Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Objective To explore the possible mechanisms of Galectin - 1(Gal - 1)protein in promoting the invasion and migration of gastric cancer cells. Methods After treated with different concentrations(0,1,5 μg/ mL)of Gal - 1 protein, the Trans - well model was used to analyze the invasion and migration ability of gastric cancer. WB and gelatin zymography method were used to detect the MMP - 9 expression and active form change in gastric cancer cells after Gal - 1 stimulate, in order to explore the possible molecular mechanisms of Gal - 1 protein in promoting the invasion and migration of gastric cancer cells. Results In cell migration assay,the number of gastric cancer cells BGC - 823 treated with 1and 5 μg/ mL Gal - 1 stimulate were 117 ± 8. 19 and 167 ± 7. 55,higher than that treated with 0 μg/ mL(P < 0. 05). The number of gastric cancer cells 7 901 treated with 1and 5 μg/ mL Gal - 1 stimulate were 151 ± 5. 13 and 190. 3 ± 6. 8,higher than that treated with 0 μg/ mL(P < 0. 05). In cell invasion assay,the number of gastric cancer cells BGC - 823 treated with 1and 5μg/ mL Gal - 1 stimulate were 51 ± 3. 6 and 76. 7 ± 9. 07,higher than that treated with 0 μg/ mL(P < 0. 05). The number of gastric cancer cells 7 901 treated with 1and 5 μg/ mL Gal - 1 stimulate were 74. 0 ± 7. 21 and 105. 3 ± 11. 37,higher than that treated with 0 μg/ mL(P < 0. 05). The migration and invasion level were significantly increased in gastric cancer cells after Gal - 1 stimulate. The MMP - 9 expression level and active form change in gastric cancer cells were also increased after Gal - 1 stimulate. Conclusion Gal - 1cound significantly promote gastric cancer cell migration and invasion by up - regulated the MMP - 9 expression and active its enzyme activity.

OBJECTIVETo explore the exfoliated cancer cell contamination in different surgical materials during the malignant gastrectomy.

METHODSNinety gastric cancer patients undergoing gastrectomy were prospectively enrolled in this study. The operation materials of these 90 gastrectomy were divided into 5 groups: surgical instruments (A), gloves for surgeons (B), gloves and gauzes of scrub nurse (C), gauzes for hemostasis (D), anastomosis instrument (E). The rinse fluid of materials was cultured to verify positive cancer cells. Associations among different pathological stages, differentiations, materials and positive cancer cells rates were examined.

RESULTSStage II and III patients had higher positive rates of exfoliated cancer cell contamination than stage I patients [26.5 (9/34) and 47.5% (21/46) vs. 10.0% (1/10),P=0.046]. Low differentiated adenocarcinoma group had higher positive rate than moderately and well differentiated adenocarcinoma groups [44.8% (26/58) vs. 16.7% (4/24) and 12.5% (1/8), P=0.020]. Positive cancer cell rates of 5 kinds of materials were as follows: 12.2% (11/90) in A group, 6.7% (6/90) in B group, 22.2% (20/90) in C group, 15.6% (14/90) in D group and 3.3% (3/90) in E group, and the differences were significant (P<0.01).

CONCLUSIONDifferent operation materials have different risks to be contaminated by cancer cells, which is associated with the contact frequency, cancer staging and pathological classification.

Adult ; Aged ; Equipment Contamination ; Female ; Gastrectomy ; Humans ; Male ; Middle Aged ; Neoplasm Seeding ; Prospective Studies ; Stomach Neoplasms ; pathology ; surgery ; Surgical Equipment

BACKGROUNDAndrographolide has been shown to have anticancer activity on diverse cancer cell lines representing different types of human cancers. The aim of this research was to investigate the anticancer and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line.

METHODSCell proliferation and IC50 were evaluated using MTT assay, cell-cycle analysis with flow cytometry apoptotic effects with Annexin-V/propidium iodide double-staining assay, and morphologic structure with transmission electron microscopy. Immunohistochemistry and reverse-transcription PCR was used to analyze Bcl-2, Bax, and caspase-3 expressions.

RESULTSAndrographolide showed a time- and concentration-dependent inhibitory effects on BGC-823 cell growth. Compared to controls, the number of cells in the G0-G1-phase increased significantly, S and G2-M-phase cells decreased after 48 hours of treatment with andrographolide, and both early and late apoptotic rates increased significantly compared to the controls, all in a concentration-dependent manner. Bax and caspase-3 expressions were markedly increased, and Bcl-2 expression was decreased.

CONCLUSIONSAndrographolide inhibits BGC-823 cell growth and induces BGC-823 cell apoptosis by up-regulating Bax and caspase-3 expressions and down-regulating Bcl-2 expression. Andrographolide may be useful as a potent and selective agent in the treatment of human gastric cancers.

Apoptosis ; drug effects ; Caspase 3 ; analysis ; genetics ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Stomach Neoplasms ; drug therapy ; pathology ; bcl-2-Associated X Protein ; analysis ; genetics

OBJECTIVETo establish serum protein fingerprint model for early diagnosis of pancreatic cancer with surface enhanced laser desorption/ionization time of flight-mass spectrometry (SELDI-TOF-MS) and bioinformatics techniques.

METHODSA total of 73 samples were analyzed in this study, including 31 cases of pancreatic cancers, 22 cases of pancreatitis and 20 healthy individuals. Samples were first analyzed by SELDI-TOF-MS and two patterns of differentiation model were constructed with support vector machine arithmetic method.

RESULTSThe pattern 1 model differentiating pancreatic cancer patients from healthy individuals had a specificity and a sensitivity of both 100.0%. The pattern 2 model differentiating pancreatic cancer from pancreatitis had a specificity of 95.5% and a sensitivity of 93.5%.

CONCLUSIONSELDI-TOF-MS technique combined with bioinformatics can facilitate to identify biomarkers for pancreatic cancer.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; Blood Proteins ; analysis ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms ; blood ; diagnosis ; Protein Array Analysis ; methods ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods ; Support Vector Machine

BACKGROUNDThe ideal post-gastrectomy reconstruction procedure should maintain the normal digestive function and restore intestinal transit to improve the patient quality of life. The aim of this study was to evaluate the effects of integral continual jejunal interposition after subtotal gastrectomy on the nutritional status, glucose levels, and gastric-intestinal motility.

METHODSThe study investigated the effects of the integral continual jejunal interposition, the Billroth I and Billroth II operations, and the isolated jejunal interposition following subtotal distal gastrectomy on the blood glucose, insulin, routine blood parameters, liver function, and myoelectrical activity in Beagle dogs.

RESULTSThe weights of the dogs decreased during the first post-operative weeks. Dogs in the integral continual jejunal interposition, Billroth I, and Billroth II groups gained significantly more weight by 8 weeks. The prognosis nutrition index of the dogs decreased in the first 2 post-operative weeks and increased significantly by 4 weeks in the integral continual jejunal interposition and Billroth I groups. The group with duodenal exclusion (Billroth II) had significantly higher glucose levels compared to the normal control group. The insulin curve was much higher in dogs that underwent the Billroth I, continual jejunal interposition, and isolated jejunal interposition than the Billroth II and normal groups. The frequencies of fasting and postprandial jejunal pacesetter potentials (PPs) were greater in the continual jejunal interposition and Billroth I groups than that in the isolated jejunal interposition and Billroth II groups. The percentage of aboral propagation of PPs was greater in the continual jejunal interposition group than the Billroth I, isolated jejunal interposition, and Billroth II groups.

CONCLUSIONContinual jejunal interposition after subtotal gastrectomy avoids jejunal transection, maintains the duodenal passage and food storage bags, and reduces the influence of blood glucose and insulin.

Animals ; Dogs ; Gastrectomy ; methods ; Gastroenterostomy ; methods ; Jejunum ; pathology ; surgery ; Reconstructive Surgical Procedures ; methods

BACKGROUNDAssessment of lymph node metastasis (LNM) is important in early gastric cancer (EGC) and affects treatment decisions. However, the relationship between clinicopathological characteristics and LNM in EGC remains unclear. This study therefore explored favorable predictors of LNM in EGC.

METHODSA total of 716 specimens from gastric cancer patients who underwent curative gastrectomy between 1996 and 2003 at Zhejiang Provincial People's Hospital were reviewed. Forty-five cases were EGC, and clinicopathological characteristics such as gender, age, tumor size, location, gross type, differentiation, invasion depth, and vessel involvement were assessed to identify predictive factors for LNM and survival time.

RESULTSThe overall cumulative 5-year survival rate of EGC patients was 88.92%. Among these, 22.4% developed LNM, which was associated with a poor 5-year survival rate of only 72.7%. Patients with tumors larger than 2 cm in diameters, with depth of tumor invasion to the submucosa, and with positive lymphatic or nerve involvement were also inclined to have poorer survival performances. EGC limited to the mucosa but poorly differentiated also had a high risk for LNM. Multivariate analysis identified lymphatic invasion and tumor size as independent prognosis factors related to survival in EGC patients.

CONCLUSIONSCareful planning is required in EGC patients at high risk of lymph node metastases. Endoscopic mucosal resection or endoscopic submucosal dissection and laparoscopic partial gastrectomy should be cautiously used in EGC, and curative gastrectomy including lymphatic dissection and postoperative adjuvant therapy might be considered to improve the prognosis.

Adult ; Aged ; Female ; Gastrectomy ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Stomach Neoplasms ; mortality ; surgery ; Treatment Outcome

Diabetes surgery is a new concept in recent years, which means controlling blood sugar or curing diabetes through some surgical methods. From the commencement of bariatric surgery in the 1950s to the discovery of the special function of decreasing blood sugar after these surgeries in 1970s, and then the fast developing of diabetes surgery in the past 30 years, now there seems be a different answer to the question that if we can cure diabetes. In this article, we review the historical evolution, surgical procedure, potential mechanism and outlook of diabetes surgery.
Bariatric Surgery ; methods ; Diabetes Mellitus, Type 2 ; surgery ; Humans

OBJECTIVETo study the clinical value of uncut Roux-en-Y esophagojejunostomy with distal jejunal pouch on behalf of the stomach (URYAJP) surgery in the digestive tract reconstruction after total gastrectomy.

METHODSA retrospective analysis of radical resection of the whole stomach in 486 cases of gastric cancer patients, divided into the URYAJP group (n = 189), the P-loop Roux-en-Y behalf of the stomach surgery (PRY) group (n = 150) and pure Roux-en-Y reconstruction (RY) group (n = 147). Three groups were compared in patients with surgical reconstruction time, the occurrence of postoperative complications, the postoperative weight after 6, 12 and 24 months, the single meal food intake and prognostic nutritional index (PNI) and Visick points class situation after 12 and 24 months.

RESULTS(1) The URYAJP group and RY group had no significant difference in digestive tract reconstruction time ((37 ± 6) minutes and (38 ± 6) minutes respectively), but PRY group was significantly prolonged ((47 ± 6) minutes, t = 7.52 and 6.54, P < 0.05). (2) In the comparison of the incidence of complications, URYAJP group has 2.1% rate of Roux stay syndrome (RSS) incidence, significantly less than PRY group (21.3%) and RY group (19.7%) (χ² = 14.84, P < 0.05). (3) In the comparison the postoperative nutritional status, URYAJP group clear asset, showing the degree of ((3.1 ± 1.0) kg) weight loss after 12 months (t = 25.03 and 22.99, P < 0.05). And after 12, 24 months, a single meal eating reached the preoperative level is 94.8% and 96.9% in URYAJP group, while PRY group and RY group is less than 50% (χ(2) = 61.10, 69.17, 65.17 and 73.29, P < 0.05). URYAJP Group reach the preoperative levels of PNI in 24 months after surgery, while PRY and RY group were still lower than per-operation (t = 106.97 and 100.37, P < 0.05). (4) The Visick points class I-II postoperative 12 and 24 months in URYAJP group were 92.7% and 93.8%, significantly better than group B and C (χ² = 10.63, 14.19, 10.10 and 10.74, P < 0.05).

CONCLUSIONSURYAJP surgery give full play to maintain intestinal continuity, simple operation, and advantages of food storage bags, it can reduce the long-term postoperative complications, improve the nutritional status of patients and improve quality of life. It is worthy of promoting a way of gastrointestinal reconstruction.

Aged ; Anastomosis, Roux-en-Y ; methods ; Female ; Follow-Up Studies ; Gastrectomy ; Humans ; Jejunum ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Stomach Neoplasms ; surgery ; Treatment Outcome

OBJECTIVETo compare the surgical outcomes between laparoscopic and open wedge resection for gastrointestinal stromal tumors of the stomach.

METHODSClinical data of 18 cases undergoing laparoscopic wedge resection from June 2000 to August 2009 at the Zhejiang Provincial People's Hospital were compared with 30 patients treated by open surgery. The perioperative parameters and prognosis data of the two groups were compared.

RESULTSCompared to the open group, laparoscopic group was found with longer operative time, less blood loss, less requirement of postoperative analgesia, earlier resumption of oral intake, earlier return of first flatus, and shorter postoperative hospital stay(all P<0.05). There were no postoperative deaths in both groups. Postoperative complication rate was significantly lower in the laparoscopic group(5.5% vs. 33.3%, P<0.05). The postoperative recurrence rates were 11.8%(2/17) and 10.7%(3/28); the 5-year survival rates were 78% and 63%, respectively, and the difference was not statistically significant(P>0.05).

CONCLUSIONLaparoscopic wedge resection is a feasible treatment option for GISTs of the stomach.

Adult ; Female ; Gastrectomy ; methods ; Gastrointestinal Stromal Tumors ; diagnosis ; pathology ; surgery ; Humans ; Laparoscopy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies