Search

Background: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). Methods: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. Results: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. Conclusion: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis compares the efficacy of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) to conventional interbody fusion in lumbar degenerative diseases (LDD). Methods: An extensive literature search was conducted in PubMed, Web of Science, and the Cochrane Library. Research related to UBE-TLIF published up to November 2022 was reviewed. The relevant articles were selected based on inclusion and exclusion criteria, as well as an evaluation of the quality of the data extraction literature. Meta-analysis was performed using Review Manager 5.3 software. Results: This meta-analysis included six high-quality case–control trials (CCTs) involving 621 subjects. The clinical outcomes assessment showed no statistical differences in complication rates, fusion rates, leg pain VAS scores, or ODI scores. After UBE-TLIF, low back pain VAS scores were significantly improved with less intraoperative blood loss and a shorter hospital stay. A longer time was required for UBE-TLIF, however. Conclusion: Despite the lack of sufficient high quality randomized controlled trials (RCTs) in this study, the results of this meta-analysis suggest that UBE-TLIF is more effective than open surgery in terms of length of stay, blood loss reduction during surgery, and improved low back pain after surgery. Nevertheless, the evidence will be supplemented in the future by more and better quality multicenter randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: The growth arrest and DNA damage-inducible gene gamma (GADD45G), an important member of GADD45 family, has been connected to the development of certain human cancers. Our previous studies have confirmed that GADD45G expression could be upregulated by 4-methoxydalbergione (4MOD) in liver cancer cells, but its potential pathological role in hepatocellular carcinoma (HCC) has not been fully understood. This study aimed to determine potential role of GADD45G in HCC, and the effects of 4-methoxydalbergione (4MOD) on the regulation of GADD45G expression in vivo were also analyzed. Methods: Publicly available data and in-house immunohistochemistry (IHC) experiments were utilized to explore the expression profiles and clinical significance of GADD45G in HCC samples. Functional enrichment analysis based on GADD45G co-expression genes was used to excavate the molecular mechanism of GADD45G in HCC. We also conducted in vivo experiment on BALB/c nude mice to excavate the inhibitory effect of 4MOD on HCC and to evaluate the differences in the expression of GADD45G in xenograft tissues between the 4MOD-treated and untreated groups. Results: GADD45G displayed significant low expression in HCC tissues. Downregulated expression of GADD45G was positively correlated with some high risk factors in HCC patients and predicted worse prognosis of HCC patients. There was a close association of GADD45G mRNA expression and immune cells, including neutrophils, NK cells, CD8 T cells, and macrophages. Co-expressed genes of GADD45G were involved in several pathways including cell cycle, carbon metabolism, and peroxisome. 4MOD could significantly suppress the growth of HCC in vivo, and this inhibitory effect was dependent on the upregulation of GADD45G expression. Conclusion: GADD45G expression can be used as a new clinical biomarker for HCC and GADD45G may be a potential target for the anti-cancer effect of 4MOD in liver cancer. [ABSTRACT FROM AUTHOR]

Background: Epicardial adipose tissue (EAT) accumulation is associated with multiple cardiometabolic risk factors and prognosis of heart failure with preserved ejection fraction (HFpEF). The correlation between EAT density and cardiometabolic risk and the effect of EAT density on clinical outcome in HFpEF remain unclear. We evaluated the relationship between EAT density and cardiometabolic risk factors, also the prognostic value of EAT density in patients with HFpEF. Methods: We included 154 HFpEF patients who underwent noncontrast cardiac computed tomography (CT) and all patients received follow-up. EAT density and volume were quantified semi-automatically. The associations of EAT density and volume with cardiometabolic risk factors, metabolic syndrome and the prognostic impact of EAT density were analyzed. Results: Lower EAT density was associated with adverse changes in cardiometabolic risk factors. Each 1 HU increase in fat density, BMI was 0.14 kg/m2 lower (95% CI 0.08–0.21), waist circumference was 0.34 cm lower (95% CI 0.12–0.55), non-HDL-cholesterol was 0.02 mmol/L lower (95% CI 0–0.04), triglyceride was 0.03 mmol/L lower (95% CI 0.01–0.04), fasting plasma glucose was 0.05 mmol/L lower (95% CI 0.02–0.08), TyG index was 0.03 lower (95% CI 0.02–0.04), Log2(TG/HDL-C) was 0.03 lower (95% CI 0.02–0.05), METS-IR was 0.36 lower (95% CI 0.23–0.49), MetS Z-score was 0.04 lower (95% CI 0.02–0.06), and Log2(CACS + 1) was 0.09 lower (95% CI 0.02–0.15). After adjusting for BMI and EAT volume, the associations of non-HDL-cholesterol, triglyceride, fasting plasma glucose, insulin resistance indexes, MetS Z-score, and CACS with fat density remained significant. The area under the curve (AUC) for the presence and severity of metabolic syndrome was greater in EAT density than volume (AUC: 0.731 vs 0.694, 0.735 vs 0.662, respectively). Over a median follow-up of 16 months, the cumulative incidence of heart failure readmission and composite endpoint increased with lower level of EAT density (both p < 0.05). Conclusions: EAT density was an independent impact factor of cardiometabolic risk in HFpEF. EAT density might have better predictive value than EAT volume for metabolic syndrome and it might have prognostic value in patients with HFpEF. [ABSTRACT FROM AUTHOR]

Background: To determine whether maintaining ventilation during cardiopulmonary bypass (CPB) with a different fraction of inspired oxygen (FiO2) had an impact on the occurrence of postoperative pulmonary complications (PPCs).Methods: A total of 413 adult patients undergoing elective cardiac surgery with CPB were randomly assigned into three groups: 138 in the NoV group (received no mechanical ventilation during CPB), 138 in the LOV group (received a tidal volume (VT) of 3-4 ml/kg of ideal body weight with the respiratory rate of 10-12 bpm, and the positive end-expiratory pressure of 5-8 cmH2O during CPB; the FiO2 was 30%), and 137 in the HOV group (received the same ventilation parameters settings as the LOV group while the FiO2 was 80%).Results: The primary outcomes were the incidence and severity of PPCs during hospitalization. The composite incidence of PPCs did not significantly differ between the NoV (63%), LOV (49%) and HOV (57%) groups (P = 0.069). And there was also no difference regarding the incidence of PPCs between the non-ventilation (NoV) and ventilation (the combination of LOV and HOV) groups. The LOV group was observed a lower proportion of moderate and severe pulmonary complications (grade ≥ 3) than the NoV group (23.1% vs. 44.2%, P = 0.001).Conclusion: Maintaining ventilation during CPB did not reduce the incidence of PPCs in patients undergoing cardiac surgery.Trial Registration: Chinese Clinical Trial Registry ChiCTR1800015261. Prospectively registered 19 March 2018. http://www.chictr.org.cn/showproj.aspx?proj=25982. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that there is an association between FMR1 CGG repeats and ovarian dysfunction. The aim of this study is to assess the association between the number of CGG repeats in FMR1 in Chinese patients with premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR). Methods: This is a cross-sectional, case-control study, which enrolled 124 patients with POI, 57 patients with DOR and 111 normal menopausal controls. The demographic details along with other clinical data were recorded. The FMR1 CGG repeats were analyzed by polymerase chain reaction and microfluidic capillary electrophoresis. Results: We could detect two premutation carriers in the POI group (1.6%) and one in the control group (0.9%). No premutation carriers were identified in the DOR group. The frequency of FMR1 premutations was not different between POI or DOR and controls. The most common CGG repeat was 29 and 30, and the repeat length for allele 2 had a secondary peak around 36–39 repeats. The CGG repeats were divided into groups of five consecutive values, and the distribution of allele 1 in the POI group was different from that in the control group (P < 0.001). No statistically significant differences were found for allele 1 between DOR group vs. controls, and for allele 2 between three groups (P > 0.05). Conclusions: The study shows that the frequency of FMR1 premutations is relatively low (1.6%) in Chinese women with POI. The distribution of allele 1 CGG repeat in patients with POI showed difference from that in healthy women. [ABSTRACT FROM AUTHOR]

Objectives: Cerebral venous sinus thrombosis (CVST) can cause sinus obstruction and stenosis, with potentially fatal consequences. High-resolution magnetic resonance imaging (HRMRI) can diagnose CVST qualitatively, although quantitative screening methods are lacking for patients refractory to anticoagulation therapy and who may benefit from endovascular treatment (EVT). Thus, in this study, we used radiomic features (RFs) extracted from HRMRI to build machine learning models to predict response to drug therapy and determine the appropriateness of EVT. Materials and methods: RFs were extracted from three-dimensional T1-weighted motion-sensitized driven equilibrium (MSDE), T2-weighted MSDE, T1-contrast, and T1-contrast MSDE sequences to build radiomic signatures and support vector machine (SVM) models for predicting the efficacy of standard drug therapy and the necessity of EVT. Results: We retrospectively included 53 patients with CVST in a prospective cohort study, among whom 14 underwent EVT after standard drug therapy failed. Thirteen RFs were selected to construct the RF signature and CVST-SVM models. In the validation dataset, the sensitivity, specificity, and area under the curve performance for the RF signature model were 0.833, 0.937, and 0.977, respectively. The radiomic score was correlated with days from symptom onset, history of dyslipidemia, smoking, fibrin degradation product, and D-dimer levels. The sensitivity, specificity, and area under the curve for the CVST-SVM model in the validation set were 0.917, 0.969, and 0.992, respectively. Conclusions: The CVST-SVM model trained with RFs extracted from HRMRI outperformed the RF signature model and could aid physicians in predicting patient responses to drug treatment and identifying those who may require EVT. [ABSTRACT FROM AUTHOR]

Background: This multi-center, cross-sectional study intended to explore the prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with polycystic ovary syndrome (PCOS). Methods: Patients who met the PCOS Rotterdam diagnostic criteria were enrolled in 6 centers in China, and age-matched healthy volunteers were also recruited. Data were collected including medical history, physical characteristics, and blood tests (liver function, blood lipids, blood glucose and insulin, sex hormones, etc.). Transvaginal or transrectal ultrasound was employed to identify polycystic ovarian morphology (PCOM). The serological score Liver Fat Score (LFS) >-0.640 was used for the diagnosis of NAFLD, and the diagnosis of MAFLD was made according to the 2020 new definition. Results: A total of 217 PCOS patients and 72 healthy controls were included. PCOS patients had impaired glucose and lipid metabolism, higher liver enzymes and LFS. Both NAFLD (33.6%) and MAFLD (42.8%) was more prevalent in PCOS patients than in controls (4.2%, P < 0.001). Logistic regression results showed that HOMA-IR ≥ 3.54 and ALT ≥ 18.2 were independently associated with NAFLD (P < 0.001) and MAFLD (P ≤ 0.001). The prevalence of NAFLD was significantly higher in PCOS patients with free androgen index (FAI) > 8 (53.8% versus 17.4%, P < 0.001) and BMI ≥ 24 kg/m2 (57.3%, 11.3%, P < 0.001). Conclusion: The prevalence of NAFLD/MAFLD in PCOS patients was significantly higher than that in healthy controls and was independently associated with HOMA-IR and ALT. PCOS patients with overweight and elevated FAI have a higher prevalence of fatty liver. [ABSTRACT FROM AUTHOR]

Background Long non-coding RNAs (lncRNAs) have different functions in cells. They work as signals, decoys, guides, and scaffolds. Altered lncRNA levels can affect the expression of gene products. There are seldom studies on the role of lncRNAs in inflammatory bowel disease (IBD). Results Quantitative RT-PCR showed that DQ786243 was significantly overexpressed in clinical active CD patients compared with clinical inactive CD patients (P = 0.0118) or healthy controls (P = 0.002). CREB was also more highly expressed in active CD than in inactive CD (P = 0.0034) or controls (P = 0.0241). Foxp3 was interestingly lower in inactive CD than in active CD (P = 0.0317) or controls (P = 0.0103), but there were no apparent differences between active CD and controls. CRP was well correlated with DQ786243 (r = 0.489, P = 0.034), CREB (r = 0.500, P = 0.029) and Foxp3 (r = 0.546, P = 0.016). At 48 hours after DQ786243 transfection, qRT-PCR showed both CREB (P = 0.017) and Foxp3 (P = 0.046) had an increased mRNA expression in Jurkat cells. Western blot showed the same pattern. After DQ786243 transfection, CREB phosphorylation ratio (p-CREB/t-CREB) was increased (P = 0.0043). Conclusion DQ786243 can be related with severity of CD. It can affect the expression of CREB and Foxp3 through which regulates the function of Treg. CREB itself seems not the mediator of DQ786243 to up-regulate Foxp3. The phosphorylation of CREB might play a more important role in the process. [ABSTRACT FROM AUTHOR]

Background: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). Methods: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2−/−) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. Results: The Lrrk2−/−-HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2−/− group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2−/−-HE mice presented no severer neuronal injury than the other genotypes. Conclusions: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver. [ABSTRACT FROM AUTHOR]

Background: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. Methods: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a−/− and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. Results: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. Conclusions: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis. [ABSTRACT FROM AUTHOR]

Background: To investigate the effects and immunological mechanisms of the traditional Chinese medicine Xinjiaxiangruyin on controlling influenza virus (FM1 strain) infection in mice housed in a hygrothermal environment. Methods: Mice were housed in normal and hygrothermal environments, and intranasally infected with influenza virus (FM1). A high-performance liquid chromatography fingerprint of Xinjiaxiangruyin was used to provide an analytical method for quality control. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure messenger RNA expression of Toll-like receptor 7 (TLR7), myeloid differentiation primary response 88 (MyD88), and nuclear factor-kappa B (NF-κB) p65 in the TLR7 signaling pathway and virus replication in the lungs. Western blotting was used to measure the expression levels of TLR7, MyD88, and NF-κB p65 proteins. Flow cytometry was used to detect the proportion of Th17/T-regulatory cells. Results: Xinjiaxiangruyin effectively alleviated lung inflammation in C57BL/6 mice in hot and humid environments. Guizhimahuanggebantang significantly reduced lung inflammation in C57BL/6 mice. The expression of TLR7, MyD88, and NF-κB p65 mRNA in lung tissue of WT mice in the normal environment, GZMHGBT group was significantly lower than that in the model group (P < 0.05). In WT mice exposed to the hot and humid environment, the expression levels of TLR7, MyD88, and NF-κB p65 mRNA in the XJXRY group were significantly different from those in the virus group. The expression levels of TLR7, MyD88, and NF-κB p65 protein in lung tissue of WT mice exposed to the normal environment, GZMHGBT group was significantly lower than those in the model group. In WT mice exposed to hot and humid environments, the expression levels of TLR7, MyD88, and NF-κB p65 protein in XJXRY group were significantly different from those in the virus group. Conclusion: Guizhimahuanggebantang demonstrated a satisfactory therapeutic effect on mice infected with the influenza A virus (FM1 strain) in a normal environment, and Xinjiaxiangruyin demonstrated a clear therapeutic effect in damp and hot environments and may play a protective role against influenza through downregulation of the TLR7 signal pathway. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as a crucial contributor to the development, advancement, and resistance to treatment. This review article explores the implications of the PI3K pathway in predictive, preventive, and personalized medicine for BC. It emphasizes the identification of predictive biomarkers, such as PIK3CA mutations, and the utility of molecular profiling in guiding treatment decisions. The review also discusses the potential of targeting the PI3K pathway for preventive strategies and the customization of therapy based on tumor stage, molecular subtypes, and genetic alterations. Overcoming resistance to PI3K inhibitors and exploring combination therapies are addressed as important considerations. While this field holds promise in improving patient outcomes, further research and clinical trials are needed to validate these approaches and translate them into clinical practice. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects individuals across their lifespan. Early diagnosis and intervention are crucial for improving outcomes. However, current diagnostic methods are often time-consuming, and costly, making them inaccessible to many families. In the current study, we aim to test caregiver-child interaction as a potential tool for screening children with ASD in clinic. Methods: We enrolled 85 preschool children (Mean age: 4.90 ± 0.65 years, 70.6% male), including ASD children with or without developmental delay (DD), and typical development (TD) children, along with their caregivers. ASD core symptoms were evaluated by Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule-Calibrated Severity Scores (ADOS-CSS). Behavioral indicators were derived from video encoding of caregiver-child interaction, including social involvement of children (SIC), interaction time (IT), response of children to social cues (RSC), time for caregiver initiated social interactions (GIS) and time for children initiated social interactions (CIS)). Power spectral density (PSD) values were calculated by EEG signals simultaneously recorded. Partial Pearson correlation analysis was used in both ASD groups to investigate the correlation among behavioral indicators scores and ASD symptom severity and PSD values. Receiver operating characteristic (ROC) analysis was used to describe the discrimination accuracy of behavioral indicators. Results: Compared to TD group, both ASD groups demonstrated significant lower scores of SIC, IT, RSC, CIS (all p values < 0.05), and significant higher time for GIS (all p values < 0.01). SIC scores negatively correlated with CARS (p = 0.006) and ADOS-CSS (p = 0.023) in the ASD with DD group. Compared to TD group, PSD values elevated in ASD groups (all p values < 0.05), and was associated with SIC (theta band: p = 0.005; alpha band: p = 0.003) but not IQ levels. SIC was effective in identifying both ASD groups (sensitivity/specificity: ASD children with DD, 76.5%/66.7%; ASD children without DD, 82.6%/82.2%). Conclusion: Our results verified the behavioral paradigm of caregiver-child interaction as an efficient tool for early ASD screening. [ABSTRACT FROM AUTHOR]

Background: Postoperative pain is one of the most common complications after surgery. In order to detect early and intervene in time for moderate to severe postoperative pain, it is necessary to identify risk factors and construct clinical prediction models. This study aimed to identify significant risk factors and establish a better-performing model to predict moderate to severe acute postoperative pain after orthopedic surgery under general anesthesia. Methods: Patients who underwent orthopedic surgery under general anesthesia were divided into patients with moderate to severe pain group (group P) and patients without moderate to severe pain group (group N) based on VAS scores. The features selected by Lasso regression were processed by the random forest and multivariate logistic regression models to predict pain outcomes. The classification performance of the two models was evaluated through the testing set. The area under the curves (AUC), the accuracy of the classifiers, and the classification error rate for both classifiers were calculated, the better-performing model was used to predict moderate to severe acute postoperative pain after orthopedic surgery under general anesthesia. Results: A total of 327 patients were enrolled in this study (228 in the training set and 99 in the testing set). The incidence of moderate to severe postoperative pain was 41.3%. The random forest model revealed a classification error rate of 25.2% and an AUC of 0.810 in the testing set. The multivariate logistic regression model revealed a classification error rate of 31.3% and an AUC of 0.764 in the testing set. The random forest model was chosen for predicting clinical outcomes in this study. The risk factors with the greatest and second contribution were immobilization and duration of surgery, respectively. Conclusions: The random forest model can be used to predict moderate to severe acute postoperative pain after orthopedic surgery under general anesthesia, which is of potential clinical application value. [ABSTRACT FROM AUTHOR]

Background: Invasion and metastasis are the main causes of unfavourable prognosis in patients diagnosed with bladder cancer. The efficacy of immunotherapy in bladder cancer remains suboptimal due to the presence of an immunosuppressive microenvironment. The novel protein family with sequence similarity 171B (FAM171B) has been identified, but its precise role and mechanism in bladder cancer remain unclear. Methods: In this study, we conducted an analysis to investigate the associations between FAM171B expression and the prognosis and clinicopathological stage of bladder cancer. To this end, we utilized RNA sequencing data from the TCGA and GEO databases, as well as tumor tissue specimens obtained from our clinical centre. RNA sequencing analysis allowed us to examine the biological function of FAM171B at the transcriptional level in bladder cancer cells. Additionally, we used immunoprecipitation and mass spectrometry to identify the protein that interacts with FAM171B in bladder cancer cells. The effects of FAM171B on modulating tumor-associated macrophages (TAMs) and vimentin-mediated tumor progression, as well as the underlying mechanisms, were clarified by phalloidin staining, immunofluorescence staining, ELISA, RNA immunoprecipitation, flow cytometry and a bladder cancer graft model. Results: FAM171B expression exhibits strong positive correlation with poor survival outcomes and advanced clinicopathological stages in patients with bladder cancer. FAM171B significantly promoted bladder cancer growth and metastasis, accompanied by TAM accumulation in the microenvironment, in vivo and in vitro. Through studies of the molecular mechanism, we found that FAM171B contributes to tumor progression by stabilizing vimentin in the cytoplasm. Additionally, our research revealed that FAM171B enhances the splicing of CCL2 mRNA by interacting with heterogeneous nuclear ribonucleoprotein U (HNRNPU), ultimately leading to increased recruitment and M2 polarization of TAMs. Conclusions: In this study, we identified FAM171B as a potent factor that promotes the progression of bladder cancer. These findings establish a solid theoretical foundation for considering FAM171B as a potential diagnostic and therapeutic biomarker for bladder cancer. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on the ventilation management during cardiopulmonary bypass (CPB), and the anesthesiologists or the surgeons usually ventilate the lungs with different ventilation strategies or keep them static. Better outcomes are more likely to occur when the ventilation is administered during CPB according to the existing literatures. However, the use of high fraction of inspired oxygen (FiO2) is debatable in cardiac surgery. And the potential effects of strategies combining low tidal volume (VT) ventilation with different FiO2 during CPB on postoperative pulmonary complications (PPCs) are unclear.Design: The VONTCPB trial is a single-center, prospective, double-blinded, randomized, controlled trial. We are going to recruit total 420 elective cardiac surgery patients with median sternotomy under CPB, who will be equally randomized into three different ventilation strategy groups: NoV, LOV and HOV. (1) The NoV group receives no mechanical ventilation during CPB; (2) the LOV group receives a low VT of 3-4 ml/kg of ideal body weight (IBW) with the respiratory rate (RR) of 10-12 acts/min, and the positive end-expiratory pressure (PEEP) of 5-8 cmH2O during CPB; the FiO2 is 30%; (3) the HOV group receives a low VT of 3-4 ml/kg of IBW with the RR of 10-12 acts/min, and the PEEP of 5-8 cmH2O during CPB; the FiO2 is 80%. The primary endpoints are the incidence of the composite of PPCs and the PPCs score. The secondary endpoints refer to the incidence of the oxygenation index (PaO2/FiO2 ratio) < 300 mmHg at three time points (the moment arriving in the ICU, 6 and 12 h after arrival in the ICU), the surgical incision healing grade, the intubation time, the stay of ICU, the length of hospital stay, and mortality at 30 days after the surgery.Discussion: The VONTCPB trial is the first study to assess the effects of strategies combining low tidal volume (VT) ventilation with different FiO2 during CPB on patients' outcomes.Trial Registration: ChiCTR1800015261 . Registered on 20 March 2018. [ABSTRACT FROM AUTHOR]

Background: Influenza virus is a single-stranded RNA virus that causes influenza in humans and animals. About 600 million people around the world suffer from influenza every year. Upon recognizing viral RNA molecules, TLR7 (Toll-like receptor) initiates corresponding immune responses. Traditional Chinese Medicines (TCMs), including Yinqiao powder, Xinjiaxiangruyin and Guizhi-and-Mahuang decoction, have been extensively applied in clinical treatment of influenza. Although the therapeutic efficacy of TCMs against influenza virus in vivo was reported previously, its underlying mechanisms are not clearly understood. This study aimed to investigate the immunological mechanisms in the treatment of influenza virus infected mice with three Chinese herbal compounds as well as the effect on TLR7/NF-κB signaling pathway during recovery. Methods: Wild type and TLR7 KO C57BL/6 mice were infected with influenza virus FM1 and then treated with three TCMs. The physical parameters of mice (body weight and lung index) and the expression levels of components in TLR7/NF-κB signaling pathway were evaluated. Results: After viral infection, Guizhi-and-Mahuang decoction and Yinqiao powder showed better anti-viral effect under normal condition. Compared to the viral control group, expression levels of TLR7, MyD88, IRAK4 and NF-κB were significantly reduced in all treatment groups. Furthermore, the three TCM treatment groups showed poor therapeutic efficacy and no difference in viral load compared to the viral control group in TLR7 KO mice. Conclusion: Our study indicated that Guizhi-and-Mahuang decoction and Yinqiao powder might play a crucial role of anti-influenza virus by regulating TLR7/NF-κB signal pathway. [ABSTRACT FROM AUTHOR]

Background: High-altitude cerebral edema (HACE) is the severe type of acute mountain sickness (AMS) and life threatening. A subclinical inflammation has been speculated, but the exact mechanisms underlying the HACE are not fully understood. Methods: Human volunteers ascended to high altitude (3860 m, 2 days), and rats were exposed to hypoxia in a hypobaric chamber (5000 m, 2 days). Human acute mountain sickness was evaluated by the Lake Louise Score (LLS), and plasma corticotrophin-releasing hormone (CRH) and cytokines TNF-α, IL-1β, and IL-6 were measured in rats and humans. Subsequently, rats were pre-treated with lipopolysaccharide (LPS, intraperitoneal (ip) 4 mg/kg, 11 h) to induce inflammation prior to 1 h hypoxia (7000 m elevation). TNF-α, IL-1β, IL-6, nitric oxide (NO), CRH, and aquaporin-4 (AQP4) and their gene expression, Evans blue, Na(+)-K(+)-ATPase activity, p65 translocation, and cell swelling were measured in brain by ELISA, Western blotting, Q-PCR, RT-PCR, immunohistochemistry, and transmission electron micrography. MAPKs, NF-κB pathway, and water permeability of primary astrocytes were demonstrated. All measurements were performed with or without LPS challenge. The release of NO, TNF-α, and IL-6 in cultured primary microglia by CRH stimulation with or without PDTC (NF-κB inhibitor) or CP154,526 (CRHR1 antagonist) were measured. Results: Hypobaric hypoxia enhanced plasma TNF-α, IL-1β, and IL-6 and CRH levels in human and rats, which positively correlated with AMS. A single LPS injection (ip, 4 mg/kg, 12 h) into rats increased TNF-α and IL-1β levels in the serum and cortex, and AQP4 and AQP4 mRNA expression in cortex and astrocytes, and astrocyte water permeability but did not cause brain edema. However, LPS treatment 11 h prior to 1 h hypoxia (elevation, 7000 m) challenge caused cerebral edema, which was associated with activation of NF-κB and MAPKs, hypoxia-reduced Na(+)-K(+)-ATPase activity and blood-brain barrier (BBB) disruption. Both LPS and CRH stimulated TNF-α, IL-6, and NO release in cultured rat microglia via NF-κB and cAMP/PKA. Conclusions: Preexisting systemic inflammation plus a short severe hypoxia elicits cerebral edema through upregulated AQP4 and water permeability by TLR4 and CRH/CRHR1 signaling. This study revealed that both infection and hypoxia can cause inflammatory response in the brain. Systemic inflammation can facilitate onset of hypoxic cerebral edema through interaction of astrocyte and microglia by activation of TLR4 and CRH/CRHR1 signaling. Anti-inflammatory agents and CRHR1 antagonist may be useful for prevention and treatment of AMS and HACE. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease that exhibits a high degree of heterogeneity, marked by unpredictable disease flares and significant variations in the response to available treatments. The lack of optimal stratification for RA patients may be a contributing factor to the poor efficacy of current treatment options. The objective of this study is to elucidate the molecular characteristics of RA through the utilization of mitochondrial genes and subsequently construct and authenticate a diagnostic framework for RA. Mitochondrial proteins were obtained from the MitoCarta database, and the R package limma was employed to filter for differentially expressed mitochondrial genes (MDEGs). Metascape was utilized to perform enrichment analysis, followed by an unsupervised clustering algorithm using the ConsensuClusterPlus package to identify distinct subtypes based on MDEGs. The immune microenvironment, biological pathways, and drug response were further explored in these subtypes. Finally, a multi-biomarker-based diagnostic model was constructed using machine learning algorithms. Utilizing 88 MDEGs present in transcript profiles, it was possible to classify RA patients into three distinct subtypes, each characterized by unique molecular and cellular signatures. Subtype A exhibited a marked activation of inflammatory cells and pathways, while subtype C was characterized by the presence of specific innate lymphocytes. Inflammatory and immune cells in subtype B displayed a more modest level of activation (Wilcoxon test P < 0.05). Notably, subtype C demonstrated a stronger correlation with a superior response to biologics such as infliximab, anti-TNF, rituximab, and methotrexate/abatacept (P = 0.001) using the fisher test. Furthermore, the mitochondrial diagnosis SVM model demonstrated a high degree of discriminatory ability in distinguishing RA in both training (AUC = 100%) and validation sets (AUC = 80.1%). This study presents a pioneering analysis of mitochondrial modifications in RA, offering a novel framework for patient stratification and potentially enhancing therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B-cell lymphoma (DLBCL) is a spectrum of disease comprising more than 30% of non-Hodgkin lymphomas. Although studies have identified several molecular subgroups, the heterogeneous genetic background of DLBCL remains ambiguous. In this study we aimed to develop a novel approach and to provide a distinctive classification system to unravel its molecular features.Method: A cohort of 342 patient samples diagnosed with DLBCL in our hospital were retrospectively enrolled in this study. A total of 46 genes were included in next-generation sequencing panel. Non-mutually exclusive genetic signatures for the factorization of complex genomic patterns were generated by random forest algorithm.Results: A total of four non-mutually exclusive signatures were generated, including those with MYC-translocation (MYC-trans) (n = 62), with BCL2-translocation (BCL2-trans) (n = 69), with BCL6-translocation (BCL6-trans) (n = 108), and those with MYD88 and/or CD79B mutations (MC) signatures (n = 115). Comparison analysis between our model and traditional mutually exclusive Schmitz's model demonstrated consistent classification pattern. And prognostic heterogeneity existed within EZB subgroup of de novo DLBCL patients. As for prognostic impact, MYC-trans signature was an independent unfavorable prognostic factor. Furthermore, tumors carrying three different signature markers exhibited significantly inferior prognoses compared with their counterparts with no genetic signature.Conclusion: Compared with traditional mutually exclusive molecular sub-classification, non-mutually exclusive genetic fingerprint model generated from our study provided novel insight into not only the complex genetic features, but also the prognostic heterogeneity of DLBCL patients. [ABSTRACT FROM AUTHOR]

Background: Propofol is an intravenous anesthetic agent that commonly induces significant neuroapoptosis. MicroRNAs (miRNAs) have been reported to participate in the regulation of propofol exposure-mediated neurotoxicity. MiR-215, as one of miRNAs, was found to regulate nerve cell survival. However, the mechanism through which miRNAs regulate propofol exposure-mediated neurotoxicity is still unclear. Methods: Real-time PCR was used to detect miR-215 expression level. Cell viability was measured using MTT assay. Cell apoptosis was examined via flow cytometry analysis. ROS, MDA, LDH and SOD levels were assayed through ELISA kits. Dual luciferase reporter assay identified the interaction between miR-215 and large tumor suppressor 2 (LATS2). Protein level was detected using western blot analysis. Results: MiR-215 expression was downregulated in propofol-treated rat hippocampal neurons. MiR-215 mimics promoted cell viability and reduced apoptosis in propofol-treated neonatal rat hippocampal neuron. MiR-215 mimics also caused inhibition of oxidative stress as evidenced by suppression of ROS, MDA and LDH levels as well as increase of SOD level. In addition, we found that large tumor suppressor 2 (LATS2) is a target of miR-215 and miR-215 mimics decreased LATS2 level in propofol-treated neonatal rat hippocampal neuron. Further, LATS2 overexpression suppressed the effect of miR-215 on propofol-induced apoptosis and oxidative stress in neonatal rat hippocampal neuron. Conclusion: Taken together, we demonstrate that miR-215 attenuates propofol-induced apoptosis and oxidative stress in neonatal rat hippocampal neuron by targeting LATS2, suggesting that miR-215 may provide a new candidate for the treatment of propofol exposure-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: Current methods for gene-set or pathway analysis are usually designed to test the enrichment of a single gene-set. Once the analysis is carried out for each of the sets under study, a list of significant sets can be obtained. However, if one wishes to further prioritize the importance or strength of association of these sets, no such quantitative measure is available. Using the magnitude of p-value to rank the pathways may not be appropriate because p-value is not a measure for strength of significance. In addition, when testing each pathway, these analyses are often implicitly affected by the number of differentially expressed genes included in the set and/or affected by the dependence among genes. Results: Here we propose a two-stage procedure to prioritize the pathways/gene-sets. In the first stage we develop a pathway-level measure with three properties. First, it contains all genes (differentially expressed or not) in the same set, and summarizes the collective effect of all genes per sample. Second, this pathway score accounts for the correlation between genes by synchronizing their correlation directions. Third, the score includes a rank transformation to enhance the variation among samples as well as to avoid the influence of extreme heterogeneity among genes. In the second stage, all scores are included simultaneously in a Bayesian logistic regression model which can evaluate the strength of association for each set and rank the sets based on posterior probabilities. Simulations from Gaussian distributions and human microarray data, and a breast cancer study with RNA-Seq are considered for demonstration and comparison with other existing methods. Conclusions: The proposed summary pathway score provides for each sample an overall evaluation of gene expression in a gene-set. It demonstrates the advantages of including all genes in the set and the synchronization of correlation direction. The simultaneous utilization of all pathway-level scores in a Bayesian model not only offers a probabilistic evaluation and ranking of the pathway association but also presents good accuracy in identifying the top-ranking pathways. The resulting recommendation list of ranked pathways can be a reference for potential target therapy or for future allocation of research resources. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the predictive value of the initial screening characteristics of women with anovulatory polycystic ovary syndrome (PCOS) who did or did not respond to 2.5 mg letrozole (LET). Methods: The clinical and laboratory characteristics of women with PCOS who underwent LET treatment were evaluated. Women with PCOS were stratified according to their responses to LET (2.5 mg). The potential predictors of their responses to LET were estimated using logistic regression analysis. Results: Our retrospective study included 214 eligible patients with a response to 2.5 mg LET (n = 131) or no response to 2.5 mg LET (n = 83). PCOS patients who responded to 2.5 mg LET showed better outcomes than those who did not (2.5 mg LET) for pregnancy rate, live birth rate, pregnancy rate per patient, and live birth rate per patient. Logistic regression analyses showed that late menarche (odds ratio [OR], 1.79 [95% confidence intervals (CI), 1.22–2.64], P = 0.003), and increased anti-müllerian hormone (AMH) (OR, 1.12 [95% CI, 1.02–1.23], P = 0.02), baseline luteinizing hormone (LH)/ follicle stimulating hormone (FSH) (OR, 3.73 [95% CI, 2.12–6.64], P < 0.001), and free androgen index (FAI) (OR, 1.37 [95% CI, 1.16–1.64], P < 0.001) were associated with a higher possibility of no response to 2.5 mg LET. Conclusions: PCOS patients with an increased LH/FSH ratio, AMH, FAI, and late menarche may need an increased dosage of LET for a treatment response, which could be helpful in designing a personalized treatment strategy. [ABSTRACT FROM AUTHOR]

Background: To assess the correlation between clinical and biochemical hyperandrogenism parameters in polycystic ovary syndrome (PCOS) according to age. Methods: This prospective study included 256 PCOS patients diagnosed according to the Rotterdam criteria in a university-based hospital. Androgen levels were measured using liquid chromatography-tandem mass spectrometry. Hirsutism, acne, and alopecia were assessed using the modified Ferriman-Gallwey (mF-G) score, Comprehensive Acne Severity Scale (CASS), and the Ludwig scale, respectively. The correlation between biochemical and clinical hyperandrogenism parameters was assessed in younger and older women with PCOS. Results: The 256 PCOS patients were classified by age into two groups: age 18–29 years (n = 151) and age 30–40 years (n = 84). In women with PCOS, mF-G was significantly positively correlated with the free androgen index (FAI), dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S). CASS had a significant positive correlation with DHEA. mF-G was positively correlated with FAI in those aged 18–29 years, but the correlations were not significant in those aged 30–40 years. The positive correlation between specific body regions of clinical hyperandrogenism, especially mF-G of chin, lower abdomen, and thighs, and testosterone, as well as with FAI, was highest in those aged 18–29 years. In those aged 30–40 years clinical hyperandrogenism was mainly affected by DHEA, DHEA-S, and dihydrotestosterone. Conclusion: The correlation between biochemical and clinical hyperandrogenism parameters varied with age in our East Asian population. Clinical hyperandrogenism was positively correlated with FAI in younger women with PCOS. The correlation between biochemical and clinical hyperandrogenism was not significant in older women with PCOS. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that monotherapy with apatinib, an oral tyrosine kinase inhibitor, has promising efficacy for treating recurrent or metastatic (RM) nasopharyngeal carcinoma (NPC) patients. In this study, we aimed to assess the efficacy and safety of apatinib combined with capecitabine as a second-line therapy or beyond for treating RM-NPC patients who failed the first-line platinum-based chemotherapy. Methods: In this single-arm, phase II study, we enrolled RM-NPC patients who had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The sample size was determined using Simon’s two-stage design. All patients were administered with apatinib 500 mg once daily and capecitabine 1000 mg/m2 twice per day on days 1–14 of each 21-day cycle. The primary endpoint was the objective response rate (ORR), and the secondary endpoints comprised disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: We enrolled 64 patients from September 2018 to August 2020. The ORR and DCR were 39.1% (95% CI, 27.1–52.1) and 85.9% (95% CI, 75.0–93.4), respectively. The median DoR was 14.4 months (95% CI, 7.8–21.0). As of April 20, 2021, the median follow-up duration was 12.0 months. The median PFS was 7.5 months (95% CI, 5.0–10.0) and the median OS was 15.7 months (95% CI, 11.3–20.1). The most common toxicities of any grade were anemia (75.0%), hand-foot syndrome (65.6%), and proteinuria (64.0%). Grade 3–4 toxicities were observed in 36 (56.3%) patients, with hypertension (14.1%), mucositis (12.4%), and fatigue (10.9%) most commonly observed. Conclusions: Apatinib plus capecitabine shows promising efficacy as a second-line treatment option in pretreated platinum-refractory RM-NPC patients. Dose selection of this combination needs further investigation considering the toxicity. Trial registration: Chi-CTR1800017229. [ABSTRACT FROM AUTHOR]

Background: To evaluate the incidence of neck muscle spasm in nasopharyngeal carcinoma (NPC) patients that received intensity-modulated radiotherapy (IMRT), and to analyse the patient- and treatment-related risk factors associated with neck muscle spasm.Methods: A sample of 152 IMRT-treated, biopsy-proven, nondisseminated NPC patients were retrospectively analysed. All had documented IMRT treatment plans and had returned for follow-up review at 4 years post-radiotherapy. Spasm of the sternocleidomastoid (SCM) muscle was graded from 0 to 3 (absent to severe) and this grade served as the clinical endpoint. Risk factors were identified using logistic regression analysis.Results: Within 4 years of radiotherapy, neck muscle spasm developed in 23.68% of the patients; Grades 0, 1, 2 and 3 were respectively assigned to 83.55, 7.57, 6.58 and 2.30% of assessed SCMs. Multivariate analysis indicated that gender, N stage, V60 (percentage of SCM volume that received >60 Gy) were independent prognostic variables, and that the optimal threshold for using V60 to predict neck muscle spasm was 61.92% (sensitivity = 0.900, specificity = 0.953).Conclusions: Gender, N stage and V60 were independent predictive factors for post-radiotherapy neck muscle spasm, and a V60 of ≤61.92% in the SCM was relatively safe. [ABSTRACT FROM AUTHOR]

Background: Zinc finger and bric-a-brac/tramtrack/broad (ZBTB) domain-containing proteins have been reported to be associated with many tumors' development. However, in tumor initiation and progression, the role of ZBTB9, one of the protein family, and its prognostic value were yet to be elucidated in Liver Hepatocellular Carcinoma (LIHC). Methods: We used R software and online bioinformatics analysis tools such as GEPIA2, cBioPortal, TIMER2, Metascape, UALCAN, STRING, TISIDB, and COSMIC to investigate ZBTB9's characteristics and function in LIHC, including abnormal expression, carcinogenic role, related signaling pathways and prognostic value. Furthermore, cell experiments (such as formation, wound healing, and transwell assays) and analyses based on clinical samples (such as immunohistochemistry (IHC) and promoter methylation analysis) were conducted to verify pivotal conclusions. Results: ZBTB9 was overexpressed in LIHC samples compared to adjacent normal tissues. Through the analysis of genomic alteration and promoter hypomethylation, the clinical value and etiology of abnormal expression of ZBTB9 were preliminarily exlpored. Subsequent evidence showed that it could result in tumor progression and poor prognosis via activating cell cycle, DNA repair, MYC, and KRAS-associated signaling pathways as well as rendering immune dysregulation. After the knockdown of ZBTB9, evidently inhibited capacities of tumor cells proliferation and migration were observed. These results together indicated that ZBTB9 could be a promising prognostic biomarker and had the potential value to offer novel therapeutic targets for LIHC treatment. Conclusions: ZBTB9 was identified as a novel biomarker to predict the prognosis and tumor progression in LIHC, and a promising therapeutic target to invert tumor development. [ABSTRACT FROM AUTHOR]

Background: This study uses scientometrics methodology to reveal the status quo and emerging issues of collaboration in health management.Methods: We searched all the articles with the keyword "health management" in the period 1999-2011 in Web of Knowledge, then 3067 articles were found. Methods such as Social network analysis (SNA), co-authorship, co-word analysis were used in this study.Results: Analysis of the past 13 years of research in the field of health management indicates that, whether the production of scientific research, or authors, institutions and scientific research collaboration at the national level, collaboration behavior has been growing steadily across all collaboration types. However, the international scientific research cooperation about health management study between countries needs to be further encouraged. 17 researchers can be seen as the academic leaders in this field. 37 research institutions play a vital role in the information dissemination and resources control in health management. The component analysis found that 22 research groups can be regarded as the backbone in this field. The 8 institution groups consisting of 33 institutions form the core of this field. USA, UK and Australia lie in the center by cohesive subgroup analysis; Based on keywords analysis, 44 keywords with high frequency such as care, disease, system and model were involved in the health management field.Conclusions: This study demonstrates that although it is growing steadily, collaboration behavior about health management study needs to be enhanced, especially between different institutions or countries/regions, which would promote the progress and internationalization of health management. Besides, researchers should pay attention to the cooperation of representative scholars and institutions, as well as the hot areas of research, because their experience would help us promote the research development of our nation. [ABSTRACT FROM AUTHOR]

Background: Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. Methods: This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. Results: ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: − 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. Conclusions: Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. Trial registration: Registered at chictr.org.cn (registration number: ChiCTR1800019150, registration date: 27/10/2018). [ABSTRACT FROM AUTHOR]

Background: Spray-as-you-go (SAYGo) airway topical anesthesia and nerve block are common techniques used during awake tracheal intubation. However, their effects have not been described during double-lumen tube intubation. We report on a prospective randomized study that aimed to compare the intubation effects of SAYGo and nerve block patients undergoing thoracic surgery. Methods: Sixty-six American Society of Anesthesiologists (ASA) physical status I and II patients were scheduled to undergo double-lumen tube (DLT) tracheal intubation for thoracic surgery. The patients were randomly assigned into control (Group C), ultrasound (Group U), and flexible intubation scope (Group F) groups with 22 cases in each group. Patients in Group C were induced with a standard anesthetic regimen. Patients in Groups U and F were treated with superior laryngeal nerve (SLN) block combined with transtracheal injection (TTI) and given a SAYGo airway topical anesthesia before intubation. Hemodynamic variables during intubation process were recorded as the primary outcome. Additional patient data were recorded including the occurrence of adverse events, the level of hoarseness, the occurrence of sore throats, memory function and the level of patient satisfaction with anesthesia. Results: The blood pressure (BP) and heart rate (HR) of patients in group C was significantly increased 1 min after tracheal intubation (P < 0.05) compared to before anesthesia. The BP and HR of patients in Groups U and F remained stable. 10 cases of hypertension were observed in Group C, 6 cases in Group U and 1 case in Group F. In Group C, tachycardia was observed in 9 patients along with 9 cases in Group U and 4 cases in Group F. In Group U, 4 patients experienced puncture and bleeding were and 8 patients had a poor memory of TTI. No significant differences were found in the incidence of hoarseness, sore throats, and satisfaction with anesthesia in postoperative follow-up. Conclusions: SAYGo airway topical anesthesia and SLN block combined with the TTI technique can inhibit the cardiovascular response during DLT tracheal intubation. The SAYGo technique has fewer complications and more advantages compared to other approaches. [ABSTRACT FROM AUTHOR]

Background: The interaction between tumor microenvironment (TME) and tumors offers various targets in mounting anti-tumor immunotherapies. However, the prognostic biomarkers in endometrial carcinoma (EC) are still limited. Here, we aimed to analyze the TME features and identify novel prognostic biomarkers for EC. Methods: ESTIMATE, CIBERSORT, protein-protein interaction (PPI) network, univariate and multivariate Cox regression, and functional enrichment analysis were performed to identify immune- and survival-related hub genes as well as possible molecular mechanisms. The limma package and deconvolution algorithm were adopted to estimate the abundance of tumor-infiltrating immune cells (TICs) and their relationship with the target gene. In the validation section, tissue microarrays (TMAs) of EC and multiplex immunohistochemistry (m-IHC) were evaluated to validate the expression of TNFRSF4, and its correlation with immune markers, including CD4, CD8, and FOXP3. Besides, the receiver operating characteristic (ROC) curve was plotted to determine the diagnostic performance of TNFRSF4, CD4, CD8, and FOXP3 in EC. Results: Two genes, TNFRSF4 and S1PR4, were screened out from 386 intersection differential expression genes (DEGs) shared by ImmuneScore and StromalScore in EC. Highlighted by TNFRSF4, we found that it was not only positively correlated with the TICs (mainly CD4+ T cells, CD8+ T cells, and Tregs) but significantly related to the prognosis in patients of EC, both verified by data from The Cancer Genome Altas (TCGA)-EC database and clinical samples. At the same time, the expression trend of TNFRSF4 was further confirmed by an integrated meta-analysis based on six microarrays from the Gene Expression Omnibus database (GEO). Conclusions: Collectively, TNFRSF4, a previously unrecognized key player in EC, could serve as a potential biomarker for prognosis prediction and immunomodulation of EC. [ABSTRACT FROM AUTHOR]

Background: The interaction between tumor microenvironment (TME) and tumors offers various targets in mounting anti-tumor immunotherapies. However, the prognostic biomarkers in endometrial carcinoma (EC) are still limited. Here, we aimed to analyze the TME features and identify novel prognostic biomarkers for EC.Methods: ESTIMATE, CIBERSORT, protein-protein interaction (PPI) network, univariate and multivariate Cox regression, and functional enrichment analysis were performed to identify immune- and survival-related hub genes as well as possible molecular mechanisms. The limma package and deconvolution algorithm were adopted to estimate the abundance of tumor-infiltrating immune cells (TICs) and their relationship with the target gene. In the validation section, tissue microarrays (TMAs) of EC and multiplex immunohistochemistry (m-IHC) were evaluated to validate the expression of TNFRSF4, and its correlation with immune markers, including CD4, CD8, and FOXP3. Besides, the receiver operating characteristic (ROC) curve was plotted to determine the diagnostic performance of TNFRSF4, CD4, CD8, and FOXP3 in EC.Results: Two genes, TNFRSF4 and S1PR4, were screened out from 386 intersection differential expression genes (DEGs) shared by ImmuneScore and StromalScore in EC. Highlighted by TNFRSF4, we found that it was not only positively correlated with the TICs (mainly CD4+ T cells, CD8+ T cells, and Tregs) but significantly related to the prognosis in patients of EC, both verified by data from The Cancer Genome Altas (TCGA)-EC database and clinical samples. At the same time, the expression trend of TNFRSF4 was further confirmed by an integrated meta-analysis based on six microarrays from the Gene Expression Omnibus database (GEO).Conclusions: Collectively, TNFRSF4, a previously unrecognized key player in EC, could serve as a potential biomarker for prognosis prediction and immunomodulation of EC. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional imaging techniques as magnetic resonance enterography (MRE) may offer additional information on transmural inflammation, stricturing and fistulising complications in Crohn's disease (CD). The purpose of our study was to evaluate the diagnostic accuracy of Magnetic Resonance Imaging (MRI) combined with Diffusion-weighted Imaging (DWI) and MRE for determination of inflammation in small bowel CD. Methods: MR imaging examination was performed with a GE Signa EXCITE 3.0 T MRI scanner. The optimal b value in DWI with a learning cohort of patients was determined. The diagnostic accuracy for active lesions and disease activity were accessed by MRE combined with DWI. Results: The b value 800 s/mm² group showed the highest diagnostic sensitivity (74.19%) for diagnostic assessment of active Crohn's lesions on DWI. MRE combined with DWI showed the highest sensitivity (93.55%), specificity (89.47%) and diagnostic accuracy (92%) compared with MRE or DWI alone. The segmental MR score (MR-score-S) showed a significantly positive correlation with the Capsule Endoscopy Crohn's Disease Activity Index Score (CECDAI-S) (r = 0.717, p < 0.01). The total MR score (MR-score-T) showed significant association with C-reactive protein (CRP) (r = 0.445, p = 0.019) and erythrocyte sedimentation rate (ESR) (r = 0.688, p < 0.01). Conclusions: MRE combined with DWI improves the diagnostic accuracy for active lesions and correlates the endoscopic disease activity. MRE with DWI could represent a non-invasive tool in assessing active inflammation in CD. [ABSTRACT FROM AUTHOR]

Background Brassinosteriods (BRs) are a group of important phytohormones that have major effects on plant growth and development. To fully elucidate the function of BRs, a sensitive BR assay is required. However, most of the previously reported methods are tedious and time-consuming due to multiple pretreatment steps. Therefore, it is of great significance to develop a method to increase the throughput and detection sensitivity of BR analysis. Results We established a novel analytical method of BRs based on magnetic solid phase extraction (MSPE) combined with in situ derivatization (ISD). TiO2-coated magnetic hollow mesoporous silica spere(TiO2/MHMSS) was served as a double identity- a microextraction sorbent and "microreactor" for the capture and derivatization of BRs in sequence. BRs were first extracted onto TiO2/MHMSS through hydrophilic interaction. The BR-adsorbed TiO2/MHMSS was then employed as a "microreactor" for the derivatization of BRs with 4-(N,N-dimethyamino)phenylboronic acid (DMAPBA). The MSPE-ISD method was simple and fast, which could be accomplished within 10 min. Furthermore, the derivatives of BRs showed better MS response because they were incorporated with tertiary amino groups. Uniquely, endogenous BRs were detected in only 100 mg fresh weight plant tissue. Conclusion Our proposed MSPE-ISD method for the determination of endogenous BRs is rapid and sensitive. It can be applied to the analysis of endogenous BRs in 100 mg fresh plant tissue (Brassica napus L. (B. napus L)). The proposed strategy for plant sample preparation may be extended to develop analytical methods for determination of a wide range of analytes with poor MS response in other complex sample matrices. [ABSTRACT FROM AUTHOR]

Background: To identify the radiation volume effect and significant dosimetric parameters for temporal lobe injury (TLI) and determine the radiation dose tolerance of the temporal lobe (TL) in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT).Methods: Twenty NPC patients with magnetic resonance imaging (MRI)-diagnosed unilateral TLI were reviewed. Dose-volume data was retrospectively analyzed.Results: Paired samples t-tests showed all dosimetric parameters significantly correlated with TLI, except the TL volume (TLV) and V₇₅ (the TLV that received ≥75 Gy, P = 0.73 and 0.22, respectively). Receiver operating characteristic (ROC) curves showed V₁₀ and V₂₀ (P = 0.552 and 0.11, respectively) were the only non-significant predictors from V₁₀ to V₇₀ for TLI. D(0.5cc) (dose to 0.5 ml of the TLV) was an independent predictor for TLI (P < 0.001) in multivariate analysis; the area under the ROC curve for D(0.5cc) was 0.843 (P < 0.001), and the cutoff point 69 Gy was deemed as the radiation dose limit. The distribution of high dose 'hot spot' regions and the location of TLI were consistent.Conclusions: A D0.5cc of 69 Gy may be the dose tolerance of the TL. The risk of TLI was highly dependent on high dose 'hot spots' in the TL; physicians should be cautious of such 'hot spots' in the TL during IMRT treatment plan optimization, review and approval. [ABSTRACT FROM AUTHOR]

Background : Leeches are classic annelids that have a huge diversity and are closely related to people, especially medicinal leeches. Medicinal leeches have been widely utilized in medicine based on the pharmacological activities of their bioactive ingredients. Comparative genomic study of these leeches enables us to understand the difference among medicinal leeches and other leeches and facilitates the discovery of bioactive ingredients. Results : In this study, we reported the genome of Whitmania pigra and compared it with Hirudo medicinalis and Helobdella robusta. The assembled genome size of W. pigra is 177 Mbp, close to the estimated genome size. Approximately about 23% of the genome was repetitive. A total of 26,743 protein-coding genes were subsequently predicted. W. pigra have 12346 (46%) and 10295 (38%) orthologous genes with H. medicinalis and H. robusta, respectively. About 20 and 24% genes in W. pigra showed syntenic arrangement with H. medicinalis and H. robusta, respectively, revealed by gene synteny analysis. Furthermore, W. pigra, H. medicinalis and H. robusta expanded different gene families enriched in different biological processes. By inspecting genome distribution and gene structure of hirudin, we identified a new hirudin gene g17108 (hirudin_2) with different cysteine patterns. Finally, we systematically explored and compared the active substances in the genomes of three leech species. The results showed that W. pigra and H. medicinalis exceed H. robusta in both kinds and gene number of active molecules. Conclusions : This study reported the genome of W. pigra and compared it with other two leeches, which provides an important genome resource and new insight into the exploration and development of bioactive molecules of medicinal leeches. [ABSTRACT FROM AUTHOR]

Background: Massive hemoptysis due to aspergilloma is a rare but life-threatening complication. Bronchial artery embolization is recommended as a definitive treatment for massive hemoptysis. Polyvinyl alcohol is widely used in bronchial artery embolization. A very small number of studies have reported disrupted polyvinyl alcohol, which may cause ectopic embolism.Case Presentation: This case highlights an unusual phenomenon in which polyvinyl alcohol fragments appeared on pathological examination in a 61-year-old man, ethnic Han, with massive hemoptysis caused by aspergilloma for whom bronchial artery embolization failed. Lobectomy was carried out successfully. Hematoxylin and eosin stain provides clear images of polyvinyl alcohol fragments, while alpha-smooth muscle cell actin and cluster of differentiation-34 immunohistochemistry revealed their localization in bronchioles.Conclusion: Thus far, only two cases of polyvinyl alcohol fragments in the lung have been reported, and the mechanism has not been elucidated. These two cases revealed no counter-indication for the use of polyvinyl alcohol. However, in some cases of off-target embolization causing fatal complications, such as stroke, paraplegia, and myocardial, polyvinyl alcohol fragmentation needs to be taken into consideration. [ABSTRACT FROM AUTHOR]

Objective: Researchers have revealed the combined functions of long noncoding RNAs (lncRNAs) and microRNA (miRNAs) in polycystic ovary syndrome (PCOS). This study aimed to understand the role of nuclear-enriched abundant transcript 1 (NEAT1) and miR-381 involving insulin-like growth factor 1 (IGF1) in PCOS. Methods: PCOS rat model was established by dehydroepiandrosterone induction. NEAT1, miR-381 and IGF1 expression in ovarian granulosa cells of PCOS patients and ovarian tissues of PCOS rats were tested. Bioinformatics website and dual luciferase reporter gene assay were utilized to verify the relationship between NEAT1 and miR-381 and that between miR-381 and IGF1. Levels of sex hormone, pathological changes and ovarian granulosa cell apoptosis in ovarian tissues of PCOS rats were detected. Ovarian granulosa cell proliferation and apoptosis were analyzed in vitro. Results: NEAT1 and IGF1 expression increased while miR-381 expression decreased in the ovarian granulosa cells of patients with PCOS and the ovarian tissues of PCOS rats. In in vivo experiments, interference with NEAT1 improved the levels of sex hormones, alleviated pathological changes and suppressed ovarian granulosa cell apoptosis in the ovarian tissues of PCOS rats. In in vitro cell experiments, interference with NEAT1 suppressed apoptosis and enhanced cell proliferation of ovarian granulosa cells. NEAT1 interference-mediated effect would be reversed by up-regulating miR-381. NEAT1 acted as a ceRNA to adsorb miR-381 to target IGF1. Overexpression of IGF1 reversed the inhibitory effect of miR-381 on ovarian granulosa cell apoptosis. Conclusion: Interference with NEAT1 increases miR-381 and reduces IGF1 levels, effectively improving the levels of sex hormones and reducing the pathological damage of ovarian tissue in rats with PCOS. [ABSTRACT FROM AUTHOR]

Objective: Researchers have revealed the combined functions of long noncoding RNAs (lncRNAs) and microRNA (miRNAs) in polycystic ovary syndrome (PCOS). This study aimed to understand the role of nuclear-enriched abundant transcript 1 (NEAT1) and miR-381 involving insulin-like growth factor 1 (IGF1) in PCOS. Methods: PCOS rat model was established by dehydroepiandrosterone induction. NEAT1, miR-381 and IGF1 expression in ovarian granulosa cells of PCOS patients and ovarian tissues of PCOS rats were tested. Bioinformatics website and dual luciferase reporter gene assay were utilized to verify the relationship between NEAT1 and miR-381 and that between miR-381 and IGF1. Levels of sex hormone, pathological changes and ovarian granulosa cell apoptosis in ovarian tissues of PCOS rats were detected. Ovarian granulosa cell proliferation and apoptosis were analyzed in vitro. Results: NEAT1 and IGF1 expression increased while miR-381 expression decreased in the ovarian granulosa cells of patients with PCOS and the ovarian tissues of PCOS rats. In in vivo experiments, interference with NEAT1 improved the levels of sex hormones, alleviated pathological changes and suppressed ovarian granulosa cell apoptosis in the ovarian tissues of PCOS rats. In in vitro cell experiments, interference with NEAT1 suppressed apoptosis and enhanced cell proliferation of ovarian granulosa cells. NEAT1 interference-mediated effect would be reversed by up-regulating miR-381. NEAT1 acted as a ceRNA to adsorb miR-381 to target IGF1. Overexpression of IGF1 reversed the inhibitory effect of miR-381 on ovarian granulosa cell apoptosis. Conclusion: Interference with NEAT1 increases miR-381 and reduces IGF1 levels, effectively improving the levels of sex hormones and reducing the pathological damage of ovarian tissue in rats with PCOS. [ABSTRACT FROM AUTHOR]

Background: Endoscopic resection has been used for high-grade intraepithelial neoplasia (HGIN) and superficial esophageal squamous cell carcinoma (ESCC) with limited risk of lymph node metastasis. However, some of these lesions cannot be accurately diagnosed based on forceps biopsy prior to treatment. In this study we aimed to investigate how to solve this histological discrepancy and avoid over- and under-treatment.Methods: The medical records of patients with superficial esophageal squamous cell neoplasia who underwent endoscopic resection at our hospital from January 2012 to December 2019 were reviewed retrospectively. The histological discrepancy between the biopsy and resected specimens was calculated and its association with clinicopathological parameters was analyzed.Results: A total of 137 lesions from 129 patients were included. The discrepancy rate between forceps biopsy and resected specimens was 45.3% (62/137). Histological discrepancy was associated with the histological category of the biopsy (p < 0.001). In addition, 17 of the 30 (56.7%) biopsies that was diagnosed as indefinite/negative for neoplasia or low-grade intraepithelial neoplasia were upgraded to HGIN or ESCC after resection. The upgrade was due to lesion size ≥ 10 mm (p = 0.002) and type B intrapapillary capillary loops (p < 0.001). Moreover, 34 of the 83 biopsies that were diagnosed with HGIN were upgraded to ESCC after resection, which was related to lesion size (p = 0.001), location (p = 0.018), and pink color sign (p = 0.002).Conclusions: Histological discrepancy between forceps biopsy and resected specimens is common in clinical practice. Recognizing the risk factors for each histological category of biopsy may reduce these discrepancies and improve clinical management. [ABSTRACT FROM AUTHOR]

Background: Intra-cytoplasmic sperm injection (ICSI) is used in assisted reproductive technology (ART) laboratories. However, there is no consensus regarding the precise time intervals within ICSI cycles [oocyte pick up (OPU), oocyte denudation (DN), and ICSI], and results are inconsistent and contradictory. Thus, we aim to evaluate whether there is a concordance regarding the time intervals used in different laboratories and a concrete time that gives better laboratory and reproductive results. Methods: A systematic review of the literature until July 25, 2020, was performed with the keywords "Oocyte Denudation/Denudation/Oocyte," "Intra-cytoplasmic Sperm Injection/ICSI," "Oocyte/Oocyte maturation/ cumulus," and "Cumulus removal/ removal." Articles and abstracts in English and involving human subjects referring to the effects of oocyte DN time on embryo development and clinical outcomes were included. Results: Of the 294 evaluated articles, 24 (including 20 full articles and 4 abstracts) were included in this review. Eighteen studies analysed the effect of OPU-DN time on embryo development and clinical outcomes. Most of these studies concluded that OPU-DN time did not influence ICSI outcomes, but some suggested that oocytes should be incubated for a short time before DN to improve oocyte maturity and enhance ICSI outcomes. In addition to reports on positive or negligible effects, adverse effects were reported in 12 studies on DN-ICSI timing. Neither OPU-DN nor DN-ICSI time could improve live birth rate. Conclusions: Oocytes should be pre-incubated for a short duration (preferably < 4 h) before DN according to the ART laboratory schedule. More randomised controlled trials are warranted to clarify the effect of DN-ICSI timing on ICSI outcomes. [ABSTRACT FROM AUTHOR]

Background: Subjects with chronic respiratory symptoms and preserved pulmonary function (PPF) may have small airway dysfunction (SAD). As the most common means to detect SAD, spirometry needs good cooperation and its reliability is controversial. Impulse oscillometry (IOS) may complete the deficiency of spirometry and have higher sensitivity. We aimed to explore the diagnostic value of IOS to detect SAD in symptomatic subjects with PPF.Methods: The evaluation of symptoms, spirometry and IOS results in 209 subjects with chronic respiratory symptoms and PPF were assessed. ROC curves of IOS to detect SAD were analyzed.Results: 209 subjects with chronic respiratory symptoms and PPF were included. Subjects who reported sputum had higher R5-R20 and Fres than those who didn't. Subjects with dyspnea had higher R5, R5-R20 and AX than those without. CAT and mMRC scores correlated better with IOS parameters than with spirometry. R5, R5-R20, AX and Fres in subjects with SAD (n = 42) significantly increased compared to those without. Cutoff values for IOS parameters to detect SAD were 0.30 kPa/L s for R5, 0.015 kPa/L s for R5-R20, 0.30 kPa/L for AX and 11.23 Hz for Fres. Fres has the largest AUC (0.665, P = 0.001) among these parameters. Compared with spirometry, prevalence of SAD was higher when measured with IOS. R5 could detect the most SAD subjects with a prevalence of 60.77% and a sensitivity of 81% (AUC = 0.659, P = 0.002).Conclusion: IOS is more sensitive to detect SAD than spirometry in subjects with chronic respiratory symptoms and PPF, and it correlates better with symptoms. IOS could be an additional method for SAD detection in the early stage of diseases. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is an intractable neurodegenerative disorder in the elderly population, currently lacking a cure. Trichostatin A (TSA), a histone deacetylase inhibitor, showed some neuroprotective roles, but its pathology-improvement effects in AD are still uncertain, and the underlying mechanisms remain to be elucidated. The present study aims to examine the anti-AD effects of TSA, particularly investigating its underlying cellular and molecular mechanisms. Methods: Novel object recognition and Morris water maze tests were used to evaluate the memory-ameliorating effects of TSA in APP/PS1 transgenic mice. Immunofluorescence, Western blotting, Simoa assay, and transmission electron microscopy were utilized to examine the pathology-improvement effects of TSA. Microglial activity was assessed by Western blotting and transwell migration assay. Protein-protein interactions were analyzed by co-immunoprecipitation and LC-MS/MS. Results: TSA treatment not only reduced amyloid β (Aβ) plaques and soluble Aβ oligomers in the brain, but also effectively improved learning and memory behaviors of APP/PS1 mice. In vitro study suggested that the improvement of Aβ pathology by TSA was attributed to the enhancement of Aβ clearance, mainly by the phagocytosis of microglia, and the endocytosis and transport of microvascular endothelial cells. Notably, a meaningful discovery in the study was that TSA dramatically upregulated the expression level of albumin in cell culture, by which TSA inhibited Aβ aggregation and promoted the phagocytosis of Aβ oligomers. Conclusions: These findings provide a new insight into the pathogenesis of AD and suggest TSA as a novel promising candidate for the AD treatment. [ABSTRACT FROM AUTHOR]

Background: One of the most challenging tasks for bladder cancer diagnosis is to histologically differentiate two early stages, non-invasive Ta and superficially invasive T1, the latter of which is associated with a significantly higher risk of disease progression. Indeed, in a considerable number of cases, Ta and T1 tumors look very similar under microscope, making the distinction very difficult even for experienced pathologists. Thus, there is an urgent need for a favoring system based on machine learning (ML) to distinguish between the two stages of bladder cancer.Methods: A total of 1177 images of bladder tumor tissues stained by hematoxylin and eosin were collected by pathologists at University of Rochester Medical Center, which included 460 non-invasive (stage Ta) and 717 invasive (stage T1) tumors. Automatic pipelines were developed to extract features for three invasive patterns characteristic to the T1 stage bladder cancer (i.e., desmoplastic reaction, retraction artifact, and abundant pinker cytoplasm), using imaging processing software ImageJ and CellProfiler. Features extracted from the images were analyzed by a suite of machine learning approaches.Results: We extracted nearly 700 features from the Ta and T1 tumor images. Unsupervised clustering analysis failed to distinguish hematoxylin and eosin images of Ta vs. T1 tumors. With a reduced set of features, we successfully distinguished 1177 Ta or T1 images with an accuracy of 91-96% by six supervised learning methods. By contrast, convolutional neural network (CNN) models that automatically extract features from images produced an accuracy of 84%, indicating that feature extraction driven by domain knowledge outperforms CNN-based automatic feature extraction. Further analysis revealed that desmoplastic reaction was more important than the other two patterns, and the number and size of nuclei of tumor cells were the most predictive features.Conclusions: We provide a ML-empowered, feature-centered, and interpretable diagnostic system to facilitate the accurate staging of Ta and T1 diseases, which has a potential to apply to other types of cancer. [ABSTRACT FROM AUTHOR]

Background: The comparisons of molecular characterization and antibiotic resistance of Klebsiella pneumoniae (KP) isolates from humans and other animal hosts are not well studied. Our goal was to compare the molecular epidemiology of KP strains that were isolated from urban rodents, shrews, and healthy people. Results: K. pneumoniae (KP) isolates were isolated from fecal samples of rodents, shrews and healthy adults in 2015 in southern China. In total, 465 fecal samples were collected, of which 85 from rodents, 105 from shrews, and 275 from healthy adults. Antimicrobial susceptibility and production of extended-spectrum β-lactamases (ESBL) of the isolates were tested. PCR-based methods were used to detect specific genes, including ESBL genes (blaTEM, blaSHV, and blaCTX-M) in ESBL-producing isolates, capsular serotypes (K1, K2, K5, K20, K54, and K57) in hypervirulent KPs (hvKPs), and virulence genes (magA, wcaG, rmpA, uge, kfu, and aerobactin) in hvKP isolates. Multilocus sequence type (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to exclude the homology of these isolates. The carriage rate of KP in urban rodents and shrews (78.42%) was higher than that in healthy adults (66.18%) (χ2 = 8.206, P = 0.004). The prevalence rates of ESBL-producing isolates among rodents, shrews, and humans were 7.94, 12.79, and 17.03%, respectively. The positive rates of CTX-M, TEM and SHV types in ESBL-producing isolates were 29.79, 27.66, and 17.02%, respectively. Serotype K1, K5, K20, and K57 were detected in both small mammals and humans. PFGE typing revealed thirty-six clusters. PFGE cluster A was clustered by samples of shrews and healthy adult, with a similarity of 88.4%. MLST typing revealed thirty-eight types. ST23 and ST35 were detected in samples of shrews and healthy adults. ST37 was detected in samples of 2 rodents and a healthy adult. Conclusions: Overlapping serotypes of hvKP were observed in both the animals and humans. The same PFGE or MLST types were also found in isolates derived humans, rodents and shrews. Therefore, urban rodents and shrews might play a certain role in the transmission of drug-resistant and hypervirulent KP. [ABSTRACT FROM AUTHOR]

Purpose: To assess toxicity and quality-of-life (QOL) after carbon ion radiotherapy (CIRT) at the Shanghai Proton and Heavy Ion Center (SPHIC) and identify clinical factors that correlate with urinary, bowel and sexual function.Methods: Sixty-four patients with localized prostate cancer admitted from July 2015 to January 2018 underwent CIRT. At baseline and 5 time-points after radiotherapy, we assessed patients' QOL using the 26-item edition of the Expanded Prostate Cancer Index-Composite (EPIC-26) Chinese version. Logistic regression was performed to identify clinical factors associated with acute genitourinary (GU) toxicity and relative QOL.Results: By the end of CIRT, urinary irritation/obstruction temporarily declined (- 7.92 ± 1.76, p < .001). For urinary incontinence, bowel and sexual QOL, the scores remained stable at 2-year follow-up. The occurrences of acute Grade 1 and 2 GU toxicity were 20.3 and 10.9%, respectively, and of late Grade 1 and 2 GU toxicity were 3.1 and 1.6%, respectively. No acute or late gastrointestinal (GI) toxicity occurred. Transurethral resection of the prostate (TURP) was a risk factor that predicted a decline in urinary related QOL, and age made a difference to bowel-related QOL. For sexual QOL, castration status was a remarkable risk factor. An international prostate symptom score (IPSS) ≥8 increased the risk of Grade 1-2 acute GU toxicity 5.3-fold.Conclusion: Patients with prostate cancer had favorable QOL after CIRT. IPSS ≥8 was a risk factor to acute GU toxicity, and TURP predicted a decline in urinary QOL. Age was related to bowel QOL, and castration status was associated with sexual QOL.Trial Registration: Carbon Ion Radiotherapy for the Treatment of Localized Prostate Cancer, NCT02739659 . Registered April 15, 2016. [ABSTRACT FROM AUTHOR]

Background: The prognostic impact of long-term glycemic variability on clinical outcomes in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) remains unclear. We determined and compared hemoglobin A1c (HbA1c) variability and clinical outcomes for patients with HF with preserved ejection fraction (HFpEF), HF with mid-range ejection fraction (HFmrEF) and HF with reduced ejection fraction (HFrEF) in a prospective longitudinal study. Methods: Patients with HF and T2DM, undergone 3 or more HbA1c determinations during the first 18 months, were then followed for 42 months. The primary outcome was death from any cause. Secondary outcome was composite endpoints with death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF and HFrEF. Results: Of 902 patients enrolled, 32.2% had HFpEF, 14.5% HFmrEF, and 53.3% HFrEF. During 42 months of follow-up, 270 (29.9%) patients died and 545 (60.4%) patients experienced composite endpoints of death and HF readmission. The risk of all-cause death or composite endpoints was lower for HFpEF than HFrEF. Moreover, higher HbA1c variability was associated with higher all-cause mortality or composite endpoints and HbA1c variability was an independent predictor of all-cause mortality or composite endpoints, regardless of EF. Conclusions: This prospective longitudinal study showed that the all-cause death and composite events was lower for HFpEF than HFrEF. HbA1c variability was independently and similarly predictive of death or combined endpoints in the three HF phenotypes. [ABSTRACT FROM AUTHOR]

Background: The therapeutic efficacy of serial casting on idiopathic scoliosis has been gradually documented. However, literatures on serial casting for congenital scoliosis (CS) remain extremely rare. This paper aimed to compare the treatment outcomes of serial casting between CS and non-CS patients to comprehensively evaluate the therapeutic characteristics of serial casting on CS patients. Methods: A total of 23 early-onset scoliosis cases were included and divided into congenital scoliosis (CS, n = 8) and non-congenital group (non-CS, n = 15). Therapeutic outcomes including the major curve Cobb angle, thoracic kyphosis angle, lumbar lodosis angle, and thoracic spine growing rate were compared between groups at precast, after the first cast, and at the latest follow-up, respectively. Results: All patients received the first cast at the age of 3.25 ± 1.20 years and 5.70 ± 1.18 times of cast corrections. The average casting time was 17.17 ± 3.38 months, and the mean follow-up time was 23.91 ± 12.28 months. Both CS and non-CS groups had significant decrease in Cobb angle after the first cast and at the latest follow-up (all P < 0.05). Cobb angle was significantly lower in non-CS group than in CS group at both time points (all P < 0.01). The correction rate of Cobb angle was significantly higher in non-CS group than in CS group (around 50 vs. 20%, both P < 0.01). The mean thoracic growth rate was significantly lower in CS group than in non-CS group (0.72 ± 0.20 vs. 1.42 ± 0.22 cm/year, P < 0.001). At the latest follow-up, there are 2 cases receiving growing rod surgery, 8 cases wearing a brace, and 13 cases continuing serial casting. Conclusions: Although the therapeutic efficacy of casting on CS patients is not as good as that on non-CS patients, casting is still an efficient treatment option for CS patients to delay the need for initial surgery. [ABSTRACT FROM AUTHOR]

Background: Phytohormones play crucial roles in almost all stages of plant growth and development. Accurate and simultaneous determination of multiple phytohormones enabled us to better understand the physiological functions and the regulatory networks of phytohormones. However, simultaneous determination of multiple phytohormones in plant is still a challenge due to their low concentrations, structural and chemical diversity, and complex matrix of plant tissues. Therefore, development of a simple and selective method for the simultaneous determination of multiple phytohormones is highly needed. Results: We developed a clean-up strategy for profiling of multiple phytohormones, which can overcome the challenge of structural and chemical diversity. By using a one-step dispersive solid-phase extraction (DSPE) combined with UPLC-MS/MS, 54 phytohormones including auxins, ABA, SA, JA, GAs and CKs were simultaneously analyzed from a single rice sample extract. Using the developed method, we investigated the spatiotemporal distribution of phytohormones in rice. The profiling of various tissues of rice at different growth stages revealed the complexity of metabolic regulation and allocations of phytohormone species. Conclusion: A rapid one-step method was developed for the simultaneous analysis of six groups of phytohormones, including cytokinins, auxins, salicylic acid, jasmonates, abscisic acid and gibberellins in a single run, using UPLC-ESI-MS/MS. The proposed method was successfully applied to investigate spatiotemporal distribution of multiple phytohormones in rice. The spatiotemporal information obtained may be helpful for better understanding of phytohormones functions throughout life cycle of rice when integrated into transcriptome and other omics data. [ABSTRACT FROM AUTHOR]