Clinical knowledge-based ECG abnormalities detection using dual-view CNN-Transformer and external attention mechanism.

BACKGROUND: Automatic abnormalities detection based on Electrocardiogram (ECG) contributes greatly to early prevention, computer aided diagnosis, and dynamic analysis of cardiovascular diseases. In order to achieve cardiologist-level performance, deep neural networks have been widely utilized to extract abstract feature representations. However, the mechanical stacking of numerous computationally intensive operations makes traditional deep neural networks suffer from inadequate learning, poor interpretability, and high complexity. METHOD: To address these limitations, a clinical knowledge-based ECG abnormalities detection model using dual-view CNN-Transformer and external attention mechanism is proposed by mimicking the diagnosis of the clinicians. Considering the clinical knowledge that both the detailed waveform changes within a single heartbeat and the global changes throughout the entire recording have complementary roles in abnormalities detection, we presented a dual-view CNN-Transformer to extract and fuse spatial-temporal features from different views. In addition, the locations of the ECG where abnormalities occur provide more information than other areas. Therefore, two external attention mechanisms are designed and added to the corresponding views to help the network learn efficiently. RESULTS: Experiment results on the 9-class dataset show that the proposed model achieves an average F1-score of 0.854±0.01 with a higher interpretability and a lower complexity, outperforming the state-of-the-art model. CONCLUSIONS: Combining all these excellent features, this study provides a credible solution for automatic ECG abnormalities detection.

Supermolecules as a quality markers of herbal medicinal products.

Herbal medicines have greatly contributed to human health worldwide for thousands of years. In particular, traditional Chinese medicine plays an essential role in the prevention and treatment of COVID-19. With the exponentially increasing use and global attention to herbal medicinal products (HMPs), efficacy and safety have become major public concerns in many countries. In general, the quantification and qualification of quality markers (Q-markers) is the most common way to solve this issue. In the last few decades, small molecules, including flavonoids, terpenes, phenylpropanoids, alkaloids, phenols, and glycosides have been extensively investigated as Q-markers for HMP quality control. With the development of biotechnology in the last decade, scientists have begun to explore HMPs macromolecules, including polysaccharides and DNA, for their establishment as Q-markers. In recent years, supermolecules with stronger biological activities have been found in HMPs. In this review, we summarize and discuss the current Q-markers for HMP quality control; in particular, the possibility of using supermolecules as Q-markers based on structure and activity was discussed.

Berberine Suppresses Mice Depression Behaviors and Promotes Hippocampal Neurons Growth Through Regulating the miR-34b-5p/miR-470-5p/BDNF Axis.

BACKGROUND: Berberine has been found to inhibit the progression of depression disorder, but its specific mechanism is still unclear. MicroRNA (miRNA) is considered to play an important role in the progression of depression. However, it is unclear whether Berberine is involved in the regulation of depression progression through miRNA. METHODS: The chronic unpredictable mild stress (CUMS) mice model was constructed. Mice depression behaviors were evaluated by sucrose preference test (SPT) and forced swim test (FST). Quantitative real-time PCR was employed to assess the expression of miR-34b-5p, miR-470-5p and brain-derived neurotrophic factor (BDNF). The protein expression of BDNF was examined using Western blot analysis. In addition, the viability and apoptosis of hippocampal neurons were determined using cell counting kit 8 assay, flow cytometry and TUNEL assay. The interaction between BDNF and miR-34b-5p or miR-470-5p was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. RESULTS: Our data indicated that Berberine could inhibit CUMS mice depression behaviors and enhance hippocampal neurons growth by targeting miR-34b-5p and miR-470-5p. In addition, we found that BDNF was a target of miR-34b-5p and miR-470-5p. Overexpressed BDNF could reverse the regulation of miR-34b-5p and miR-470-5p on CUMS mice depression behaviors and hippocampal neurons growth. Furthermore, Berberine could promote BDNF expression to regulate CUMS mice depression behaviors and hippocampal neurons growth. CONCLUSION: Berberine might inhibit the progression of depression disorder by regulating the miR-34b-5p/miR-470-5p/BDNF axis.

The physical microenvironment of hematopoietic stem cells and its emerging roles in engineering applications.

Stem cells are considered the fundamental underpinnings of tissue biology. The stem cell microenvironment provides factors and elements that play significant roles in controlling the cell fate direction. The bone marrow is an important environment for functional hematopoietic stem cells in adults. Remarkable progress has been achieved in the area of hematopoietic stem cell fate modulation based on the recognition of biochemical factors provided by bone marrow niches. In this review, we focus on emerging evidence that hematopoietic stem cell fate is altered in response to a variety of microenvironmental physical cues, such as geometric properties, matrix stiffness, and mechanical forces. Based on knowledge of these biophysical cues, recent developments in harnessing hematopoietic stem cell niches ex vivo are also discussed. A comprehensive understanding of cell microenvironments helps provide mechanistic insights into pathophysiological mechanisms and underlies biomaterial-based hematopoietic stem cell engineering.

Quantitative and Qualitative Analyses of Psychological Experience and Adjustment of In Vitro Fertilization-Embryo Transfer Patients.

BACKGROUND The aim of this study was to quantitatively analyze the psychosocial characteristics of in vitro fertilization-embryo transfer (IVF-ET) couples and normal couples, and to identify the influencing factors of psychological characteristics and pregnancy outcomes. MATERIAL AND METHODS There were 260 infertile couples undergoing IVF-ET and 277 healthy couples of childbearing age in Shengjing Hospital of China Medical University recruited into 2 groups. Psychosocial characteristics were compared to analyze the influencing factors of pregnancy outcomes after IVF-ET. In-depth interviews (n=11) and infertility-related forum posts (n=12) were adopted to obtain the data related to the psychological experience and adjustment. Nvivo 11 software was utilized to collect and analyze the data. RESULTS The levels of anxiety and depression in the IVF-ET group were significantly higher (both P<0.01), the total scores of marital quality scale and social support scale were significantly lower (both P<0.05), immature defense mechanism score was significantly higher (P<0.05), and mature defense mechanism score (P<0.05) was significantly lower than those in the control group. Bod mass index (BMI), family's rural residence, marital quality, and immature and mature defense mechanisms were influencing factors of depression in IVF-ET female patients (all P<0.05). Marital quality, mature and immature defense mechanisms, concealment factors, and Harm Avoidance (HA) score were influencing factors of depression in IVF-ET males (all P<0.05). The age of the female patient was an independent influencing factor of IVF-ET pregnancy success rate (P<0.01). CONCLUSIONS The mental health levels of IVF-ET patients were worse than those of fertile couples. The younger the female infertile patient, the higher pregnancy rate of IVF-ET.

Potential link between genetic polymorphisms of catechol-O-methyltransferase and dopamine receptors and treatment efficacy of risperidone on schizophrenia.

OBJECTIVE: The current study aimed to explore the association of single nucleotide polymorphisms (SNPs) within catechol-O-methyltransferase (COMT) and dopamine receptors with schizophrenia and genetic association with risperidone treatment response. METHODS: A total of 690 schizophrenic patients (case group) were selected and 430 healthy people were included as the controls. All patients received risperidone treatment continuously for 8 weeks. Next, peripheral venous blood samples were collected and were subjected to polymerase chain reaction-restriction fragment length polymorphism to amplify and genotype the SNPs within COMT and dopamine receptors. Then, correlation analysis was conducted between Positive and Negative Syndrome Scale improvement rates and SNPs within COMT and the dopamine receptor gene. RESULTS: The allele of DRD1 rs11749676 (A) emerged as a key element in reducing schizophrenia risk with statistical significance (P<0.001). Remarkably, alleles of COMT rs165774 (G), DRD2 rs6277 (T), and DRD3 rs6280 (C) were associated with raised predisposition to schizophrenia (all P<0.001). Regarding DRD1 rs11746641, DRD1 rs11749676, DRD2 rs6277, and DRD3 rs6280, the case group exhibited a lesser frequency of heterozygotes in comparison with wild homozygotes genotype (all P<0.001). SNPs (COMT rs4680, DRD2 rs6275, DRD2 rs1801028, and DRD2 rs6277) were remarkably associated with improvement rates of PANSS total scores (P<0.05). SNPs (COMT rs165599 and DRD2 rs1801028) were significantly associated with risperidone efficacy on negative symptoms (P<0.05). CONCLUSION: COMT SNPs and dopamine receptor SNPs were correlated with prevalence of schizophrenia and risperidone treatment efficacy of schizophrenia.

Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation During Angiotensin II Hypertension.

Angiotensin II (AngII) hypertension increases distal tubule Na-Cl cotransporter (NCC) abundance and phosphorylation (NCCp), as well as epithelial Na(+) channel abundance and activating cleavage. Acutely raising plasma [K(+)] by infusion or ingestion provokes a rapid decrease in NCCp that drives a compensatory kaliuresis. The first aim tested whether acutely raising plasma [K(+)] with a single 3-hour 2% potassium meal would lower NCCp in Sprague-Dawley rats after 14 days of AngII (400 ng/kg per minute). The potassium-rich meal neither decreased NCCp nor increased K(+) excretion. AngII-infused rats exhibited lower plasma [K(+)] versus controls (3.6±0.2 versus 4.5±0.1 mmol/L; P<0.05), suggesting that AngII-mediated epithelial Na(+) channel activation provokes K(+) depletion. The second aim tested whether doubling dietary potassium intake from 1% (A1K) to 2% (A2K) would prevent K(+) depletion during AngII infusion and, thus, prevent NCC accumulation. A2K-fed rats exhibited normal plasma [K(+)] and 2-fold higher K(+) excretion and plasma [aldosterone] versus A1K. In A1K rats, NCC, NCCpS71, and NCCpT53 abundance increased 1.5- to 3-fold versus controls (P<0.05). The rise in NCC and NCCp abundance was prevented in the A2K rats, yet blood pressure did not significantly decrease. Epithelial Na(+) channel subunit abundance and cleavage increased 1.5- to 3-fold in both A1K and A2K; ROMK (renal outer medulla K(+) channel abundance) abundance was unaffected by AngII or dietary K(+) In summary, the accumulation and phosphorylation of NCC seen during chronic AngII infusion hypertension is likely secondary to potassium deficiency driven by epithelial Na(+) channel stimulation.

A peer victimisation scale based on a behavioural consequences measurement strategy.

INTRODUCTION: An accurate assessment of peer victimisation (i.e. bullying) is a necessary precondition for research and intervention. Most assessment instruments use the 'list of acts' measurement strategy, which does not account for the actual physical and psychological damage inflicted by bullying. To resolve this limitation, this study developed a peer victimisation scale (PVS) that includes harmful consequences for judgement and measurement of peer victimisation. METHODS: The PVS is a 40-item self-report questionnaire designed to assess the four aspects of peer victimisation: physical, verbal, relational, and interference and control. A total of 1,469 Grade 3-8 students (49.9% male) were recruited to test the psychometric properties of the PVS. Another 420 Grade 3-8 students were examined by a modified PVS supplemented with a semi-structured interview for scale validation and establishment of the cut-off points for severe bullying. Incidence, age and gender distribution of peer victimisation were also analysed. RESULTS: The PVS demonstrated good internal consistency reliability (Cronbach's alpha 0.73-0.83) and test-retest reliability two weeks later (correlation coefficient [r] = 0.71-0.80). The scores for each dimension were significantly and positively correlated with the scores from the questionnaire-interview sample (r = 0.73-0.78), and modestly correlated with the scores for symptoms of anxiety and depression (r = 0.36-0.54). CONCLUSION: The results were consistent with the measurement constructs, demonstrating that the PVS is a reliable and effective instrument for assessing peer victimisation in children. It may enable more reliable longitudinal studies assessing the impact of peer victimisation to be conducted.

Short-term nonpressor angiotensin II infusion stimulates sodium transporters in proximal tubule and distal nephron.

In Sprague Dawley rats, 2-week angiotensin II (AngII) infusion increases Na(+) transporter abundance and activation from cortical thick ascending loop of Henle (TALH) to medullary collecting duct (CD) and raises blood pressure associated with a pressure natriuresis, accompanied by depressed Na(+) transporter abundance and activation from proximal tubule (PT) through medullary TALH. This study tests the hypothesis that early during AngII infusion, before blood pressure raises, Na(+) transporters' abundance and activation increase all along the nephron. Male Sprague Dawley rats were infused via osmotic minipumps with a subpressor dose of AngII (200 ng/kg/min) or vehicle for 3 days. Overnight urine was collected in metabolic cages and sodium transporters' abundance and phosphorylation were determined by immunoblotting homogenates of renal cortex and medulla. There were no significant differences in body weight gain, overnight urine volume, urinary Na(+) and K(+) excretion, or rate of excretion of a saline challenge between AngII and vehicle infused rats. The 3-day nonpressor AngII infusion significantly increased the abundance of PT Na(+)/H(+) exchanger 3 (NHE3), cortical TALH Na-K-2Cl cotransporter 2 (NKCC2), distal convoluted tubule (DCT) Na-Cl cotransporter (NCC), and cortical CD ENaC subunits. Additionally, phosphorylation of cortical NKCC2, NCC, and STE20/SPS1-related proline-alanine-rich kinase (SPAK) were increased; medullary NKCC2 and SPAK were not altered. In conclusion, 3-day AngII infusion provokes PT NHE3 accumulation as well as NKCC2, NCC, and SPAK accumulation and activation in a prehypertensive phase before evidence for intrarenal angiotensinogen accumulation.

Salt Sensitivity in Response to Renal Injury Requires Renal Angiotensin-Converting Enzyme.

Recent evidence indicates that salt-sensitive hypertension can result from a subclinical injury that impairs the kidneys' capacity to properly respond to a high-salt diet. However, how this occurs is not well understood. Here, we showed that although previously salt-resistant wild-type mice became salt sensitive after the induction of renal injury with the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester hydrochloride; mice lacking renal angiotensin-converting enzyme, exposed to the same insult, did not become hypertensive when faced with a sodium load. This is because the activity of renal angiotensin-converting enzyme plays a critical role in (1) augmenting the local pool of angiotensin II and (2) the establishment of the antinatriuretic state via modulation of glomerular filtration rate and sodium tubular transport. Thus, this study demonstrates that the presence of renal angiotensin-converting enzyme plays a pivotal role in the development of salt sensitivity in response to renal injury.

D-cycloserine augmentation in behavioral therapy for obsessive-compulsive disorder: a meta-analysis.

OBJECTIVE: To evaluate the overall effect of D-cycloserine (DCS) augmentation on exposure and response prevention (ERP) therapy for obsessive-compulsive disorder (OCD). METHODS: Clinical studies on the effect of DCS augmentation on ERP therapy for OCD compared to placebo were included for meta analysis. The primary outcome was the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Meta-analyses were performed with a random-effect model or a fixed-effect model using the Cochrane Review Manager (RevMan, version 5.2) to calculate the odds ratio and the mean difference, with their corresponding 95% confidence intervals. RESULTS: A total of six studies was included in the current meta-analyses, and their data were extracted. Among them, four were for analyses of DCS and Y-BOCS at midtreatment, six for analysis at posttreatment, and four at 3-month follow-up. Besides, three of the six eligible studies were included in the meta-analysis of the DCS and Clinical Global Impression-Severity Scale at posttreatment, and three in the meta-analysis of DCS and proportions of treatment responders and of subjects attaining clinical remission status criteria at posttreatment. Our meta-analyses do not reveal a significant effect of DCS augmentation in ERP therapy for OCD patients, except when measured at midtreatment. Compared to the placebo group, DCS augmentation did show a trend toward significantly lower/decreased Y-BOCS; when measured at posttreatment and in the subpopulation of DCS taken before some of the ERP sessions, DCS augmentation showed a trend toward significantly lower/decreased Y-BOCS. CONCLUSION: Our result suggested that with the careful optimization of DCS-augmented ERP therapy by fine-tuning timing and dosing of DCS administration and number and frequency of ERP sessions, DCS may enhance the efficacy of ERP therapy in reducing the symptomatic severity of OCD patients, especially at early stage of the treatment; therefore, DCS augmentation could possibly reduce treatment cost, reduce treatment drop and refusal rate, and help to improve access to the limited number of experienced therapists.

Clinical predictors of familial depression in Han Chinese women.

BACKGROUND: A number of clinical features potentially reflect an individual's familial vulnerability to major depression (MD), including early age at onset, recurrence, impairment, episode duration, and the number and pattern of depressive symptoms. However, these results are drawn from studies that have exclusively examined individuals from a European ethnic background. We investigated which clinical features of depressive illness index familial vulnerability in Han Chinese females with MD. METHODS: We used lifetime MD and associated clinical features assessed at personal interview in 1,970 Han Chinese women with DSM-IV MD between 30-60 years of age. Odds Ratios were calculated by logistic regression. RESULTS: Individuals with a high familial risk for MD are characterized by severe episodes of MD without known precipitants (such as stress life events) and are less likely to feel irritable/angry or anxious/nervous. CONCLUSIONS: The association between family history of MD and the lack of a precipitating stressor, traditionally a characteristic of endogenous or biological depression, may reflect the association seen in other samples between recurrent MD and a positive family history. The symptomatic associations we have seen may reflect a familial predisposition to other dimensions of psychopathology, such as externalizing disorders or anxiety states.