This protocol aims to demonstrate the integration of indocyanine green (ICG) fluorescence imaging into laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) to enable real-time visualization of the biliary tree and minimize the risk of common bile duct (CBD) injury. Adult patients with benign or low-grade malignant tumors of the pancreatic head are selected. Preoperatively, 5 mg of ICG is administered intravenously to achieve optimal hepatic uptake and biliary excretion. During LDPPHR, a near-infrared camera system is employed to detect fluorescence and delineate the CBD and its anatomical relationships. Trocars are placed to optimize instrument access, and stepwise dissection exposes the pancreas and biliary tract. Fluorescence imaging guides precise skeletonization and protection of the CBD during pancreatic head separation. The pancreatic neck is divided using ultrasonic energy; reconstruction is performed via duct-to-mucosa pancreaticojejunostomy. Intraoperative ultrasound is utilized as an adjunct to confirm anatomical margins and vascular proximity. Postoperative management includes drain placement and monitoring guided by amylase measurements. In a series of six patients, this protocol enabled accurate biliary identification, prevented bile duct injury, and was associated with favorable outcomes. This fluorescence-guided technique enhances surgical safety and may facilitate the adoption of organ-preserving strategies in selected pancreatic head lesions.

Background Pancreatic cancer (PC) is a fatal human malignancy with a poor prognosis. Corosolic acid (CRA) is a triterpenoid, has been reported to have inhibitory effects on tumor growth. However, the role of CRA on PC has not been explored. Here, we aimed to uncover the molecular mechanisms of CRA in PC progression. Methods Cell viability, lactate dehydrogenase (LDH) release, cell apoptosis and senescence were detected by cell counting kit-8 (CCK-8), LDH, flow cytometry and senescence associated-β-galactosidase (SA-β-gal) assay. Levels of relevant proteins and oxidative stress (OS) markers were evaluated by Western blot and enzyme-linked immunosorbent assay (ELISA). A xenograft tumor model was established to explore the in vivo effects of CRA on PC. Results We found that CRA inhibited PC cell viability and promoted LDH release in a dose-dependent manner, but had no significant effect on human normal pancreatic ductal epithelial cells HPDE6C7. CRA increased OS-induced cell apoptosis and senescence in HAPC and SW1990 cells. And CRA decreased the levels of anti-apoptotic protein Bcl-2, and elevated the expression of pro-apoptotic protein Bax and senescence-associated proteins P21 and P53. Besides, CRA decreased tumor growth in xenograft models. Furthermore, CRA inactivated the Janus kinase-2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in HAPC and SW1990 cells. Functional experiments demonstrated that activation of the JAK2/STAT3 pathway by the JAK2 activator coumermycin A1 (C-A1) or the STAT3 activator colivelin (col) reduced the contribution effect of OS, apoptosis and senescence by CRA. Conclusion Taken together, our findings indicated that CRA exerted anti-cancer effects in PC by inhibiting the JAK2/STAT3 pathway.

Cholesterol overloading stress damages normal cellular functions in hepatocytes and induces metabolic disorders to facilitate the development of multiple diseases, including cardiovascular diseases, which seriously degrades the life quality of human beings. Recent data suggest that the Berberis vulgaris L. extract berberine is capable of regulating cholesterol homeostasis, which is deemed as potential therapeutic drug for the treatment of cholesterol overloading–associated diseases, but its detailed functions and molecular mechanisms are still largely unknown. In the present study, we evidenced that berberine suppressed cell apoptosis in high-cholesterol-diet mice liver and cholesterol-overloaded mice hepatocytes. Also, cholesterol overloading promoted reactive oxygen species (ROS) generation to trigger oxidative damages in hepatocytes, which were reversed by co-treating cells with both berberine and the ROS scavenger N-acetylcysteine (NAC). Moreover, the underlying mechanisms were uncovered, and we validated that berberine downregulated Keap1, and upregulated Nrf2 to activate the anti-oxidant Nrf2/HO-1 signaling pathway in cholesterol overloading–treated hepatocytes, and both Keap1 upregulation and Nrf2 downregulation abrogated the suppressing effects of berberine on cell apoptosis in the hepatocytes with cholesterol exposure. Taken together, we concluded that berberine activated the anti-oxidant Keap1/Nrf2/HO-1 pathway to eliminate cholesterol overloading–induced oxidative stress and apoptotic cell death in mice hepatocytes, and those evidences hinted that berberine might be used as putative therapeutic drug for the treatment of cholesterol overloading–associated cardiovascular diseases.

原发性肝内胆管结石(PIS)是我国西南地区高发和难治性疾病,在初始治疗后,部分患者仍需要再次甚至多次手术.近年来有大量研究发现部分特异性菌群能在肝内胆管定植,导致胆道系统慢性感染及炎症.这些特异菌群可产生β-葡萄糖醛酸苷酶等代谢产物,在色素性结石的形成中起着重要作用,被称为"致石菌群".本文对PIS发病机理中致石菌群的作用研究进展予以分析探讨,以期为PIS患者提供更多的治疗方式.

PURPOSE To explore the effects of aspirin on the proliferation and apoptosis of human pancreatic cancer cells and its potential molecular mechanism. METHODS This study included patients with pancreatic cancer who were divided into experimental group and control group. The cell proliferation ability was detected via cell counting kit-8 (CCK-8) assay and colony forming ability via colony formation assay. In addition, changes in proteins in the phosphatidyl inositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway were assessed using Western blotting, and rescue experiment was conducted to investigate whether aspirin can affect cell proliferation by inhibiting the PI3K/Akt/mTOR signaling pathway. RESULTS The results of CCK-8 assay showed that the proliferation rate of PANC-1 cells was decreased in a time- and dose-dependent manner after they were treated with aspirin at different concentrations. Colony formation assay confirmed that cell colony forming ability was significantly reduced with the increase in aspirin treatment concentration (p<0.05). Besides, the apoptosis rate and the number of cells in the experimental group were higher and larger than those in the control group (p<0.05). According to Western blotting results, the protein expressions of PI3K, phosphorylated (p)-Akt and p-mTOR were decreased after aspirin treatment. Rescue experimental results manifested that insulin-like growth factor 1 (IGF-1) supplementation remarkably elevated the expressions of PI3K, p-Akt and p-mTOR compared with phosphate-buffered saline (PBS) supplementation. It was found in CCK-8 assay that IGF-1 supplementation markedly reversed the inhibition of aspirin on the proliferation of PANC-1 cells in comparison with PBS supplementation. CONCLUSIONS Aspirin inhibits the proliferation and promotes the apoptosis of pancreatic cancer cells by inactivating the PI3K/Akt/mTOR signaling pathway.

ObjectiveTo investigate whether local treatment based on limited segmental resection can improve the prognosis of colorectal liver oligometastases (CRLOM) compared with other non-surgical treatment method, as well as the individualized regimen of this treatment method. MethodsA retrospective analysis was performed for the clinical data of 74 CRLOM patients who underwent local treatment in The First Affiliated Hospital of Kunming Medical University from January 2012 to December 2018, and according to the treatment method, they were divided into surgical group with 39 patients and non-surgical group with 35 patients. Treatment regimen and complications were compared between the two groups. The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves and calculate median disease-free survival (DFS) time and overall survival (OS) time, and the log-rank test was used for survival analysis. ResultsAmong the 39 patients in the surgical group, 23 underwent laparotomy and 16 underwent laparoscopy; as for the surgical procedure, 11 underwent limited segmental/subsegmental resection alone, 21 underwent limited segmental/subsegmental resection combined with wedge resection of small lesions, and 7 underwent limited segmental/subsegmental resection combined with radiofrequency ablation (RFA); 5 patients experienced postoperative complications, with bleeding in 1 patient, biliary fistula in 1 patient, and pleural effusion in 3 patients. Among the 35 patients in the non-surgical group, 18 underwent ultrasound- or CT-guided RFA combined with transarterial chemoembolization (TACE), 5 underwent TACE alone, 9 underwent RFA, and 3 underwent stereotactic body radiotherapy; as for postoperative complications, 1 patient experienced liver abscess after TACE, and 1 experienced pneumothorax after RFA. No patient died within 30 days after treatment. The surgical group had a DFS time of 38 months (95% confidence interval ［CI］: 31.3-44.9) and an OS time of 27 months (95% CI: 19.9-34.0), and the non-surgical group had a DFS time of 64 months (95% CI: 57.6-70.1) and an OS time of 43 months (95% CI: 36.2-50.0), with significant differences between the two groups (χ2=6.072 and 11.685, P=0.014 and 0.001). The surgical group had a 1-year survival rate of 92.3% and a 5-year survival rate of 41.0%, while the non-surgical group had a 1-year survival rate of 82.8% and a 5-year survival rate of 14.3%. ConclusionCompared with non-local surgical treatment, local treatment based on limited segmental resection can significantly improve the prognosis of CRLOM in patients with colorectal cancer. The surgical procedure should be individualized according to lesion characteristics.

Objective:To evaluate the safety and efficacy of limited segmental resection (LSR) combined with enucleation and/or ablation for multiple colorectal liver metastases.Methods:The clinical data of 42 patients with colorectal liver metastases who underwent LSR combined with enucleation and/or ablation in our department form Jan 2012 to Dec 2017 were retrospectively reviewed. The surgical procedures, clinical data and outcomes were calculated and analyzed.Results:All the patients were undergone the operations according to the previous plan successfully. The procedures included LSR combined with enucleation (n=21), with radiofrequency ablation (n=4), with enucleation and radiofrequency ablation (n=17). The average of operation time was (232.5±147.8)min, and the volumes of intraoperative blood loss were (304.2±151.4)ml. 121 lesions were resected. The resection margin in 88% of all patients was ≥1 mm. The morbidity rat was 12%. There was not liver failure and perioperative dead in all patients. The times of diseases-free survival time was 29 mon(95% CI: 22.7-35.3 mon). The 1-, and 5-years overall survival rate were 83% and 45% respectively. Conclusions:LSR combined with enucleation and ablation is safe and effective technique for multiple colorectal liver metastases patients. It could not only retain residual functional liver volume to the maximum but alsoget radical rection.