Effects of anlotinib on the malignant phenotype of glioma cells by mediating NF-κB signaling pathway / 中国药房

OBJECTIVE To investigate the effects of anlotinib on the malignant phenotype of glioma cells by regulating the nuclear factor-κB （NF-κB） signaling pathway. METHODS Human glioma T98G cells were cultured in vitro， and 5-fluorouracil was used as positive control to investigate the effects of different concentrations of anlotinib （5， 10， 20 μmol/L） on the ability of proliferation， adhesion， migration and invasion， the expressions of epithelial-mesenchymal transition （EMT） related proteins [E-cadherin， N-cadherin， vimentin and fibronectin （FN）]. NF- κB signaling pathway inhibitor （BAY 11-7082） and activator （prostratin） were additionally used to verify the possible mechanism of the above effects of anlotinib. RESULTS Anlotinib with 5， 10， 20 μmol/L could significantly decrease the activity of cell proliferation （except for 5 μmol/L anlotinib group）， migration rate， and the number of adherent cells and invasive cells， could significantly up-regulate the expression of E-cadherin protein while down-regulate the expressions of N-cadherin， vimentin and FN protein （P＜0.05）； the effect of 20 μmol/L anlotinib was similar to that of positive control （P＞0.05）. Compared with 10 μmol/L anlotinib， pathway inhibitor could significantly decrease the ability of proliferation， adhesion， migration and invasion， and the expressions of N-cadherin， vimentin， FN and phosphorylated NF-κB p65 protein， while could significantly up-regulate the expression of E-cadherin protein （P＜0.05）； above indexes were reversed significantly by pathway activator （P＜0.05）. CONCLUSIONS Anlotinib may inhibit the proliferation， adhesion， migration and invasion of human glioma T98G cells， which may be associated with the inhibition of the NF-κB signaling pathway， thus inhibiting cell EMT-like processes.

Clinical Characteristics of Chronic Myeloid Leukemia Patients with Deletion and Non-deletion of ASS Gene on Derivative Chromosome 9 / 肿瘤防治研究

Objective To investigate the clinical characteristics of patients with chronic myeloid leukemia (CML) in chronic phase with deletion and non-deletion of the argininosuccinate synthesis gene (ASS gene) on the derivative chromosome 9. Methods The clinical data of patients with CML initially treated with imatinib and BCR/ABL1/ASS1 3-color fusion probe to detect ASS gene deletion were analyzed. The patients were divided into deletion group (n=27) and non-deletion group (n=92). Clinical characteristics, treatment effects, and prognosis were analyzed. Results The average age of 119 patients was 37.22±12.72 years old. The sokal score differed between the deletion and non-deletion groups (χ2=4.304, P=0.038). No statistically significant difference in other general characteristics was found (P > 0.05). The 3-month CCyR rate, 6-month CCyR rate, and BCR-ABLIS≤ 1% rate in the deletion group were lower than those in the non-deletion group (P < 0.05). The median follow-up of 119 patients was 35.0 (3.0-60.0) months. The PFS in the deletion group was lower than that in the non-deletion group (χ2=4.293, P=0.038). Overall survival was not significantly different between the two groups (χ2=0.008, P=0.931). Conclusion The deletion of the ASS gene in patients with chronic CML is related to the poor efficacy of imatinib treatment, poor prognosis, and high risk of disease progression.

Research progress on the application of combining radiotherapy and systemic therapy in breast cancer / 国际肿瘤学杂志

Compared with single therapy, radiotherapy combined with chemotherapy, endocrine therapy, molecular targeted therapy and immunological therapy can not only shorten the treatment cycle, but also improve the local control rate and prolong the survival of patients. However, the safety of combined therapy still needs to be further clarified to comprehensively evaluate the feasibility. Therefore, exploring the efficacy and safety of radiotherapy combined with systematic therapy will provide evidence for clinical benefits.

Factors affecting the geometry variations of surgical clips in radiotherapy after breast-conserving surgery / 中华放射医学与防护杂志

Objective:To investigate the variations and related influencing factors of the volumes, positions, and morphologies of geometries formed by surgical clips in intensity-modulated radiation therapy (IMRT) for whole breasts after breast-conserving surgery.Methods:A retrospective analysis was conducted on 18 patients treated with IMRT from October 2021 to September 2022 after breast-conserving surgery. Set-up errors were obtained by reading the coordinate information of tumor bed surgical clips according to the cone beam CT (CBCT) images at 0, 10, 20, 30, 40, and 50 Gy sequentially. Geometries were constructed using the convex hull program, and the volumes ( Vct and V0-5) of geometries were then calculated based on the localization CT images and the six CBCT images, respectively. The centroid displacements ( D0-5) and degrees of inclusion ( DI0-5) of these geometries were compared. The t-test or rank-sum test was used to analyze the effects of radiation doses on V0-5, D0-5, and DI0-5. The Pearson correlation analysis was conducted to analyze the correlations between D0-5 and corresponding set-up errors in three-dimensional directions, and the correlations of average V0-5 variation ( AV), average D0-5 ( AD), and average DI0-5 ( ADI) with the body mass index (BMI), the volume of a breast ( VB), the breast axial height ( H), and the time interval from surgery to radiotherapy ( T) each. The influences of quadrants ( Q) where geometries are located and states ( S) of geometries adhering to or away from the chest walls on AV, AD, and ADI were analyzed through one-way ANOVA. Results:The differences between D5 and D0, between D5 and D1, and between D5 and D2 were statistically significant ( t = -3.27, -4.52, -3.38, P < 0.05), respectively. The differences between DI5 and DI0, between DI5 and DI1, between DI5 and DI2 were statistically significant ( t = 2.53, 2.70, 2.64, P < 0.05), respectively. D1 and D4 correlated with the set-up errors in the superior-inferior dimension, and D3 correlated with the set-up errors in the left-right dimension ( r = 0.50, 0.56, 0.53, P < 0.05). The AD was related to BMI, VB, and H ( r = 0.54, 0.48, 0.50, P < 0.05). There were statistically significant differences in AV and ADI of geometries away from ( S3) and near ( S2) chest walls ( F = 2.66, 3.83, P < 0.05). The AD differences of geometries between S3 and the state adhering to chest walls ( S1) and between S3 and S2 were statistically significant ( F = 7.46, P < 0.05), respectively. Conclusions:The geometries are relatively constant volumes during whole-breast radiotherapy. However, their positions and morphologies vary greatly in the late course. The volume variation ratios, centroid displacements, and degrees of inclusion of geometries are all affected by the states of their attachments to the chest walls. The centroid displacements correlate with breast morphologies and BMI. The radiotherapy plan modification can be individualized.

Construction of a nomogram prediction model for survival after radical surgery for intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To study the factors influencing survival after radical resection in patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram on survival prediction.Methods:The clinical data of 139 patients with ICC who underwent radical resection at the People's Hospital of Zhengzhou University from June 2018 to December 2021 were retrospectively analyzed. There are 69 males and 70 females, aged (59.5±10.2) years old. These patients were divided into two groups based on a 3: 1 ratio by using the random number method: the test group ( n=104) and the validation group ( n=35). Data from the test group was used to construct a nomagram and data from the validation group was used to validate the predictive power of the nomagram. Univariate and multivariate Cox regression analyses were used to analyse factors influencing survival on the test group patients and to construct a nomogram. The predictive accuracy of the nomogram was determined by receiver operating characteristic (ROC) curves, concordance index (C-index) and calibration curves. Results:The results of the multivariate regression analysis showed that a combined hemoglobin, albumin, lymphocyte and platelet immunoinflammation (HALP) score <37.1 ( HR=1.784, 95% CI: 1.047-3.040), CA19-9 > 35U/ml ( HR=2.352, 95% CI: 1.139-4.857), poorly differentiated tumor ( HR=2.475, 95% CI: 1.237-4.953) and vascular invasion ( HR=1.897, 95% CI: 1.110-3.244) were independent risk factors that affected prognosis of patients with ICC after radical resection (all P<0.05). The AUCs of the nomogram in the test group in predicting the overall survival at 1, 2 and 3 years of patients with ICC after radical resection were 0.808, 0.853 and 0.859, respectively. There was good consistency between the prediction of the nomogram and actual observation. The predicted C-index of the total survival period of the test group was 0.765 (95% CI: 0.704-0.826), and the C-index of the validation group was 0.759 (95% CI: 0.673-0.845). Conclusion:A HALP score <37.1, CA19-9>35 U/ml, poorly differentiated tumour and vascular invasion were independent risk factors for prognosis of ICC patients after radical resection. The nomogram was established based on the above factors and showed good performance in predicting overall survival after radical resection in patients with ICC.

Construction and evaluation of a nomogram prediction model for survival after radical surgical resection of intrahepatic cholangiocarcinoma based on the albumin-bilirubin index / 中华肝胆外科杂志

Objective:To construct a nomogram prediction model for survival after radical surgical resection of intrahepatic cholangiocarcinoma (ICC) based on the albumin-bilirubin index (ALBI), and to evaluate its predictive efficacy.Methods:From January 2016 to January 2020, 170 patients with ICC who underwent radical surgical resection at the People's Hospital of Zhengzhou University were retrospectively analyzed. There were 90 males and 80 females, aged (58.5±10.6) years old. Based on a ratio of 7∶3 by the random number table, the patients were divided into the training set ( n=117) and the internal validation set ( n=53). The training set was used for nomogram model construction, and the validation set was used for model validation and evaluation. Follow up was conducted through outpatient reexamination and telephone contact. The Kaplan-Meier method was used for survival analysis, and a nomogram was drawn based on variables with a P<0.05 in multivariate Cox regression analysis. The predictive strength of the predictive model was evaluated by analyzing the consistency index (C-index), calibration curve, and clinical decision curve of the training and validation sets. Results:Multivariate Cox regression analysis showed that carbohydrate antigen 19-9 (CA19-9) ≥37 U/ml ( HR=1.99, 95% CI: 1.10-3.60, P=0.024), ALBI≥-2.80 ( HR=2.43, 95% CI: 1.40-4.22, P=0.002), vascular tumor thrombus ( HR=2.34, 95% CI: 1.40-3.92, P=0.001), and the 8th edition AJCC N1 staging ( HR=2.18, 95% CI: 1.21-3.95, P=0.010) were independent risk factors affecting postoperative survival of ICC patients after curative resection. The predictive model constructed based on the above variables was then evaluated, and the C-index of the model was 0.76. Calibration curve showed the predicted survival curve of ICC patients at 3 years after surgery based on the model was well-fitted to the 45° diagonal line which represented actual survival. Clinical decision curve analysis showed that the model had a significant positive net benefit in both the training and validation sets. Conclusion:The nomograph model for survival rate after radical resection of ICC was constructed based on four variables: ALBI, CA19-9, vascular tumor thrombus, and AJCC N staging (8th edition) in this study. This model provided a reference for more accurate prognosis evaluation and treatment selection plan for ICC patients.

Inflammatory markers-based preoperative differentiation model of intrahepatic cholangiocarcinoma and combined hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To establish and validate a preoperative differentiateon model of intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular carcinoma (CHC) based on the inflammatory markers and conventional clinical indicators.Methods:The clinical data of 116 patients with ICC or CHC admitted to Henan Provincial People's Hospital from January 2018 to March 2023 were retrospectively analyzed, including 74 males and 42 females, aged (58.5±9.4) years old. The data of 83 patients were used to establish the differentiation model as the training group, including 50 cases of ICC and 33 cases of CHC. The data of 33 patients were used to validate the model as the validation group, including 20 cases of ICC and 13 cases of CHC. The clinical data including the platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), prognostic inflammatory index (PII), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were collected and analyzed. The receiver operating characteristic (ROC) curve was used to analyze the best cut-off values of PLR, SII, PII, PNI, NLR and LMR. Univariate and multivariate logistic regression analysis were used to determine the differential factors between ICC and CHC. The R software was used to draw the nomogram, calculate the area under the curve (AUC) to evaluate the model accuracy, and draw the calibration chart and the decision curve to evaluate the predictive efficacy of the model.Results:Univariate logistic regression analysis showed that liver cirrhosis, history of hepatitis, alpha fetoprotein, carbohydrate antigen 199, gamma-glutamyltransferase (GGT), PLR, PNI and inflammation score (IS) could be used to differentiate ICC from CHC (all P<0.05). The indicators identified in univariate analysis were included in multivariate logistic regression analysis. The results showed that absence of liver cirrhosis, GGT>60 U/L, PNI>49.53, and IS<2 indicated the pathology of ICC (all P<0.05). Based on the above four factors, a nomogram model was established to differentiate the ICC and CHC. The AUC of ROC curve of the nomogram model in the training and validation groups were 0.851 (95% CI: 0.769-0.933) and 0.771 (95% CI: 0.594-0.949), respectively. The sensitivities were 0.760 and 0.750, and the specificities were 0.818 and 0.769, respectively. The calibration chart showed that the predicted curve fitted well to the reference line. The decision curve showed that the model has a clear positive net benefit. Conclusion:The nomogram model based on inflammatory markers showed a good differentiation performance of ICC and CHC, which could benefits the individualized treatment.

Effect of shikonin on inflammatory response in rats with knee osteoarthritis by regulating NF-κB/ERK signaling pathway / 中国免疫学杂志

Objective:Constructing a rat model of knee osteoarthritis,to explore effects of shikonin on inflammatory response,NF-κB/extracellular regulated protein kinase(ERK)pathway in knee osteoarthritis rats,and the possibility of NF-κB/ERK signaling pathway as a new target for shikonin.Methods:Seventy-two male SD rats were collected,and randomly separated into sham operation group,arthritis group,nimesulide group,shikonin group,shikonin+ERK activation group and shikonin+NF-κB activation group,with 12 rats per group.A rat model of knee osteoarthritis was constructed,and the arthritis indexes of rats in each group were evaluated to judge the model construction;safranin fast green staining and HE staining were performed to observe the pathology of knee cartilage of rats in each group;ELISA was performed to measure levels of IL-1β,IL-6 and TNF-α in serum and cartilage tissue of rats in each group;Western blot was performed to measure NF-κB p65,ERK,p-NF-κB p65 and p-ERK protein expressions in cartilage tissue.Results:Cartilage tissue of rats in sham operation group had no obvious protrusions,and the safranine staining was completely stained;compared with sham operation group,cartilage of arthritis group showed protrusions,and the staining was completely lost,the arthritis index,serum and cartilage tissue TNF-α,IL-6,IL-1β contents,cartilage tissue NF-κB p65,ERK protein phosphoryla-tion degrees were increased significantly(P<0.05);compared with arthritis group,cartilage tissue of nimesulide group and shikonin group gradually recovered,the safranine staining was increased,the arthritis index,serum and cartilage tissue TNF-α,IL-6,IL-1β contents,cartilage tissue NF-κB p65,ERK protein phosphorylation degrees were reduced significantly(P<0.05);compared with shi-konin group,shikonin+ERK activation group and shikonin+NF-κB activation group showed a slower recovery of cartilage tissue and se-rious loss of safranine staining,the arthritis index,serum and cartilage tissue TNF-α,IL-6,IL-1β contents,cartilage tissue NF-κB p65,ERK protein phosphorylation degrees were increased significantly(P<0.05);there was no significant difference of each index be-tween shikonin group and nimesulide group(P>0.05).Conclusion:Shikonin can relieve knee osteoarthritis by regulating the NF-κB/ERK pathway and inhibiting the activation of related proteins.

Position of the diaphragm influenced by the filling degree of the abdominal and pelvic cavity / 中华放射医学与防护杂志

Objective:To explore the affects of the filling degree of the abdominal and pelvic cavity to the position of the diaphragm.Methods:The computed tomography (CT) images of 25 patients from 137 CT scans stored in the Picture Archiving and Communication System of the First Affiliated Hospital of Soochow University from March 2018 to September 2020 were reviewed and analyzed retrospectively. Every patient was scanned 4-7 times. The outline of the abdominal and pelvic cavity from the diaphragmatic dome to the superior margin of pubic symphysis was drawn at every cross section, and then the filling volumes of the abdominal and pelvic cavities and the overall filling volume were calculated. For the same patient within 4-7 CT scans, per pair of different images was compared randomly and 379 comparison pairs were obtained. The volume change rate (△ VR) of the abdominal and pelvic cavity and the height difference (△ H) of the diaphragmatic dome were calculated. The images with "larger overall filling volume of the abdominal and pelvic cavity and higher diaphragmatic dome" were defined as consistent group, and those with "larger overall filling volume and lower diaphragmatic dome" were defined as inconsistent group. The percentage of images in the consistent group in all samples and the percentage of images showing deep inspiration in the inconsistent group in all samples were calculated. △ VR and △ H were compared between the consistent and inconsistent groups. △ VR of the abdomen and pelvic cavities in the consistent group was compared using the Mann-Whitney test. The correlations between △ VR of the abdomen and pelvic cavities and the elevation of the diaphragmatic dome in the consistent group were analyzed using Spearman correlation analysis. The average elevation of the diaphragmatic dome in all samples and the consistent group was simulated if the filling volume of the abdomen and pelvic cavity was increased by 500 ml. Results:The percentage of images in the consistent group in all samples was 67.28%. The percentage of images showing deep inspiration in the inconsistent group in all samples was 26.39%. There were significant differences in △ VR and △ H of the abdomen and pelvic cavity between the consistent and inconsistent groups ( Z=-4.95, -5.49, P<0.05). In the consistent group, there were significant differences in △ VR between the abdominal cavity and pelvic cavity ( Z=-7.53, P<0.05), and the elevation of the diaphragmatic dome was correlated with the △ VR of the abdominal cavity ( rs=0.43, P<0.05). The simulated calculation showed that an average increase of 500 ml in the filling volume of the abdominal and pelvic cavity result ed in an average elevation of 4.54 and 8.43 mm in the diaphragmatic dome in all samples and the consistent group, respectively. Conclusions:The filling degree of the abdominal and pelvic cavity may be one of the main factors affecting the position of the diaphragm and the precision of radiotherapy for relevant organs near the diaphragm, especially the filling degree of the abdominal cavity. It is recommended to repeat the filling degree of the abdominal and pelvic cavity by CT localization scanning as much as possible during radiotherapy.

A simulation study on the position variations of skin markers at different parts relative to the pelvic cavity / 中华放射医学与防护杂志

Objective:To analyze the activity of skin markers at different parts of the body surface and the correlations between their displacement deviations and pelvic filling volumes during conventional abdominal and pelvic radiotherapy.Methods:A retrospective analysis was conducted on 15 patients receiving abdominal and pelvic radiotherapy with four times of computed tomography (CT) in the First Affiliated Hospital of Soochow University from January 2020 to January 2022. All CT images were divided into nine parts from the upper edge of L3 to the upper edge of the pubic symphysis: upper, middle, and lower parts in the right portion; upper, middle, and lower parts in the central portion; and upper, middle, and lower parts in the left part portions, No. 1-9 in sequence. The same blood-vessel or fascia intersection points near the same skin parts receiving the same dose fraction were used as the markers for skin positioning during simulated radiotherapy. The relative coordinates of the markers were measured, with the same point at the lower edge behind the L5 vertebral body set as the coordinate origin. Through pairwise comparison of each patient′s four CT images, the three-dimensional displacement deviations and activity were calculated for all markers. In the left-right (L-R), superior-inferior (S-I), and anterior-posterior (A-P) directions, the differences in the displacement activity of the markers in the nine parts were compared using both the non-parametric Kruskal-Wallis test and the Descriptives. The correlations between the three-dimensional displacement deviations of all markers and the A-P displacement deviations of the No. 5 marker were analyzed using the Pearson correlation analysis.Results:Differences existed in the displacement activity of the nine-part markers in the L-R, S-I, and A-P directions ( H=36.66, 66.20, 92.15, P<0.05). No. 3 and 9 markers exhibited lower overall three-dimensional displacement activity (median: 2.40-3.75 mm) than other markers. The No. 5 marker manifested the highest A-P displacement activity, with a median of 9.20 mm. The A-P displacement deviation of No. 5 marker was correlated using the L-R displacement deviations of the No. 1, 2, 3, 7, 8 and 9 markers ( r=-0.36 to 0.49, P<0.05), the S-I displacement deviations of the No. 4, 5, 6, and 9 markers ( r=-0.34 to -0.24, P<0.05), and the A-P displacement deviations of the No. 1, 2, 3, 4, 6, 7, 8 and 9 markers ( r=0.33-0.91, P<0.05). Conclusions:Skin markers drawn in bilateral acetabular regions serve as the best choices for reposition in pelvic radiotherapy. Conventional skin markers made at the central parts are prone to suffer deviations in the S-I direction due to the influence of the abdominal and pelvic filling volumes.

Construction and evaluation of a predictive nomogram model for the prognosis of intrahepatic cholangiocarcinoma patients undergoing curative resection based on the albumin-bilirubin score and tumor burden score grade / 中华肝胆外科杂志

Objective:A predictive nomogram model for the prognosis of intrahepatic cholangiocarcinoma (ICC) patients after curative resection was constructed based on the albumin-bilirubin score and tumor burden score (ATS) grade, and the predictive performance of the nomogram model was evaluated.Methods:Retrospective analysis of clinical data was made, from ICC patients who underwent curative resection at Zhengzhou University People's Hospital and Zhengzhou University Cancer Hospital from January 2016 to January 2020. A total of 258 patients were included in the study, with 140 males and 118 females, with an average age of (56.5±9.5) years. The 258 ICC patients were randomly divided into a training set ( n=174) and a testing set ( n=84) in a 7∶3 ratio. Single-factor and multi-factor Cox regression analyses were performed to identify prognostic factors for ICC patients of the training set, and then a nomogram model was constructed. The performance of the nomogram model was evaluated by using the concordance index (C-index), calibration curve, and risky decision curve analysis. Results:In the training set, univariate Cox regression analysis indicated that albumin-bilirubin (ALBI), tumor burden score (TBS), carcinoembryonic antigen (CEA), tumor differentitation, lymphvascular invasion and ATS significantly influenced overall survival after radical resection for ICC (all P<0.05). Multifactorial Cox regression analysis revealed that ATS grade, CEA, tumor differentiation, lymphovascular invasion, and AJCC N stage are independent risk factors for the prognosis of ICC patients after curative resection (all P<0.05). Assessment of the postoperative survival prediction model based on multifactorial Cox regression yielded a C-index of 0.775(95% CI: 0.747-0.841) for the training set and 0.731(95% CI: 0.668-0.828) for the testing set. The calibration curves for both the training and testing sets indicated strong predictive capability of the model. Additionally, the risk decision curve also suggested high net benefit of the model. Conclusions:The preoperative ATS grade is an independent factor affecting the survival after ICC radical resection. The nomogram model constructed based on ATS grade demonstrates excellent predictive value for postoperative prognosis in ICC patients.

Vasorelaxant effects and mechanism of polyphenol compound LM 49 on isolated thoracic aorta of rats / 中国药房

OBJECTIVE To study the vasorelaxant effects and mechanism of polyphenol compound 2，4′，5′-trihydroxy-5，2′- dibromo-diphenyl-methanone（LM49）on isolated aortic rings of rats. METHODS Thoracic aortic vascular rings of rats were collected. Using the diastolic rate as index ， the effects of different concentrations of LM 49 on endothelium-intact and endothelium-denuded aortic rings pre-contracted by norepinephrine （NE，1×10－6 mol/L）or KCl （60 mmol/L）were investigated. After pre-culturing vascular rings by nitric oxide synthase inhibitor L-nitro-arginine methyl ester （L-NAME，0.1 mmol/L） and cyclooxygenase inhibitor indomethacin （1×10－5 mol/L），as well as pre-culturing vascular rings by 4 potassium channel blockers [BaCl 2（0.1 mmol/L），tetraethylammonium（TEA，5 mmol/L），4-aminopyridine（4-AP，0.1 mmol/L）and glibenclamide （1×10－5 mol/L）]，the vasorelaxant effect of different concentrations of LM 49 on the vascular rings were investigated by using the same method. With the percentage of vasoconstriction as the index ，using KCl （60 mmol/L），NE（1×10－6 mol/L），calcium channel blocker verapamil （1×10－6 mol/L）and sarcoplasmic Δ 基金项目 重大新药创制国家科技重大专项 （No.2018ZX097- reticulum Ca 2 +-adenosine triphosphate （ATP） enzyme pump inhibitor thacarotene （TG，1×10－6 mol/L）to induce the release of calcium in vascular rings in the absence of calcium. CaCl was added cumulatively ，and the effect of LM 49 on the cxyw06，vasoconstriction caused by calcium influx induced by CaCl 2 was investigated. RESULTS 3×10－6，5×10－6，1×10－5 mol/L LM49 had a significant relaxation effect on NE and KCl precontracted vascular rings （P＜0.01）； whether the endothelium was removed or not had no significant effect on the vasodilation of LM 49（P＞0.05）. After L-NAME ，indomethacin， TEA and 4-AP was pre-incubated ，different concentrations of LM 49 had no significant effects on aortic rings precontracted by NE （P＞0.05）. Glibenclamide and BaCl 2 could inhibit the vasorelaxant effects of LM 49 on aortic rings precontracted by NE （P＜0.01）. In the absence of calcium ，LM49 could inhibit the contraction caused by calcium influx induced by accumulated CaCl 2 after pre-incubation with KCl ，NE，verapamil and TG （P＜0.01）. CONCLUSIONS LM49 evokes significant relaxation of isolated aortic vascular rings without endothelium dependence ；the mechanism of which is inducing ATP-sensitive potassium channel ， inward rectifier potassium channel open and restraining extracellular Ca 2 + influx via voltage-gated calcium channel ， receptor-operated calcium channel and store-operated calcium channel.

Risk factors of development of combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To determine the risk factors for development of combined hepatocellular-cholangiocarcinoma (CHC) and intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of patients with ICC or CHC confirmed by pathology at Henan Provincial People's Hospital from January 2012 to December 2018 were retrospectively analyzed. Of 225 patients with ICC or CHC, there were 90 males and 135 females, aged (58.7±10.4) years old. Based on the pathological type, there were 172 patients in the ICC group and 53 patients in the CHC group. The healthy control group was selected from 450 individuals who underwent routine health examination in the same hospital, and there were 189 males and 261 females, aged (56.7±9.3) years old. Univariate and multivariate logistic regression were used to analyze the risk factors of ICC and CHC.Results:The risk factors of ICC included hepatitis B surface antigen (HBsAg) (+ )/hepatitis B core antibody (anti-HBc) (+ ) ( OR=9.373, 95% CI: 4.784-18.363, P<0.001), hepatitis C virus antibody (HCV-Ab) (+ ) ( OR=7.151, 95% CI: 1.195-42.776, P=0.031), diabetes mellitus ( OR=3.118, 95% CI: 1.733-5.612, P<0.001) and hepatolithiasis ( OR=18.650, 95% CI: 5.210-66.767, P<0.001). The risk factors of CHC included HBsAg (+ )/anti-HBc(+ )( OR=54.891, 95% CI: 17.434-172.822, P<0.001) and HCV-Ab (+ ) ( OR=37.785, 95% CI: 5.720-249.611, P<0.001). Conclusion:HBV infection, HCV infection, hepatolithiasis, diabetes mellitus and cirrhosis were risk factors for ICC. HBV and HCV infection were risk factors of CHC.

Effect of down-regulation of lncRNA LINC00263 targeting miR-4458 on regulating radiosensitivity of breast cancer SK-BR-3 cells / 中华放射肿瘤学杂志

Objective:To evaluate the effect of down-regulating lncRNA LINC00263 targeting miR-4458 on the proliferation, migration, invasion and radiosensitivity of breast cancer SK-BR-3 cells.Methods:The expression differences of LINC00263 in breast cancer tissues, adjacent tissues, normal breast epithelial cells and breast cancer cells were determined by qRT-PCR. Transfection of LINC00263 shRNA in breast cancer SK-BR-3 cells down-regulated the expression of LINC00263, and the cloning experiment was used to detect the radiosensitivity. Breast cancer SK-BR-3 cells were treated with 6 Gy irradiation. CCK-8 assay was employed to detect cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Transwell chamber test was performed to detect cell migration and invasion. Western blot was used to detect the expression levels of C-Caspase-3 and C-Caspase-9, MMP-2 and MMP-9 proteins. Bioinformatics software predicted that LINC00263 and miR-4458 had complementary binding sites, and the luciferase reporter system was utilized determine the targeting relationship between LINC00263 and miR-4458. LINC00263 shRNA and miR-4458 inhibitor were co-transfected into breast cancer SK-BR-3 cells, and 6 Gy irradiation was given to detect the changes in cell proliferation, apoptosis, invasion and migration.Results:The expression level of LINC00263 in breast cancer tissues was higher than that in adjacent tissues. The expression level of LINC00263 in breast cancer cells was higher compared with that in normal breast epithelial cells. The radiosensitivity of breast cancer SK-BR-3 cells was increased after transfection of LINC00263 shRNA. Transfection of LINC00263 shRNA and radiation exerted a synergistic effect, jointly inhibited breast cancer cell proliferation, migration and invasion, promoted cell apoptosis, up-regulated the expression levels of C-Caspase-3 and C-Caspase-9 proteins in cells, and down-regulated those of MMP-2 and MMP-9 proteins. Down-regulation of LINC00263 targetedly up-regulated miR-4458 expression. miR-4458 inhibitor reversed the inhibitory effect of LINC00263 shRNA combined with radiation on the proliferation, migration, invasion and apoptosis promotion of breast cancer SK-BR-3 cells.Conclusion:Down-regulating lncRNA LINC00263 targeting miR-4458 inhibits the proliferation, migration and invasion of breast cancer SK-BR-3 cells, and improves cell radiosensitivity.

Research Progress of Catheter-based Irreversible Electroporation for Tissue Ablation / 中国医疗器械杂志

Irreversible electroporation (IRE) is an emerging tissue ablation technique. Compared with thermal ablation technique such as radiofrequency, IRE can achieve focal ablation in a shorter time without heat sink effect while sparing the tissue scaffold. IRE has been demonstrated to be a feasible therapeutic modality for the liver, pancreatic, and prostatic cancer. In recent years, several studies regarding of catheter-directed IRE for digestive tract, bronchus, urinary tract, and myocardium have been performed, which preliminarily demonstrated the safety and efficacy of IRE for tissue ablation under endoscopic or interventional technique. This study summarized the research progress of catheter-directed IRE for tissue ablation. The critical technique and future direction of catheter-based IRE are prosp.

Research progress of physical therapy technology for pancreatic cancer / 国际外科学杂志

Early diagnosis of pancreatic cancer remains difficult, and it progresses rapidly. Only a small part of patients are eligible for initial resection at the time of diagnosis, most patients need to benefit from palliative treatment. As a kind of palliative treatment, physical therapy aims to control the growth of primary tumors, relieve patients′ symptoms and improve their quality of life. In recent years, with the development of basic science, the physical treatment of tumors has also been continuously innovated. It has become an important part of comprehensive treatment measures for pancreatic cancer, and is of great significance for improving the prognosis of pancreatic cancer patients. This article summarizes the physical therapy methods related to the treatment of pancreatic cancer, including radiofrequency ablation and radiotherapy, etc.

The clinical significance of Th17 cells in patients with myelodysplastic syndrome and iron overload / 中华内科杂志

Objective To study the significance of Th17 cells in patients with myelodysplastic syndrome (MDS) and iron overload.Methods A total of 77 patients with MDS admitted to Guangzhou First People's Hospital were enrolled from January 2017 to December 2018,who were divided into iron overload group (37 cases) with serum ferritin (SF) over 1000 μg/L and non-ferrous overload group(40 cases).CD4+T cells in peripheral blood (PB) and bone marrow (BM) were sorted by flow cytometry.The ratio of Th17 cells and cells with abnormal karyotype were compared.IL-17 and IL-6 protein and RNA expression were detected by ELISA and quantitative real-time PCR(qRT-PCR).Results The proportions of Th17 cells in PB and BM in iron overload group were significantly higher than those in non-iron overload group [(41.06± 0.96)％ vs.(26.80± 1.21)％;(47.39± 1.60)％ vs.(34.29± 1.03)％;P＜0.01].The Th17 positive cells with abnormal karyotype in iron overload group were more than those in non-iron overload group[(4.96±0.53)％ vs.(3.67±0.12)％ in PB;(10.06±1.67)％ vs.(4.36±0.43)％ in BM;P＜0.01].Similarly,the protein levels as well as mRNA expression of IL-6 and IL-17 in patients with iron overload were significantly higher than those in non-iron overload group (P＜0.01 both in PB and BM).Conclusions As hematopoietic regulators secreted by Th17 cells,the expression of IL-6 and IL-17 in MDS patients with iron overload are elevated.This may predict the influence of these factors to the differentiation of Th 17 cells.

Effect of high voltage electric field on cell growth, apoptosis of human pancreatic cancer cell line PANC-1 / 中华肝胆外科杂志

Objective To investigate the effects of high intensity electric field on cell growth,apoptosis and microstructure of human pancreatic cancer cell line PANC-1.Methods The PANC-1 cells in the logarithmic growth period were selected,and cells in the high voltage electrical treatment group were treated with high voltage electric field 250,500,750,1000 V/cm,respectively.The effects of different high voltage electric fields on cell growth and microstructure of PANC-1 cells were determined by cell viability,cell death staining,apoptosis detection,transmission electron microscopy and scanning electron microscopy.Results Compared with control group,the high voltage electric pulse significantly inhibited the growth of PANC-1 cells in the field dependent manner.Moreover,when the field was more than 500 V/cm,the cell viability was significantly decreased (P＜0.05).High voltage electric pulse could induce cell apoptosis.When the field was higher than 750 V/cm,serious necrosis was noticed.In the 1000 V/cm group,the integrity of cell membrane and the structure of organelles was seriously damaged.Conclusion High voltage electric pulse could significantly inhibit the growth of PANC-1 cells and would be a promising method in cancer treatment.

Relationship between the severity of iron overload in peripheral blood CD4+T cells and the key transcription factors of RORrt, IRF8, STAT3 for cell proliferation and differentiation in elderly patients with myelodysplastic syndrome / 中华老年医学杂志

Objective To investigate the effects RORrt (RORrt),IRF8 (IRF8) and STAT3 (STAT3) in peripheral blood CD4+T cells on the cell proliferation and differentiation in elderly patients with iron-overload myelodysplastic syndrome(MDS).Methods A prospective case-control study was conducted.Twenty-two elderly hospitalized patients(12 males and 10 females)aged 60-78 years with iron-overload MDS from Jan.2017 to Dec.2018 were enrolled and considered as the observation group.Twenty MDS patients without iron overload hospitalized in the same period were selected as the non-iron overload group,and 26 healthy elderly people were considered as the healthy control group.Peripheral blood monocytes(PBM)were prepared and resident CD4+T cells were sorted by flow cytometry.The mRNA and protein expression levels of transcription factors of RORrt,p-STAT3 and IRF8 were detected by quantitative real time polymerase chain reaction(qRT-PCR)and Western blotting.Results In peripheral blood CD4+T cells,the mRNA expression level of RORrt and p-STAT3 were higher and that of IRF8 was lower in the iron-overload group than in the non-iron overload group and the healthy control group(42.634± 18.613 vs.21.289 ± 15.158 and 22.520 ± 9.896;29.710±9.689 vs.12.355±4.681 and 9.818±3.845;19.293±8.258 vs.23.785±12.498 and 69.619±23.768,P＜0.01).In peripheral blood CD4+T cells,the protein expression level of RORrt and p-STAT3 was higher,and that of IRF8 was lower in the iron overload group than in the non-iron overload group and healthy control group(P＜0.01).Conclusions The abnormalities of the mRNA and protein expression levels of transcription factors of RORrt,IRF8 and p-STAT3 in CD4+ T cells play a fundamental role in the pathogenesis of iron overload MDS in elderly patients.

Analysis of risk factors of early acute kidney injury after liver transplantation from DCD donor liver / 器官移植

Objective To analyze the risk factors of early acute kidney injury (AKI) after liver transplantation from donation after cardiac death(DCD) donor liver. Methods Clinical data of 184 donors and recipients undergoing liver transplantation from DCD donor liver were retrospectively analyzed. According to the incidence of early AKI, all participants were divided into the AKI and non-AKI groups. The patients in the AKI group were subject to AKI staging. Baseline data, preoperative, intraoperative and postoperative related parameters were statistically compared between two groups. The cumulative survival rate and clinical prognosis of patients in non-AKI group and AKI group with different staging were statistically analyzed by Kaplan-Meier curve analysis. Results Among 184 patients, 68 cases (37.0%) presented with early AKI after liver transplantation including 31 stage 1 AKI, 26 stage 2 AKI and 11 stage 3 AKI, mainly occurring within postoperative 3 d. Univariate analysis revealed that preoperative levels of albumin <35 g/L, preoperative levels of serum sodium ≤137 mmol/L, operation time>7.5 h, intraoperative hemorrhage volume>3 000 mL, intraoperative red cell infusion volume>15 U and intraoperative urine amount ≤100 mL/h were the risk factors of early AKI after liver transplantation (all P<0.05). Multi-variate Logistic regression analysis demonstrated that intraoperative red cell infusion >15 U was an independent risk factor of early AKI after liver transplantation [odds ratio(OR) 1.061, 95% confidence interval(CI)1.008-1.118,P=0.024].Result of Kaplan-Meier survival curve suggested that the cumulative survival rate was gradually reduced along with the aggravation of AKI with statistical significance (all P<0.05). Conclusions The incidence of early AKI following liver transplantation is relatively high. The severity of early AKI is intimately correlated with the short- and long-term prognosis of the recipients. A large quantity of intraoperative red blood cell infusion is an independent risk factor of AKI.