be adequately treated with thyroid hormone replacement. Further investigation of the underlying biological mechanism and potential therapeutic implications are required.

Effect of Calcium Dobesilate in Preventing Contrast-Induced Nephropathy in Patients with Diabetes and Chronic Kidney Disease.

OBJECTIVES: This study assessed the protective effect of calcium dobesilate against contrast-induced nephropathy (CIN) after coronary angiography (CAG) or percutaneous coronary intervention (PCI) in patients with diabetes and chronic kidney disease (CKD). METHODS: A total of 130 patients with diabetes and CKD estimated glomerular filtration rate: 30-90 mL/min/1.73m2 were enrolled and included in the analysis. They were divided into experimental (n=65) and control groups (n=65). Patients in the experimental group were administered oral calcium dobesilate (500 mg) three times daily for 2 days before and 3 days after the procedure. The serum creatinine (SCr), cystatin C (Cys C), and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured before and after the procedure. RESULTS: The mean SCr level at 24h after the procedure was found to be significantly lower in the experimental group than in the control group (79.1±19.6 µmol/L vs. 87.0±19.3 µmol/L, p=0.023). However, the Cys C and NGAL levels were not significantly different between the two groups at all measurement time points (all p>0.05). The incidence of CIN defined by the SCr level was significantly lower in the experimental group than in the control group (3 [4.6%] vs. 13 [20.0%], p=0.017). However, the incidence of CIN defined by the Cys C level was not statistically different between the two groups (7 [10.8%] vs. 7 [10.8%], p=1.000). CONCLUSIONS: This study revealed that calcium dobesilate has no preventive effect against CIN in patients with diabetes and CKD.

ABL allosteric inhibitors synergize with statins to enhance apoptosis of metastatic lung cancer cells.

Targeting mitochondrial metabolism has emerged as a treatment option for cancer patients. The ABL tyrosine kinases promote metastasis, and enhanced ABL signaling is associated with a poor prognosis in lung adenocarcinoma patients. Here we show that ABL kinase allosteric inhibitors impair mitochondrial integrity and decrease oxidative phosphorylation. To identify metabolic vulnerabilities that enhance this phenotype, we utilized a CRISPR/Cas9 loss-of-function screen and identified HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway and target of statin therapies, as a top-scoring sensitizer to ABL inhibition. Combination treatment with ABL allosteric inhibitors and statins decreases metastatic lung cancer cell survival in vitro in a synergistic manner. Notably, combination therapy in mouse models of lung cancer brain metastasis and therapy resistance impairs metastatic colonization with a concomitant increase in animal survival. Thus, metabolic combination therapy might be effective to decrease metastatic outgrowth, leading to increased survival for lung cancer patients with advanced disease.

LncRNA GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 to promote wound healing in diabetic foot ulcers.

A diabetic foot ulcer (DFU) is one of the most devastating complications of diabetes. It has been reported that lncRNA GAS5 plays a vital role in wound healing in DFUs. However, the specific mechanism remains unclear. In this research, we aimed to investigate the role of GAS5 in wound healing in DFUs as well as the underlying mechanism. qPCR or western blotting was performed to measure the expression levels of GAS5, HIF1A, VEGF and TAF15. CCK-8 or EdU assays, flow cytometry, wound healing assays and tube formation assays were carried out to assess the proliferation, apoptosis, wound healing and in vitro angiogenesis of HUVECs, respectively. RNA pull-down and RIP assays were performed to verify the interaction between GAS5 and TAF15. ChIP and luciferase assays were conducted to verify the binding of TAF15 to the HIF1A promoter. In the DFU mouse model, H&E and Masson staining were used to determine epidermal and dermal thickness and collagen formation. GAS5 and HIF1A were downregulated in the skin tissues of DFU patients, and GAS5 overexpression promoted cell proliferation, wound healing and tubule formation in HG-treated HUVECs. In addition, GAS5 facilitated HIF1A expression by interacting with TAF15. Rescue assays demonstrated that the suppression of HIF1A/VEGF pathway activation partially reversed the functional roles of GAS5 in HUVECs. Furthermore, GAS5 accelerated wound healing by activating the HIF1A/VEGF pathway in mice with DFUs. GAS5 activates the HIF1A/VEGF pathway by binding to TAF15, resulting in accelerated wound healing in DFUs. Our findings may provide a theoretical basis for the clinical treatment of DFUs.

Safety application of muscle relaxants and the traditional low-frequency ventilation during the flexible or rigid bronchoscopy in patients with central airway obstruction: a retrospective observational study.

BACKGROUND: Bronchoscopy treatments of central airway obstruction (CAO) under general anesthesia are high-risky procedures, and posing a giant challenge to the anesthesiologists. We summarized and analyzed our clinical experience in patients with CAO undergoing flexible or rigid bronchoscopy, to estimate the safety of skeletal muscle relaxants application and the traditional Low-frequency ventilation. METHODS: Clinical data of 375 patients with CAO who underwent urgent endoscopic treatments in general anesthesia from January 2016 to October 2019 were retrospectively reviewed. The use ratio of skeletal muscle relaxants, dose of skeletal muscle relaxants used, the incidence of perioperative adverse events, adequacy of ventilation and gas exchange, post-operative recovery between rigid bronchoscopy and flexible bronchoscopy therapy, and risk factors for postoperative ICU admission were evaluated. RESULTS: Of the 375 patients with CAO, 204 patients were treated with flexible bronchoscopy and 171 patients were treated with rigid bronchoscopy. Muscle relaxants were used in 362 of 375 patients (including 313 cisatracurium, 45 rocuronium, 4 atracurium, and 13 unrecorded). The usage rate of muscle relaxants (96.5% in total) was very high in patients with CAO who underwent either flexible bronchoscopy (96.6%) or rigid bronchoscopy (96.5%) therapy. The dosage of skeletal muscle relaxants (Cisatracium) used was higher in rigid bronchoscopy compared with flexible bronchoscopy therapy (10.8 ± 3.8 VS 11.6 ± 3.6 mg, respectively, p < 0.05). No patient suffered the failure of ventilation, bronchospasm and intraoperative cough either in flexible or rigid bronchoscopy therapy. Hypoxemia was occurred in 13 patients (8 in flexible, 5 in rigid bronchoscopy) during the procedure, and reintubation after extubation happened in 2 patients with flexible bronchoscopy. Sufficient ventilation was successfully established using the traditional Low-frequency ventilation with no significant carbon dioxide accumulation and hypoxemia occurred both in flexible and rigid bronchoscopy group (p > 0.05). Three patients (1 in flexible and 2 in rigid) died, during the post-operative recovery, and the higher grade of American Society of Anesthesiologists (ASA) and obvious dyspnea or orthopnea were the independent risk factors for postoperative ICU admission. CONCLUSION: The muscle relaxants and low-frequency traditional ventilation can be safely used both in flexible and rigid bronchoscopy treatments in patients with CAO. These results may provide strong clinical evidence for optimizing the anesthesia management of bronchoscopy for these patients.

Comparison of Different Hydration Strategies in Patients with Very Low-Risk Profiles of Contrast-Induced Nephropathy.

BACKGROUND Hydration remains the mainstay of contrast-induced nephropathy (CIN) prevention, and new biomarkers of cystatin C (Cys C) and neutrophil gelatinase-associated lipocalin (NGAL) have been suggested. This study aimed to explore whether hydration is essential in patients with very low-risk profiles of CIN who are undergoing coronary angiography. MATERIAL AND METHODS A total of 150 patients were enrolled and randomly distributed to 3 groups: the Preventive Group (n=50, saline hydration was given 6 h before the procedure until 12 h after the procedure), the Remedial Group (n=50, saline hydration was given after procedure for 12 h), and the No Hydration (NH) group (n=50, saline was only given during the procedure). Serum creatinine (Cr), Cys C, and urinary NGAL were tested 3 times at different times. RESULTS Six patients were excluded because of Mehran risk score >2. There was no CIN among 144 individuals. At 24 h and at 72 h after the procedure, we found no significant differences in the levels of Cr and Cys C (0.72±0.11 mg/L for the Preventive Group, 0.67±0.14 mg/L for the Remedial Group, and 0.70±0.1 6 mg/L for the NH Group) among the 3 groups. Urinary NGAL also did not differ significantly among the 3 groups at 6 h or at 48 h (6.31±6.60 ng/ml for the Preventive Group, 5.00±5.86 ng/ml for the Remedial Group, and 6.97±6.37 ng/ml for the NH Group) after the procedure. Subgroup analysis in patients who underwent percutaneous coronary intervention (PCI) showed that there was no significant difference in serum Cr, Cys C, or urinary NGAL at different time points among the 3 groups. CONCLUSIONS Saline hydration during the perioperative period might be unnecessary in patients with very low-risk profiles of CIN.

The inhibitory mechanism of methyl jasmonate on Aspergillus flavus growth and aflatoxin biosynthesis and two novel transcription factors are involved in this action.

As the most toxic and carcinogenic mycotoxin, aflatoxin B1 (AFB1) biosynthesis depends on a series of enzymatic reactions and a complicated regulatory system. Methyl jasmonate (MeJA) is one of stress associated phytohormones. In this study, MeJA could inhibit A. flavus growth and AFB1 production with a dose-dependent manner. SEM and TEM analysis indicated that morphological ultrastructure deteriorations were observed in A. flavus treated with MeJA. RNA-Seq indicated that the initial-steps aflatoxins (AFs) genes were no drastic difference, but the middle- and later- steps genes were significantly down-regulated, which might be due to the decreases of global regulators, especially AtfB. More importantly, two novel regulators (AFLA_085880 and AFLA_015850) were involved in the inhibition, and were recognized as the critically positive regulators for AFs productions. The two genes mutants also showed significantly decrease expressions of AFs cluster genes and AFs associated regulators, and subsequent AFB1 biosynthesis. This research partly clarified inhibitory mechanism of MeJA and made some contributions to the elimination of AFs contamination.

Association of attention-deficit/hyperactivity disorder with diabetes mellitus in US adults.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder that usually persists into adulthood. However, limited evidence is available regarding its influence on adult health outcomes beyond neuropsychiatric comorbidities. This study aimed to examine the association of ADHD with diabetes in US adults. METHODS: We analyzed data from the National Health Interview Survey (NHIS), a leading health survey of a nationally representative sample in the United States. We included adults aged 20-79 years who participated in the NHIS 2007 and 2012. Physician-diagnosed ADHD and diabetes were reported during an in-person household interview. Logistic regression with survey sampling weights was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of diabetes. RESULTS: This analysis included 52 821 adults (weighted mean age 45.5 years; 48.6% males). Among them, 1642 participants reported a diagnosis of ADHD and 4631 reported a diagnosis of diabetes. In the multivariable analysis adjusting for age, sex, race/ethnicity, education level, family income level, smoking, alcohol drinking, physical activity, and body mass index, the OR of diabetes among adults with ADHD vs those without ADHD was 1.54 (95% CI, 1.16-2.04). In the stratified analyses, the significant association of ADHD with diabetes remained in most strata, and the associations were not significantly modified by age, sex, race/ethnicity, or obesity status. CONCLUSIONS: In a nationally representative sample of US adults, we found a significant association between a history of ADHD diagnosis and diabetes.

DDESVSFS: A simple, rapid and comprehensive screening tool for the Differential Diagnosis of Epileptic Seizures VS Functional Seizures.

OBJECTIVE: Functional seizures (FS) are often misclassified as epileptic seizures (ES). This study aimed to create an easy to use but comprehensive screening tool to guide further evaluation of patients presenting with this diagnostic dilemma. MATERIALS AND METHODS: Demographic, clinical and diagnostic data were collected on patients admitted for video-EEG monitoring for clarification of their diagnosis. Upon discharge, patients were classified as having ES vs FS. Using the collected characteristics and video-EEG diagnosis, we created a multivariable logistic regression model to identify predictors of ES. Then, we trained an integer-coefficient model with the most frequently selected predictors, creating a pointing system coined DDESVSFS, with scores ranging from -17 to +8 points. RESULTS: 43 patients with FS and 165 patients with ES were recruited. In the final integer-coefficient model, 8 predictors were identified as significant in differentiating ES from FS: normal electroencephalogram (-3 points), predisposing factors for FS (-3 points), increased number of comorbidities (-3 points), semiology suggestive of FS (-4 points), increased seizure frequency (-4 points), longer disease duration (+3 points), antiepileptic polypharmacy (+2 points) and compliance with antiepileptic drugs (+3 points). Cumulative scores of ≤ -9 points carried <5% predictive value for ES, while cumulative scores of ≥ -1 points carried >95% predictive value. The model performed well (AUC: 0.923, sensitivity: 0.945, specificity: 0.698). CONCLUSIONS: We propose DDESVSFS as a simple, rapid and comprehensive prediction score for the Differential Diagnosis of Epileptic Seizures VS Functional Seizures. Large prospective studies are needed to evaluate its utility in clinical practice.