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It has been shown that non-coding RNAs (ncRNAs) play an important regulatory role in pathophysiological processes involving inflammation. The vascular endothelial growth factor A (VEGFA) gene also participates in the inflammatory process. However, the relationships between ncRNAs and VEGFA are currently unclear. Here, this study was designed to determine the relationship between long non-coding RNA (lncRNA) H19, mircoRNA29b (miR-29b), and VEGFA in the development of diabetes mellitus (DM). We demonstrate that H19 is upregulated and miR-29b downregulated in individuals with DM and directly binds miR-29b. VEGFA is the target of miR-29b in the vascular endothelium of individuals with DM. We found that positive modulation of miR29b and inhibition of H19 and VEGFA significantly attenuates high glucose-induced endothelial inflammation and oxidative stress. We also found that the protein kinase B/endothelial nitric oxide synthase (AKT/eNOS) signal pathway in endothelial cells is activated through regulation of miR29b and H19 endogenous RNAs. We conclude that H19 suppression protects the endothelium against high glucose-induced inflammation and oxidative stress in endothelial cells by upregulation of miR-29b and downregulation of VEGFA through AKT/eNOS signal pathway activation. These results suggest a novel link between dysregulated ncRNA expression, inflammation, and the signaling pathway in the vascular endothelium of individuals with DM, indicating a promising strategy for preventing cardiovascular disease in such individuals.

Abstract Background Recent studies have verified that long noncoding RNAs (lncRNAs) involved in many biological functions and play crucial roles in human cancers progression, the study aimed to detect the association between long non-coding RNA HOXA11-AS and epithelial–mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC). Methods The lncRNA HOXA11-AS expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assays in 78 paired of tumor tissue and adjacent normal tissue samples in NSCLC patients. Kaplan–Meier survival curves and log-rank test was used to examine the association between lncRNA HOXA11-AS expression and the over survival time in NSCLC patients. Transwell invasion assay was performed to detect the cell invasion ability. QRT-PCR and western-blot analysis detected the mRNA and protein expression of EMT related transcription factors ZEB1/ZEB2, Snail1/2 and EMT marker E-cadherin and N-cadherin in NSCLC cells. RIP and Chromatin immunoprecipitation assays were performed to analyze the association between lncRNA HOXA11-AS and miR-200b expression in NSCLC cells. Results The lncRNA HOXA11-AS expression levels were significantly higher in NSCLC tissues compared with adjacent normal tissues and higher HOXA11-AS expression levels had a poor prognosis in NSCLC patients. Furthermore, knockdown of lncRNA HOXA11-AS in A549 and H1299 cells dramatically inhibited cell invasive abilities. Besides, the transcription levels and protein levels of EMT related transcription factors ZEB1/ZEB2, Snail1/2, and EMT maker N-cadherin were down-regulated after lncRNA HOXA11-AS was knocked down, but the mRNA and protein expression levels of EMT maker E-cadherin was increasing in A549 and H1299 cells. The mechanistic findings showed demonstrated that HOXA11-AS interacted with EZH2 and DNMT1 and recruited them to the miR-200b promoter regions to repress miR-200b expression in NSCLC cells, which promoted cell EMT in NSCLC. Conclusions Our results showed that up-regulation of lncRNA HOXA11-AS predicted a poor prognosis and lncRNA HOXA11-AS promoted cell epithelial–mesenchymal transition (EMT) by inhibiting miR-200b expression in NSCLC.

Abstract Background In the post-pandemic era of higher education, hybrid teaching has emerged as a prevalent approach and is anticipated to persist as a defining trend in the future teaching reforms worldwide. However, despite its widespread adoption, certain limitations have become apparent. The objective of this study is to identify the genuine factors that impact students’ performance, explore strategies that teachers can employ to enhance their teaching effectiveness and enhance students’ academic self-efficacy. Methods The study was performed among undergraduate medical students enrolled in Physiology course at Harbin Medical University in 2020 and 2022. Since 2020, influenced by the COVID-19 pandemic, a hybrid teaching method based on an established offline teaching model called BOPPPS was implemented. A questionnaire was performed in both 2020 and 2022 to evaluate students’ satisfaction and efficiency of our hybrid teaching. A comparison was also carried out on the final examination scores of students majoring in Pharmacy and Clinical Pharmacy across the years 2020 to 2022. Results The final examination scores of students in 2022 were significantly lower than those in 2020 and 2021 both in Pharmacy and Clinical Pharmacy majors. There was also a decrease of the score in students of Clinical Pharmacy in 2021 compared to 2020. The questionnaire indicated that over half (52.0%) of the students in 2022 preferred offline teaching method, in contrast to 39.1% in 2020. There were obvious changes in students from 2020 to 2022 about the disadvantages of hybrid teaching, the improvement of students’ learning ability and the duration of students’ autonomous learning. Through cross statistical analysis, online learning styles, learning ability improvement and students’ learning burden have been identified as the primary factors influencing their preference for future teaching method. Conclusions Hybrid teaching is still a necessary trend in the future teaching reform base on its multiple advantages. However, in order to improve the teaching outcomes and foster students’ participation and learning initiatives, it is imperative to undertake additional reforms in the future teaching process.

Abstract The synthesis of dynamic chiral lanthanide complex emitters has always been difficult. Herein, we report three pairs of dynamic chiral EuIII complex emitters (R/S -Eu-R-1, R = Et/Me; R/S -Eu-Et-2) with aggregation-induced emission. In the molecular state, these EuIII complexes have almost no obvious emission, while in the aggregate state, they greatly enhance the EuIII emission through restriction of intramolecular rotation and restriction of intramolecular vibration. The asymmetry factor and the circularly polarized luminescence brightness are as high as 0.64 (5 D 0 → 7 F 1) and 2429 M−1cm−1 of R -Eu-Et-1, achieving a rare double improvement. R -Eu-Et-1/2 exhibit excellent sensing properties for low concentrations of CuII ions, and their detection limits are as low as 2.55 and 4.44 nM, respectively. Dynamic EuIII complexes are constructed by using chiral ligands with rotor structures or vibration units, an approach that opens a door for the construction of dynamic chiral luminescent materials.

Abstract Background The long-term effectiveness of cognitive behavioural therapy (CBT) in medicated attention-deficit/hyperactivity disorder (ADHD) adults with residual symptoms needs to be verified across multiple dimensions, especially with respect to maladaptive cognitions and psychological quality of life (QoL). An exploration of the mechanisms underlying the additive benefits of CBT on QoL in clinical samples may be helpful for a better understanding of the CBT conceptual model and how CBT works in medicated ADHD. Methods We conducted a secondary analysis of a randomised controlled trial including 98 medicated ADHD adults with residual symptoms who were randomly allocated to the CBT combined with medication (CBT + M) group or the medication (M)-only group. Outcomes included ADHD-core symptoms (ADHD Rating Scale), depression symptoms (Self-rating Depression Scale), maladaptive cognitions (Automatic Thoughts Questionnaire and Dysfunctional Attitude Scale), and psychological QoL (World Health Organization Quality of Life-Brief Version-psychological domain). Mixed linear models (MLMs) were used to analyse the long-term effectiveness at one-year follow-up, and structural equation modeling (SEM) was performed to explore the potential mechanisms of CBT on psychological QoL. Results ADHD patients in the CBT + M group outperformed the M-only group in reduction of ADHD core symptoms (d = 0.491), depression symptoms (d = 0.570), a trend of reduction of maladaptive cognitions (d = 0.387 and 0.395, respectively), and improvement of psychological QoL (d = − 0.433). The changes in above dimensions correlated with each other (r = 0.201 ~ 0.636). The influence of CBT on QoL was mediated through the following four pathways: 1) changes in ADHD core symptoms; 2) changes in depressive symptoms; 3) changes in depressive symptoms and then maladaptive cognitions; and 4) changes firstly in depressive symptoms, maladaptive cognitions, and then ADHD core symptoms. Conclusions The long-term effectiveness of CBT in medicated ADHD adults with residual symptoms was further confirmed. The CBT conceptual model was verified in clinical samples, which would be helpful for a deeper understanding of how CBT works for a better psychological QoL outcome. Trial registration ChiCTR1900021705 (2019-03-05).

Abstract Background Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive. Results We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster. Conclusions A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL − Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.

ABSTRACT Background The aim was to identify the nutritional indexes, construct a prognostic model, and develop a nomogram for predicting individual survival probability in pan‐cancers. Methods Nutritional indicators, clinicopathological characteristics, and previous major treatment details of the patients were collected. The enrolled patients were randomly divided into training and validation cohorts. Least absolute shrinkage and selection operator (Lasso) regression cross‐validation was used to determine the variables to include in the cox regression model. The training cohort was used to build the prediction model, and the validation cohort was used to further verify the discrimination, calibration, and clinical effectiveness of the model. Results A total of 2020 patients were included. The median OS was 56.50 months (95% CI, 50.36–62.65 months). In the training cohort of 1425 patients, through Lasso regression cross‐validation, 13 characteristics were included in the model. Cox proportional hazards model was developed and visualized as a nomogram. The C‐indexes of the model for predicting 1‐, 3‐, 5‐, and 10‐year OS were 0.848, 0.826, 0.814, and 0.799 in the training cohort and 0.851, 0.819, 0.814, and 0.801 in the validation cohort. The model showed great calibration in the two cohorts. Patients with a score of less than 274.29 had a better prognosis (training cohort: HR, 6.932; 95% CI, 5.723–8.397; log‐rank p

Abstract Background The consolidation tumor ratio (CTR) is a predictor of invasiveness in peripheral T1N0M0 lung adenocarcinoma. However, its association with spread through air spaces (STAS) remains largely unexplored. We aimed to explore the correlation between the CTR of primary tumors and STAS in peripheral T1N0M0 lung adenocarcinoma. Methods We collected data from patients who underwent surgery for malignant lung neoplasms between January and November 2022. Univariate and multivariate analyses following propensity-score matching with sex, age, BMI, were performed to identify the independent risk factors for STAS. The incidence of STAS was compared based on pulmonary nodule type. A smooth fitting curve between CTR and STAS was produced by the generalized additive model (GAM) and a multiple regression model was established using CTR and STAS to determine the dose-response relationship and calculate the odds ratio (OR) and 95% confidence interval (CI). Results 17 (14.5%) were diagnosed with STAS. The univariate analysis demonstrated that the history of the diabetes, size of solid components, spiculation, pleural indentation, pulmonary nodule type, consolidation/tumor ratio of the primary tumor were statistically significant between the STAS-positive and STAS-negative groups following propensity-score matching(p = 0.047, 0.049, 0.030, 0.006, 0.026, and

Abstract Background Autistic traits (ATs) are frequently reported in children with Attention-Deficit/Hyperactivity Disorder (ADHD). This study aimed to examine ATs in children with ADHD from both behavioral and neuroimaging perspectives. Methods We used the Autism Spectrum Screening Questionnaire (ASSQ) to assess and define subjects with and without ATs. For behavioral analyses, 67 children with ADHD and ATs (ADHD + ATs), 105 children with ADHD but without ATs (ADHD − ATs), and 44 typically developing healthy controls without ATs (HC − ATs) were recruited. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data and analyzed the mean amplitude of low-frequency fluctuation (mALFF) values (an approach used to depict different spontaneous brain activities) in a sub-sample. The imaging features that were shared between ATs and ADHD symptoms or that were unique to one or the other set of symptoms were illustrated as a way to explore the “brain–behavior” relationship. Results Compared to ADHD-ATs, the ADHD + ATs group showed more global impairment in all aspects of autistic symptoms and higher hyperactivity/impulsivity (HI). Partial-correlation analysis indicated that HI was significantly positively correlated with all aspects of ATs in ADHD. Imaging analyses indicated that mALFF values in the left middle occipital gyrus (MOG), left parietal lobe (PL)/precuneus, and left middle temporal gyrus (MTG) might be specifically related to ADHD, while those in the right MTG might be more closely associated with ATs. Furthermore, altered mALFF in the right PL/precuneus correlated with both ADHD and ATs, albeit in diverse directions. Conclusions The co-occurrence of ATs in children with ADHD manifested as different behavioral characteristics and specific brain functional alterations. Assessing ATs in children with ADHD could help us understand the heterogeneity of ADHD, further explore its pathogenesis, and promote clinical interventions.

Abstract Background Testis is the only organ supporting sperm production and with the largest number of proteins and tissue-specific proteins in animals. In our previous studies, we have found that knockdown of ocnus (ocn), a testis-specific gene, resulted in much smaller testis with no germ cells in Drosophila melanogaster. However, the molecular consequences of ocn knockdown in fly testes are unknown. Results In this study, through iTRAQ quantitative proteomics sequencing, 606 proteins were identified from fly abdomens as having a significant and at least a 1.5-fold change in expression after ocn knockdown in fly testes, of which 85 were up-regulated and 521 were down-regulated. Among the differential expressed proteins (DEPs), apart from those proteins involved in spermatogenesis, the others extensively affected biological processes of generation of precursor metabolites and energy, metabolic process, and mitochondrial transport. Protein-protein interaction (PPI) analyses of DEPs showed that several kinases and/or phosphatases interacted with Ocn. Re-analyses of the transcriptome revealed 150 differential expressed genes (DEGs) appeared in the DEPs, and their changing trends in expressions after ocn knockdown were consistent. Many common down-regulated DEGs and DEPs were testis-specific or highly expressed in the testis of D. melanogaster. Quantitative RT-PCR (qRT-PCR) confirmed 12 genes appeared in both DEGs and DEPs were significantly down-regulated after ocn knockdown in fly testes. Furthermore, 153 differentially expressed phosphoproteins (DEPPs), including 72 up-regulated and 94 down-regulated phosphorylated proteins were also identified (13 phosphoproteins appeared in both up- and down-regulated groups due to having multiple phosphorylation sites). In addition to those DEPPs associated with spermatogenesis, the other DEPPs were enriched in actin filament-based process, protein folding, and mesoderm development. Some DEPs and DEPPs were involved in Notch, JAK/STAT, and cell death pathways. Conclusions Given the drastic effect of the ocn knockdown on tissue development and testis cells composition, the differences in protein abundance in the ocn knockdown flies might not necessarily be the direct result of differential gene regulation due to the inactivation of ocn. Nevertheless, our results suggest that the expression of ocn is essential for Drosophila testis development and that its down-regulation disturbs key signaling pathways related to cell survival and differentiation. These DEPs and DEPPs identified may provide significant candidate set for future studies on the mechanism of male reproduction of animals, including humans.

With the global epidemic and prevention of the COVID-19, long COVID-19 sequelae and its comprehensive prevention have attracted widespread attention. Long COVID-19 sequelae refer to that three months after acute COVID-19, the test of SARS-CoV-2 is negative, but some symptoms still exist, such as cough, prolonged dyspnea and fatigue, shortness of breath, palpitations and insomnia. Its pathological mechanism is related to direct viral damage, immunopathological response, endocrine and metabolism disorders. Although there are more effective methods for treating COVID-19, the treatment options available for patients with long COVID-19 remain quite limited. Psychophysical therapies, such as exercise, oxygen therapy, photobiomodulation, and meditation, have been attempted as treatment modalities for long COVID-19, which have the potential to promote recovery through immune regulation, antioxidant effects, and neuroendocrine regulation. Neuroendocrine regulation plays a significant role in repairing damage after viral infection, regulating immune homeostasis, and improving metabolic activity in patients with long COVID-19. This review uses oxytocin as an example to examine the neuroendocrine mechanisms involved in the psychophysical therapies of long COVID-19 syndrome and proposes a psychophysical strategy for the treatment of long COVID-19.

Abstract Background Biologically targeted radiation therapy treatment planning requires voxel-wise characterisation of tumours. Dynamic contrast enhanced (DCE) DCE MRI has shown promise in defining voxel-level biological characteristics. In this study we consider the relative value of qualitative, semi-quantitative and quantitative assessment of DCE MRI compared with diffusion weighted imaging (DWI) and T2-weighted (T2w) imaging to detect prostate cancer at the voxel level. Methods Seventy prostate cancer patients had multiparametric MRI prior to radical prostatectomy, including T2w, DWI and DCE MRI. Apparent Diffusion Coefficient (ADC) maps were computed from DWI, and semi-quantitative and quantitative parameters computed from DCE MRI. Tumour location and grade were validated with co-registered whole mount histology. Kolmogorov–Smirnov tests were applied to determine whether MRI parameters in tumour and benign voxels were significantly different. Cohen’s d was computed to quantify the most promising biomarkers. The Parker and Weinmann Arterial Input Functions (AIF) were compared for their ability to best discriminate between tumour and benign tissue. Classifier models were used to determine whether DCE MRI parameters improved tumour detection versus ADC and T2w alone. Results All MRI parameters had significantly different data distributions in tumour and benign voxels. For low grade tumours, semi-quantitative DCE MRI parameter time-to-peak (TTP) was the most discriminating and outperformed ADC. For high grade tumours, ADC was the most discriminating followed by DCE MRI parameters Ktrans, the initial rate of enhancement (IRE), then TTP. Quantitative parameters utilising the Parker AIF better distinguished tumour and benign voxel values than the Weinmann AIF. Classifier models including DCE parameters versus T2w and ADC alone, gave detection accuracies of 78% versus 58% for low grade tumours and 85% versus 72% for high grade tumours. Conclusions Incorporating DCE MRI parameters with DWI and T2w gives improved accuracy for tumour detection at a voxel level. DCE MRI parameters should be used to spatially characterise tumour biology for biologically targeted radiation therapy treatment planning.

Abstract In Drosophila ovary, niche is composed of somatic cells, including terminal filament cells (TFCs), cap cells (CCs) and escort cells (ECs), which provide extrinsic signals to maintain stem cell renewal or initiate cell differentiation. Niche establishment begins in larval stages when terminal filaments (TFs) are formed, but the underlying mechanism for the development of TFs remains largely unknown. Here we report that transcription factor longitudinals lacking (Lola) is essential for ovary morphogenesis. We showed that Lola protein was expressed abundantly in TFCs and CCs, although also in other cells, and lola was required for the establishment of niche during larval stage. Importantly, we found that knockdown expression of lola induced apoptosis in adult ovary, and that lola affected adult ovary morphogenesis by suppressing expression of Regulator of cullins 1b (Roc1b), an apoptosis-related gene that regulates caspase activation during spermatogenesis. These findings significantly expand our understanding of the mechanisms controlling niche establishment and adult oogenesis in Drosophila.

ObjectiveTo develop a Thyroid Cancer Self-Perceived Discrimination Scale (TCSPDS) to identify patients at high risk for psychological problems and to test its reliability, validity and acceptability.MethodsUsing classical test theory, a total of 176 thyroid cancer patients from November 2021 to October 2022 were recruited to develop the TCSPDS. Item analysis was used to improve the preliminary TCSPDS. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and structural equation model (SEM) were used to test the construct validity of the final TCSPDS. Pearson correlation coefficient was used to analyze the validity coefficient between TCSPDS and EORTC QLQ-C30 to test the criterion-related validity (CRV) of the final TCSPDS. The internal consistency coefficient (Cronbach’s alpha coefficient), split half reliability (Spearman-Brown coefficient) and test-retest reliability were used to verify the reliability of the final TCSPDS. The questionnaire completion time and effective response rate were used to validate the acceptability of the final TCSPDS.ResultsThe TCSPDS consisted of 20 items and was divided into 3 subscales: 8 items for stigma, 6 items for self-deprecation, and 6 items for social avoidance. The TCSPDS had good validity (χ2/df=1.971, RMSEA=0.074, GFI=0.921, CFI= 0.930, IFI=0.932, TLI=0.901, Validity coefficient=0.767), reliability (Cronbach’s alpha=0.867, Spearman-Brown coefficient=0.828, test-retest reliability coefficient=0.981) and acceptability [average completion time (15.01 ± 1.348 minutes) and an effective response rate of 95.14%]. Patients with higher TCSPDS scores reported a lower quality of life (P

Background/objectivesAdults with attention-deficit/hyperactivity disorder (ADHD) have more maladaptive cognitions, emotional problems and a poorer quality of life (QoL). A verification of the psychological model in clinical samples is needed for a better understanding of the mechanisms of ADHD diagnosis on QoL via maladaptive cognitions, emotional symptoms, and their interactions.Methods299 ADHD participants and 122 healthy controls were recruited. ADHD core symptoms, maladaptive cognitions, emotional symptoms and psychological QoL were rated. Pearson’s correlation and structural equation modeling were analyzed to explore the relationship and influence of ADHD diagnosis on QoL.ResultsMore maladaptive cognitions, emotional symptoms, and poorer QoL were found in the ADHD group, and the dysfunctional attitudes were on par between ADHD with or without medication (p = 0.368). Moderate to strong correlations were found between emotional symptoms, maladaptive cognitions and QoL, and ADHD core symptoms presented correlations among the above scores (r = 0.157 ~ 0.416, p

ObjectiveThis study aimed to explore both impairments in attention function in patients with major depressive disorder (MDD) and the efficacy of escitalopram monotherapy or combination therapy with agomelatine.MethodsA total of 54 patients with MDD and 46 healthy controls (HCs) were included. Patients were treated with escitalopram for 12 weeks; those who presented with severe sleep impairments were also given agomelatine. Participants were evaluated using the Attention Network Test (ANT), which included tests of alerting, orienting, and executive control networks. Concentration, instantaneous memory, and resistance to information interference were tested using the digit span test, and the logical memory test (LMT) was used to evaluate abstract logical thinking. The Hamilton Depression Rating Scale−17 items, Hamilton Anxiety Rating Scale, and Pittsburgh Sleep Quality Index were used to assess depression, anxiety, and sleep quality, respectively. Patients with MDD were assessed at the end of weeks 0, 4, 8, and 12. HCs were assessed once at baseline.ResultsCompared with HCs, patients with MDD showed significantly different alerting, orienting, and executive control functions of attention networks. Treatment with escitalopram alone or combined with agomelatine significantly improved LMT scores at the end of weeks 4, 8, and 12 and restored scores to the level of HCs at the end of week 8. Total Toronto Hospital Test of Alertness scores in patients with MDD increased significantly after 4 weeks of treatment. The ANT executive control reaction time in patients with MDD decreased significantly after 4 weeks of treatment, with this decrease lasting until the end of week 12, but scores did not return to the levels of HCs. Combined treatment with escitalopram and agomelatine led to more improvement in ANT orienting reaction time and was accompanied by a greater reduction of total scores on the Hamilton Depression Rating Scale−17 items and Hamilton Anxiety Rating Scale compared with escitalopram monotherapy.ConclusionsPatients with MDD showed overall impairments in three domains of attention networks as well as the LMT and a test of subjective alertness. Escitalopram monotherapy significantly improved the LMT scores and the executive control function scores in the ANT at the end of the fourth week of treatment, and the improvement was more extensive with combined escitalopram and agomelatine treatment.

ObjectivesThere is an ongoing debate about the restrictive inattentive (RI) presentation of attention deficit hyperactivity disorder (ADHD). The current study aimed to systematically investigate the clinical, neuropsychological, and brain functional characteristics of children with ADHD restrictive inattentive presentation.MethodsA clinical sample of 789 children with or without ADHD participated in the current study and finished clinical interviews, questionnaires, and neuropsychological tests. Those individuals with a diagnosis of ADHD were further divided into three subgroups according to the presentation of inattentive and/or hyperactive/impulsive symptoms, the ADHD-RI, the ADHD-I (inattentive), and the ADHD-C (combined) groups. Between-group comparisons were carried out on each clinical and neuropsychological measure using ANCOVA, with age and sex as covariates. Bonferroni corrections were applied to correct for multiple comparisons. Two hundred twenty-seven of the subjects also went through resting-state functional magnetic resonance imaging scans. Five ADHD-related brain functional networks, including the default mode network (DMN), the dorsal attention network (DAN), the ventral attention network, the executive control network, and the salience network, were built using predefined regions of interest (ROIs). Voxel-based group-wise comparisons were performed.ResultsCompared with healthy controls, all ADHD groups presented more clinical problems and weaker cognitive function. Among the ADHD groups, the ADHD-C group had the most clinical problems, especially delinquent and aggressive behaviors. Regarding cognitive function, the ADHD-RI group displayed the most impaired sustained attention, and the ADHD-C group had the worst response inhibition function. In terms of brain functional connectivity (FC), reduced FC in the DMN was identified in the ADHD-C and the ADHD-I groups but not the ADHD-RI group, compared to the healthy controls. Subjects with ADHD-I also presented decreased FC in the DAN in contrast to the control group. The ADHD-RI displayed marginally significantly lower FC in the salience network compared to the ADHD-I and the control groups.ConclusionThe ADHD-RI group is distinguishable from the ADHD-I and the ADHD-C groups. It is characterized by fewer externalizing behaviors, worse sustained attention, and better response inhibition function. The absence of abnormally high hyperactive/impulsive symptoms in ADHD-RI might be related to less impaired brain function in DMN, but potentially more impairment in the salience network.

Abstract Background Online teaching has become increasingly common in higher education of the post-pandemic era. While a traditional face-to-face lecture or offline teaching remains very important and necessary for students to learn the medical knowledge systematically, guided by the BOPPPS teaching model, combination of online and offline learning approaches has become an unavoidable trend for maximizing teaching efficiency. However, in physiological education, the effectiveness of combined online teaching and offline teaching models remains poorly assessed. The present study aims at providing an assessment to the hybrid teaching model. Methods The study was performed among undergraduate medical students of Class 2017 ~ 2019 in the Physiology course in Harbin Medical University during 2018-2020. Based on established offline teaching model with BOPPPS components in 2018, we incorporated online teaching contents into it to form a hybrid BOPPPS teaching model (HBOPPPS, in brief), preliminarily in 2019 and completely in 2020. HBOPPPS effectiveness was assessed through comparing the final examination scores of both objective (multi-choice and single answer questions) and subjective (short and long essays) questions between classes taught with different modalities. Results The final examination score of students in Class 2019 (83.9 ± 0.5) who were taught with the HBOPPPS was significantly higher than that in Class 2017 (81.1 ± 0.6) taught with offline BOPPPS and in Class 2018 (82.0 ± 0.5) taught with immature HBOPPPS. The difference mainly attributed to the increase in average subjective scores (41.6 ± 0.3 in Class 2019, 41.4 ± 0.3 in Class 2018, and 38.2 ± 0.4 in Class 2017). In the questionnaire about the HBOPPPS among students in Class 2019, 86.2% responded positively and 79.4% perceived improvement in their learning ability. In addition, 73.5% of the students appreciated the reproducibility of learning content and 54.2% valued the flexibility of HBOPPPS. Lastly, 61.7% of the students preferred the HBOPPPS relative to BOPPPS in future learning. Conclusions HBOPPPS is likely a more effective teaching model and useful for enhancing effectiveness of Physiology teaching. This is attributable to the reproducibility and flexibility as well as the increased learning initiatives.

Background/purpose: Oral lichenoid reactions (OLRs) are commonly characterized by the infiltration and activation of inflammatory cells at the interface of the oral mucosa. This study aimed to compare the cytokine profiles between intralesional and peripheral plasma from patients with OLRs and elucidate the cytokine profile in the OLR microenvironment. Materials and methods: A total of 26 paired intralesional and peripheral plasma samples were collected from patients with OLRs. A panel of 15 cytokines was measured using a Luminex assay. The reticular, erythema, and ulcerative score was used to evaluate the degree of OLR severity. Results: IL-10 was detected in a fewer number of intralesional samples (19/26) compared to peripheral samples (26/26, p = 0.01). The intralesional plasma exhibited significantly elevated levels of granzyme B (median 108.94 vs. 16.00), TGF-β1 (mean 30448.92 vs. 10199.04), TGF-β2 (mean 1659.73 vs. 1308.49), and TGF-β3 (mean 914.33 vs. 573.13) compared to the peripheral plasma (p = 0.001, p

ObjectiveTo evaluate performance of the ABC (Age, Biomarkers, Clinical history)-bleeding risk score in estimating major bleeding risk in Chinese patients with atrial fibrillation (AF) on oral anticoagulation (OAC) therapy in real-world practice.MethodsData were collected from the Chinese Atrial Fibrillation Registry study (CAFR). Patients were stratified into low-, medium-, and high-risk groups based on ABC-bleeding risk score with 1-year major bleeding risk ( 2%) and modified HAS-BLED score (≤1, 2, and > 2 points). Cox proportional-hazards (Cox-PH) models were used to determine the association of major bleeding incidence with bleeding scores. Harrell’s C-index of the two scores were compared. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) at 1 year were employed to evaluate the reclassification capacity. The calibration curve was plotted to compare the predicted major bleeding risk using ABC-bleeding risk score with the observed annualized event rate. The decision analysis curves (DCA) were performed to show the clinical utilization of two scores in identifying major bleeding events.ResultsThe study included 2,892 AF patients on OAC therapy. After the follow-up of 3.0 years, 48 patients had major bleeding events; the incidence of a bleeding event in the low-, medium-, and high-risk groups according to ABC-bleeding risk score was 0.31% (reference group, HR = 1.00),0.51% (HR = 1.83, 95%CI: 0.91–3.69, P = 0.09), and 1.49% (HR = 4.92, 95%CI: 2.34–10.30, P < 0.001), respectively. Major bleeding incidence had an independent association with growth differentiation factor 15 (GDF-15) level (HR = 2.16, 95%CI: 1.27–3.68, P = 0.005) after adjusting components of the HAS-BLED score and cTnT-hs level. The ABC-bleeding score showed a Harrell’s C-index of 0.67 (95%CI: 0.60–0.75) in estimating major bleeding risk, which was non-significant compared to the modified HAS-BLED score (0.67 vs. 0.63; P = 0.38). NRI and IDI also revealed comparable reclassification capacity of ABC-bleeding risk score compared with HAS-BLED score (14.6%, 95%CI: −10.2%, 39.4%, P = 0.25; 0.2%, 95%CI −0.1 to 0.9%, P = 0.64). Cross-tabulation of the two scores showed that the ABC-bleeding score outperformed the HAS-BLED score in identifying patients with a high risk of major bleeding. The calibration curve showed that the ABC-bleeding risk score overestimated the observed major bleeding risk. DCA did not show any difference in net benefit when using either of the scores.ConclusionThis study verified the value of the ABC-bleeding risk score in assessing major bleeding risk in Chinese patients with AF on OAC therapy in real-world practice. Despite the overestimation of major bleeding risk, ABC-bleeding score performed better in stratifying patients with a high risk than the modified HAS-BLED score. Combining the two scores could be a clinically practical strategy for precisely stratifying AF patients, especially those at a high risk of major bleeding, and further supporting the optimization of OAC treatment.

Fragmentation is a universal phenomenon associated with rock avalanches, resulting in an abundance of complex sedimentological structures. If studied in detail, these structures can provide insights into rock avalanche emplacement processes. Here, six typical avalanche cases are carefully analyzed in conjunction with an analogue experiment. Findings reveal the carapace facies is characterized by clast-supported structures composed of large blocks with sedimentological structures that include retained stratigraphic sequences, imbricate structures, and jigsaw structures. The body facies presents a high degree of fragmentation, with block-rich zones, fine matrix-rich zones, jigsaw structures, and inner shear zones. The basal facies displays the highest degree of fragmentation, however, it is mainly composed of millimeter grains with thin shear strips. Consistent with the field investigations, differential fragmentation is also observed in the analogue tests, with the vertical dimension of the carapace facies mainly fragmented along the lines of pre-existing structures; the body facies fragmented with an abundance of new fractures; and the basal facies fragmented into fine grains. Meanwhile, layer sequences preserved in longitudinal and vertical profiles are also observed in the analogue tests, indicating a low disturbance in the propagation. We, therefore, propose that a process characterized by a sparse state, dominated by collisions, minor disturbance, and pervasive dynamic fragmentation likely occurs in the carapace facies, with fragmentation mainly controlled by the breakage of pre-existing, fully-persistent structures. The body facies is mainly controlled by the fracturing of the weak, less-persistent structures, and the basal facies displays the highest degree of fragmentation with an abundance of new fractures. In the entire propagation, the avalanche mass displays low-disturbance laminar flow.

We assessed interactions between the astrocytic volume-regulated anion channel (VRAC) and aquaporin 4 (AQP4) in the supraoptic nucleus (SON). Acute SON slices and cultures of hypothalamic astrocytes prepared from rats received hyposmotic challenge (HOC) with/without VRAC or AQP4 blockers. In acute slices, HOC caused an early decrease with a late rebound in the neuronal firing rate of vasopressin neurons, which required activity of astrocytic AQP4 and VRAC. HOC also caused a persistent decrease in the excitatory postsynaptic current frequency, supported by VRAC and AQP4 activity in early HOC; late HOC required only VRAC activity. These events were associated with the dynamics of glial fibrillary acidic protein (GFAP) filaments, the late retraction of which was mediated by VRAC activity; this activity also mediated an HOC-evoked early increase in AQP4 expression and late subside in GFAP-AQP4 colocalization. AQP4 activity supported an early HOC-evoked increase in VRAC levels and its colocalization with GFAP. In cultured astrocytes, late HOC augmented VRAC currents, the activation of which depended on AQP4 pre-HOC/HOC activity. HOC caused an early increase in VRAC expression followed by a late rebound, requiring AQP4 and VRAC, or only AQP4 activity, respectively. Astrocytic swelling in early HOC depended on AQP4 activity, and so did the early extension of GFAP filaments. VRAC and AQP4 activity supported late regulatory volume decrease, the retraction of GFAP filaments, and subside in GFAP-VRAC colocalization. Taken together, astrocytic morphological plasticity relies on the coordinated activities of VRAC and AQP4, which are mutually regulated in the astrocytic mediation of HOC-evoked modulation of vasopressin neuronal activity.

Abstract Background Catheter ablation is widely used in atrial fibrillation (AF) management. In this study, we are aimed to investigate the incidence of postprocedural cognitive decline in a larger population undergoing AF ablation under local anesthesia, and to evaluate the associated risk factors. Methods This study included 287 patients with normal cognitive functions, with 190 ablated AF patients (study group) and 97 AF patients who are awaiting ablation (practice group). We assessed the neuropsychological function of each patient for twice (study group: 24 h prior to ablation and 48 h post ablation; practice group: on the day of inclusion and 72 h later but before ablation). The reliable change index was used to analyze the neuropsychological testing scores and to identify postoperative cognitive dysfunction (POCD) at 48 h post procedure. Patients in the study group accepting a 6-month follow up were given an extra cognitive assessment. Results Among the ablated AF patients, 13.7% (26/190) had POCD at 48 h after the ablation procedure. Multivariable analysis revealed that, a minimum intraoperative activated clotting time (ACT)

In this work, a new (Y, Gd)H2 precipitate was identified and systematically investigated in the as-cast Mg-6Gd-3Y-0.5Zr alloy by XRD, SEM with EDS, TEM with EDS techniques and thermodynamics analysis. Results show that the as-cast alloy contains α-Mg, Mg24(Gd, Y)5, and (Y, Gd)H2 phase. The (Y, Gd)H2 phase usually forms near the eutectic phase Mg24(Gd, Y)5 or in the α-Mg grains, displaying a rectangle-shape. The Mg24(Gd, Y)5 and (Y, Gd)H2 phases crystalize in bcc and fcc structure, respectively, and the (Y, Gd)H2 phase has a semi-coherent relationship with α-Mg matrix. The thermodynamics calculation results reveal that the hydrogen dissolved in the melt leads to the formation of hydrides. It is also found that the (Y, Gd)H2 hydride can form directly from the liquid phase during solidification. Additionally, it can precipitate by the decomposition of Mg24(Gd, Y)5 phase due to absorbing hydrogen from the remaining melt.

Abstract A significant proportion of the land area of Heilongjiang Province, China, is composed of saline–alkaline soil, which severely inhibits maize growth. Although Trichoderma treatment is widely regarded as a promising strategy for improving the soil environment and promoting plant growth, the mechanism through which Trichoderma asperellum enhances maize resistance to saline–alkaline stress is not clear. In this study, we explored the effect of T. asperellum application at different concentrations to soil saline–alkaline environment on the seedlings of two maize cultivars, assessing the biochemical parameters related to oxidation resistance. Increasing spore densities of T. asperellum suspension effectively regulated the soil ion balance in the rhizosphere of maize seedlings, reduced the soil pH by 2.15–5.76% and sodium adsorption ratios by 22.70–54.13%, increased soil nutrient content and enzyme activity, and improved the soil environment for seedling growth. Additionally, T. asperellum treatment increased the maize seedling content of osmo-regulating substances and rate of glutathione:oxidised glutathione (43.86–88.25%) and ascorbate:oxidised ascorbate (25.26–222.32%) by affecting the antioxidant enzyme activity in the roots, increasing reactive oxygen species scavenging, and maintaining the osmotic balance and metabolic homeostasis under saline–alkaline stress. T. asperellum also improved the saline–alkaline tolerance of maize seedlings by improving the root growth characteristics. Moreover, results showed that Trichoderma applied at high concentration had the greatest effect. In conclusion, improvement in the saline–alkaline tolerance of maize seedlings by T. asperellum under saline–alkaline soil conditions may be achieved through diverse effects that vary among maize cultivars.

Coronavirus disease 2019 or COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a significant threat to the health of human beings. While wearing mask, maintaining social distance and performing self-quarantine can reduce virus spreading passively, vaccination actively enhances immune defense against COVID-19. However, mutations of SARS-CoV-2 and presence of asymptomatic carriers frustrate the effort of completely conquering COVID-19. A strategy that can reduce the susceptibility and thus prevent COVID-19 while blocking viral invasion and pathogenesis independent of viral antigen stability is highly desirable. In the pathogenesis of COVID-19, endocrine disorders have been implicated. Correspondingly, many hormones have been identified to possess therapeutic potential of treating COVID-19, such as estrogen, melatonin, corticosteroids, thyroid hormone and oxytocin. Among them, oxytocin has the potential of both treatment and prevention of COVID-19. This is based on oxytocin promotion of immune-metabolic homeostasis, suppression of inflammation and pre-existing comorbidities, acceleration of damage repair, and reduction of individuals’ susceptibility to pathogen infection. Oxytocin may specifically inactivate SARS-COV-2 spike protein and block viral entry into cells via angiotensin-converting enzyme 2 by suppressing serine protease and increasing interferon levels and number of T-lymphocytes. In addition, oxytocin can promote parasympathetic outflow and the secretion of body fluids that could dilute and even inactivate SARS-CoV-2 on the surface of cornea, oral cavity and gastrointestinal tract. What we need to do now is clinical trials. Such trials should fully balance the advantages and disadvantages of oxytocin application, consider the time- and dose-dependency of oxytocin effects, optimize the dosage form and administration approach, combine oxytocin with inhibitors of SARS-CoV-2 replication, apply specific passive immunization, and timely utilize efficient vaccines. Meanwhile, blocking COVID-19 transmission chain and developing other efficient anti-SARS-CoV-2 drugs are also important. In addition, relative to the complex issues with drug applications over a long term, oxytocin can be mobilized through many physiological stimuli, and thus used as a general prevention measure. In this review, we explore the potential of oxytocin for treatment and prevention of COVID-19 and perhaps other similar pathogens.

PurposeThe purpose of this study was to evaluate the efficacy and safety of low power micro radiofrequency (RF) therapy (μRFthera®) through urethra in the treatment of overactive bladders (OAB) through a prospective, single-blind, placebo-controlled, multi-center clinical protocol.Materials and MethodsOne hundred and fourteen patients with refractory OAB were randomized at 2:1 ratio, treatment to control undergoing same procedures except only the micro-RF treatment group at turned “on” setting in energy. Bladder diaries recorded during the screening period (3 days before enrollment) and during follow-up period on week 1, 3, and 7, respectively. The patients in control could choose receiving an energized treatment during extension stage.ResultsThe treatment efficacy was 76.1%. There was 49.80% rate improvement compared to control (95%CL 32.48%, 67.13%). The crude rate ration (RR) was 2.89, 95% CI (1.67–5.01) with p < 0.001 in uni-variate analysis, while the RR became 2.94, 95% CI (1.67–5.16) with p < 0.001 after adjusted potential confounding factors in multi-variate analysis. Statistically significant improvements have been demonstrated in the frequency of urination, urgency, nocturia, and quality of life (QoL) scores.ConclusionsMicro RF therapy is safe and effective for the treatment of OAB. The main treatment-related complications were catheterization related complications.Clinical Trial RegistrationZhejiang Device Registration Certificate No. 202090909, www.chictr.org.cn, Clinical Trial Accession Number: ChiCTR2100050096.

Oxytocin (OT), a nonapeptide, has a variety of functions. Despite extensive studies on OT over past decades, our understanding of its neural functions and their regulation remains incomplete. OT is mainly produced in OT neurons in the supraoptic nucleus (SON), paraventricular nucleus (PVN) and accessory nuclei between the SON and PVN. OT exerts neuromodulatory effects in the brain and spinal cord. While magnocellular OT neurons in the SON and PVN mainly innervate the pituitary and forebrain regions, and parvocellular OT neurons in the PVN innervate brainstem and spinal cord, the two sets of OT neurons have close interactions histologically and functionally. OT expression occurs at early life to promote mental and physical development, while its subsequent decrease in expression in later life stage accompanies aging and diseases. Adaptive changes in this OT system, however, take place under different conditions and upon the maturation of OT release machinery. OT can modulate social recognition and behaviors, learning and memory, emotion, reward, and other higher brain functions. OT also regulates eating and drinking, sleep and wakefulness, nociception and analgesia, sexual behavior, parturition, lactation and other instinctive behaviors. OT regulates the autonomic nervous system, and somatic and specialized senses. Notably, OT can have different modulatory effects on the same function under different conditions. Such divergence may derive from different neural connections, OT receptor gene dimorphism and methylation, and complex interactions with other hormones. In this review, brain functions of OT and their underlying neural mechanisms as well as the perspectives of their clinical usage are presented.

Abstract Background The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. Case presentation A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. Conclusions The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.

Endothelial dysfunction and apoptosis have key roles in the initiation and progression of atherosclerosis (AS). AS has been demonstrated to be associated with a high‑fat diet, which may increase endothelial permeability and apoptosis; however, the exact mechanisms underlying the development of AS remain poorly understood. MicroRNAs (miRNAs) are vital for the regulation of cardiovascular disease, and dysregulated miRNAs have been implicated in AS. The present study investigated whether miRNA (miR)‑126 regulates high‑fat diet‑induced endothelial permeability and apoptosis by targeting transforming growth factor β (TGFβ), a secreted protein that controls cellular proliferation and apoptosis. In the present study, apolipoprotein E (apoE)‑/‑ mice were fed a high‑fat diet in order to establish a model of AS. Mice were subcutaneously injected with a miR‑126 mimic, a miR‑126 antagomir or control miRNA. Reverse transcription‑quantitative polymerase chain reaction was used to assess miR‑126 expression, and a fluorometric assay was used to evaluate caspase‑3 activity. The effects of miR‑126 on the endothelial permeability of the aortic intima were also explored. Western blotting and immunohistochemical analysis were used to investigate the effects of miR‑126 on B‑cell lymphoma‑2 (Bcl‑2) and transforming growth factor (TGF) β protein expression levels. Furthermore, a luciferase assay was performed to verify whether TGFβ may be a direct target gene of miR‑126. In apolipoprotein E‑knockout mice, a high‑fat diet reduced miR‑126 expression and induced apoptosis as determined by the upregulation of caspase‑3 activity. A miR‑126 antagomir increased endothelial permeability and apoptosis in mice fed a high‑fat diet. By contrast, an miR‑126 mimic attenuated endothelial permeability and apoptosis. The reduction in miR‑126 was associated with a reduction in protein expression levels of Bcl‑2 and an increase of TGFβ in mice fed a high‑fat diet. In addition, the present study demonstrated that miR‑126 reduced TGFβ expression following binding to the 3'‑untranslated region of TGFβ mRNA. The current study demonstrated a role for miR‑126 in AS and identified TGFβ as a direct target of miR‑126. Furthermore, the present study demonstrated that miR‑126 contributed to endothelial permeability and apoptosis, and suggested that the downregulation of TGFβ may be involved in the molecular mechanisms underlying the actions of miR‑126. miR‑126 may therefore have potential as a novel therapeutic target for the treatment of AS. [ABSTRACT FROM AUTHOR]

Abstract Background The coronavirus disease 2019 (COVID-19) has been declared a global pandemic by the World Health Organization. Patients with cancer are more likely to incur poor clinical outcomes. Due to the prevailing pandemic, we propose some surgical strategies for gastric cancer patients. Methods The ‘COVID-19’ period was defined as occurring between 2020 and 01-20 and 2020-03-20. The enrolled patients were divided into two groups, pre-COVID-19 group (PCG) and COVID-19 group (CG). A total of 109 patients with gastric cancer were enrolled in this study. Results The waiting time before admission increased by 4 days in the CG (PCG: 4.5 [IQR: 2, 7.8] vs. CG: 8.0 [IQR: 2,20]; p = 0.006). More patients had performed chest CT scans besides abdominal CT before admission during the COVID-19 period (PCG: 22 [32%] vs. CG: 30 [73%], p = 0.001). After admission during the COVID period, the waiting time before surgery was longer (PCG: 3[IQR: 2,5] vs. CG: 7[IQR: 5,9]; p

Abstract Background Oral lichen planus (OLP) is a relatively common mucocutaneous disorder, and its causative factors and pathogenesis are not fully understood. Existing studies on the association between hematinic deficiencies and OLP are limited and inconsistent. The aim of this study was to assess the hematinic deficiencies in a cohort of OLP patients and evaluate the correlation between hematinic deficiencies and OLP. Methods A total of 236 OLP patients and 226 age-and-gender-matched healthy controls were enrolled in this study. The levels of hemoglobin (Hb), serum folate, vitamin B12 and ferritin were measured and compared between OLP patients and healthy controls. An REU (reticular/hyperkeratotic, erosive/erythematous, ulcerative) scoring system was adopted and compared between the OLP patients with and without hematinic deficiencies. The correlation between hematinic deficiencies and OLP was analyzed. Results The frequencies of serum ferritin and vitamin B12 deficiency in OLP patients were both significantly higher than those of the healthy controls. According to gender and age, the profiles of hematinic deficiencies in OLP patients were significantly different. As for the REU score, no significant difference existed between OLP patients with and without hematinic deficiencies. Both serum ferritin deficiency and serum vitamin B12 deficiency were significantly correlated with OLP. Conclusions The present study suggested a significant association between hematinic deficiencies and OLP. Iron, folate, and vitamin B12 levels in OLP patients should be monitored routinely. Further studies are warranted to explore the interactions between OLP and hematinic deficiencies.

Background: “Atrial fibrillation Better Care” (ABC) pathway has been proposed to improve the management of patients suffered from atrial fibrillation (AF). This integrated or holistic management approach comprise of three aspects, including “A” Avoid stroke or Anticoagulation; “B” Better symptom control with rate or rhythm control strategies; “C” Cardiovascular risk factor and Concomitant diseases management. We aimed to confirm the beneficial evidence of ABC pathway compliance in a Chinese AF cohort.Method and Results: From the Chinese Atrial Fibrillation registry (CAFR) dataset, a total of 19,187 non-valvular AF patients were enrolled, of which 4.365 (22.8%) were ABC pathway compliant (ABC compliance group). During a median follow-up of 4.1 ± 1.8 years, The incident rate of all-cause death in ABC compliance group and non-ABC compliance group is 2.7 and 1.1 per 100 person-year (p < 0.001), the incident rate of ischemic stroke is 1.3 and 0.8% per 100 person-year (p < 0.001), the incident rate of composite outcome, which consist of all-cause death, ischemic stroke and intracranial hemorrhage, is 3.8 and 1.9 per 100 person-year (p < 0.001). On Cox multivariable analysis, ABC pathway shows an independently association with reduction of all-cause death [hazard ratio (HR) = 0.82; 95% confidence interval (CI) = 0.70–0.95] and the composite outcome (HR 0.86, 95% CI 0.76–0.96). The increasingly components of ABC integrated care compliance is associated with lower risk of all-cause death and composite events.Conclusion: In a large cohort of Chinese AF patients, ABC pathway compliance shows an independently association with reduction of all-cause death and composite outcome of all-cause death, ischemic stroke and intracranial hemorrhage. Better compliance of ABC integrated care contributes to lower HR for adverse events.

Previous studies have shown that nicotine could impair the germ cell cyst breakdown and the primordial follicle assembly by autophagy. In this paper, we discovered that luteinizing hormone (LH) and follicle-stimulating hormone (FSH) could counteract the damage caused by nicotine of mouse germ cell cyst breakdown. The neonatal mice were separately intraperitoneally injected with nicotine, nicotine plus LH, nicotine plus FSH, and saline (control) for 4 days. Compared with the nicotine group, the quality of oocytes and the number of follicles were remarkably increased in the nicotine plus LH group or nicotine plus FSH group. LH and FSH could alleviate nicotine-induced oocyte autophagy by different pathways. LH reduced the nicotine-induced autophagy by restoring the phosphorylation level of adenosine 5′-monophosphate-activated protein kinase α-1, while FSH by downregulating the phosphorylation level of Forkhead box class O 1. In addition, in a subsequent study of 6-week mice in different treated groups, we found that LH and FSH supplementation significantly improved normal maturation rates, fertilization rates, and embryo’s developmental potential of oocytes in oocytes exposed to nicotine. Taken together, these results suggested that LH and FSH could counteract the damage caused by nicotine and finally ensure normal germ cell cyst breakdown and early embryo development.

Maternal social stress among breastfeeding women can be adapted in chronic process. However, neuroendocrine mechanisms underlying such adaptation remain to be identified. Here, we report the effects of 2 hr/day unfamiliar male rat invasion (UMI) stress on maternal behaviors in lactating rats during postpartum day 8 (UMI8) to postpartum day 12 (UMI12). Rat dams at UMI8 presented signs of maternal anxiety, depression, and attacks toward male intruder. These changes partially reversed at UMI12 except the sign of anxiety. In the supraoptic nucleus (SON), UMI12 but not UMI8 significantly increased the expression of c-Fos and phosphorylated extracellular signal-regulated protein kinase 1/2. At UMI8 but not UMI12, length of glial fibrillary acidic protein (GFAP, astrocytic cytoskeletal element) filaments around oxytocin (OT) neurons was significantly longer than that of their controls; the amount of GFAP fragments at UMI12 was significantly less than that at UMI8. Expression of cystathionine β-synthase (CBS, enzyme for H 2 S synthesis) at UMI12 was significantly higher than that at UMI8. CBS expression did not change significantly in the somatic zone of the SON but decreased significantly at the ventral glia lamina at UMI8. In brain slices of the SON, aminooxyacetate (a CBS blocker) significantly increased the expression of GFAP proteins that were molecularly associated with CBS. Aminooxyacetate also reduced the firing rate of OT neurons whereas Na 2 S, a donor of H 2 S, increased it. The adaptation during chronic social stress is possibly attributable to the increased production of H 2 S by astrocytes and the subsequent retraction of astrocytic processes around OT neurons.

Wolbachia is a group of intracellular symbiotic bacteria that widely infect arthropods and nematodes. Wolbachia infection can regulate host reproduction with the most common phenotype in insects being cytoplasmic incompatibility (CI), which results in embryonic lethality when uninfected eggs fertilized with sperms from infected males. This suggests that CI-induced defects are mainly in paternal side. However, whether Wolbachia-induced metabolic changes play a role in the mechanism of paternal-linked defects in embryonic development is not known. In the current study, we first use untargeted metabolomics method with LC-MS to explore how Wolbachia infection influences the metabolite profiling of the insect hosts. The untargeted metabolomics revealed 414 potential differential metabolites between Wolbachia-infected and uninfected 1-day-old (1d) male flies. Most of the differential metabolites were significantly up-regulated due to Wolbachia infection. Thirty-four metabolic pathways such as carbohydrate, lipid and amino acid, and vitamin and cofactor metabolism were affected by Wolbachia infection. Then, we applied targeted metabolomics analysis with GC-MS and showed that Wolbachia infection resulted in an increased energy expenditure of the host by regulating glycometabolism and fatty acid catabolism, which was compensated by increased food uptake. Furthermore, overexpressing two acyl-CoA catabolism related genes, Dbi (coding for diazepam-binding inhibitor) or Mcad (coding for medium-chain acyl-CoA dehydrogenase), ubiquitously or specially in testes caused significantly decreased paternal-effect egg hatch rate. Oxidative stress and abnormal mitochondria induced by Wolbachia infection disrupted the formation of sperm nebenkern. These findings provide new insights into mechanisms of Wolbachia-induced paternal defects from metabolic phenotypes.

The endosymbiotic Wolbachia bacteria frequently cause cytoplasmic incompatibility (CI) in their insect hosts, where Wolbachia-infected males cross with uninfected females, leading to no or fewer progenies, indicating a paternal modification by Wolbachia. Recent studies have identified a Wolbachia protein, CidB, containing a DUB (deubiquitylating enzyme) domain, which can be loaded into host sperm nuclei and involved in CI, though the DUB activity is not necessary for CI in Drosophila melanogaster. To investigate whether and how Wolbachia affect protein ubiquitination in testes of male hosts and are thus involved in male fertility, we compared the protein and ubiquitinated protein expressions in D. melanogaster testes with and without Wolbachia. A total of 643 differentially expressed proteins (DEPs) and 309 differentially expressed ubiquitinated proteins (DEUPs) were identified to have at least a 1.5-fold change with a p-value of Wolbachia. Four genes coding for DEUPs in ubiquitin proteasome pathways were knocked down, respectively, in Wolbachia-free fly testes. Among them, Rpn6 and Rpn7 knockdown caused male sterility, with no mature sperm in seminal vesicles. These results reveal deubiquitylating effects induced by Wolbachia infection, suggesting that Wolbachia can widely deubiquitinate proteins that have crucial functions in male fertility of their hosts, but are not involved in CI. Our data provide new insights into the regulatory mechanisms of endosymbiont/host interactions and male fertility.

Oxytocin (OT), a neuropeptide produced in the supraoptic (SON) and paraventricular (PVN) nuclei, is not only essential for lactation and maternal behavior but also for normal immunological activity. However, mechanisms underlying OT regulation of maternal behavior and its association with immunity around parturition, particularly under mental and physical stress, remain unclear. Here, we observed effects of OT on maternal behavior in association with immunological activity in rats after cesarean delivery (CD), a model of reproductive stress. CD significantly reduced maternal interests to the pups throughout postpartum day 1-8. On postpartum day 5, CD decreased plasma OT levels and thymic index but increased vasopressin, interleukin (IL)-1β, IL-6 and IL-10 levels. CD had no significant effect on plasma adrenocorticotropic hormone and corticosterone levels. In the hypothalamus, CD decreased corticotropin-releasing hormone contents in the PVN but increased OT contents in the PVN and SON and OT release from hypothalamic implants. CD also increased c-Fos expression, particularly in the cytoplasm of OT neurons. Lastly, CD depolarized resting membrane potential and increased spike width while increasing the variability of the firing rate of OT neurons in brain slices. Thus, CD can increase hypothalamic OT contents and release but reduce pituitary release of OT into the blood, which is associated with depressive-like maternal behavior, increased inflammatory cytokine release and decreased relative weight of the thymus.