Objective To investigate the effects of AFP enhancer/pgk promoter driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα) in vivo.Methods The previously constructed AFpg promoter-driven DN-PP2Acα was recombined into an adenovirus,and the expression of PP2Ac was tested using Western blot.Cell growth was tested using the MTT and flat plate clone formation assays.In vivo studies were performed in tumor xenograft models.Results AFpg promoter-driven expression of DN-PP2Acα exerted cytotoxic effects against the AFP-positive human hepatoma cell line HepG2,but did not affect AFP-negative human hepatoma cells (SKHEP-1) or normal human liver cells (L-02).Moreover,AFP enhancer/pgk promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts,but did not affect AFP-negative SK-HEP-1 tumors.Conclusion The recombinant AFP enhancer/pgk promoter-driven DN-PP2Acα expression adenovirus presented selective cytotoxicity against AFP-positive hepatoma cells and provides a useful gene therapy strategy to selectively target hepatocellular carcinoma.

Objective To investigate the diagnosis and surgical management of adult choledochal cyst.Methods The clinical data of 58 adult patients with congenital choledochal cyst who were admitted to the First Affiliated Hospital of Nanjing Medical University from January 1997 to December 2010 were retrospectively analyzed.All patients were diangosed by the B ultrasonography,computed tomography (CT),Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP). Surgical procedures were selected according to the diagnosis and Todani classification.All data were analyzed using the t test or chi-square test.Results The accurate rates of B sonography,CT,MRCP and ERCP were 78％ (45/58),92％ (23/25),9/9 and 5/5,respectively.Forty-one patients underwent complete excision of the cyst + hepaticojejunostomy (2 patients were converted from laparotomy due to abdominal adhesions),2 underwent resection of the cyst and involed hepatic segments + hepaticojejunostomy,8 underwent laparoscopic excision of the cyst + hepaticojejunostomy,1 underwent left hemihepatectomy,3 underwent pancreaticoduodenectomy ( including partial hepatectomy in 1 patient),2 underwent common bile duct exploration + cholecystectomy due to acute obstructive suppurative cholangitis,1 underwent external drainage of choledochal cyst due to advanced malignance.The mean operation time and postoperative duration of hospital stay of patients who received open and laparoscopic excision of the cyst and hepaticojejunostomy were (235 ± 70) minutes,(320 ± 50) minutes,and ( 10.0 ± 2.3 ) days,( 12.6 ±6.6) days,respectively,with significant differences between the 2 groups (t =3.157,2.162,P ＜ 0.05).The postoperative morbidities of patients who received open and laparoscopic excision of the cyst and hepaticojejunostomy were 18％ (7/39) and 3/8,respectively,with no significant difference (x2 =1.515,P ＞ 0.05 ).Canceration of the choledochal cyst was observed in 6 patients( 10％ ).No perioperative mortality was observed,and the operative complication rate was 24％ (14/58).The duration of the follow up ranged from 1 to 15 years,no severe long-term complications were observed in patients with benign lesions.Four of the 6 patients with malignancy died in 1 year after operation,the other 2 patients survived for 3 years and 5 years,respectively.Conclusions Abdominal B ultrasonography should be the first choice for diagnosing adult congenital choledochal cyst,while MRCP is the gold standard.Surgical intervention should be timely considered once diagnosed. Complete excision of the cyst combined with Roux-en-Y hepaticojejunostomy is the first choice of treatment.

ObjectiveTo investigate the effects of protein phosphatase 2A (PP2A) inhibitors on the viability of pancreatic cancer cell line PANC-1 and its mechanism.MethodsPANC-1 cells were treated with PP2A inhibitors Cantharidin or Okadiac acid.The activity degree of NF-κB pathway was tested by Western blot.NF-κB pathway was blocked from all sectors by PP2Acα plamid transfection,NF-κB inhibition of protein kinase α (IKKα) and NF-κB inhibitor α (IκBα) dominant negative mutant and p65 interfering plasmid.Cell viability was determined by MTT.ResultsPP2A inhibitors could induce phosphorylation of IKKα,further phosphorylation of IκBα and degradation and followed by the release of p65 into nucleus.When PP2Acα,IKKα dominant negative mutant and IκBα dominant negative mutant were overexpressed,or p65 was interfered,the inhibition rate of Cantharidin on cell viability decreased (31.85±13.37) ％,(23.48±8.98)％,(22.63±5.81)％ and (20.88±3.24)％respectively,and the inhibition rate of Okadiac acid on cell viability decreased (40.17 ± 11.65)％,(27.34±14.28)％,(24.85±3.39)％ and (27.08±3.81)％ respectively.ConclusionsPP2Ainhibitors play a role in preventing pancreatic cancer through PP2Acα/IKKα/IκBα/p65 pathway.

Objective To investigate the apoptosis induction effect of Cantharidin on pancreatic cancer cell line PANC1 and CFPAC-1 and possible mechanism. Methods PANC1 and CFPAC-1 was treated with Cantharidin. Cell growth was determined by MTT. Apoptosis was measured by flow cytometry. Caspase activity was measured by using enzyme chemical method. Apoptosis-related gene expressions were determined by using RT-PCR and Western blotting. Results Cantharidin significantly inhibited the growth of pancreatic cancer cells PANC1, CFPAC-1 and induced apoptosis in a dose-dependent manner. Seventy-two hours after 10 μmol/L Cantharidin treatment, the inhibitory rates of PANC1, CFPAC-1 were (52.95 ± 6.34)％ and (71.21 ±6.30)％. Twenty-four hours after treatment, the early and later period apoptotic cell of PANC1 was increased from 7.35％ to 24.89％, from 6.36％ to 17.73％. The early and later period apoptotic cell of CFPAC was increased from 6.39％ to 24.70％, from 9.21％ to 12.58％ (P＜0.01). Activity of caspase 8 and caspase 9 in PANC1 cells was (155.8 + 11.5)％ and (194.6 ± 14.7)％ when compared with that of control group. Activity of caspase 8 and caspase 9 in CFPAC- 1 was ( 182.5 ± 24.3 ) ％ and ( 215.8 ± 12.2) ％when compared with that of control group ( P ＜ 0. 01 ). The expression of pro-apoptotic genes, TNF-α,TRAILR1, TRAILR2, Bad, Bak and Bid was elevated, the expression of anti-apoptotic Bcl-2 gene was decreased. Conclusions Cantharidin can induce apoptosis in pancreatic cancer cell lines by activating caspase,up-regulating the expression of pro-apoptotic genes and down-regulating the expression of anti-apoptotic genes.

Objective To summarize the experience in the diagnosis and treatment of solid pseudopapillary tumors of the pancreas. Methods Ten consecutive patients who underwent surgery with pathologically confirmed solid pseudopapillary tumors of the pancreas between October 2005 and December 2008 were retrospectively reviewed. Results All of the 10 patients were female and the median age at diagnosis was 24 years (range, 11 -39 years). Abdominal discomfort or pain were the most common presenting symptoms. 4 patients had palpable abdominal mass at physical examination. The tumors appeared on ultrasonography and/or CT, MRI as solid or cystic masses. The preoperative serum biochemical parameters and tumor markers level were within the normal range. All the patients underwent surgical treatment. The tumors were located in the head/neck (n = 6) or the distal part (n = 4) of the pancreas. The surgical procedures included enucleation (n=3) , distal pancreatectomy (n=3 , two with preservation of the spleen, one combined with splenectomy, distal gastrectomy and partial colectomy) , segmental pancreatectomy with pancreaticojejunostomy (n=3) and pancreaticoduodenectomy (n = 1). Pancreatic fistula (n = 2) was observed postoperatively and resolved with conservative treatment. The median resected tumor size was 5. 9 cm. All patients were alive and remained recurrence and metastasis free after a median followk-up of 19. 2 months (range, 8～42 months). Conclusions Solid pseudopapillary tumor of the pancreas was rare neoplasm occurred predominantly in young women with low malignant potential. Aggressive resection should be attempted and could result in excellent prognosis.

Objective:In this study, the liver, spleen, and hepatic portal vein in the portal venous phase images of abdominal enhanced computed tomography (CT) are artificially segmented and annotated, and the radiomics features are extracted from them. A model for predicting portal pressure in patients with hepatitis B virus (HBV) related cirrhosis is constructed by combining radiomics features with clinical indicators.Methods:A total of 171 patients who had abdominal enhancement CT examination and trans-jugular hepatic venous pressure gradient (HVPG) measurement at the same time were enrolled from January 2016 to May 2020 in the Zhongshan Hospital Affiliated to Fudan University. The liver, spleen, and hepatic portal vein in the portal venous phase images of the CT were manually labeled by using ITK-SNAP 3.8 software. The radiomics features of these three sites were extracted using Python programming, and an HVPG prediction model was established.Results:A total of 171 patients was included in the study. The average age was (51.1±10.3)years, of which 134(78.4%) were males, and the average HVPG was 16.87±5.695. A total of 2 553 radiomics features were extracted from three sites of the portal venous phase images of abdominal enhanced CT in each patient. The 2 553 features extracted were screened using LASSO, and by combing with clinical features and radiomics features, the predictive model of HVPG was obtained: m_HVPG=31.622+ 0.028 8T×total bile acids-6.31(portal venous wavelet-LHH_glcm_ClusterShade)=0.253(portal venous wavelet-LHL_glszm_LargeAreaLowGrayLevelEmphasis)-20.9(spleen wavelet-LLH_glcm_Correlation)-0.000 127(liver original_shape_SurfaceArea)+ 2.79(liver wavelet-LLH_glcm_ClusterShade). The coefficient of determination R2 was 0.345. Conclusions:The study suggests that radiomics features of the liver, spleen, and portal venous combined with clinical features may be used as a non-invasive method to assess the portal pressure in patients with HBV-related cirrhosis.

Electrocardiogram (ECG) detection is a routine and effective cardiac problem detection project. Traditional electrocardiogram detection has limitations in cardiac arrhythmia and other heart disease detection and diagnosis, such as effectiveness, real-time and so on. Based on the advanced mobile networking and wearable design concept, this paper designs and implements a dynamic ECG real-time monitoring system with low power embedded system and Bluetooth 4.0 wireless communication. Its main functions include 24-hour dynamic ECG signal real-time acquisition, processing, wireless communication, display and storage, real-time analysis of typical arrhythmia, recording and alarm, professional doctors real-time reading and diagnosis, dynamic ECG sharing and cloud platform automatic analysis and diagnosis. Both the physiological signal generator and the actual patient's wear test showed that the design and function of the wearable dynamic ECG real-time monitoring terminal based on the mobile networking could meet and apply to the patients with cardiac monitoring needs in the house, hospital, nursing home, outdoor and many other places.
Electrocardiography ; Electrocardiography, Ambulatory ; Humans ; Internet ; Signal Processing, Computer-Assisted ; Wearable Electronic Devices

OBJECTIVETo investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.

METHODSA cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.

RESULTSPatients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R=0.076, P=0.033).

CONCLUSIONSThe imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.

Adult ; Antineoplastic Agents ; administration & dosage ; pharmacokinetics ; Benzamides ; Combined Modality Therapy ; Cross-Sectional Studies ; Female ; Gastrectomy ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; administration & dosage ; pharmacokinetics ; Male ; Middle Aged ; Piperazines ; Pyrimidines ; Tandem Mass Spectrometry