Ying Yu

Cognitive impairment is a major public health concern, and the liver–brain axis has attracted growing interest. Gamma-glutamyl transferase (GGT) is a serum marker of liver function, but its association with cognitive outcomes remains uncertain. We conducted a cross-species analysis. In 5xFAD mice (n = 52), we examined serum liver markers and spatial cognition using the Morris water maze. In NHANES 2011–2014 (n = 3181, aged ≥60 years), we evaluated liver markers and low cognitive performance (LCP) using multivariable logistic regression. We also performed virtual hepatic GGT1 knockout in a human liver single-cell atlas and integrated GTEx liver co-expression, transcription factor enrichment, and WGCNA analyses. In mice, GGT–cognition associations largely attenuated after strain adjustment, but a positive association with platform crossings emerged (r = 0.321, p = 0.02). In NHANES, serum GGT was inversely associated with LCP (Q4 vs. Q1 OR = 0.54, p < 0.001), with a nonlinear association and an inflection point near 19 U/L. Virtual hepatic GGT1 knockout identified eight immunoglobulin-related genes associated with SPI1 and oxidative stress-related pathways. These parallel findings are hypothesis-generating. A testable hypothesis is that lower hepatic GGT1 activity or serum GGT is associated with upregulated cholangiocyte immunoglobulin-related programs and poorer cognition.

Introduction: Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). Qifuyin is a promising herbal formula used clinically for cognitive decline, but its effects on ApoE4-associated cognitive and systemic phenotypes remain unclear. This study aimed to evaluate the effects of Qifuyin on cognitive performance in ApoE4 transgenic mice and to preliminarily explore its associations with lipid metabolism and gut microbiota alterations. Methods: Ten-month-old ApoE4 transgenic mice were treated with Qifuyin by gavage for 321 days, once daily for the first 123 days and once every two days thereafter. Cognitive function was assessed using the step-down test, novel object recognition test (NORT), and Morris water maze test (MWM). Aging- and frailty-related phenotypes were evaluated using senescence grading scores. Serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (ApoB) levels were measured to assess lipid metabolism. Gut microbiota composition and functional profiles were analyzed by 16S rRNA and metagenomic sequencing. Results: Qifuyin treatment significantly reduced error counts and prolonged latency in the stepdown test, increased the 24h preference index in the NORT, shortened escape latency, and increased platform crossings in the MWM in ApoE4 transgenic mice. High-dose Qifuyin reduced aging scores in males and in all doses in females and in the pooled dataset. Qifuyin decreased serum TG and ApoB levels, and increased serum HDL-C levels. 16S rRNA sequencing indicated that Qifuyin increased alpha diversity and shifted beta diversity toward the control profile. At the phylum level, Qifuyin altered the relative abundances of Firmicutes, Bacteroidota, Cyanobacteria, and Synergistota. At the family and genus levels, Qifuyin treatment was associated with increased abundances of Helicobacteraceae, Bacteroidaceae, Helicobacter, and Bacteroides, and a reduced abundance of Ruminococcaceae. Metagenomic annotation analysis showed altered abundances of K02003, K06147, COG1961, CBM37, and GH35-related features. Discussion: These findings suggest that Qifuyin may benefit ApoE4-associated cognitive and systemic dysfunction through its integrated effects on lipid metabolism and gut microbiota alterations. The microbiota-related changes observed in this study may provide a potential link between peripheral metabolic regulation and cognitive improvement, although their mechanistic significance requires further validation. Conclusions: Qifuyin improved cognitive performance and lipid metabolism, and was associated with alterations in gut microbiota composition in ApoE4 transgenic mice. These findings suggest that Qifuyin may exert beneficial effects on cognitive and systemic phenotypes in this model, while the biological significance of specific microbial changes warrants further investigation.

Background/Objectives: Alzheimer’s disease (AD) is characterized by amyloid-beta accumulation and neuroinflammation, yet the molecular target of Ginsenoside Rg1 remains elusive. This study aimed to elucidate the neuroprotective mechanism of Ginsenoside Rg1, specifically investigating its interaction with C-C motif chemokine receptor 3 (CCR3). Methods: We utilized 5xFAD transgenic mice and CCR3-overexpressing BV2 microglial cells. Behavioral assessments, enzyme-linked immunosorbent assays, quantitative real-time polymerase chain reaction, molecular docking, and surface plasmon resonance were employed to evaluate cognitive function and molecular pathways. Results: Ginsenoside Rg1 treatment significantly ameliorated spatial learning and memory deficits. Quantitatively, Rg1 reduced cortical amyloid-beta 1–40 levels (p < 0.05) and bound directly to CCR3 with a dissociation constant of 3.599 × 10⁻⁵ mol/L. This inhibition suppressed neuroinflammation and restored neurotrophic factors, including Brain-derived neurotrophic factor. Conclusions: CCR3 is a novel pharmacological target for Ginsenoside Rg1, providing a precise molecular basis for its neuroprotective effects. Future research should focus on clarifying the pharmacokinetic profile and brain bioavailability of Ginsenoside Rg1 to facilitate clinical translation.

With the rapid aging of the global population, the incidence of cognitive dysfunction is on the rise. The efficacy of existing clinical medications has been less than satisfactory, leading researchers to explore traditional medicinal practices. Tibetan medicine, a vital segment of traditional medicine, has been extensively utilized for the treatment of mental, psychological, and neurological conditions. Modern clinical and experimental pharmacological studies have shown that Rhodiola L., Terminalia chebula Retz., Sibiraea laevigata (L.) Maxim., Centella asiatica (L.) Urban, Gymnadeniaconopsea (L.) R. Br., Crocus sativus L., Ganoderma lucidum (Curtis) P. Karst., Seventy Flavor Pearl Pills, Twenty-Five Flavor Coral Pills, Ruyi Treasure Pills, and Twenty-Five Flavor Pearl Pills have effects on improving cognitive dysfunction. This review meticulously examines the research progress on these Tibetan medicinal substances for their role in mitigating cognitive dysfunction, with the goal of providing valuable insights for the development of novel therapeutic approaches to cognitive deterioration.

Background: Shugan Jieyu Capsule (SJC) is a pure Chinese medicine compound prepared with Hypericum perforatum and Acanthopanacis senticosi. SJC has been approved for the clinical treatment of depression, but the mechanism of action is still unclear. Objective: Network pharmacology, molecular docking, and molecular dynamics simulation (MDS) were applied in the present study to explore the potential mechanism of SJC in the treatment of depression. Methods: TCMSP, BATMAN-TCM, and HERB databases were used, and related literature was reviewed to screen the effective active ingredients of Hypericum perforatum and Acanthopanacis Senticosi. TCMSP, BATMAN-TCM, HERB, and STITCH databases were used to predict the potential targets of effective active ingredients. GeneCards database, DisGeNET database, and GEO data set were used to obtain depression targets and clarify the intersection targets of SJC and depression. STRING database and Cytoscape software were used to build a protein-protein interaction (PPI) network of intersection targets and screen the core targets. The enrichment analysis on the intersection targets was conducted. Then the receiver operator characteristic (ROC) curve was constructed to verify the core targets. The pharmacokinetic characteristics of core active ingredients were predicted by SwissADME and pkCSM. Molecular docking was performed to verify the docking activity of the core active ingredients and core targets, and molecular dynamics simulations were performed to evaluate the accuracy of the docking complex. Results: We obtained 15 active ingredients and 308 potential drug targets with quercetin, kaempferol, luteolin, and hyperforin as the core active ingredients. We obtained 3598 targets of depression and 193 intersection targets of SJC and depression. A total of 9 core targets (AKT1, TNF, IL6, IL1B, VEGFA, JUN, CASP3, MAPK3, PTGS2) were screened with Cytoscape 3.8.2 software. A total of 442 GO entries and 165 KEGG pathways (p <0.01) were obtained from the enrichment analysis of the intersection targets, mainly enriched in IL-17, TNF, and MAPK signaling pathways. The pharmacokinetic characteristics of the 4 core active ingredients indicated that they could play a role in SJC antidepressants with fewer side effects. Molecular docking showed that the 4 core active components could effectively bind to the 8 core targets (AKT1, TNF, IL6, IL1B, VEGFA, JUN, CASP3, MAPK3, PTGS2), which were related to depression by the ROC curve. MDS showed that the docking complex was stable. Conclusion: SJC may treat depression by using active ingredients such as quercetin, kaempferol, luteolin, and hyperforin to regulate targets such as PTGS2 and CASP3 and signaling pathways such as IL-17, TNF, and MAPK, and participate in immune inflammation, oxidative stress, apoptosis, neurogenesis, etc.

Background: Patients with gastric cancer (GC) are more likely to be infected with 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the prognosis is worse. It is urgent to find effective treatment methods. Objective: This study aimed to explore the potential targets and mechanism of ursolic acid (UA) on GC and COVID-19 by network pharmacology and bioinformatics analysis. Methods: The online public database and weighted co-expression gene network analysis (WGCNA) were used to screen the clinical related targets of GC. COVID-19-related targets were retrieved from online public databases. Then, a clinicopathological analysis was performed on GC and COVID-19 intersection genes. Following that, the related targets of UA and the intersection targets of UA and GC/COVID-19 were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome Analysis (KEGG) pathway enrichment analyses were performed on the intersection targets. Core targets were screened using a constructed protein-protein interaction network. Finally, molecular docking and molecular dynamics simulation (MDS) of UA and core targets were performed to verify the accuracy of the prediction results. Results: A total of 347 GC/COVID-19-related genes were obtained. The clinical features of GC/COVID-19 patients were revealed using clinicopathological analysis. Three potential biomarkers (TRIM25, CD59, MAPK14) associated with the clinical prognosis of GC/COVID-19 were identified. A total of 32 intersection targets of UA and GC/COVID-19 were obtained. The intersection targets were primarily enriched in FoxO, PI3K/Akt, and ErbB signaling pathways. HSP90AA1, CTNNB1, MTOR, SIRT1, MAPK1, MAPK14, PARP1, MAP2K1, HSPA8, EZH2, PTPN11, and CDK2 were identified as core targets. Molecular docking revealed that UA strongly binds to its core targets. The MDS results revealed that UA stabilizes the protein-ligand complexes of PARP1, MAPK14, and ACE2. Conclusion: This study found that in patients with gastric cancer and COVID-19, UA may bind to ACE2, regulate core targets such as PARP1 and MAPK14, and the PI3K/Akt signaling pathway, and participate in antiinflammatory, anti-oxidation, anti-virus, and immune regulation to exert therapeutic effects.

Background. In recent years, traditional Chinese exercises (TCEs) have been gradually used to reduce the blood pressure levels of patients with essential hypertension. However, there are several types of TCEs, and there is no comparative study on the antihypertensive effects of various TCEs in patients with essential hypertension. Objective. The objective is to compare the therapeutic effects of Taijiquan (TJQ), Baduanjin (BDJ), Wuqinxi (WQX), and Yijinjing (YJJ) on essential hypertension and provide a reference for clinical treatment and scheme optimization. Methods. The China National Knowledge Infrastructure (CNKI), Wanfang, China Scientific Journal Database, China Biology Medicine database (CBM), PubMed, Embase, Cochrane Library, and Web of Science databases were searched to collect all randomized controlled trials (RCTs) of TCEs in the treatment of essential hypertension. The search time was from the establishment of each database to November 2021. After data extraction and quality evaluation, the network meta-analysis was performed with Stata 16.0 and ADDIS 1.16.8. Results. Finally, 45 RCTs involving 3864 patients were included. Network meta-analysis showed that YJJ had the best effect in reducing systolic blood pressure, and the difference was statistically significant [MD = −14.27, 95% CI = (−20.53∼−8.08), ]. The best probability ranking was YJJ ( ) > TJQ ( ) > WQX ( ) > BDJ ( ). In terms of reducing diastolic blood pressure, the treatment effect of YJJ was the best, and the difference was statistically significant [MD = −7.77, 95% CI (−12.19∼−3.33), ]. The best probability ranking was YJJ ( ) > TJQ ( ) > WQX ( ) > BDJ ( ). Conclusion. The results showed that TCEs significantly reduced systolic and diastolic blood pressure compared with the control group, and YJJ might be the best choice. However, a larger sample, multicenter, double-blinded, high-quality RCTs are needed to make clear conclusions.

Background:: Traditional Chinese medicine has accumulated rich resources and experience through clinical research to explore the prevention and treatment of chronic cerebral circulatory insufficiency, but current medicine lacks in-depth research and confirmation on the established protocols and mechanism of prescribed TCMs at the macro and micro levels. Objective:: To explore the prescription of Chinese medicines for the treatment of chronic cerebral circulation insufficiency (CCCI) and to explore the mechanism of core drugs. Methods:: 229 Chinese prescriptions for CCCI were collected from CNKI, CBM, VIP and WANFANG databases for this study. The frequency and association rules of drugs were analyzed and the core drugs by TCMISSV2.5 software was extracted. The active ingredients and targets were obtained by TCMSP, and genes of CCCI were collected from the DisGeNET, OMIM, DrugBank disease databases. The intersection targets of herbal medicine and disease were imported into the STRING database for PPI network. The key targets were screened by the network topology algorithm. The Systems Dock website was used to verify the molecular docking. The GOEAST and DAVID tools were used to perform GO and KEGG pathway analysis with the key target genes. Results:: 117 drugs involved in 229 prescriptions were identified, 2 core drugs were identified. We identified 8 active ingredients, which were mandenol, myricanone, perlolyrine, senkyunone, wallichilide, sitosterol, beta-sitosterol and stigmasterol. 371 herbal targets predicted and 335 disease targets. The enrichment analysis showed that the core herbal medicines could prevent CCCI by 15 key signaling pathways. Conclusion:: There are direct or indirect connections in key signaling pathways, which not only participate in energy metabolism, hormone regulation, signal transduction, but also play a role in the comprehensive intervention of nervous system, immune system, circulatory system and other systems, which is consistent with the comprehensive pathogenesis of CCCI induced by multiple factors.

Background: Hand-foot-mouth is a viral infectious disease characterized by fever, hand foot rash and oral mucosal herpes caused by a variety of enteroviruses. It is often found in preschool children, and its immune system is not well developed, so it is very susceptible to infection by pathogens and epidemics, resulting in rapid progress of the disease. At present, the commonly used Chinese patent medicine oral liquid in our country has good clinical efficacy of antiviral, antibacterial, antiphlogistic and improving immunity, but there is no evidence to compare the clinical efficacy and safety of a variety of oral liquid of Chinese patent medicine. Therefore, this study is aim to use the network meta-analysis to integrate the clinical relevant evidence of direct and indirect comparative relationship, and to conduct quantitative comprehensive statistical analysis and sequencing after the aggregation of different Chinese patent medicine oral liquid with the same evidence body, and then the best clinical medication scheme is selected, which can provide reference value and evidence-based theoretical evidence for clinical optimization of drug selection. Methods: Comprehensive retrieval of CNKI, VIP, CBM, and WANFANG database and the Cochrane Library, PubMed, Web of Science and EMBASE database. Search and publish the clinical RCT of these 7 kinds of oral liquid of Chinese patent medicine compared with ribavirin or oral liquid of Chinese patent medicine. The retrieval time is from the establishment of the database to October 31st, 2021. The 2 first authors will screen the literatures that meets the inclusion criteria, extract the data independently according to the predesigned rules, and evaluate the literature quality and bias risk of the included research according to the Cochrane manual standard. Data merging and network meta-analysis were carried out with R programming software to evaluate the ranking probability of all interventions. Results: This network meta-analysis and probability ranking will identify the best Chinese patent medicine oral liquid treatment for Hand-foot-mouth. Conclusion: This study will provide systematic evidence-based medicine evidence for Chinese patent medicine oral liquid treatment for Hand-foot-mouth, and help clinicians, patients with poststroke depression and decision-makers to make more effective, safer and economic optimal treatment plan in the decision-making process. Registration number: INPLASY202210032. The protocol for this systematic review was registered on INPLASY and is available in full on the inplasy.com (https://inplasy.com/inplasy-2022–1-0032/).

Review question / Objective: The type of study was clinical randomized controlled trial (RCT). The object of study is the patients with HFMD. There is no limit to gender and race. In the case of clear diagnosis standard, curative effect judgment standard and consistent baseline treatment, the experimental group was treated with pure oral liquid of traditional Chinese medicine(A: Fuganlin oral liquid, B: huangzhihua oral liquid, C: Lanqin oral liquid, D: antiviral oral liquid, E: Huangqin oral liquid, F: Pudilan oral liquid, G: Shuanghuanglian oral liquid.)and the control group was treated with ribavirin or any oral liquid of traditional Chinese medicine. The data were extracted by two researchers independently, cross checked and reviewed according to the pre-determined tables. The data extraction content is (1) Basic information (including the first author, published journal and year, research topic). (2) Relevant information (including number of cases, total number of cases, gender, age, intervention measures, course of treatment of the experimental group and the control group in the literature). (3) Design type and quality evaluation information of the included literature. (4) Outcome measures (effective rate, healing time of oral ulcer, regression time of hand and foot rash, regression time of fever, adverse reactions.). The seven traditional Chinese medicine oral liquids are comparable in clinical practice, but their actual clinical efficacy is lack of evidence-based basis. Therefore, the purpose of this study is to use the network meta-analysis method to integrate the clinical relevant evidence of direct and indirect comparative relationship, to make quantitative comprehensive statistical analysis and sequencing of different oral liquid of traditional Chinese medicine with the same evidence body for the treatment of the disease, and then to explore the advantages and disadvantages of the efficacy and safety of different oral liquid of traditional Chinese medicine to get the best treatment plan, so as to provide reference value and evidence-based medicine evidence for clinical optimization of drug selection. Condition being studied: Hand foot mouth disease (HFMD) is a common infectious disease in pediatrics caused by a variety of enteroviruses. Its clinical manifestations are mainly characterized by persistent fever, hand foot rash, oral herpes, ulcers, etc. Because it is often found in preschool children, its immune system development is not perfect, so it is very vulnerable to infection by pathogens and epidemic diseases, resulting in rapid progress of the disease. A few patients will also have neurogenic pulmonary edema Meningitis, myocarditis and other serious complications even lead to death, so effectively improve the cure rate, shorten the course of disease, prevent the deterioration of the disease as the focus of the study. In recent years, traditional Chinese medicine has played an important role in the research of antiviral treatment. Many clinical practices have confirmed that oral liquid of traditional Chinese medicine can effectively play the role of antiviral and improve the body's immunity.