OBJECTIVE To construct an insulin-resistant(IR)small intestinal organoid model of mice and study the protective effect of flavanomarein(FM)on the intestinal mucosal barrier in the model.METHODS ①Small intestinal organoid models of C57BL/6J and db/db of mice were constructed.The expressions of Ki-67,E-cadherin(E-cad),lysozyme(Lyz)and mucin-2(Muc-2)in small intestinal organ-oids were detected by 3D immunofluorescence.RT-qPCR was used to detect the expressions of fibro-nectin(Fn),glucagon-like peptide-1(GLP-1)and peotide YY(PYY)mRNA while Western blotting was used to detect the expressions of Fn,GLP-1 and PYY protein.The Lyz secretion level was detected by ELISA.② Small intestinal organoids were divided into five groups:C57BL/6J mice 'small intestinal organ-oids as the normal control group,db/db mice' intestinal organoids as the IR model group,db/db mice small intestinal organoids with flavanomarein 25,50 and 100 μmol·L-1 intervention for 48 h as IR model+ FM groups.RT-qPCR was used to detect the expression of Lyz mRNA while Western blotting was used to detect the expression of Lyz protein.RESULTS ① On the 6th day of small intestinal organoid culture,a ring structure with a clear luminal structure was formed and an IR mouse small intestinal organoid model was established.3D Immunofluorescence detection showed that the established small intestinal organoids all expressed Ki-67,E-cad,Lyz and MUC-2.Compared with the normal control group,the expres-sion of Fn mRNA in the IR model group was significantly increased(P<0.05)while the expressions of GLP-1 and PYY mRNA were significantly decreased(P<0.05).Compared with the normal control group,the expression of Fn protein in the IR model group was significantly decreased(P<0.05)while the expressions of GLP-1 and PYY protein were significantly increased(P<0.05).ELISA results showed that compared with the normal control group,the secretion levels of Lyz in the IR model group were signifi-cantly decreased(P<0.01).② RT-qPCR results showed that compared with the normal control group,the expression of Lyz mRNA in the IR model group was significantly decreased(P<0.01).Compared with the IR model group,the expression of Lyz mRNA in the IR model+FM 50 and 100 μmol·L-1 groups was significantly increased(P<0.05,P<0.01).Western blotting results showed that compared with the normal control group,the expression of Lyz protein in the IR model group was significantly decreased(P<0.01).Compared with the IR model group,the expression of Lyz protein in the IR model+FM 50 and 100 μmol·L-1 groups was significantly increased(P<0.05,P<0.01).CONCLUSION The constructed IR mouse small intestinal organoid model provides a more complete in vitro research model for exploring the pathophysiological mechanism by which drug interventions help repair the intestinal mucosal barrier.FM may maintain the intestinal mucosal barrier by reversing the decrease in Lyz expression levels in IR mice,thereby improving IR.

Anti-angiogenic drugs (AADs), which mainly target the vascular endothelial growth factor-A signaling pathway, have become a therapeutic option for cancer patients for two decades. During this period, tremendous clinical experience of anti-angiogenic therapy has been acquired, new AADs have been developed, and the clinical indications for AAD treatment of various cancers have been expanded using monotherapy and combination therapy. However, improvements in the therapeutic outcomes of clinically available AADs and the development of more effective next-generation AADs are still urgently required. This review aims to provide historical and perspective views on tumor angiogenesis to allow readers to gain mechanistic insights and learn new therapeutic development. We revisit the history of concept initiation and AAD discovery, and summarize the up-to-date clinical translation of anti-angiogenic cancer therapy in this field.

Crohn’s disease is a chronic intestinal inflammatory disorder of unknown etiology. Although the pharmacotherapies for Crohn’s disease are constantly updating, nutritional support and adjuvant therapies have recently gained more attention. Due to advancements in clinical nutrition, various clinical nutritional therapies are used to treat Crohn’s disease. Doctors treating inflammatory bowel disease can now offer several diets with more flexibility than ever. The Crohn’s disease exclusion diet is a widely used diet for patients with active Crohn’s disease. The Crohn’s disease exclusion diet requires both exclusion and inclusion. Periodic exclusion of harmful foods and inclusion of wholesome foods gradually improves a patient’s nutritional status. This article reviews the Crohn’s disease exclusion diet, including its structure, mechanisms, research findings, and clinical applications.

Objective     To analyze the risk factors for postoperative length of stay (PLOS) after mediastinal tumor resection by robot-assisted non-endotracheal intubation and to optimize the perioperative process. Methods    The clinical data of patients who underwent Da Vinci robot-assisted mediastinal tumor resection with non-endotracheal intubation at the Department of Thoracic Surgery, General Hospital of Northern Theater Command from 2016 to 2019 were retrospectively analyzed. According to the median PLOS, the patients were divided into two groups. The univariate analysis and multivariate logistic regression were used to analyze risk factors for prolonged PLOS (longer than median PLOS). Results    A total of 190 patients were enrolled, including 92 males and 98 females with a median age of 51.5 (41.0, 59.0) years. The median PLOS of all patients was 3.0 (2.0, 4.0) d. There were 71 patients in the PLOS>3 d group and 119 patients in the PLOS≤3 d group. Multivariate logistic regression showed that indwelled thoracic catheter [OR=11.852, 95%CI (2.384, 58.912), P=0.003], preoperative symptoms of muscle weakness [OR=4.814, 95%CI (1.337, 17.337), P=0.016] and postoperative visual analogue scale>5 points [OR=6.696, 95%CI (3.033, 14.783), P<0.001] were independent factors for prolonged PLOS. Totally no tube (TNT) allowed patients to be discharged on the first day after surgery. Conclusion    Robot-assisted mediastinal tumor resection with non-endotracheal intubation can promote rapid recovery. The methods of optimizing perioperative process are TNT, controlling muscle weakness symptoms and postoperative pain relief.

Objective:To investigate the clinical advantages of absorbable barbed wires in laparoscopy combined with choledochoscopy treatment of gallbladder polyps.Methods:The clinical data of 103 patients with gallbladder polyps who received laparoscopy combined with choledochoscopy treatment in The First People's Hospital of Lianyungang from February 2016 to March 2018 were retrospectively analyzed. Sixty-five patients in the observation group underwent gallbladder wall sutures with absorbable barbed wires, and thirty-eight patients in the control group underwent gallbladder wall sutures with common absorbable wires. The operative time, gallbladder wall suture time, intraoperative blood loss, average hospitalization time, and postoperative bile leakage were compared between the two groups.Results:There were no significant differences in intraoperative blood loss and average hospitalization time between the two groups ( P = 0.312, P = 0.114). In the observation group, gallbladder wall suture time and operative time were (5.58 ± 1.14) minutes and (60.71 ± 11.03) minutes, respectively, which were shorter than (6.32 ± 1.04) minutes and (68.24 ± 9.61) minutes in the control group ( t = 3.23, 3.50, P = 0.002, 0.001). No bile leakage occurred in the observation group and bile leakage occurred in four (10.5%) patients in the control group. There was a significant difference in bile leakage between the observation and control groups ( χ2 = 4.57, P = 0.032). Conclusion:Absorbable barbed wires for gallbladder wall sutures during operation in laparoscopy combined with choledochoscopy treatment of gallbladder polyps is safe and feasible. It can markedly shorten gallbladder wall suture time and operative time, decrease the incidence of bile leakage, and has a clinical advantage over common absorbable wires.

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.

Objective To determine the radiation dose of sensitive organs under different protective methods in lung CT scanning environment, and to explore the best protective scheme of corresponding organs. Methods Annealed thermoluminescence dose elements were placed in the stomach, liver, colon, and thyroid gland of a simulated human body model. The dose effect experiment of protective methods included non-protective group, half lead apron group, and full lead apron group. The dose effect experiment of protective thickness included 0.50 mmpb full lead apron group and 0.35 mmpb full lead apron group. The same exposure conditions of lung CT scan were used in the above experiments. Results Compared with the non-protective group, the exposure dose of the stomach, liver, colon, and thyroid gland increased significantly in the half lead apron group (P < 0.05), and the exposure dose of the thyroid gland and colon decreased significantly in the full lead apron group (P < 0.05). There were no significant differences in the exposure dose of the liver, stomach, and colon in the simulated human body model between the 0.35 mmpb full lead apron group and the 0.50 mmpb full lead apron group. Conclusion For lung CT scan, the protective measure of lead apron may not reduce the exposure dose of subjects. The protective thickness of lead apron does not necessarily have a substantial influence on the exposure dose of human body.

The functionality of DNA biomacromolecules has been widely excavated, as therapeutic drugs, carriers, and functionalized modification derivatives. In this study, we developed a series of DNA tetrahedron nanocages (Td),

Objective    To investigate the preoperative localization of pulmonary glabrous nodules. Methods    A total of 192 patients admitted to General Hospital of  Northern Theater Command from April 2012 to September 2019 were selected for the study. There were 95 males and 97 females at an age of 56.47±11.79 years. All patients completed preoperative examination, and were divided into a positioning group (n=97) and a non-positioning group (n=95) according to whether the preoperative positioning was performed. And the surgical indicators between the two groups were compared. According to the substance of ground-glass opacity, they were divided into a pure ground-glass nodules group (n=23) and a mixed ground-glass nodules group (n=74) in the positioning group and a pure ground-glass nodules group (n=14) and a mixed ground-glass nodules group (n=81) in the non-positioning group . According to the size and distance of the nodules from the pleura and whether the nodules could be detected, the corresponding linear function was obtained. Results    The operative time of methylene blue localization group was shorter than that of the no localization group. In the scatter plot, the corresponding diameter and depth of the nodules and the corresponding coordinate points which can be explored were described. And linear regression was performed on all the coordinate points to obtain the linear function: depth=0.648×diameter–1.446 (mm). It can be used as an indication for the preoperative localization of pure ground-glass nodules in Da Vinci robotic surgery. Linear function: depth=0.559 5×diameter+0.56 (mm). It can be used as an indication of preoperative localization of mixed ground-glass nodules in Da Vinci robotic surgery. Conclusion    This equation can be used as a preoperative indication for clinical peripheral pulmonary ground-glass nodules.

Objective    To explore the feasibility of robotic sleeve lobectomy and bronchoplasty and to summarize the experience of quality control and technical process management. Methods    From January to December 2018, our hospital completed robotic sleeve lobectomy and bronchoplasty for 5 patients, including the upper right lung lobe in 2 patients, the middle right lung lobe in 1 patient and the lower left lung lobe in 2 patients. There were 3 males and 2 females with an age of 56.6 (39-75) years. The surgical approach was the same as the surgical incision of the robotic lobectomy. During the operation, the lobes were separated, all enlarged mediastinal lymph nodes were cleaned, pulmonary hilum was dissected, pulmonary arteriovenous vessels and bronchi were exposed, and pulmonary vessels were treated. After exposing the main bronchi, the bronchi were cut off at the distal end of the lesion, and the lobes where the lesion was located (including lesions) were excised by sleeve type and the bronchi were continuously sutured with 3-0 Prolene from the back wall for anastomosis. After the anastomosis, no air leakage was found in the expanded lung, and the anastomosis was no longer wrapped. Results    The operation time was 147.4 (100-192) min, including bronchial anastomosis time 17.6 (14-25) min. Intraoperative blood loss was 60.0 (20-100) mL, and 20 (9-37) lymph nodes were dissected. Three patients had squamous cell carcinoma, 1 adenocarcinoma, and 1 neuroendocrine tumor. All patients showed negative results in the freezing pathology of bronchial stump during operation. All patients recovered well after surgery, without perioperative complications, and the anastomosis was smooth. Postoperative hospital stay was 10.8 (7-14) days. The patients were followed up for 6 to 12 months without anastomotic stenosis or other complications. Conclusion    Since the robot system is a special instrument with 3D vision and 7 degrees of freedom for movable joints, the robotic bronchial suture is more flexible and accurate. The robotic sleeve lobectomy and bronchoplasty are safe and feasible.