SHG was sulfated by chlorosulfonic acid-pyridine method, and six samples which we got were prepared in different reaction conditions. There is a characteristic absorption peak near 260 nm in UV spectra and there are two characteristic absorption peaks near 1240 cm(-1) and 810 cm(-1) in the FT-IR. Degree of sulfation (DS) was calculated by elemental analysis and turbidimetry. Under the same conditions the absorption peaks become strong with the DS increase. The anticoagulant activity of SHG and sulfated modification samples was evaluated by the classic coagulant assays of prothrombin time (PT), activated partial thrombin time (APTT) live enzymes, and plasma thrombin time (TT). Results show that sulfated SHG has a good anticoagulant activity in vitro, and DS increased activity within a certain range.

Objective To analyze the viability of extended distal pancreatectomy and the associated prognostic factors.Methods The data of 57 patients with pancreatic adenocarcinoma who underwent standard distal pancreatectomy (DP) or extended distal pancreatectomy (EDP) from January 2011 to December 2014 were reviewed retrospectively.Thirty-five patients were performed with DP and 22 with EDP.Operation safety and survival benefit between DP and EDP were compared by t-test or x2 test.Cox regression analysis was used to explore the prognostic indicators.Results Compared to DP group,operation time((255 ±91)min vs.(208 ±80)min)(t =2.066,P =0.044) and ratio of blood transfusion (50.0％ vs.17.1％) (x2 =12.836,P =0.008) were greater in EDP group,respectively.There were no significant differences in amount of intraoperative blood loss and postoperative duration of hospitalization.Delayed gastric emptying was greater in EDP(22.7％ vs.2.9％) (Z =-2.251,P =0.027),while other complications had no differences.Mortality and ratio of relaparotomy also showed no differences.Median survival following DP was 13.1 months compared to 8.2 months following EDP.There was no difference in survival between DP and EDP.According to the results of multivariate analysis,tumor size (RR =1.275,P =0.03) and perioperative blood transfusions(RR =2.673,P =0.04) were independent prognostic factors.Conclusions Though patients with pancreatic adenocarcinoma who undergo EDP have a worse pathologic staging,they will gain a comparable long-term survival to the patients undergo DP.Tumor size and perioperative blood transfusions are independent prognostic factors.

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.

Objective To analyze the viability of extended distal pancreatectomy and the associated prognostic factors.Methods The data of 57 patients with pancreatic adenocarcinoma who underwent standard distal pancreatectomy (DP) or extended distal pancreatectomy (EDP) from January 2011 to December 2014 were reviewed retrospectively.Thirty-five patients were performed with DP and 22 with EDP.Operation safety and survival benefit between DP and EDP were compared by t-test or x2 test.Cox regression analysis was used to explore the prognostic indicators.Results Compared to DP group,operation time((255 ±91)min vs.(208 ±80)min)(t =2.066,P =0.044) and ratio of blood transfusion (50.0％ vs.17.1％) (x2 =12.836,P =0.008) were greater in EDP group,respectively.There were no significant differences in amount of intraoperative blood loss and postoperative duration of hospitalization.Delayed gastric emptying was greater in EDP(22.7％ vs.2.9％) (Z =-2.251,P =0.027),while other complications had no differences.Mortality and ratio of relaparotomy also showed no differences.Median survival following DP was 13.1 months compared to 8.2 months following EDP.There was no difference in survival between DP and EDP.According to the results of multivariate analysis,tumor size (RR =1.275,P =0.03) and perioperative blood transfusions(RR =2.673,P =0.04) were independent prognostic factors.Conclusions Though patients with pancreatic adenocarcinoma who undergo EDP have a worse pathologic staging,they will gain a comparable long-term survival to the patients undergo DP.Tumor size and perioperative blood transfusions are independent prognostic factors.

Objective:To explore the relationship and underlying mechanism between exosomes derived from doxorubicin-resistant osteosarcoma cells and MDR1 and miRNAs. Methods:MG63 and U2OS cell lines were selected to construct doxorubicin-resistant strains, and the 50% inhibitory concentration (half maximal inhibitory concentration, IC 50) of drug-resistant and sensitive strains was detected by MTT, and fluorescence staining was performed at intervals of 15 min between 15 and 120 min to detect the change of fluorescence intensity. RT-PCR and Western Blot were used to detect the expression levels of MDR1 P-gp to verify the drug resistance of osteosarcoma cells. Exosomes were identified by particle size analysis and Western Bolt detection. The endocytosis of PKH26-labeled exosomes from doxorubicin-resistant cells was observed, and the proliferation level and migration of exosomes from doxorubicin-resistant cells co-cultured with osteosarcoma cells were detected by MTT assay and cell scratch assay. The differential expression levels of miRNAs in osteosarcoma-sensitive and drug-resistant cells were verified by sequencing and bioinformatics analysis and RT-PCR assay. Tumor growth, serum exosome identification and mRNA expression level of miR-21-5p in tumor-bearing nude mice between normal osteosarcoma cell group and drug-resistant group, drug-resistant+normal exosome group, drug-resistant+drug-resistant+drug-resistant exosome group were observed. MDR1 expression level in tumor tissue was detected by RT-PCR, Western Blot and immunohistochemistry. Results:The IC 50 of two adriamycin resistant strains were 2.21 vs. 11.81 μg/ml and 0.93 vs. 11.81 μg/ml, respectively, and the fluorescence intensity decreased faster than that of normal strains. The relative mRNA expression levels of MDR1 in two cell lines were normal 1.12±0.16, 1.02±0.11 and drug-resistant 2.15±0.10, 2.127±0.12, respectively. The relative protein expression of P-gp was normal 0.92±0.11, 0.73±0.10 and drug-resistant 0.46±0.03, 0.30±0.04, the differences were statistically significant ( P<0.05). Drug-resistant exosomes can enter osteosarcoma cells through endocytosis and concentrate in the cytoplasm when co-cultured with normal strains. Osteosarcoma cells were co-cultured with drug-resistant exosomes at 2, 4, 6, and 8 μg/ml adriamycin, respectively. Compared with normal group, the proliferation level in drug-resistant group was significantly increased. Compared with the normal cell group 35.95±3.92, 6.72±3.55 and the normal exosome group 51.22±5.55, 19.31±1.93, the drug-resistant cell group 54.20±9.32, 19.24±2.88 and drug-resistant exosome group 76.40±5.41, 30.26±4.87, all had significantly higher cell mobility, the difference was statistically significant ( P<0.05). Exosome sequencing and biogenic analysis of 10 highly upregated miRNAs to validate mRNA expression differences between normal and drug-resistant strains by RT-PCR, showing a significant increase in miR-21-5p expression level of drug-resistant strains (5.89±0.26 vs. 0.99±0.06; 1.05±0.07 vs. 8.80±0.93, P<0.05), the difference was statistically significant ( P<0.05). In MG63 and U2OS, the normal cell group and drug-resistant cell group, and the normal exosome group and drug-resistant exosome group were compared, the tumor volume and the terminal tumor weight of nude mice were increased to varying degrees. MRNA relative expression levels of miR-21-5p in serum exosomes of nude mice after drug intervention were 0.86±0.07 and 0.86±0.05 in normal cell group, respectively. The values were 1.13±0.12, 1.14±0.12 in drug-resistant cell group, 0.71±0.05, 0.75±0.03 in normal exosome group, and 0.90±0.07, 0.93±0.04 in drug-resistant exosome group. Compared with normal and drug-resistant strains, the expression levels of normal and drug-resistant exosome groups were increased, with statistical significance ( P<0.05). Conclusion:The exosomes of drug-resistant cells in osteosarcoma could enhance the proliferation level and migration ability of cells through intercellular transfer of MDR1 and miRNAs. The expression of MDR1 and miR-21-5p in drug-resistant cells and tumor-forming nude mouse serum and tumor tissues were up-regulated which suggested that it might be involved in regulating the drug resistance process of osteosarcoma.

With the continuous progress of research methodology in the real world and the growing maturity of artificial intelligence technology， a method for conducting “quantitative” research to guide clinical practice based on traditional Chinese medicine （TCM） diagnosis and treatment data was gradually developed. However， there is still a need for further improvements in the overall design of studies and the transformation of findings into clinical practice. Based on this， we put forward a comprehensive overall design concept and application approach for real-world study and artificial intelligence research based on clinical diagnosis and treatment data of TCM. This approach consists of five steps： Constructing a research-based database with a large sample size and high data quality； Mining and classification of core prescriptions； Conducting cohort studies to evaluate the effectiveness of core prescriptions； Utilizing case-control studies to clarify the dominant population； Establishing predictive models to achieve precision medicine. Additionally， it is imperative for researchers to establish a standardized system for collecting TCM variables and processing data， optimize the determination and measurement methods of confounding factors， further improve and promote methodologies， and strengthen the training of interdisciplinary talents. By following this research method， we anticipate that the clinical translation of research findings will be facilitated， leading to advancements in TCM precision medicine. Real-world study and artificial intelligence research share similar research foundations， and clinical applications complement each other. In the future， the two will merge together.