Mechanism of total flavonoids of Rhododendra simsii in alleviating ischemic brain injury / 中国中药杂志

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.

Research progress of DNA methylation in the diagnosis of early colorectal cancer / 国际外科学杂志

Colorectal cancer is a common tumor of the digestive system with a high degree of malignancy. Most patients are in the advanced stages of the disease when they develop symptoms. Although the detection rate of traditional screening methods is improving with advances in imaging and the popularity of colonoscopy, the diagnosis of early, asymptomatic colon cancer is still unsatisfactory. Therefore, it is particularly important to further study the occurrence and development mechanism of colorectal cancer and obtain new ideas for the diagnosis and treatment.? In recent years, with the deepening of epigenetics research, the role of DNA methylation in the pathogenesis of colorectal cancer has gradually attracted attention. This paper will review the research progress of DNA methylation in colorectal cancer′s diagnosis and treatment.

Influence of fatty liver donor in the prognosis of benign liver disease liver transplantation / 国际外科学杂志

Objective:To explore the influence of fatty liver donor on the prognosis of benign liver disease liver transplantation.Methods:The clinical data of 229 recipients and donors who underwent liver transplantation at Beijing Chaoyang Hospital affiliated to Capital Medical University from January 2015 to December 2019 due to benign liver diseases were retrospectively analyzed. According to the degree of fatty degeneration of the donor liver, the patients were divided into non-fatty liver group( n=168), mild-medium fatty liver group( n=43), and severe fatty liver group( n=18). First, the overall prognosis after liver transplantation was analyzed, the general data of the donor and recipient were compared, and the perioperative complications of the three groups were compared. Finally, survival analysis was performed to compare the long-term prognosis of the three groups. Measurement data with the normal distribution were represented as ( Mean± SD), comparisons among groups were analyzed using t test. Comparisons of counting data between groups were analyzed using chi-square test. The theoretical frequency was less than 1. Fisher exact probability method was used, and variance analysis was used for the comparison among the multiple groups. Results:The overall 1-year, 3-year, and 5-year survival rates of the patients were 86.9%, 70.7%, 70.7%, respectively, and the average survival time was 53.1 months. The general data of donors and recipients were not significantly different among the three groups. The probability of perioperative transplanted liver failure, delayed liver function recovery, and acute kidney injury in recipients with severe fatty liver was significantly higher than that of mild to moderate fatty liver group and non-fatty liver group ( P<0.05). The results of survival analysis showed that the 1-year, 3-year, and 5-year survival rates of the non-fatty liver group were 90.5%, 71.7%, 71.7%, the mild-moderate group were 88.4%, 76.7%, 64.0% and the severe fatty liver group were 61.1%, 49.4%, 49.4%, the survival rate of patients with severe fatty liver was significantly lower than that of the other two groups ( P<0.05). Conclusion:Donor weight-grade steatosis leads to a higher incidence of transplanted liver failure, delayed liver function recovery, acute kidney injury, and worse long-term prognosis.

In vitro functional similarity assessment of a proposed biosimilar BAT1706 to bevacizumab / 药学学报

Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality, safety, and efficacy. BAT1706 is being developed by Bio-Thera Solutions, Ltd. as a proposed biosimilar candidate to bevacizumab reference product (Avastin®). Bevacizumab acts by specifically binding to vascular endothelial growth factor A (VEGF-A), and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells, then blocking the downstream signaling pathway mediated by ligand-receptor, and inhibiting endothelial angiogenesis, thus inhibiting tumor growth. Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin®. BAT1706 and Avastin® showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity, as well as inhibitory activity of VEGF receptor (VEGFR)-2 tyrosine kinase autophosphorylation. Both products exhibited similar binding of the Fcγ receptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Overall, the results demonstrate that BAT1706 and Avastin® are highly similar in terms of in vitro functional activities.

Correlation between preoperative CA19-9/GGT ratio and postoperative long-term survival of distal cholangiocarcinoma / 中华肝胆外科杂志

Objective:This research aimed to study the relationship between preoperative CA19-9/GGT ratio and postoperative long-term survival in patients with distal cholangiocarcinoma.Methods:The clinical data of 121 patients with distal cholangiocarcinoma who underwent radical pancreaticoduodenectomy (PD) at the Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2013 to December 2019 were retrospectively analyzed. The ROC curve was drawn based on the preoperative CA19-9/GGT ratio and postoperative 1-year survival. Using the best cut-off value of CA19-9/GGT ratio, the 121 patients were divided into two groups: the low ratio group (CA19-9/GGT≤0.12, n=53) and the high ratio group (CA19-9/GGT>0.12, n=68). The clinical data of the two groups were compared, and the risk factors of long-term survival were analyzed. Results:There were 72 male and 49 female patients, aged (64.9±9.2) years. When compared with the high ratio group, the low ratio group had significantly less requirement for preoperative jaundice reduction, lower CA19-9, higher GGT, better tumor differentiation, and more patients without lymph node metastasis (all P<0.05). The median follow-up time was 26 months. The 1-, 3- and 5-year survival rates of the low vs. high ratio groups were 89.4% vs. 64.7%, 64.4% vs. 14.1%, 48.7% vs. 14.1%, respectively (all P<0.001). Multivariate analysis showed that CA19-9/GGT ratio>0.12 ( RR=2.802, 95% CI: 1.494-5.256), poor differentiation ( RR=1.855, 95% CI: 1.106-3.111) and lymph node metastasis ( RR=1.891, 95% CI: 1.129-3.169) were independent risk factors for long-term survival ( P<0.05). Conclusion:The ratio of CA19-9/GGT could be used as an index to predict long-term survival of patients with distal cholangiocarcinoma after PD. The smaller the ratio, the better was the long-term prognosis.

Study on potential mechanism of hyperoside on improving ischemia/reperfusion injury based on network pharmacology / 中国药理学与毒理学杂志

OBJECTIVE To predict the potential targets of hyperoside (Hyp) on improving ischemia/reperfusion injury by network pharmacology, and explore its possible mechanism combined with related literature. METHODS The action targets of Hyp and ischemia/reperfusion injury were obtained by TCMSP, Swiss Target Prediction, Pharm Mapper, Simi?larity ensemble approach, Online Mendelian Inheritance in Man, DisGENT and database. The common targets of drugs and diseases were screened by Omishare and STRING database respectively, and the protein-protein interaction (PPI) network map was constructed. Then the interaction network between Hyp and disease targets was constructed by Cyto?scape software and topological cross-linking analysis was carried out. Then the interaction network between Hyp and disease targets was constructed and cross-linked analysis was carried out by using Cytoscape software. The gene ontol?ogy (GO) of the core target was analyzed by David database, and then the related pathways of the core target were enriched by KEGG database. RESULTS A total of 54 GO enrichment processes were obtained by GO enrichment anal?ysis of 44 common genes, including 38 biological processes (BP), 15 cell composition (CC) processes, and 1 molecular functional (MF) process. 43 items were obtained by signal pathway enrichment analysis in KEGG database. CONCLU?SION It is suggested that the mechanism of Hyp may be related to PI3K-Akt, RAP1, RAS, VEGF and other signal trans?duction pathways. The above results laid a theoretical foundation for the study of the mechanism and clinical application of the treatment of ischemia/reperfusion injury.

Effects of total flavonoids of Rhododendra simsii on ameliorating brain injury via G protein-coupled SOCE pathway mediated by STIM and Orai in subacute phase of ischemia/reperfusion / 中国药理学与毒理学杂志

OBJECTIVE To explore the effect of total flavonoids of Rhododendra simsii (TFR) on improving cerebral ischemia/reperfusion injury (CIRI) and its relationship with STIM/Orai-regulated operational Ca2+influx (SOCE) pathway. METHODS Oxygen-glucose deprivation/reoxygenation (OGD/R) PC12 cells were used to simulate CIRI in vitro, and the intracellular Ca2+ concentration and apoptosis rate of PC12 cells were detected by laser confocal microscope and flow cytometry, respectively. The regulation of STIM/Orai on SOCE was analyzed by STIM/Orai gene silencing and STIM/Orai gene overexpression. The CIRI model was established by MCAO in SD rats. The activities of inflammatory cyto?kines IL-1, IL-6 and TNF-αin serum were detected by ELISA. The pathological changes of ischemic brain tissue and the infarction of rat brain tissue were detected by HE staining and TTC staining. The protein and mRNA expression levels of STIM1, STIM2, Orai1, caspase-3 and PKB in brain tissue were detected by Western blotting and RT-qPCR, respectively. RESULTS The results of in vitro experiment showed that the fluorescence intensity of Ca2+ and apoptosis rate in PC12 cells treated with TFR were significantly lower than those in OGD/R group, and this trend was enhanced by SOCE antagonist 2-APB. STIM1/STIM2/Orai1 gene silencing significantly reduced apoptosis and Ca2+overload in OGD/R model, while TFR combined with overexpression of STIM1/STIM2/Orai1 aggravated apoptosis and Ca2+overload. In the in vivo experiment, TFR significantly reduced the brain histopathological damage, infarction of brain tissue, the contents of IL-1, IL-6 and TNF-α in the serum in MCAO rats and down-regulated the expression of STIM1, STIM2, Orai1 and caspase-3 protein and mRNA in the brain tissue, and up-regulated the expression of PKB. The above effects were enhanced by the addition of 2-APB. CONCLUSION The above results indicate that TFR may reduce the contents of inflammatory factors and apoptosis, decrease Ca2+ overload and ameliorate brain injury by inhibiting SOCE pathway mediated by STIM and Orai, suggesting that it has a protective effect against subacute CIRI.

Risk factors of lymph node metastasis in distal cholangiocarcinoma / 中华普通外科杂志

Objective:To analyze the risk factors of lymph node metastasis of distal cholangiocarcinoma.Methods:We retrospectively analyzed the clinical data of 123 patients of distal cholangiocarcinoma in Beijing Chaoyang Hospital between Jan 2011 and Dec 2019. All patients underwent pancreatoduodenectomy. The prognosis was evaluated according to the follow-up results. The survival rate was compared by log-rank test. Logistic regression was used to analyze the risk factors for lymph node metastasis.Results:One hundred and twenty-three patients successfully underwent the operations, 6 patients died during the perioperative time. The overall 1-year, 3-year and 5-year survival rates were 75.2%, 41.9% and 31.5%. The median survival time was 44.7 months. Fifty-one patients had lymph node metastasis, and the rate of lymph node metastasis was 41.5%. The median survival time was 55.5 months and 27.5 months for patients without and with lymph node metastasis, respectively. Correspondingly, the survival rates of 1-year, 3-year, 5-year were 83.0%, 50.7%, 42.5% vs. 63.5%, 19.0%, 19.0% ( P=0.000). Multivariate analysis showed that preoperative CA19-9 ( RR=7.064, 95% CI: 2.489-20.051) and portal venous system invasion ( RR=4.610, 95% CI: 1.252-16.972) were independent risk factors for lymph node metastasis. Conclusions:Lymph node metastasis is an important factor affecting the long-term survival of patients with distal cholangiocarcinoma. Preoperative CA19-9 level and portal venous system invasion are independent risk factors for lymph node metastasis.

Prognosis and related risk factors in patients who underwent surgical resection for pancreatic cancer with portal vein invasion / 中华肝胆外科杂志

Objective:To evaluate the prognosis and related risk factors in patients who underwent surgical resection for pancreatic cancer with portal vein invasion.Methods:The clinical data of 66 patients with pancreatic cancer with portal vein invasion who underwent pancreatic combined with vascular resection and reconstruction at the Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University between January 2011 and December 2018 were retrospectively studied. There were 30 males and 36 females. Their age ranged from 35 years to 81 years, with a mean of 61.5 years. Post-operative survival outcomes were evaluated on follow-up, and the related risk factors for prognosis were analyzed. Kaplan-Meier method was used to construct survival curves, and the survival rates were compared by the log-rank test. Multivariate Cox regression was used to analyze prognostic factors.Results:All 66 patients successfully underwent the operations. There was no perioperative death. The postoperative complication rate was 28.8% (19/66). Sixty-five patients were followed up (follow-up rate 98.5%, 65/66). The overall 1-, 2- and 3-year survival rates were 53.3%, 30.4%, 23.4%, respectively, with a median survival of 13 months. Multivariate analysis showed that preoperative CA19-9 >400 U/ml ( RR=1.871, 95% CI: 1.123-3.117) and depth of venous invasion ( RR=1.713, 95% CI: 1.072-2.736) were independent risk factors of prognosis. The higher the preoperative CA19-9, and the deeper the venous invasion, the worse was the prognosis. Conclusion:Long-term prognosis of pancreatic carcinoma patients with portal vein invasion was poor. Preoperative CA19-9 >400 U/ml and depth of vascular invasion were the main risk factors of prognosis for patients with pancreatic carcinoma and portal vein invasion after surgical resection.

Clinical value of surgical treatment for pancreatic carcinoma with portal venous system invasion / 中华胰腺病杂志

Objective:To analyze the value and significance of surgical operation in the treatment of pancreatic carcinoma with portal venous system invasion.Methods:The clinical data of 66 patients of pancreatic carcinoma with portal venous system invasion admitted in Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2011 to December 2018 were retrospectively analyzed. Vascular resection and reconstruction was used on all patients who underwent radical resection for pancreatic carcinoma (portal vein system invasion group). The operation procedure was made according to the location of the pancreatic carcinoma, and the vascular reconstruction procedure was made according to the type and location of portal venous system invasion. The intraoperative and perioperative situation of the patients were analyzed. Then 129 patients of pancreatic carcinoma without portal venous system invasion in the same period were selected as the control group, and the long-term prognosis between the two groups was compared.Results:The operation was successfully in 66 patients. According to the location of the pancreatic carcinoma, 55 patients underwent pancreatoduodenectomy, 8 patients underwent total pancreatoduodenectomy and 3 patients underwent distal pancreatectomy. According to the type and location of portal venous system invasion, 43 patients underwent allogeneic vascular replacement, 16 patients underwent segmental resection with end-to-end anastomosis, and 7 patients underwent wedge resection with primary closure. There was no perioperative death in this group. The incidence of postoperative complications was 28.8%(19/66), and the incidence of biochemical fistula was 9.1%(6/66), intraperitoneal infection was 7.6%(5/66), intraperitoneal hemorrhage was 4.5%(3/66), delayed gastric emptying was 4.5%(3/66), pancreatic fistula of Grade C was 1.5%(1/66) and biliary fistula was 1.5%(1/66). All the patients were discharged successfully, and the postoperative hospital stay was (20.8±9.7) days. 65 patients were followed up, and the follow-up rate was 98.5%. The median survival time of portal venous system invasion group and control group was 13 months and 22 months, respectively. The overall 1-year, 2-year and 3-year survival rates of portal venous system invasion group and control group were 53.3%, 30.4%, 23.4% and 73.1%, 45.8% and 40.1%, respectively ( P=0.006). Conclusions:Prognosis of pancreatic carcinoma patients with portal venous system invasion was poor, but it was safe and feasible to perform surgery for such patients. During the operation, different ways of venous reconstruction can be used according to the specific situation of venous invasion.

Identification of the feature genes of pancreatic cancer-associated diabetes mellitus based on the pancreatic cancer cohort from TGCA / 中华胰腺病杂志

Objective:To investigate the genetic characteristics of pancreatic cancer-associated diabetes mellitus (PCDM) and screen out the possible molecular markers for PCDM.Methods:The clinical data of pancreatic cancer (PC) cohort from The Cancer Genome Atlas (TCGA) were selected and collected, and the patients were divided into PCDM( n=11) and PC groups( n=109) according to whether the patients were diagnosed as diabetes within 2 years of PC diagnosis. Then, the mRNA microarray data of genome expression were extracted from TCGA PC cohort, and the differentially expressed genes (DEGs) were screened out by the " limma" package of R software based on (|log2 fold change|>2 and P<0.05). The functions of DEGs were revealed with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, a protein-protein interaction (PPI) network was constructed with the STRING database, and the hub genes were identified by the molecular complex detection (MCODE) module of Cytoscape software. Results:The analysis showed that among 20 531 genes, 47 genes were significantly upregulated, and 60 genes were significantly downregulated in the PCDM group. GO analyses revealed that 107 DEGs were mainly involved in the positive regulation of secretory function in terms of biological function (gene number=9, P<0.01); in the regulation of receptor function of molecular function (gene number=10, P<0.01); and in the intracavitary components of cytoplasmic microtubules of cellular components (gene number=8, P<0.01). The results of KEGG pathway enrichments revealed that DEGs mainly affected PCDM via cytokine interactions (gene number=8, P<0.01). Finally, five hub genes, including GNG8, CNR2, GALR2, CXCL13, and NPY2R, were identified for PCDM in PPI network analysis. Conclusions:The feature genes of PCDM are mainly different from PC in terms of secretion function, receptor function, cytoplasmic microtubule composition, and cytokine interaction. Five genes including GNG8, CNR2, GALR2, CXCL13, and NPY2R may become potential molecular markers for PCDM.

Mechanism and treatment of anastomotic scar after choledochostomy / 国际外科学杂志

Choledochojejunostomy is used in biliary diseases and part of the pancreas disease after surgical treatment of biliary reconstruction, the process of healing of biliointestinal anastomosis, involves a variety of inflammatory factors and different regulatory pathways, and eventually scarring is inevitable. Excessive scar response will result in anastomotic scar stricture, which will have to be treated..At present, interventional therapy is the main method to treat the scar stricture of biliointestinal anastomosis.On the whole, the treatment of bilioenteric anastomotic scar is relatively lagging behind, and there are many potential early treatment options worthy of attention, in order to better prevent and treat scar.The purpose of this article is to review the mechanism and treatment of choledochojejunostomy and anastomotic scar formation.

Prognosis and related risk factors of distal cholangiocarcinoma after surgical treatment / 国际外科学杂志

Objective:To evaluate the prognosis and related risk factors of distal cholangiocarcinoma after surgical treatment.Methods:The clinical data of 123 patients of distal cholangiocarcinoma in Beijing Chaoyang Hospital between January 2011 and December 2019 were retrospectively analyzed, which including 72 males and 51 females, the average age was (64.9±9.2) years (range from 29 to 84 years). All patients underwent pancreatoduodenectomy. The observation measures contains: (1) Perioperative outcomes; (2) Follow-up outcomes; (3) Risk factors for long-term survival of distal cholangiocarcinoma. Follow-up was carried out to understand the long-term survival of patients, and follow-up method contains the outpatient reexamination and telephone. The deadline of follow-up date was March 2020. The normal distribution data were expressed by ( Mean± SD), and the non-normal distribution data were expressed by M ( P25, P75). Count data were expressed by cases and percentage. Kaplan-Meier method was used to calculate and draw the survival curve. Log-rank test was used to compare the survival rate. Cox proportional risk model was used in multivariate factor analysis. Results:(1) Perioperative outcomes: In our research, all of 123 patients were successfully completed the operations, and 6 patients dead during the perioperative. (2) Follow-up outcomes: The incidence of postoperative complications was 27.6%(34/123). One hundred and twenty-one patients were followed up, the follow-up rate was 98.4%, and the median follow-up time was 41.0 months.The overall 1-year, 2-year, 3-year and 5-year survival rates were 71.8%, 50.5%, 35.5% and 30.2%. And the median survival time was 42.7 months. (3) Risk factors for long-term survival of distal cholangiocarcinoma: Multivariate analysis showed that preoperative CA19-9 ( RR=1.470, 95% CI: 1.028-2.101), portal venous system invasion ( RR=2.020, 95% CI: 1.012-4.035) and tumor differentiation ( RR=1.735, 95% CI: 1.195-2.520) were independent risk factors for the prognosis. Conclusions:Radical pancreatoduodenectomy is the best treatment for distal cholangiocarcinoma. Preoperative CA19-9 level, portal venous system invasion and tumor differentiation are independent risk factors for the prognosis.

Application of FOLFIRINOX regimen in conversion therapy of unresectable pancreatic cancer / 国际外科学杂志

Pancreatic cancer is a common malignant tumor of the digestive system with high degree of malignancy and difficulty in diagnosis.Patients with unresectable pancreatic cancer can regain the opportunity to receive surgical treatment with a combination of treatments known as conversion therapy. FOLFIRINOX regimen (Oxaliplatin+ Irinotecan+ 5-Fluorouracil+ Calcium folate) is an effective convesion therapy for unresectable pancreatic cancer, increasing surgical resection rate and prolongation of survival.This review aims to review the application of the FOLFIRINOX regimen in conversion therapy of unresectable pancreatic cancer.

Expression of plasma Dickkopf-1 in patients with rheumatoid arthritis and its correlation with peripheral blood T cell subsets / 北京大学学报(医学版)

OBJECTIVE@#To detect the levels of Dickkopf-1 (DKK-1) in the plasma of patients with rheumatoid arthritis (RA), and to analyze their correlation with peripheral blood T cell subsets and clinical indicators.@*METHODS@#Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma DKK-1 levels in 32 RA patients and 20 healthy controls, and to record the various clinical manifestations and laboratory indicators of the RA patients, and flow cytometry to detect peripheral blood T cell subsets in the RA patients (Including Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4+CD161+T, CD8+T, CD8+CD161+T cells). The plasma DKK-1 levels between the two groups were ompared, and its correlation with peripheral blood T cell subsets and clinical indicators analyzed.@*RESULTS@#(1) The plasma DKK-1 concentration of the RA patients was (124.97±64.98) ng/L. The plasma DKK-1 concentration of the healthy control group was (84.95±13.74) ng/L. The plasma DKK-1 level of the RA patients was significantly higher than that of the healthy control group (P < 0.05), and the percentage of CD8+CD161+T cells in the peripheral blood of the RA patients was significantly higher than that of the healthy control group (P < 0.05). (2) The plasma DKK-1 level was positively correlated with erythrocyte sedimentation rate (r=0.406, P=0.021), DAS28 score (r=0.372, P=0.036), immunoglobulin G(r=0.362, P=0.042), immunoglobulin A(r=0.377, P=0.033); it had no correlation with age, course of disease, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptide antibody, immunoglobulin M, complement C3, complement C4, white blood cell, neutrophil ratio. (3) The plasma DKK-1 level in the RA patients was positively correlated with the percentage of peripheral blood CD161+CD8+T cells (r=0.413, P=0.019);it had no correlation with Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4+CD161+T, CD8+T cells. (4) The percentage of CD161+CD8+T cells was negatively correlated with erythrocyte sedimentation rate (r=-0.415, P=0.004), C-reactive protein (r=-0.393, P=0.007), DAS28 score(r=-0.392, P=0.007), rheumatoid factor (r=-0.535, P < 0.001), anti-citrullinated protein antibody (r=-0.589, P < 0.001), immunoglobulin G(r=-0.368, P=0.012) immunoglobulin M (r=-0.311, P=0.035); it had no correlation with age, disease course, immunoglobulin A, complement C3, complement C4, white blood cell, and neutrophil ratio.@*CONCLUSION@#RA patients' plasma DKK-1 levels and the percentage of CD8+CD161+T cells in T cell subsets in peripheral blood increase, which may be related to the secretion of proinflammatory cytokines in patients; DKK-1 is involved in the regulation of bone homeostasis and can be used as a marker of bone destruction in RA.

Role of Gq-PLC-IP3 signal transduction pathway in calcium-sensing receptor-mediated proliferation of A549 cells / 解剖学报

Objective: To explore the signal transduction pathway of calcium-sensing receptor (CaSR) mediating hypoxia-induced proliferation of A549 cells of human non-small cell lung cancer. Methods: The A549 cells were randomly divided into several groups which conclude control group, hypoxia group (H), hypoxia + CaSR agonist group (H + Gd), hypoxia + CaSR inhibitor group (H + NPS) and phospholipase C(PLC) pathway inhibitor group (H + Gd +U73122). Expression of CaSR and proliferating cell nuclear antigen (PCNA) in A549 cells under different treatments was analyzed by Western blotting. The changes of intracellular calcium ion concentration were detected by confocal laser scanning microscope. The effects of cell proliferation cycle and proliferation index were gauged by flow cytometry under different drugs. HE staining was used to observe the changes of cell number with different drugs. Results: The expression levels of CaSR and PCNA in A549 cells increased by hypoxia. Meanwhile, cell proliferation index and cell number were also upregulated. GdCl3(CaSR agonist) could amplify the effect of hypoxia, and NPS2390 (CaSR inhibitor) could reduce the effect of hypoxia. All effects mentioned above could be inhibited by U73122 (PLC pathway inhibitor). Conclusion: Hypoxia-induced CaSR can mediate the proliferation of A549 cells through Gq-PLC-IP, signal transduction pathway.

Research on patent quality of Chinese listed traditional Chinese medicine enterprises from R&D investment perspective / 中国中药杂志

In recent years,the number of patent applications for traditional Chinese medicine( TCM) inventions has increased rapidly,but the authorization rate has declined. Listed TCM enterprises are a group of active innovators in this field,so this paper analyzes their patent quality by combining patent application and authorization with R&D investment of enterprises in order to explore a practical way to improve the quality of TCM patents. The conclusions are as follows: the R&D investment of listed TCM enterprises is insufficient and the gap between enterprises is large; the number of patent applications is within a reasonable range,but some enterprises still have abnormal patent applications,and patent quality needs to be improved; in addition,the patent operation capacity of enterprises still needs to be improved. In this phenomenon,enterprises should improve R&D investment,strengthen the level of technological innovation,improve the ability of patent operation,and consciously eliminate the output of " abnormal patents"; the patent administrative department should optimize policy direction which is beneficial to the improvement of patent quality,grasp the normal and reasonable examination scale,and jointly improve the quality of TCM patents.

Response to US review rules on patent subject matter of traditional Chinese medicine compositions / 中国中药杂志

The United States Patent and Trademark Office(USPTO) issued Interim Guidance on Patent Subject Matter Eligibility on December 16， 2014， bringing certain effects to the review rules on patent application of Chinese medicine compositions. Based on the Interim Guidance， cases analysis was used in this paper to analyze the patent subject matter issues of traditional Chinese medicine compositions in the United States. The researches have shown that the application documents should be properly written in the United States when the patent for Chinese medicine compositions is applied， which can improve the probability of authorization.

Expressions and clinical significance of GAS1, IL-1RAP and PRF1 in patients with ALK positive anaplastic large cell lymphoma / 中华血液学杂志

Objective@#To investigate the expressions of growth arrest-specific protein (GAS1), IL-1 receptor accessory protein (IL-1RAP) and perforin (PRF1) in patients with anaplastic lymphoma kinase positive, anaplastic large cell lymphoma (ALK+ ALCL) and their relationships with clinical significances and the prognoses of ALK+ ALCL.@*Methods@#Twenty-six formalin-fixed paraffin-embedded (FFPE) samples of ALK+ ALCL patients who were diagnosed from January 2011 to September 2016 were collected. Twelve FFPE samples of patients with ALK+ALCL, 13 FFPE samples of patients with peripheral T cell lymphoma (not otherwise specified) (PTCL-NOS) and 8 FFPE samples of patients with angioimmunoblastic T-cell lymphoma (AITL) were used as control groups. RQ-PCR and immunohisto-chemical staining were used to detect the mRNA and protein expressions of GAS1, IL-1RAP and PRF1. The clinical data were analyzed.@*Results@#①The expression levels of GAS1, IL-1RAP and PRF1 gene and protein in ALK+ ALCL group were higher than those of the control groups (P<0.05), but the expression levels had no statistically significant differences between the control groups (P>0.05). ②Patients with elevated lactate dehydrogenase (LDH) (0.77 vs 1.38, z=-3.292, P=0.001) or International prognostic index (IPI)≥3(0.62 vs 1.29, z=-2.495, P=0.013) had lower expression level of GAS1. Patients with stage Ⅲ/Ⅳ disease (0.89 vs 1.18, z=-2.212, P=0.027) or IPI≥3 (0.48 vs 1.13, z=-2.008, P=0.045) had lower expression level of PRF1. IL-1RAP expression level was not associated with clinical features. ③ALK+ ALCL patients in complete remission (CR) group had higher expression levels of GAS1 and PRF1 than patients in non-remission (NR) group (P values were 0.016 and 0.009). ④Kaplan-Meier survival analysis showed that patients with high expression levels of GAS1 and PRF1 had longer median overall survival and progression-free survival than patients with low expression levels of GAS1 and PRF1.@*Conclusion@#GAS1, IL-1RAP and PRF1 could be molecular markers for ALK+ ALCL patients. They have potential diagnostic value and can be used for differential diagnosis in some difficult cases. ALK+ ALCL patients with high expression levels of GAS1 or PRF1 have better curative effects and prognoses.

Content Determination of Four Index Components in Compound Baizhi Zhitong Capsules by QAMS Method / 中国中医药信息杂志

Objective To develop a new method for content determination of chlorogenic acid, ferulic acid, and isoimperatorin in Compound Baizhi Zhitong Capsules through quantitative analysis of multi-components by single-marker (QAMS) method by setting imperatorin as internal standard substance. Methods HPLC was adopted. The chromatographic column of Thermo Hypersil GOLD (4.6 mm×250 mm, 5 μm) was used; the mobile phase was composed of acetonitrile and 0.2％ formic acid in gradient elution; the flow speed was 1 m L/min; the detection wavelength were 320 nm (chlorogenic acid, ferulic acid) and 300 nm (imperatorin and isoimperatorin). The relative analysis correction factors of imperatorin to other three components were established by setting imperatorin as internal standard substance. Results The relative analysis correction factors of chlorogenic acid, ferulic acid, and isoimperatorin in Compound Baizhi Zhitong Capsules were 1.16, 2.00, and 1.00, which had a high reproducibility. There was no significant difference between QAMS and external standard method. Conclusion The QAMS method for Compound Baizhi Zhitong Capsules by setting imperatorin as internal standard substance is accurate and feasible, which can be used as a useful quality control method for Compound Baizhi Zhitong Capsules.