ObjectiveTo investigate the mechanism by which Wumeiwan suppresses the development and progression of colorectal cancer（CRC） through the regulation of fatty acid metabolic reprogramming， thereby providing new experimental evidence for the prevention and treatment of CRC. MethodsA total of 120 C57BL/6 mice were randomly divided into the blank group， model group， Wumeiwan high-， medium-， and low-dose groups（54， 27， 13.5 g·kg^-1）， and the mesalazine group（0.01 g·kg^-1）， with 20 mice in each group. Except for the blank group， all mice were subjected to azoxymethane（AOM）/dextran sulfate sodium（DSS） treatment to establish an inflammation-associated CRC model. One week after AOM injection， mice in the treatment groups received intragastric administration of the designated drugs， while the blank and model groups received an equal volume of purified water， continuing until 20 d after the intervention endpoint. Hematoxylin-eosin（HE） staining was used to observe colonic histopathological alterations， and immunohistochemistry for vascular endothelial growth factor（VEGF） was performed to evaluate neovascularization and tumor invasion. Metabolomics combined with Kyoto Encyclopedia of Genes and Genomes（KEGG） and metabolite set enrichment analysis（MSEA） was applied to identify key CRC-related metabolic pathways， which were further validated by transcriptomic Gene Ontology（GO） enrichment and gene heatmap analysis. Subsequently， Western blot was performed to determine the expression levels of core proteins in these pathways， and immunofluorescence was used to analyze their localization and co-expression patterns in tissues， thereby elucidating the mechanism of Wumeiwan from multiple biological dimensions. ResultsCompared with the blank group， mice in the model group exhibited a significant decrease in body weight and a significant increase in the disease activity index（DAI） score（P<0.05）， with pronounced colonic mucosal damage accompanied by aggravated tumor invasion. Compared with the model group， Wumeiwan intervention markedly improved body weight loss and reduced DAI score， attenuated mucosal injury， and significantly decreased VEGF expression level（P<0.05）. Multi-omics analysis revealed that differential metabolites and genes across groups were commonly enriched in fatty acid metabolism， fatty acid biosynthesis， and other lipid-related pathways. Relative to the blank group， the model group showed significant upregulation levels of fatty acid synthesis-related genes， including sterol regulatory element-binding protein 1（SREBP1）， fatty acid synthase（FASN）， stearoyl-CoA desaturase 1（SCD1）， as well as saturated fatty acids（P<0.05）. Compared with the model group， treatment with Wumeiwan significantly reduced the expression of key genes involved in fatty acid metabolic pathways， including SREBP1， FASN， and SCD1（P<0.05）. Western blot results further confirmed that proteins in this pathway were significantly elevated in the model group， whereas they were markedly downregulated following Wumeiwan treatment（P<0.05）. Immunofluorescence analysis demonstrated enhanced co-localization of SREBP1 with the cancer-associated fibroblast（CAF） marker α-smooth muscle actin（SMA） in the model group， whereas this co-localization signal was attenuated after Wumeiwan intervention（P<0.05）. ConclusionWumeiwan can improve survival outcomes and alleviate colonic pathological damage in CRC mice， its therapeutic mechanism may be closely associated with the regulation of fatty acid metabolic reprogramming mediated by the SREBP1/FASN/SCD1 signaling pathway.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective:To analyze the effect of alprostadil on renal hemodynamic parameters in patients with severe lupus nephritis (LN) complicated with acute kidney injury (AKI).Methods:The clinical data of 130 patients with severe LN complicated with AKI from August 2020 to August 2023 in Affiliated Hospital of Jining Medical University were retrospectively analyzed. Among them, 66 patients were treated with continuous renal replacement therapy (CRRT) (CRRT group), and 64 patients were treated with CRRT combined with alprostadil (combination group). All patients of both groups were treated 10 d. The efficacy, renal function (serum creatinine, blood urea nitrogen and 24 h urinary protein quantitation), renal hemodynamic parameters and serum inflammatory factors were compared between two groups. The renal hemodynamic parameters included peak systolic velocity (PSV), resistance index (RI) and end diastolic velocity (EDV)), serum inflammatory factors (procalcitonin (PCT); and the inflammatory factor included procalcitonin (PCT), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).Results:The total effective rate in combination group was significantly higher than that in CRRT group: 96.88% (62/64) vs. 81.82% (54/66), and there was statistical difference ( χ2 = 7.67, P<0.01). There were no statistical difference in the indexes before treatment between two groups ( P>0.05). The serum creatinine, blood urea nitrogen, 24 h urinary protein quantitation, RI, PCT, TNF-α and IL-6 after treatment in combination group were significantly lower than those in CRRT group: (82.16 ± 16.66) μmol/L vs. (128.55 ± 21.06) μmol/L, (6.15 ± 1.66) nmol/L vs. (10.28 ± 2.45) nmol/L, (1.21 ± 0.42) g vs. (2.06 ± 0.52) g, (0.51 ± 0.12) cm/s vs. (0.61 ± 0.24) cm/s, (0.65 ± 0.12) μg/L vs. (0.89 ± 0.18) μg/L, (3.26 ± 0.34) μg/L vs. (6.82 ± 1.14) μg/L and (26.62 ± 3.62) μg/L vs. (40.55 ± 8.14) μg/L, the PSV and EDV were significantly higher than those in CRRT group: (25.66 ± 3.62) cm/s vs. (22.05 ± 1.84) cm/s and (10.92 ± 1.85) cm/s vs. (8.34 ± 1.26) cm/s, and there were statistical differences ( P<0.01). Conclusions:Alprostadil combined with CRRT can effectively improve renal function and renal hemodynamic in patients with severe LN complicated with AKI, enhance therapeutic efficacy, and inhibit the release of proinflammatory cytokines such as PCT.

Objective To observe the value of preoperative magnetization transfer imaging(MTI)for predicting postoperative pancreatic fistula(POPF)after distal pancreatectomy(DP).Methods A total of 65 patients with pancreatic tumor who underwent DP and preoperative MR scanning were retrospectively enrolled and divided into clinically relevant POPF(CR-POPF)group(n=14,with grade B or C fistula),biochemical fistula group(n=31,postoperative drain fluid amylase level exceeding 3 times the upper limit of normal)and non-fistula group(n=20,postoperative drain fluid amylase level not exceeding 3 times the upper limit of normal)based on postoperative records.Clinical data and magnetization transfer ratio(MTR)of pancreatic tissue at the surgical margin were compared among 3 groups.The predictive value of MTR for CR-POPF was evaluated according to the area under the curve(AUC)of receiver operating characteristic(ROC)curve.Results Patients' age,intraoperative blood loss and the proportion of pancreatic ductal adenocarcinoma in both CR-POPF group and biochemical fistula group were lower than those in non-fistula group(all adjusted P＜0.05),while no significant difference was found between the former two groups(all adjusted P＞0.05).MTR of pancreatic tissue at the surgical margin in CR-POPF group was lower than that in both biochemical fistula group and non-fistula group(both P＜0.05),whereas no statistical difference was detected between the latter two groups(P＞0.05).The AUC of MTR for predicting CR-POPF after DP was 0.727.Conclusion Preoperative MTI could be used to predict POPF after DP.

Helicobacter pylori(Hp)is a major pathogen that causes peptic ulcer,mucosa-associated tissue lymphoma and gastric cancer.Adhesion colonization is a prerequisite for the pathogenesis of Hp.After infec-tion,Hp first uses urease to neutralize gastric acid,and then it adapts to the environment through motility and chemotactic swimming of flagella.Finally,Hp adheres to gastric epithelial cells through outer membrane pro-teins.Some outer membrane proteins have the biological effect of transporting virulence factors,mediating in-flammation and assisting Hp to produce pathological changes on human body.This paper reviews the mecha-nism of main colonization factors of Hp.

Objective To compare the effectiveness of femoral neck system(FNS)and inverted triangle cannulated screws(ITCS)in the treatment of femoral neck fractures in young adults.Methods A retrospective study was conducted on 106 young and middle-aged patients who had been surgically treated for femoral neck fracture at our hospital from December 2020 to June 2022.The patients were assigned to FNS group(57 cases)or ITCS group(49 cases)according to the different internal fixations.The operation time,intraoperative fluoroscopy frequency,intraoperative blood loss,extra assisted reduction procedures(Kirschner wire prying reduction or open reduction),hospital stays,healing time,complications,postoperative recovery,and follow-up duration were compared between the two groups.Results The operation time,fluoroscopy frequency,and healing time in the FNS group were less than those in the ITCS group(P<0.001).The shortening degree and length of femoral neck in moderate and severe patients of the FNS group were lower than those of the ITCS group(P<0.001).The Harris score of the FNS group was higher than that of the ITCS group 12 months after surgery(P<0.001).There was no significant difference in intraoperative blood loss,reduction assistance,Garden index,or hospital stays between the two groups(P>0.05).Conclusion FNS is a better choice for internal fixation in patients with femoral neck fractures than ITCS,with faster recovery and less postoperative complications.

Objective To compare the effectiveness of femoral neck system(FNS)and inverted triangle cannulated screws(ITCS)in the treatment of femoral neck fractures in young adults.Methods A retrospective study was conducted on 106 young and middle-aged patients who had been surgically treated for femoral neck fracture at our hospital from December 2020 to June 2022.The patients were assigned to FNS group(57 cases)or ITCS group(49 cases)according to the different internal fixations.The operation time,intraoperative fluoroscopy frequency,intraoperative blood loss,extra assisted reduction procedures(Kirschner wire prying reduction or open reduction),hospital stays,healing time,complications,postoperative recovery,and follow-up duration were compared between the two groups.Results The operation time,fluoroscopy frequency,and healing time in the FNS group were less than those in the ITCS group(P<0.001).The shortening degree and length of femoral neck in moderate and severe patients of the FNS group were lower than those of the ITCS group(P<0.001).The Harris score of the FNS group was higher than that of the ITCS group 12 months after surgery(P<0.001).There was no significant difference in intraoperative blood loss,reduction assistance,Garden index,or hospital stays between the two groups(P>0.05).Conclusion FNS is a better choice for internal fixation in patients with femoral neck fractures than ITCS,with faster recovery and less postoperative complications.

Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC50)of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal"dead ends"and"safe bets"for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogen-oxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.