Objective To explore the preparation and quality control of As2 O3 nanoparticle .Methods PEG‐PLA was used as the vector material to prepare As2 O3 nanoparticle with ultrasonic emulsification method ,and the VEGFR‐2 was coupled to obtain VEGFR‐2/As2 O3‐PEG‐PLA nanoparticle .The particle size distribution ,Zata potential ,loading efficiency (LE) ,encapsulation effi‐ciency(EE) ,drug release in vitro and stability was determined ,and morphological characteristics was observed by transmission elec‐tron microscope(TEM) .Tweety‐four hepatocellular carcinoma nude mices were randomly divided into VEGFR‐2/As2O3‐PEG‐PLA nanoparticles group and As2 O3‐PEG‐PLA nanoparticles group ,by tail vein injection of nanoparticles .High performance liquid chro‐matography was used to determine content of As2 O3 .After 21 d ,six nude mices in each group were killed ,and the immunohisto‐chemistry and western blot method was used to detect the expression of VEGFR‐2 .Results The particle size of VEGFR‐2/As2 O3‐PEG‐PLA was determined to be (141 .9 ± 13 .2)nm ,Zata potential was (10 .2 ± 1 .1)mV .It was found to spherical or oval shape , with uniform size and dispersibility under TEM .LE and EE was (5 .51 ± 1 .83)% and (62 .12 ± 5 .98)% ,respectively .Drug release in vitro showed that VEGFR‐2/As2 O3‐PEG‐PLA exhibited controlled release effect ,with half of the release time as 10 h .Besides , VEGFR‐2/As2 O3‐PEG‐PLA showed a good stability in 3 days .Compared with As2 O3‐PEG‐PLA nanoparticles group ,the concen‐tration of As2 O3 in tumor and liver tissue was high ,the concentration of As2 O3 in blood ,heart ,kidney tissue was low ,the expression of VEGFR‐2 in tumor tissue was low in VEGFR‐2/As2O3‐PEG‐PLA nanoparticles group(P< 0 .05) .Conclusion The prepared As2 O3 nanoparticle using PEG‐PLA as vector and VEGFR‐2 as target showed uniform size ,high EE and LE ,good stability .And it preliminarily proved that VEGFR‐2 could be targeted in nude mice .

Objective To prepare the immunoconjugate composed of Adriamycin nanoparticles and VEGFR 2 monoclonal antibody(conjugate of ADM-NP and VEGFR 2-MAb) and study its pharmacokinetics property. Methods Adriamycin nanoparticles were prepared by using double emulsion method, with PLA and O-CMC as materials. Conjugate of ADM-NP and VEGFR 2-MAb was prepared by using molecule conjugate technology. Immunoreactivity of the conjugate with type IV collagenase and H 22 cell were analyzed by using ELISA. Pharmacokinetics parameters of the immunoconjugate were obtained by using SD rats as study objects. Results The prepared ADM-NP was sphere particles under SEM, which diameters were (160±34) nm. The drug loading rate and entrapment rate were (30.15±3.5)% and (80.56±4.24)% respectively. Conjugate of ADM-NP and VEGFR 2-MAb was successfully prepared, which had immunoreactivity with type IV collagenase and H 22 cell. The immunoconjugate showed good ADM control-release ability and could prolong the retention time of ADM in vivo. Conclusion Conjugate of ADM-NP and VEGFR 2-MAb keeps the immunoreactivity of VEGFR 2-MAb and shows good ADM control-release ability.

Pancreatic cancer is an aggressive malignant tumor with poor prognosis. On the one hand, it has a narrow therapeutic window due to the lack of specific markers and obvious clinical symptoms. Once diagnosed, it has often developed to an advanced stage. On the other hand, located in a vital region of the body, pancreatic operation is difficult and the postoperative recurrence rate is high. Therefore, surgical treatment is only sui-table for a small number of early patients. Pancreatic cancer has a tumor microenvironment with the characteristic of dense stroma, hypoxia, paucity of blood vessels and highly immunosuppression. It is often insensitive to traditional radiation and chemotherapy. Therefore, strategies targeting on tumor microenvironment have a potential prospect. This article reviews the research progress in tumor microenvironment of pancreatic cancer, in order to provide the references in the further research and treatment of pancreatic cancer.

Objective:To explore the analgesic methods in ambulatory laparoscopic cholecystectomy (LC) patients.Methods:Three hundred patients were randomly divided into six groups receiving different analgesic regimen. VAS scores, postoperative blood pressure, CRP, IL-6, and the occurrence of postoperative adverse effects were recorded at 2, 4, 8, and 12 h postoperatively.Results:The success rate of ambulatory LC in this study was 66.22%. The dynamic VAS scores of patients in each group gradually decreased with time elapsing, with groups B and C being significantly lower than group A at 2 h and 4 h postoperatively ( P<0.05). Groups D, E and F were significantly different from group A at all postoperative time points ( P<0.05). There was a statistically significant difference at 8 h and 12 h postoperatively in group B vs. group D and group C vs. group E (all P<0.05). There was significant difference at the 12 h postoperatively between groups (B and C) compared to group F ( P<0.05). There was a significant difference in CRP and IL-6 between the groups (all P<0.05). Postoperative dizziness, nausea and delayed discharge were significantly higher in patients using analgesic pumps ( P<0.05). Conclusion:Local infiltration of ropivacaine combined with postoperative parecoxib sodium drip is a recommended analgesic regimen.

Purpose: This study was performed to analyze the rule of confluence of the caudate lobe bile duct (CLD) into the left hepatic duct (LHD) and to discuss the protective strategy during left hemihepatectomy. Methods: MRI of 400 patients and T-tube angiography images of 100 patients were collected, and the imaging rules of the confluence of the CLD into the LHD were summarized. The clinical data of 33 patients who underwent left hemihepatectomy using the protective strategy were analyzed. Results: MRI and T-tube angiography images showed that the length from the confluence point of the CLD into the LHD to the confluence of the left and right hepatic ducts was 1.19 ± 0.40 cm and 1.26 ± 0.39 cm, respectively. The average angle between the longitudinal axis of the 2 bile ducts was 68.27° ± 22.59° and 66.58 ± 22.88°, respectively. Coronal and cross-sectional images showed that inflow from the foot side to the cranial side was noted in 79.8% and 82.0% of patients, respectively, and inflow from the dorsal to the ventral side was observed in 84.5% and 88.0%, respectively. Based on these imaging rules, the safe transection length and plane were summarized, and the CLD was effectively protected in 33 cases of left hemihepatectomy. Conclusion In left hemihepatectomy, the LHD should be transected at least 1.5 cm away from the confluence of the left and right hepatic ducts, and the plane of transection should be oblique to the dorsal side at an angle of 45° with the LHD, these parameters represent an effective strategy to protect the CLD.

Objective To investigate the clinical efficacy of laparoscopic spleen-preserving distal pancreatectomy (Kimura method and Warshaw method) for benign lesions of pancreatic body and tail.Methods The retrospective cohort study was conducted.The clinicopathological data of 39 patients with benign lesions of pancreatic body and tail who underwent laparoscopic spleen-preserving distal pancreatectomy in the Second Affiliated Hospital of Nanchang University between March 2008 and January 2018 were collected.Of 39 patients,28 undergoing Kimura method (splenic artery and vein-preserving distal pancreatectomy) were allocated into the Kimura group,and 11 undergoing Warshaw method (cutting splenic vessels and preserving short gastric vessels)due to serious adhesion between pancreatic body and tail and splenic hilum were allocated into the Warshaw group.Observation indicators:(1) operation situations;(2) postoperative situations;(3) follow-up situations.Followup using outpatient examination and telephone interview was performed to detect blood glucose level and tumor recurrence of patients up to March 2018.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were described as M (range) and comparison between groups was done using nonparametric rank-sum test.Comparisons of count data were analyzed using chi-square test or Fisher exact probability.Results (1) Operation situations:39 patients received laparoscopic spleen-preserving distal pancreatectomy,operation time and volume of intraoperative blood loss of 39 patients were respectively (194 ±58)minutes and 100 mL (range,30-800 mL).The operation time and volume of intraoperative blood loss were respectively (197±56)minutes,100 mL (range,30-800 mL) in the Kimura group and (186±63)minutes,150 mL (range,30-450 mL) in the Warshaw group,with no statistically significant difference between groups (t =0.494,Z =-0.597,P＞ 0.05).(2) Postoperative situations:time to anal exsufflation and duration of hospital stay were respectively (2.6±0.8)days,(9.2±7.3)days in 39 patients and (2.4±0.6)days,(7.5±4.2)days in the Kimura group and (2.8±1.3)days,(13.5±11.1)days in the Warshaw group,with no statistically significant difference between groups (t=-0.720,-1.736,P＞0.05).Seven patients had postoperative complications.The incidence of complication was 2/28 in the Kimura group,1 patient with pancreatic leakage at 5 days postoperatively was cured by 15-day B ultrasound guided catheter drainage,and 1 who was diagnosed as pulmonary infection by chest CT examination at 5 days postoperatively was discharged from hospital after 8-day anti-infection and sputum-inductive treatments.The incidence of complication was 5/11 in the Warshaw group,3 patients with sustained fever at 5 and 7 days postoperatively who were diagnosed as grade 1 splenic infarction by epigastric enhanced CT examination were improved and discharged from hospital by antibiotic and low molecular weight heparin treatments,and then epigastric enhanced CT re-examination at 3 months postoperatively showed recovery of splenic perfusion;1 with pancreatic leakage at 7 days postoperatively was cured by 18-day conservative treatment;1 who was diagnosed as delayed gastric emptying by upper gastrointestinal contrast at 16 days postoperatively was improved and then discharged from hospital by 15-day placement of intestinal feeding tube and nutrition support therapy.There were statistically significant differences in the incidences of overall complication and splenic infarction between groups (x2 =5.485,4.878,P＜0.05) and no statistically significant difference in the incidence of other complications between groups (P＞0.05).(3) Follow-up situations:39 patients were followed up for 12 months (range,2-64 months).During the follow-up,six patients had normal blood glucose level,and all patients had good quality of life,without recurrence.Conclusions Laparoscopic spleen-preserving distal pancreatectomy for the benign lesions of pancreatic body and tail is satisfactory in short-and long-term curative effects.The incidences of complication and splenic infarction of Kimura method are lower than that of Warshaw method.

Objective: Currently, parathyroid hormone (PTH) is mainly measured by the second generation intact PTH (iPTH) assay which detects both full-length (1-84)PTH and (7-84)PTH fragments. The third generation whole PTH (wPTH) assay however has turned out to be specific for (1-84) PTH. The aim of this study is to investigate the features of plasma iPTH, (1-84)PTH, (7-84)PTH levels in patients with stage 5 chronic kidney disease (CKD), and evaluate the effects of parathyroidectomy (PTX) on above markers in severe secondary hyperparathyroidism (SHPT) patients. Methods: A cross-sectional study including 90 controls and 233 stage 5 CKD patients, and a prospective follow-up study in 31 severe SHPT patients were conducted. Plasma iPTH and (1-84)PTH levels were measured by the second and third generation assay, respectively. Circulating (7-84)PTH level was calculated by subtracting the (1-84)PTH value from the iPTH value. Results: Plasma levels of iPTH, (1-84)PTH, (7-84)PTH were higher (P<0.01), and (1-84)PTH/iPTH was lower (P<0.01) in stage 5 CKD patients than in controls. For severe SHPT patients with PTX (n=74), plasma iPTH, (1-84)PTH and (7-84)PTH concentrations were significantly increased compared to non-PTX group (n=159) (P<0.01), and the increase of (7-84)PTH level was more striking than (1-84)PTH. Meanwhile, the value of (1-84)PTH/iPTH was decreased (P<0.01). Plasma iPTH level was strongly correlated with (1-84)PTH level (r=0.980, P<0.01) in stage 5 CKD patients. Also, both iPTH and (1-84)PTH levels were positively correlated with serum alkaline phosphatase, dialysis vintage and serum phosphorus (P<0.01). After PTX (median interval of follow-up: 7.1 months), plasma iPTH, (1-84)PTH, (7-84)PTH concentrations were decreased (by 92.9%, 89.7%, 95.8%, P<0.01, respectively) greatly and (1-84)PTH/iPTH was increased (P<0.01). Conclusions In stage 5 CKD patients, plasma iPTH, (1-84)PTH, (7-84)PTH levels are greatly increased while (1-84)PTH/iPTH is decreased, and PTX can significantly improve abnormality of above markers in severe SHPT patients. The second generation PTH assay overestimates the severity of SHPT, and the accurate measurement of (1-84)PTH by the third assays is more conducive to diagnosis and treatment of CKD and SHPT patients.

Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8IFN- T cells and the upregulation of cytotoxic T-cell related genes including , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.