The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate ⁺" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.

AIM To investigate the protective effect of Sanfeng Tongqiao Dropping Pills against house dust mite(HDM)-induced allergic asthma in mice.METHODS Compared to the intact BALB/c mice in the blank control group,the BALB/c mice randomly assigned into the model group,the dexamethasone group(0.67 mg/kg),and the low-dose,medium-dose,and high-dose Sanfeng Tongqiao Dropping Pills groups(15,30 and 60 mg/kg),were induced into acute allergic asthma models via weekly intraperitoneal sensitization with 0.1 mL HDM solution(0.5 mg/mL)for three weeks followed by three consecutive daily intranasal challenges with 10 μL HDM solution(2.5 mg/mL)starting in the third week.The drug administered continuously 7 days after the last excitation.The mice had their airway reactive Penh value detected,their pulmonary pathological changes observed by HE staining,their blood eosinophils(EOS)counted,their Th2 cytokines in lung tissue and serum IgE levels detected by ELISA,and their number of peripheral blood mononuclear cells(PBMC)and pulmonary Th2 cells detected by flow cytometry.Chronic allergic asthma was induced in grouped BALB/c mice through repeated intranasal challenges with 10 μL HDM solution(2.5 mg/mL)administered five times weekly for five consecutive weeks.Drug treatment continued for 14 days following the final challenge.After the final treatment,the mice had their pulmonary pathological changes observed by HE staining,and their levels of Th2 cytokines in B ALF and lung tissue and serum IgE detected by ELISA.RESULTS Compared to the blank control group,the acute allergic asthma model group exhibited increases in Penh value,EOS count and IgE level in serum,IL-4 and IL-5 levels in lung tissue(P＜0.01);obvious pulmonary inflammatory cells infiltration,and thickened airway wall;and increase in pulmonary number of Th2 cells(P＜0.01).Compared to the model group,the groups intervened with Sanfeng Tongqiao Dropping Pills demonstrated decreased Penh value,serum EOS count,IgE level and IL-5 level in lung tissue(P＜0.05,P＜0.01);reduced pulmonary inflammatory infiltration and alleviated airway wall thickening;and decreased number of pulmonary Th2 cells.Compared to the blank group,the chronic allergic asthma model group showed obvious pulmonary inflammatory infiltration and airway wall thickening;and increased EOS count and IgE level in serum,IL-4 and IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).Compared to the model group,the groups intervened with either medium-dose or high-dose Sanfeng Tongqiao Dropping Pills demonstrated reduced pulmonary inflammatory infiltration;and decreased serum EOS count,IgE level,IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).CONCLUSION Sanfeng Tongqiao Dropping Pills reduce Th2 cells in peripheral blood and lung tissue,suppress type 2 inflammation,and thereby alleviate allergic asthma.

A pyrene-phenol-based fluorescent probe PyP which showed typical intramolecular charge transfer(ICT)and monomer-excimer activities was synthesized by using pyrene carboxaldehyde hydrazone and 4-tert-butyl-2,6-diformylphenol as the raw materials.The effects of solvents on PyP were studied,and the results showed that the color of protic polar solvents(Ethanol,N,N-dimethylformamide,methanol and H2O)were successfully identified.Based on the solvent polarity-regulated PyP monomer-excimer switching,the rapid and highly sensitive ratiometric probe,"Turn-off"and"Turn-on"multimodal probes were established for detection of trace water content in organic solvents(Dimethyl sulfoxide,N,N-dimethylformamide,ethanol and methanol),with detection limits(3σ/k)of 0.0021％,0.046％,0.062％and 0.024％.The method was successfully used to detect water content in dimethyl sulfoxide,N,N-dimethy lformamide,ethanol and methanol commercial organic solvents,with recoveries ranging from 97.2％to 108.0％.The developed method showed good accuracy and stability,and had good application prospect.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.