Abstract The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways. castrationresistant castration resistant (CRPC methods MMP12 MMP 12 (MMP)-1 ECM (ECM components However MMP-1 understood action coculture co culture MMP12. 12. CD36CPT1 CDCPT CD36 CPT1 CD CPT CD36/CPT P62LC3 PLC P62 LC3 P LC P62/LC pathways respectively Moreover MMP12knockdown MMPknockdown knockdown growth results MMP1 1 (MMP)- MMP- CD36CPT CD3 P62LC P6 (MMP) (MMP

Abstract Introduction: The mouse heterotopic cardiac transplant model has been extensively used to explore transplant immunity. Although the cuff technique facilitates the operation, the procedure remains difficult, and vessel eversion is the most difficult step. Cuff movement and everted vessel wall slippage are the main adverse factors in vessel eversion. Traditional strategies to prevent these factors focus on cuff fixation, while more steps or surgical instruments would be required. Methods: According to the reported protocols and our experience, the vessel eversion skills were modified and used for transplantation. Cardiac grafts from C57BL/6(H-2b) or BALB/c(H-2d) mice were transplanted into C57BL/6(H-2b) mice. The operating times of recent 90 operations, which were divided into 9 groups according to their sequence, were summarized and analyzed. Results: The mouse cervical cardiac transplantation was successfully performed by using the modified vessel eversion skills. The cuff movement, which is the most important adverse factor to prevent vessel eversion, was effectively prevented. In the recent 90 operations, the total operating time was 47.3±7.9 min and the success rate was 98%. Conclusions: The modified surgical skills simplify the vessel eversion in mouse cervical cardiac transplantation with cuff technique, characterized by less cuff movement, fewer steps, and surgical instruments. Using these surgical skills, the transplant can be performed in a short time.

ABSTRACT Aim: Both submucosal tunneling endoscopic resection (STER) and endoscopic full-thickness resection (EFTR) are effective methods for gastric fundus submucosal tumors (SMTs). However, there is little data that compares the two methods. The aim of this study was to compare the safety and efficacy of STER and EFTR for the treatment of SMTs in the gastric fundus. Methods: Clinical data was retrospectively collected from patients with gastric fundus SMTs who underwent STER or EFTR at our hospital from April 2011 to May 2016. Epidemiological data (gender, age), tumor size, procedure-related parameters, complications, postoperative hospital stay, cost and follow-up data were compared. Results: A total of 43 patients were enrolled: 15 underwent STER and the remaining 28 cases underwent EFTR. There were no significant differences between the two groups with regard to gender, age, tumor size, en bloc resection rate, operation time, pathohistological results and cost (p > 0.05). However, patients who underwent EFTR had a longer suture time, required a larger number of clips for closure and a prolonged postoperative hospital stay (p < 0.05). No recurrence was noted in either the STER or the EFTR group during a mean follow-up of 12.1 and 22.8 months, respectively. Conclusions: The treatment efficacy of STER and EFTR for the treatment of gastric fundus SMTs was comparable. However, STER has some advantages over EFTR in terms of suture time, the number of clips required for closure and postoperative hospital stay.

Background and aim: Both peroral endoscopic myotomy (POEM) and pneumatic dilation (PD) has proved to be effective for treating achalasia in patients aged ≥ 65 years. However little is known about the comparison between POEM and PD. The aim of the study was to compare the safety and efficacy of POEM and PD for the treatment of achalasia in these patients. Methods: We retrospectively reviewed the medical records of patients aged 65 years-old or more who received POEM or PD for the treatment of achalasia at our hospital from January 2010 to December 2015, they were divided into the POEM group and the PD group. Demographics and data about safety and efficacy were collected retrospectively and compared between the two groups. Results: A total of 31 patients were enrolled, and 21 of them received POEM, while the other 10 received PD. The treatment success (Eckardt score ≤ 3) rate of POEM and PD at 3, 6, 12, 24 and 36 months after the treatment were comparable (p > 0.05). Treatment failure was noticed in 3 cases, 1 of them was in the POEM group and the other 2 in the PD group, there was no significant difference (p > 0.05). Multivariate analysis showed that sigmoid-type achalasia was a predictive factor of treatment failure. No severe complications were observed during operation and periodical follow-up. Conclusion: Short-term and intermediate efficacy of POEM and PD for treating achalasia in patients aged ≥ 65 years was comparable. A large scale, randomized study with long-term follow-up is necessary in order to make a definitive conclusion.

Response surface methodology (RSM) was used for statistical optimization of jiean-peptide (JAA) production by Bacillus subtilis ZK8 cells adsorbed on wood chips to form a novel fermentation system. The Plackett-Burman design was used in the first step to evaluate the effects of eight factors, including six fermentation medium components and two cell adsorption conditions. Among the variables screened, soybean meal hydrolysate (SMH) and MgSO4·7H2O in the fermentation medium had significanteffects on JAA production. In the second step, the concentrations of SMH and MgSO4·7H2O were further optimized using central composite designs and response surface analysis. The optimized concentration of SMH and MgSO4·7H2O was 24% (v/v) and 0.38% (w/v), respectively, which increased the production of JAA in a shake flask system by 41% relative to optimization of a single variable component of the culture medium.