2.Fabrication of multifunctional bismuth-doped iron nanoparticle and its radiotherapy sensitization in glioblastoma
Yuanyuan NIU ; Ming YU ; Fengyi DU ; Siyuan CHEN ; Tian ZHAO ; Yuhao XU ; Qianwen ZHOU ; Xiujian XU
Chinese Journal of Tissue Engineering Research 2017;21(18):2821-2827
BACKGROUND:Bismth-doped iron nanoparticles modified by hyaluronic acid (HA-BiIOPs) not only act as an effective MRI contrast agent, but also as a radiotherapy sensitizer.OBJECTIVE:To fabricate the HA-BiIOPs and to observe its effect to enhance the radiosensitivity of glioblastoma cells U87MG under X-ray radiation.METHODS:HA-BiIOPs were synthesized using hydrothermal polyol method. (1) Cytotoxicity: A cytotoxicity test was carried out on U87MG cells and rat vascular smooth muscle cells (VSMCs). Cell proliferation rate of two kinds of cells cultured with different concentrations of HA-BiIOPs (0, 12.5, 25, 50, 100, 200, 400 mg/L) at 24 hours after culture were determined by cell counting kit-8 assay. (2) Histological analysis: ICR mice were sacrificed after intravenous injection of HA-BiIOPs, and pathological changes of mouse visceral organs were observed under an optical microscope. (3) Cellular uptake: The HA-BiIOPs after entered into the cytoplasm were observed by Prussian blue staining. (4) Radiosensitization test: U87MG cells at Logarithmic growth stage were cultured in culture medium as control group, subjected to X-ray irradiation (0, 3, 6, 9 Gy) as radiotherapy group, cultured in HA-BiIOPs (0, 12.5, 25, 50, 100, 200 and 400 mg/L) as HA-BiIOPs group or subjected to HA-BiIOPs culture plus X-ray irradiation as combined therapy group. Then, the cell proliferation rate and cloning efficiency were measured at 24 hours after treatment.RESULTS AND CONCLUSION:(1) The HA-BiIOPs at different concentrations were non-cytotoxic for VSMC and U87MG cells. (2) After intravenous injection of HA-BiIOPs, there was no obvious toxicity to the mouse susceptible organs. (3) After 6 hours of culture, the HA-BiIOPs could be internalized by U87MG cells. (4) The proliferation rate of U87 cells was negatively correlated with the concentration of HA-BiIOPs (0-200 mg/L) and X-ray dose (0-9 Gy). Especialy, the combination of 6 Gy X-ray irradiation with 200 mg/L HA-BiIOPs dramatically decreased the cell viability that was decreased to (41±7)%. In the combined therapy group with 6 Gy X-ray and 100 mg/L HA-BiIOPs, the cells proliferation rate was significantly lower than that in the control and radiotherapy groups (P < 0.05). These results indicate that HA-BiIOPs have a radiosensitizative effect on glioblastoma cells U87MG.
3.Efficacy and safety of oxycodone hydrochloride injection for postoperative analgesia in patients undergoing operation under general anesthesia: a prospective, randomized, blind, multicenter, positive-controlled,clinical trial
Xing XU ; Xinmin WU ; Zhanggang XUE ; Xiangrui WANG ; Lize XIONG ; Ming TIAN ; Chen YAO
Chinese Journal of Anesthesiology 2013;(3):269-274
Objective To evaluate the efficacy and safety of oxycodone hydrochloride injection for postoperative analgesia in patients undergoing the operation under general anesthesia in a prospective,randomized,blind,multicenter,positive-controlled,clinical trial.Methods Two hundred and forty ASA Ⅰ or Ⅱ patients of both sexes,aged 18-64 yr,weighing 40-95 kg,scheduled for elective abdominal operation or orthopedic surgeries under general anesthesia,were randomly divided into 2 groups (n =120 each):morphine sulfate injection group (group M) and oxycodone hydrochloride injection group (group O).Morphine or oxycodone 1 mg was injected intravenously when the patients complained of pain after tracheal extubation or removal of the laryngeal mask,and administration was repeated if necessary until VAS≤40 mm.Then patient-controlled intravenous analgesia (PCIA) (100 ml,0.5 mg/ml) with morphine or oxycodone was used for postoperative analgesia (lasting for 48 h).The PCIA pump was set up with a 1 ml bolus dose,a 5 min lockout interval and background infusion at a rate of 0.5 mg/h.Pain at rest and during movement was assessed using VAS score at 3,24 and 48 h after administration,and non-inferiority test was performed.Total morphine or oxycodone consumption,requirement for rescue analgesic,the number of unsuccessfully delivered dose,the number of attempts,and the level of patient' s satisfaction were recorded within 48 h after operation.The adverse events were recorded and laboratory examinations (blood and urine routine test,blood biochemical examination) were performed within 72 h after administration.Results There was no significant difference in the VAS scores at rest and during movement at different time points,requirement for rescue analgesic,the number of unsuccessfully delivered doses and attempts,level of patient' s satisfaction,total morphine or oxycodone consumption,and adverse events between the two groups (P > 0.05).No serious adverse event occurred in the two groups.The most common adverse event was nausea,followed by vomiting.There was no significant difference in the incidences and degree of nausea and vomiting between the two groups (P > 0.05).The incidences of nausea and vomiting in patients underwent orthopedic surgeries were significantly lower in group O than in group M (P < 0.05).The other adverse events were fewer and abnormal laboratory examinations were rare in the two groups.95% confidence interval of the difference between the mean VAS scores at rest and during movement at each time point was within 15 mm (boundary values of non-inferiority testing) in the two groups.Conclusion PCIA with oxycodone hydrochloride injection is safe and effective in reducing pain after moderate or major operation,and the analgesic efficacy is similar to that of morphine sulfate injection,however,the development of nausea and vomiting is reduced when PCIA with oxycodone hydrochloride injection is used for orthopedic surgeries as compared with that when morphine sulfate injection is used and the ratio between the analgesic efficacy of the two drugs is close to 1∶1.
4.Changes of dendritic cells subsets and their HLA-DR expression in peripheral blood of breast cancer patients
Dunyun SHI ; Qiongli ZHANG ; Jiliang LIU ; Geng TIAN ; Yun XU ; Ming LI ; Mingchun WANG
Chinese Journal of Pathophysiology 2000;0(07):-
AIM:To explore the changes of the subsets and HLA-DR expression of dendritic cells and their concerning cytokine levels in peripheral blood of patients with breast cancer.METHODS:The subsets of the precussors of dendritic cells(pDC)in the peripheral blood of 57 cases of patients with breast cancer before operation and a week or six months after operation and 20 cases of healthy controls were analyzed by four-color FCM.The levels of IL-12p40,IL-10,IFN-? and IL-4 in the plasmas were tested by ELISA.RESULTS:Among 57 cases of patients with breast cancer,2 cases in Ⅲ phase and 4 cases in Ⅳphase expressed deficiency of pDC,the ratios of pDC1/pDC2 in the other cases inⅠ,Ⅱ,Ⅲ,Ⅳ phase were respectively 1.62?0.59,1.41?0.63,0.91?0.32,0.81?0.29 before operation,which were markedly lower than those in controls(1.94?0.44).The ratios of pDC1/pDC2 in the cases inⅠ,Ⅱ,Ⅲ phase were 1.71?0.47,1.52?0.54,1.04?0.36 a week after operation,which were the same as those in pre-operation,but markedly lower than those in controls.The ratios of pDC1/pDC2 in the cases inⅠ,Ⅱ,Ⅲ phase were 1.92?0.72,1.63?0.65,1.28?0.34 six months after operation,which were markedly higher than those in pre-operation,meanwhile,to compare with controls,those were still lower for patients in Ⅱ,Ⅲ phase except in Ⅰphase.No difference between patients and controls in the expression of HLA-DR of pDCs and the levels of IL-12p40,IL-10,IFN-?,IL-4 in plasmas and the ratios of IL-12p40/IL-10,IFN-?/IL-4 was observed.CONCLUSION:The ratios of pDC1/pDC2 in peripheral blood of patients with breast cancer inⅠ-Ⅳ phase are decreased.Parts of patients in Ⅲ,Ⅳ phase are deficiency of pDCs.HLA-DR expression of DCs and the ability of DCs which secret the concerning cytokines do not change as pDC subsets change.pDC subsets improve markedly inⅡ,Ⅲ phase patients and recover to the normal level inⅠphase patients after operation.
5.PID1 based connection of insulin resistance to hepatocellular carcinogenesis
Ming XIANG ; Qian-Qian XU ; Sen-Lin LI ; Bao-Tian WANG ; Ya-Li TUO
Chinese Journal of Pharmacology and Toxicology 2018;32(4):316-316
OBJECTIVE To investigate the effect of phosphotyrosine interaction domain containing 1 (PID1, NYGGF4) onpromotion of IR and HCC, and explore its underlying mechanisms. METHODS Lentivirus were used to mediate the knockdown of PID1 in HFD induced IR mouse model as well as ob/ob mice. Intraperitoneal glucose and insulin tolerance were performed 4 weeks after lentivirus injection. Hydrodynamics-based transfection was applied to induce the liver specific overexpression of PID1. Flow cytometry was exerted to detect the proportion and function of immune cells.qRT-PCR and Western blot were used to detect the expression of downstream pathways of PID1. Liquid chromatography-mass spectrometry (LC-MS) and co-immunoprecipitation (Co-IP) were conducted to identify proteins interacting with PID1.Chromatin immunoprecipitation(ChIP)was operated to measure the modification of H3K4me3 of PID1 promoter.RESULTS PID1 restriction improved insulin resistance,hyperglycemia and fatty liver. Conversely, hepatic knockdown of PID1 attenuated liver xenografted tumor growth. Moreover,PID1 liver-specific protooncogenes via hydrodynamics-based transfection established a primary hepatocellular carcinoma mouse model,induced an immunosuppressive environment,with the reduction of CD3+,CD4+,CD8+T cells,retarded maturation of dendritic cells(DCs),pronounced differentiation of regulatory T cells(Tregs),and recruitment of MDSC.In addition,PID1 overexpression activated prolifer-ation related genes, promoted anti-inflammatory genes, suppressed pro-inflammatory genes, induced glycolysis and lipid metabolism genes to facilitate tumorigenesis in liver. Importantly, PID1 exerted its tumor-promoting function through binding to epidermal growth factor receptor(EGFR)and activation of downstream KRAS/ERK pathway.As such,PID1 exist trimethylation of histone H3 at lysine 4(H3K4me3) modification and IR up-regulated the expression of PID1 by activation the H3K4me3 modification. CONCLUSION PID1 is a new gene that exerts both liver cancer-promoting and insulin resistance inducing function.IR accelerates liver cancer development and progression partially dependent on the activation of PID1.
6.99Tcm-MIBI scintigraphy for the assessment of preoperative chemotherapy response of osteosarcoma
Ming, XU ; Xiu-chun, YU ; Qiang, WANG ; Xiu-yi, ZHAO ; Jun, TIAN ; Ji-yuan, DING
Chinese Journal of Nuclear Medicine 2010;30(3):158-162
Objective To investigate the value of 99Tcm-methoxyisobutylisonitrile (MIBI) scintigraphy in assessing the preoperative chemotherapy response and multidrug resistance of osteosarcoma.Methods From January 2007 to October 2008, 12 patients (female:4, male:8; mean age:16.3 years,range:8-27 years) underwent early (10min) and delayed (120 min) 99Tcm-MIBI scintigraphy before and after preoperative chemotherapy.Seven cases had osteosarcoma at the distal femurs, 2 at the proximal tibias, 2 at the upper end of humerus and 1 at the fibula.The tumor-to-background ratio (T/B) and washout rate (WR) were calculated.Tumor necrosis was classified according to Huvos criterion after limb salvage surgery.Immunohistochemical staining for P-glycoprotein(gp) was examined.Spearman correlation analysis and t-test were performed.Results According to Huvos criterion, 7 patients were classified as good responders with more than 90% of tumor cell necrosis and 5 as poor responders with less than 90% of tumor cell necrosis.R value (ratio of early phase T/B after and before chemotherapy) was significantly lower in good responders than that in poor responders (0.473 ± 0.21 vs 0.998 ± 0.06, t= 5.342, P= 0.000 ).R value was significantly correlated with the degree of tumor cell necrosis ( rs=- 0.87, P= 0.000 ).WR was significantly higher in patients with positive P-gp expression than that in patients with negative P-gp expression ((38.36 ±18.64)% vs (6.40±5.87)%, t= -3.278, P=0.008).There was significant correlation between the WR and P-gp expression (rs = 0.91, P= 0.001 ).Conclusion 99Tcm-MIBI scintigraphy is a feasible non-invasive technique to assess the chemotherapy response and to detect P-gp expression of osteosarcoma.
7.Value of intracavitary contrast-enhanced ultrasound via abdomen in fistulas difficult to diagnose before operation
Yujun CHEN ; Ren MAO ; Xiaohua XIE ; Wenshuo TIAN ; Ming XU ; Shuling CHEN ; Minhu CHEN ; Xiaoyan XIE
Journal of Chinese Physician 2017;19(6):807-809
Objective To evaluate the value of intra-cavitary contrast-enhanced ultrasound (IC-CEUS) via abdomen in fistulas difficult to diagnose before operation.Methods Clinical data of 12 patients with preoperative clinical suspicion of Crohn's Disease (CD) complications of fistula were enrolled in the study.Colonoscopy,cystoscope,or CT/MR has not confirmed the diagnosis of intra abdominal fistulas.IC-CEUS were performed by locally-injection of contrast agent in abdominal abscess,observing fistula and the relationship with the adjacent organs in CEUS mode.Diagnostic criteria were surgical findings.Results Fistulas in 10 patients were detected by IC-CEUS,including 7 cases of Ileo-mesenteric fistuls,2 cases of il eo-vesical fistulas,and 1 case of colo-vesical fistula.The accuracy rate of IC-CEUS in diagnosis of fistulas difficult to diagnose before operation in Crohn's disease was 83.3% (10/12).No severe adverse events occurred during and after IC-CEUS procedure.Conclusions Our preliminary study shows that IC-CEUS is feasible in detecting abdominal fistula with high accuracy.It might be used as the alternative imaging tech nique for detecting fistulas when CT and MR are insufficient.
8.Mechanism of Neural Stem and Progenitor Cells Mediated by Hypoxia Inducible Factor-1α in Ischemic Stroke Model (review)
Dongyuan ZHANG ; Ming LI ; Zhengze WANG ; Wenran ZHANG ; Xiaodan XU ; Liying ZHANG ; Shen TIAN
Chinese Journal of Rehabilitation Theory and Practice 2017;23(3):319-322
Hypoxia inducible factor-1αis a kind of hypoxia response factor. Acute cerebral ischemia and anoxia can induce up-regula-tion of hypoxia inducible factor-1α, and the downstream genes, which plays a role in both the energy metabolism and collateral circulation after cerebral ischemia. Neural stem and progenitor cells regeneration also benefit the functional outcome after ischemic stroke. Hypoxia in-ducible factor-1αmay induce proliferation and differentiation of neural stem and progenitor cells through Notch, Wnt/β-catenin pathways, etc., in the ischemic stroke model.
9.Epidemiological characteristics of multi-drug resistant tuberculosis and pre-extensively drug resistant tuberculosis in Changsha, 2018-2021
XU Ming-zhong ; WANG Xiao-jun ; XIONG Zi ; SONG Li-xin ; TIAN Bin
China Tropical Medicine 2023;23(5):479-
Abstract: Objective To understand the situation of drug-resistant tuberculosis screening and epidemiological characteristics of multi-drug resistant tuberculosis (MDR-TB) and pre-extensively drug resistant tuberculosis (pre-XDR-TB) in Changsha, in order to provide a scientific basis for improving the quality of drug-resistant tuberculosis prevention and control in the city. Methods Demographic information and drug susceptibility date of etiologically positive pulmonary tuberculosis patients in Changsha from 2018 to 2021 were collected, the successful rate of resistance screening, incidence and tendency in MDR-TB and pre-XDR-TB in patients included in this study were statistically analyzed accordingly. Results From 2018 to 2021, the successful screening rates were 86.2%, 87.7%, 81.9% and 71.5% for MDR-TB and 82.2%, 84.8%, 76.9% and 68.2% for pre-XDR-TB, respectively. In each year, MDR-TB patients identified accounted for 7.6% (101/1 222), 6.5%(124/1 774), 6.6%(110/1 555) and 6.3%(99/1 478), and pre-XDR-TB patients identified accounted for 3.6%(46/1 219), 3.8%(69/1 766), 4.4%(69/1 495) and 4.6%(69/1 436), correspondingly. The incidence of MDR-TB showed a slowly downward trend, while the incidence of pre-MDR-TB showed a slowly upward trend, with neither decreasing nor increasing trends being statistically significant ((χ2=1.947,0.806,P>0.050). The incidence of MDR-TB in the retreatment failure population was 66.6% (2/3), and the others, failure initial treatment and recrudescence populations were 23.5% (19/81), 16.7% (2/12) and 15.2% (70/461), respectively. Similar to the incidence above, the incidence of pre-XDR-TB was 16.7% (2/12) among patients who failed in initial treatment, and 12.2% (9/74), 9.8% (43/439), and 4.5% (2/44) among the others, recrudescence and returned patients, respectively. The incidence rates of MDR-TB and pre-XDR-TB in different populations were significantly different (χ2=117.600,59.030,P<0.05). Conclusions There are still areas for improvement in tuberculosis drug resistance surveillance system in Changsha. On the premise of paying attention to patients in retreatment failure, other, initial treatment failure and relapse patients, high sensitivity molecular drug susceptibility testing, and scientifically efficient screening strategies must be explored.
10.Comparison of shear wave elastography and quasi-static elastography in the evaluation of radiofrequency ablation:ex vivo experiment
Baoxian LIU ; Guangliang HUANG ; Wenshuo TIAN ; Ming XU ; Manxia LIN ; Xiaohua XIE ; Xiaoyan XIE
Chinese Journal of Ultrasonography 2017;26(4):350-354
Objective To investigate the value of shear wave elastography (SWE) and quasi-static elastography in the evaluation of radiofrequency ablation of pork.Methods Twelve pieces of fresh pork were underwent radiofrequency ablation (RFA) with different target temperatures.Before and after RFA,conventional ultrasound (US),SWE and quasi-static elastography were conducted to visualize the boundaries of RFA zones.The size of ablation zones obtained from conventional ultrasound,SWE and quasi-static elastography measurement were observed and detected the correlativity with pathology findings.Moreover,the Young's modulus and stain ratio of ablated zone were recorded.Results Most ablated boundaries were clearly delineated by both elastography techniques,except one with a low target temperature of 70 ℃.The sizes of ablated zones measured by SWE and quasi-static elastography were closely correlated with pathological findings.However,no ablated zones could be visualized by conventional US.Before and after RFA,the mean,minimum and maximum values of Young's modulus were (24.2 ± 3.8) kPa vs (97.6 ± 29.1) kPa,(9.2 ± 0.7)kPa vs (44.5 ± 7.7)kPa and (29.9 ± 3.8)kPa vs (181.5 ± 36.7)kPa,respectively (all P <0.001).With the increase of target temperature of RFA,the Young's modulus values and the mean strain ratio were significantly increased (all P < 0.01).Conclusions Both SWE and quasi-static elastography are useful tools for evaluating the ablation,which are superior to conventional US.Moreover,SWE can be used to monitor the procedure of ablation.