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BACKGROUND Focal nodal hyperplasia (FNH) is a common benign tumor of the liver. It occurs mostly in people aged 40-50 years and 90% of the patients are female. FNH can be cured by local resection. How to locate and judge the tumor boundary in real time is often a challenge for surgeons. AIM To summarize the technique and feasibility of robotic resection of FNH guided by indocyanine green (ICG) fluorescence imaging. METHODS The demographics and perioperative outcomes of a consecutive series of patients who underwent robotic resection of liver FNH guided by ICG fluorescence imaging between May 1, 2018 and September 30, 2019 were retrospectively analyzed. ICG was injected through the median elbow vein in all the patients at a dose of 0.25 mg/kg 48 h before the operation. During the operation, the position of FNH in the liver was located in the fluorescence mode of the Da Vinci Si robot operating system and the tumor boundary was determined during the resection. RESULTS Among the 23 patients, there were 11 males and 12 females, with a mean age of 30.5 ± 9.3 years. Twenty-two cases completed robotic resection, while one (4.3%) case converted to open surgery. In the robotic surgery group, the operation time was 35-340 min with a median of 120 min, the intraoperative bleeding was 10-800 mL with a median of 50 mL, and the postoperative hospital stay was 1-7 d with a median of 4 d. Biliary fistula occurred in two (8.7%) patients after robotic operation and they both recovered after conservative treatment. One (4.3%) patient received blood transfusion and there was no death in this study. The postoperative hospital stay in the small tumor group was significantly shorter than that in the large tumor group (P < 0.05). CONCLUSION ICG fluorescence imaging can guide the surgeon to perform robotic resection of liver FNH by locating the tumor and displaying the tumor boundary in real time. It is a safe and feasible method to ensure the complete resection of the tumor.

Sleeve gastrectomy (SG) has been proven effective in the treatment of obesity and type 2 diabetes. We hypothesized that SGLT3 may play an important role in the mechanism of glucose control and weight loss after SG.Daily body weight and food intake were measured in SG and sham-operated mice. Glucose tolerance test, SGLT3 agonist (αMG), and SGLT1 inhibitor (phlorizin) perfusion experiments were used to detect changes in intestinal SGLT3 and SGLT1 activity following SG. Expression of SGLT3a and SGLT1 was assessed at 2 weeks, 1 month after surgery by quantitative PCR and fluorescence immunoassay. Hematoxylin and eosin staining was used to detect morphological changes in the villi. SGLT3 and SGLT1 expression was measured after stimulation of human intestinal epithelial cells (HIEC).Both the body weight and daily food intake of the SG-treated mice decreased within 30 days after surgery. Oral glucose absorption was significantly reduced at 30 days. The intestinal stimulation proved that SG can improve glucose metabolism, which can be reversed by αMG and enhanced by phlorizin. Villus height and surface area of the intestine in SG mice decreased after surgery. mRNA expression of SGLT3a and SGLT1 decreased at 2 weeks and 1 month after SG, immunofluorescence also confirmed these changes. HIEC stimulation confirmed that αMG could increase the expression of SGLT3 and SGLT1, but the expression of SGLT1 was down regulated when phlorizin was added to the medium.The results suggest that reducing SGLT3 expression might contribute to lowering blood glucose and controlling body weight after SG.

Background Surgical views with high resolution and magnification have enabled us to recognize the precise anatomical structures that can be used as landmarks during minimally invasive distal pancreatectomy (MIDP). This study aimed to validate the usefulness of anatomy-based approaches for MIDP before and during the Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (February 24, 2021). Methods Twenty-five international MIDP experts developed clinical questions regarding surgical anatomy and approaches for MIDP. Studies identified via a comprehensive literature search were classified using Scottish Intercollegiate Guidelines Network (SIGN) methodology. Online Delphi voting was conducted after experts had drafted the recommendations, with the goal of obtaining >75% consensus. Experts discussed the revised recommendations in front of the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting. Results Four clinical questions were addressed, resulting in 10 recommendations. All recommendations reached at least a 75% consensus among experts. Conclusions The expert consensus on precision anatomy for MIDP has been presented as a set of recommendations based on available evidence and expert opinions. These recommendations should guide experts and trainees in performing safe MIDP and foster its appropriate dissemination worldwide.

BACKGROUND The impact of resection margin status on long-term survival after pancreaticoduodenectomy (PD) for patients with pancreatic head carcinoma remains controversial and depends on the method used in the histopathological study of the resected specimens. This study aimed to examine the impact of resection margin status on the long-term overall survival of patients with pancreatic head carcinoma after PD using the tumor node metastasis standard. METHODS Consecutive patients with pancreatic head carcinoma who underwent PD at the Chinese People's Liberation Army General Hospital between May 2010 and May 2016 were included. The impact of resection margin status on long-term survival was retrospectively analyzed. RESULTS Among the 124 patients, R0 resection was achieved in 85 patients (68.5%), R1 resection in 38 patients (30.7%) and R2 resection in 1 patient (0.8%). The 1- and 3-year overall survival (OS) rates were significantly higher for the patients who underwent R0 resection than the rates for those who underwent R1 resection (1-year OS rates: 69.4% vs 53.0%; 3-year OS rates: 26.9% vs 11.7%). Multivariate analysis showed that resection margin status and venous invasion were significant risk factors for OS. CONCLUSION Resection margin was an independent risk factor for OS for patients with pancreatic head carcinoma after PD. R0 resection was associated with significantly better OS after surgery.

Robotic surgery has been increasingly applied in pancreatic surgery and showed many advantages over conventional open surgery. The robotic pancreaticoduodenectomy (RPD) is a surgical option for primary nonampullary duodenal adenocarcinoma (PNDA). However, whether RPD is superior to open pancreaticoduodenectomy (OPD) for PNDA has not been reported. The comparative study was designed to analyze the short- and long-term outcomes of RPD versus OPD on patients with PNDA.Demographics, perioperative, and survival outcomes among patients who underwent RPD (n = 49) versus OPD (n = 43) for PNDAs between January 2013 and March 2018 were collected and analyzed RESULTS: Demographic characteristics were comparable between the RPD group and the OPD group. The RPD group demonstrated a decreased estimated blood loss (100 vs. 200 ml, p 0.001), time to oral intake (4.0 vs. 4.0 days, p = 0.04), and postoperative hospital stay (12.9 vs. 15.0 days, p = 0.01) compared with the OPD group. However, no differences were observed between the two groups in terms of operative time and the rates of major complications, grade B and C POPF, PPH, grade B and C DGE, biliary fistular, reoperation, and 90-day readmission. No patient died within 90 days. There were no significant differences in tumor size, differentiation, TNM stage, number of harvested lymph nodes, and the rates of nerve invasion, lymph node invasion, R0 resection, and the median overall survival between the two groups (p 0.05) CONCLUSIONS: RPD is a safe, feasible, and effective treatment for PNDA compared with OPD and can be used as an alternative for surgeons in the treatment of PNDA. Further multicenter randomized controlled trials are needed to evaluate the effectiveness of RPD in patients with PNDA.

Background Suturing the proximal pancreatic stump and performing pancreaticoenterostomy for the distal pancreatic stump following central pancreatectomy is a conventional procedure. This reconstruction after resection of the pathological pancreatic lesion brings changes in anatomy and physiology. In this study, an innovative one-stage robotic end-to-end pancreatic anastomosis was reported to replace the conventional pancreaticoenterostomy following central pancreatectomy. Materials and methods The clinical data of 11 consecutive patients who underwent robotic central pancreatectomy with end-to-end pancreatic anastomosis between August 2017 and December 2017 were analyzed retrospectively. Results All operations were completed successfully without any conversion to open surgery. Nine patients had benign tumors, one had a mass-forming chronic pancreatitis, and one had an isolated pancreatic metastasis from a renal cancer. The mean gap left after central pancreatectomy was 4.3 ± 1.0 cm. The median operative time was 121 (range, 105 to 199) min. The median blood loss was 50 (range, 20 to 100) ml. Seven (63.6%) patients developed complications which included Clavien–Dindo Grade I complications in five patients, a Grade II complication in one patient, and a Grade IIIa complication in one patient. Seven patients developed a Grade B postoperative pancreatic fistula, and two patients a biochemical leak. There was no Grade C or worse pancreatic fistula. Magnetic resonance cholangiopancreatography at postoperative 6 months showed no stricture in any of the main pancreatic ducts. Three patients had an asymptomatic and small pancreatic pseudocyst. Conclusion Robotic central pancreatectomy with end-to-end pancreatic anastomosis was safe and feasible. It restores the normal anatomy of the pancreas. With its good short-and long-term outcomes, it could be an alternative reconstructive method to pancreaticoenterostomy following central pancreatectomy.

Background The anatomical structure around the pancreatic head is very complex, and it is important to understand its precise anatomy and corresponding anatomical approach to safely perform minimally invasive pancreatoduodenectomy (MIPD). This consensus statement aimed to develop recommendations for elucidating the anatomy and surgical approaches to MIPD. Methods Studies identified via a comprehensive literature search were classified using the Scottish Intercollegiate Guidelines Network method. Delphi voting was conducted after experts had drafted recommendations, with a goal of obtaining >75% consensus. Experts discussed the revised recommendations with the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting. Results Three clinical questions were addressed, providing six recommendations. All recommendations reached at least a consensus of 75%. Preoperatively evaluating the presence of anatomical variations and superior mesenteric artery (SMA) and superior mesenteric vein (SMV) branching patterns was recommended. Moreover, it was recommended to fully understand the anatomical approach to SMA and intraoperatively confirm the SMA course based on each anatomical landmark before initiating dissection. Conclusions MIPD experts suggest to surgical trainees to perform resection based on precise anatomical landmarks for safe and reliable MIPD.

BACKGROUND Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a mucin-producing tumor that develops from the epithelial lining of the main pancreatic duct or branch pancreatic ducts. Here, we assessed the feasibility and safety of various robotic pancreatectomy approaches to treating IPMN, and short- and long-term outcomes of robotic IPMN resection. METHODS Data from patients who underwent robotic pancreatectomy for IPMN between 2012 and 2019 at our hospital were retrospectively analyzed. The survival outcomes for patients were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS Of the 174 patients who underwent robotic pancreatectomy, 120 and 54 patients had benign or malignant tumors, respectively. Patients with malignant IPMN had lost more weight in the 6 months prior to surgery (P = .008), and a higher serum level of CA19-9 (P

Robotic central pancreatectomy has been applied for 20 years with the advantage of minimally invasive surgery. The general pancreatic reconstruction approaches include pancreaticojejunostomy and pancreaticogastrostomy. Recently, our group reported a few preliminary cases of application of end-to-end pancreatic anastomosis in robotic central pancreatectomy. This novel approach has not been compared with the conventional approach on a large scale. The objective of this study is to compare end-to-end pancreatic anastomosis with pancreaticojejunostomy after robotic central pancreatectomy based on the perioperative and long-term outcomes. Clinical data consist of demographics, clinicopathologic characteristics, perioperative and long-term outcomes of patients who underwent robotic central pancreatectomy from March 2015 to December 2019 were collected and analyzed. Seventy-four patients received a robotic central pancreatectomy with either end-to-end pancreatic anastomosis (n = 52) or pancreaticojejunostomy (n = 22). End-to-end pancreatic anastomosis was associated with shorter operative time and reduced blood loss. Despite a higher incidence of clinically relevant postoperative pancreatic fistula (69.2% vs. 36.4%, p = 0.009), the newer anastomotic technique was also associated with earlier removal of nasogastric tube and resumption of oral intake. Long-term results, in terms of either endocrine or exocrine function, were not affected by the anastomotic technique. We have shown the feasibility of robotic central pancreatectomy with end-to-end pancreatic anastomosis. Despite streamlined technique, the newer anastomosis appears to improve early post-operative results while preserving endocrine and exocrine functions in the long-term period. Evaluation of the true potential of robotic central pancreatectomy with end-to-end pancreatic anastomosis requires a prospective and randomized study enrolling a large number of patients.

Background: Indoleamine 2,3-dioxygenase (IDO), an enzyme for tryptophan metabolism through the kynurenine pathway, exhibits an immunosuppressive effect and induces immune tolerance in tumor cells. The effects of IDO on pancreatic cancer are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO in pancreatic cancer. Methods: We evaluated the protein expression of IDO in PANC-1, CFPAC-1, and BxPC-3 cell lines with or without 48 h treatment by 500 U/ml interferon-γ (IFN-γ). We performed immunohistochemical staining and Western blot analysis for IDO expression in both pancreatic cancer and normal pancreas tissues obtained from Chinese PLA General Hospital from July 2012 to December 2013. Survival analysis was performed to correlate IDO expression and histopathologic parameters with overall survival. The Kaplan-Meier method and Cox proportional hazards regression model were conducted. Results: PANC-1, CFPAC-1, and BxPC-3 cell lines expressed IDO at the protein level, and the relative expression amount increased after stimulation with 500 U/ml IFN-γ. Immunohistochemical analysis results revealed that high IDO expression was observed in 59% of pancreatic adenocarcinoma tissues. Compared with normal pancreatic tissues, pancreatic adenocarcinoma showed significantly higher IDO expression levels, especially among patients with high tumor node metastasis (TNM) stages (χ2= 4.550, P = 0.030), poor histological differentiation (χ2 = 5.690, P = 0.017), and lymph node metastasis (χ2 = 4.340 P = 0.037). Kaplan-Meier survival curves showed that high IDO expression was correlated with low survival rates (hazard ratio [HR] = 0.49 P = 0.009). Multivariate analysis using Cox proportional hazards model indicated that lymph node metastasis (HR = 0.35 P = 0.010) and IDO expression (HR = 0.42 P = 0.020) were two independent prognostic predictors of pancreatic adenocarcinoma. Conclusions: The study confirmed that high IDO expression in pancreatic adenocarcinoma was related to poor prognosis of patients. These findings provided evidence that IDO was involved in pancreatic adenocarcinoma progression and might serve as a relevant therapeutic target. Key words: Immunohistochemistry; Indoleamine 2,3-dioxygenase; Pancreatic Neoplasms; Prognosis

BACKGROUND With the advancement of robotic pancreaticoduodenectomy (RPD), several reconstruction methods have been advocated to make RPD more effective and safer. In this study, we investigated the safety and effectiveness of RPD using a left retrocolic (L-port) technique and compared it with those of RPD using an antecolic technique. METHODS Between October 2015 and August 2016, we retrospectively reviewed consecutive cases of RPD before and after introducing the L-port technique for gastrointestinal reconstruction. The L-port technique was mainly performed for retrocolic gastrojejunal reconstruction and some cases of duodenojejunal reconstruction. The perioperative and postoperative outcomes were compared in the two groups. RESULTS Eighty-three cases of RPD were retrieved for statistical analysis. Compared with the antecolic group, the L-port group was significantly associated with a shorter operative time (median time [IQR] 345 [307-384] min vs. 390 [370-455] min, P

Background Robotic surgery is increasingly being used in hepatectomy. Previous studies comparing the robotic and laparoscopic minor hepatectomy have been documented, but comparative studies on robotic and laparoscopic hemihepatectomy (LH) involving a large patient cohort are rare. The objective of this study was to compare perioperative outcomes between robotic and LH. Methods Data on the demographics, clinicopathologic characteristics, and perioperative outcomes of consecutive patients who underwent robotic or LH in a single center between November 2011 and July 2017 were analyzed. Results A total of 92 patients underwent robotic and 48 LH. Multiple linear regression analysis showed no significant difference in perioperative outcomes including operative time, postoperative hospital stay, postoperative complications, and mortality between the groups. Compared to the laparoscopic cohort, the robotic cohort had a significantly less estimated blood loss (120.24 mL; 95% confidence interval, 53.72-186.76) and a significantly lower conversation rate (1.09% vs 10.42%; P = .034). Stratified and interaction analyses demonstrated that disease type had an interaction effect on the association between the operative approach and the estimated blood loss. Conclusions Robotic hemihepatectomy was safe and feasible in selected patients. It had similar perioperative outcomes as LH and was better than LH regarding estimated blood loss and open conversion.

Backgrounds Retroperitoneoscopic surgery has shown advantages in urological surgery. However, its application in pancreatic surgery for neoplasm is rare. Robotic surgical system with its magnified view and flexible instruments may provide a superior alternative to conventional laparoscopic system in retroperitoneoscopic surgery. We aimed to evaluate the safety, feasibility, and short-term outcomes in a series of patients treated by robotic retroperitoneoscopic pancreatic surgery. Case presentation Between March 2016 and May 2016, four patients with solitary pancreatic neuroendocrine neoplasms were treated with robotic retroperitoneoscopic surgery. Prospective collected clinical data were retrospectively analyzed. Three patients underwent distal pancreatectomy (one combined with resection of left adrenal adenoma), and one patient enucleation. The mean operative time was 80 min (range 30–110 min). The estimated blood loss was insignificant. There was no conversion to open procedure. The mean postoperative hospital stay was 5.25 days (range 4–6 days). The mean tumor size was 1.375 cm (range 1.0–1.8 cm) in diameter. All patients’ blood glucose level returned to normal range within 1 week postoperatively. Two patients had pancreatic biochemical leak. No patients underwent subsequent treatment, and no recurrence occurred during the 12-month follow-up period. Conclusions This study preliminarily indicates that robotic retroperitoneoscopic pancreatic surgery is safe and feasible for neoplasms in the dorsal portion of distal pancreas in selected patients, with some potential advantages of straightforward access, simple and fine manipulation, short operative time, and fast recovery.

Central pancreatectomy is carried out for the treatment of benign or low-malignant potential tumors located in the pancreatic neck or proximal part of pancreatic body. With technological development, the robotic surgical system has shown its advantage in minimally invasive surgery and been increasingly applied in central pancreatectomy. However, reconstruction of the continuity of pancreas with end-to-end anastomosis after robotic central pancreatectomy has not been applied. In this study, we report surgical techniques for robotic central pancreatectomy with end-to-end anastomosis. The pancreas is reconstructed by duct-to-duct anastomosis of the pancreatic duct with a pancreatic stent inserted in the two stumps of pancreatic duct, and by end-to-end anastomosis of the pancreatic parenchyma. Compared with traditional central pancreatectomy with pancreaticoenteric anastomosis, this approach decreases the operative injury to the patient, and also conserves the integrity and continuity of the digestive duct and pancreatic duct. The robotic surgical system integrated with multiple instruments with flexible and precise movement is particularly suitable for the dissection and reconstruction of the pancreatic duct. We found that robotic central pancreatectomy with end-to-end anastomosis is safe and feasible, and we need more experience to evaluate its best indications and long-term outcomes.

This study aims to develop a new agent, the 32P-chromic phosphate–poly(l-lactide) (32P-CP-PLLA) seed and to explore its anticancer effect against prostate cancer (Pca) with local lymphatic metastasis in nude mice. 32P-CP-PLLA seeds of sustained release and nude mouse models of Pca with lymphatic metastasis were prepared. After 4 weeks, the tumor nude mouse models were randomly assigned into five groups. 32P-CP-PLLA seeds (3.7, 7.4, 14.8, and 0 MBq) and 32P-CP (14.8 MBq) were implanted in the tumor tissues of the nude mouse models. The following were discussed in this study: (1) the distributions of 32P-CP-PLLA, (2) the pathological and morphological changes in the tumor and regional lymph nodes, and (3) the changes in white blood cell (WBC) and platelet counts in peripheral blood for toxic reactions. The homemade 32P-CP-PLLA seed was a regular green cylinder, with an even distribution of mass and radioactivity. After implantation, single-photon emission computed tomograph (SPECT) showed that 32P ...

The present study aimed to explore the effects and possible mechanisms of recombinant human endothelin (ET)-1 on cyclooxygenase (COX)-2 expression in human hormone refractory prostate cancer PC3 cells. PC3 cells were treated with 100 nmol/l ET-1 for the indicated times (3, 6, 9, 12 and 24 h) and concentrations (0.1, 1, 10 and 100 nmol/l) for 24 h. Moreover, 100 nmol/l ET-1 was used to treat PC3 cells alone or in combination with endothelin A receptor (ET(A)R) antagonist BQ123 (1 μmol/l), endothelin B receptor (ET(B)R) antagonist BQ788 (1 μmol/l), MAPK/extracellular signal-regulated kinase kinase (MEK)-selective inhibitor, PD98059 (10 μmol/l), p38 mitogen-activated protein kinase (MAPK) antagonist SB203580 (5 μmol/l) or epidermal growth factor receptor (EGFR) antagonist AG1478 (0.1 μmol/l) for 24 h. COX-2 mRNA and protein expression was detected in the PC3 cells by reverse transcription-polymerase chain reaction and Western blot analysis. ET-1 induced a time- and dose-dependent increase in the mRNA and protein expression of COX-2 in the PC3 cells. BQ123, LY294002, SC203580 and AG1478 prevented the expression of COX-2 in the PC3 cells (P0.05), while BQ788 did not. ET-1 induced the up-regulation of COX-2 in the PC3 cells. ET(A)R may be involved in the process. Several signaling pathways, including p42/44 MAPK, p38 MAPK and EGFR, are therefore implicated in the regulation of COX-2 expression.

The small (SK3) and intermediate (IK1) conductance calcium-activated potassium channels could have key roles in the endothelium-dependent hyperpolarization factor pathway, which is believed to contribute to normal penile erection function. We aimed to investigate the expression of SK3 and IK1 in diabetic rodents. The experimental diabetes model was induced in 8-week-old male Sprague–Dawley rats (250–300 g) by a single administration of streptozotocin. Both the diabetes mellitus group (DM group, n = 20) and the control group (NDM group, n = 10) were injected with a low dose of apomorphine to allow for the measurement and comparison of the corresponding penile erections. The mRNA and protein expression levels of SK3 and IK1 were measured by reverse transcription polymerase chain reaction and western blot, respectively. Erectile function was significantly decreased in the DM group compared with control group (P < 0.05). The mRNA and protein expression levels of SK3 and IK1 were reduced in the cavernous tissue of diabetic rats compared with the control group (P < 0.05). Diabetes inhibits mRNA and protein expression of both SK3 and IK1 in the cavernous tissue of diabetic rats. This could play a key role in the development of erectile dysfunction in diabetic rats.

Our previous work demonstrated that berberine (BBR) increases insulin receptor (InsR) expression and improves glucose utility both in vitro and in animal models. Here, we study the InsR-up-regulating and glucose-lowering activities of BBR in humans. Our results showed that BBR increased InsR messenger RNA and protein expression in a variety of human cell lines, including CEM, HCT-116, SW1990, HT1080, 293T, and hepatitis B virus-transfected human liver cells. Accordingly, insulin-stimulated phosphorylations of InsR beta-subunit and Akt were increased after BBR treatment in cultured cells. In the clinical study, BBR significantly lowered fasting blood glucose (FBG), hemoglobin A(1c), triglyceride, and insulin levels in patients with type 2 diabetes mellitus (T2DM). The FBG- and hemoglobin A(1c)-lowering efficacies of BBR were similar to those of metformin and rosiglitazone. In the BBR-treated patients, the percentages of peripheral blood lymphocytes that express InsR were significantly elevated after therapy. Berberine also lowered FBG effectively in chronic hepatitis B and hepatitis C patients with T2DM or impaired fasting glucose. Liver function was improved greatly in these patients by showing reduction of liver enzymes. Our results confirmed the activity of BBR on InsR in humans and its relationship with the glucose-lowering effect. Together with our previous report, we strongly suggest BBR as an ideal medicine for T2DM with a mechanism different from metformin and rosiglitazone.

We identify berberine (BBR), a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. Oral administration of BBR in 32 hypercholesterolemic patients for 3 months reduced serum cholesterol by 29%, triglycerides by 35% and LDL-cholesterol by 25%. Treatment of hyperlipidemic hamsters with BBR reduced serum cholesterol by 40% and LDL-cholesterol by 42%, with a 3.5-fold increase in hepatic LDLR mRNA and a 2.6-fold increase in hepatic LDLR protein. Using human hepatoma cells, we show that BBR upregulates LDLR expression independent of sterol regulatory element binding proteins, but dependent on ERK activation. BBR elevates LDLR expression through a post-transcriptional mechanism that stabilizes the mRNA. Using a heterologous system with luciferase as a reporter, we further identify the 5' proximal section of the LDLR mRNA 3' untranslated region responsible for the regulatory effect of BBR. These findings show BBR as a new hypolipidemic drug with a mechanism of action different from that of statin drugs.

In tumors the process of apoptosis occurs over an interval of time after chemotherapy. It is important to determine the best time for detecting apoptosis by in vivo imaging. In this study, we evaluated the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using a (99)Tc(m)-labeled Annexin V recombinant with ten consecutive histidines (His10-Annexin V) in a mouse model.(99)Tc(m)-His10-Annexin V was prepared by one step direct labeling; radio-chemical purity (RCP) and radio-stability was tested. The binding of (99)Tc(m)-His10-Annexin V to apoptotic cells was validated in vitro using camptothecin-induced Jurkat cells. In vivo bio-distribution was determined in mice by dissection. The human H460 NSCLC tumor cell line (H460) tumor-bearing mice were treated with intravenous paclitaxel 24, 48 and 72 hours later. (99)Tc(m)-His10-Annexin V was injected intravenously, and planar images were acquired at 2, 4 and 6 hours post-injection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROI analysis and they reflected specific binding of (99)Tc(m)-His10-Annexin V. Mice were sacrificed after imaging. Caspase-3, as the apoptosis detector, was determined by flow cytometry, and DNA fragmentation was analyzed by the terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Nonspecific accumulation of protein was estimated using bovine serum albumin (BSA). The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity.(99)Tc(m)-His10-Annexin V had a RCP98% and high stability 2 hours after radio-labeling, and it could bind to apoptotic cells with high affinity. Bio-distribution of (99)Tc(m)-His10-Annexin V showed predominant uptake in kidney, relatively low uptake in myocardium, liver and gastrointestinal tract, and rapid clearance from blood and kidney was observed. The T/NT was significantly increased after paclitaxel treatment, whereas it was low in untreated tumors (T/NT = 1.43 ± 0.18). The %ID/g activity in Group 2 (24 hours), Group 3 (48 hours) and Group 4 (72 hours) after treatment was 2.55 ± 0.73, 3.35 ± 1.10, and 3.4 ± 0.96, respectively. Whereas in the non-treated group, Group 1, %ID/g was 1.10 ± 0.18. The radiotracer uptake was positively correlated to the apoptotic index (r = 0.852, P0.01), as well as caspase-3 activity (r = 0.816, P0.01).This study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using (99)Tc(m)- His10-Annexin V.

Aim The study aims to investigate the gene expression profiling of insulin signaling pathway and mitochondrial biogenesis and function in the skeletal muscle of KK mice. Methods KK mice were divided into the following groups: KK control group, basal medium (M199) only; KK fibroblast group, with human fibroblast transplantation; KK myoblast group, with human skeletal myoblast transplantation. C57BL mice received hSkM transplantation as a normal control. Cells were transplanted into mice hind limb skeletal muscle. All animals were treated with cyclosporine for 6 weeks only. The mice were sacrificed in a fasting state at 12 weeks after treatment. Hind limb skeletal muscle was harvested and used for study of gene expression profiling. Results hSkMs survived extensively in mice skeletal muscle at 12 weeks after cell transplantation. Glucose tolerance test showed a significant decrease of blood glucose in the mice of KK myoblast group compared to the KK control and fibroblast groups. Transcriptional patterns of insulin signaling pathway showed alterations in KK myoblast as compared with KK control group (23 genes), KK fibroblast group (7 genes), and C57BL group (8 genes). Transcriptional patterns of mitochondrial biogenesis and function also had alterations in KK myoblast as compared with KK control group (27 genes), KK fibroblast group (9 genes), and C57BL group (6 genes). Conclusions These data demonstrated for the first time that hSKM transplantation resulted in a change of gene transcript in multiple genes involved in insulin signaling pathway and mitochondrial biogenesis and function.

To study the effects of implantation brachytherapy with delayed-release particles of 32P-chromic phosphate-poly (L-lactide) (32P-CP-PLLA) on prostate cancer (PCa) in nude mice.We established a subcutaneous transplantable PCa model in nude mice, and randomly divided them into six groups, Groups A, B and C implanted intratumorally with 32P-CP-PLLA delayed-release particles at 3.7, 7.4 and 14.8 MBq, Groups D, E and F with 125I particles at the same doses as the former three, and another six nude mice were included in Group G as the blank control. Then we killed the mice at 21 days after the treatment, observed the effects of the particles on the morphology of the tumor and their inhibition of tumor growth, counted WBCs and platelets (PLTs) in the peripheral blood, and detected the toxic reaction of the blood.At 21 days after the treatment, the solid tumor tissues exhibited bleeding and necrotic changes, and the rates of tumor inhibition were positively correlated with the doses of administration. Groups A, B and C showed statistically significant differences from Groups D, E, F and G in the rate of tumor inhibition ([ 65.72 +/- 6.95]%, [77.58 +/- 4.32]% and [82.64 +/- 4.03]% versus [35.61 +/- 5.61]%, [43.30 +/- 6.94]% and [69.01 +/- 4.98]%), WBC count ([1.72 +/- 0.37] x 10(9)/L, [1.23 +/- 0.27] x 10(9)/L and [0.86 +/- 0.25] x 10(9)/L versus [1.45 +/- 0.40] x 10(9)/L, [0.51 +/- 0.24] x 10(9)/L, [0.37 +/- 0.26] x 10(9)/L and [3.96 +/- 0.26] x 10(9)/L), PLT count ([1.18 +/- 0.11] x 10(11)/L, [0.97 +/- 0.10] x 10(11)/L and [0.72 +/- 0.11] x 10(11)/L versus [0.97 +/- 0.15] x 10(11)/L, [0.76 +/- 0.16] x 10(11)/L, [0.64 +/- 0.12] x 10(11)/L and [2.89 +/- 0.21] x 10(11)/L) and body weight ([18.60 +/- 0.66] g, [17.60 +/- 0.39] g and [16.90 +/- 0.68] g versus [17.86 +/- 0.60] g, [15.56 +/- 0.39] g, [14.61 +/- 0.65] g and [19.95 +/- 0.73] g) (P0.01).Intratumoral implantation of 32P-CP-PL-LA is a safe, simple and effective radionuclide interventional therapy for prostate cancer.

To investigate the effects of the epidermal growth factor on the mRNA expression of endothelin-1 and its receptors (ET(A)R, ET(B)R) in hormone refractory prostate cancer (HRPC) PC-3 cell lines.PC-3 cells were cultured in vitro. After the treatment with EGF, the mRNA expressions of endothelin-1, ET(A)R and ET(B)R were detected by RT-PCR in PC-3 cell lines. The levels of the mRNA expression of endothelin-1 and its receptors were examined at different time points by RT-PCR.The expressions of endothelin-1 and ET(A)R mRNA but not the mRNA expression of ET(B)R was observed in PC-3 cell lines. After 24 hours of treatment with EGF, the expressions of endothelin-1 and ET(A)R in PC-3 cell lines were both up-regulated and there was significant difference (P0.05) between the experimental and control groups. Different expression levels of endothelin-1 and ET(A)R mRNA were noted at different time points of EGF intervention, up-regulated with the increase of treatment time, and with significant difference (P0.05).EGF can up-regulate the mRNA expressions of endothelin-1 and ET(A)R in PC-3 cell lines and play a great role in prostate cancer progression, which may offer a substructure of molecular biology for the treatment of HRPC.

Objective To evaluate the efficacy of 99mTc-labeled C2A probe in detection of apoptosis of non-small cell lung cancer (NSCLC) cells after chemotherapy.Imaging studies were performed in NSCLC H460-bearing mice. The mice were divided into 2 groups: the paclitaxel-treated group and control group. 99mTc-C2A was injected intravenously at 12, 24, 48 and 72 h after chemotherapy. Images were acquired at 3 h and 6 h after injection using a pinhole collimator. The regions of interest (ROI) were drawn in tumor area and contralateral nomal tissue, and the ratio of T/NT were caculated. The tumor sections were stained by HE and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-nick-end labeling) staining to confirm the presence of apoptosis. Activated caspase-3 was also analyzed with flow cytometry.Little uptake of 99mTc-C2A was found in baseline images, but tumor uptake increased very much after chemotherapy, the T/NT ratio was 1.79 +/- 0.34, 2.23 +/- 0.33 and 2.78 +/- 0.34, respectively. The T/NT ratio of control was 1.48 +/- 0.23. Tumor uptake (% ID/g) of 99mTc-C2A in chemotherapy groups were 2.82 +/- 0.90, 3.13 +/- 0.48 and 3.52 +/- 1.18, respectively. Tumor uptake (% ID/g) in the control group was 1.21 +/- 0.51. It in paclitaxel-treatment groups were 2.82 +/- 0.90, 3.13 +/- 0.48 and 3.51 +/- 1.18, respectively, significantly higher than that in untreated mice. Furthermore, the uptake of 99mTc-C2A correlated well with apoptotic index (r = 0.56, P0.01), and activated caspase-3 (r = 0.59, P0.01).Our preliminary results demonstrated that 99mTc-C2A imaging in vivo for detection of cell death in solid tumors is feasible and well correlated with TUNEL staining and activated caspase-3. The C2A holds promise and warrants further development as a molecular probe to early predict cancer treatment efficacy.

To characterize the immune responses including local and systemic immunity induced by infection with H pylori, especially with CagA+ H pylori strains and the underlying immunopathogenesis.A total of 711 patients with different gastric lesions were recruited to determine the presence of H pylori infection and cytotoxin associated protein A (CagA), the presence of T helper (Th) cells and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMCs), expression of plasma cytokines, and RNA and protein expression of IFN-gamma and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test, urea [(14)C] breath test, immunoblotting test, flow cytometry , real time RT-PCR and immunohistochemistry.Of the patients, 629 (88.47%) were infected with H pylori; 506 (71.16%) with CagA+ and 123 (17.30%) with CagA- strains. Among patients infected with CagA+ H pylori strains, Th1-mediated cellular immunity was associated with earlier stages of gastric carcinogenesis, while Th2-mediated humoral immunity dominated the advanced stages and was negatively associated with an abundance of Treg cells. However, there was no such tendency in Th1/Th2 polarization in patients infected with CagA- H pylori strains and those without H pylori infection.Polarization of Th cell immune responses occurs in patients with CagA+ H pylori infection, which is associated with the stage and severity of gastric pathology during the progression of gastric carcinogenesis. This finding provides further evidence for a causal role of CagA+ H pylori infection in the immunopathogenesis of gastric cancer.

(99)Tc(m) labeled C2A domain of synaptotagmin I ((99)Tc(m)-Syt I-C2A) is used for noninvasive detection of vulnerable atherosclerotic plaque.Recombinant C2A domain of synaptotagmin I, overexpressed in E. Coli, was thiolated with 2-iminothiolane (2-IT) and labeled with (99)Tc(m). Atherosclerotic plaques were produced in 5 rabbits by deendothelialization of the abdominal aorta and the rabbits were fed with cholesterol diet for 3 months. Three rabbits not manipulated served as normal controls. All animals were injected with (99)Tc(m)-Syt I-C2A and underwent in vivo imaging thereafter. Aortas were then explanted for ex vivo imaging and histological characterization.In deendothelialized animals, intense radio-uptake in abdominal aorta, showed by gamma camera at 2 h after injection, was visualized and T/B was 3.25 +/- 0.51 by ROI measurement, quantitative uptake ratio of abdominal aortas with atherosclerotic lesions to thoracic aortas was 8.39 +/- 1.74 in ex vivo imaging. The mean uptake in specimens of abdominal aortas with lesions was 12.6-fold higher than in control abdominal aortas, and 10.2-fold higher than in thoracic aortas of deendothelialized animals by gamma-counter.(99)Tc(m)-Syt I-C2A has a high affinity for vulnerable atherosclerotic plaque and is a suitable a gent for the noninvasive detection of vulnerable atherosclerotic plaque.

To evaluate the value of (99 m)Tc-sandostatin scintigraphy in targeted diagnosis of pancreas carcinoma and the correlation with expression of somatostatin receptor (SSTR) reporter gene in tumor tissue.Nude mice bearing human pancreas carcinoma xenograft were established in advance. (99 m)Tc-sandostatin imaging was performed in 18 nude mice and tumor to normal tissue ratio (T/NT) was calculated. mRNA expression of SSTR1, SSTR2 and SSTR5 in tumor tissue was detected by RT-PCR.Out of 18 nude mice, 13 mice showed intense uptake of (99 m)Tc-sandostatin. Six hours after (99 m)Tc-sandostatin administration, the T/NT ratio was 2.53 +/- 0.84. Five mice showed negative findings, and the T/NT ratio was 1.04 +/- 0.06. Positive correlations were obtained between the T/NT ratio and the expression of SSTR1 and SSTR2 mRNA, especially SSTR2 (r = 0.807, P0.01).High expression of SSTR1, SSTR2 and SSTR5 mRNA were found in human pancreas tumor xenograft in nude mice, especially SSTR2. There is a significant correlation between the tumor uptake of (99 m)Tc-sandostatin and SSTR2 mRNA level. This approach may allow SSTR-targeted diagnosis and therapy of human pancreas cancer.

Single nucleotide polymorphism (SNP) has been regarded as the third generation of heredity markers with many marked characteristics. It has been developed many new experimental techniques for detecting SNP in recent years, such as TaqMan probe technique, gene chip technique, denaturing high performance liquid chromatograph, matrix assisted laser desorption ionization-time off light mass spectrometry and minisequencing technique. Great progress has been made in researches on human tumors with SNP as heredity markers. This article reviews the genes and SNP related to the development of prostate cancer, including prostate specific antigen response component, enzymes, hormones and their receptors, cell cycle regulating protein, cytokines, adhesion molecules, vitamins and so on, and aims to explore the possible mechanism of the disease.

To evaluate the clinical value of (99)Tc(m)-sandostatin receptors imaging ((99)Tc(m)-sandostatin) in detection of lung tumors in comparison with fludeoxyglucose F18 dual head coincidence imaging ((18)F-FDG DHC).Fifty-six consecutive patients (40 men, 16 women; mean age: 62 years, range 35 - 80 years) with pulmonary neoplasm were referred for evaluation. All underwent sandostatin scintigraphy using hybrid SPECT/CT. (18)F-FDG DHC imaging was also performed in 23 patients using the same camera. The tumor uptake of (99)Tc(m)-sandostatin and (18)F-FDG DHC were measured respectively and expressed as the ratio of T/Nr and T/Nm. Final clinical diagnosis was confirmed by histopathological study.Out of 56 cases, 46 were confirmed to be malignant and 10 benign. The sensitivity, specificity and accuracy of (99)Tc(m)-sandostatin in diagnosis of lung cancer were 95.7%, 90.0%, 94.6%, respectively. The positive predictive value (PPR) was 97.8%, and the negative predictive value (NPR) was 81.8%. In the 23 patients underwent both methods, the sensitivity, specificity and accuracy of (18)F-FDG DHC were 100%, 60.0%, 82.6%, respectively; the PPR was 76.5%, and the NPR 100%. Out of 13 patients with malignant neoplasms, 6 patients had regional lymph node metastasis, and all of 10 abnormal lymph nodules showed high uptake of FDG, while (99)Tc(m)-sandostatin imaging only 2 regional metastasized lymph nodes in one patient. T/N(r) and T/N(m) were 3.15 +/- 1.30, and 10.61 +/- 4.35 respectively. There was no relationship between sandostatin uptake and glucose metabolism.(99)Tc(m)-sandostatin scintigraphy is a promising noninvasive imaging technique for detection of the primary tumor of lung cancer but of limited value in the detection of lymph node metastasis.

To explore the clinical application of anti-human seminal plasma phospholipase A2 (PLA2) monoclonal antibody (McAb) for male infertility.Enzyme-linked immunoabsorbent assay (ELISA), immunocytochemistry(ICC), as well as flow cytometry (FCM) analysis were established using two strains anti-human seminal plasma PLA2 McAb prepared by our laboratory to detect the PLA2 content in human seminal plasma and the anterior head region of spermatozoa, respectively. Then the PLA2 content in male infertile patients were compared with that in normal control with fertility. The seminal routine analysis was performed by computer-assisted semen analysis (CASA).The PLA2 content of infertile groups were (31.13 +/- 14.49) ng/ml in azoospermic patients, (17.71 +/- 12.45) ng/ml in oligospermic patients and (16.46 +/- 11.31) ng/ml in patients with normal sperm density, which were all higher than that of normal controls [(8.09 +/- 3.15) ng/ml, P0.01]; There was significantly negative correlation between PLA2 content in seminal plasma and sperm density(r = -0.602, P0.05), while there was insignificant correlation between PLA2 and sperm motility or percentage of motility. The PLA2 content in the anterior head region of spermatozoon of male infertile groups was significantly lower than that of normal controls by ICC and FCM(P0.01).PLA2 in human seminal plasma is closely related to male fertility, and the PLA2 deficiency in the head of spermatozoa may be one of the reasons causing male infertility. The methods detecting PLA2 content in seminal plasma and the head of spermatozoa can provide powerful evidences for exploring the mechanism of male infertility.

To establish and evaluate the anti-human seminal plasma phospholipase A2 (PLA2) monoclonal antibody (McAb).After having been separated and purified from human seminal plasma by PEG precipitation, Sephacryl S-300 column chromatography, DEAE-Sephadex A-25 column chromatography and HA column chromatography, PLA2 was regarded as an antigen to immune BALB/C mouse to produce anti-human seminal plasma PLA2 McAb. The PLA2 McAb sensitivity and specificity were performed by ELISA technique and Western-blot analysis, respectively.The molecular weight of PLA2 depurated with 245 fold purification from human seminal plasma was about 34,900, while the sensitivity and typing of its McAb were 1:5(6)-1:5(8) and IgM (kappa) with a satisfied Western-Blot results.The PLA2, which had not been reported in international and domestic papers, may be a new type of PLA2. The establish of its McAb will provide significant tools for the research of the relationship between PLA2 in human seminal plasma and male fertility.

Heatstroke is a serious medical emergency. Because heat shock proteins (HSPs) are regulated in vitro and in vivo by heat stress (1), they may also affect the likelihood or severity of heatstroke. Animal experiments have shown that heat stress upregulates expression of heat shock protein 70 (HSP70), thereby protecting against organ injury (2). We investigated levels of serum HSP70 and HSP70 antibody in patients with mild or severe heatstroke, as well as in normal controls.

Antibodies against heat shock or stress proteins (Hsps) have been reported in a number of diseases in which they may be involved in the pathogenesis of the disease or may be of use for prognosis. Heat-induced diseases, such as heat cramps, heat exhaustion, or heat stroke, are frequent in hot working or living environments. There are still few investigations on the presence and possible significance of autoantibodies against Hsps in heat-induced illnesses. Using an immunoblotting technique with recombinant human Hsps, we analyzed the presence and titers of antibodies against Hsp60, Hsp71, and Hsp90alpha, and Hsp90beta in a group of 42 young male patients who presented with acute heat-induced illness during training. We also examined the presence of antibody against Hsp71 in a second group of 57 patients with acute heat-induced illness and measured the changes in titers of anti-Hsp71 antibodies in 9 patients hospitalized by emergency physicians. In the first group of young persons exercising in a hot environment, the occurrence of antibodies against Hsp71 and Hsp90alpha was significantly higher among individuals with symptoms of heat-induced illness (P < 0.05) than in the matched group of nonaffected exercising individuals. Moreover titers of antibody against Hsp71 were higher in individuals of the severe and mild heat-induced illness groups, the highest titer being found in the most severe cases. The results from the second group of 57 heat-affected patients exposed to extreme heat were similar. Again, patients with the more severe heat-induced symptoms showed a significantly higher incidence of antibodies to Hsp71 than controls and the titer of anti-Hsp71 was higher in the severely affected group. Finally, in a study of 9 patients, it was observed that the titer of anti-Hsp71 decreased during recovery from severe heat symptoms. These results suggest that measurement of antibodies to Hsps may be useful in assessing how individuals are responding to abnormal stress within their living and working environment and may be used as one biomarker to evaluate their susceptibility to heat-induced diseases.