OBJECTIVE: Paridis Rhizoma (Chonglou in Chinese), a traditional Chinese herbal medicine, has been shown have strong anti-tumor effects. Paris saponin VII (PSVII), an active constituent isolated from Paridis Rhizoma, was demonstrated to significantly suppress the proliferation of BxPC-3 cells in our previous study. Here, we aimed to elucidate the anti-pancreatic ductal adenocarcinoma (PDAC) effect of PSVII and the underlying mechanism. METHODS: Cell viability was determined by CCK-8, colony formation, and cell migration assays. Cell apoptosis and reactive oxygen species (ROS) production were measured by flow cytometry with annexin V/propidine iodide (Annexin V/PI) and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. Pyroptosis was evaluated by morphological features, Hoechst 33342/PI staining assay, and release of lactate dehydrogenase (LDH). JC-1 fluorescent dye was employed to measure mitochondrial membrane potential. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine the levels of proteins or mRNAs. The effect in vivo was assessed by a xenograft tumor model. RESULTS: PSVII inhibited the viability of PDAC cells (BxPC-3, PANC-1, and Capan-2 cells) and induced gasdermin E (GSDME) cleavage, as well as the simultaneous cleavage of Caspase-3 and poly (ADP-ribose) polymerase 1 (PARP). Knockdown of GSDME shifted PSVII-induced pyroptosis to apoptosis. Additionally, the effect of PSVII was significantly attenuated by Z-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone (Z-DEVD-FMK), on the induction of GSDME-dependent pyroptosis. PSVII also elevated intracellular ROS accumulation and stimulated Bax and Caspase-3/GSDME to conduct pyroptosis in PDAC cells. The ROS scavenger N-acetyl cysteine (NAC) suppressed the release of LDH and inhibited Caspase-9, Caspase-3, and GSDME cleavage in PDAC cells, ultimately reversing PSVII-induced pyroptosis. Furthermore, in a xenograft tumor model, PSVII markedly suppressed the growth of PDAC tumors and induced pyroptosis. CONCLUSION These results demonstrated that PSVII exerts therapeutic effects through Caspase-3/GSDME-dependent pyroptosis and may constitute a novel strategy for preventing chemotherapeutic resistance in patients with PDAC in the future.

Objective:To investigate the clinical, imaging and endoscopic characteristics of idiopathic mesenteric phlebosclerosis (IMP).Methods:From January 2010 to December 2020, 14 patients with IMP diagnosed and treated at the Quzhou Hospital Affiliated to Wenzhou Medical University (Quzhou People′s Hospital) were enrolled. All patients underwent abdominal X-ray, contrast enhanced computed tomography (CT) and endoscopy. Three cases accepted double-contrast barium enema and 11 cases underwent endoscopic biopsy. Three of the 14 IMP patients underwent surgery and pathological examination because of intestinal perforation or intestinal obstruction that failed conservative treatment. The general data (such as gender, drinking history, etc.), clinical symptoms, complications, imaging (abdominal X-ray, CT, double-contrast barium enema) and endoscopic features were retrospectively analyzed. Descriptive method was used for statistical analysis.Results:Among the 14 IMP patients, 13 cases were male and one case was female. All the 13 male cases had long history of drinking Chinese herbal medicine wine, among them, 8 patients consumed acanthopanax bark wine. Complications occurred in 7 cases, including 5 cases of intestinal obstruction and 2 cases of intestinal perforation. The clinical symptoms of 14 IMP patients were nonspecific, mostly manifested as abdominal pain (11 cases), abdominal distension (6 cases), diarrhea (6 cases), nausea and vomiting (4 cases), and constipation (2 cases). Abdominal X-ray images mainly showed multiple irregular calcifications along involved colon. The images of 3 patients received double-contrast barium enema demonstrated shallowness or disappearance of semilunar folds, rigid colonic wall, narrowed lumen and " thumb printing". The typical CT images indicated edema and thickening of the involved intestinal wall, blurred mesenteric fat space, spot, thread-like, and curved calcification of mesenteric vein and colonic wall. Typical endoscopic findings included dark-purple colored mucosa, congestion, edema, erosion and ulceration, and focal nodular surface and visible varicose veins.Conclusions:IMP has typical imaging and endoscopic characteristics, and the combination of them can diagnose and evaluate IMP more accurately.

Objective To observe the clinical effect of Xiaoaiping Injection combined with gemcitabine and carboplatin in the treatment ofⅢB and Ⅳ non-small cell lung cancer (NSCLC).Methods Totally 106 NSCLC patients from Huangshi Central Hospital of Edong Medical Group were sellected in this study.The patients were divided into gemcitabine and carboplatin control group (n =53)and Xiaoaiping Injection combined with gemcitabine and carboplatin observation group (n =53).The clinical efficacy and adverse reactions were compared between two groups.Results After four cycles of treatment,the effective rate and control rate in observation group were 39.6％ and 77.4％,and those in control group were 35.8％ and 75.5％.There was no significant difference between the two groups.The decline rates of white blood cells,hemoglobin,and platelet in observation group were 41.5％,37.7％,and 45.3％,which were significantly lower than those of 64.2％,62.3％,and 69.8％ in control group (P ＜ 0.05).There was no significant difference of renal function injury,liver function damage,nausea,vomiting,dizziness,headache,diarrhea,and constipation between two groups.In observation group,the median survival time was 8.4 months,time to tumor progression was 5.3 months,and 1 year survival rate was 26.4％.In control group,the median survival time was 7.7 months,time to tumor progression was 4.2 months,and 1 year survival rate was 11.3％.There was significant difference between two groups (P ＜ 0.05).Conclusion Xiaoaiping Injection combined with gemcitabine and carboplatin can reduce the hematologic toxicity of chemotherapy drug in the treatment of ⅢB and Ⅳ NSCLC,and improve long-term clinical outcomes.combined with gemcitabine and carboplatin can reduce the hematologic toxicity of chemotherapy drug in the treatment ofⅢB and Ⅳ NSCLC,and improve long-term clinical outcomes.