POU2F1/DNMT3a Pathway Participates in Neuropathic Pain by Hypermethylation-Mediated LRFN4 Downregulation Following Oxaliplatin Treatment.

Evidence demonstrates that DNA methylation is associated with the occurrence and development of various neurological diseases. However, the potential target genes undergoing DNA methylation, as well as their involvement in the chemotherapy drug oxaliplatin-induced neuropathic pain, are still unclear. Here, Lrfn4, which showed hypermethylation in the promoter regions, was screened from the SRA methylation database (PRJNA587622) following oxaliplatin treatment. MeDIP and qPCR assays identified that oxaliplatin treatment increased the methylation in Lrfn4 promoter region and decreased the expression of LRFN4 in the spinal dorsal horn. The assays with gain and loss of LRFN4 function demonstrated that LRFN4 downregulation in spinal dorsal horn contributed to the oxaliplatin-induced mechanical allodynia and cold hyperalgesia. Moreover, oxaliplatin treatment increased the DNA methyltransferases DNMT3a expression and the interaction between DNMT3a and Lrfn4 promoter, while inhibition of DNMT3a prevented the downregulation of LRFN4a induced by oxaliplatin. We also observed that the transcriptional factor POU2F1 can bind to the predicted sites in DNMT3a promoter region, oxaliplatin treatment upregulated the expression of transcriptional factor POU2F1 in dorsal horn neurons. Intrathecal injection of POU2F1 siRNA prevented the DNMT3a upregulation and the LRFN4 downregulation induced by oxaliplatin. Additionally, intrathecal injection of DNMT3a siRNA or POU2F1 siRNA alleviated the mechanical allodynia induced by oxaliplatin. These findings suggested that transcription factor POU2F1 upregulated the expression of DNMT3a, which subsequently decreased LRFN4 expression through hypermethylation modification in spinal dorsal horn, thereby mediating neuropathic pain following oxaliplatin treatment.

Right hemicolectomy and multivisceral resection of right colon cancer: A report of 21 cases.

The long- and short-term outcomes in 21 patients with right colon cancer after right hemicolectomy and multivisceral resection surgery were investigated. Short-term therapeutic effects and long-term survival rate were retrospectively analyzed in patients with right colon cancer. These individuals underwent right hemicolectomy in combination with multivisceral resections including pancreatic head, duodenum, kidney, liver, gallbladder, and abdominal wall at the Department of General Surgery in the Henan Tumor Hospital between January 2003 and August 2014. The patients had an average age of 58.9 years (range: 39-78). Three patients had metastatic invasion only to the duodenum; meanwhile 18 patients had invasion to the duodenum and other adjacent organs. The median survival time was 41 months (95% CI: 6.972-75.028) with one death in the perioperative period. No patients lost follow-up. One-, 3-, and 5-year survival rate was 75%, 56%, and 43%, respectively. It was concluded that indications for surgery should be tightly controlled. Favorable clinical outcomes of right hemicolectomy and multivisceral resection surgery were demonstrated for patients with right colon cancer at the T4 stage.

[Common types of massive intraoperative haemorrhage, treatment philosophy and operating skills in pelvic cancer surgery].

OBJECTIVE: To explore the common types of massive intraoperative bleeding, clinical characteristics, treatment philosophy and operating skills in pelvic cancer surgery. METHODS: We treated massive intraoperative bleeding in 19 patients with pelvic cancer in our department from January 2003 to March 2012. Their clinical data were retrospectively analyzed. The clinical features of massive intraoperative bleeding were analyzed, the treatment experience and lessons were summed up, and the operating skills to manage this serious issue were analyzed. RESULTS: In this group of 19 patients, 7 cases were of presacral venous plexus bleeding, 5 cases of internal iliac vein bleeding, 6 cases of anterior sacral venous plexus and internal iliac vein bleeding, and one cases of internal and external iliac vein bleeding. Six cases of anterior sacral plexus bleeding and 4 cases of internal iliac vein bleeding were treated with suture ligation to stop the bleeding. Six cases of anterior sacral and internal iliac vein bleeding, one cases of anterior sacral vein bleeding, and one case of internal iliac vein bleeding were managed with transabdominal perineal incision or transabdominal cotton pad compression hemostasis. One case of internal and external iliac vein bleeding was treated with direct ligation of the external iliac vein and compression hemostasis of the internal iliac vein. Among the 19 patients, 18 cases had effective hemostasis. Their blood loss was 400-1500 ml, and they had a fair postoperative recovery. One patient died due to massive intraoperative bleeding of ca. 4500 ml. CONCLUSIONS: Most of the massive intraoperative bleeding during pelvic cancer surgery is from the presacral venous plexus and internal iliac vein. The operator should go along with the treatment philosophy to save the life of the patient above all, and to properly perform suture ligation or compression hemostasis according to the actual situation, and with mastered crucial operating hemostatic skills.

[Effects of splenic flexure and sigmoid colon variation on the types of anastomosis after left colectomy].

OBJECTIVE: To explore the effects of splenic flexure and sigmoid colon variation on anastomosis after left colectomy. METHODS: The clinical data of 76 descending colon patients were collected retrospectively from March 2004 to April 2011 at our hospital. Statistical analysis was performed for the types of splenic flexure and sigmoid colon with regards to the choice of anastomosis. RESULTS: There were mesenteric type (n = 55), mobile type (n = 7) and adhesive type (n = 14) for splenic flexure. And among 61 regular types, 15 were of variable type for sigmoid colon variation. There was significant difference of anastomosis between the types of sigmoid colon variation [43 (78.2%) vs 5 (71.4%) vs 9 (64.3%), P > 0.05] while no significant difference existed between the types of splenic flexure [I type 56(91.8%) vs II type 1 (14.3%), III or IV type 0, P < 0.05]. CONCLUSION: A clinician should pay more attention to the types of sigmoid colon variation. And it helps to select the right approach of anastomosis after left colectomy.

[Direct dissection of urogenital diaphragm in abdominoperineal resection].

OBJECTIVE: To compare the clinical outcomes of two operative approaches of perineal dissection in rectal carcinoma undergoing abdominoperineal resection. METHODS: A randomized controlled trial was conducted in a total of 126 patients with rectal cancer undergoing the Miles operation from June 2007 to June 2011 at Henan Provincial Cancer Hospital. They were divided into 2 groups. One group (Group A) underwent a direct dissection of urogenital diaphragm while another group (Group B) received the traditional operative method. And the duration of perineal surgery, rupture of rectum or tumor, urethral injury and the post-operative rate of perineal hemorrhage were compared between 2 groups. RESULTS: Group A had a shorter duration of perineal surgery ((16 ± 5) min vs (23 ± 5) min, P = 0.032). And the differences were significant statistically. However the rupture of rectum or tumor, urethral injury and the post-operative rate of perineal hemorrhage were equivalent for two groups (1 vs 5, 2 vs 5, 0 vs 1, 1 vs 3, all P > 0.05). CONCLUSION: A direct dissection of urogenital diaphragm offers more clinical advantages over the traditional operative method in abdominoperineal resection.

Combined BRM270 and endostatin inhibit relapse of NSCLC while suppressing lung cancer stem cell proliferation induced by endostatin.

Endostatin (ES, ENDO) has been reported to suppress the growth of tumors while inducing the proliferation of lung cancer stem cells (LCSCs), causing a poor prognosis for lung cancer. In this study, we aimed to clarify whether BRM270 can inhibit the proliferation of cancer stem cells (CSCs). Endostatin + BRM270 showed anti-tumor effects by reducing tumor volume and increasing survival. Administration of BRM270 reduced the number of aldehyde dehydrogenase-positive (ALDH+) cells and the level of ALDH1A1 expression in tumors by increasing the level of miR-128 while decreasing the levels of BMI-1, ABCC-5, E2F3, and c-MET. The luciferase activity of miR-128 promoter was increased by an increasing concentration of BRM270. In addition, BMI-1, ABCC-5, E2F3, and c-MET were identified as candidate targets of miR-128, and the overexpression of miR-128 significantly reduced mRNA/protein levels of BMI-1, ABCC-5, E2F3, and c-MET in A549 and H460 cells. Administration of BRM270 inhibited the expression of BMI-1, ABCC-5, E2F3, and c-MET in a dose-dependent manner. In this study, we showed for the first time that the combined administration of endostatin and BRM270 achieved anti-tumor effects while suppressing the proliferation of stem cells.

Autophagy and pulmonary disease.

Autophagy is a process of cell self-renewal that is dependent on the degradation of the cytoplasmic proteins or organelles of lysosomes. Many diseases, such as metabolic diseases, cancer, neurodegenerative diseases, and lung diseases, have been confirmed to be associated with elevated or impaired levels of autophagy. At present, studies have found that autophagy participates in the regulation of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, pulmonary hypertension, acute lung injury, lung cancer, and other pulmonary diseases. Using recent literature on the signal transduction mechanisms of autophagy and the effects of autophagy signalling on lung diseases, this review intends to clarify the mechanisms of lung disease to guide the treatment of related diseases. The reviews of this paper are available via the supplemental material section.

[Treatment outcomes of multivisceral resection for locally advanced right colon cancer].

OBJECTIVE: To investigate long-term survival after multivisceral resection in patients with locally advanced right colon cancer. METHODS: The clinical data and survival of 13 patients with locally advanced right colon cancer were retrospectively analyzed. RESULTS: There were 8 males and 5 females with a mean age of 58.6 years. Location of the primary tumor included hepatic flexure(n=6), transverse colon(n=2), and ascending colon(n=5). Three patients had duodenal invasion alone, 9 had involvement of duodenum and other organs, and 1 had pancreas and stomach involvement. Right colectomy and pancreaticoduodenectomy and(or) resection of other organs were performed. The 1-, 3-, and 5-year survival rates were 69%, 54%, and 30%, respectively. CONCLUSION: Right colectomy combined with multivisceral resection is a promising procedure for selected patients with locally advanced colon cancer.

[Anatomy of splenic flexure and surgical treatment in 52 patients with non-obstructive splenic flexure colon cancer].

OBJECTIVE: To investigate the anatomic characteristics of splenic flexure, surgical techniques, and oncologic outcomes in 52 patients with non-obstructive splenic flexure colon cancer. METHODS: Clinical data of 52 patients with non-obstructive splenic flexure colon cancer from March 2004 to March 2011 in the Department of General Surgery at the Henan Province Tumor Hospital were analyzed retrospectively. RESULTS: There were 37 patients of regular type, 5 of mobile type, and 10 of adhesive type. All the patients received radical operation. Eighteen patients received pre-small intestine anastomosis, including 12 cases with regular type, 4 with mobile type, and 2 with adhesive type. The difference in pre-small intestine anastomosis among the three types was not statistically significant(P=0.062). In addition, 32 cases received retro-ileum anastomosis. There were no significant differences in operative time, intraoperative blood loss, number of lymph node dissection and positive lymph node, and postoperation complication rate among the three types. Follow up was available in all the cases. Five-year survival rates of cases with regular type, mobile type and adhesive type were 62.5%, 59.2% and 58.7% respectively(P>0.05). CONCLUSIONS: Radical resection can provide satisfactory survival for splenic flexure colon cancer patients. The anatomy of splenic flexure does not affect the type of anastomosis. Retro-ileum anastomosis is a simple and effective method for reconstruction after radical resection of the tumor.