α­hederin overcomes hypoxia­mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway.

Currently, chemoresistance is a major challenge that directly affects the prognosis of patients with colorectal cancer (CRC). In addition, hypoxia is associated with poor prognosis and therapeutic resistance in patients with cancer. Accumulating evidence has shown that α­hederin has significant antitumour effects and that α­hederin can inhibit hypoxia­mediated drug resistance in CRC; however, the underlying mechanism remains unclear. In the present study, viability and proliferation assays were used to evaluate the effect of α­hederin on the drug resistance of CRC cells under hypoxia. Sequencing analysis and apoptosis assays were used to determine the effect of α­hederin on apoptosis under hypoxia. Western blot analysis and reverse transcription­quantitative PCR were used to measure apoptosis­related protein and mRNA expression levels. Furthermore, different mouse models were established to study the effect of α­hederin on hypoxia­mediated CRC drug resistance in vivo. In the present study, the high expression of Bcl2 in hypoxic CRC cells was revealed to be a key factor in their drug resistance, whereas α­hederin inhibited the expression of Bcl2 by reducing AKT phosphorylation in vitro and in vivo, and promoted the apoptosis of CRC cells under hypoxia. By contrast, overexpression of AKT reversed the effect of α­hederin on CRC cell apoptosis under hypoxia. Taken together, these results suggested that α­hederin may overcome hypoxia­mediated drug resistance in CRC by inhibiting the AKT/Bcl2 pathway. In the future, α­hederin may be used as a novel adjuvant for reversing drug resistance in CRC.

Laparoscopic Management of Spontaneous Colonic Perforation: A Single Institution Study of 52 Patients.

BACKGROUND: Spontaneous colonic perforation (SCP) is associated with an devastating result. The use of laparoscopy for SCP remains controversial. This study aimed to compare the postoperative outcomes of patients who received either laparoscopic or open surgery and to evaluate the efficacy of laparoscopic surgery and the risk factors affecting prognosis. PATIENTS AND METHODS: A retrospective study of patients who underwent surgery for SCP from January 2005 to December 2020 was performed. Demographic data, intraoperative variables, length of stay, and surgical complications were retrieved. RESULTS: A total of 52 patients were postoperatively diagnosed with SCP. Thirty (57.69%) procedures were performed using laparoscopic surgery (group A) and 22 (42.31%) were performed using open surgery (group B). There were no significant differences between groups A and B in terms of age, sex, chronic concomitant disease, chronic constipation, incentives, imaging findings, preoperative diagnosis, American Society of Anesthesiologists (ASA) score, Mannheim Peritonitis Index (MPI), operation time, days to resumption of liquids, site of perforation, surgical procedures, or types of perforation ( P >0.05). The incidence of wound infection in group A was significantly lower than that in group B ( P <0.05), but there was no significant difference in the incidence of abdominal abscess between the 2 groups ( P >0.05). Significant differences were found in days to start walking and days to resumption of solids between the 2 groups ( P <0.05). Group B had a longer length of hospital stay than group A ( P <0.05). After multivariate analysis, the independent variables associated with worse perioperative complications were an age of 65 years and older, an ASA score of ≥3, and an MPI of >26. CONCLUSIONS: The prognosis of SCP is poor. The operation should follow principles that are simple, rapid, and effective. If there are no contraindications, laparoscopy may be the preferred method. Hartmann procedure is a promising surgical strategy. The age, ASA score, and MPI may indicate the severity and prognosis of SCP.

Effect of complete reduction of hernia sac and transection of hernia sac during laparoscopic indirect inguinal hernia repair on seroma.

INTRODUCTION: This study investigated the effect of complete reduction and transection of the hernia sac during laparoscopic indirect inguinal hernia repair on seroma. METHODS: Retrospective analysis was performed on 1763 cases undergoing laparoscopic indirect inguinal hernia repair in three centers from January 2017 to September 2019, among them, 311 patients with transection of hernia sac and 1452 patients with reduction of hernia sac, the data of the two groups were tested by t-test. Logistic univariate analysis was performed on 233 cases of postoperative seroma, and variables p < 0.05 in univariate analysis were included for multivariate analysis. Then, the transection group and the reduction group were matched with 1:1 propensity score matching, and the caliper value was set at 0.05. Finally, 274 patients matched in each group were analyzed by univariate analysis again to evaluate whether the transection of hernia sac had an impact on postoperative seroma. RESULTS: The results of univariate analysis of 233 patients with postoperative seroma showed that: ASA-3 p = 0.031, classification-L3 p < 0.001, surgery-TEP p < 0.001, transect group p = 0.005. The results of multivariate analysis show that: ASA-3 p < 0.001, classification-L3 p < 0.001, surgery-TEP p < 0.001, transect group p = 0.020. The results of univariate analysis after propensity score matching showed that transection of the hernia sac is significant for postoperative seroma (p < 0.001). CONCLUSION: Transection of the hernia sac during laparoscopic indirect inguinal hernia repair can significantly lead to postoperative seroma.

Exosomal miR-122-5p is Related to the Degree of Myelosuppression Caused by Chemotherapy in Patients with Colorectal Cancer.

PURPOSE: As rapidly dividing cells are usually the target of anticancer chemotherapy, it is inevitable that rapidly dividing normal cells become damaged, with myelosuppressive effects being a serious side effect of this therapy. Many recent studies have found that exosomal microRNAs (miRNAs) are related to the occurrence of some diseases. PATIENTS AND METHODS: Small RNA sequencing was used to investigate differential exosomal miRNAs with the same expression trend between groups after chemotherapy: MildA (before chemotherapy in patients with mild myelosuppression) and MildB (after chemotherapy in patients with mild myelosuppression); SevereA (before chemotherapy in patients with severe myelosuppression) and SevereB (after chemotherapy in patients with severe myelosuppression). A Venn diagram was generated to screen exosomal miRNAs related to chemotherapy. Small RNA sequencing was also used to investigate differentially expressed exosomal miRNAs among these groups, and exosomal miRNAs related to myelosuppression after chemotherapy was explored using a Venn diagram. RT-qPCR was applied to further verify the sequencing results. We performed target gene prediction and functional analysis for candidate exosomal miRNAs. RESULTS: Compared with that in the MildA or SevereA group, an increase in exosomal miR-122-5p was found in the MildB or SevereB group, and the expression level was lower in the SevereB group than in the MildB group. However, we found no notable difference in its expression level between the MildA and SevereA groups. Similar results were not obtained for the remaining miRNAs. RT-qPCR confirmed the screening results. Further analyses indicated that exosomal miR-122-5p targets CDK4 to inhibit the cell cycle. CONCLUSION: The expression level of exosomal miR-122-5p in the serum of patients with colorectal cancer correlates with the severity of myelosuppression caused by chemotherapy, and miR-122-5p targets CDK4 to inhibit cell cycle progression.

A preliminary multicenter evaluation of endoscopic sublay repair for ventral hernia from China.

BACKGROUND: For ventral hernia, endoscopic sublay repair (ESR) may overcome the disadvantages of open sublay and laparoscopic intraperitoneal onlay mesh repair. This retrospective study presents the preliminary multicenter results of ESR from China. The feasibility, safety, and effectiveness of ESR were evaluated; its surgical points and indications were summarized. METHODS: The study reviewed 156 ventral hernia patients planned to perform with ESR in ten hospitals between March 2016 and July 2019. Patient demographics, hernia characteristics, operative variables, and surgical results were recorded and analyzed. RESULTS: ESR was performed successfully in 153 patients, 135 with totally extraperitoneal sublay (TES) and 18 with transabdominal sublay (TAS). In 19 patients, TES was performed with the total visceral sac separation (TVS) technique, in which the space separation is carried out along the peritoneum, avoiding damage to the aponeurotic structure. Endoscopic transversus abdominis release (eTAR) was required in 17.0% of patients, and only 18.3% of patients required permanent mesh fixation. The median operative time was 135 min. Most patients had mild pain and resume eating soon after operation. No severe intraoperative complications occurred. Bleeding in the extraperitoneal space occurred in two patients and was stopped by nonsurgical treatment. Seroma and chronic pain were observed in 5.23 and 3.07% of patients. One recurrence occurred after TAS repair for an umbilical hernia. CONCLUSION: ESR is feasible, safe, and effective for treating ventral hernias when surgeons get the relevant surgical skills, such as the technique of "partition breaking," TVS, and eTAR. Small-to-medium ventral hernias are the major indications.

Regulator of G-protein signalling 3 and its regulator microRNA-133a mediate cell proliferation in gastric cancer.

BACKGROUND AND STUDY AIMS: Regulator of G-protein signalling 3 (RGS3) plays a pivotal role in Wnt signalling and epithelial-mesenchymal transition. RGS3 overexpression in gastric cancer suggests that RGS3 and its regulators have the potential to serve as therapeutic targets for gastric cancer. Therefore, we aimed to investigate the roles of RGS3 and its regulator microRNA-133a in gastric cancer tumorigenesis. MATERIAL AND METHODS: mRNA and protein expression levels of RGS3 in 107 paired human gastric cancer tissues and gastric cancer cells were examined using qRT-PCR and immunoblotting, respectively. The relationship between RGS3/microRNA-133a expression and clinicopathological characteristics was assessed using t-test. TargetScan, miRanda and MicroCosm Targets were employed to predict the binding site on the 3'-untranslated region of RGS3 that is targeted by microRNA-133a. Moreover, dual-luciferase reporter assay was performed to validate target prediction. microRNA-133a expression level in gastric cancer tissues and cell lines was determined by qRT-PCR. Finally, the proliferation activity of gastric cancer cells was evaluated using Cell Counting Kit-8 and bromodeoxyuridine incorporation assays. RESULTS: RGS3 expression level markedly increased in both gastric cancer tissues and cells compared with that in the corresponding normal tissues and cells. However, microRNA-133a expression level markedly decreased in gastric cancer tissues and cells and was negatively correlated with RGS3 expression. Higher RGS3 and lower microRNA-133a expression levels were associated with a larger tumour size, lymph node metastasis, local invasion and advanced tumour-node-metastasis stage in gastric cancer. Dual-luciferase reporter assay verified that microRNA-133a targeted RGS3 via mRNA 3'-untranslated region binding. Finally, microRNA-133a inhibited gastric cancer cell proliferation, whereas RGS3 overexpression attenuated this inhibitory effect. CONCLUSION: MicroRNA-133a is a regulator of RGS3 in gastric cancer and the microRNA-133a-RGS3 axis possibly participates in the malignant progression of gastric cancer.

Liensinine inhibited gastric cancer cell growth through ROS generation and the PI3K/AKT pathway.

Liensinine, an isoquinoline alkaloid extracted from the seed embryo of Nelumbo nucifera Gaertn, has been shown to exhibit various phrenological effects, including anti­cancer activity. The aim of this study is to investigate the effects and mechanisms of liensinine in human gastric cancer cells. In this study, we found liensinine can significantly inhibit gastric cancer cell proliferation in vitro and in vivo. Liensinine inducedgastric cancer cell apoptosis by increasing cleaved PARP, caspased 3 and caspased 9. Moreover, liensinine induced cycle arrest by downregulatingcyclinD1/cyclin­dependent kinase4 and phosphorylated protein kinase B. Furthermore, we found liensinine increases ROS levels and inhibits the PI3K/AKT pathway. These data suggested that liensinine might represent a novel and effective agent against gastric cancer.

Effect of peripherally inserted central catheter (PICC) parenteral nutrition on immune function and nutritional support after radical gastrectomy for gastric cancer.

Objective of the present study was to investigate the effects of peripherally inserted central catheter (PICC) parenteral nutrition support on immune function and nutritional support in patients undergoing radical gastrectomy for gastric cancer. 140 patients who underwent radical gastrectomy for gastric cancer were selected as participants and were divided into study group and the control group by random number table, with 70 cases in each group. Patients in the two groups underwent standard gastrectomy under general anesthesia by the same group of doctors. The study group received postoperative PICC catheter parenteral nutrition, and the control group received central venous catheter (CVC) nutrition support. Comparative study was done using t test and Chi-square test. The serum levels of ALB, TFN, PA, Hb, CD4+, CD8+, CD4+/CD8+, IgA, IgG, IgM and CD3+ in the two groups were observed before and after treatment, and the postoperative complications of the two groups were compared. After treatment, the levels of ALB, TFN, PA and Hb in the two groups were significantly increased (P<0.05). Levels of CD3+, CD4+, CD4+/CD8+, IgA, IgG and IgM also amplified significantly after treatment in both the groups, while CD8+ decreased significantly (P<0.05). What's more, the improvement degree of the study group was significantly greater than that of the control group (P<0.05). The time of drawing drainage tube, recovering intestinal function, getting off bed and the length of hospital stay in the study group were significantly shorter than those in the control group (P<0.05). The incidence of postoperative complications in the study group and control group were 8.6% (6/70 cases) and 11.4% (8/70 cases) respectively, and there was no significant difference (P>0.05). PICC catheter parenteral nutrition support and improve the nutritional status of patients, it was proved a safe and effective nutritional support which improve the cellular immune function and accelerated the recovery of gastrointestinal function.

Laparoscopic Appendectomy for Complicated Acute Appendicitis in the Elderly: A Single-center Experience.

BACKGROUND: The use of laparoscopic appendectomy for complicated acute appendicitis remains controversial in the elderly. This study aimed to compare the postoperative outcomes of elderly patients who received either laparoscopic appendectomy or open appendectomy. PATIENTS AND METHODS: A single-centre retrospective analysis of the clinical records of elderly patients (age, above 65 y) who underwent operations from January 2012 to November 2015 was performed. Demographic data, intraoperative variables, length of stay, and surgical complications were retrieved. RESULTS: A total of 145 elderly patients were preoperatively diagnosed with acute appendicitis. There were 43 (29.66%) complicated and 102 (70.34%) uncomplicated appendicitis cases. A total of 65 (44.83%) procedures were performed using the open technique (OA group) and 80 (55.17%) using the laparoscopic technique (LA group). In the laparoscopic group, 19 (23.75%) patients had complicated acute appendicitis (CLA group), and 61 (76.25%) had uncomplicated acute appendicitis (UCLA group). In the complicated group, 19 (44.19%) patients underwent operation using the laparoscopic technique (CLA group) and 24 (55.81%) using the open technique (COA group). There were no significant differences between the LA and OA groups in terms of age, sex distribution, duration of symptoms, American Society of Anesthesiologists score, white blood cells, complicated appendicitis, operation time, drain apposition, days to resumption of liquids, and postoperative complications (P>0.05). Significant differences were found in days to start walking and days to resumption of solids in the LA group (P<0.05). The OA group had a longer length of hospital stay than the LA group (P<0.05). Postoperative complications were not significantly different between the groups (P>0.05). The CLA group had a significantly longer duration of symptoms, operation times, days to resumption of liquids, and days to resumption of solids than the UCLA group (P<0.05). The COA group had significantly longer days to walking and hospital stays than the CLA group (P<0.05). CONCLUSIONS: Our study demonstrated that using LA to treat complicated acute appendicitis in the elderly was not associated with additional surgical complications. Therefore, it seems feasible to use LA as a safe technique for complicated acute appendicitis in the elderly.