Objective To investigate the effect of argatroban on C-reactive protein (CRP) and therapeutic efficacy in patients of malignant tumor complicated by acute lower limbs deep venous thrombosis (DVT).Methods 56 patients of malignant tumor complicated by acute lower limbs DVT were randomly divided into two groups.In observation group (n =28),argatroban was given intravenously as anticoagulation.Urokinase as thrombolysis and warfarin as anticoagulation were used in the control group (n =28).The concentrations of serum CRP were detected before treatment and on the 14th day of post-treatment in observation group and control group.Recanalization and therapeutic effect of DVT were compared.Results Before treatment,there was no significant differences in the serum CRP concentrations between observation group and control group [(46.44±28.82) mg/L vs (45.96±29.40) rmg/L,F =0.004,P =0.951].On the 14th day of post-treatment,the CRP concentrations in observation group and control group were lower than those of pretreatment (F =25.996,P ＜ 0.05,F =4.828,P ＜ 0.05).Compared with the 14th day of post-treatment,the CRP concentration of observation group was lower than that of control group [(16.97±10.22) mg/L vs (31.63± 18.07) mg/L,F =13.965,P ＜ 0.01].Recanalization rate of observation group on the 14th day of post-treatment (96.43 ％,27/28) was higher than that in control group (67.86 ％,19/28) (x2 =8.204,P =0.017).Therapeutic effect rate of observation group on the 14th day of post-treatment (96.43 ％,27/28) was higher than that in control group (75.00 ％,21/28) (x2 =6.205,P =0.045).Conclusion Argatroban can decrease serum level of CRP in patient of malignant tumor complicated by acute lower limbs DVT,which is favorable for improvement of clinical effectiveness.

Objective To compare the efficacies of intralesional hyaluronidase(HAase), intralesional dexamethasone(DEX), and intralesional HAase plus intralesional DEX on skin damage caused by vinorelbine extravasation in a rat model. Methods After establishing an animal model with vinorelbine extravasation in each lower extremity of 40 Sprague-Dawley rats, we treated the rats with intralesional HAase,intralesional DEX, intralesional HAase plus intralesional DEX,intralesional saline,or received no treatment as control.The wound area on 1 d, 4 d, 8 d, 12 d, 18 d, 24 d, 30 d and the time of healing were observed and compared.Results The wound area on 1 d, 4 d, 8 d, 12 d, 18 d and 24 d was significantly lower in intralesional HAase group, intralesional DEX group,intralesional HAase plus intralesional DEX group,and intralesional saline group than that in control group (P ＜0.05), and that was significantly lower in intralesional HAase group and intralesional HAase plus intralesional DEX group than that in intralesional DEX group and intralesional saline group (P ＜0.05). The healing time was significantly shorter in 4 therapy groups than that in control group [(25.1±3.1) d, (27.9±2.8) d, (23.0±3.2) d, and (28.4±3.9) d vs.(31.2±3.0) d, P ＜0.05], and that was significantly lower in intralesional HAase group and intralesional HAase plus intralesional DEX group than that in intralesional DEX group and intralesional saline group (P ＜0.05). Conclusion The monotherapy with intralesional HAase or intralesional DEX, with decreasing the extent of skin damage and shortening the healing time, is effective therapy for skin damage caused by vinorelbine extravasation, and the monotherapy with intralesional Haase is more efficacious. The efficacy of intralesional HAase plus intralesional DEX seems better than that of monotherapy.

Objective To investigate the implication of C-reactive protein in development and prognosis of acute lower limb deep venous thrombosis (DVT) complicated by malignant tumor.Methods34patients with acute lower limb DVT complicated by malignant tumor(observation group),34 patients with acute lower limb DVT complicated by operation or wound(case control group)and 34 normal volunteers (normal control group) were included in this study.The observation group and case control group were treated with conventional therapy such as thrombolysis and anticoagulation.The serum concentrations of CRP before treatment and 14 days after treatment were detected. Recanalization of lower limb DVT and therapeutic efficacy were compared between observation group and case control group.ResultsThe serum concentrations of CRP in observation group before treatment were significantly higher than those in case control group and normal control group [(47.72±29.88) mg/L vs (30.04±15.84) mg/L and (6.19±2.99) mg/L,F =38.444,P ＜ 0.01].At the 14th day of post-treatment,the serum CRP concentrations in observation group and case control group were significantly lower than those before treatment (P ＜0.05).At the 14th day of post-treatment,the CRP concentrations of observation group and case control groups were significantly decreased,although those of observation group were still significantly higher than those of case control group and normal control [(32.77±19.68) mg/L vs (7.76±7.52) mg/L and (6.19±2.99) mg/L,F =50.087,P ＜ 0.01].However,there was no significant difference between case control group and normal control group on the 14th day of post-treatment (F =1.277,P =0.263).The recanalization rate of observation group at the 14th day of post-treatruent were significantly lower than those in case control group(x2 =7.731,P =0.021).The therapeutic effect rate of observation group at the 14th day of post-treatment were also significantly lower than those in case control group (x2 =6.969,P =0.031).ConclusionCRP may play important roles in occurrence,development and therapeutic effect of acute lower limb DVT complicated by malignant tumor.

Objective To investigate the expression of bone sialoprotein (BSP) in prostate cancer and its clinical significance. Methods Prostate cancer tissues of different pathological grades (68 cases) and benign prostatic hyperplasia tissues (22 cases) were selected. SP method was used to detect the expression of BSP. Serum total prostate-specific antigen (tPSA) levels of prostate cancer were detected by electrochemiluminescence immunoassay before the operation. Results Compared with no or low expression in the adjacent normal glandular tissues, the detectable levels of BSP were examined in most of the prostate cancer tissues. The expression rate of BSP in prostate cancer tissues was higher than that in benign prostatic hyperplasia tissues [76.47%(52/68) vs 13.64%(3/22),χ2=27.614, P<0.001]. The expression rates of BSP in well differentiated, moderately differentiated and poorly differentiated tissues according to cell differentiating degree (Gleason system) were 75.0 % (12/16), 77.5 % (31/40) and 75.0 % (9/12) respectively. There was no significant difference in various pathological grading (χ2=0.057, P=0.972). The expression rates of BSP in pathological stage pT2, pT3 and pT4 tissues were 62.16%(23/37), 95.24%(20/21) and 90.0%(9/10) respectively. A statistically significant association was found between BSP expression and pathological stage (χ2=9.338, P=0.009). Serum tPSA level of prostate cancer group with BSP expression was higher than that with no BSP expression [(69.06±25.52)μg/L vs (38.00±21.64)μg/L, F=19.355, P<0.001]. Conclusion The high expression of BSP in prostate cancer has a relationship with pathological stage and serum tPSA level, it may play an important role in the biological behaviour of prostate cancer.

Objective To analyze the efficacy and safety of CyberKnife combined with temozolomide (TMZ) in treatment of brain metastasis of non-small cell lung cancer (NSCLC). Methods From March 2013 to March 2016, 62 NSCLC patients with brain metastases in department of oncology of the 187th Hospital of PLA were divided into two groups according to the random number table method, the CyberKnife combined with TMZ group (CyberKnife + TMZ group, 31 cases) and simple CyberKnife group (CyberKnife group, 31 cases). Hypofractionated radiation of CyberKnife was given 18-36 Gy in 1-5 fractions of 5-25 Gy. CyberKnife+ TMZ group was given temozolomide 150 mg·m-2·d-1 for 5 days in first cycle, then every 28 days they received temozolomide therapy from the second to the sixth cycles: 200 mg·m-2·d-1 for 5 days. The clinical symptom remission rate after the treatment of CyberKnife in one week, the effective rate after CyberKnife in 3 months, the median intracranial progression-free survival time, overall survival, and the incidences of adverse reaction were comparatively analyzed. Results The clinical symptom remission rates of CyberKnife+TMZ group and CyberKnife group after the treatment of CyberKnife in one week were 93.6 ％ (29/31) and 96.8 ％ (30/31). There was no significant difference in the clinical symptom remission rates (χ2= 1.207, P=0.547). The effective rates of the two groups after CyberKnife in 3 months were 93.6 ％ (29/31) and 90.3 ％(28/31). There was no significant difference in the effective rates (χ2 = 0.695, P= 0.706). The median intracranial progression-free survival time in CyberKnife + TMZ group (14.0 months) was significantly higher than that in the CyberKnife group (9 months) (χ2=8.977, P=0.003), and the median overall survival time in CyberKnife + TMZ group (15.0 months) was also significantly higher than that in the CyberKnife group (12.0 months) (χ2 = 5.190, P= 0.023). There was no significant difference in the adverse reaction of the central nervous system between the two groups (χ2=0.746, P=0.689), but the adverse reactions of the digestive system (χ2 = 6.062, P= 0.014) and the hematologic system (χ2 = 6.613, P= 0.010) in CyberKnife + TMZ group were significantly higher than those in the CyberKnife group. Systemic adverse reactions of the two groups were tolerated by most patients. Conclusions CyberKnife combined with TMZ is a feasible therapeutic option for NSCLC patients with brain metastases. This therapy can improve the median survival time to cerebral progression of the disease and the median overall survival time.

Objective:To explore the characteristics of T lymphocyte subsets and cytokines in hyperlipidemia-induced acute pancreatitis (HLAP) and its prognostic value.Methods:This study included 184 patients with acute pancreatitis (AP) admitted to the First Affiliated Hospital of Xiamen University from January 2018 to May 2021. Based on disease etiology, there were 92 HLAP cases and 92 non-hyperlipidemia-induced AP (NHLAP) cases. Stratified by disease severity according to 2012 Atlanta classification criteria, the patients were divided into the severe subgroup (SAP) and non-severe subgroup (NSAP). Peripheral venous blood samples were taken from all patients on day 1, 3, and 5 after admission. T lymphocyte subsets were determined by flow cytometry, and cytokines were detected by flow fluorometry. The number of CD4 +% and CD8 +% and the expression of cytokines were compared by Student’s t test or Mann-Whitney U analysis. Logistic regression analyses were performed to identify risk factors for severe AP, and a receiver operating characteristic (ROC) curve was constructed to predict severe AP. Statistical significance was taken as P<0.05. Results:Compared with the NHLAP group, patients in the HLAP group had lower CD4 +%, while higher levels of IL-2 on day 1 ( P<0.05), and had also lower CD4 +%, while higher levels of IL-4, IL-6, and IL-10 on day 3 ( P<0.05). Furthermore, IL-6 and IL-10 levels of the HLAP group were significantly increased compared to the NHLAP group on day 5 ( P<0.05). IL-10 levels in the SAP subgroup were significantly higher than those in the NSAP subgroup on day 1 ( P<0.05). Compared with the NSAP subgroup, the SAP subgroup had elevated levels of IL-2, IL-4, IL-6, IL-10 and IFN-γ on day 3 (all P<0.05), and had lower CD4 +%, while increased levels of IL-6 and IL-10 on day 5 (all P<0.05). Multivariate Logistic regression analysis showed that IL-10 was an immune indicator of independent risk factor for severe AP in the HLAP group on day 1 ( OR=1.139, 95% CI: 1.038-1.251, P<0.05). Finally, ROC analysis showed that the area under the curve of IL-10 to assess HLAP with severe AP was 0.772, and the best cut-off value for predicting severe AP was 5.6 pg/mL, with a sensitivity of 83.3% and a specificity of 68.8%. Conclusions:Changes of CD4 +% and cytokines are different between the HLAP and NHLAP groups. IL-10 can be used as a predictor of early disease severity in patients with HLAP.

Objective:To summarize the characteristics and difficulties of minimal invasive surgery for adolescent with pancreatic head tumor.Methods:The data of adolescent younger than 28 years old with pancreatic head tumor treated at Department of Gastroenterology and Pancreatic Surgery, Zhejiang Province People′s Hospital from January 2014 to December 2019 were analyzed retrospectively. Fifteen cases were enrolled, included 5 males and 10 females. The median age was 20 years(range: 11 to 27 years) and the body mass index was (19.8±2.3)kg/m 2(range: 17.3 to 21.6 kg/m 2). Results:Standard pancreaticoduodenectomy was performed in 12 cases, including 9 cases of laparoscopic surgery and 3 cases of robotic-assisted surgery, and laparoscopic pancreaticoduodenectomy with resection of hepatic flexure of colon was performed on 1 case, and robotic-assisted duodenum-preserving pancreatic head resection with pancreatogastrostomy was performed on other 2 cases. The operative time was (269.0±65.1)minutes(range: 150 to 410 minutes), and the blood loss was (135.6±52.7)ml(range: 50 to 400 ml). Six patients got postoperative complications with gastrointestinal bleeding biochemical leakage and intestinal obstruction( n=1), pancreatic biochemical leakage( n=1), bile leakage( n=1), chylous leakage( n=1), wound infection( n=1), hepatic injury( n=1). The median postoperative hospital stay was 13 days(range: 9 to 22 days).The pathologic findings were solid pseudopapillary neoplasms( n=8), neuroendocrine neoplasms( n=3), introductal papillary mucinous neoplasm( n=1), cystic fibroma( n=1), serous cystadenoma( n=1), Ewing sarcoma( n=1).The median follow-up was 37 months(range: 2 to 75 months).The patient with Ewing sarcoma was diagnosed as liver metastasis at 41 months after surgery and died at 63 months after surgery.All the other patients survived without tumor.Three patients got the long-term complication of bile duct. Conclusions:Most of pancreatic head tumors for adolescent are benign or low malignant. Minimally invasive surgery be the first choice, and function-preserving surgery should be taken into account as much as possible.Perioperative management and communication is essential as the parents pay much attention to the quality of life after surgery.

Objective To investigate the role of delta/notch-like epidermal growth factor-related receptor(DNER)in gastric cancer and its regulatory mechanism.Methods The mRNA and protein levels of DNER in gastric cancer tissues and cells were detected with quantitative real time polymerase chain reaction(qRT-PCR)and Western blot.Gastric cancer cell line SGC7901 with silenced DNER expression was constructed,and cells were treated with mitochondrial dynamin-related protein 1(DRP1)inhibitor Mdivi-1.CCK-8 assay,Transwell assay,and flow cytometry were used to detect cell viability,invasion ability and apoptosis,respectively.Western blot was used to detect DNER protein levels,apoptosis-associated proteins[Cysteinyl aspartate-specific proteinase-3(Caspase-3),Bcl-2 Associated X(Bax)],autophagy associated proteins[microtubule-associated protein 1 light chain 3-Ⅱ/Ⅰ,LC3 Ⅱ/Ⅰ),p62,PTEN induced putative kinase 1(PINK1)and Parkin],and mitochondrial fission and fusion protein[DRP1,mitochondrial fission factor(MFF),mitochondrial fission protein 1(FIS1),Optic Atrophy 1(OPA1),mitofusin 1(MFN1)and MFN2]levels.Results The expression levels of DNER mRNA and protein in gastric cancer tissues were higher than those in adjacent normal tissues(t=-52.485,-46.955),while expression levels of DNER mRNA and protein in gastric cancer cells were higher than those in normal gastric epithelial cells(F=60.551,60.652),and the differences were significant(P＜0.001).Silencing DNER inhibited the proliferation and invasion of SGC7901 cells,induced apoptosis,and increased the expression of apoptosis-related proteins,with significant differences(t=8.026～25.903,all P＜0.05).Silenced DNER increased LC3 Ⅱ/Ⅰ ratio(t=18.086),decreased p62 protein level(t=6.747),promoted the aggregation of PINK1 and Parkin proteins in mitochondria(t=15.630,18.171),inhibited the expression of mitochondrial fusion proteins OPA1,MFN1 and MFN2(t=12.835,8.963,9.732),and promoted the expression of mitochondrial fission proteins DRP1,MFF and FIS1(t=16.034,16.939,15.971),with significant differences(all P＜0.05).Mdivi-1 treatment could counteract the effects of silencing DNER on mitochondrial autophagy,proliferation,invasion and apoptosis of gastric cancer cells.Conclusion DNER can reduce mitochondrial autophagy by inhibiting mitochondrial dynamic imbalance,promote cell proliferation and invasion,and inhibit cell apoptosis,thus promoting the progression of gastric cancer.

Background:Circular RNAs(circRNAs)are covalently closed single-stranded RNAs with multiple biological functions.CircRNA.0007127 is derived from the carbon catabolite repression 4-negative on TATA-less(CCR4-NOT)complex subunit 2(CNOT2),which was found to regulate tumor cell apoptosis through caspase pathway.Methods:Potential circRNA.0007127 target microRNAs(miRNAs)were analyzed by miRanda,TargetScan,and RNAhybrid software,and the miRNAs with binding sites for apoptosis-related genes were screened.The roles of circRNA.0007127 and its downstream target,microRNA(miR)-513a-5p,were validated by quantitative real-time polymerase chain reaction(qPCR),flow cytometry,mitochondrial membrane potential,immunofluorescence,western blot,and caspase-8(CASP8)protein activity in vitro in H2O2-induced K-562 cells.The circRNA.0007127-miR-513a-5p and CASP8-miR-513a-5p interactions were verified by luciferase reporter assays.Results:Silencing circRNA.0007127 decreased cell apoptosis by inhibiting CASP8 pathway activation in K-562 cells.Compared with the control group,the expression of CASP8 was reduced by 50％and the 43-kD fragment of CASP8 protein was significantly reduced(P≤0.05).The luciferase reporting assay showed that circRNA.0007127 combined with miR-513a-5p or CASP8,with extremely significant differences(P≤0.001).The overexpression of miR-513a-5p inhibited the gene expression level of CASP8 in a human myeloid leukemia cell model(75％change)and the level of a 43-kD fragment of CASP8 protein(P≤0.01).The rescue experiment showed that cotransfection with circRNA.0007127 small-interfering RNA(siRNA)and the miR-513a-5p inhibitor increased CASP8 gene expression and the apoptosis rate,suggesting that the miR-513a-5p inhibitor is a circRNA.0007127 siRNA antagonist.Conclusions:CircRNA.0007127 regulates K-562 cell apoptosis through the miR-513a-5p/CASP8 axis,which can serve as a novel powerful molecular target for K-562 cells.

Objective:To summarize the characteristics and difficulties of minimal invasive surgery for adolescent with pancreatic head tumor.Methods:The data of adolescent younger than 28 years old with pancreatic head tumor treated at Department of Gastroenterology and Pancreatic Surgery, Zhejiang Province People′s Hospital from January 2014 to December 2019 were analyzed retrospectively. Fifteen cases were enrolled, included 5 males and 10 females. The median age was 20 years(range: 11 to 27 years) and the body mass index was (19.8±2.3)kg/m 2(range: 17.3 to 21.6 kg/m 2). Results:Standard pancreaticoduodenectomy was performed in 12 cases, including 9 cases of laparoscopic surgery and 3 cases of robotic-assisted surgery, and laparoscopic pancreaticoduodenectomy with resection of hepatic flexure of colon was performed on 1 case, and robotic-assisted duodenum-preserving pancreatic head resection with pancreatogastrostomy was performed on other 2 cases. The operative time was (269.0±65.1)minutes(range: 150 to 410 minutes), and the blood loss was (135.6±52.7)ml(range: 50 to 400 ml). Six patients got postoperative complications with gastrointestinal bleeding biochemical leakage and intestinal obstruction( n=1), pancreatic biochemical leakage( n=1), bile leakage( n=1), chylous leakage( n=1), wound infection( n=1), hepatic injury( n=1). The median postoperative hospital stay was 13 days(range: 9 to 22 days).The pathologic findings were solid pseudopapillary neoplasms( n=8), neuroendocrine neoplasms( n=3), introductal papillary mucinous neoplasm( n=1), cystic fibroma( n=1), serous cystadenoma( n=1), Ewing sarcoma( n=1).The median follow-up was 37 months(range: 2 to 75 months).The patient with Ewing sarcoma was diagnosed as liver metastasis at 41 months after surgery and died at 63 months after surgery.All the other patients survived without tumor.Three patients got the long-term complication of bile duct. Conclusions:Most of pancreatic head tumors for adolescent are benign or low malignant. Minimally invasive surgery be the first choice, and function-preserving surgery should be taken into account as much as possible.Perioperative management and communication is essential as the parents pay much attention to the quality of life after surgery.