[Analysis of risk factors associated with postoperative pancreatic fistula after robotic-assisted distal pancreatectomy].

Objective: To investigate pertinent risk factors for postoperative pancreatic fistula(POPF) after robotic-assisted distal pancreatectomy(RDP). Methods: This is a retrospective cohort study. Clinical data of 1 211 patients who underwent various methods of distal pancreatectomy at the Department of General Surgery,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,between January 2021 and December 2023 were retrospectively collected. Among the 1 211 patients,440 cases were in the robot-assisted group(173 males and 267 females),with an age(M(IQR)) of 55(29)years;720 cases were in the open surgery group (390 males and 330 females),with an age of 64(15)years;and 51 cases were in the laparoscopic group(17 males and 34 females),with an age of 56(25)years. These 440 patients who underwent RDP were divided into two cohorts based on the presence of clinically relevant pancreatic fistulas(grades B and C). Univariate and multivariate analysis were performed on 27 factors related to POPF. Univariate analysis methods included independent sample t-test,Mann-Whitney U test,and χ2 test,while multivariate analysis utilized binary logistic regression. Results: After stratification by pathological type,there was no significant difference in the incidence of pancreatic fistula between the robot-assisted group and the open surgery group(benign tumor:χ2=1.200,P=0.952;malignant tumor:χ2=0.391,P=0.532). The surgical duration of the RDP group (Z1=15.113,P1<0.01; Z2=4.232, P2<0.01) was significantly shorter than that of the open surgery and laparoscopic groups,so as the intraoperative blood loss (Z1=12.530,P1<0.01;Z2=2.550,P2=0.032). Postoperative hospital stay in the RDP group was significantly shorter than that in the open surgery group (Z1=10.947, P1<0.01), but not different from that in the laparoscopic group (P2>0.05). All 440 patients underwent successful surgery,of which there was only 1 case who underwent a conversion to open surgery. A total of 104 patients(23.6%) developed clinically relevant pancreatic fistulas,and no perioperative mortality was observed. Univariate analysis revealed that 6 factors were associated with POPF after RDP: gender(χ2=12.048,P=0.001),history of smoking (χ2=6.327,P=0.012),history of alcohol consumption (χ2=17.597,P<0.01),manual pancreas division (χ2=9.839,P=0.002),early elevation of amylase in drainage fluid (Z=5.187,P<0.01),and delayed gastric emptying (χ2=4.485,P=0.034). No statistically significant association with POPF was found for the remaining factors(all P>0.05).The cut-off value for the early amylase level in the drainage fluid was determined to be 7 719.5 IU/ml,with an area under curve of 0.676 determined by receiver operating characteristic curve analysis. Binary logistic regression analysis identified a history of alcohol consumption(P=0.002,95%CI: 0.112 to 0.623), manual pancreas division(P=0.001,95%CI:1.446 to 4.082),early amylase level of drainage fluid ≥7 719.5 IU/ml(P<0.01,95%CI:0.151 to 0.438),and delayed gastric emptying (P=0.020, 95%CI: 1.131 to 4.233) as independent risk factors for POPF of RDP. Conclusion: Patients with pancreatic body and tail tumors who receive RDP therapy are at increased risk of developing a pancreatic fistula if they have a history of alcohol consumption,manual pancreas division,early elevation of amylase in drainage fluid to ≥7 719.5 IU/ml, or delayed gastric emptying.

[The application of full-length urethral preservation without anastomosis in single-port laparoscopic radical prostate cancer].

Objective: To preliminarily examine the feasibility and outcome of single-port laparoscopic radical prostatectomy with full-length urethral preservation (FLUP-SPRP). Method: This study was a prospective case series study. A total of 25 patients with prostate cancer who met the enrollment criteria and agreed to this surgical procedure from March 2022 to December 2022 were collected at the Department of Urology, the Second Affiliated Hospital of Nanjing Medical University. The age of the patients was (67.2±7.6) years (range: 61 to 76 years). This novel procedure was performed by an experienced surgeon who performed single hole radical prostatectomy skillfully. Patient urinary control, tumor control, and related surgical complications after surgery were regularly monitored. Postoperative urinary control was evaluated using the daily amount of urine pad, 0 to 1 piece of urine pad was to restore urinary control, and 0 to 1 piece of pad within 24 hours after catheter removal was immediate urinary control. Result: All prodecures were successfully completed without transit to open surgery. The surgical time was (128.4±22.4) minutes (range: 100 to 145 minutes), the intraoperative blood loss was (68.2±13.7) ml (range: 50 to 120 ml). The urethral injury occurred in 4 cases during surgery and was repaired by sutures. The urinary control recovery rates within 24 hours, 1 week, 4 weeks, and 7 weeks after surgery were 80.0%, 84.0%, 92.0% and 100%, respectively. Postoperative large section pathology revealed 1 case with a positive basal margin of the prostate and negative margins of all prostate glands around the urethra. Postoperative complications included urinary tract infection in 3 cases, urodynia in 2 cases, and acute urinary retention in 1 case. MRI follow-up 3 months after surgery showed normal anatomy of the bladder and urethra. The follow-up values of prostate specific antigen at 3 and 6 months after surgery were less than 0.1 µg/L. Conclusions: The preliminary results of this study indicate that the FLUP-SPRP procedure is safe and feasible. The early results of postoperative urinary control and oncology are as expected.

[Pay attention to whole cycle management of pancreatic cancer].

The prognosis for pancreatic cancer is extremely poor. To improve the prognosis of pancreatic cancer, it is urgently needed to improve early detection to advance treatment. And basically, it is also necessary to emphasise basic research to find novel therapies. By promoting the disease-centered multidisciplinary team model, researchers should achieve high-quality closed-loop process management of the entire life cycle which consists of prevention, screening, diagnosis, treatment, rehabilitation,and follow-up, with the objective of establishing a standard clinical process to improve the outcome in essence. This article summarized the progress of pancreatic cancer at different stages of the whole cycle management recently and shared the experience of pancreatic cancer treatment from the author's team in the past ten years.

Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

[Diagnostic value of different serological markers and correlation analysis with disease phenotype in inflammatory bowel disease].

Objective: To explore the diagnostic value of different serological markers and the correlation with disease phenotype in inflammatory bowel disease (IBD). Methods: The clinical data of 445 IBD patients in Peking Union Medical College Hospital from June 2010 to December 2020 were retrospectively collected, including 223 cases of ulcerative colitis (UC) [111 males, 112 females, with a median age of 46(20,79) years] and 222 cases of Crohn's disease (CD) [147 males, 75 females, with a median age of 39 (19, 72) years]. The positive rates of serum anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), goblet cell autoantibodies (GAB) and pancreatic autoantibodies (PAB) in the two groups were analyzed. The sensitivity, specificity, positive predictive value and negative predictive value of UC and CD were calculated. Logistic regression was performed to analyze the relationship between different combinations of antibodies and disease phenotype. Results: The positive rates of ASCA and PAB in CD patients were 34.7% (77/222) and 38.3% (85/222), respectively, which were higher than those in UC patients [10.3% (23/223) and 4.5% (10/223), P<0.001]. The positive rate of ANCA in UC patients was 50.2% (112/223), which was higher than that in CD patients [5.4% (12/222), P<0.001]. The positive rates of serum GAB in CD and UC patients were 21.6% (48/222) and 28.3% (63/223), respectively, with no significant difference (P=0.760). In patients with CD, the sensitivity of mono-marker ASCA (+), dual-marker ASCA (+) ANCA (-), quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) in diagnosing CD was 34.7%, 32.9%, 20.7%, the specificity was 89.7%, 95.5%, 100.0%, the positive predictive value was 77.0%, 90.1%, 100.0%, and the negative predictive value was 58.0%, 58.7%, 55.9%, respectively. In patients with UC, the sensitivity of mono-marker ANCA (+), dual-marker ANCA (+) ASCA (-), quadruple-marker ANCA (+) ASCA (-) PAB (-) GAB (+) in diagnosing UC was 50.2%, 40.4%, 24.2%, the specificity was 94.6%, 95.5%, 100.0%, the positive predictive value was 90.3%, 90.0%, 100.0%, and the negative predictive value was 65.4%, 61.4%, 56.8%, respectively. Mono-marker ASCA (+) (OR=3.39, 95%CI: 1.59-7.21), dual-marker ASCA (+) ANCA (-) (OR=2.87, 95%CI: 1.34-6.14), triple-marker ASCA (+) ANCA (-) GAB (-) (OR=3.09, 95%CI: 1.31-7.31) and quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) (OR=3.15, 95%CI: 1.56-8.03) were associated with stenosis and/or penetrating type CD. The mono-marker ANCA (+) (OR=2.69, 95%CI: 1.42-5.12) and dual-marker ANCA (+) ASCA (-) (OR=2.11, 95%CI: 1.03-4.16) were associated with extensive colonic lesions in UC. Conclusion: Based on ASCA or ANCA, the combination with PAB or GAB, is conducive to IBD diagnosis, and is associated with stenosis and/or penetrating type of CD and extensive type of UC.

[Hydroxynitone suppresses hepatic stellate cell activation by inhibiting TGF-ß1 phosphorylation to alleviate CCl4-induced liver fibrosis in rats].

OBJECTIVE: To investigate the effect of hydronidone on CCl4-induced liver fibrosis in rats and explore the possible mechanism. METHODS: Sixty-six male SD rats were randomized into 5 groups, including a control group (n=10), a liver fibrosis model group (n=20), 2 hydronidone dose groups (100 and 250 mg/kg; n=12), and a pirfenidone (250 mg/kg) treatment group (n= 12). Rat models of liver fibrosis were established by subcutaneous injection of CCl4 in all but the control group. Hydronidone and pirfenidone were given daily at the indicated doses by intragastric administration for 6 weeks. After the treatments, serum samples were collected from the rats for detecting liver function parameters, and hydroxyproline content in the liver tissue was determined. Inflammation and fibrosis in the liver tissue were observed using HE staining and Sirius Red staining. In the cell experiment, human hepatic stellate cell line LX-2 was stimulated with TGF-ß1 and treated with hydronidone or pirfenidone, and the expression levels of α-SMA, collagen type I and phosphorylated Smad3, phosphorylated p38, phosphorylated ERK1/2 and phosphorylated Akt were detected with Western blotting. RESULTS: In the rat models of liver fibrosis, treatment with hydronidone obviously improved the liver functions, reduced the content of hydroxyproline in the liver tissue, and significantly alleviated liver fibrosis (P < 0.05). In LX-2 cells, hydronidone dose-dependently decreased the expression levels of α-SMA and collagen type I. In TGF- ß1-stimulated cells, the phosphorylation levels of Smad3, P38, ERK, and Akt increased progressively with the extension of the treatment time, but this effect was significantly attenuated by treatment with hydronidone (P < 0.05). CONCLUSION: Hydronidone can inhibit the phosphorylation of the proteins in the TGF-ß signaling pathway, thereby preventing TGF-ß1-mediated activation of hepatic stellate cells, which may be a possible mechanism by which hydronidone alleviates CCl4-induced liver fibrosis in rats.

The inhibitory effect of LINC00261 upregulation on the pancreatic cancer EMT process is mediated by KLF13 via the mTOR signaling pathway.

PURPOSE: The long noncoding RNA LINC00261 was reported to be involved in carcinogenesis and has been validated as a tumor suppressor in pancreatic cancer (PC); however, how LINC00261 is regulated has not been fully examined. Here, we attempted to investigate the upstream and downstream targets of LINC00261 in PC. METHODS: LINC00261 expression in PC tissues was examined by the Gene Expression Omnibus (GEO) datasets and the Gene Expression Profiling Interactive Analysis (GEPIA) database. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were performed to detect the expression level of LINC00261 in PC cells. The location of LINC00261 in PC cells was identified by RNA fluorescence in situ hybridization (RNA-FISH). Cell Counting Kit-8 (CCK-8), cell apoptosis assay, transwell invasion and migration assays testified the critical role of LINC00261 in PC. The luciferase reporter assay was applied to confirm the binding of LINC00261 to its upstream transcription factor KLF13. The changes in LINC00261 related target protein levels were analyzed by Western blotting assay. RESULTS: LINC00261 was significantly lower in PC tissues and was mainly concentrated in the nucleus. Overexpression of LINC00261 inhibited the invasion and migration of PC cells. Mechanistically, transcription factor KLF13 was confirmed to inhibit the epithelial-mesenchymal transition (EMT) process of PC cells by promoting the transcription of LINC00261 and suppressing the expression of metastasis-associated proteins, such as matrix metalloproteinase MMP2 and vimentin, thus inhibiting the metastasis of PC. CONCLUSION: LINC00261 regulates PC cell metastasis through the "KLF13-LINC00261-mTOR-P70S6K1-S6" signaling pathway, which provides a significant set of potential PC therapeutic targets.

MiR-593-5p inhibited proliferation and migration of lung adenocarcinoma by targeting ICAM-1.

OBJECTIVE: The aim of this study was to investigate the role of microRNA-593-5p (miR-593-5p) in the development of lung adenocarcinoma (LA). PATIENTS AND METHODS: The expression level of miR-593-5p in LA tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Luciferase reporter gene assay and Western blot were performed to evaluate the interaction between miR-593-5p and intercellular cell adhesion molecule-1 (ICAM-1). Furthermore, the effects of the miR-593-5p/ICAM-1 axis on A549 cells were determined by MTS, colony formation assay, and transwell assay, respectively. RESULTS: MiR-593-5p was significantly downregulated in both clinical samples and cell lines. The bioinformatics analysis predicted that miR-593-5p could complementarily bind to the 3'-UTR of ICAM-1. Luciferase reporter gene assay confirmed that ICAM-1 was the direct target of miR-593-5p. Western blot results demonstrated that miR-593-5p could effectively reduce the protein expression of ICAM-1 in cells. In vitro experiments indicated that the proliferation and migration of A549 cells were significantly inhibited by miR-593-5p transfection. However, the overexpression of ICAM-1 could effectively reverse the inhibitory effects of miR-593-5p in vitro. These results indicated that the inhibitory effects of miR-593-5p on LA were achieved by regulating ICAM-1 expression. CONCLUSIONS: MiR-593-5p/ICAM-1 axis might be a potential therapeutic target for the diagnosis and treatment of LA.

[Diagnostic value of serum alpha-fetoprotein, alpha-fetoprotein variant and abnormal prothrombin in primary hepatocellular carcinoma].

Objective: To explore the diagnostic value of single or combined detection of serum tumor markers alpha-fetoprotein (AFP), α-fetoprotein (AFP)-L3 and abnormal clotting (PIVKA-II) in the primary hepatic carcinoma. Methods: Serum AFP, AFP-L3 and PIVKA-II of 56 cases with primary hepatic carcinoma, 46 cases with cirrhosis, 45 cases with other liver disease and 41 healthy persons (control group) were examined by chemiluminescence method, and the differences in the levels of AFP, AFP-L3 and PIVKA-II in each group were compared. Results: Serum level of AFP, AFP-L3 and PIVKA-II in patients with primary liver cancer was significantly higher than that of the cirrhosis, other liver disease and control groups, and the difference was statistically significant (P < 0.05). The receiver operating characteristic curve analysis showed that the areas under the curve for the diagnosis of primary hepatic carcinoma by AFP, AFP-L3 and PIVKA-II were 0.887, 0.846 and 0.885, respectively. The combined use of the three tumor markers for the diagnosis of primary hepatic carcinoma increased the area under the curve to 0.899. Among the single detection, AFP had the highest sensitivity of 91.07% and PIVKA-II had the highest specificity at 88.63%. In the combined detection, AFP/PIVKA-II combination had the highest sensitivity of 94.64 %, while the AFP + AFP-L3 + PIVKA-II combination had the highest specificity at 98.48%. Conclusion: Combined detection of AFP, AFP-L3 and PIVKA-II could improve the diagnostic specificity and the sensitivity of primary hepatic carcinoma; thereby make up the deficiency of single detection and improve the early diagnosis rate.

Difference in the frequency of pouchitis between ulcerative colitis and familial adenomatous polyposis: is the explanation in peripouch fat?

AIM: Patients with ulcerative colitis (UC) have an unexplained higher incidence of pouchitis and a greater amount of peripouch fat compared with patients with familial adenomatous polyposis (FAP). The aims of this study were to compare the peripouch fat areas between patients with UC and patients with FAP, and to explore relationship between peripouch fat and pouchitis or chronic antibiotic-refractory pouchitis (CARP). METHOD: Patients with an abdominal CT image from our prospectively maintained Pouch Database were included. Abdominal fat and peripouch fat were measured on CT images at different levels or planes. Comparisons of peripouch fat and CARP were performed before and after propensity score matching. RESULTS: A total of 277 patients with UC and 40 patients with FAP were included. Compared with patients with FAP, patients with UC were found to have a higher incidence of pouchitis (58.5% vs 15.0%, P < 0.001) and CARP (24.5% vs 2.5%, P = 0.002) and a higher total peripouch fat area (P = 0.030) and mesenteric peripouch fat area (P = 0.022) at Level-3. Univariate and multivariate analyses showed that diagnosis (UC vs FAP) and peripouch fat areas at Level-3 and Level-5 were independent risk factors for CARP. With propensity score matching, 38 pairs of patients with UC and FAP were matched successfully. After matching, patients with UC were found to have higher total peripouch fat area and higher mesenteric peripouch fat area at Level-3, and a higher incidence of pouchitis (57.9% vs 13.2%, P < 0.001) and CARP (23.7% vs 2.6%, P = 0.007). CONCLUSION: Our study demonstrates that patients with UC have more peripouch fat than those with FAP, which may explain the difference in the frequency of pouchitis and CARP between these groups of patients.

Resveratrol protects myocardial apoptosis induced by ischemia-reperfusion in rats with acute myocardial infarction via blocking P13K/Akt/e-NOS pathway.

OBJECTIVE: To elucidate the protective role of resveratrol (RSV) in myocardial apoptosis induced by ischemia-reperfusion injury in rats with acute myocardial infarction (AMI), and to explore its underlying mechanism. MATERIALS AND METHODS: The AMI rat model was successfully established by ligation of the left anterior descending coronary artery. Rat cardiomyocytes were isolated and cultured. Cells were divided into four groups, including: control group (no specific treatment), AMI group (acute ischemia-reperfusion treatment), AMI+RSV group (RSV pretreatment for 24 h before acute ischemia-reperfusion) and AMI+ RSV+LY group (RSV pretreatment combined with 40 µmol/L phosphatidylinositide 3-kinases (PI3K) pathway inhibitor LY294002 for 24 h before acute ischemia-reperfusion). Morphology of apoptotic cardiomyocytes in each group was observed by Hoechst staining. The proliferation, apoptosis and cell cycle progression of cardiomyocytes were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry, respectively. Finally, the protein levels of genes relative to PI3K/Akt/eNOS pathway were detected by Western blot. RESULTS: Hoechst staining showed a large number of necrotic cells, cell retraction, enhanced refractive index and enlarged cell gap in AMI group. A small number of necrotic cells were found in AMI+RSV group, which was significantly fewer than that of AMI group. Meanwhile, remaining cells presented normal morphology. However, a great number of necrotic cells were observed in AMI+RSV+LY group, which was obviously more than that of AMI+RSV group. Compared with control group, cells in AMI group showed significantly decreased proliferative rate, increased early phase, late phase and total one of apoptosis. In AMI group, the ratio of G0/G1 phase was remarkably increased, whereas those of S and G2/M phases were decreased. Moreover, the expression levels of phosphorylated Akt (p-Akt) and phosphorylated e-NOS (p-eNOS) were significantly downregulated in AMI group. In AMI+RSV group, cell apoptosis, cell cycle progression and levels of p-Akt and p-eNOS showed the opposite trends as those of AMI group. However, LY294002 pretreatment reversed the protective role of RSV in cellular behaviors of cardiomyocytes. CONCLUSIONS: RSV protects cardiomyocyte apoptosis from ischemia-reperfusion injury through regulating phosphorylation levels of proteins relative to PI3K/Akt/e-NOS pathway.

Effectiveness of telephone-based interventions on health-related quality of life and prognostic outcomes in breast cancer patients and survivors-A meta-analysis.

The aim of this meta-analysis was to evaluate the effect of telephone-based interventions on prognostic outcomes and health-related quality of life (HRQoL) in breast cancer patients and survivors. A systematic search of the Cochrane Library, Web of science, Medline, EMBASE, CNKI and CBM database was carried out. Randomised, controlled trials (RCTs) examining the effects of telephone-based intervention versus a control group receiving no telephone intervention, on prognostic outcomes and HRQoL with breast cancer were included. A meta-analysis was conducted to quantify the effects of telephone-based interventions on anxiety, depression, fatigue, self-efficiency, physiological function, social-domestic function and quality of life. In total, 14 studies involving 2002 participants were included. Due to the effect of telephone-based interventions, statistically significant results were found on anxiety (standard mean difference [SMD] = -0.16, 95% confidence intervals [CI] [0.01, 0.30], p = .04), self-efficiency (SMD = 0.22, 95% CI [-0.34, -0.10], p = .0004), social-domestic function (SMD = 0.19, 95% CI [-0.35, -0.03], p = .02) and quality of life (SMD = 0.54, 95% CI [-1.00, -0.08], p = .02). Although the effects on depression, fatigue and physiological function were in the expected direction, these effects were not statistically significant (p > .05) based on the insufficient evidence.

[Retroperitoneal laparoscopic debridement therapy for infected severe acute pancreatitis].

Objective: To investigate the feasibility and availability of retroperitoneal laparoscopic debridement therapy for patients with infected severe acute pancreatitis. Methods: Clinical data of 6 patients with severe acute pancreatitis who underwent retroperitoneal laparoscopic necrotic tissue debridement therapy in the Severe Acute Pancreatitis Center of Sir Run Run Hospital between August 2014 and October 2015 was retrospectively analyzed. The laparoscopic instruments and sponge forceps were used to remove necrotic tissue under retroperitoneal space, and double-cavity drainage tube was left for continuous washing. The perioperative indicators were collected and analyzed. Results: Two of six patients underwent two surgeries, and the others underwent one surgery, with an average operation time of (220.0±58.3) minutes and a mean hospital stay time of 62.6 days (35-117 days). One patient underwent re-operation after 33 days because of intraperitoneal hemorrhage, and another patient suffered pancreatic pseudocyst after the surgery, but no one died in hospital. Conclusion: Retroperitoneal laparoscopic debridement therapy is an additional choice for patients with infected severe acute pancreatitis, especially for those who had limited necrosis under retroperitoneal space. Furthermore, the therapy is in line with the concept of minimally invasive surgery and enhanced recovery after surgery.

Long noncoding RNA ASAP1-IT1 promotes cancer stemness and predicts a poor prognosis in patients with bladder cancer.

Urinary bladder cancer (UBC) is one of the most common urogenital malignancies. Cancer stem-like cells (CSCs) play a vital role in tumor development and recurrence. Long noncoding RNAs (lncRNAs) are reported to influence cancer progression via transcriptional, posttranscriptional or epigenetic regulation. Dysregulation of several lncRNAs has been implicated in UBC. In our study, we found that an uncharacterized lncRNA, ASAP1-IT1, was overexpressed in UBC tissues compared with adjacent non-malignant tissues. High ASAP1-IT1 expression levels in UBC specimens were correlated with advanced tumor stage, higher clinical stage, poor pathological differentiation and bad overall survival. We further found that depletion of ASAP1-IT1 in T24 cells by RNA interference reduced the stemness of bladder cancer, whereas forced overexpression of ASAP1-IT1 in J82 cells enhanced cancer cell stemness by sphere assay, ALDEFLUOR and flow cytometry assay on CD44+ population. Our data suggest that ASAP1-IT1 plays an oncogenic role in bladder cancer and can be used as a potential prognostic and therapeutic target.

Intra-articular injection of microRNA-140 (miRNA-140) alleviates osteoarthritis (OA) progression by modulating extracellular matrix (ECM) homeostasis in rats.

OBJECTIVE: Disruptions of extracellular matrix (ECM) homeostasis are key events in the pathogenesis of osteoarthritis (OA). MicroRNA-140 (miRNA-140) is expressed specifically in cartilage and regulates ECM-degrading enzymes. Our objective in this study was to determine if intra-articular injection of miRNA-140 can attenuate OA progression in rats. DESIGN: miRNA-140 levels in human normal and OA cartilage derived chondrocytes and synovial fluid were assessed by polymerase chain reaction (PCR). After primary human chondrocytes were transfected with miRNA-140 mimic or inhibitor, PCR and western blotting were performed to quantify Collagen II, MMP-13, and ADAMTS-5 expression. An OA model was induced surgically in rats, and subsequently treated with one single intra-articular injection of miRNA-140 agomir. At 4, 8, and 12 weeks after surgery, OA progression were evaluated macroscopically, histologically, and immunohistochemically in these rats. RESULTS: miRNA-140 levels were significantly reduced in human OA cartilage derived chondrocytes and synovial fluid compared with normal chondrocytes and synovial fluid. Overexpressing miRNA-140 in primary human chondrocytes promoted Collagen II expression and inhibited MMP-13 and ADAMTS-5 expression. miRNA-140 levels in rat cartilage were significantly higher in the miRNA-140 agomir group than in the control group. Moreover, behavioural scores, chondrocyte numbers, cartilage thickness and Collagen II expression levels in cartilage were significantly higher, while pathological scores and MMP-13 and ADAMTS-5 expression levels were significantly lower in the miRNA-140 agomir group than in the control group. CONCLUSION: Intra-articular injection of miRNA-140 can alleviate OA progression by modulating ECM homeostasis in rats, and may have potential as a new therapy for OA.

Histone demethylase JMJD1A promotes urinary bladder cancer progression by enhancing glycolysis through coactivation of hypoxia inducible factor 1α.

High aerobic glycolysis not only provides energy to cancer cells, but also supports their anabolic growth. JMJD1A, a histone demethylase that specifically demethylates H3K9me1/2, is overexpressed in multiple cancers, including urinary bladder cancer (UBC). It is unclear whether JMJD1A could promote cancer cell growth through enhancing glycolysis. In this study, we found that downregulation of JMJD1A decreased UBC cell proliferation, colony formation and xenograft tumor growth. Knockdown of JMJD1A inhibited glycolysis by decreasing the expression of genes participated in glucose metabolism, including GLUT1, HK2, PGK1, PGM, LDHA and MCT4. Mechanistically, JMJD1A cooperated with hypoxia inducible factor 1α (HIF1α), an important transcription factor for glucose metabolism, to induce the glycolytic gene expression. JMJD1A was recruited to the promoter of glycolytic gene PGK1 to demethylate H3K9me2. However, the JMJD1A (H1120Y) mutant, which loses the demethylase activity, failed to cooperate with HIF1α to induce the glycolytic gene expression, and failed to demethylate H3K9me2 on PGK1 promoter, suggesting that the demethylase activity of JMJD1A is essential for its coactivation function for HIF1α. Inhibition of glycolysis through knocking down HIF1α or PGK1 decelerated JMJD1A-enhanced UBC cell growth. Consistent with these results, a positive correlation between JMJD1A and several key glycolytic genes in human UBC samples was established by analyzing a microarray-based gene expression profile. In conclusion, our study demonstrates that JMJD1A promotes UBC progression by enhancing glycolysis through coactivation of HIF1α, implicating that JMJD1A is a potential molecular target for UBC treatment.

The protumorigenic potential of FTY720 by promoting extramedullary hematopoiesis and MDSC accumulation.

FTY720 (also called fingolimod) is recognized as an immunosuppressant and has been approved by the Food and Drug Administration to treat refractory multiple sclerosis. However, long-term administration of FTY720 potentially increases the risk for cancer in recipients. The underlying mechanisms remain poorly understood. Herein, we provided evidence that FTY720 administration potentiated tumor growth. Mechanistically, FTY720 enhanced extramedullary hematopoiesis and massive accumulation of myeloid-derived suppressor cells (MDSCs), which actively suppressed antitumor immune responses. Granulocyte-macrophage colony-stimulating factor (GM-CSF), mainly produced by MDSCs, was identified as a key factor to mediate these effects of FTY720 in tumor microenvironment. Furthermore, we showed that FTY720 triggers MDSCs to release GM-CSF via S1P receptor 3 (S1pr3) through Rho kinase and extracellular signal-regulated kinase-dependent pathway. Thus, our findings provide mechanistic explanation for the protumorigenic potentials of FTY720 and suggest that targeting S1pr3 simultaneously may be beneficial for the patients receiving FTY720 treatment.

[The effect of tanshinone â ¡A potentiates the effects of Cisplatin in Fadu cells in vitro through downregulation of survivin].

Objective:The aim of this study is to investigate the inhibitory effect and mechanism of tanshinone ⅡA combined with cisplatin on tumor Fadu cells in pharyngeal squamous cell carcinoma. Method:Cytotoxicity was determined by CCK8 assay. Flow cytometry was used to detect apoptosis and cell cycle distribution. Western blotting was used to assess the protein expression of related signaling proteins. Result:Compared with the two single drug groups treated with Tan ⅡA and DDP respectively, the combination group showed significantly higher anti-proliferative rate (P<0.01), arrested cell cycle at S phase, and resulted in observably higher apoptotic cell fractions in human hypopharyngeal squamous cell carcinomas Fadu cells; Western blotting showed that the protein expression of cleaved caspase 3 and cleaved PARP increased ,while survivin significantly decreased in the cells treated with the combination of tanshinone ⅡA and cisplatin. Conclusion:Tanshinone ⅡA potentiates the efficacy of Cisplatin in Fadu cells, which may be attributed to the downregulation of survivin protein expression.