0 8*!cm) found by ultrasound. As a result tentative diagnosis of Mirizzi's syndrome was established in 54 cases accounting for 0 56% of all LC patients.Results Laparoscopic procedure was successful in 46 out of 50 type Ⅰ cases. Four cases suffering from iatrogenic bile duct injury received primary repairment under laparoscopy. Fistulae repairment was successful laparoscopically in 3 out of 4 cases of type Ⅱ Mirizzi syndrome.Conclusion Type Ⅰ and type Ⅱ Mirizzi syndromes can be safely and successfully managed under laparoscopy in the hand of careful and skilled operators.

Objective To discuss the effect of Billroth Ⅱ gastrectomy on glucose metabolism in patients with gastric cancer complicated with type 2 diabetes mellitus(T2 DM).Methods A retrospective study on the serum level of glucose in 7 patients with gastric cancer complicated with T2 DM undergone Billroth Ⅱ gastrectomy.The therapeutic regime for T2DM after the operation was also analyzed.Results Billroth Ⅱ gastrectomy was completed in all of the 7 patients by open surgery(3) or laparoscopy(4).No serious intra- and post-operative complications occurred in the series.The preoperative level of fasting plasma glucose(FPG) was between 6.6 and 9.0 mmol/L(mean 8.1 mmol/L) and glycosylated hemoglobin concentrations(HbA1c) between 6.8% and 9.5%(mean 7.8%).While 1 to 8 months after the surgery,the FPG decreased to 4.8-7.9 mmol/L(mean 6.4 mmol/L) and HbA1c 5.5% to 7.2%(mean 6.3%).According to the criteria from ADA,4 patients were cured and 3 were improved.Conclusion Billroth Ⅱ gastrectomy is effective for type 2 diabetes mellitus in patients with gastric cancer.

Objective:To discuss the clinical feature, diagnosis, and treatment course of pancreatic acinar cell carcinoma (ACC) to guide clinical practice and improve prognosis of patients. Methods:Clinical data of 15 patients with pathologically confirmed pancreatic acinar cell carcinoma between December 1994 and March 2014 in Tianjin Medical University Cancer Institute and Hospital were retro-spectively studied. Results:The patients include eight males and seven females with a median age of 44. Tumors in these patients appeared in different parts of the pancreas. Eight patients had tumor in the head, six in the body and tail, and one in the uncinate process. The tumor size ranged from 3 cm to 18 cm, with an average diameter of 6.67 cm. The patients presented less jaundice and the tumor markers remained constant, specifically, no increase was reported. Six patients had metastasis before their operation. Twelve patients received radical resection, while the other three received palliative treatment. The preoperative and intraoperative diagnoses were not exact. The final diagnosis depended on pathologic confirmation after surgery or puncture. The immunohistochemical results of trypsin and chymotrypsin were positive in the patients who were examined. The postoperative chemotherapy was usually based on gemcitabine. The average survival time was 20.6 months. Conclusion:Pancreatic acinar cell carcinoma has special clinical features, and clinicians tend to regard it as low-grade malignancy. The attitude towards ACC should be positive.

Objective To investigate the effect of shRNA-mediated down-regulation of the receptor for activated C kinase 1 (RACK1) gene on the chemotherapeutic sensitivities in human lung adenocarcinoma cell line A549.Methods The shRNA recombinant plasmid targeting to human RACK1 gene was designed and transferred into A549 cells by lipofectin technique.The protein level of RACK1 was measured by Western blot to confirm the function of shRNA plasmid.Drug sensitivities of A549 cells to cisplatin,gemcitabine,pemetrexed and paclitaxel were analyzed by MTT assay.The protein expression of LRP and MRP were detected by Western blot.Results After 24 hours transfection,the relative expression quantity of RACK1 protein in RACK1-shRNA group was 0.267± 0.470,which was significantly lower than that in vector-shRNA group (0.821±0.109) and control group (0.842±0.060) (F =54.438,P ＜ 0.05).The results of MTT showed that the growth of A549 cells in the RACK1-shRNA group was markedly inhibited.The sensitivities of A549 cells to cisplatin and paclitaxel were significantly enhanced compared with that in the vector-shRNA group and control group (P ＜ 0.05).The relative expression quantity of LRP and MRP protein in RACK1-shRNA group were 0.163±0.056 and 0.246±0.050,which were lower than that in vector-shRNA group and control group (F LRP =19.430,F MRP =61.548,both P ＜ 0.05).Conclusion Targeted gene silencing of RACK1 improves the sensitivity of A549 cells to the ascisplatin and paclitaxel medicines,which might be achieved through down-regulation of the expression of LRP and MRP.

Objective To evaluate the feasibility of getting retroperitoneal lymph node biopsy via technique of natural orifice transluminal endoscopic surgery(NOTES)in human being with current available devices.Methods We performed trans-gastric endoscopic biopsy of retroperitoneal lymph node with the aid of laparoscopy in a 50-year-old man,who presented with abdominal pain and enlarged retroperitoneal lymph nodes and signed a written informed consent before the procedure.After routine anesthesia and abdominal skin sterilization,a pneumoperitoneum was induced with a Veress needle placed in the umbilical area,followed by the introduction of a 5-mm trocar.Gastral cavity Was sterilized with antibiotics and povidone iodine.Under laparoscopie optical control,we made a styliform incision in the anterior wall of gastric corpus with a needle knife,and enlarged the incision by a dilatation balloon and then entered the peritoneal cavity with a sterile endoscope.We got two biopsies from the enlarged lymph node with a heat forceps assisted by laparoscopy.The specimen was taken out by retrieval basket through the stomach.The gastric incision Was closed with metal clips.Results The biopsy by means of NOTES was successfully performed without intra-or postoperative complications.The diagnosis was confirmed as lymphoma pathologically.The patient received chemotherapy and was discharged on the sixth postoperative day.There was no short or long-term complication.Conclusion Transgastric access for laparoscopy-assisted biopsy of retroperitoneal lymph node is feasible and safe in human being.

Objective To evaluate the nutritional status of morbid obesity (MO) before and after laparoscopic adjustable gastric banding (LAGB), and the safety of LAGB.Methods LAGB was performed in 15 cases from Jun.2003 to Nov.2003.Patients′ nutritional parameters were determined before and 1, 3 and 6 months postoperatively.Results There was a significant reduction of weight and body mass index (BMI) ( P 0.05).Conclusion No major nutritional deficiencies were found following LAGB.It is an effective and safe procedure for the treatment of morbid obesity.

Objective To analyze pathological and ultrasound imaging features of breast cancer in young women. Methods The pathological and ultrasound imaging data of 42 young female breast cancer patients(≤35 years old,the young group)between January 2016 and October 2017 from the Fourth Affiliated Hospital of China Medical University were retrospectively analyzed. Meanwhile, 62 elder female breast cancer patients (> 60 years old, the elder group) simultaneously diagnosed by pathology (age≥60 years) were randomly selected as the control group. Results The vessel carcinoma embolus rate and lymph node metastasis positive rate in the young group were higher than those in the elder group [31.0 % (13/42) vs. 29.0 %(18/62),59.5 %(25/42)vs.38.7 %(24/62)],and there was no difference between the two groups(χ2=16.187, χ2= 5.749, both P< 0.05). Compared with the elder group, the expression of estrogen receptor (ER) in the young group was lower (χ2= 11.598, P = 0.001). The positive rates of Ki-67 and human epidermal growth factor receptor-2 (HER-2) in the young group were higher (χ2= 5.396, P = 0.024; χ2= 5.166, P =0.026). Inhomogeneous internal echo of breast cancer, microcalcifications, flow classification (grade Ⅱ-Ⅲ) and resistance index (RI) ratio in the young group were higher than those in the elder group [83.3 % (35/42) vs. 59.7 % (37/62), P = 6.576; 57.1 % (24/42) vs. 22.6 % (14/62), P = 12.899; 78.6 % (33/42) vs. 58.1 % (36/62), P = 4.716; 83.3 % (35/42) vs. 59.7 % (37/62), P= 6.578], and the differences were statistically significant (all P < 0.05). Conclusion The young female breast cancer patients have a higher rate of malignancy,invasion and metastasis rate compared with the elder breast cancer patients.

Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 µmol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*