Effect of Keishi-bukuryo-gan on asymptomatic cerebral infarction for short term

無症候性脳梗塞患者に対する桂枝茯苓丸の効果を検討した。142例(男性32例,女性110例,平均年齢68.9才)を対象とし,副作用のため内服を中止した3例を除く139例に対して,桂枝茯苓丸エキス1日量7.5gを12週間投与した。投与開始時と比較して,改訂長谷川式簡易知能評価スケール,Apathyスケール(やる気スケール),SDS(うつ状態スケール)は有意に改善した。また,頭重感,頭痛,めまいの自覚症状も桂枝茯苓丸の投与により改善し,拡張期血圧は投与前に比べ有意に低下した。これらの結果から,桂枝茯苓丸が無症候性脳梗塞に伴う認知機能の低下,精神症状や自覚症状の悪化に対して有効である可能性が示唆された。 The efficacy of Keishi-bukuryo-gan in patients suffering from asymptomatic cerebral infarction was studied. 142 patients, 32 males and 110 females, with a mean age of 68.9 years, were enrolled and analyzed, and 139 completed the study. They were given Keishi-bukuryo-gan extract (7.5g/day) three times a day for 12 weeks. In comparison to the beginning of the study, Keishi-bukuryo-gan showed improvement with statistical significance in the mean revised version of Hasegawa\u27s dementia scale, Apathy scale and Self-rating depression scale. The number of patients with subjective symptoms as headdullness, headache and dizziness decreased by the treatment with Keishi-bukuryo-gan, and diastolic blood pressure was decreased with statistical significance as compared to the beginning of the study. These results suggest that Keishi-bukuryo-gan is effective against dysfunction of acknowledgment, emotional disorder and subjective symptoms with asymptomatic cerebral infarction

Current smoking status may be associated with overt albuminuria in female patients with type 1 diabetes mellitus: a cross-sectional study

Background There are very few clinical reports that have compared the association between cigarette smoking and microangiopathy in Asian patients with type 1 diabetes mellitus (T1DM). The objective of this study was to assess the relationships between urinary protein concentrations and smoking and gender-based risk factors among patients with T1DM. Methods A cross-sectional study of 259 patients with T1DM (men/women = 90/169; mean age, 50.7 years) who visited our hospital for more than 1 year between October 2010 and April 2011 was conducted. Participants completed a questionnaire about their smoking habits. Patient characteristics included gender, age, body mass index, blood pressure, hemoglobin A1c, lipid parameters, and microangiopathy. Diabetic nephropathy (DN) was categorized as normoalbuminuria (NA), microalbuminuria (MA), or overt albuminuria (OA) on the basis of the following urinary albumin/creatinine ratio (ACR) levels: NA, ACR levels less than 30 mg/g creatinine (Cr); MA, ACR levels between 30 and 299 mg/g Cr; and OA, ACR levels over 300 mg/g Cr. Results The percentages of current nonsmokers and current smokers with T1DM were 73.0% (n = 189) and 27.0% (n = 70), respectively. In addition, the percentage of males was higher than that of females (52.2% versus 13.6%) in the current smoking population. The percentage of DN was 61.8% (n = 160) in patients with NA, 21.6% (n = 56) in patients with MA, and 16.6% (n = 43) in patients with OA. The percentage of males among OA patients was also higher than that of females (24.4% versus 12.4%). However, current smoking status was associated with OA in females with T1DM only [unadjusted odds ratio (OR), 4.13; 95% confidence interval (CI), 1.45–11.73, P < 0.01; multivariate-adjusted OR, 5.41; 95% CI, 1.69–17.30, P < 0.01]. Conclusions Based on our results in this cross-sectional study of Asian patients with T1DM, smoking might be a risk factor for OA among female patients. Further research is needed of these gender-specific results

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements