lncRNA SNHG9 enhances liver cancer stem cell self-renewal and tumorigenicity by negatively regulating PTEN expression via recruiting EZH2.

Liver cancer stem cell (CSC) self-renewal and tumorigenesis are important causes of hepatocellular carcinoma (HCC) recurrence. We purposed to investigate the function of long noncoding RNA small nucleolar RNA host gene 9 (SNHG9) in liver CSC self-renewal and tumorigenesis in this study. Flow cytometry was carried out to separate CD133+ Populations and CD133- Populations from HCC cell lines. A combination of CD133+ cells and Matrigel matrix was subcutaneously injected to create the NOD-SCID mouse xenograft tumor model. Colony formation test and spheroids formation assay were carried out to clarify the impact of SNHG9 on the self-renewal of liver CSCs. RNA immunoprecipitation, RNA-pull down, and chromatin immunoprecipitation were performed on CD133+ cells to elucidate the mechanism of SNHG9 regulating PTEN expression. We found that SNHG9 was highly expressed in HCC clinical samples, HCC cells, and CD133+ cells. In vitro, interference with SNHG9 prevented the formation of colonies and spheroids in liver CSC cells and primary HCC cells. In vivo, interference with SNHG9 reduced the tumor volume and weight. SNHG9 could bind to EZH2, and SNHG9 interference suppressed EZH2 recruitment and H3K27me3 levels in the PTEN promoter region. In addition, SNHG9 inhibition promoted PTEN expression while having little impact on EZH2 levels. Interference with SNHG9 inhibited liver CSC self-renewal and tumorigenesis by up-regulating PTEN levels. In conclusion, by binding to EZH2, SNHG9 down-regulated PTEN levels, promoting liver CSC self-renewal and tumor formation, and exacerbating HCC progression.

The Association Between Visceral Obesity and Postoperative Outcomes in Elderly Patients With Colorectal Cancer.

Background: The impact of visceral obesity on the postoperative complications of colorectal cancer in elderly patients has not been well studied. This study aims to explore the influence of visceral obesity on surgical outcomes in elderly patients who have accepted a radical surgery for colorectal cancer. Methods: Patients aged over 65 year who had undergone colorectal cancer resections from January 2015 to September 2020 were enrolled. Visceral obesity is typically evaluated based on visceral fat area (VFA) which is measured by computed tomography (CT) imaging. Univariate and multivariate analyses were performed to analyze parameters related to short-term outcomes. Results: A total of 528 patients participated in this prospective study. Patients with visceral obesity exhibited the higher incidence of total (34.1% vs. 18.0%, P < 0.001), surgical (26.1% vs. 14.6%, P = 0.001) and medical (12.6% vs. 6.7%, P = 0.022) complications. Based on multivariate analysis, visceral obesity and preoperative poorly controlled hypoalbuminemia were considered as independent risk factors for postoperative complications in elderly patients after colorectal cancer surgery. Conclusions: Visceral obesity, evaluated by VFA, was a crucial clinical predictor of short-term outcomes after colorectal cancer surgery in elderly patients. More attentions should be paid to these elderly patients before surgery.

Sodium-glucose co-transporter 1 (SGLT1) differentially regulates gluconeogenesis and GLP-1 receptor (GLP-1R) expression in different diabetic rats: a preliminary validation of the hypothesis of "SGLT1 bridge" as an indication for "surgical diabetes".

Background: Sodium-glucose co-transporter 1 (SGLT1) may play a synergistic role in gluconeogenesis (GNG) and glucagon-like peptide-1 (GLP-1) expression. We proposed the hypothesis of a "SGLT1 bridge" as an indication for "surgical diabetes" that was preliminary validated in the present study. Methods: We selected nonobese diabetic Goto-Kakizaki (GK) rats and Zuker diabetic fat (ZDF) rats to represent advanced and early diabetes, respectively. Based on glucose gavage with or without SGLT1 inhibitor phlorizin, the rats were divided into 4 groups: Gk-Glu, GK-P, ZDF-Glu, and ZDF-P. The expressions of SGLT1, GLP-1 receptor (GLP-1R), glucose-6 phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase-1 (Pck1) were determined by immunohistochemistry (IHC) or quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the effects of phlorizin were analyzed. Results: Glucose tolerance was worse in GK rats and the homeostasis model assessment-insulin resistance (HOMA-IR) was higher in ZDF rats, indicating different pathophysiological conditions between the different diabetic rats. GK rats showed higher activity of duodenal SGLT1 (P=0.022) and jejunal SGLT1 mRNA expression (P=0.000) and lower SGLT1 mRNA expression in the liver (P=0.000) and pancreas (P=0.000). Phlorizin effectively inhibited the activity of duodenal SGLT1 in both GK rats (P=0.000) and ZDF rats (P=0.000). In ZDF rats, the expression of GLP-1R mRNA was downregulated in the jejunum (P=0.001) and upregulated in the pancreas (P=0.021) by phlorizin, but there were no regulatory effects on GLP-1R mRNA in the jejunum and pancreas of GK rats. As for the regulatory effects on GNG, phlorizin upregulated Pck1 mRNA in the duodenum (P=0.000) and the jejunum (P=0.038), whereas it downregulated hepatic G6Pase mRNA in ZDF rats (P=0.005) and Pck1 mRNA expression in GK rats (P=0.001), suggesting that SGLT1 inhibitor may have upregulated intestinal GNG in ZDF rats and downregulated hepatic GNG in both ZDF and GK rats. Conclusions: SGLT1 showed synergistic regulatory effects on the entero-insular axis (EIA) and the gut-brain-liver axis (GBLA), preliminarily validating the hypothesis of a "SGLT1 bridge". The distinct expression of SGLT1 and its differentially regulatory effects on diabetic rats with different pathophysiological conditions may provide probable potential indications involved in the "Surgical Diabetes" that is supposed as the inclusion for diabetic surgery.

Effect of GLIM-defined malnutrition on postoperative clinical outcomes in patients with colorectal cancer.

BACKGROUND: Malnutrition is common in colorectal cancer patients. Malnutrition is recognized as a risk factor for adverse postoperative outcomes, yet there are no consistent diagnostic criteria for it. Thus, the Global Leadership Initiative on Malnutrition published new universal criteria. We aimed to investigate the prevalence of malnutrition with the application of Global Leadership Initiative on Malnutrition criteria, and explore the correlations between Global Leadership Initiative on Malnutrition-defined malnutrition and postoperative clinical outcomes in colorectal cancer patients. METHODS: We included a cohort of 918 patients who underwent radical resection surgery for colorectal cancer from July 2014 to October 2019. Malnutrition was diagnosed based on the Global Leadership Initiative on Malnutrition criteria. The associations between nutritional status and postoperative clinical outcomes were analyzed by the Kaplan-Meier method, logistic and Cox regression analyses. RESULTS: Among the included patients, 23.6% were diagnosed as malnutrition based on Global Leadership Initiative on Malnutrition criteria. Global Leadership Initiative on Malnutrition-defined malnutrition was associated with total postoperative complications [odds ratio: 1.497 (1.042-2.152), P = 0.029]. Further, Global Leadership Initiative on Malnutrition-diagnosed malnutrition was an independent risk factor for overall survival [hazard ratio: 1.647 (1.048-2.587), P = 0.030] and disease-free survival [hazard ratio: 1.690 (1.169-2.441), P = 0.005]. CONCLUSIONS: The Global Leadership Initiative on Malnutrition criteria is effective to assess malnutrition. Preoperative malnutrition is associated with postoperative complications, overall survival and disease-free survival in colorectal cancer patients after radical resection surgery.

Identification of APEX2 as an oncogene in liver cancer.

BACKGROUND: DNA damage is one of the critical contributors to the occurrence and development of some cancers. APEX1 and APEX2 are the most important molecules in the DNA damage, and APEX1 has been identified as a diagnostic and prognostic biomarker in liver hepatocellular carcinoma (LIHC). However, the expression of APEX2 and its functional mechanisms in LIHC are still unclear. AIM: To examine the expression of APEX2 and the potential mechanism network in LIHC. METHODS: We conducted a pan-cancer analysis of the expression of APEX1 and APEX2 using the interactive TIMER tool. GEO datasets, including GSE14520, GSE22058, and GSE64041, were used to compare the APEX2 expression level in tumor tissues and adjacent non-tumor tissues. Then, we calculated the 5-year survival rate according to the web-based Kaplan-Meier analysis. We included the TCGA liver cancer database in GSEA analysis based on the high and low APEX2 expression, showing the potential mechanisms of APEX2 in LIHC. After that, we conducted Pearson correlation analysis using GEPIA2. Next, we performed quantitative polymerase chain reaction (qPCR) assay to examine the APEX2 levels in normal liver cell line LO2 and several liver cancer cell lines, including HepG2, Huh7, SMMC7721, and HCCLM3. APEX2 in HCCLM3 cells was knocked down using small interfering RNA. The role of APEX2 in cell viability was confirmed using CCK-8. Dual-luciferase reporter assay was performed to examine the promoter activity of CCNB1 and MYC. RESULTS: APEX1 and APEX2 are both highly expressed in the tumor tissues of BLCA, BRCA, CHOL, COAD, ESCA, HNSC, LIHC, LUAD, LUSC, READ, and STAD. APEX2 overexpression in LIHC was validated using GSE14520, GSE22058, and GSE64041 datasets. The survival analysis showed that LIHC patients with high expression of APEX2 had a lower overall survival rate, even in the AJCC T1 patients. High level of APEX2 could indicate a lower overall survival rate in patients with or without viral hepatitis. The GSEA analysis identified that kinetochore and spindle microtubules are the two main cellular components of APEX2 in GO Ontology. APEX2 was also positively associated with molecular function regulation of chromosome segregation and DNA replication. The results of KEGG analysis indicated that APEX2 expression was positively correlated with cell cycle pathway and pro-oncogenic MYC signaling. Pearson correlation analysis showed that APEX2 had a significant positive correlation with CCNB1 and MYC. APEX2 level was higher in liver cancer cell lines than in normal liver LO2 cells. Small interfering RNA could knock down the APEX2 expression in HCCLM3 cells. Knockdown of APEX2 resulted in a decrease in the viability of HCCLM3 cells as well as the expression and promoter activity of CCNB1 and MYC. CONCLUSION: APEX2 is overexpressed in LIHC, and the higher APEX2 level is associated with a worse prognosis in overall survival. APEX2 is closely involved in the biological processes of chromosome segregation and DNA replication. APEX2 expression is positively correlated with the pro-oncogenic pathways. Knockdown of APEX2 could inhibit the cell viability and CCNB1 and MYC pathways, suggesting that APEX2 is an oncogene in LIHC, which could be a potential pharmaceutic target in the anti-tumor therapy.

LncRNA SOCS2-AS1 inhibits progression and metastasis of colorectal cancer through stabilizing SOCS2 and sponging miR-1264.

Abnormal expression of long noncoding RNA (lncRNA) is involved in human cancers, including colorectal cancer (CRC). However, their functional mechanism is largely unknown. In this study, we explored the roles of lncRNA SOCS2-AS1 in modulating CRC progression. We showed that SOCS2-AS1 was lowly expressed in CRC tissues and cells. SOCS2-AS1 downregulation predicted a poor prognosis in patients with CRC. SOCS2-AS1 overexpression significantly suppressed CRC cell proliferation, colony formation, EdU incorporation, cell-cycle, migration and invasion in vitro while SOCS2-AS1 knockdown led to an opposite phenotype. SOCS2-AS1 overexpression inhibited CRC growth and metastasis in vivo. Mechanistically, we discovered that SOCS2-AS1 was positively correlated with SOCS2 expression in CRC tissues. SOCS2-AS1 contributes to SOCS2 expression through restraining miR-1264. Additionally, we showed that SOCS2 silencing abrogated the suppressive effects of SOCS2-AS1 overexpression. Taken together, our results identified a novel regulatory loop in which SOCS2-AS1/miR-1264/SOCS2 axis suppresses CRC progression.

Laparoscopic-assisted colorectal surgery benefits visceral obesity patients: a propensity-matched analysis.

BACKGROUND: We aimed to determine the safety and effectiveness of laparoscopic-assisted surgery (LAS) in visceral obesity patients with colorectal cancer (CRC). PATIENTS AND METHODS: We retrospectively collected the clinical data of consecutive patients who underwent colorectal surgery for CRC between August 2014 and July 2018. The third lumbar vertebra visceral fat area was measured to diagnose visceral obesity. One-to-one propensity score matching was performed to compare the short-term outcomes between the open surgery (OS) and LAS in visceral obesity patients. Univariate and multivariate analyses were performed to evaluate the risk factors of postoperative complications. RESULTS: A total of 280 visceral obesity patients were included in this study with 140 patients for each group. Compared with the OS group, the LAS group had more lymph nodes harvested, longer surgical duration, and shorter postoperative hospital stay. The overall incidence of complications in OS was significantly higher than LAS (32.1 vs. 20.0%, P=0.021). Multivariate analysis revealed that age of at least 65 years (odds ratio: 1.950, 95% confidence interval: 1.118-3.403; P=0.019) was an independent risk factor for postoperative complications, whereas LAS (odds ratio: 0.523, 95% confidence interval: 0.302-0.908; P=0.021) was a protective factor. CONCLUSION: LAS in visceral obesity patients with CRC was a safer and less invasive alternative than open surgery, with fewer complications within the first 30 days postoperatively.

Ileal transposition rapidly improves glucose tolerance and gradually improves insulin resistance in non-obese type 2 diabetic rats.

BACKGROUND: Many studies have confirmed that ileal transposition can improve type 2 diabetes mellitus (T2DM), accompanied by increased glucagon-like peptide-1 (GLP-1). We performed the experiment on diabetic rats to evaluate the effects and mechanisms of ileal transposition on the glycemic metabolism. METHODS: Twenty Goto-Kakizaki (GK) rats were randomly divided into the ileal transposition group (IT group) and the sham operation group (Sham group). Weight, food intake, fasting plasma glucose (FPG), fasting insulin (F-ins), oral glucose tolerance test (OGTT) and GLP-1 were determined at baseline and 1, 4, 8, 16 and 24 weeks post-operatively. The homeostasis model assessment-insulin resistance (HOMA-IR) index and the area under the curve (AUC) during OGTT were measured. Histological determination of the GLP-1 receptor (GLP-1R) was performed on the pancreas and ileum 24 weeks post-operatively. RESULTS: In comparison with the Sham group, the IT group showed a higher GLP-1 level and lower AUC at 4, 8, 16 and 24 weeks post-operatively (all P < 0.05) and a lower FPG, F-ins levels and HOMA-IR at 8, 16 and 24 weeks post-operatively (all P < 0.05). Compared with baseline levels, the plasma GLP-1, AUC and FPG levels decreased significantly at each post-operative time point in the IT group (all P < 0.05), but not in the Sham group (all P > 0.05); F-ins and HOMA-IR significantly decreased at 8, 16 and 24 weeks post-operatively in the IT group (all P < 0.05). GLP-1R expression in the IT group was significantly higher than that of the Sham group in both the pancreas and the ileum at 24 weeks post-operatively (P < 0.05). CONCLUSIONS: Ileal transposition ameliorated glucose metabolism without reduction in weight or food intake in GK rats, which may be induced by the increased GLP-1 expression. However, the delayed improvement of insulin resistance, accompanied by decreased plasma insulin levels, might not directly result from the increased GLP-1.

CircRNA_100290 promotes colorectal cancer progression through miR-516b-induced downregulation of FZD4 expression and Wnt/ß-catenin signaling.

Accumulating evidence indicates that circular RNAs (circRNA) exert crucial functions in the development and advance of cancers. CircRNA_100290 has been reported to promote proliferation in oral cancer. However, whether it participates in colorectal cancer (CRC) remains unclear. Here, our report showed that circRNA_100290 level was significantly increased in CRC tissues and cell lines. Besides, circRNA_100290 expression was positively correlated with tumor metastasis while inversely correlated with prognosis. Silencing circRNA_100290 markedly reduced cell proliferation rate, inhibited migration and invasion abilities, but promoted apoptosis in vitro. Mechanistically, our data revealed circRNA_100290 was a competing endogenous RNA (ceRNA) of FZD4 by sponging miR-516b, leading to activation of Wnt/ß-catenin pathway. Rescue assay indicated that FZD4-induced activation of ß-catenin pathway is indispensable for the function of circRNA_100290 in CRC. In summary, our study for the first time revealed a novel regulatory loop of circRNA_100290/miR-516b/FZD4/Wnt/ß-catenin implicated in CRC progression.

[Zhu's trocar placement in laparoscopic appendectomy in the treatment of complicated appendicitis].

OBJECTIVE: To evaluate the feasibility and efficacy of Zhu's trocar placement (ZTP) in laparoscopic appendectomy (LA) in the treatment of complicated appendicitis. METHODS: Clinical data of 139 complicated appendicitis patients undergoing LA at the First Affiliated Hospital of Wenzhou Medical University from June 2013 to December 2017 were retrospectively analyzed. ZTP-LA group comprised 59 cases and its procedure was as follows: 10 mm umbilical trocar was used as lens port; 12 mm trocar at crossing point of umbilical hole horizontal line and right midclavicular line was used as main operating port; 5 mm trocar at the crossing point of horizontal line 0-3 cm below umbilicus and right anterior axillary line was used as assist operating port with the drainage function for Douglas fossa and right iliac fossa; The operator and the assistant stood on the right side and the left side of the patient respectively. Traditional three-port group comprised 80 cases (8 cases converted to laparotomy, 72 cases enrolled finally) and its procedure was as follows: 10 mm lens port below umbilicus; 10-12 mm main operating port at lateral border of left lower rectus abdominis; 5 mm assist operating port above pubis; The operator and the assistant stood on left side of the patient. The operative time, time to oral semi-fluid, postoperative hospital stay, cost during hospitalization, and postoperative morbidity of complication were compared between two groups. RESULTS: Baseline data such as gender, age, WBC count, percentage of leukocyte, pathological finding and type were not significantly different between two groups(all P>0.05). The conversion rate in ZTP-LA was significantly lower than that in traditional three-port group [0%(0/59) vs. 10.0%(8/80),χ²=4.552,P=0.033]. Compared with traditional three-port group, ZTP-LA group showed shorter operative time [(47.8±20.1) minutes vs. (66.0±27.3) minutes, t=4.383,P<0.001], shorter time to oral semi-fluid [(35.0±20.7) hours vs. (59.3±32.8) hours, t=5.158,P<0.001], shorter postoperative hospital stay [(4.1±1.6) days vs. (5.5±2.2) days, t=4.162, P<0.001], lower postoperative morbidity of complication [3.4% (2/59) vs. 18.1%(13/72), χ²=6.879, P=0.009], lower incidence of postoperative intra-abdominal abscess [0%(0/59) vs. 11.1%(8/72), χ²=5.179, P=0.023], lower incidence of paralytic ileus [1.7%(1/59) vs. 12.5%(9/72), χ²=3.946, P=0.047] and less cost during hospitalization[(13 585±2909) yuan vs.(16 861±5334) yuan, t=4.463, P<0.001]. CONCLUSION: ZTP-LA is safe, feasible and effective with advantages of faster recovery and less cost in the treatment of complicated appendicitis.

Hsa_circ_0103809 promotes cell proliferation and inhibits apoptosis in hepatocellular carcinoma by targeting miR-490-5p/SOX2 signaling pathway.

BACKGROUND: Circular RNAs (circRNAs) represent a class of non-coding RNAs that are emerging as important regulators during tumorigenesis and provide potential targets for cancer intervention. However, the expression profiles and functions of circRNAs in hepatocellular carcinoma (HCC) have not been completely clarified. Herein, the role of hsa_circ_0103809 was investigated in HCC tissues and cell lines. METHODS: High-throughput circRNA sequencing was performed to detect the expression profiles of circRNA in HCC tissues. The CCK-8, wound healing and flow cytometry were performed to measure the cell viability, migration and apoptosis in HCC cells. The expression levels of gene and protein in HCC tissues and cell lines were assayed by RT-qPCR and western blotting, respectively. Immunohistochemical staining was used to assess the protein expression of SOX2 in HCC tissues. RESULTS: We discovered that hsa_circ_0103809 was significantly increased in HCC tissues and cell lines. Knockdown of hsa_circ_0103809 inhibited proliferation and migration and induced apoptosis in HCC cell lines. Investigation to the molecular mechanisms of hsa_circ_0103809 in HCC cells had revealed that hsa_circ_0103809 directly suppressed miR-490-5p, which targeted to the 3'-UTR of SOX2. Hsa_circ_0103809 loss-of-function could increase the expression of miR-490-5p as well as decreased the expression of SOX2. Furthermore, we found that si-0103809 induced growth and migration inhibition and apoptosis could be reversed by transfected with miR-490-5p inhibitors or SOX2 in HCC cells. CONCLUSION: Our findings suggested that hsa_circ_0103809 might facilitate HCC malignant progression, at least partially, by regulating miR-490-5p/SOX2 signaling pathway.

Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway.

BACKGROUND: Nano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer. METHODS: The chitosan nano-particles were prepared by using the ionic gelation method. The characterizations of the nano-particles were determined by transmission electron microscopy. The cytotoxicity was detected by MTT assay, and the endocytosis, cell apoptosis and cell cycle were examined by flow cytometry. The protein level was analyzed with western blot. The dual luciferase reporter assay was performed to assess the interaction between p53 and the promoter of PRC1, and chromatin immune-precipitation was used to verify the binding between them. RESULTS: The FA-CS-DOX nano-particles were irregular and spherical particles around 30-40 nm, with uniform size and no adhesion. No significant difference was noted in doxorubicin release rate between CS-DOX and FA-CS-DOX. FA-CS-DOX nano-particles showed stronger cytotoxicity than CS-DOX. FA-CS-DOX nano-particles promoted the apoptosis and arrested cell cycle at G2/M phase, and they up-regulated p53. FA-CS-DOX nano-particles inhibited cell survival through p53/PRC1 pathway. CONCLUSION: Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer by promoting apoptosis and arresting cell cycle at G2/M phase through p53/PRC1 pathway.

Sleeve gastrectomy with duodenojejunal end-to-side anastomosis in the treatment of type 2 diabetes: the initial experiences in a Chinese population with a more than 4-year follow-up.

BACKGROUND: Gastric bypass has been thought to be associated with a risk of gastric cancer, particularly in Asia. Sleeve gastrectomy with duodenojejunal end-to-side anastomosis (SG-DJESA) was suggested to be a better-designed procedure to avoid this risk, and it also has other advantages. OBJECTIVE: We aimed to evaluate the clinical efficacy and feasibility of SG-DJESA in the treatment of nonobese patients with type 2 diabetes (T2D). SETTING: University Hospital, China. METHODS: We present prospective data from 7 consecutive T2D patients with gastric precancerosis who underwent SG-DJESA from December 15, 2011 to June 8, 2013. The group had a mean body mass index of 27.7 kg/m2. The glycometabolic parameters, including fasting plasma glucose, 2-hour postprandial plasma glucose, fasting insulin, fasting C-peptide, glycated hemoglobin, lipometabolic parameters, and anemia-related indicators were collected at baseline and at 1, 3, 6, 12, 24, and 48 months postoperatively. Remission was defined according to the "outcome reporting standards" conducted by the American Society for Metabolic and Bariatric Surgery. RESULTS: Along with a decrease in antidiabetic medication requirements, body mass index, fasting plasma glucose, 2-hour postprandial plasma glucose, and glycated hemoglobin decreased significantly at each postoperative time point, compared with the preoperative baseline (P<.05, respectively). Four patients (4/7, 57.1%) achieved a complete remission of T2D at 12 months and maintained remission at the 4-year follow-up time; 1 patient (1/7, 14.3%) achieved a partial remission at 6 months but had recurrence at 12 months postoperatively; and the other 2 patients (2/7, 28.6%) achieved improvement during the follow-up time. There were no deaths during the follow-up period. One patient had a postoperative anastomotic bleed and recovered under conservative treatment. Another patient had iron deficiency anemia 8 weeks after surgery and recovered after taking an oral iron supplement for 1 month. No other serious perioperative complications or postoperative malnutrition occurred. CONCLUSIONS: SG-DJESA is an effective and safe procedure for nonobese patients with T2D and could be recommended as a treatment option for T2D patients with gastric precancerosis. A larger sample size may be required for better evaluation.

Sphingosine kinase 1: A novel independent prognosis biomarker in hepatocellular carcinoma.

Sphingosine kinase 1 (Sphk1) is an oncogenic kinase that is responsible for the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P). Mounting evidence suggests that Sphk1 serves a crucial role in the proliferation and development of a variety of human cancer cells. However, the role of Sphk1 in hepatocellular carcinoma (HCC) has not been fully elucidated. Therefore, the expression of Sphk1 was examined in 127 formalin-fixed, paraffin-embedded HCC tissues using immunohistochemistry, and its clinical implications and prognostic significance were analyzed. As a result, the expression of Sphk1 in HCC tissue was revealed to be significantly higher than in normal tissue (P<0.01). In addition, Sphk1 expression was significantly associated with tumor size, tumor stage and histological differentiation (all P<0.05). The patients with low Sphk1 expression had higher overall survival and recurrence-free survival rates compared with patients with high Sphk1 expression. Furthermore, Sphk1-specific shRNA was used to downregulate the expression of Sphk1 in HCC cell lines, including hepatoblastoma G2 and HCC-9724. The CRISPR/Cas9 based transcription activation system was used to upregulate Sphk1 expression in the normal live cell, L02. Cell proliferation, mRNA expression and protein expression were measured using Cell Counting Kit-8, reverse transcription polymerase chain reaction and western blot analysis in the transfected cells. To the best of our knowledge, the present study provides the first evidence that Sphk1 promotes HCC cell proliferation and is involved in tumor progression. Notably, the data presented suggest that Sphk1 may be a potential independent prognosis biomarker for the treatment of HCC.

Laparoscopic surgery assisted by colonoscopy for a submucosal cecal fecalith presenting as acute appendicitis: A case report.

RATIONALE: A cecal submucosal fecalith is extremely rare and is likely to be misdiagnosed as appendicitis with an incarcerated fecalith. PATIENT CONCERNS: This review presents the case of a female patient complaining of recurrent abdominal pain in the right lower quadrant, similar to the clinical symptoms of appendicitis. Physical examination revealed an abdominal tenderness in the right lower quadrant without rebound tenderness or muscular tension. An ultrasound examination found a mass located in the right lower abdomen. Computed tomography showed a high-density shadow in the cecal cavity. DIAGNOSES: A fecalith was detected in the submucosal cecal wall. The postoperative pathologic examination showed that the fecalith was located in the submucosa. INTERVENTIONS: A partial cecal excision was performed under laparoscopic surgery assisted by colonoscopy. OUTCOMES: The patient was discharged 1 week after surgery without postoperative complications. LESSONS: Fecaliths should be considered in the differential diagnosis of submucosal occupying lesions of the cecum.

Clinical value of the neutrophil/lymphocyte ratio in diagnosing adult strangulated inguinal hernia.

BACKGROUND: Diagnosis of incarcerated inguinal hernia (IIH) is not difficult, but currently, there are no diagnostic criteria that can be used to differentiate it from strangulated inguinal hernia (SIH). This research aimed to evaluate the clinical value of the neutrophil/lymphocyte ratio (NLR) in diagnosing SIH. METHODS: We retrospectively analyzed 263 patients with IIH who had undergone emergency operation. The patients were divided into two groups according to IIH severity: group A, patients with pure IIH validated during operation as having no bowel ischemia; group B, patients with SIH validated during operation as having obvious bowel ischemia, including bowel necrosis. We statistically evaluated the relation between several clinical features and SIH. The accuracy of different indices was then evaluated and compared using receiver operating characteristic (ROC) curve analyses, and the corresponding cutoff values were calculated. RESULT: Univariate analysis showed eight clinical features that were significantly different between the two groups. They were then subjected to multivariate analysis, which showed that the NLR, type of hernia, and incarcerated organ were significantly related to SIH. ROC curve analysis showed that the NLR had the largest area under the ROC curve. CONCLUSION: Among the different clinical features, the NLR appears to be the best index in diagnosing SIH.

One-pot synthesis of water-soluble, ß-cyclodextrin-based polyrotaxanes in a homogeneous water system and its use in bio-applications.

A small, nano-sized, water-soluble polyrotaxane (PR) was synthesized using a highly efficient one-pot synthesis strategy in a homogeneous water system, formed from ß-cyclodextrin-(COOH)2, poly(propylene glycol)bis(2-aminopropyl ether) (PPG, 2 kDa) and a mono-(6-azido-6-desoxy)-ß-cyclodextrin stopper via room temperature click chemistry. ß-cyclodextrin-(COOH)2 and PR were characterized by one- and two-dimensional NMR as well as by high resolution transmission electron microscopy (HR-TEM). The number of carboxyl groups in one PR was determined by 1H NMR. Two-dimensional diffusion-ordered NMR spectroscopy (2D DOSY) and nuclear Overhauser enhancement spectroscopy (2D NOESY) show that ß-cyclodextrin-(COOH)2 and PPG successfully formed an inclusion complex. HR-TEM revealed the morphology of water-soluble PR as a spherical nanoparticle with a size of approximately 3.5 nm ± 1.5 nm. PR was labeled with rhodamine to assess its biocompatibility and cell membrane penetrability in vitro. The in vivo real-time fluorescent imaging biodistribution experiments indicated that water-soluble PR can actively target tumor sites using an enhanced permeability and retention (EPR) effect, with a significantly prolonged blood circulation time in tumor-bearing mice.

Efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a meta-analysis.

BACKGROUND: What benefits and toxicities patients acquire from the use of bevacizumab combined with firstline chemotherapy remains controversial. This study was performed to evaluate the efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer (mCRC). METHODS: Several databases, including PubMed, Embase, and Cochrane Library, were searched up to April 30, 2013. Eligible studies were only randomized, controlled trials (RCTs) with a direct comparison between mCRC patients treated with and without bevacizumab. Overall risk ratio (RR), hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed or random-effects models depending on the heterogeneity of the included trials. RESULTS: Six RCTs, including 1582 patients in chemotherapy plus bevacizumab group and 1484 patients in chemotherapyalone group, were included. Overall, the addition of bevacizumab to first-line chemotherapy increased overall response rate (ORR) by 4.5%, prolonged both progression-free survival (PFS) and overall survival (OS), and increased the rate of total Grades 3 or 4 adverse events (G3/4AEs) by 6.9%. Significant differences were found in ORR (RR = 1.22 (95% CI 1.01-1.46), P = 0.03), PFS (HR = 0.60 (95% CI 0.47-0.77), P < 0.0001), OS (HR = 0.83 (95% CI 0.70-0.97), P = 0.02), and any G3/4AEs (OR = 1.56 (95% CI 1.29-1.89), P < 0.00001). CONCLUSION: Bevacizumab is a valuable addition to the current first-line chemotherapy regimens used in patients with mCRC, because of conferring a significant improvement in ORR, PFS, and OS, even though it increased adverse events.

[Laparoscopic total mesorectal excision combined with intersphincteric resection for ultra-low rectal cancer].

OBJECTIVE: To evaluate clinical outcomes after laparoscopic total mesorectal excision (TME) combined with intersphincteric resection (ISR) for ultra-low rectal tumors. METHODS: Clinical data of 36 patients with ultra-low rectal tumor undergoing laparoscopic TME combined with ISR were analyzed retrospectively. RESULTS: The median distance from the inferior margin of the tumor to the anal verge was 3.4 (2.0-5.0) cm. There were 33 cases of well/moderately differentiated adenocarcinoma and 3 rectal malignant villous adenoma. There were 16 patients with stage I disease, 15 with stage II A, 3 with stage III A, and 1 with III B. Postoperatively, one patient developed stenosis at the end ileostomy and 3 anastomotic leakage. After a median follow-up of 16(4-49) months, one patient developed local recurrence at the anastomosis and one case died of liver metastasis. In the 19 patients who had a minimum follow-up of one year, the bowel movements frequency ranged from 1-4 times per day, and these patients were able to withhold defecation for more than 5 minutes. CONCLUSIONS: Laparoscopic TME combined with ISR can achieve oncologic clearance, sphincter preservation, and minimal invasiveness for ultra-lower rectal cancer. However, patients selection should be cautious.