Prognostic value of hyperthermic intraperitoneal chemotherapy in gastric cancer with synchronous peritoneal metastases: a real-world retrospective study.

PURPOSE: Peritoneal metastasis in gastric cancer (GC) is a late-stage condition with a poor prognosis. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a popular treatment for peritoneal metastases. Here, we aim to investigate the real-world application and efficacy of HIPEC alone for GC patients with synchronous peritoneal metastases. METHODS: We conducted a retrospective analysis on GC patients with synchronous peritoneal metastasis at the Sixth Affiliated Hospital of Sun Yat-sen University between January 2011 and December 2022. Survival analyses and Cox regression models were performed based on overall survival (OS) and cancer-specific survival (CSS), and subgroup analysis was used to determine the prognostic value of HIPEC across different treatment. RESULTS: We enrolled 250 patients, of whom 120 (48%) received HIPEC while 130 (52%) did not. HIPEC showed no survival benefit for GC patients (P = 0.220 for OS and P = 0.370 for CSS). However, subgroup analysis found that HIPEC can only improve OS and CSS when combined with primary tumor resection (P = 0.034 for OS and P = 0.036 for CSS). Moreover, survival analyses also demonstrated that HIPEC independently improved OS (HR for OS = 0.58, 95% CI 0.37-0.92, P = 0.020) and CSS (HR for CSS = 0.58, 95% CI 0.37-0.93, P = 0.024) for patients who underwent primary site resection, but not for those who did not. CONCLUSION: HIPEC can improve survival in GC patients with synchronous peritoneal metastases who have primary tumor resection, but not in those without primary tumor resection.

Adiponectin Alleviates Intestinal Fibrosis by Enhancing AMP-Activated Protein Kinase Phosphorylation.

BACKGROUND: Intestinal fibrosis is a common complication of Crohn's disease (CD). Adiponectin reportedly exerts anti-inflammatory effects in various disease models, including colitis models. AIMS: In this study, we aimed to determine the effects of adiponectin on intestinal fibrosis and the underlying mechanisms. METHODS: A murine model of intestinal fibrosis was established by administering increasing doses of 2,4,6-trinitrobenzene sulfonic acid to Balb/c mice via enema for 7 weeks. Primary human fibroblasts were isolated from the colon tissues of patients with CD. The fibroblasts were incubated with transforming growth factor (TGF)-ß1 to establish a fibrosis model in vitro. Pathway inhibitors were used to verify the potential signaling pathways involved in the anti-fibrogenic effect of adiponectin. RESULTS: Compared with the normal mesentery, adiponectin expression was significantly increased in the hypertrophic mesentery of patients with CD. Intraperitoneal injection of adiponectin significantly decreased the activity of myeloperoxidase and the expression of pro-inflammatory cytokines (tumor necrosis factor α and interleukin 6) in the colon of fibrosis model mice, whereas the expression of the anti-inflammatory cytokine interleukin 10 was substantially increased. Moreover, adiponectin treatment inhibited colon shortening, decreased colon weight, and reduced fibrotic protein deposition in the model mice. Adiponectin reduced the phosphorylation of Smad2 and collagen deposition induced by TGF-ß1 in primary human intestinal fibroblasts, with an increase in AMP-activated protein kinase (AMPK) phosphorylation. Furthermore, this phenomenon was reversed by the AMPK inhibitor. CONCLUSIONS: Adiponectin can protect against intestinal fibrosis by enhancing the phosphorylation of AMPK and inhibiting the activity of the TGF-ß1/Smad signaling pathway.

Gallbladder Cancer Progression Is Reversed by Nanomaterial-Induced Photothermal Therapy in Combination with Chemotherapy and Autophagy Inhibition.

INTRODUCTION: Gallbladder cancer (GBC) is the most common malignancy in biliary tract with extremely poor prognosis. Photothermal therapy (PTT) shows great promises for tumor therapy, which causes tumor cell death via selectively directed heating released by nanoparticles under the near-infrared irradiation. Through degrading damaged organelles and misfolded proteins in autophagosomes, autophagy plays a vital role in maintaining the intracellular homeostasis. The present study attempted to combine chemotherapy and autophagy blocking with PTT. MATERIALS AND METHODS: We purchased multi-walled carbon nanotubes from Nanostructured and Amorphous Materials and performed PTT using an 808-nm diode laser. The cytotoxic effects of PTT and chemotherapy in vitro were assessed by cell viability analysis. The effects of PTT and chemotherapy on autophagy in vitro were assessed by GFP-LC3 and Western blot. And these results were confirmed by in vivo experiment. RESULTS: Both PTT and chemotherapy could trigger cytoprotective autophagy to tolerate the cellular stresses and prolong the survival of GBC cell; therefore, the blocking of autophagy could enhance the efficacy of PTT and chemotherapy in GBC treatment in vitro and in vivo. CONCLUSION: Chemotherapeutic drug doxorubicin and autophagy inhibitor chloroquine could enhance the efficacy of nanoparticle-mediated hyperthermia in GBC.

Molecular epidemiology of colistin-resistant Enterobacteriaceae in inpatient and avian isolates from China: high prevalence of mcr-negative Klebsiella pneumoniae.

Whether chromosomal and transmissible mechanisms contribute simultaneously to colistin resistance in Klebsiella pneumoniae and Escherichia coli remains unknown. This study aims to identify the underlying mechanisms of colistin resistance in inpatient and avian K. pneumoniae and E. coli in China. We retrospectively screened 2353 Enterobacteriaceae isolates from inpatients at multiple centers during 2011-2014, and 168 avian isolates from one slaughterhouse in 2013 for the presence of MCR-1/MCR-2. Mutations and transcriptional levels of the chromosomal RamA, PhoPQ, and PmrAB genes were determined by PCR and RT-qPCR. The transferability and genetic characteristics of the underlying colistin-resistance genes were detected by conjugation and whole-genome sequencing. The MIC90 for colistin in colistin-resistant K. pneumoniae (ColRKP, 128 mg/L, N = 17) was 16-fold higher than in colistin-resistant E. coli (ColREC, 8 mg/L, N = 33). The dominant sequence types of ColRKP were ST2018 and ST37, whereas ColREC displayed diversity. The chromosomal genes ramA, pmrB, and phoQ were not associated with colistin resistance in ColRKP. The transcriptional levels of PmrB in ColREC were 7.5-fold greater than in colistin-susceptible isolates. The carrying rates of MCR-1 in ColREC and ColRKP were 100% (33/33) and 23.5% (4/17), respectively. Plasmid IncI2 (~60 kb) carrying MCR-1 could be transferred to recipient E. coli EC600 with frequencies ranging from 8.74 × 10-6 to 1.31 × 10-4. No transferable genes were identified in mcr-1-negative ColRKP. MCR-1 combined with upregulated PmrB was associated with low-level colistin resistance in ColREC. However, two-thirds of the ColRKP isolates were mcr-negative and need to be studied further.