Peptide encoded by lncRNA BVES-AS1 promotes cell viability, migration, and invasion in colorectal cancer cells via the SRC/mTOR signaling pathway.

Long non-coding RNAs (lncRNAs) have been revealed to harbor open reading frames (ORFs) that can be translated into small peptides. The peptides may participate in the pathogenesis of colorectal cancer (CRC). Herein, we investigated the role of a lncRNA BVES-AS1-encoded peptide in colorectal tumorigenesis. Through bioinformatic analysis, lncRNA BVES-AS1 was predicted to have encoding potential and to be associated with poor prognosis of patients with CRC. In CRC cells, BVES-AS1 was validated to encode a 50-aa-length micro-peptide, named BVES-AS1-201-50aa, through a western blotting method. BVES-AS1-201-50aa enhanced cell viability and promoted the migratory and invasive capacities of HCT116 and SW480 CRC cells in vitro, validated via CCK-8 assay and transwell assay, respectively. Immunofluorescence assay showed that BVES-AS1-201-50aa increased the expression of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 9 (MMP9) in CRC cells. We further verified that BVES-AS1-201-50aa targeted and activated the Src/mTOR signaling pathway in CRC cells by co-immunoprecipitation (Co-IP) experiment, qualitative proteomic analysis, and western blotting. Our findings demonstrated that BVES-AS1 could encode a micro-peptide, which promoted CRC cell viability, migration, and invasion in vitro. Our current work broadens the diversity and breadth of lncRNAs in human carcinogenesis.

Analysis of Prevention and Treatment of Anastomotic Leakage after Sphincter-Preserving Surgery for Middle- and Low-Grade Rectal Cancer under Laparoscopy.

Background: Anastomotic leakage is one of the most serious complications that can occur after laparoscopic-assistedsphincter-preserving surgery for middle- and low-grade rectal cancer. Objectives: To explore the cause, prevention, and treatment of anastomotic leakage after sphincter-preserving surgery for middle- and low-grade rectal cancer under laparoscopy. Methods: The clinical data from patients with mid- and low-grade rectal cancer who underwent laparoscopic-assistedanus-preserving surgery in the anorectal surgery department of our hospital have been analyzed. Patients with a definite diagnosis, indications for laparoscopic surgery, and sphincter-preserving surgery were included in the analysis, and patients with a protective loop ileostomy and laparotomy were excluded. Results: Among the 126 patients with middle- and low-grade rectal cancer undergoing sphincter-preserving surgery under laparoscopy. There were 75 male patients and 51 female patients, ranging in age from 37 to 89 years old, with an average age of 60.2 ± 6.7. The distance from the lower edge of the rectal tumor to the anal edge was ≤10 cm. 6 developed anastomotic leakage after the operation (leakage rate of 4.7%). Moreover, turbid purulent fluid was drained from the abdominal drainage tube in three patients on the third and fourth days after the operation, and the abdominal drainage tube drained serous drainage in three more patients on the fifth and sixth days, with signs of peritonitis appearing locally. All patients received continuous flushing and negative pressure drainage with a self-made double cannula and symptomatic treatment, and all were cured and discharged. Conclusion: Many factors can cause anastomotic leakage after this operation, and adequate perioperative preparation, meticulous operation during surgery, and careful postoperative management are key factors in preventing it.

Multi-Transcriptomic Analysis Reveals the Heterogeneity and Tumor-Promoting Role of SPP1/CD44-Mediated Intratumoral Crosstalk in Gastric Cancer.

GC is a fatal disease with high heterogeneity and invasiveness. Recently, SPP1 has been reported to be involved in the tumor progression of multiple human cancers; however, the role of SPP1 in GC heterogeneity and whether it is associated with the invasiveness and mortality of GC remain unclear. Here, we combined multiple RNA sequencing approaches to evaluate the impact of SPP1 on GC. Through bulk RNA sequencing (bulk RNA-seq) and immunohistochemistry (IHC), we found that SPP1 was highly expressed in GC, and high levels of SPP1 were associated with macrophage infiltration, an advanced tumor stage, and higher mortality for advanced GC patients. Furthermore, through simultaneous single-cell and spatial analysis, we demonstrated that SPP1+ macrophages are tumor-specific macrophages unique to cancer and enriched in the deep layer of GC tissue. Cell-cell communication analysis revealed that SPP1/CD44 interactions between SPP1+ macrophages and their localized tumor epithelial cells could activate downstream target genes in epithelial cells to promote dynamic changes in intratumor heterogeneity. Moreover, these activated genes were found to be closely associated with poor clinical GC outcomes and with cancer-related pathways that promote GC progression, as shown by survival analysis and enrichment analysis, respectively. Collectively, our study reveals that tumor-specific SPP1+ macrophages drive the architecture of intratumor heterogeneity to evolve with tumor progression and that SPP1 may serve as a prognostic marker for advanced GC patients, as well as a potential therapeutic target for GC.

Down-regulation of long non-coding RNA XIST aggravates sepsis-induced lung injury by regulating miR-16-5p.

This study aims to explain the role and related mechanisms of long non-coding RNA (lncRNA) X inactive specific transcript (XIST) in sepsis-induced acute lung injury (ALI). The in vivo septic models and in vitro septic model were established. In animal models, the lung injury of the rats was evaluated after XIST was overexpressed. In cell models, the effects of XIST and microRNA (miR)-16-5p on ALI was detected by MTT assay, Western blot and ELISA. The interaction between XIST and miR-16-5p was investigated by bioinformatics analysis, dual-luciferase reporter assay, RIP assay and RNA pull-down assay. We found that XIST expression was down-regulated in lung tissues of septic rats and lipopolysaccharide-stimulated cells, while the expression of miR-16-5p was up-regulated. Down-regulation of XIST significantly promoted pulmonary edema, increased the levels of TNF-α, IL-1ß and malondialdehyde, inhibited the cell viability and decreased the level of superoxide dismutase. Mechanistically, it was confirmed that XIST could sponge miR-16-5p, and thus repress its expression, and the transfection of miR-16-5p mimics could reverse the effects of XIST over-expression in the cell model. Collectively, it is concluded that XIST reduces sepsis-induced ALI via regulating miR-16-5p.

Failure of enhanced recovery programs after laparoscopic radical gastrectomy: a single-center retrospective study.

BACKGROUND: Enhanced recovery programs (ERPs), as a rapid rehabilitation method, have been widely used in gastric cancer patients. Although many related studies have confirmed their effectiveness, some patients may still experience poor clinical outcomes. This study analyzed risk factors associated with ERP failure after laparoscopic radical gastrectomy. METHODS: We analyzed the outcomes of 212 patients who underwent ERP following laparoscopic radical gastrectomy between March 2017 and December 2019. The ERP included preoperative education, short periods of fasting, non-mechanical intestinal preparation, early ambulation and oral feeding. ERP failure was defined as more than 7 days of hospitalization due to postoperative complications, unplanned readmission within 30 days of surgery, or death. RESULTS: The mean patient age was 62 years (range 39-89 years). Surgical procedures included total gastrectomy (n = 161) and distal gastrectomy (n = 51). Overall, 38 (17.9%) patients failed to complete the program, with no mortality. Univariable analysis (P < 0.15) revealed that ERP failure was associated with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) grade, tumor location, preoperative education, combined operation, long operation time, and significant blood loss. Multivariable analysis (P < 0.05) showed that age, ASA grade III, combined operation and preoperative education were independent risk factors for ERP failure. CONCLUSIONS: We showed that an advanced age, a high ASA grade, lack of a preoperative education and combined surgery were independent risk factors associated with ERP failure after laparoscopic gastrectomy. Therefore, a preoperative patient evaluations and education are important for the success of ERPs.

[Application of contralateral mastoplasty in breast reconstruction after breast cancer surgery].

Objective: To introduce a contralateral mastoplasty in breast reconstruction with prosthesis after breast cancer surgery in order to gain bilateral breasts symmetry. Methods: Between January 2016 and June 2018, 11 female patients with breast cancer were treated, aged 34-64 years old (mean, 49.6 years). There were 5 cases in left side and 6 cases in right side. There were 3 cases of invasive carcinoma and 8 cases of intraductal carcinoma. The diameter of tumor was 0.2-4.1 cm (mean, 2.5 cm). The disease duration ranged from 1 to 15 months (mean, 6 months). According to Regnault grading criteria, there were 7 cases of mild breast ptosis and 4 cases of moderate breast ptosis. Simple nipple-sparing mastectomy and reconstruction using prosthesis of the affected side, and folding and lifting of the nipple-areolar complex of the healthy side were performed. Results: The operation time was 144-188 minutes (mean, 158 minutes). The hospital stay was 6-9 days (mean, 7.5 days). Postoperatively, poor incision healing occurred in 1 case and healed after symptomatic treatment. The other incisions healed well and no surgical-related complications occurred. All patients were followed up 6-30 months (mean, 16 months). At 3 months after operation, the expert group adopted the self-made rating scale to evaluate the bilateral breasts symmetry, and the score was 8-10 (mean, 8.9). The patients were evaluated for their satisfaction according to the self-made score scale, and the score was 8-10 (mean, 9.1). Conclusion: After immediate breat reconstruction with prosthesis after breast cancer surgery, the satisfied bilateral breasts appearances and symmetry can be obtained by contralateral mastoplasty.

Effects of duodenal transection timing on clinical short-term outcomes of patients with laparoscopic spleen-preserving splenic hilar lymphadenectomy for advanced proximal gastric cancer.

BACKGROUND: To determine the optimal timing of duodenal transection in patients undergoing laparoscopic-assisted total gastrectomy (LATG) in combination with laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPL) for advanced proximal gastric cancer (APGC). METHODS: One hundred twenty-seven patients with APGC who received LATG with duodenal transection as well as LSPL between January 2017 and July 2018 were retrospectively recruited in this study. According to the different transection timing, the patients were allocated into two groups: a conventional group (CG) who received the duodenal transection prior to the LSPL and an experimental group (EG) who were given LSPL before the duodenum was transected. Clinical short-term outcomes were compared in the two groups. RESULTS: Analysis of the demographical and clinical characteristics showed that the two groups were comparable with no significant differences between CG and EG in the study patients regardless of their body mass indices (BMI). The intraoperative and postoperative indicators for clinical short-term outcomes were compared between the CG and EC, and results indicated that the EG had significant shorter mean time of LSPL and total operation time than those in the CG (P < 0.05). Of note, the numbers of patients with intraoperative injury and the volume of blood loss during the LSPL procedure were significantly reduced in the EG versus CG (P < 0.05). For the obese APGC patients, administration of LSPL prior to duodenal transection significantly increased the number of dissected No.10 lymph nodes (LNs) (P < 0.05). The other intraoperative and postoperative indicators did not show any differences between the two comparison groups. CONCLUSIONS: Our findings demonstrated that duodenal transection timing was significantly associated with clinical short-term outcomes of APGC patients. The duodenal transection prior to the LSPL is superior overall to the conventional transection timing in the treatment of APGC patients with LATG and LSPL in combination.

Prognostic value of presepsin for outcomes and complications in enterocutaneous fistula complicated by abdominal sepsis.

BACKGROUND: Enterocutaneous fistula (ECF) poses a supreme challenge for the surgeons associated with abdominal sepsis, fluid electrolyte imbalance and undernutrition. Individual prognostic stratification is pivotal in the clinical management. Presepsin is a novel biomarker showing diagnostic and prognostic value in sepsis. We aimed to evaluate the prognostic value of presepsin in ECF. METHODS: Consecutive patients with ECF were enrolled if diagnosed as abdominal sepsis from June 2014 to June 2015. Serum concentration of presepsin at admission was measured, and medical records including demographics, medical history, treatment modalities, complications and outcomes were collected. Kaplan-Meier curves was drawn to demonstrate the cumulative incidence of source control of infection and fistula closure, and Cox regression analysis was performed to identify independent factors. Association between presepsin and other markers was evaluated by Pearson's correlation coefficient. RESULTS: 71 patients were included with the median presepsin concentration of 726 pg/mL at admission. Baseline presepsin levels showed predictive potential in successful source control of intra-abdominal infection but not in fistula closure. Patients with higher presepsin had more severe intra-abdominal infection as denoted by higher levels of WBC, CRP and PCT, as well as high risks of complications and failure of fistula closure compared with those having lower presepsin (≤726 pg/mL). Presepsin concentration was positively associated with APACHE II score, CRP and PCT. CONCLUSIONS: Presepsin shows prognostic values for source control of abdominal sepsis and clinical courses of ECF. This index may help stratify patients, facilitating the monitoring and adjustment of the therapeutic regimen at an early stage.

Quercetin Suppresses the Migration and Invasion in Human Colon Cancer Caco-2 Cells Through Regulating Toll-like Receptor 4/Nuclear Factor-kappa B Pathway.

OBJECTIVE: The migration and invasion features, which were associated with inflammatory response, acted as vital roles in the development of colon cancer. Quercetin, a bioflavonoid compound, was widely spread in vegetables and fruits. Although quercetin exerts antioxidant and anticancer activities, the molecular signaling pathways in human colon cancer cells remain unclear. Hence, the present study was conducted to investigate the suppression of quercetin on migratory and invasive activity of colon cancer and the underlying mechanism. MATERIALS AND METHODS: The effect of quercetin on cell viability, migration, and invasion of Caco-2 cells was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound-healing assay, and transwell chambers assay, respectively. The protein expressions of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) p65, mitochondrial membrane potential-2 (MMP-2), and MMP-9 were detected by Western blot assay. The inflammatory factors, such as tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (Cox-2), and interleukin-6 (IL-6), in cell supernatant were detected by enzyme-linked immunosorbent assay. RESULTS: The concentration of quercetin <20 µM was chosen for further experiments. Quercetin (5 µM) could remarkably suppress the migratory and invasive capacity of Caco-2 cells. The expressions of metastasis-related proteins of MMP-2, MMP-9 were decreased, whereas the expression of E-cadherin protein was increased by quercetin in a dose-dependent manner. Interestingly, the anti-TLR4 (2 µg) antibody or pyrrolidine dithiocarbamate (PDTC; 1 µM) could affect the inhibition of quercetin on cell migration and invasion, as well as the protein expressions of MMP-2, MMP-9, E-cadherin, TLR4, and NF-κB p65. In addition, quercetin could reduce the inflammation factors production of TNF-α, Cox-2, and IL-6. CONCLUSION: The findings suggested for the 1(st) time that quercetin might exert its anticolon cancer activity via the TLR4- and/or NF-κB-mediated signaling pathway. SUMMARY: Quercetin could remarkably suppress the migratory and invasive capacity of Caco-2 cellsThe expressions of metastasis-related proteins of mitochondrial membrane potential-2 (MMP-2), MMP-9 were decreased, whereas the expression of E-cadherin protein was increased by quercetin in a dose-dependent mannerThe anti-toll-like receptor 4 (TLR4) antibody or pyrrolidine dithiocarbamate affected the inhibition of quercetin on cell migration and invasion, as well as the protein expressions of MMP-2, MMP-9, E-cadherin, TLR4, and nuclear factor-kappa B p65Quercetin could reduce the inflammation factors production of tumor necrosis factors-α, cyclooxygenase-2, and interleukin-6. Abbreviations used: MTT: 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphen yltetrazolium bromide, TLR4: Toll-like receptor 4, NF-κB: Nuclear factor-kappa B, MMP-2: Mitochondrial membrane potential-2, MMP-9: Mitochondrial membrane potential-9, TNF-α: Tumor necrosis factor-α, Cox-2: Cyclooxygenase-2, IL-6: Interleukin-6, ELISA: Enzyme-linked immunosorbent assay, PDTC: Pyrrolidine dithiocarbamate, ROS: Reactive oxygen species, DMSO: Dimethyl sulfoxide, FBS: Fetal bovine serum, DMEM: Dulbecco modified Eagle medium, OD: Optical density, IPP: Image Pro-plus, PBS: Phosphate buffered saline, SD: Standard deviation, ANOVA: One-way analysis of variance, SPSS: Statistical Package for the Social Sciences, ECM: Extracellular matrix, TLRs: Toll-like receptors, LPS: Lipopolysaccharide.

Hand-assisted laparoscopic total gastrectomy with regional lymph node dissection for advanced gastric cancer.

BACKGROUND AND OBJECTIVES: Laparoscopic-assisted distal gastrectomy has been applied to the treatment of gastric cancer. However, there have been few reports on the laparoscopic-assisted total gastrectomy for advanced gastric cancer, mainly because of the difficulty of the procedure. METHODS: Here, we report a series of cases where the hand-assisted laparoscopic total gastrectomies with regional lymph node dissection were performed successfully. RESULTS: The average operative time was 245 minutes. The mean blood loss was 110 mL. The number of dissected lymph nodes per patient was beyond 15 nodes satisfying a reliable evaluation of nodal status. All resection specimens had no residual tumor at the proximal or distal resection margins. The mean oral feeding was 3.6 days. The mean postoperative length of stay was 8.7 days. CONCLUSIONS: The hand-assisted laparoscopic D2 total gastrectomy for advanced gastric cancer is both technically feasible and safe.

[Systematic reviews of mini-invasive surgery versus standard approaches for total knee arthroplasty].

OBJECTIVE: To conduct a systematic review to compare the early efficacies of minimally invasive surgery (MIS) versus conventional approaches in TKA (total knee arthroplasty). METHODS: Randomized controlled trials (RCTs) and clinical controlled trials (CCTs) were retrieved from the databases of MEDLINE (1996.6 - 2010.12), EMBASE (1996.6 - 2010.12), PubMed (1996 - 2010.12) and Cochrane Library (Issue 2, 2012). Journal of Orthopedics (from establishment to December 2010) and Orthopedic Journal of China (from establishment to December 2010) were manually searched. Both RCTs and CCTs were included. The data were extracted by two reviewers with designed extraction form RevMan 4.2.8 software for data analysis. The criteria were as follows: (1) operative duration and reduced blood loss; (2) VAS (visual analog scale) score; (3) faster recovery of ROM (range of movement); (4) quadriceps muscle strength; (5) component positioning malalignment; (6) tibiofemoral angle; (7) rate of complications. RESULTS: A total of 18 RCTs were included. Compared with the standard TKA procedure, the MIS group had a longer operative duration (WMD (weighted mean difference) 14.16, 95%CI (confidence interval) (12.61, 15.71)); reduced blood loss (WMD 8.31, 95%CI (6.16, 10.46)); lower VAS score at Days 3-5 post-operation (WMD 4.99, 95%CI (4.19, 5.78)); better Mean Knee Society scores at Week 6 post-operation (WMD 4.99, 95%CI (4.19, 5.78)), improvement in ROM occurred more rapidly at Month 3 post-TKA (WMD 14.59, 95%CI (8.39, 20.80)). Although the differences were not statistically significant, tibiofemoral angle was more precise in the standard group and the rate of component malalignment occurred more frequently in the MIS group (WMD 0.20, 95%CI (-0.12, 0.52)) (RR 1.57, 95%CI (0.88, 2.83)). CONCLUSION: MIS leads to a faster recovery than conventional surgery with a shorter operative duration, a reduced blood loss, a lower VAS score and a faster recovery of ROM and quadriceps muscle strength. However, the rates of component malalignment and complications occur more frequently in the MIS group. Potential benefits in long-term survival rate and functional improvement require further investigations.

[Comparison of clinical results between high-flexion and standard cruciate-stabling prostheses in total knee arthroplasty].

OBJECTIVE: To compare the clinical results between high-flexion and standard cruciate-stabling prostheses in total knee arthroplasty (TKA) by using the 36-item short form health survey (SF-36). METHODS: Between August 2007 and January 2009, 98 patients (106 knees) underwent TKA with standard cruciate-stabling prostheses (standard group), and 46 patients (50 knees) underwent TKA with high-flexion prostheses (high-flexion group). In standard group, there were 30 males (32 knees) and 68 females (74 knees) with an age of (70.0 +/- 3.5) years, including 78 cases (82 knees) of osteoarthritis (OA) and 20 cases (24 knees) of rheumatoid arthritis (RA) with a disease duration of (14.5 +/- 3.3) years; the Hospital for Special Surgery Scoring System (HSS) and the range of motion (ROM) were 56.1 +/- 21.6 and (89.0 +/- 16.1) degrees, respectively. In high-flexion group, there were 8 males (10 knees) and 38 females (40 knees) with an age of (68.6 +/- 8.9) years, including 44 cases (47 knees) of OA and 2 cases (3 knees) of RA with a disease duration of (13.9 +/- 4.1) years; the HSS and ROM were 58.9 +/- 25.3 and (91.0 + 19.3) degrees, respectively. There was no significant difference in the general data (P > 0.05) between 2 groups, so the clinical data of 2 groups had comparability. RESULTS: In standard group, poor wound healing and persistent headache caused by cerebrospinal fluid leakage occurred in 1 case, respectively. In high-flexion group, transient common peroneal nerve palsy occurred in 1 case. There was significant difference (P < 0.05) in the hospitalization expense between standard group [yen(39,000 +/- 6000)] and high-flexion group [yen (52,000 +/- 8 000)]. The follow-up time was 12-26 months (18 months on average) in standard group (91 cases, 98 knees) and 11-19 months (13 months on average) in high-flexion group (44 cases, 47 knees). The SF-36 showed significant difference in role-physical score (P < 0.05), but no significant difference in other 7 indices scores (P > 0.05). At the final follow- up, the ROM was (129.1 +/- 19.2) degrees in high-flexion group and (123.6 +/- 16.7) degrees in standard group; showing significant difference (P < 0.05). The HSS was 91.2 +/- 17.6 in high-flexion group and 92.5 +/- 14.5 in standard group; showing no significant difference (P > 0.05). CONCLUSION: After TKA, the ROM in high-flexion group is superior to that in standard group, but there is no obvious advantages in terms of the HSS and SF-36 outcomes.

[Systematic review of anterior versus posterior surgical treatments of thoracolumbar fractures].

OBJECTIVE: To evaluate the effectiveness of anterior versus posterior surgical treatments of thoracolumbar fractures. METHODS: Randomized controlled trials (RCTs) and clinical controlled trials (CCTs) were identified from MEDLINE (1966 - 2006.7), EMBASE (1966 - 2006.7), PubMed (1996 - 2006.7), Cochrane Library (Issue 2, 2006).We hand-searched Chinese Journal of Orthopedics (from establishment to May 2006) and Orthopaedic Journal of China (from establishment to May 2006). RCTs and CCTs were included. Data were extracted by two reviewers with designed extraction form. RevMan 4.2.8 software was used for data analysis. RESULTS: Two RCTs and four prospective clinical trials were included. The combined results showed that compare with posterior surgical management, anterior approach in the treatment of thoracolumbar fractures proved the less incidence of complications; better neurologic recovery and corrected kyphosis angle; more complete and reliable decompression of the canal. However, there was not difference between the two groups in the general status outcomes. CONCLUSIONS: To compare with posterior fixation system, anterior surgical managements in the thoracolumbar spinal trauma might be the optimal choices because the lower rates of complications and loss of corrected kyphosis angle; better neurologic recovery, also. Besides, due to the lack of Evidence-based guidelines for the treatment of thoracolumbar spinal injuries, the results which indicated above need further study.

[Reversal of multidrug resistance in drug-resistant cell line EAC/ADR by cepharanthine hydrochloride and its mechanism].

AIM: To investigate the correlation between reversal effect of cepharanthine hydrochloride (CH) on multidrug resistance (MDR) in drug-resistant cell line EAC/ADR and the nuclear transcription factor-KB (NF-KB). METHODS: Cytotoxicity was determined by the tetrazolium (MTT) assay in vitro. An EAC/ADR cell homograft model was established to investigate the effect of CH on reversing MDR in vivo. The constitutive activity and activation of NF-KB by drugs were measured by Dot-Enzyme-linked Immune Sorbent Assay (Dot-ELISA). RESULTS: CH was shown to potentiate the cytotoxicity of ADR, a 13- fold reversal effect of resistance was achieved in vitro. In mice bearing EAC/ADR cell homografts, CH was found to prolong the survival time of animals bearing tumor. Increase in life span over control was 75. 37%. In addition, the constitutive activity of NF-KB and activation of NF-KB by chemotherapy were lowered by CH. CONCLUSION: The findings suggest that CH is able to reverse drug resistance and its mechanism may be related to suppressing the constitutive activity and activation of NF-KB by drugs.