OBJECTIVES: To investigate the protective mechanism of quercetin, the core component of Zuo Gui Wan, against Alzheimer's disease through the PI3K/AKT signaling pathway, based on network pharmacology, molecular docking, and cell experi-ments. METHODS: The active components of Zuo Gui Wan were identified by searching TCMSP, PubChem, Swiss Target Prediction, and BATMAN-TCM databases, and their potential targets were predicted. The target information was standardized using Uniprot, and Alzheimer's disease-related target genes were obtained from Drugbank, GeneCards, and OMIM. The intersection of these datasets was used to identify the potential targets of Zuo Gui Wan for treating Alzheimer's disease. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The protein-protein interaction (PPI) network of potential targets was visualized using Cytoscape 3.10.1 software and the STRING database. The key active compounds and core potential targets for treating Alzheimer's disease with Zuo Gui Wan were identified through calculation. Based on the enrichment analysis results and literature, quercetin and the PI3K/AKT pathway were selected for verification. Molecular docking and binding ability prediction between quercetin and the core target AKT were performed using CB-Dock2, and visualization was conducted with AutoDock and PyMOL software. Finally, Aβ_1-42-induced HT-22 mouse hippocampal neuronal cells were used to construct an Alzheimer's disease cell model. Quercetin, the PI3K inhibitor LY294002, and the activator EGF were used as interventions. The groups were divided as follows: Control, Aβ_1-42, Aβ_1-42+Quercetin 2.5 μM, Aβ_1-42+Quercetin 5 μM, Aβ_1-42+Quercetin 10 μM, Aβ_1-42+EGF, and the PI3K/AKT modulation group: Control, LY294002, LY294002+Quercetin 10 μM, LY294002+EGF. CCK-8 assays were performed to detect cell viability, while JC-1, Calcein AM-PI, and Hoechst staining were used to assess cell apoptosis. Western blotting was employed to detect the expression of relevant target proteins. RESULTS: Network pharmacology and cell experiments collectively demonstrate that the key active ingredient of Zuo Gui Wan, quercetin, targets core proteins such as AKT1 and GSK3β through a network-based approach, significantly enriching the PI3K/AKT pathway. Molecular docking results indicate that quercetin has a strong binding affinity with AKT. Experimental validation in the Aβ_1-42 oligomer-induced HT-22 model reveals that quercetin significantly activates the PI3K/AKT signaling pathway, which is inhibited by Aβ_1-42 oligomers, as well as Bcl-2 protein expression. It also suppresses the expression of Cleaved Caspase 3/Caspase 3, BAX, and Cytochrome C proteins. JC-1, Hoechst 33342, and Calcein AM-PI staining results further show that quercetin can significantly alleviate apoptosis induced by Aβ_1-42 oligomers in HT-22 cells. Treatment with the PI3K inhibitor LY294002 in HT-22 cells leads to reduced cell viability and decreased expression of p-AKT/AKT and Bcl-2 proteins, while increasing the expression of Cleaved Caspase 3/Caspase 3, BAX, and Cytochrome C proteins. Additionally, apoptosis levels increase as observed in JC-1, Hoechst 33342, and Calcein AM-PI staining, all of which can be reversed by quercetin and the PI3K agonist EGF. CONCLUSIONS Quercetin, the key active ingredient of Zuo Gui Wan, exerts its protective effects against Alzheimer's disease by regulating the PI3K/AKT signaling pathway, inhibiting neuronal cell damage and apoptosis.

Marine work environment is associated with unique risk factors,such as high salinity,high humidity,noise and vibration,and chemical pollution.Males make up the majority of marine workers.Prolonged exposure to these environmental factors may have adverse effects on male fertility,resulting in sperm quality reduction,endocrine disorder,and reproductive organ damage.Therefore,the potential harm of marine work environment to male reproductive health deserves attention.This review focused on the key exposure factors in marine work environment,and systematically explored the factors affecting male fertility,mechanisms,and physiological pathways.The aim is to provide scientific evidences to improve marine work environment,develop protective measures,and safeguard the reproductive health of workers,while also offering guidance for future research in this field.

Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.

Platinum-based chemotherapy is used for non-small cell lung cancer (NSCLC). However, it has side effects and minimum efficacy against lung cancer metastasis. In this study, platinum-curcumin complexes were loaded into pH and redox dual-responsive nanoparticles (denoted as Pt-CUR@PSPPN) to facilitate intracellular release and synergistic anti-cancer effects. Pt-CUR@PSPPN was prepared by a nano-precipitation method and had a diameter of ∼100 nm. The nanoparticles showed increased anti-cancer effects both and . In addition, Pt-CUR@PSPPN blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2, resulting in enhanced anti-metastatic activity. Furthermore, reduced side effects were also observed. In conclusion, Pt-CUR@PSPPN provided a novel and attractive therapeutic strategy for NSCLC.

Objective To investigate the expression and significance of inducible nitric oxide synthase (iNOS), platelet-derived growth factor (PDGF)-B and lipopolysaccharide (LPS) in rat models with Budd-Chiari syndrome (BCS) . Methods BCS model was established by partial ligation of inferior vena cava in the posterior segment of the liver. The experimental rats were divided into control group (n=20), model group (n=20) and sham group (n=20) . Liver tissues were collected for immunohistochemistry, HE and Masson staining, and the expression levels of iNOS, PDGF-B and LPS were determined. Results The LPS value in model group was higher than that in both control group and sham group (P=0.001) . The mRNA and protein expressions of iNOS and PDGF-B in model group were higher than those in both control group and sham group (P=0.001) . Statistically significant differences in mRNA and protein expressions of iNOS and PDGF-B existed between each other among the subgroups (P=0.001) . In model group iNOS was positively correlated with PDGF-B and LPS; liver fibrosis was positively correlated with LPS and negatively correlated with PDGFB. Conclusion The damage and repair of BCS is a complicated process. The iNOS, PDGF-B and LPS may play different roles in different stages of BCS. How to regulate their balance in liver fibrosis may be a direction that deserves further study.

OBJECTIVETo evaluate the diagnostic value of dynamic monitoring of C-reactive protein (CRP) in drainage fluid in predicting early anastomotic leakage after colorectal surgery.

METHODSThis study enrolled 172 patients, who were diagnosed as colorectal cancer before operation and underwent radical surgery, without residual tumor tissues by postoperative pathology and perioperative infection, at the Tianjin Medical University Cancer Hospital between July 2015 and January 2016. The C-reactive(CRP) protein level in drainage fluid was continuously monitored from postoperative days (POD) 1 to 5. CRP level was compared between anastomotic leakage (AL) group and non-anastomotic leakage (NAL) group. Receiver operating characteristics (ROC) curve was used to estimate the value of monitoring CRP in drainage fluid to predict anastomotic leakage after colorectal surgery.

RESULTSAmong 172 patients, 101 cases were male and 71 cases were female, with age of (59.9±10.3) years. Anastomotic leakage occurred after colorectal surgery in 24 cases(14.0%, AL group ) and other 148 cases were defined as NAL group. Other than body mass index (BMI), differences in baseline data were not statistically significant between two groups. The CRP lever in AL group and NAL group showed rising trend from POD1 to POD4 [Day 1: (6.7±8.4) g/L vs. (8.0±10.6) g/L; Day 2: (24.8±14.6) g/L vs. (28.3±21.1) g/L, Day 3: (54.8±26.5) g/L vs. (53.8±27.6)g/L, Day 4: (62.0±32.2) g/L vs. (58.4±30.7) g/L], while the differences were not significant (all P>0.05). At POD 5, the CRP lever of AL group increased continuously, while that of NAL group decreased with significant difference [(65.3±38.9) g/L vs. (44.7±39.5) g/L, t=-2.85, P=0.005]. Further stratification analysis on AL group revealed CRP level in early AL (AL occurrence POD 10) showed rising trend from POD 1 to 4, then decreased slightly at POD 5, but whose differences were not significant (all P>0.05). ROC curve was drawn with AL condition as state variables and CRP level as test variables. The AUC of POD 1 to 4 was 0.425, 0.487, 0.510, 0.522 respectively and the AUC of POD 5 was the largest, 0.657 (95%CI:0.537-0.777). The largest Youden Index was 0.274. The critical value of CRP was 27.15 g/L. When this value was used as the point of tangency to predict the occurrence of AL, the sensitivity was 87.5%, the specificity was 39.9%, positive predictive value was 19.1%, and negative predictive value was 95.2%.

CONCLUSIONContinuous increase of CRP level in abdominal drainage fluid from POD 1 to POD 5 indicates the occurrence of AL after colorectal cancer operation, especially the detection of CRP level at POD 5 is important.