Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Objective:To identify independent risk factors for early recurrence following curative resection of resectable pancreatic cancer and establish a nomogram prediction model.Methods:Clinical data from 405 patients with resectable pancreatic cancer treated at Renji Hospital, Shanghai Jiao Tong University School of Medicine from February 2010 to December 2020 were retrospectively reviewed. Patients were stratified into a training cohort (265 patients form February 2010 to December 2018) and a validation cohort (140 patients from January 2019 to December 2020) based on surgery dates. Optimal cutoff values for clinical variables were determined using X-tile software. Independent risk factors were identified through univariate and multivariate Cox proportional hazards regression analyses. Kaplan-Meier curves for recurrence-free survival (RFS) were generated across subgroups, and a nomogram was developed to predict early recurrence (within 1 year post-surgery). Time-dependent receiver operating characteristic (tROC) curves was drawn and area under the curve (AUC) metrics were utilized to evaluate predictive accuracy, while model reliability was assessed by calibration curves. Individualized risk scores derived from the nomogram were stratified into high- and low-risk groups using X-tile-derived cutoff values. Survival differences between groups were analyzed via log-rank tests. The clinical application value was judged by decision curve analysis (DCA) compared to TNM staging. Results:In the training cohort, 139 patients (52.45%) experienced early recurrence, with a median RFS of 11.1 months [interquartile range ( IQR): 6.0-26.0]. The validation cohort reported 70 early recurrences (50.00%) and a median RFS of 11.8 months ( IQR: 4.9-21.4). Univariate analysis revealed significant associations between early recurrence and tumor diameter, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), systemic immune-inflammation index (SⅡ), and prognostic nutritional index (PNI). Multivariate analysis identified tumor diameter ≥3.75 cm ( HR=1.718, 95% CI 1.223-2.412, P=0.002), CA19-9≥218 U/ml ( HR=1.567, 95% CI 1.107-2.220, P=0.011), CA125≥20.98 U/ml ( HR=2.501, 95% CI 1.768-3.539, P<0.001), SⅡ≥388.28 ( HR=1.708, 95% CI 1.096-2.662, P=0.018), and PNI<53.18 ( HR=0.596, 95% CI 0.404-0.879, P=0.009) as independent risk factors for early recurrence. The nomogram achieved AUC values of 0.771 and 0.708 in the training and validation cohorts, respectively. Calibration curves demonstrated strong agreement between predicted and observed survival probabilities. Kaplan-Meier analysis revealed significantly lower 1-year RFS rates in high-risk versus low-risk groups for both cohorts (training: HR=3.65, 95% CI 2.45-5.44, P<0.001; validation: HR=2.37, 95% CI 1.39-4.06, P=0.001). DCA indicated superior net benefit of the nomogram over TNM staging across threshold probabilities of 0.2-0.9. Conclusions:The proposed nomogram effectively integrates clinical and serological biomarkers to preoperatively assess early recurrence risk in resectable pancreatic cancer patients, offering enhanced precision for clinical decision-making.

Objective:To identify independent risk factors for early recurrence following curative resection of resectable pancreatic cancer and establish a nomogram prediction model.Methods:Clinical data from 405 patients with resectable pancreatic cancer treated at Renji Hospital, Shanghai Jiao Tong University School of Medicine from February 2010 to December 2020 were retrospectively reviewed. Patients were stratified into a training cohort (265 patients form February 2010 to December 2018) and a validation cohort (140 patients from January 2019 to December 2020) based on surgery dates. Optimal cutoff values for clinical variables were determined using X-tile software. Independent risk factors were identified through univariate and multivariate Cox proportional hazards regression analyses. Kaplan-Meier curves for recurrence-free survival (RFS) were generated across subgroups, and a nomogram was developed to predict early recurrence (within 1 year post-surgery). Time-dependent receiver operating characteristic (tROC) curves was drawn and area under the curve (AUC) metrics were utilized to evaluate predictive accuracy, while model reliability was assessed by calibration curves. Individualized risk scores derived from the nomogram were stratified into high- and low-risk groups using X-tile-derived cutoff values. Survival differences between groups were analyzed via log-rank tests. The clinical application value was judged by decision curve analysis (DCA) compared to TNM staging. Results:In the training cohort, 139 patients (52.45%) experienced early recurrence, with a median RFS of 11.1 months [interquartile range ( IQR): 6.0-26.0]. The validation cohort reported 70 early recurrences (50.00%) and a median RFS of 11.8 months ( IQR: 4.9-21.4). Univariate analysis revealed significant associations between early recurrence and tumor diameter, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), systemic immune-inflammation index (SⅡ), and prognostic nutritional index (PNI). Multivariate analysis identified tumor diameter ≥3.75 cm ( HR=1.718, 95% CI 1.223-2.412, P=0.002), CA19-9≥218 U/ml ( HR=1.567, 95% CI 1.107-2.220, P=0.011), CA125≥20.98 U/ml ( HR=2.501, 95% CI 1.768-3.539, P<0.001), SⅡ≥388.28 ( HR=1.708, 95% CI 1.096-2.662, P=0.018), and PNI<53.18 ( HR=0.596, 95% CI 0.404-0.879, P=0.009) as independent risk factors for early recurrence. The nomogram achieved AUC values of 0.771 and 0.708 in the training and validation cohorts, respectively. Calibration curves demonstrated strong agreement between predicted and observed survival probabilities. Kaplan-Meier analysis revealed significantly lower 1-year RFS rates in high-risk versus low-risk groups for both cohorts (training: HR=3.65, 95% CI 2.45-5.44, P<0.001; validation: HR=2.37, 95% CI 1.39-4.06, P=0.001). DCA indicated superior net benefit of the nomogram over TNM staging across threshold probabilities of 0.2-0.9. Conclusions:The proposed nomogram effectively integrates clinical and serological biomarkers to preoperatively assess early recurrence risk in resectable pancreatic cancer patients, offering enhanced precision for clinical decision-making.

Objective:To evaluate the effect of prophylactic octreotide administration on pancreaticoduodenectomy (PD)associated postoperative pancreatic fistula (POPF), total complications, peri-operative death and postoperative in-hospital days.Methods:From January 2020 to August 2021, 148 patients who underwent PD in the Department of Biliary-Pancreatic Surgery in Ren Ji Hospital affiliated with School of Medicine of Shanghai Jiao Tong University were recruited into this single-center randomized control double-blinded clinical trial. Patients were randomly assigned into octreotide group ( n=74) and control group ( n=74). Octreotide group was subcutaneously injected with 0.1 mg (1 ml) octreotide after preoperative anesthesia, and was subcutaneously injected with the same dose every 8 hours for 5 days, with a total of 16 doses. Control group was injected with 1 ml normal saline in the same way, and relevant clinical data and indicators of the two groups were recorded. The primary endpoint was clinically relevant pancreatic fistula, and the secondary endpoints were total complications, perioperative death and postoperative in-hospital days. Univariate and multivariate logistic regression analysis were used to screen the risk factors of clinically related POPF after PD. Results:120 patients were finally enrolled, including 61 in octreotide group and 59 in control group. There were no significant differences on age, gender ratio, body mass index, preoperative surgery rate of jaundice reduction, preoperative major biochemical indicators, operation time, intraoperative blood loss, pancreatic duct diameter, pancreatic texture and pathological type composition ratio. The total incidence of clinical relevant POPF was 8.3%, and there were no significant differences on biochemical leakage (4.9% vs 8.5%, P=0.435), grade B fistula (4.9% vs 8.5%, P=0.435) and grade C fistula (1.6% vs 1.7%, P=0.981). The total complication incidence (24.5% vs 28.8%, P=0.601), perioperative mortality (0 vs 3.3%, P=0.147) and postoperative in-hospital days (20.6±11.1 d vs 19.5±12.2 d, P=0.633) were not significantly different between two groups. Univariate analysis showed that preoperative serum albumin level <30 g/L( P<0.001) and pathological type of pancreatic ductal adenocarcinoma ( P=0.036) were independent risk factors for POPF after PD, while multivariate analysis found no statistically significant risk factors. Conclusions:Octreotide can neither reduce the incidences of POPF, total complications and postoperative mortality, nor shorten postoperative in-hospital days. However, for patients with preoperative hypoproteinemia and (or) the pathological type of pancreatic duct adenocarcinoma, the prophylactic use of octreotide during PD and after PD may reduce the occurrence of POPF.

Objective To investigate the prognostic factors of survival for patients with duodenal papilla carcinoma (DPC) after pancreaticoduodenectomy.Methods 98 DPC patients undergoing pancreaticoduodenectomy with follow-up from Jan 2010 to Dec 2017 at Renji Hospital,School of Medicine,Shanghai Jiao Tong University were analyzed retrospectively.Results 80 Cases were followed up.The 1,3,and 5 year survival rates of 80 patients were 89.9％,72.4％,and 66.6％,respectively.Univariate analysis showed tumor size,T stage,N stage,TNM stage,tissue differentiation degree were related to postoperative survival(all P ＜0.05).Multivariate analysis showed that tumor size,N stage,TNM stage,and tissue differentiation degree were independent factors influencing postoperative prognosis(all P ＜ 0.05).Conclusions Tumor size,N stage,TNM stage and tumor tissue differentiation degree were independent factors influencing the prognosis of DPC after pancreaticoduodenectomy,suggesting that early diagnosis,early treatment and radical resection were the key to improve the postoperative prognosis of DPC.

Objective To evaluate the safety,efficacy of interventional treatment for late postpancreaticoduodenectomy hemorrhage (LPPH).Methods From Jan 2008 to Dec 2017,678 patients underwent pancreaticoduodenectomy (PD).33 patients (4.9％) suffered from LPPH.30 of these 33 patients underwent diagnostic angiography and endovascular treatment,either transcatheter arterial embolization (TAE,n =21) or covered stent placement (CSP,n =9),and the other 3 underwent laparotomy.Results The incidence of LPPH is 4.9％ with a 12％ motality.The most common presentation is bleeding from abdominal drainage (24.2％) and melena (24.2％).The incidence of sentinel bleeding (SB) is 45.5％ and postoperative pancreatic fistula (POPF) is 69.7％.Intra-abdominal infection were identified in 24 patients (72.7％) and the most common pathogenic bacteria is pseudomonas aeruginosa (11/24,45.8％).The mean time between PD operation and LPPH was 17.4 days.In 21 patients receiving TAE,4 got liver damage and 2 with liver abscesses,1 died.The most common site of LPPH is GDA stump and re-bleeding occurred in 5 patients.9 patients by CSP got bleeding under control.In all 7 re-bleeding patients,2 were saved by CSP,1 was saved by TAE,while the other 4 died.Conclusion Early intervention plays an important role for LPPH.CSP is better than TAE.

Objective To study the impact of lymph node metastasis on prognosis of patients with pancreatic cancer and to evaluate predictors of postoperative survival of these patients.Methods The clinical data on patients with pancreatic cancer who underwent pancreatic cancer radical surgery in our hospital from January 2002 to December 2013 were reviewed and analyzed.Data on lymph node metastasis,number of lymph node dissection,number of positive lymph nodes and positive lymph ratio were analyzed.Results Of 101 patients,the 6-month,1-year and 2-year survival rates were 84.2％,56.6％ and 28.5％,respectively.The median survival was 13.8 months.Univariate and multivariate analyses showed lymph node metastasis,a positive lymph node ratio,number of lymph node dissection and positive lymph nodes were independent influential factors of prognosis.Results of subgroup analysis showed the number of lymph node dissection was a prognostic factor for pNO patients,while a positive lymph ratio had no impact on survival of pN1 patients.In the subgroup of patients with pancreatic head cancer,lymph node metastasis was associated with prognosis but not in the subgroup of patients with pancreatic body and tail carcinoma.Conclusions For patients with pancreatic head cancer,lymph node metastasis was closely correlated with prognosis.In addition,factors including lymph node metastasis,number of lymph node dissection,a positive lymph node ratio and number of positive lymph nodes were independent influential factors of prognosis for patients with pancreatic head cancer.However,for pN1 patients,a positive lymph node ratio has no influence on prognosis.

OBJECTIVETo evaluate the pancreaticojejunostomy procedures selection strategy in pancreaticoduodenectomy and to analyze risk factors of pancreatic fistula.

METHODSClinical data of 352 patients who received pancreaticoduodenectomy from September 2009 to September 2012 were retrospectively analyzed. For patients with soft pancreas, binding pancreaticojejunostomy was applied to 153 patients. For patients with hard pancreas, duct-to-mucosa pancreaticojejunostomy (DMPJ) was applied (199 cases). The clinical efficacy and incidence of postoperative complications were compared among 2 groups. Risk factors of pancreatic fistula were screened out from many factors by univariate and multivariate analysis.

RESULTSThe overall incidence of pancreatic leakage was 13.9% (49/352). There were no significant difference in incidences of pancreatic leakage (χ(2) = 0.512), peritoneal bleeding (χ(2) = 0.784), abdominal infection (χ(2) = 1.161), digestive dysfunction rate (χ(2) = 4.753) and mean duration of hospital stay (t = 2.13) among 2 groups (all P > 0.05). The results of multivariate analysis showed pancreatic tube diameter < 3 mm (OR = 5.748), preoperative total bilirubin level > 171 µmol/L (OR = 5.112), duration of preoperative jaundice > 8 weeks (OR = 5.090), preoperative albumin level < 30 g/L (OR = 4.464) were independent risk factors of pancreatic fistula (all P < 0.05).

CONCLUSIONSBunding pancreatojejunostomy was as good as soft pancreatic; for duct diameter ≥ 3 mm suggested using duct-to-mucosa pancreaticojejunostomy. For the risk factors for pancreatic leakage actively cooperate with preoperative nutritional support and timely treatment of jaundice, the incidence of postoperative pancreatic leakage will be further reduced.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Fistula ; Pancreaticoduodenectomy ; Pancreaticojejunostomy ; methods ; Postoperative Complications ; Retrospective Studies ; Risk Factors

Objective To analyze the risk factors of pancreatic fistula after pancreaticoduodenectomy,in order to provide evidence to reduce post-operative complication in clinical practice.Methods The clinical data of 352 patients with malignancy who received pancreaticoduodenectomy at the Shanghai Renji Hospital from September 2009 to September 2012 were retrospectively analyzed.The patients were divided into pancreatic fistula group and non-pancreatic fistula group.Peri-operative risk factors of pancreatic fistula after pancreaticoduodenectomy were analyzed by univariate and multivariate logistic regression analysis.Results Forty-nine cases of pancreatic fistula occurred,and the incidence rate of pancreatic fistula was 13.9％ (49/352).Univariate and multivariate logistic regression analysis showed sex,age,history of diabetes,operation time,intra-operative blood loss,vessel reconstruction,pancreatic tube placement,anastomosis time,type of digestive tract reconstruction were not risk factors of pancreatic fistula; however,brittle pancreatic tissue,diameter of pancreatic duct ＜3 mm,pre-operative total bilirubin level ＞ 171 μmol/l,duration of preoperative jaundice ＞ 8 weeks,pre-operative albumin level ＜30 g/L were the independent risk factors of pancreatic fistula (P ＜ 0.05).Conclusions Brittle pancreatic tissue,small pancreatic duct,high level of serum bilirubin,long duration of preoperative jaundice,low level of serum albumin are the independent risk factors of pancreatic fistula after pancreaticoduodenectomy.