Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Objective To explore the mechanism of Kangliu Zengxiao Jiandu Prescription(KLJD)in enhancing the efficacy of cisplatin chemotherapy in non-small cell lung cancer(NSCLC)through network pharmacology and in vivo/in vitro experiments.Methods Components of KLJD were screened via the TCMSP database to identify active components and potential targets.Lung cancer-related genes were obtained from the GeneCards and OMIM databases.GO and KEGG pathway enrichment analysis was performed on drug-disease intersection targets using the Metascape database;molecular docking was performed between core target proteins and main active components.A Lewis lung cancer mouse model was established,and intervened with KLJD and cisplatin.Organ indexes and tumor inhibition rate were counted,and Western blot and RT-PCR were used to detect the expressions of key pathway target proteins and mRNA;A549 and H1299 cells were intervened with KLJD,and Western blot was used to detect key target protein expressions.Results Network pharmacology identified 74 active components and 20 key targets of KLJD,primarily involved in biological processes such as cell proliferation and inflammatory response,and pathways in cancer and PI3K/AKT signaling pathway;molecular docking revealed stable binding between EGFR and major compounds.Animal experiments demonstrated that,compared with the model group,the KLJD group showed significantly higher tumor inhibition rate(P<0.01)and downregulation of EGFR,AKT and PI3K protein and mRNA expression in tumor tissues(P<0.05).Compared with the cisplatin group,the combination group exhibited significantly enhanced tumor inhibition rate(P<0.01),elevated thymic and splenic indices(P<0.01),and decreased EGFR,PI3K and AKT protein and mRNA expressions(P<0.01).Cell experiments showed that KLJD concentration-dependently inhibited A549 and H1299 cell proliferation(IC50:14.72 mg/mL and 14.68 mg/mL,respectively).Combined with cisplatin,KLJD synergistically down-regulated EGFR PI3K and AKT protein expressions(P<0.01).Conclusion KLJD effectively enhances cisplatin's chemotherapeutic efficacy in NSCLC by inhibiting the EGFR/PI3K/AKT pathway while improving immune organ function.Its mechanism likely involves multi-target regulation,including suppression of tumor proliferation,promotion of apoptosis,and modulation of the immune microenvironment.

The prevalence of summer endogenous fever is closely related to the climate of summer.Based on Li Dongyuan's yin-fire theory,this article proposed that summer-heat,irregular diet,excessive consumption of cold foods,poor living habits,and summer damp-heat internal invasion damaging the spleen can all lead to the generation of yin-fire,thereby causing endogenous fever.The core pathogenesis of summer endogenous fever lies in spleen deficiency with yang collapse,which results into the blockage of qi movement and the production of yin-fire.The yin-fire persists throughout the entire course of the disease.Treatment of summer endogenous fever should focus on eliminating yin-fire,primarily by addressing the spleen via boosting qi and raising yang to restore the spleen's ascending and stomach's descending functions,thereby dispersing yin-fire.Clearing heat and resolving dampness can purge yin-fire and then the spleen qi's circulation is restored.By analyzing the pathological changes of dampness accumulation into phlegm,fire-heat damaging yin and liver stagnation with kidney deficiency,the disease progression can be predicted.Correspondingly,comprehensive therapy of resolving phlegm,nourishing yin,soothing liver,and tonifying kidney can be employed to prevent further deterioration.Based on Li Dongyuan's yin-fire theory,Shengyang Yiwei Decoction(mainly composed of Astragali Radix,Pinelliae Rhizoma,Ginseng Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Angelicae Pubescentis Radix,Saposhnikoviae Radix,Paeoniae Radix Alba,Notopterygii Rhizoma et Radix,Citri Reticulatae Pericarpium,Poria,Bupleuri Radix,Alismatis Rhizoma,Atractylodis Macrocephalae Rhizoma,and Coptidis Rhizoma)can be used as a fundamental prescription to treat summer endogenous fever caused by yin-fire,with modifications tailored to specific clinical presentations.This theoretical exploration may provide a reference for the clinical management of summer endogenous fever.

Abdominal obesity represents the predominant obesity phenotype in China.Compared to peripheral obesity,individuals with abdominal obesity are more prone to metabolic disorders,cardiovascular diseases,and higher mortality rates.Catgut embedding therapy at acupoints has demonstrated significant clinical efficacy in preventing and treating abdominal obesity.However,standardized clinical guidelines for its application in abdominal obesity management have not yet been established.This review comprehensively summarizes the clinical applications of catgut embedding therapy for simple abdominal obesity and abdominal obesity with various complications,aiming to provide clinical evidence and theoretical guidance for its use in preventing and treating abdominal obesity.

Objective To discuss the prediction value of the early efficacy of hepatic arterial infusion chemotherapy(HAIC)in treating stage Ⅱ-Ⅲ hepatocellular carcinoma(HCC).Methods The clinical data of 81 patients with stage Ⅱ-Ⅲ HCC,who received at least 3 times of HAIC at the Nanchang Municipal Central Hospital of China from November 2021 to March 2024,were retrospectively analyzed.CT or MRI was used to compare patient's local tumor response after each treatment cycle.Based on modified Response Evaluation Criteria in Solid Tumors(mRECIST),the curative effects of patients after receiving the first,the second,and the last HAIC treatment were compared between each other.The prediction value of the early efficacy of HAIC in treating patients with stage Ⅱ-Ⅲ HCC was analyzed.Results In the 67 patients,the efficacy of the last time HAIC was equal or similar to that of the first time HAIC,and in the remaining 14 patients the efficacy of the last time HAIC was different from that of the first time HAIC,with an efficacy prediction rate of 82.72％.The efficacy of the last time HAIC was equal or similar to that of the second time HAIC in 71 patients,and in the remaining 10 patients the efficacy of the last time HAIC was different from that of the second time HAIC,with an efficacy prediction rate of 87.65％.Conclusion In treating stage Ⅱ-Ⅲ HCC with HAIC,the early efficacy can be used to predict the final efficacy after completion of the total treatment course.

Objective:To investigate the effects and its related mechanism of placenta-derived mesenchymal stem cells(PMSCs)on the lipopolysaccharides(LPS)damaged astrocytes.Methods:Primary astrocytes were isolated from the cerebral cortex of neonatal rats.The expression of glial fibrillary acidic protein(GFAP)was identified using immu-nofluorescence staining to evaluate the purity of the primary astrocytes.PMSCs were cocultured with LPS-treated astro-cytes.The expression levels of factors related to inflammation including interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),arginase-1(Arg-1),S100 calcium-bind-ing protein A10(S100A10),and TGF-β/Smad signaling pathway-related proteins such as transforming growth factor beta 1(TGF-β1),transforming growth factor beta type I receptor(TβRⅠ),transforming growth factor beta type II re-ceptor(TβRⅡ),phospho-Smad2 and phospho-Smad3(p-Smad2,p-Smad3)in astrocytes from each group were detec-ted using real time RT-PCR or Western blot techniques.Results:Astrocytes at the third passage exhibited an 80%pos-itivity rate for GFAP.After treated with 10 μg/ml LPS,the astrocytes expression levels of pro-inflammatory factors IL-1β,iNOS,IL-6,and TNF-α were significantly increased(P<0.05),while their expression levels of the anti-inflam-matory factors of Arg-1 and S100A10 were significantly decreased(P<0.05).Meanwhile,their expression levels of TGF-β/Smad signaling pathway related proteins of TGF-β1,TβRⅠ,TβRⅡ,p-Smad2 and Smad3 were increased(P<0.05).After the LPS damaged astrocytes were cocultured with PMSCs,their expression levels of pro-inflammatory factors IL-1β,iNOS,IL-6,and TNF-α were significantly decreased(P<0.05),while their expression levels of the anti-inflammatory factors of Arg-1 and S100A10 were significantly increased(P<0.05).Also,their expression levels of TGF-β/Smad signaling pathway related proteins of TGF-β1,TβRⅠ,TβRⅡ,p-Smad2,and Smad3 were decreased(P<0.05).Conclusion:PMSCs may inhibit the activation of A1 astrocytes through the TGF-β/Smad signaling path-way,by which reducing the astrocytic activation.

Objective:To investigate the effects and its related mechanism of placenta-derived mesenchymal stem cells(PMSCs)on the lipopolysaccharides(LPS)damaged astrocytes.Methods:Primary astrocytes were isolated from the cerebral cortex of neonatal rats.The expression of glial fibrillary acidic protein(GFAP)was identified using immu-nofluorescence staining to evaluate the purity of the primary astrocytes.PMSCs were cocultured with LPS-treated astro-cytes.The expression levels of factors related to inflammation including interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),arginase-1(Arg-1),S100 calcium-bind-ing protein A10(S100A10),and TGF-β/Smad signaling pathway-related proteins such as transforming growth factor beta 1(TGF-β1),transforming growth factor beta type I receptor(TβRⅠ),transforming growth factor beta type II re-ceptor(TβRⅡ),phospho-Smad2 and phospho-Smad3(p-Smad2,p-Smad3)in astrocytes from each group were detec-ted using real time RT-PCR or Western blot techniques.Results:Astrocytes at the third passage exhibited an 80%pos-itivity rate for GFAP.After treated with 10 μg/ml LPS,the astrocytes expression levels of pro-inflammatory factors IL-1β,iNOS,IL-6,and TNF-α were significantly increased(P<0.05),while their expression levels of the anti-inflam-matory factors of Arg-1 and S100A10 were significantly decreased(P<0.05).Meanwhile,their expression levels of TGF-β/Smad signaling pathway related proteins of TGF-β1,TβRⅠ,TβRⅡ,p-Smad2 and Smad3 were increased(P<0.05).After the LPS damaged astrocytes were cocultured with PMSCs,their expression levels of pro-inflammatory factors IL-1β,iNOS,IL-6,and TNF-α were significantly decreased(P<0.05),while their expression levels of the anti-inflammatory factors of Arg-1 and S100A10 were significantly increased(P<0.05).Also,their expression levels of TGF-β/Smad signaling pathway related proteins of TGF-β1,TβRⅠ,TβRⅡ,p-Smad2,and Smad3 were decreased(P<0.05).Conclusion:PMSCs may inhibit the activation of A1 astrocytes through the TGF-β/Smad signaling path-way,by which reducing the astrocytic activation.

Objective To investigate the lung protection effect of remazolam under lung protection ventilation strategy in elderly patients undergoing laparoscopic upper abdominal surgery.Methods A prospective randomized controlled study was conducted on 60 patients aged 60 years or older who were scheduled to undergo laparoscopic upper abdominal surgery,including cholecystectomy,common bile duct choledocholithotomy,partial hepatectomy,and subtotal gastrectomy from October 2023 to October 2024.The patients were divided into 2 groups by random number table method:30 patients in the observation group received lung protective ventilation strategy and remazolam administration,and 30 patients in the control group received lung protective ventilation strategy and propofol administration.The inflammatory response indexes(TNF-α,IL-6,and hs-CRP),stress indexes(SOD,NE,and Cor),anesthesia quality(VAS score and Ramsay score),lung function(FVC,FEV1,and MVV％),blood gas indexes(pH,Lac,PaO2,and PaCO2),recovery quality(tracheal tube extubation time,respiratory recovery time,and awakening time),and pulmonary complications were compared between the two groups.Results In the observation group,the serum levels of inflammatory markers of TNF-α,IL-6,and hs-CRP at 2,12,and 24 h postoperatively were all lower than those in the control group(all P=0.000).Regarding stress response indicators,the serum SOD levels in the observation group were higher than those in the control group at 2,12,and 24 h postoperatively,while the NE and Cor levels were lower(all P=0.000).The VAS scores at 24 h postoperatively,and the Ramsay scores at 2 and 24 h postoperatively in the observation group were lower than those in the control group(all P=0.000).In the observation group,the FVC,FEV1,and MVV％were all higher than those in the control group at 48 h postoperatively(P＜0.05).The PaO2 level in the observation group was higher than that in the control group at 24 h postoperatively,and the Lac level was lower(P＜0.05).The respiratory recovery time and awakening time in the observation group were both shorter than those in the control group(P＜0.05).There were no significant differences between the two groups in extubation time and pulmonary complications(P＞0.05).Conclusions The lung protection effect of remazolam under lung protection ventilation strategy is better than that of propofol in elderly patients undergoing laparoscopic upper abdominal surgery.The lung protective effects may be achieved by alleviating perioperative stress response,improving oxygenation function,effective sedation,and reducing inflammatory response.

Objective To investigate the lung protection effect of remazolam under lung protection ventilation strategy in elderly patients undergoing laparoscopic upper abdominal surgery.Methods A prospective randomized controlled study was conducted on 60 patients aged 60 years or older who were scheduled to undergo laparoscopic upper abdominal surgery,including cholecystectomy,common bile duct choledocholithotomy,partial hepatectomy,and subtotal gastrectomy from October 2023 to October 2024.The patients were divided into 2 groups by random number table method:30 patients in the observation group received lung protective ventilation strategy and remazolam administration,and 30 patients in the control group received lung protective ventilation strategy and propofol administration.The inflammatory response indexes(TNF-α,IL-6,and hs-CRP),stress indexes(SOD,NE,and Cor),anesthesia quality(VAS score and Ramsay score),lung function(FVC,FEV1,and MVV％),blood gas indexes(pH,Lac,PaO2,and PaCO2),recovery quality(tracheal tube extubation time,respiratory recovery time,and awakening time),and pulmonary complications were compared between the two groups.Results In the observation group,the serum levels of inflammatory markers of TNF-α,IL-6,and hs-CRP at 2,12,and 24 h postoperatively were all lower than those in the control group(all P=0.000).Regarding stress response indicators,the serum SOD levels in the observation group were higher than those in the control group at 2,12,and 24 h postoperatively,while the NE and Cor levels were lower(all P=0.000).The VAS scores at 24 h postoperatively,and the Ramsay scores at 2 and 24 h postoperatively in the observation group were lower than those in the control group(all P=0.000).In the observation group,the FVC,FEV1,and MVV％were all higher than those in the control group at 48 h postoperatively(P＜0.05).The PaO2 level in the observation group was higher than that in the control group at 24 h postoperatively,and the Lac level was lower(P＜0.05).The respiratory recovery time and awakening time in the observation group were both shorter than those in the control group(P＜0.05).There were no significant differences between the two groups in extubation time and pulmonary complications(P＞0.05).Conclusions The lung protection effect of remazolam under lung protection ventilation strategy is better than that of propofol in elderly patients undergoing laparoscopic upper abdominal surgery.The lung protective effects may be achieved by alleviating perioperative stress response,improving oxygenation function,effective sedation,and reducing inflammatory response.

Objective To explore the mechanism of Kangliu Zengxiao Jiandu Prescription(KLJD)in enhancing the efficacy of cisplatin chemotherapy in non-small cell lung cancer(NSCLC)through network pharmacology and in vivo/in vitro experiments.Methods Components of KLJD were screened via the TCMSP database to identify active components and potential targets.Lung cancer-related genes were obtained from the GeneCards and OMIM databases.GO and KEGG pathway enrichment analysis was performed on drug-disease intersection targets using the Metascape database;molecular docking was performed between core target proteins and main active components.A Lewis lung cancer mouse model was established,and intervened with KLJD and cisplatin.Organ indexes and tumor inhibition rate were counted,and Western blot and RT-PCR were used to detect the expressions of key pathway target proteins and mRNA;A549 and H1299 cells were intervened with KLJD,and Western blot was used to detect key target protein expressions.Results Network pharmacology identified 74 active components and 20 key targets of KLJD,primarily involved in biological processes such as cell proliferation and inflammatory response,and pathways in cancer and PI3K/AKT signaling pathway;molecular docking revealed stable binding between EGFR and major compounds.Animal experiments demonstrated that,compared with the model group,the KLJD group showed significantly higher tumor inhibition rate(P<0.01)and downregulation of EGFR,AKT and PI3K protein and mRNA expression in tumor tissues(P<0.05).Compared with the cisplatin group,the combination group exhibited significantly enhanced tumor inhibition rate(P<0.01),elevated thymic and splenic indices(P<0.01),and decreased EGFR,PI3K and AKT protein and mRNA expressions(P<0.01).Cell experiments showed that KLJD concentration-dependently inhibited A549 and H1299 cell proliferation(IC50:14.72 mg/mL and 14.68 mg/mL,respectively).Combined with cisplatin,KLJD synergistically down-regulated EGFR PI3K and AKT protein expressions(P<0.01).Conclusion KLJD effectively enhances cisplatin's chemotherapeutic efficacy in NSCLC by inhibiting the EGFR/PI3K/AKT pathway while improving immune organ function.Its mechanism likely involves multi-target regulation,including suppression of tumor proliferation,promotion of apoptosis,and modulation of the immune microenvironment.