Objective To evaluate the independent and combined associations of nighttime sleep duration and midday napping duration with all-cause mortality and premature death in Chinese older adults and to examine potential sex-specific differences. Methods This longitudinal cohort study analyzed 11,054 adults aged ≥60 years from the China Health and Retirement Longitudinal Study 2018–2020. Sleep is a key factor in the health of older adults, but prior research has focused on nighttime sleep in Western populations, with limited attention to the culturally common practice of midday napping in China and no systematic analysis of sex differences. Nighttime sleep and daily midday napping durations were collected using standardized questionnaires. Two-year all-cause mortality and premature death were tracked as the primary outcomes. Cox regression, restricted cubic spline analysis, and multiple sensitivity analyses were performed. The proportional hazards assumption was verified using Schoenfeld residuals (all p > 0.05). Results After adjustment for covariates (age, sex, education level, marital status, smoking, alcohol consumption, and number of chronic diseases), daily napping ≥60 min was independently associated with a higher risk of all-cause mortality (overall hazard ratio = 1.289, p = 0.013; males: hazard ratio = 1.298, p = 0.049). The “long sleep + long nap” pattern (>8 h nighttime sleep + ≥60 min nap) was associated with the highest risk of all-cause mortality (hazard ratio = 3.048, p < 0.001). Males with 8–10 h of nighttime sleep had an elevated risk of all-cause mortality (hazard ratio = 3.095, p = 0.001), whereas females with 4–6 h of nighttime sleep had a lower risk of premature death (hazard ratio = 0.522, p = 0.039). Restricted cubic spline analysis confirmed a nonlinear U-shaped association between nighttime sleep duration and all-cause mortality. Conclusions In Chinese older adults, prolonged daily napping (≥60 min) was associated with a higher risk of mortality after adjustment for covariates. Sex-specific differences were observed, although the formal interaction test did not reach statistical significance (p = 0.112). Nighttime sleep of 6–8 h and avoiding daily napping ≥60 min may be associated with a lower risk of mortality; however, as this was an observational study, causal inference cannot be established.

Ephedra can improve chronic obstructive pulmonary disease (COPD). Pseudoephedrine (PSE) is a main active ingredients of ephedra. It has anti-inflammatory pharmacological properties. Its effect on COPD and its possible mechanism have not been elucidated. The COPD rat model was constructed by systemic cigarette smoke exposure combined with lipopolysaccharide (LPS) tracheal instillation. BEAS-2B cells were treated using cigarette smoke extract; PSE was administered for treatment. The senescence level of rat lung tissue and bronchial epithelial cells was evaluated through staining, immunofluorescence and western blot. The mitochondrial damage of rats and BEAS-2B cells was detected by transmission electron microscopy, JC-1 probe, MitoSOX Red probe and kits. In addition, the lung function indexes of rats were detected by animal lung function analysis system. Hematoxylin and eosin (HE) staining analyzed the pathological damage. Enzyme-linked immunosorbent assay (ELISA), kit and immunohistochemistry were used to evaluate inflammation and oxidative stress. Western blot detected phosphoinositide 3-kinase/ protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) axis protein. PSE significantly reduced senescent cells, apoptosis rate and P21 level in rat lung tissue and BEAS-2B cells, significantly increased the levels of zonula occludens-1 (ZO-1) and adenosine triphosphate (ATP), restored mitochondrial structure, and visible mitochondrial cristae. It also inhibited reactive oxygen species (ROS) levels and mitochondrial excessive fission. PSE also significantly improved lung function in rats, increased mean alveolar number (MAN), reduced pro-inflammatory factors, and increased superoxide dismutase (SOD) levels. PSE markedly suppressed p-p85, p-AKT and p-mTOR protein expressions. In addition, the PI3K/AKT agonist 740Y-P weakened the effect of PSE on improving COPD. PSE inhibited PI3K/AKT/mTOR axis, improved lung tissue senescence, mitochondrial dysfunction and pathological damage, and reduced airway inflammation and oxidative stress damage, thereby alleviating COPD.

Background:With the accelerating trend of population aging, increasing attention has been paid to the health status and quality of life among older adults. However, the underlying mechanisms linking pain and life satisfaction remain not fully elucidated. This research intended to explore the mediating role of sleep quality in the association between pain and life satisfaction. Methods:The present research enrolled 9481 participants aged 60 and above from wave 2020 of the China Health and Retirement Longitudinal Study (CHARLS). We employed linear regression and bootstrap methods to examine the mediating role of sleep quality in the association between pain and life satisfaction. Results:Following adjustment for confounding variables, pain was negatively associated with life satisfaction (β = -0.097, P < 0.001) and was associated with poorer sleep quality (r = -0.27, P < 0.001). The mediating effect of sleep quality accounted for 26.5% of the total effect of pain on life satisfaction, and the size of the mediating effect was a×b =-0.0077 (95% CI: -0.0089, -0.0064). Conclusion:Among Chinese older adults, pain was associated with lower life satisfaction both directly and indirectly through its association with poorer sleep quality. This finding suggests that in addressing the health challenges of an aging society, it is essential to focus not only on the management of pain itself but also on improving sleep quality among older adults, thereby potentially enhancing their overall life satisfaction.

OBJECTIVE:To develop a core outcome set (COS) for clinical trials on post COVID-19 condition (PCC), that is, what, when, and how to measure PCC. METHOD:A comprehensive collection of outcomes (including their measurement methods and phases) was launched via literature review and clinician and patient surveys. Two rounds of Delphi surveys were conducted under the predefined criteria for rating, followed by a consensus meeting to finalize the COS for PCC (COS-PCC). RESULTS:Fifty-two outcomes within 7 categories and 206 measurement methods were identified. Sixty participants from five stakeholder groups completed the first round of the Delphi survey and 41 the second. Consensus was reached among 36 representatives on four domains of respiratory, physical, neuropsychological, and health conditions, including nine core outcomes and their respective measurement methods of priority: dyspnea (modified Medical Research Council scale), cough (Leicester Cough Questionnaire), exercise capacity (6-min walk test), fatigue (Fatigue Severity Scale), pain (Numerical Rating Scale), sleeping disturbance (Pittsburgh Sleep Quality Index), anxiety (Generalized Anxiety Disorder Scale-7), depression (Patient Health Questionnaire-9), and health status (36-item Short Form Health Survey); 16 optional measurement methods achieved consensus for supplement. Measuring phases of each core outcome were prioritized by importance through short and long terms of PCC. CONCLUSIONS:The COS-PCC highlights the key PCC concerns and provides an essential outcome set for PCC assessment in clinical trials and evidence synthesis. With improving the understanding of PCC and accumulating research evidence, the COS-PCC needs to be continuously updated and improved in practice.

Background:Yinghuang Decoction is an herbal formula that is used for the treatment of sepsis. This study used network pharmacology and molecular docking methods to explore the potential mechanism of Yinghuang Decoction against sepsis. Methods:The active ingredients, target genes, and sepsis-related differentially expressed genes (DEGs) were acquired from the public database. The intersection genes were obtained, and the function enrichment analysis was performed. Next, the herbs-active ingredients-genes-disease and protein-protein interaction networks were constructed using Cytoscape v3.7.2. Subsequently, the hub genes were identified using the CytoHubba plugin. The immune cell levels were evaluated by the single-sample Gene Set Enrichment Analysis (ssGSEA). Furthermore, molecular docking was carried out. Finally, the pharmacokinetics and toxicity of active ingredients were predicted. Results:A total of 7 hub genes (ESR1, PTGS2, CACNB4, KCNMA1, GMPS, AHR, PRKCA) and 11 active ingredients were obtained. These hub genes were significantly correlated with immune cells that are significantly dysregulated in sepsis, such as immature B cells. Among them, three hub genes (CACNB4, GMPS, and PRKCA) exhibited relatively stable diagnostic performance for sepsis (AUC above 0.7). Four active ingredients, linoleic acid, palmitic acid, kaempferol, and afzelin, had good binding affinities with ESR1, PRKCA, and PTGS2, respectively. The four active ingredients met Lipinski's rule principles and were not hepatotoxic or carcinogenic. Real-time qPCR validated the expression of hub genes in sepsis patients, which could reverse after Yinghuang Decoction treatment. Conclusion:This study exhibited the multiple active ingredients and hub genes of Yinghuang Decoction against sepsis and might offer new insight for advancing its research in sepsis treatment. Due to limited sample size, the expressions of hub genes should be validated in the larger cohorts.

[This corrects the article DOI: 10.3389/fnut.2023.1285494.].

BackgroundChanges in the gut microbiota are closely related to insomnia, but the causal relationship between them is not yet clear.ObjectiveTo clarify the relationship between the gut microbiota and insomnia and provide genetic evidence for them, we conducted a two-sample Mendelian randomization study.MethodsWe used a Mendelian randomized two-way validation method to discuss the causal relationship. First, we downloaded the data of 462,341 participants relating to insomnia, and the data of 18,340 participants relating to the gut microbiota from a genome-wide association study (GWAS). Then, we used two regression models, inverse-variance weighted (IVW) and MR-Egger regression, to evaluate the relationship between exposure factors and outcomes. Finally, we took a reverse MR analysis to assess the possibility of reverse causality.ResultsThe combined results show 19 gut microbiotas to have a causal relationship with insomnia (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.01, 1.05; p=0.000 for class. Negativicutes; OR: 1.03; 95% CI: 1.01, 1.05; p=0.000 for order.Selenomonadales; OR: 1.01; 95% CI: 1.00, 1.02; p=0.003 for genus.RikenellaceaeRC9gutgroup). The results were consistent with sensitivity analyses for these bacterial traits. In reverse MR analysis, we found no statistical difference between insomnia and these gut microbiotas.ConclusionThis study can provide a new direction for the causal relationship between the gut microbiota (class.Negativicutes, order.Selenomonadales, genus.Lactococcus) and insomnia and the treatment or prevention strategies of insomnia.

Background:Sepsis is a potentially lethal organ immune dysfunction induced by infection, with the stomach being the first organ to be attacked. Emodin has anti-inflammatory and gastrointestinal functions, but its therapeutic effect on intestinal injury in sepsis remains unclear. This study sought to investigate the role of emodin in treating intestine damage brought on by sepsis. Methods:Between June 2021 and July 2023, Lipopolysaccharide (LPS) was used to stimulate human intestinal epithelial cells NCM460 to create a septic cell model, and treatment was regulated by rhodopsin. Transient receptor potential melastatin 7 (TRPM7) expression was used to check that the LPS induction conditions were acceptable. About the proliferation of the NCM460 cells, the effects of overexpressing TRPM7 and silencing TRPM7 were assessed. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide test. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 expression in the cells was detected using enzyme-linked immunosorbent assays. TRPM7 messenger RNA expression was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Western blot determined the levels of TRPM7, Bcl2-associated X (Bax), and B-cell lymphoma-2 (Bcl2) protein expression levels. The terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling (TUNEL) technique was used to measure the apoptosis rate. Results:The levels of the inflammatory factors and Bax expression in the cells and the cell apoptosis rate steadily increased as the LPS-induced concentration increased. In contrast, cell viability and the Bcl2 expression levels gradually decreased. In this study, we treated the cells with LPS at a concentration of 25 μg/mL for 12 hours. It was detected that the knockdown of TRPM7 expression decreased the effect of LPS induction, while boosting the expression of TRPM7 boosted the effectiveness. Treatment with emodin lowered TRPM7 expression, increasing cell survival, and Bcl2 expression levels while decreasing the apoptosis rate, inflammatory factors, and Bax expression levels. Conclusion:Emodin may alleviate sepsis-induced intestinal injury by down-regulating the TRPM7 gene. These findings suggest that emodin may hold promise as a therapeutic agent for treating intestinal injury in sepsis. If further validated through additional research and clinical trials, emodin or similar compounds could potentially be developed into safe and effective medications for sepsis patients.

目的 基于PI3K/AKT/NF-κB信号通路探讨英黄汤对脓毒症大鼠的保护作用.方法 2022 年 8-12 月于河北省中医药科学院附属医院动物实验室进行实验,将240 只雄性SD大鼠按随机数字表法分为假手术组、模型组、地塞米松组、英黄汤低剂量组、英黄汤中剂量组、英黄汤高剂量组,每组 40 只.每组 20 只大鼠用于观察 7d内生存率,剩余20 只大鼠造模给药72h后,通过检测凝血相关指标、肺组织湿重/干重(W/D)比值、BALF中总蛋白含量、肝肾功能相关指标,观察英黄汤的干预作用;通过HE染色观察英黄汤对肺、肝、肾组织的病理变化;通过检测血清中IL-6、IL-1β、TNF-α水平以及肺组织中IL-6、IL-1β、TNF-α基因表达,观察英黄汤对炎性因子的影响;通过Western-blot方法检测英黄汤对肺组织中PI3K/AKT/NF-κB通路的影响.结果 英黄汤中高剂量组大鼠生存率均高于地塞米松组.造模给药72h后,与假手术组相比,模型组大鼠血清中PLT、Fib含量显著降低,PT、APTT、TT时间显著延长;BALF中总蛋白含量、W/D比值、ALT、AST、SCr、BUN水平显著增加;肺、肝、肾组织病理明显损伤;血清中IL-6、IL-1β、TNF-α水平及肺组织中IL-6、IL-1β、TNF-α基因水平显著增高;p-PI3K/PI3K、p-AKT/AKT、p-P65/P65 蛋白比值均显著增高.与模型组相比,地塞米松组、英黄汤各剂量组大鼠血清中 PLT、Fib 含量显著增加(F/P = 39.161/<0.001、11.233/<0.001),PT、APTT时间显著缩短(F/P =32.933/<0.001、22.177/<0.001);BALF中总蛋白、W/D比值、ALT、AST、SCr、BUN 水平显著降低(F/P = 27.160/<0.001、29.291/<0.001、20.553/<0.001、10.567/<0.001、28.450/<0.001、11.374/<0.001);肺、肝、肾组织损伤明显改善;血清中 IL-6、IL-1β、TNF-α 水平显著降低(F/P = 26.967/<0.001、38.238/<0.001、34.333/<0.001),肺组织中 IL-6、IL-1β、TNF-α 基因表达降低;p-PI3K/PI3K、p-AKT/AKT、p-P65/P65 比值显著减小(F/P =22.826/<0.001、21.432/<0.001、83.294/<0.001).结论 英黄汤可以改善脓毒症大鼠凝血功能障碍,保护肺肝肾功能,降低炎性水平,可能与抑制PI3K/AKT/NF-κB信号通路活化有关.

AimTobacco smoke exposure and vitamin D (VD) status were both associated with insomnia. However, the combined effect of smoking and VD on insomnia has not been discussed. This study aimed to explore the role of VD in the association between tobacco smoke exposure and insomnia.MethodsData on adults were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2005–2008 for this cross-sectional study. Weighted univariate and multivariate logistic regression analyses were used to explore the associations between serum cotinine, serum VD, and insomnia. A surface diagram was drawn to reflect the effect of VD on the association between serum cotinine and insomnia. In addition, the potential regulating effect of VD in subgroups of smoking status was also performed. The evaluation index was odds ratios (ORs) with 95% confidence intervals (CIs).ResultsAmong the eligible participants, 1,766 had insomnia. After adjusting for covariates, we found that elevated serum cotinine levels were associated with higher odds of insomnia [OR = 1.55, 95% CI: (1.22, 1.97)]. However, the relationship between serum VD level and insomnia was not significant (P = 0.553). Higher serum cotinine levels were also associated with higher odds of insomnia [OR = 1.52, 95% CI: (1.17, 1.98)] when serum VD level was <75 nmol/L; however, this relationship became non-significant when serum VD concentration was elevated (P = 0.088). Additionally, the potential regulating effect of VD was also found in adults who were not smoking.ConclusionVD may play a potential regulative role in the association between tobacco smoke exposure and insomnia. Further studies are needed to clarify the causal relationships between VD, tobacco smoke exposure, and insomnia.

Sepsis is a systemic inflammatory response syndrome caused by bacteria and other pathogenic microorganisms. Every year, approximately 31.5 million patients are diagnosed with sepsis, and approximately 5.3 million patients succumb to the disease. In this study, we identified biomarkers for diagnosing sepsis analyzed the relationships between genes and Immune cells that were differentially expressed in specimens from patients with sepsis compared to normal controls. Finally, We verified its effectiveness through animal experiments. Specifically, we analyzed datasets from four microarrays(GSE11755、GSE12624、GSE28750、GSE48080) that included 106 blood specimens from patients with sepsis and 69 normal human blood samples. SVM-RFE analysis and LASSO regression model were carried out to screen possible markers. The composition of 22 immune cell components in patients with sepsis were also determined using CIBERSORT. The expression level of the biomarkers in Sepsis was examined by the use of qRT-PCR and Western Blot (WB). We identified 50 differentially expressed genes between the cohorts, including 2 significantly upregulated and 48 significantly downregulated genes, and KEGG pathway analysis identified Salmonella infection, human T cell leukemia virus 1 infection, Epstein−Barr virus infection, hepatitis B, lysosome and other pathways that were significantly enriched in blood from patients with sepsis. Ultimately, we identified COMMD9, CSF3R, and NUB1 as genes that could potentially be used as biomarkers to predict sepsis, which we confirmed by ROC analysis. Further, we identified a correlation between the expression of these three genes and immune infiltrate composition. Immune cell infiltration analysis revealed that COMMD9 was correlated with T cells regulatory (Tregs), T cells follicular helper, T cells CD8, et al. CSF3R was correlated with T cells regulatory (Tregs), T cells follicular helper, T cells CD8, et al. NUB1 was correlated with T cells regulatory (Tregs), T cells gamma delta, T cells follicular helper, et al. Taken together, our findings identify potential new diagnostic markers for sepsis that shed light on novel mechanisms of disease pathogenesis and, therefore, may offer opportunities for therapeutic intervention.

Background: The inhibitors of the Proprotein convertase subtilis kexin 9 (PCSK9) and 3-Hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) have significant cholesterol-lowering effects, and are potent agents in reducing the incidence of cardiovascular disease. Currently, some studies have reported that it is also strongly and positively associated with the incidence of sepsis. However, we doubt their relationship.Objective: We attempted to evaluate the association between PCSK9 Inhibitor and HMGCR inhibitor and sepsis by mendelian randomization (MR)method.Methods: We extracted SNPs for PCSK9 and HMGCR from the genome-wide association study (GWAS) database for European ancestry. Coronary heart disease (CHD) was used as a positive control, and we took a drug-targeted MR analysis to analyze the causal relationship between them. Finally, we performed a meta-analysis of the preliminary results. IVW method results from 5 datasets suggest that HMGCR inhibitors do not reduce the risk of sepsis. But 3 datasets suggest that HMGCR inhibitors can reduce the risk of sepsis.Results: We failed to find significant association between PCSK9 Inhibitor and HMGCR Inhibitor and sepsis. IVW method results from 8 datasets suggest that PCSK9 inhibitors do not reduce the risk of sepsis. Meta-analysis showed that PCSK9 inhibitors [I2=5%, (OR [95%] = 1.05 [0.99 to 1.12], p=0.39)] and HMGCR inhibitors[I2=74%, (OR [95%] = 0.96 [0.73 to 1.26], p<0.01)] had no significant effect on sepsis.Conclusion: This study does not support the association of PCSK9 Inhibitor and HMGCR Inhibitor with sepsis.Funding: This work was supported by the Hebei Natural Science Foundation (No.H2022423369) and the Hebei Provincial Government Funding the Training of Excellent Clinical Medical Talents and Basic Research Projects (No.2016034829).Declaration of Interest: The authors declare that there is no conflict of interest regarding the publication of this paper.

BackgroundThe negative effects of insomnia on adolescents’ development, academic performance, and quality of life place a burden on families, schools, and society. As one of the most important research directions for insomnia, adolescent insomnia has significant research value, social value, and practical significance. Unfortunately, there is no bibliometric analysis in this field of study. This study aims to analyze published articles using bibliometrics, summarize the current research progress and hot topics in this field systematically and exhaustively, and predict the future direction and trend of research.MethodsFor this study, the Web of Science Core Collection (WoSCC) database was searched between 2002 and 2022 for publications related to adolescent insomnia. The R–bibliometrix, VOSViewer, and CiteSpace software were utilized for bibliometric analysis.ResultsThis investigation included 2468 publications from 3102 institutions in 87 countries, led by China and the United States. This field of research has entered a period of rapid development since 2017. The journal with the most publications on adolescent insomnia is Sleep, which is also the most co–cited journal. American Journal of Psychology has the highest impact factor among the top 10 journals. These papers were written by 10605 authors; notably, Liu Xianchen emerged as the author with the highest frequency of publications, while Mary A. Carskadon was the most frequently co–cited author. Mental health and comorbid diseases were the main research directions in this field. “Depression,” “anxiety,” “mental health,” “COVID–19,” “stress,” “quality of life,” “heart rate variability,” and “attention–deficit hyperactivity disorder” were hot spots and trends in this field at the current moment.ConclusionThe research on adolescent insomnia has social value, research value, and research potential; its development is accelerating, and an increasing number of researchers are focusing on it. This study summarized and analyzed the development process, hot spots, and trends of adolescent insomnia research using bibliometric analysis, which identified the current hot topics in this field and predicted the development trend for the future.

IntroductionInsomnia is the most common form of sleep deprivation (SD) observed in clinics. Although there are differences between insomnia and SD, they have similar symptoms and the same animal model. Currently, there is a lack of microarray data on insomnia. Therefore, for now, we are going to apply the SD data to insomnia. Although many studies have explained the possible mechanisms associated with insomnia, no previous studies have considered the key genes associated with insomnia or the relationship between insomnia and immune cells. In this study, we analyzed the relationship between key genes and immune cells by identifying biomarkers for the diagnosis of insomnia. Next, we verified the efficacy of these biomarkers experimentally.MethodsFirst, we downloaded four microarrays (GSE11755, GSE12624, GSE28750, and GSE48080) from the Gene Expression Omnibus (GEO) database, which included data from 239 normal human blood samples and 365 blood specimens from patients with SD. Then, we analyzed two groups of differentially expressed genes (DEGs) and used Support Vector Machine Recursive Feature Elimination (SVM-RFE) analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) regression model to investigate these key genes. Next, we used CIBERSORT to investigate the composition of 22 immune cell components of key genes in SD patients. Finally, the expression levels of key biomarkers in sleep-deprived patients were examined by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsA total of 50 DEGs were identified: six genes were significantly upregulated, and 44 genes were significantly downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that Salmonella infection, NOD-like receptor (NLR) signaling pathway, Kaposi sarcoma-associated herpesvirus infection, and Th17 cell differentiation were significant. Based on machine learning, we identified C2CD2L, SPINT2, APOL3, PKNOX1, and A2M as key genes for SD; these were confirmed by receiver operating characteristic (ROC) analysis. Immune cell infiltration analysis showed that C2CD2L, SPINT2, APOL3, PKNOX1, and A2M were related in different degrees to regulatory T cells (Tregs), follicular T helper cells, CD8 cells, and other immune cells. The qRT-PCR experiments confirmed that the expression levels of C2CD2L concurred with the results derived from machine learning, but PKNOX1 and APOL3 did not.DiscussionIn summary, we identified a key gene (C2CD2L) that may facilitate the development of biomarkers for insomnia.

结合临床实践经验,从新冠病毒毒株的变异、中医对疫病的认识、中医的临床救治进行整理和思考,提出"浊毒犯络"的防疫思路,防治结合,分型论治,截断病势,以化浊解毒贯穿于治疗的始终.

Fructus gardeniae (FG) is a traditional Chinese medicine and health food for thousands of years of application throughout Chinese history and is still widely used in clinical Chinese medicine. FG has a beneficial impact on anxiety, depression, insomnia, and psychiatric disorders; however, its mechanism of action requires further investigation. This study aimed to investigate the effects and mechanisms of FG on sleep deprivation (SD)-induced anxiety-like behavior in rats. A model of SD-induced anxiety-like behavior in rats was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). This was accompanied by neuroinflammation and metabolic abnormalities in the hippocampus and disturbance of intestinal microbiota. However reduced SD-induced anxiety-like behavior and decreased levels of pro-inflammatory cytokines including TNF-α and IL-1β were observed in the hippocampus of rats after 7 days of FG intervention. In addition, metabolomic analysis demonstrated that FG was able to modulate levels of phosphatidylserine 18, Phosphatidylinositol 18, sn-glycero-3-phosphocholine, deoxyguanylic acid, xylose, betaine and other metabolites in the hippocampus. The main metabolic pathways of hippocampal metabolites after FG intervention involve carbon metabolism, glycolysis/gluconeogenesis, pentose phosphate, and glycerophospholipid metabolism. 16S rRNA sequencing illustrated that FG ameliorated the dysbiosis of gut microbiota in anxious rats, mainly increased the abundance of Muribaculaceae and Lactobacillus, and decreased the abundance of Lachnospiraceae_NK4A136_group. In addition, the correlation analysis demonstrated that there was a close relationship between hippocampal metabolites and intestinal microbiota. In conclusion, FG improved the anxiety behavior and inhibited of neuroinflammation in sleep-deprived rats, and the mechanism may be related to the FG regulation of hippocampal metabolites and intestinal microflora composition.

BACKGROUND:Lianhua Qingke (LH) tablets is an effective traditional Chinese medicine against various viral infections, especially in relieving coughing. However, its effects on COVID-19 are unknown.METHODS:To examine the therapeutic effectiveness of LH tablets in COVID-19 patients with mild and common types, a randomized, multicenter, controlled study was carried out. COVID-19 cases were randomized to undergo routine treatment with or without LH tablets (4 tablets, three times a day) for 14 days. The primary endpoints were the rate of achieving clinical symptom resolution and the corresponding time.RESULTS:There were 144 participants in the full analysis set (72 each in the LH and control groups). The LH group participants had elevated symptom alleviation rate at 14 days compared with control cases (FAS: 98.61% vs. 84.72%, p = 0.0026). In comparison with control group participants, the LH group participants had reduced median time to clinical symptom alleviation (median: 4 vs. 7 days, p < 0.0001). Higher resolution rates of coughing (98.44% vs. 84.51%, p = 0.0045) and expectoration (100% vs. 82.35%, p = 0.0268) were observed in the LH group. Times to recovery of fever (median: 2 vs. 3 days, p = 0.0007), coughing (median: 4 vs. 7 days, p < 0.0001), and expectoration (median: 3 vs. 6 days, p < 0.0001) were also notably shorter in the LH group. Moreover, the LH group had elevated improvement rates in chest computed tomography signs (FAS: 86.11% vs. 72.22%, p = 0.0402) and clinical cure at day 28 (FAS: 83.33% vs. 68.06%, p = 0.0326). However, no differences were found in the laboratory test and viral assay. Serious adverse events were not detected.CONCLUSION:These preliminary findings indicate LH tablets may be effective in symptomatic COVID-19, especially in relieving coughing. This trial was registered in Chinese Clinical Trial Registry (ChiCTR2100042069).

梅建强教授治疗围绝经期失眠重视围绝经期女性的生理特点与失眠的内在联系,认为围绝经期失眠以肾虚为本,肝郁为因,两者共同作用导致心神不宁而出现失眠,故提出补肾调肝安神法治疗围绝经期失眠,并自拟安神方治疗,疗效显著.

OBJECTIVETo analyze the rules of medication and principles of formulas for the treatment of coronavirus disease 2019 (COVID-19) using the traditional Chinese medicine inheritance support platform (V2.5).METHODSThe clinical data, including gender, age, clinical symptoms, frequency of traditional Chinese medicine medication and prescription information, of patients with COVID-19 and asymptomatic infection who were admitted to Hebei COVID-19 designated hospital supported by medical team of First Affiliated Hospital of Hebei University of Chinese Medicine from January to March 2021 were collected. The information data were input into the traditional Chinese medicine inheritance support platform (V2.5). The data mining and analysis were realized by the integrated association rules and complex entropy clustering analysis methods of the software, including the analysis of the frequency of each drug use, drug meridian, taste, and prescription rules, and the new prescriptions were developed.RESULTSA total of 564 patients (564 prescriptions) were enrolled, involving 200 Chinese herbs, including 357 cases of common COVID-19 and 207 cases of asymptomatic infection. The proportion of women with common COVID-19 was high, and the high incidence age group was 51-70 years old. There was no significant difference in gender of asymptomatic infection, and the high incidence age group was 1-20 years old. The main clinical manifestations of most patients were head heavy and cough, followed by low fever and cough with sputum, the main tongue coating and pulse pattern were similar in both types of patients. The frequency of traditional Chinese medicine used in patients with common type of COVID-19 from high to low was liquorice root (326 times), indian bread (264 times), pinellia tuber (263 times), bitter apricot seed (236 times), baical skullcap root (229 times), gypsum (205 times), agastache rugosus (201 times), dried tangerine peel (194 times), ephedra (184 times), and Chinese thorowax root (163 times), while that used by asymptomatic infection were baical skullcap root (174 times), liquorice root (142 times), medicated leaven (137 times), agastache rugosus (127 times), pinellia tuber (114 times), Chinese thorowax root (100 times), officinal magnolia bark (91 times), atractylodes rhizome (89 times), peony root (84 times), and milkvetch root (83 times). The two types of patients were mainly treated with warm, cold and flat drugs, and the nature and taste were mainly pungent, bitter and sweet. The meridian tropism of drugs was mainly lung, spleen and stomach. High frequency drug formulation mainly included drugs for resolving turbidity and detoxification. At the same time, seven new prescriptions for common COVID-19 and four new prescriptions for asymptomatic infection were developed.CONCLUSIONSThe primary reason for the COVID-19 occurrence and development is turbidity-toxin and the qi of plague, and resolving turbidity and detoxication are the basic treating principle. On the basis, for patients with common COVID-19, symptomatic treatment such as relieving exterior syndrome, clearing heat, resolving phlegm, and antitussive drugs should be taken into account at the same time, while the treatment of asymptomatic infections should focus more on supporting the body and eliminating the harmful pathogens.

Objective: The Chinese herbal formula Huo-Xiang-Zheng-Qi (HXZQ) is effective in preventing and treating coronavirus disease 19 (COVID-19) infection; however, its mechanism remains unclear. This study used network pharmacology and molecular docking techniques to investigate the mechanism of action of HXZQ in preventing and treating COVID-19. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to search for the active ingredients and targets of the 10 traditional Chinese medicines (TCMs) of HXZQ prescription (HXZQP). GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledge Base (PharmGKB), Therapeutic Target Database (TTD), and DrugBank databases were used to screen COVID-19-related genes and intersect them with the targets of HXZQP to obtain the drug efficacy targets. Cytoscape 3.8 software was used to construct the drug-active ingredient–target interaction network of HXZQP and perform protein–protein interaction (PPI) network construction and topology analysis. R software was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, AutoDock Vina was utilized for molecular docking of the active ingredients of TCM and drug target proteins. Results: A total of 151 active ingredients and 250 HXZQP targets were identified. Among these, 136 active ingredients and 67 targets of HXZQP were found to be involved in the prevention and treatment of COVID-19. The core proteins identified in the PPI network were MAPK1, MAPK3, MAPK8, MAPK14, STAT3, and PTGS2. Using GO and KEGG pathway enrichment analysis, HXZQP was found to primarily participate in biological processes such as defense response to a virus, cellular response to biotic stimulus, response to lipopolysaccharide, PI3K-Akt signaling pathway, Th17 cell differentiation, HIF-1 signaling pathway, and other signaling pathways closely related to COVID-19. Molecular docking results reflected that the active ingredients of HXZQP have a reliable affinity toward EGFR, MAPK1, MAPK3, MAPK8, and STAT3 proteins. Conclusion: Our study elucidated the main targets and pathways of HXZQP in the prevention and treatment of COVID-19. The study findings provide a basis for further investigation of the pharmacological effects of HXZQP.