Objective: To study the cause of rapid thrombocytopenia and organ hemorrhage in congenital heart disease (CHD) patients after interventional occlusion. Methods: A total of 665 CHD patients received interventional occlusion in our hospital from 2011-01 to 2015-12 were enrolled. The patients were divided into 3 groups according to the defects: Atrial septal defect (ASD) group,n=100, Ventricular septal defect (VSD) group,n=100 and Patent ductus arteriosus (PDA) group,n=465. Pre- and post-interventional occlusion platelet levels, the relationship between PDA occluder diameter and platelet counts were compared. Pressure difference between both sides of occluder was randomly measured in a part of patients including 50 in ASD group, 50 in VSD group and 102 in PDA group. Based on occluder diameter, the 102 PDA patients were further divided into 2 subgroups: Giant PDA,n=42 and Medium-small PDA,n=60; pressure differences between both sides of occluder were compared between 2 subgroups. Results: No severe thrombocytopenia and organ hemorrhage occurred in ASD group or VSD group. PDA group had 36/465 (7.74%) patients with severe thrombocytopenia, 18 (3.87%) with organ hemorrhage and all of them occurred in giant PDA subgroup; the diameter of PDA occluder was negatively related to post-operative to platelet counts (r=-0.659,P=0.001). For pressure difference on both sides of occluder, compared with prior operation, PDA group showed increased systolic and diastolic pressure differences and increased mean pressure difference at immediately post operation, allP< 0.05; systolic pressure difference in VSD group was (56.57±15.33) mmHg, in Medium-small PDA subgroup was (58.33±26.65) mmHg and in Giant PDA subgroup was (94.66±27.62) mmHg which was much higher than those in VSD group and Medium-small PDA subgroup, allP<0.01. Conclusion: Rapid thrombocytopenia and organ hemorrhage in CHD after interventional occlusion only happened in giant PDA patients. High pressure difference formed high-speed ifltration blood lfow which may cause scouring damage on platelets and it was the main reason for thrombocytopenia occurrence.

Aim TostudytheeffectsofCuO,ZnOand TiO2 nanoparticles on the viability and metastatic po-tential of EC-9706 and EC-109 esophageal squamous carcinomacelllineinvitro.Methods Characteristics of CuO,ZnO and TiO2 nanoparticles were detected u-sing transmission electron microscope (TEM)and dy-namic light scattering (DLS ).EC-9706 and EC-109 cells were treated with different concentrations of CuO, ZnO and TiO2 (5 ~80 mg · L-1 ).The cell prolifera-tion was analyzed by MTT assay.The cell cycle and apoptotic rates were determined by flow cytometry (FCM).The cell invasion was assayed in Transwell chambers.The expression of Bcl-2 and caspase-3 pro-tein in cells was detected by Western blot method.Re-sults CuO,ZnOandTiO2nanoparticleswerespheri-cal with primary particle size 12,20. 6,12 nm.The particles were agglomerated in water and cell culture medium with negative charge.CuO and ZnO nanoparti-cles induced decreases in EC-9706 and EC-109 cell vi-ability dose-dependently.After exposed to increasing concentrations of CuO and ZnO nanoparticles,the cell cycle analysis revealed a decreasing proportion of cells in G2/Mand S phase,and up-regulation of the cells in G0/G1 phase.Apoptotic cells also increased along with decreased cell invasion upon CuO and ZnO treatment. Nanoparticles treatment after 48 h, the activated caspase-3 expression quantity increased significantly and the Bcl-2 expression quantity decreased obviously (P<0. 05 )compared with control group.TiO2 nanop-articles had no obvious effect on the EC-9706 and EC-109 cell proliferation,cell cycle,apoptosis and inva-sion.Conclusion ComparedwithTiO2,CuOand ZnO nanoparticles can inhibit EC-9706 and EC-109 cell viability and metastatic potential,the mechanism of action involves cell cycle arrest in G0/G1 phase and apoptosis.These findings can help the development of nanoparticles as anti-cancer therapeutics for esophageal cancer.

OBJECTIVETo develop and test a scoring system to predict the risks of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy(PD).

METHODSClinic data and postoperative complications of the 445 consecutive patients who underwent a PD procedure between January 2008 and April 2015 in Peking University First Hospital were retrospectively collected and analyzed.The patients were randomly selected to modelling and validation sets at a ratio of 3∶1, respectively.The patient data were subjected to univariate and multivariate analysis in the modelling set of patients.A score predictive of POPF was designed and tested in the validation set.

RESULTSPOPF occurred in 88 of 334 patients(26.4%) in the modelling set.The multivariate analysis showed that body mass index (BMI, P<0.01) and pancreatic duct width(P=0.001) are associated with POPF independently.A risk score to predict POPF was constructed based on these factors and successfully tested.The area under the receiver operating characteristic curve were 0.829(95% CI: 0.777-0.881) on the modelling set and 0.885(95% CI: 0.825-0.945) on the validation set, respectively.

CONCLUSIONSBMI and pancreatic duct width were associated with POPF after PD. The preoperative assessment of a patient's risk for POPF is feasible.The present risk score is a valid tool to predict POPF in patients undergoing PD, to make the selection on anastomosis types, and to take precautions against POPF.

Anastomosis, Surgical ; Body Mass Index ; Humans ; Intestines ; surgery ; Multivariate Analysis ; Pancreas ; pathology ; surgery ; Pancreatic Ducts ; pathology ; Pancreatic Fistula ; pathology ; Pancreaticoduodenectomy ; adverse effects ; Postoperative Complications ; Postoperative Period ; ROC Curve ; Retrospective Studies ; Risk Factors

Objective: To explore the anatomical characteristics of the mesopancreas, to define the range of the total mesopancreas excision and to evaluate the feasibility, safety and effectiveness in the treatment of pancreatic cancer. Methods: A regional anatomical and pathological study was performed on 14 cadavers with large slices and paraffin sections. The clinical and pathological data of 58 consecutive patients underwent total mesopancreas excision for pancreatic head carcinoma from January 2013 to December 2015 were prospectively collected and analysed. The perioperative morbidity, mortality and clinical outcomes of patients underwent total mesopancreas excision were compared with the patients underwent conventional pancreaticoduodenectomy from January 2010 to December 2012. Results: The mesopancreas located in the retropancreatic area, extending from the head, neck, and uncinated process of pancreas to the aorto-caval groove, in which there were loose areolar tissue, adipose tissue, nerve plexus, lymphatic and capillaries. Although no fibrous sheath or fascia like mesocolorectum was found around the structures, a relatively fixed extent could be defined according to its embryologic and anatomic characters. In clinical practice, total mesopancreas excision was classified into two levels according to the extent of resection in this series: level Ⅰ was a"standard total mesopancreas excision" or"total mesopancreas excision in a narrow sense" , which was similar to the extent of standard resection from consensus statement of ISGPS. Level Ⅱ was defined as any procedure extending the range of level Ⅰ, called the"extended total mesopancreas excision" or"total mesopancreas excision in a broad sense". In TMpE group, the intraoperative blood loss( (461.4±184.5)ml vs. (532.2±319.8)ml, P=0.301), operation time( (368.6±92.5)minutes vs. (397.1±112.7)minutes, P=0.559), total complication rate (39.7% vs. 51.2%, P=0.250), fistula mortality (25.9% vs. 30.2%, P=0.628) were all reduced. There were significantly higher R0 rate (91.4% vs.76.7%, P=0.041) and more harvested lymph nodes (16.2 vs. 11.4, P=0.000) and lower total and local recurrence: rate (half-year local recurrence rate: 7.8% vs. 23.7%, P=0.036; one-year local recurrence rate: 18.2% vs. 39.5%, P=0.018) and longer disease-free survival (16.9 months vs. 13.4 months, P=0.044) and overall survival(22.5 months vs. 19.9 months, P>0.05) were also found in the study group. Conclusions Mesopancreas is different from mesorectum since it has no fascial envelop, which should be regarded as a surgical concept, rather than an anatomical structure. Total mesopancreas excision is safe and feasible for pancreatic head cancer and probably helps to increase the R0 resection rate and improve the clinical outcomes.

With the improvement of surgical techniques and deeper anatomical understanding, the concept of precision surgery has gradually developed. The necessity of traditional extensive organ resection for the treatment of benign and borderline tumors is being challenged due to the high risk of long-term complications. Over the past 40 years, various modified surgical techniques have emerged, with duodenum-preserving pancreatic head resection as a representative procedure. The surgical indications have gradually transitioned from chronic pancreatitis to benign and borderline tumors of the pancreatic head. The extent of resection has evolved from major partial resection and subtotal resection to total resection of the pancreatic head. The surgical approach has also progressed from traditional open surgery to minimally invasive techniques such as laparoscopic or robot-assisted surgery, reflecting updates and optimizations in treatment concepts and surgical methods. This paper discusses the development, surgical indications, and related complications of duodenum-preserving pancreatic head resection. The aim is to provide a reference for the more standardized and rational selection of this surgical procedure in clinical practice while reducing the incidence of complications.

Objective:To establish a LC-MS/MS method for determination of paraquat and diquat in plasma and urine samples.Methods:Plasma is precipitated by acetonitrile then diluent with phosphate buffer (pH=7) , urine is diluent with phosphate buffer (pH=7) , then diluent samples extracted with Oasis WCX solid-phase extraction column. Samples were analyzed using LC-MS/MS in multiple reaction monitoring (MRM) mode. The analytical column was XBridge?BEH-HILIC (100 mm×2.1 mm×2.5 μm) and the mobile phase were 100 mmol ammonium formate add 0.5% formic acid and acetonitrile. Paraquat was quantified by internal standard method and diquat by external standard method.Results:The calibration curves of paraquat and diquat were linear in the concentration range of 10.0~120.0 μg/L, the correlation coefficient (r) were 0.9985~0.9994. The limit of detection of paraquat in plasma and urine were 1.98 μg/L and 1.00 μg/L, respectively, the recovery rate were 100.2%~107.3%, the RSD were 1.6%~3.3%. The limit of detection of diquat in plasma and urine were 1.80 μg/L and 2.77 μg/L, respectively, the recovery rate were 85.3%~93.1%, the RSD were 1.8%~5.5%. Conclusion:This method is sensitive and accurate, and can simultaneously determine paraquat and diquat in plasma and urine.

With the improvement of surgical techniques and deeper anatomical understanding, the concept of precision surgery has gradually developed. The necessity of traditional extensive organ resection for the treatment of benign and borderline tumors is being challenged due to the high risk of long-term complications. Over the past 40 years, various modified surgical techniques have emerged, with duodenum-preserving pancreatic head resection as a representative procedure. The surgical indications have gradually transitioned from chronic pancreatitis to benign and borderline tumors of the pancreatic head. The extent of resection has evolved from major partial resection and subtotal resection to total resection of the pancreatic head. The surgical approach has also progressed from traditional open surgery to minimally invasive techniques such as laparoscopic or robot-assisted surgery, reflecting updates and optimizations in treatment concepts and surgical methods. This paper discusses the development, surgical indications, and related complications of duodenum-preserving pancreatic head resection. The aim is to provide a reference for the more standardized and rational selection of this surgical procedure in clinical practice while reducing the incidence of complications.

Objective:To establish a LC-MS/MS method for determination of paraquat and diquat in plasma and urine samples.Methods:Plasma is precipitated by acetonitrile then diluent with phosphate buffer (pH=7) , urine is diluent with phosphate buffer (pH=7) , then diluent samples extracted with Oasis WCX solid-phase extraction column. Samples were analyzed using LC-MS/MS in multiple reaction monitoring (MRM) mode. The analytical column was XBridge?BEH-HILIC (100 mm×2.1 mm×2.5 μm) and the mobile phase were 100 mmol ammonium formate add 0.5% formic acid and acetonitrile. Paraquat was quantified by internal standard method and diquat by external standard method.Results:The calibration curves of paraquat and diquat were linear in the concentration range of 10.0~120.0 μg/L, the correlation coefficient (r) were 0.9985~0.9994. The limit of detection of paraquat in plasma and urine were 1.98 μg/L and 1.00 μg/L, respectively, the recovery rate were 100.2%~107.3%, the RSD were 1.6%~3.3%. The limit of detection of diquat in plasma and urine were 1.80 μg/L and 2.77 μg/L, respectively, the recovery rate were 85.3%~93.1%, the RSD were 1.8%~5.5%. Conclusion:This method is sensitive and accurate, and can simultaneously determine paraquat and diquat in plasma and urine.

Objective To investigate the influence mechanism of Cordyceps sinensis (CS) on β-glycerophosphate-induced vascular smooth muscle cell (VSMC) calcification.Methods The effect of CS on VSMC cell viability was detected by CCK-8.The cellular models of rat VSMC calcification were established by treating with β-glycerophosphate (β-GP,10 mmol/L);then CS (10 mg/L),autophagy inhibitor 3-methyladenine (3-MA,5 mmol/L),and AMPK inhibitor compound C (CC,10 μmol/L) were added to the cell cultures.There were a total of 5 experiment groups:VSMC cultured in normal medium (Control),VSMC treated with β-GP,VSMC treated with β-GP and CS,VSMC treated with 3-MA,β-GP and CS,and VSMC treated with CC,β-GP and CS.The calcium nodules and calcium content were examined with alizarin red S staining and the O-cresolphthaleincomplexone method,respectively.The autophagosomes within the VSMC were observed using transmission electron microscope (TEM).Immunofluorescence showed the accumulation of microtubule-associated protein 1 light chain 3 (LC3) puncta.In addition,levels of osteogenic related proteins,autophagy related proteins,and AMPK/mTOR pathway related proteins were evaluated by Western blotting.Results CS increased the number of autophagosomes and the accumulation of LC3 puncta within VSMC.It also upregulated the protein levels of LC3 Ⅱ/LC3 Ⅰ,beclin1,α-SMA,and p-AMPK;whereas,the protein levels of Runx2 and p-mTOR,as well as calcium nodules and calcium content were reduced (all P ＜ 0.01).When the cells were pretreated with 3-MA before treating with β-GP and CS,the autophagosomes,accumulation of LC3 puncta,and protein levels of LC3 Ⅱ/LC3 Ⅰ,beclinl,and α-SMA were decreased (all P ＜ 0.01);however,the protein level of Runx2,and the calcium nodules and calcium content were increased (all P ＜ 0.01).Nevertheless,when the cells were pretreated with CC before giving β-GP and CS,the autophagosomes,the accumulation of LC3 puncta,and the expression levels of p-AMPK,LC3 Ⅱ/LC3 Ⅰ,beclin1,and α-SMA were significantly down-regulated (all P ＜ 0.01);whereas,the expression levels of Runx2 and p-mTOR,as well as calcium nodules and calcium content were increased (all P ＜ 0.01).Conclusions CS can effectively alleviate β-GP-induced VSMC calcification,which may be due to the activation of autophagy by AMPK/mTOR signaling pathway.

Objective:To investigate the application value of nectin-4 targeting radiotracer 68Ga-N188 in the diagnosis of pancreatic cancer. Methods:The prospective study was conducted. The clinicopathologic data of 16 patients diagnosed as pancreatic cancer on enhanced computed tomography (CT) who were admitted to the Peking University First Hospital from August to December 2022 were collected. There were 9 males and 7 females, aged (62±8)years. All patients underwent 18F-flurodeoxyglucose ( 18F-FDG) and 68Ga-N188 positron emission tomography (PET)/CT examination. Observation indicators: (1) distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients; (2) expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer; (3) comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Count data were described as absolute numbers or percentages. Results:(1) Distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients. Results of PET/CT examination showed that in 1 hour after injection, the maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean) of 68Ga-N188 in fat, muscle, skin, and brain tissues of 16 patients were 0.40±0.16 and 0.25±0.09, 0.68±0.20 and 0.44±0.12, 0.39±0.14 and 0.28±0.11, 0.09±0.04 and 0.05±0.02, respectively. In the tissues of the esophagus, liver, spleen, and pancreas, the above indicators were 1.53±0.48 and 1.16±0.31, 1.49±0.45 and 0.91±0.30, 1.40±0.30 and 1.02±0.24, 1.24±0.31 and 0.96±0.25, respectively. In tumor primary lesion, the above indicators were 3.28±1.02 and 2.14±0.62, respectively, showing significant differences in SUVmax and SUVmean compared with pancreatic tissue ( t=8.03, 6.75, P<0.05). The tumor background ratio in tumor primary lesion based on SUVmax was 1.82±0.58. (2) Expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer. Results of immunohistochemical staining in 16 patients showed that there were 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression. Results of PET/CT examination showed that the SUVmax of 68Ga-N188 in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 3.77±1.10 and 2.64±0.68, showing a significant difference between them ( t=2.64, P<0.05). The SUVmax of 18F-FDG in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 6.73±3.24 and 6.43±3.45, showing no significant difference between them ( t=0.17, P>0.05). (3) Comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Of the 16 patients, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 14 and 11, respectively, for the 14 pancreatic cancer patients diagnosed by postoperative histopathology. Among them, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 3 and 1 for the 3 pancreatic cancer patients receiving evaluation for chemotherapy. The SUVmax of 18F-FDG in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 2.80±0.69 and 6.97±2.11, showing a significant difference between them ( t=3.29, P<0.05). The SUVmax of 68Ga-N188 in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 3.38±1.12 and 2.93±0.50, showing no significant difference between them ( t=0.66, P>0.05). Cases with positive results of lymph node metastases in 68Ga-N188 and 18F-FDG PET/CT were 6 and 4, respectively, for the 6 pancreatic cancer patients diagnosed with lymph node metastases by postoperative histopathology, and the SUVmax of 68Ga-N188 and 18F-FDG in lymph node metastases were 2.25±1.12 and 4.02±1.27. Conclusion:68Ga-N188 PET/CT can be used for imaging diagnosis of tumor primary lesion and lymph node metastases of pancreatic cancer.