Comparison of conventional (basketing + dusting) and Moses (pop-dusting) holmium lasers during flexible ureteroscopy in the treatment of renal stones between 2 and 3 cm: a randomized clinical trial.

To investigate the feasibility of conventional (basketing + dusting) and Moses (pop-dusting) holmium lasers during flexible ureteroscopy (FURS) in the treatment of 2-3 cm renal calculi and to compare the efficiency and safety of the two methods, a total of 230 patients with 2-3 cm kidney stones who underwent FURS were randomly divided into the conventional group and the Moses group. The mode of lithotripsy in the conventional group was fragmentation and dusting. The mode of lithotripsy in the Moses group was dusting and pop-dusting. Clinical and perioperative variables and complications were compared between the two cohorts. Multivariate analyses of factors contributing to the stone-free rate (SFR) and operation time were performed. No statistically significant differences were found in the demographics, renal stone-related data, SFR, or complications between the cohorts. The laser energy was higher in the Moses cohort than in the conventional cohort (119.3 ± 15.2 vs. 92.8 ± 15.1 kJ; P < 0.001), and the operation time was shorter in the Moses cohort than in the conventional cohort (99.5 ± 18.9 vs. 105.3 ± 13.7 min; P = 0.009). When there was isolated stone, the operation time was shorter in the Moses cohort than in the conventional cohort (99.6 ± 17.5 vs. 111.4 ± 10.7 min; P < 0.001), while there was no significant difference between the two cohorts when there were multiple stones (99.5 ± 20 vs. 101.2 ± 14 min; P = 0.415). Multivariate analyses found that an increase in stone volume can decrease the SFR and prolong the operation time, and use of a Moses laser can shorten the operation time. Both holmium laser modes during FURS can effectively treat 2-3 cm renal calculi. The Moses mode is recommended as the first choice for the treatment of isolated 2-3 cm renal stones. When treating multiple stones, the efficiency of these two laser modalities is the same. TRIAL REGISTRATION: ChiCTR2200056091.

Stent Selection in Preoperative Biliary Drainage for Patients With Operable Pancreatic Cancer Receiving Neoadjuvant Therapy: A Meta-Analysis and Systematic Review.

With the increasing use of neoadjuvant therapy (NAT) in patients with pancreatic cancer to reduce tumor burden on prognosis, preoperative biliary drainage (PBD) is becoming increasingly necessary. The aim of this study was to summarize the latest evidence and compare the clinical efficacy of metal stents (MS) and plastic stents (PS) in patients undergoing neoadjuvant therapy for operable pancreatic cancer. Eligible studies were searched in PubMed, Embase and Cochrane Library from their inception to September 2021. In this study, RevMan 5.4 was used to perform the analyses. Two randomized controlled trials (RCTs) and six retrospective studies with 316 patients were included. All patients had pancreatic cancer and received NAT before surgical resection. Meta-analysis showed that the rate of endoscopic reintervention in MS (26/143, 18%) group was lower than that of PS (122/153, 80%) group (P < 0.05). The rate of stent-related complications in MS group was lower (18/118, 15%) than that of PS (52/117, 44%) group (P = 0.02). But there were no significant differences in operative time, operative blood loss, overall postoperative complications, postoperative hospitalization days and total medical costs between the two groups. For operable pancreatic cancer patients undergoing NAT surgery, MS was preferred over PS in terms of the incidence of endoscopic reintervention and stent-related complications. More clinical trials are needed in the future to confirm these data with higher levels of evidence.

Designer exosomes for targeted and efficient ferroptosis induction in cancer via chemo-photodynamic therapy.

Background: Efficient and specific induction of cell death in liver cancer is urgently needed. In this study, we aimed to design an exosome-based platform to deliver ferroptosis inducer (Erastin, Er) and photosensitizer (Rose Bengal, RB) into tumor tissues with high specificity. Methods: Exosome donor cells (HEK293T) were transfected with control or CD47-overexpressing plasmid. Exosomes were isolated and loaded with Er and RB via sonication method. Hepa1-6 cell xenograft C57BL/6 model was injected with control and engineered exosomes via tail vein. In vivo distribution of the injected exosomes was analyzed via tracking the fluorescence labeled exosomes. Photodynamic therapy was conducted by 532 nm laser irradiation. The therapeutic effects on hepatocellular carcinoma and toxic side-effects were systemically analyzed. Results: CD47 was efficiently loaded on the exosomes from the donor cells when CD47 was forced expressed by transfection. CD47 surface functionalization (ExosCD47) made the exosomes effectively escape the phagocytosis of mononuclear phagocyte system (MPS), and thus increased the distribution in tumor tissues. Erastin and RB could be effectively encapsulated into exosomes after sonication, and the drug-loaded exosomes (Er/RB@ExosCD47) strongly induced ferroptosis both in vitro and in vivo in tumor cells after irradiation of 532 nm laser. Moreover, compared with the control exosomes (Er/RB@ExosCtrl), Er/RB@ExosCD47 displayed much lower toxicity in liver. Conclusion: The engineered exosomes composed of CD47, Erastin, and Rose Bengal, induce obvious ferroptosis in hepatocellular carcinoma (HCC) with minimized toxicity in liver and kidney. The proposed exosomes would provide a promising strategy to treat types of malignant tumors.

Long noncoding RNA SLC2A1-AS1 regulates aerobic glycolysis and progression in hepatocellular carcinoma via inhibiting the STAT3/FOXM1/GLUT1 pathway.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant diseases worldwide. Despite advances in the diagnosis and treatment of HCC, its overall prognosis remains poor. Recent studies have shown that long noncoding RNAs (lncRNAs) play crucial roles in various pathophysiological processes, including liver cancer. In the current study, we report that lncRNA SLC2A1-AS1 is frequently downregulated in HCC samples, as shown by quantitative real-time polymerase chain reaction analysis. SLC2A1-AS1 deletion is significantly associated with recurrence-free survival in HCC. By performing glucose uptake, lactate production and ATP detection assays, we found that SLC2A1-AS1-mediated glucose transporter 1 (GLUT1) downregulation significantly suppressed glycolysis of HCC. In vitro Cell Counting Kit-8, colony formation, transwell assays as well as in vivo tumorigenesis and metastasis assays showed that SLC2A1-AS1 overexpression significantly suppressed proliferation and metastasis in HCC through the transcriptional inhibition of GLUT1. Results from fluorescence in situ hybridization, ChIP and luciferase reporter assays demonstrated that SLC2A1-AS1 exerts its regulatory role on GLUT1 by competitively binding to transketolase and signal transducer and activator of transcription 3 (STAT3) and inhibits the transactivation of Forkhead box M1 (FOXM1) via STAT3, thus resulting in inactivation of the FOXM1/GLUT1 axis in HCC cells. Our findings will be helpful for understanding the function and mechanism of lncRNA in HCC. These data also highlight the crucial role of SLC2A1-AS1 in HCC aerobic glycolysis and progression and pave the way for further research regarding the potential of SLC2A1-AS1 as a valuable predictive biomarker for HCC recurrence.

Up-Regulated CCDC34 Contributes to the Proliferation and Metastasis of Hepatocellular Carcinoma.

BACKGROUND: Coiled-coil domain-containing protein 34 (CCDC34), which belongs to the CCDCs family, has been recently reported to be up-regulated in various kinds of tumors. However, its role in the development of hepatocellular carcinoma (HCC) still remains unclear. MATERIALS AND METHODS: In this study, real-time polymerase chain reaction (RT-PCR) and Western blot analysis were performed to measure the mRNA and protein levels of CCDC34 in clinical samples. Kaplan-Meier method was used to analyze the relationship between CCDC34 and the prognosis in HCC patients. CCK-8 and colony formation assays were conducted to investigate CCDC34's effect on the cell proliferation, and Transwell assays were used to detect CCDC34's effect on the cell metastasis. Moreover, subcutaneous xenograft tumor model and lung metastasis model were applied to confirm the impact of CCDC34 on the HCC development. Lastly, RNA sequencing and Western blot analysis were performed to probe the underlying mechanism of CCDC34's effect on HCC. RESULTS: CCDC34 was significantly induced in HCC tissues, and the overexpression of CCDC34 predicted the poor outcomes among HCC patients. It was verified by the in vitro and in vivo experiments that CCDC34-knockdown potently inhibited the proliferation and metastasis of HCC cells. Subsequent results indicated that CCDC34 inhibition can affect the activation of protein kinase B (PKB or AKT) as well as epithelial-mesenchymal transition (EMT) process. CONCLUSION: CCDC34 is significantly associated with HCC. It will become a promising prognostic biomarker and therapeutic target against HCC.