Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional proteins. Many of these proteases exhibit a similar fold and contain an essential catalytic cysteine, offering the opportunity to inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that target the active site cysteine of the 3C protease (3C^pro) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we re-purpose these hits towards the main protease (M^pro) of SARS-CoV-2 which shares the 3C-like fold and a similar active site. The hit fragments covalently link to the catalytic cysteine of M^pro to inhibit its activity. We demonstrate that targeting the active site cysteine of M^pro can have profound allosteric effects, distorting secondary structures to disrupt the active dimeric unit.

Objective: To investigate the origin of infection and risk factors of a case with SARS-CoV-2 infection associated with overseas countries in the Ningbo-Zhoushan Port, Zhejiang Province, so as to provide the evidence for improving the COVID-19 control measures at ports. Methods: Ningbo Center for Disease Control and Prevention ( CDC ) and Beilun CDC conducted case finding and epidemiological surveys immediately after being informed. The general information, history of vaccination and the travel during the latest 14 days were collected from the positive case, and all close contacts were tracked. Saliva samples were collected for SARS-CoV-2 nucleic acid testing and whole-genome sequencing, and the sequencing results were aligned with the GISAID's EpiCoV database. The origin of infection and transmission route of the positive case was investigated. Results: A case was identified positive for SARS-CoV-2 nucleic acid during company M's routine screening in the Ningbo-Zhoushan Port on August 10, 2021, and was confirmed positive for SARS-CoV-2 nucleic acid by Beilun CDC and Ningbo CDC on August 11. Whole-genome sequencing showed SARS-CoV-2 B.1.617.2 ( Delta ) variant, which shared the highest homology with the virus sequence uploaded by Russia on June, 2021 ( Russia/MOW-RII-MH27356S/2021 ). The case was a bundling worker for overseas container ships, and reported communicated with foreign boatmen and contacted materials without protected interventions on the SINOKOR AKITA Container Ship between August 4 and 5, 2021. This ship anchored at Vladivostok, Russia from July 27 to 29, anchored at Ningbo Harbor on August 4, and departed on August 5. Then, 11 boatmen from this ship were tested positive for SARS-CoV-2 nucleic acid on August 8. One asymptomatic case was reported in this epidemic; 254 close contacts and 617 secondary close contacts were identified, and all were tested negative for SARS-CoV-2 nucleic acid. No new cases with SARS-CoV-2 infections were detected until August 25, 2021, and the emergency response was therefore terminated. Conclusions The infection was a sporadic COVID-19 epidemic associated with overseas countries, which was caused by Delta variant infection through contacts with foreign boatmen or materials by a bundling worker in Ningbo-Zhoushan Port; fortunately, no epidemic spread occurred. Intensified closed-loop management and increased frequency of SARS-CoV-2 nucleic acid test among high-risk populations, and improving the precision and rapid emergency treatment of COVID-19 epidemics are required for the containment of COVID-19 at ports.

Objective: To investigate the expression of phosphoglycerate mutase 1 (PGAM1) in the mouse testis after exposure to single heat stress (SHS). METHODS: We randomly assigned 32 C57 male mice to an SHS (n = 16) and a control group (n = 16), the former bathed in water at 43 ℃ and the latter at 25 ℃ for 15 minutes. At 1 and 7 days after exposure, we harvested the testicular tissue for observation of the morphological changes of testicular cells by HE staining and determination of the location and expression of the PGAM1 protein by immunohistochemistry and Western blot. RESULTS: The testis volume of the mice were reduced significantly, the spermatogenic tubules were disorganized, and the cells were reduced in number after heat stress and basically disappeared after 7 days. Immunohistochemistry showed extensive expression of the PGAM1 protein in the testicular spermatogenic tubules of the SHS-exposed mice, significantly higher than in the control group at 1 day after exposure, which was down-regulated in the testis tissue at 7 days, but still markedly higher than that in the control. Western blot exhibited significantly up-regulated expression of the PGAM1 protein after heat stress compared with that in the control group. CONCLUSIONS The expression of the PGAM1 protein undergoes dynamic changes in the mouse testis after exposed to single heat stress, which is related to heat stress-induced proliferation and division of testicular spermatogenic cells.
Animals ; Heat-Shock Response ; Male ; Mice ; Phosphoglycerate Mutase ; Testis

Bile acids (BAs) are amphipathic molecules important for metabolism of cholesterol, absorption of lipids and lipid soluble vitamins, bile flow, and regulation of gut microbiome. There are over 30 different BA species known to exist in humans and mice, which are endogenous modulators of at least 6 different membrane or nuclear receptors. This diversity of ligands and receptors play important roles in health and disease; however, the full functions of each individual BA

This study was conducted as a pilot project to evaluate the feasibility of building an integrate dementia platform converging preexisting dementia cohorts from several variable levels. The following four cohorts were used to develop this pilot platform: 1) Clinical Research Center for Dementia of South Korea (CREDOS), 2) Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s disease (K-BASE), 3) Environmental Pollution-induced Neurological Effects (EPINEF) study, and 4) a prospective registry in Dementia Platform Korea project (DPKR). A total of 29916 patients were included in the platform with 348 integrated variables. Among participants, 13.9%, 31.5%, and 44.2% of patients had normal cognition, mild cognitive impairment, and dementia, respectively. The mean age was 72.4 years. Females accounted for 65.7% of all patients. Those with college or higher education and those without problems in reading or writing accounted for 12.3% and 46.8%, respectively. Marital status, cohabitation, family history of Parkinson’s disease, smoking and drinking status, physical activity, sleep status, and nutrition status had rates of missing information of 50% or more. Although individual cohorts were of the same domain and of high quality, we found there were several barriers to integrating individual cohorts, including variability in study variables and measurements. Although many researchers are trying to combine pre-existing cohorts, the process of integrating past data has not been easy. Therefore, it is necessary to establish a protocol with considerations for data integration at the cohort establishment stage.

This study was conducted as a pilot project to evaluate the feasibility of building an integrate dementia platform converging preexisting dementia cohorts from several variable levels. The following four cohorts were used to develop this pilot platform: 1) Clinical Research Center for Dementia of South Korea (CREDOS), 2) Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s disease (K-BASE), 3) Environmental Pollution-induced Neurological Effects (EPINEF) study, and 4) a prospective registry in Dementia Platform Korea project (DPKR). A total of 29916 patients were included in the platform with 348 integrated variables. Among participants, 13.9%, 31.5%, and 44.2% of patients had normal cognition, mild cognitive impairment, and dementia, respectively. The mean age was 72.4 years. Females accounted for 65.7% of all patients. Those with college or higher education and those without problems in reading or writing accounted for 12.3% and 46.8%, respectively. Marital status, cohabitation, family history of Parkinson’s disease, smoking and drinking status, physical activity, sleep status, and nutrition status had rates of missing information of 50% or more. Although individual cohorts were of the same domain and of high quality, we found there were several barriers to integrating individual cohorts, including variability in study variables and measurements. Although many researchers are trying to combine pre-existing cohorts, the process of integrating past data has not been easy. Therefore, it is necessary to establish a protocol with considerations for data integration at the cohort establishment stage.

Objectives: The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) was developed in 2002 and revised in 2006, 2012, 2017. In 2021, the fifth edition was published.This edition reflected new findings and the latest trends in the areas of pharmacological treatment. The aim of this study is to present strategies and treatment options according to the subtype of depression using data from the KMAP-DD-2021. Methods: Ninety-seven psychiatrists with clinical experience in depressive disorder were selected. The questionnaires for KMAP-DD 2021 were sent to participants via mail. KMAP-DD 2021 consists of overall treatment strategies and treatment options under specific circumstances.Each treatment strategy or treatment option was evaluated with an overall score of nine and was divided into the three phases of recommendation that include primary, secondary, and tertiary. Results: For persisting depressive disorder, antidepressant monotherapy including selective serotonin reuptake inhibitor (SSRI) (escitalopram, fluoxetine, sertraline, paroxetine), serotoninnorepinephrine reuptake inhibitor (SNRI) (desvenlafaxine, venlafaxine, duloxetine, milnacipran), vortioxetine, and mirtazapine, was recommended as first-line medications. For melancholia of major depressive disorder, SSRI, SNRI, vortioxetine, and mirtazapine also were recommended as first-line medications. For mixed features, SSRI, bupropion, mirtazapine, SNRI, except for duloxetine, and milnacipran were recommended as first-line medications. For anxious distress, SSRI, mirtazapine, and SNRI, except milnacipran, were recommended as first-line medications. Conclusion The preferences of antidepressants by experts differed according to the subtype of depression. These findings suggest that experts treat patients with a major depressive disorder after considering the subtype of depression involved.

Objectives: The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) was developed in 2002 and revised in 2006, 2012, 2017. In 2021, the fifth edition was published.This edition reflected new findings and the latest trends in the areas of pharmacological treatment. The aim of this study is to present strategies and treatment options according to the subtype of depression using data from the KMAP-DD-2021. Methods: Ninety-seven psychiatrists with clinical experience in depressive disorder were selected. The questionnaires for KMAP-DD 2021 were sent to participants via mail. KMAP-DD 2021 consists of overall treatment strategies and treatment options under specific circumstances.Each treatment strategy or treatment option was evaluated with an overall score of nine and was divided into the three phases of recommendation that include primary, secondary, and tertiary. Results: For persisting depressive disorder, antidepressant monotherapy including selective serotonin reuptake inhibitor (SSRI) (escitalopram, fluoxetine, sertraline, paroxetine), serotoninnorepinephrine reuptake inhibitor (SNRI) (desvenlafaxine, venlafaxine, duloxetine, milnacipran), vortioxetine, and mirtazapine, was recommended as first-line medications. For melancholia of major depressive disorder, SSRI, SNRI, vortioxetine, and mirtazapine also were recommended as first-line medications. For mixed features, SSRI, bupropion, mirtazapine, SNRI, except for duloxetine, and milnacipran were recommended as first-line medications. For anxious distress, SSRI, mirtazapine, and SNRI, except milnacipran, were recommended as first-line medications. Conclusion The preferences of antidepressants by experts differed according to the subtype of depression. These findings suggest that experts treat patients with a major depressive disorder after considering the subtype of depression involved.

Objective: To explore the reliability and validity of the Chinese Pediatric Quality of Life Inventory（PedsQL）in influenza children. Methods: From January 2017 to February 2018,we selected laboratory-diagnosed influenza cases and healthy children according to age and gender ratio by stratified random sampling and systematic sampling method. We employed Chinese version of PedsQL 4.0 to investigate their quality of life,used Cronbach's α to evaluate the reliability,and used Pearson correlation coefficient, t-test,confirmatory factor analysis（CFA）and ROC curve to evaluate the validity. Results: Totally 300 influenza cases and 300 healthy children were surveyed,with 294（98.00%）and 295（98.33%）valid questionnaires recovered. The general Cronbach's α was 0.89,and the Cronbach's α of each dimension ranged from 0.79 to 0.84. The Pearson correlation coefficients between the items and their belonged dimension ranged from 0.537 to 0.755,between the items and other dimension ranged from 0.203 to 0.384. The CFA resulted in RMSEA of 0.06,GFI of 0.88,AGFI of 0.90,CFI of 0.91 and NFI of 0.89. The scores in total and in all the dimensions in influenza cases were significantly different with those in healthy children（P<0.05）. Taking the scores in influenza cases as a golden standard,the area under the ROC curve was 0. 985（P<0.05）,the sensitivity was 0.92,and the specificity was 0.95. When the limit score was 82.18,the Youden index was the largest. Conclusion The Chinese version of PedsQL4.0 has good reliability and validity, which can be applied to quality of life assessment in children.