19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Aim To investigate the effects of sodium lactate(NALA)on right heart failure induced by monocrotaline(MCT)-induced pulmonary arterial hy-pertension in rats and to reveal the underlying mecha-nisms.Methods Forty male Sprague-Dawley(SD)rats were randomly allocated into four groups,with ten rats in each group,namely,MCT group,NALA group,and NALA+MCT group;the MCT and NALA+MCT groups were administered a single intraperito-neal injection of MCT at 60 mg·kg-1 to induce pul-monary hypertension,and one week later,the NALA and NALA+MCT groups received intraperitoneal in-jections of NALA at 0.1 g·kg-1(once a day,for 5 weeks),while the CON and MCT groups received e-qual volumes of physiological saline(once a day,for 5 weeks);right heart function was assessed using echo-cardiography,right ventricular and pulmonary artery remodeling were evaluated via histopathological sec-tions,and the expression levels of ANP,BNP,and in-flammatory factors were measured by ELISA,along with assessments of oxidative stress levels,Western blot detection of the expression levels of proteins in the TLR4/NF-κB signaling pathway.Results Compared to the CON group,the MCT group exhibited increased RVSP and RVHI,decreased right heart function,in-creased collagen fiber deposition,and elevated oxida-tive stress and inflammatory factor expression,and the expression levels of proteins in the TLR4/NF-κB signa-ling pathway increased(P＜0.05);compared to the MCT group,the NALA+MCT group showed reduced RVSP and RVHI,improved right heart function,atten-uated pulmonary vascular remodeling,decreased ex-pression of ANP,BNP,inflammatory factors,and H2O2,along with increased antioxidant enzyme expres-sion,and the expression levels of proteins in the TLR4/NF-κB signaling pathway decreased(P＜0.05).Conclusion NALA can inhibit right ventric-ular remodeling in rats with pulmonary hypertension,and the underlying mechanism may involve the allevia-tion of inflammatory responses and oxidative stress through the inhibition of the TLR4/NF-κB signaling pathway.

Objective:To investigate the changes of serum complement C1q/tumor necrosis factor-associated protein 3 (CTRP3) in patients with rheumatoid arthritis (RA) and its clinical significance.Methods:A total of 60 RA patients admitted to Chongming Hospital affiliated to Shanghai University of Medicine & Health Sciences (Chongming Branch of Xinhua Hospital) from January 2023 to February 2024 were collected.They were divided into a plaque group (38 cases) and a plaque free group (22 cases) according to the results of carotid intima-media thickness (cIMT) by carotid artery ultrasonography. ESR, CRP, blood lipid, HOMA-IR, RF, CCP antibody and CTRP3 levels were detected, and the relationship between CTRP3 levels and disease activity and atherosclerosis in RA patients was analyzed. The statistical analysis was carried out with independent t-test, analysis of variance, Pearson correlation analysis and logistic regression. Results:Serum CTRP3 level in RA patients was lower than that in healthy control group [(116±44)ng/ml and (184±63)ng/ml, t=-6.54, P=0.004]. The CTRP3 level in RA group with plaque was lower than that in RA group without plaque [(98±28) ng/ml and (123±38)ng/ml, t=-5.57, P=0.008]. Serum CTRP3 levels in RA patients were correlated with LDL-C ( r=-0.68, P=0.011), HOMA-IR ( r=-0.74, P=0.001), RF ( r=-0.46, P=0.042), anti-CCP antibody( r=-0.54, P=0.037), DAS28 ( r=-0.66, P=0.024) were negatively correlated with cIMT ( r=-0.76, P=0.001), and positively correlated with DMARDs duration ( r=0.51, P=0.040) and flow-mediated di latatiton ( r=0.70, P=0.004). The CTRP3 level [( OR(95% CI)=0.683(0.355, 0.807), P=0.023] was an independent correlation factor affecting cIMT. Conclusion:CTRP3 level in RA patients is significantly lower than that in healthy control group, and is negatively correlated with insulin resistance, autoantibody level and disease activity, and has a protective effect on early atherosclerosis in RA patients.

[Purpose]To analyze the causes of death and potential life loss of malignant tumors in Sichuan Province from 2017 to 2022.[Methods]Data were collected from the death information registration and management system of China Disease Prevention and Control Information System,and national cause of death monitoring sites in Sichuan Province from 2017 to 2022.SAS 9.4 and Joinpoint 4.9.1.0 software were used to calculate crude cancer mortality rate,age-standardized mortality rate by Chinese standerd population(ASMRC),annual percentage change and potential years of life lost(PYLL)and potential years of life lost rate(PYLLR).[Results]From 2017 to 2022,the crude cancer mortality rate in Sichuan Province was 169.32/105,and the ASMRC was 111.26/105.The cancer mortality rate in the general population and that stratified by sex showed an increasing trend(all P＜0.05).The top 5 causes of cancer death were lung cancer,liver cancer,esophageal cancer,gastric cancer and colorectum cancer.The mortality rates of lung cancer,colorectum can-cer,female breast cancer,pancreatic cancer,lip,oral and pharyngeal malignancies all increased(all P＜0.05).From 2017 to 2022,the PYLL caused by malignant tumors in Sichuan Province was 1 520 175.00 person-year,the PYLLR was 13.98‰.[Conclusion]In Sichuan Province,the mortali-ty rate of malignant tumors is on the rise.Lung cancer and gastrointestinal cancers are the main malignancies causing life loss.Early diagnosis and treatment of key cancers should be strengthened to reduce cancer mortality.

Objective:To investigate the effect of baicalin on Th17/Treg cell balance in autoimmune myocarditis(AM)rats and its possible mechanism.Methods:AM rats were grouped into control group,model group,low-dose baicalin group[20 mg/(kg·d)],high-dose baicalin group[100 mg/(kg·d)],and high mobility group B1(HMGB1)inhibitor group;the cardiac ultrasound diagnostic instrument was applied to detect the cardiac function of rats in each group,the cardiac mass index,hematoxylin eosin(HE)staining was applied to detect myocardial pathology,ELISA was applied to detect serum levels of cytokines such as IFN-γ,IL-4,IL-17 and TGF-β,Western blot was applied to detect the expression levels of myocardial HMGB1 and receptor for advanced glycation end product(RAGE)proteins,flow cytometry was applied to detect the proportions of Th17 and Treg cells in the spleen.Results:Com-pared with the control group,the rats in the model group showed myocarditis symptoms and diffuse inflammatory cell infiltration under the endocardium,the left ventricular end diastolic diameter(LVEDd),left ventricular end systolic diameter(LVEDs),IFN-γ,IL-4,IL-17,TGF-β,the proportion of Th17 cells and the expression levels of HMGB1 and RAGE proteins increased,the left ventricular short axis shortening fraction(FS%),ejection fraction(LVEF%),cardiac mass index,and the proportion of Treg cell decreased(P<0.05);compared with the model group,the myocardial interstitial edema and inflammatory cell infiltration were reduced in the ba-icalin low and high dose groups and HMGB1 inhibitor groups,and the proportion of LVEDd,LVEDs,serum IFN-γ and IL-17,spleen Th17 cells and the expression levels of myocardial HMGB1 and RAGE protein were decreased.FS%,LVEF%,heart mass index,IL-4,TGF-β,Treg cell proportion increased;compared with the low-dose baicalin group,the symptoms of myocarditis in the high-dose baicalin group and the HMGB1 inhibitor group were obviously improved,the LVEDd,LVEDs,IFN-γ,IL-17,the proportion of Th17 cells,and the expression levels of HMGB1 and RAGE proteins decreased,the FS%,LVEF%,cardiac mass index,IL-4,TGF-β,and the proportion of Treg cells increased(P<0.05);there was no statistically obvious difference in each index between the high-dose baicalin group and the HMGB1 inhibitor group(P>0.05).Conclusion:The protective effect of baicalin on AM rats is related to the inhibition of HMGB1/RAGE axis activation.

Objective::To systematically study the mechanisms by which Yinzhihuang (YZH), a traditional Chinese medicine, ameliorates intrahepatic cholestasis of pregnancy (ICP), a liver disorder associated with significant maternal and fetal complications.Methods::This experimental study was conducted from January 2024 to August 2024, utilizing data from public databases (Traditional Chinese Medicine Systems Pharmacology, GeneCards, Online Mendelian Inheritance in Man, DisGeNET, Proteome Xchange) alongside in vitro cell culture experiments. Network pharmacology identified active components of YZH and potential therapeutic targets for ICP. Ultra-performance liquid chromatography–mass spectrometry characterized YZH oral liquid, and its effective doses were evaluated in taurocholic acid (TCA)-induced HTR-8/SVneo cells, an in vitro ICP model. ICP-related targets were gathered from multiple databases, and hub genes were selected through bioinformatics and previously identified differentially expressed proteins. Functional annotation and pathway enrichment analyses were conducted, with validation in TCA-induced cells treated with various YZH concentrations (0.1%–5.0%) compared to controls. Molecular docking confirmed predicted interactions.Results::Using network pharmacology, 104 active compounds and 241 potential targets of YZH were identified. Integration of multiple databases yielded 1897 YZH-related therapeutic targets and 3783 ICP-associated genes. Proteomic analysis identified 227 differentially expressed proteins, from which 10 hub genes were selected; among these, APOA2, COL1A1, and ADIPOQ were significantly upregulated in ICP samples. UPLC-ESI-MS/MS detected 2022 compounds, predominantly flavonoids (25.07%, 507/2022) and phenolic acids (14.44%, 292/2022). Molecular docking demonstrated strong binding affinities between several active compounds and the hub genes. In TCA-induced HTR-8/SVneo cells, 0.5% YZH treatment significantly enhanced cell viability and modulated hub gene expression, supporting a potential multi-target mechanism.Conclusion::This study systematically explored the active components and potential targets of YZH in ICP through network pharmacology, proteomics, and in vitro validation. The findings suggest that YZH may act via the PPAR signaling pathway by modulating genes such as PPARA, PPARG, ADIPOQ, and APOA2.

Objective:To investigate the effect of early enteral nutrition on intestinal function in patients with complicated intra-abdominal infection.Methods:In this study,a prospective single-center randomized controlled trial was used to select 88 patients with severe abdominal infections in the surgical intensive care ward from January 2021 to December 2023.Among them,65 patients were eligible and were randomly divided into 33cases in the intervention group(who received early enteral nutrition),and 32cases in the control group(who did not receive early enteral nutrition).The clinical baseline characteristics of the two groups,conditions such as abdominal distension and diarrhea during enteral nutrition,intra-abdominal pressure,the time to reach the standard of complete enteral nutrition,and the indexes of pre-albumin,CRP,and leukocyte count on the third and the seventh day postoperative day were observed.The t-test was used to compare between groups for normally distributed measures.The Mann-Whitney U test was used to compare between groups for skewed measures.The χ2 test or continuity-corrected χ2 test was used to compare the count data between groups.Repeated measures data were analyzed by repeated measures ANOVA.Results:The clinical baseline characteristics of the two groups were completely matched;There were significant differences in the changes of intra-abdominal pressure over time between the two groups(Fgroup=9.665,P=0.004),There were significant differences in the changes of intra-abdominal pressure over time between the two intervention group(Ftime=64.124,P<0.001)and the control group.and the trend of intra-abdominal pressure reduction in the intervention group was more significant than that in the control group(Finteractive=3.938,P=0.023);The time required for the recovery of bowel sounds was significantly shorter in the experimental group than in the control group[(19.5±3.5)h vs(35.3±4.5)h,P<0.001,t=15.829];there was no significant difference in the frequency of abdominal distention,vomiting and aspiration between the two groups(P>0.05),and the difference in the frequency of diarrhea was statistically significant(P=0.003);The time to reach the standard of enteral nutrition in the intervention group was shorter than that in the control group[(6.3±1.2)d vs(7.4±1.5)d,P=0.002];The total hospital stay of the intervention group was significantly shorter than that of the control group[(11±3.2)d vs(14±4.1)d,P=0.007].The prealbumin(0.21±0.2,0.28±0.2)g/L,CRP(175.5±23.6,45.4±14.5)mg/L,and white blood cell count(11.7±2.9,9.1±3.5)109/L of the intervention group on the 3rd and 7th days after surgery were significantly improved compared with those of the control group(P<0.05).Conclusion:Early enteral nutrition can effectively promote the recovery of intestinal function in patients with complicated intra-abdominal infection.

Objective To investigate the protective effect of verapamil on hyperuricemia nephropathy(HN)in mice through modulating TXNIP/NLRP3 inflammasome signaling pathway.Methods Thirty-two male C57BL/6J mice(8 weeks old,weighing 18～22 g)were randomly divided into a blank control group,a model group,an allopurinol group(10 mg/kg),and a verapamil group(40 mg/kg),with 8 animals in each group.Except for the control mice,the other mice were given 10%fructose water and adenine to establish a mouse model of HN.After successful establishment of model mice,the corresponding interventions were administered to the mice of the other 3 groups for 4 consecutive weeks.The levels of serum uric acid(UA),creatinine(Cr),urea(UREA),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured.HE staining was used to assess the alterations in renal morphology and the infiltration of inflammatory cells,while Masson's staining was employed to evaluate renal fibrosis.Moreover,ELISA was employed to measure the contents of IL-1β and IL-6 in kidney tissue,while serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)were detected by colorimetric assay.Furthermore,immunohistochemical staining and Western blot analysis were conducted to examine the expression of TXNIP,NLRP3,IL-1β,MMP7,FN1,CD68,and MPO proteins in the kidney.Results Compared to the control group,HN mice exhibited increased serum UA,Cr,and UREA levels(P<0.05),renal pathological changes including renal tubular regeneration,interstitial or periglomerular fibrosis and prominent infiltration of inflammatory cells,and significantly increased renal contents of IL-1β and IL-6 and serum MDA level(P<0.05),while reduced serum SOD and GSH-Px contents(P<0.05),as well as up-regulation of kidney proteins TXNIP,NLRP3,IL-1β,CD68,MPO,FN1 and MMP7(P<0.01).Verapamil treatment notably reduced serum UA and Cr levels(P<0.01),improved kidney lesions to some extents,decreased collagen volume fraction(CVF)(P<0.01),and restored pro-inflammatory cytokines and oxidative stress markers(P<0.05)when compared with the levels in the model group.Further research found that the expression of kidney proteins TXNIP,NLRP3,IL-1β,CD68,MPO,FN1,and MMP7 was significantly down-regulated by verapamil treatment(P<0.05).Conclusion Verapamil exhibits a renal protective effect on HN mice through its anti-inflammatory,antioxidant,and antifibrotic properties,and its mechanism may be related to the inhibition of the TXNIP/NLRP3 inflammasome signaling pathway.

The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum (I. dunnianum) resulted in the isolation of five pairs of new lignans (1-5), and 7 known analogs (6-12). The separation of enantiomer mixtures 1-5 to 1a/1b-5a/5b was achieved using a chiral column with acetonitrile-water mixtures as eluents. The planar structures of 1-2 were previously undescribed, and the chiral separation and absolute configurations of 3-5 were reported for the first time. Their structures were determined through comprehensive spectroscopic data analysis [nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass (HR-ESI-MS), infrared (IR), and ultraviolet (UV)] and quantum chemistry calculations (ECD). The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide (LPS)-stimulated BV-2 cells. Compounds 1a, 3a, 3b, and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that 1a down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), COX-2, and iNOS and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of I. dunnianum.
Lignans/isolation & purification* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Molecular Structure ; Plant Extracts/pharmacology* ; Illicium/chemistry* ; Cyclooxygenase 2/immunology* ; Interleukin-6/immunology* ; Nitric Oxide/metabolism* ; Cell Line ; Tumor Necrosis Factor-alpha/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Lipopolysaccharides