AIM To investigate the effect of N n butyl haloperidol iodide (F 2) on potassium currents in enzymatically isolated vascular smooth muscle cells (VSMC) from thoracic aortas and the effect of F 2 on aortic rings of rat. METHODS The whole cell patch clamp technique and the contraction of rats thoracic aortic rings were used in experiments. RESULTS The outward currents were observed when holding potential was -40 mV and the cell was depolarized from -30 mV to +100 mV (in 10 mV increase) for 400 ms. At the point of the test potential of +70 mV, solutions of F 2 (0 1,1, 5 ?mol?L -1 ) were added into bath (external) solution, which led to the increase of the outward currents from (229?28)pA,(226?57)pA and(228?42) pA to (354?29) pA ( n =6, P

AIM　To observe the effect of quateranary ammonium salt derivative (F2) of haloperidol on calcium level in vascular smooth muscle cells (VSMCs) isolated from thoracic aortas of rat. METHODS　VSMCs were loaded with Fluo-3-AM, a calcium sensitive fluorescent dye, and ［Ca2+］i was determined by the use of laser scanning confocal microscope (LCSM). RESULTS　In Ca2+ (1.26 mmol*L-1) bath solution, intracellular calcium fluorescent intensity (FI) in VSMCs was increased when application with 30 mmol*L-1 KCl, and then was inhibited after addition with F2. The FI of the ASMCs with different concentrations of F2 (0.1,1,10,100 μmmol*L-1)within three minutes were 64%±9%(n=16, P<0.05),16%±5%(n=20, P<0.01),0.6%±0.8%(n=20, P<0.01),0.1%±0.3%(n=15, P<0.01), respectively. CONCLUSION　F2 could decrease the intracellular Ca2+ level in the VSMCs by blocking the voltage-dependent calcium channel.

The Ca2+-ATPase of sarcoplasmic reticulum is a Ca2+ pump that plays a key role in regulating cytosol calcium concentration in muscle cells. It undergoes a sequential conformational transition during the transport process. According to the classical E1/E2 theory, in the E1 state the binding sites have high affinity and open to the cytoplasm, whereas in the E2 state the binding sites have low affinity and face the luminal side. Crystal structures of several states during the reaction cycle of Ca2+-ATPase have been solved recently, including a Ca2+-bound form (E1-2Ca2+), a Ca2+-unbound form stabilized by a potent inhibitor thapsigargin (TG) (E2-TG), an ATP-bound form (E1-ATP), an E1-P-ADP state, and an E2-Pi state. The details of these crystal structures and the relationship between structure and function of Ca2+-ATPase during reaction cycle were summarized, and the issues to be addressed in future research were raised.

AIM To observe the effect of quateranary ammonium salt derivative (F 2) of haloperidol on calcium level in vascular smooth muscle cells (VSMCs) isolated from thoracic aortas of rat. METHODS VSMCs were loaded with Fluo 3 AM, a calcium sensitive fluorescent dye, and [Ca 2+ ] i was determined by the use of laser scanning confocal microscope (LCSM). RESULTS In Ca 2+ (1 26 mmol?L -1 ) bath solution, intracellular calcium fluorescent intensity (FI) in VSMCs was increased when application with 30 mmol?L -1 KCl, and then was inhibited after addition with F 2. The FI of the ASMCs with different concentrations of F 2 (0 1,1,10,100 ?mmol?L -1 )within three minutes were 64%?9%( n =16, P

Objective To investigate the efficacy of vascular endothelial growth factor (VEGF) gene therapy in coronary occlusion of animal Methods 19 swine underwent left thoracotomy followed by the ligation of left anterior descending coronary artery Constructed pcD 2/hVEGF 121 eukaryotic expression plasmid was directly injected into the swine myocardium RT PCR, immunohistochemistry of VEGF and factor Ⅷ related antigen were used to detect VEGF gene expression and biological effect Coronary angiography was done to evaluate collateral circulation of the occluded artery Results High levels of VEGF mRNA and protein expression were detected There was a significant increase in the number of capillaries when compared with control group Coronary angiography showed better collateral circulation in VEGF group Conclusion Direct injection of pcD 2/hVEGF 121 eukaryotic expression plasmid can transfect the myocardium and express VEGF protein This gene product can increase capillary number and enhance collateral circulation of the occluded coronary

Objective To investigate the application value of percutaneous sinus-tract cholangioscopy in the diagnosis and treatment of residual intra-and extra-hepatic bile duct stones.Methods The retrospective cross-sectional study was conducted.The clinical data of 1 045 patients with intra-and extra-hepatic bile duct stones who underwent percutaneous sinus-tract cholangioscopy or stone extraction in the Second Affiliated Hospital of Zhejiang University from January 2003 to June 2016 were collected.Patients received percutaneous sinus-tract cholangioscopy or stone extraction at 6-8 weeks after T tube drainage.Observation indicators:(1) diagnosis and stone extraction situstions:cases with residual stones,stone extraction frequency and clearance rate;the critics of clearance rate are no residual stone dnring operation combined with B ultrasound or T-tube cholangiography;(2) postoperative complications:incidence and management of postoperative complications,prognosis and ClavienDindo classification for postoperative complication;(3) follow-up situation.T-tube was removed when there was no residual stone.Patients were followed up by outpatient examination up to April 2017.B ultrasound reexamination was performed to detect the recurrence of stone once every 3-6 months.Results (1) Diagnosis and stone extraction situstions:among 1 045 patients,results of cholangioscopy showed 147 wihout bile duct stones and 898with bile duct stones.Of 898 patients,2 618 times cholangioscopic explorations for stone extraction were performed,with a maximum frequency of 16 times,and 851 had stones clearance,with a overall clearance rate of 94.77％(851/898).The clearance rates of extra-and intra-hepatic bile duct stones were 100.00％(221/221) and 93.06％(630/677).Of 47 patients with residual stones,16 didn't receive cholangioscopy due to branches stricture or occlusion of intrahepatic duct,13 failed to take out stone due to T-tube dislodgement (9 cases) and improper placement (4 cases) induced closed T-tube sinus tract,7 had T-tube sinus tract duodenal fistula,6 gave up stone extraction,3 was due to longer sinus tract induced bending and 2 was due to T-tube sinus tract fracture.(2)Postoperative complications:among 1 045 patients,297 had level Ⅰ-Ⅱ mild complications and 13 had level Ⅲand above severe complications.The common complications included fever,vomiting,diarrhea and so on;the special complications included T-tube sinus tract duodenal fistula of 13 patients,T-tube sinus tract fracture of 4 patients,rupture of broken stones pole of 3 patients,massive hemobilia of 2 patients,acute pancreatitis of 2patients and cardiac arrest of 1 patient.The above complications were improved by symptomatic and supportive treatments.(3) Follow-up situation:among 1 045 patients,558 received long-term follow-up,with follow-up time of 10-171 months and a median time of 79 months.Eight-four patients had stone recurrence.Of 13 patients with recurrence of extrahepatic bile duct stones,7 took out stones by endoscopic retrograde cholangio pancreatography (ERCP) and 6 underwent reoperations.Of 71 patients with recurrence of intrahepatic bile duct stones,43underwent reoperations and 28 received conservative treatment.Conclusions Percutaneous sinus-tract cholangioscopy for residual intra-and extra-hepatic bile duct stones is safe and effective,with good diagnosis and treatment values and a high clerance rate.The integrity of T-tube sinus-tract is a key of complete stones removal.

OBJECTIVETo explore efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) regimen by dose attenuation in locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer(MPC).

METHODSBetween April 2014 and October 2015, 35 patients with LAPC (n=18) or MPC (n=17) were treated with mFOLFIRINOX regimen (irinotecan 135 mg/m(2), oxaliplatin 68 mg/m(2), 5-FU 2 400 mg/m(2), no bolus of 5-FU, leucovorin 400 mg/m(2)) in the Second Affiliated Hospital of Zhejiang University School of Medicine. The primary end point was progression free survival. The second end points were overall survival, objective response rate, adverse effects, surgical resection rate for LAPC.

RESULTSAmong 35 patients, 6 patients (17.1%) who dropped out and received less than 2 cycles were excluded for response analysis. Among the other 29 patients, 9 patients had grade 3 or 4 adverse effects. No patients ceased treatment due to adverse effects. The 29 patients received 5 (2-13) cycles were evaluated by efficacy and found partial remission in 16 cases, stable disease in 10 cases, progression disease in 3 cases. Response rate was 55.2%. Nine patients with LAPC accomplished surgery after neoadjuvant treatment without perioperative complication and death, and 6 patients accepted R0 resection.

CONCLUSIONSThe mFOLFIRINOX regimen used in the study is well-tolerated in Chinese population with high treatment efficacy on patients with LAPC and MPC. Further investigation of efficacy and adverse effects on more advanced pancreatic cancer patients is necessary.

Antineoplastic Combined Chemotherapy Protocols ; Camptothecin ; administration & dosage ; analogs & derivatives ; Disease Progression ; Disease-Free Survival ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Neoadjuvant Therapy ; Organoplatinum Compounds ; administration & dosage ; Pancreatic Neoplasms ; drug therapy ; Tertiary Care Centers ; Treatment Outcome

Objective:To construct enhanced computed tomography (CT)-based nomograph model, to assist physicians in differentiating gastric schwannoma from gastric stromal tumor.Methods:From January 1, 2012 to January 1, 2022, at the Second Affiliated Hospital of Zhejiang University School of Medicine and Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, 57 patients with gastric schwannoma and 275 patients with gastric stromal tumor confirmed by surgical pathology were retrospectively collected, among whom 39 patients with gastric schwannoma and 201 patients with gastric stromal tumor were enrolled in the training set, and the other 18 patients with gastric schwannoma and 74 patients with gastric stromal tumor were enrolled in the validation set. The contrast-enhanced CT imaging features (tumor size index, arterial phase CT value, venous phase CT value, necrosis, calcification, integrity of mucosal surface, and uniform enhancement, etc.) and clinical data (history of gastritis, carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen, and monocyte to lymphocyte ratio (MLR), etc.) were collected. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to screen the independent predictive factors of imaging features in the differential diagnosis of gastric schwannoma and gastric stromal tumor, and a nomograph model was constracted. Logistic regression analysis was used to analyze and screen the independent predictive factors of clinical indicators to distinguish gastric schwannoma from gastric stromal tumor, and a clinical control model was established. The receiver operating characteristic curve(ROC) was used to analyze the area under the curve (AUC) of the nomograph model in the training set and the verification set, and concordance index (CI) and decision curve analysis (DCA) were used to evaluate the predictive efficiency and clinical application value of the nomograph model. DeLong test was used for statistical analysis.Results:The results of LASSO regression analysis showed that tumor size index, arterial phase CT value, venous phase CT value, necrosis, calcification, integrity of mucosal surface, and uniform enhancement were independent predictive factors of imaging features in the differential diagnosis of gastric schwannoma and gastric stromal tumor(all P<0.05). The results of logistic regression analysis indicated that the history of gastritis ( OR=0.280, 95% confidence interval 0.138 to 0.566), CA19-9 ( OR=0.940, 95% confidence interval 0.890 to 0.993), carcinoembryonic antigen ( OR=0.794, 95% confidence interval 0.661 to 0.952), and MLR ( OR=0.087, 95% confidence interval 0.009 to 0.860) were independent predictive factors of clinical indicators in the differential diagnosis of gastric schwannoma and gastric stromal tumor ( P<0.001, =0.028, 0.013 and 0.037). The AUCs of the nomograph model in the training and validation set were 0.881 and 0.850, respectively, and the AUCs of the clinical control model in the training and validation set were 0.814 and 0.772, respectively, and the differences were statistically significant ( Z=2.57 and 1.96, P=0.005 and 0.030). The average CI of the nomograph model was 0.885. The results of DCA analysis showed that the overall benefit of the nomograph model was higher than that of the clinical control model. Conclusion:The enhanced CT-based nomograph model can effectively distinguish gastric schwannoma from gastric stromal tumor, and can help physicians to make precise clinical decisions.