Objective To observe the value of 3.0T multimodal MRI for preoperative evaluation of T stage and therapeutic efficacy of neoadjuvant for rectal cancer.Methods 3.0T multimodal MRI data,including T1WI,T2WI/diffusion weighted imaging(DWI),dynamic contrast enhanced MRI(DCE-MRI)and intravoxel incoherent motion DWI(IVIM-DWI)of 150 patients with rectal cancer were retrospectively analyzed,and the value of different sequences for evaluating T stage and therapeutic efficacy of neoadjuvant for rectal cancer were assessed.Results The sensitivity,specificity and accuracy of T1WI,T2WI/DWI,DCE-MRI and IVIM-DWI for evaluating T1-T2 and T3-T4 stage rectal cancer were all significantly different(all P＜0.05).The diagnostic efficacy of DCE-MRI and IVIM-DWI were all higher than that of T1WI and T2WI/DWI(all P＜0.05).Combination evaluation of DCE-MRI and IVIM-DWI for T stage of rectal cancer had good consistency with pathological results(Kappa=0.943,P＜0.05).Significant differences of volume transfer constant(Ktrans),true diffusion coefficient(D)and apparent diffusion coefficient(ADC)were found among different T stage rectal cancers(all P＜0.05).Totally 80 patients received neoadjuvant therapy,and significant differences of Ktrans,D and ADC were noticed between patients with good(n=32)or poor efficacy(n=48)(all P＜0.05).The area under the curve(AUC)of Ktrans,D and ADC for evaluating therapeutic efficacy of neoadjuvant for rectal cancer was 0.774,0.837 and 0.758,respectively,of the combination of above three was 0.929,higher than that of single indexes(all P＜0.05).Conclusion Combination of 3.0T DCE-MRI and IVIM-DWI was helpful for preoperative evaluating T stage and therapeutic efficacy of neoadjuvant for rectal cancer.

OBJECTIVE To explore the intestinal absorption characteristics of saikosaponins. METHODS Based on everted intestinal sac model， using accumulative absorption amount （Q） and absorption rate constant （Ka） as indexes， UHPLC-MS/MS technique as a method， the absorption of saikosaponin A， B2， C， D and F from total saponins of Bupleurum chinense （8 g/mL， by crude drug） in the duodenum， jejunum and ileum was detected. RESULTS The correlation coefficients （r） of the regression equations for the absorption of saikosaponins A， B2， C and F in the duodenum， jejunum and ileum were all higher than 0.95， while the r of saikosaponin D in the above intestinal segments was lower than 0.95； compared with the absorption of the same composition in the duodenum， the Q and Ka of saikosaponin A and C circulating in jejunum and ileum for 120 min， as well as the Q and Ka of saikosaponin F circulating in the ileum for 120 min were significantly decreased （P＜0.05）. CONCLUSIONS Saikosaponin A and the other 4 saikosaponins are all absorbed in the duodenum， jejunum and ileum； among them， saikosaponin A， B2， C and F are linearly absorbed， which conforms to the zero-order absorption characteristics， but saikosaponin D shows non- linear absorption.

Constitutively activated G proteins caused by specific mutations mediate the development of multiple malignancies. The mutated Gαq/11 are perceived as oncogenic drivers in the vast majority of uveal melanoma (UM) cases, making directly targeting Gαq/11 to be a promising strategy for combating UM. Herein, we report the optimization of imidazopiperazine derivatives as Gαq/11 inhibitors, and identified GQ262 with improved Gαq/11 inhibitory activity and drug-like properties. GQ262 efficiently blocked UM cell proliferation and migration in vitro. Analysis of the apoptosis-related proteins, extracellular signal-regulated kinase (ERK), and yes-associated protein (YAP) demonstrated that GQ262 distinctly induced UM cells apoptosis and disrupted the downstream effectors by targeting Gαq/11 directly. Significantly, GQ262 showed outstanding antitumor efficacy in vivo with good safety at the testing dose. Collectively, our findings along with the favorable pharmacokinetics of GQ262 revealed that directly targeting Gαq/11 may be an efficient strategy against uveal melanoma.

Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure-activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties.

Objective:To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer.Methods:This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants′ characteristics and screening results of the two groups were compared by χ 2 test, Fisher exact test or Wilcoxon rank-sum test. Results:A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ2=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ2=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ2=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ2=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ2=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ2=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ2=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ2=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ2=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ2=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ2=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ2=0.082, P=0.774). Conclusions:Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

Objective:To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer.Methods:This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants′ characteristics and screening results of the two groups were compared by χ 2 test, Fisher exact test or Wilcoxon rank-sum test. Results:A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ2=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ2=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ2=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ2=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ2=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ2=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ2=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ2=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ2=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ2=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ2=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ2=0.082, P=0.774). Conclusions:Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

The paper aims to study and compare the effects of Scutellaria baicalensis leaves (SLE) and Scutellaria baicalensis tea (STE) water extracts on the lifespan of Drosophila melanogaster, and explore their anti-aging mechanism through metabolomics. Lifespan, food intake and fertility were measured after administering different doses of SLE and STE to a Drosophila natural aging model, and the metabolic profile of Drosophila was analyzed by metabolomics and multivariate statistical methods. The results showed that SLE and STE (1, 3 g·L^-1) could significantly prolong the average lifespan, median life and maximum lifespan of male Drosophila, improve the fertility of Drosophila, and had no effect on the food intake. Through metabolomics technology, 14 differential metabolites related to aging were found, involving a total of five metabolic pathways. All differential metabolites were reversed after STE intervention, while 13 differential metabolites were reversed after SLE intervention. The results suggest that SLE and STE can delay aging of Drosophila, and the anti-aging mechanism is related to energy metabolism.

Objective To investigate factors affecting ampullary access of endoscopic retrograde cholangiopancreatography (ERCP) in patients undergoing Billroth Ⅱ gastrectomy.Methods A retrospective analysis was performed on data of 261 patients with Billroth Ⅱ gastrectomy who underwent ERCP at Changhai Hospital from January 2008 to December 2017.Multivariate logistic regression analysis was used to analyze the potential factors affecting successful ampullary access,and receiver operating characteristic (ROC) curve was used to assess the predictive ability of potential factors.Results A total of 345 ERCP sessions were collected.The successful ampullary access and cannulation rate were 82.3％ (284/345) and 89.1％ (253/284),respectively.The main reasons for ERCP procedural failure were unable to reach the duodenal blind end and find the papilla (66.3％,61/92) and failure of selective cannulation (33.7％,31/92).The ERCP-related complication rate was 14.2％ (49/345),with post-ERCP pancreatitis rate was 3.2％ (11/345).Multivariate logistic regression analysis indicated that the first ERCP attempt (OR=7.717,95％CI:2.581-23.068.P＜0.001),with Braun anastomosis (OR =8.737,95％CI:2.479-30.797,P =0.001),and no cap-assisted forward-viewing gastroscope (OR =2.774,95％ CI:1.283-5.997,P=0.009) were independent risk factors for failure of ampullary access.According to the B value of each risk factor in logistic regression analysis,that is,no cap-assisted as 1 point,the first ERCP attempt as 2 points,and Braun anastomosis as 2 points,the area under ROC curve was 0.773.When the cut-off point was 2.5,the sensitivity and specificity were 75.0％ and 70.8％,respectively.Conclusion The first ERCP attempt,with Braun anastomosis,and no cap-assisted forward-viewing gastroscope are risk factors for failure of ampullary access of ERCP in Billroth Ⅱ gastrectomy patients.Early identification of high-risk patients may help to improve the success rate of ampullary access.

Objective To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography ( ERCP ) in the treatment of patients with biliary and pancreatic diseases after Billroth Ⅱ gastrectomy. Methods Clinical data of 178 patients with biliary and pancreatic diseases undergoing 237 times of ERCP at the digestive endoscopy center in Changhai Hospital from January 2011 to December 2016 were retrospectively collected. The success rate of procedures and related complications were summed up. Results Among 178 patients undergoing 237 times of ERCP, the successful intubation rate of the endoscope to reach the duodenal papilla was 83. 5％ ( 198/237 ) . The success rate of selective cannulation and completing the expected intervention were 91. 4％ ( 181/198 ) and 98. 9％ ( 179/181 ) , respectively. The total success rate of ERCP was 75. 5％ (179/237), which had an increasing trend with time. The total success rate of ERCP in patients with common bile duct stone was 85. 2％ ( 127/149) , and the stone retrieval rate during the first session was 56. 7％ (72/127). The ERCP-related complication rate was 14. 3％ ( 34/237 ) , with 1. 7％ ( 4/237 ) perforation, 1. 3％ ( 3/237 ) bleeding, 3. 4％ ( 8/237 ) pancreatitis, and 8. 0％ ( 19/237 ) asymptomatic hyperamylasemia. One patient with perforation and 2 patients with severe pancreatitis died of septic shock and multiple organ failure ( 1. 3％, 3/237 ) . Most ERCP-related complications were improved by conservative treatment or second endoscopic intervention ( 91. 2％, 31/34 ) . Conclusion ERCP is effective and safe in the treatment of biliary and pancreatic diseases in patients with prior Billroth Ⅱ gastrectomy. With the development of endoscopic techniques and experience accumulation of endoscopists, the success rate of intubation, selective cannulation and therapeutic intervention can be close to those of patients with normal anatomy, and the incidence of related complications is low.

Objective To explore the effect of interleukin-6 (IL-6) and Interleukin-12(IL-12) on immune response to hepatitis B vaccination in infants of HBsAg-positive mothers.Methods A total of 91 neonates whose mothers were HBsAg-positive were included and followed up for 12 months.HBV DNA and HBV serological markers in the peripheral blood of the neonates and infants were detected with fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA),and the levels of IL-6 and IL-12 in the peripheral blood of the neonates and infants were detected with enzyme-linked immunosorbent assay (ELISA).Results The non-/hypo-response rate to hepatitis B vaccination was 35.16％ (32/91) in the 91 infants.In the neonatal period and infantile period,the level of IL-6 in non-/hypo-response group was lower than that in high-response group,while the level of IL-12 was higher than that in high-response group,and there was significant difference (P＜0.01).From the neonatal period to the infantile period,the level of IL-6 increased,while the level of IL-12 descended in both groups,and there was significant difference (P＜0.01).Furthermore,the level of anti-HBs of infants was positively correlated with the level of IL-6 (rs =0.70,0.79,P＜ 0.01),and was negatively correlated with the level of IL-12 (rs=-0.71,-0.72,P＜0.01) in the neonatal period and the infantile period.From the neonatal period to the infantile period,the increased level of IL-6 was positively associated with the level of anti-HBs (rs =-0.74,P＜0.01),while the decreased level of IL-12 was negatively associated with the level of anti-HBs (rs=-0.42,P＜0.01).The level of IL-6 was negatively correlated with the level of IL-12 in the neonatal period and the infantile period (rs=-0.68,-0.70,P＜0.01).Conclusions IL-6 might promote the immune response to hepatitis B vaccination in infants whose mothers were HBsAg-positive,while IL-12 might inhibit the immune response.IL-6 and IL-12 would affect the immune response to hepatitis B vaccination in infants of HBsAg-positive mothers at the same time.