2.Effect of gap junction on permeability of blood-brain barrier in rats after cerebral ischemia- reperfusion
Dong HAN ; Jia-Chun FENG ; Fang DENG ; Yi-Min YANG ;
Chinese Journal of Neurology 2005;0(07):-
Objective To investigate the possible mechanism of the gap junctional influence on the change in permeability of the blood-brain barrier(BBB)after reperfusion subsequent to cerebral ischemia.Methods In the test laser scanning confocal microscope(LSCM)was used to investigate the change of Cx43 levels and distribution.The MCAO/R model was induced using intraluminal suture technique first described by Longa with a little modification.A total of 60 Wistar rats were divided into 4 groups:the sham-operation group,control group,octanol-treatment group and DMSO vehicle control group. Control group were further divided into seven subgroups at different time points of reperfusion after middle cerebral artery occlusion.To observe the change in permeability of BBB,Evans blue(EB)in the brain tissue was surveyed by the means of EB fluorescent quantitation.Octanol-treatment group and DMSO vehicle control group were done at the point of the peak of permeability of BBB.Octanol,the specific blocker for gap junctions(GJ)was used in an intervention study.To compare the amount of EB with the same point of groups,the influence of octanol on BBB permeability was investigated.Results At 3 h of reperfusion after cerebral ischemia for 2 h,the permeability of BBB began to increase,reached the peak at 24 h of reperfusion and was still elevated at 72 h.The Cx43 expression formed into bigger plague and remained linear disposition in the penumbra after reperfusion subsequent to cerebral ischemia.Octanol group was done at 24 h of reperfusion after cerebral ischemia.The amount of EB of octanol group((4.924?0.296)?g/g)was significantly lower than that of corresponding operation control group(5.543?0.506)?g/g.Conclusions (1)Cx43 expression is concentrated around vessels in brain.The Cx43 forms into bigger plague and the function maybe strengthens after reperfusion.Gap junction might aggravate the disruption of BBB.(2) Octanol,the specific blocker of gap junctions,could effectively prevent the permeability of BBB from increasing and has a protective effect on BBB.
3. Comparative study of the therapeutic effect between BTD and BCD for new multiple myeloma
Medical Journal of Chinese People's Liberation Army 2020;45(10):1062-1066
Objective To investigate the clinical efficacy and safety of bortezomib-based chemotherapy regimen [BTD chemotherapy regimen (bortezomib and thalidomide combined with dexamethasone) and BCD chemotherapy regimen (bortezomib and cyclophosphamide combined with dexamethasone)] in the treatment of new multiple myeloma (MM). Methods From May 2015 to May 2019, 80 newly diagnosed MM patients hospitalized in the Department of Hematology of Sanya Central Hospital were divided into BTD group (n=40) and BCD group (n=40). Patients in BTD group were given BTD chemotherapy regimen, and BCD group patients were given BCD chemotherapy regimen. Clinical efficacy, changes in myeloma markers [serum M protein, serum free light chain (κ-λ), immunofixation electrophoresis, β2 microglobulin, bone marrow plasma cells] and adverse reactions were evaluated in the two groups after 4 courses of treatment. Overall survival (OS) and progression-free survival (PFS) in the two groups were evaluated at follow-up period. Results The overall response rate (ORR) of the BTD group was significantly higher than that of the BCD group [95.0%(38/40) vs. 75.0%(30/40)], the difference was statistically significant (P<0.05). After treatment, the levels of M protein, serum free light chain (κ-λ), immunofixation electrophoresis, β2 microglobulin and bone marrow plasma cells in the two groups were significantly lower than those before treatment, and the BTD group was significantly lower than that of the BCD group, with statistically significant differences (P<0.05). The adverse reaction rate of BTD group was lower than that of BCD group [55.0%(22/40) vs. 97.5%(39/40)], and the difference was statistically significant (P<0.05). There was no significant difference in OS and PFS time between the two groups (P>0.05). Conclusion In the bortezomib-based chemotherapy regimen, the efficacy of BTD group is significantly better than that of BCD group, which could effectively reduce the indexes of myeloma, and the adverse reactions are lower, but there would be no significant difference in OS and PFS between the two groups.
4. Protective Effect of Rhizoma Coptis on LPS-induced Injury of Rat Liver Cells
Chinese Pharmaceutical Journal 2018;53(11):869-875
OBJECTIVE: To investigate the protective effect and possible mechanism of Rhizoma Coptis(RC) on lipopolysaccharide(LPS)-induced inflammatory injury in rat hepatocytes(BRL). METHODS: LPS-induced BRL cells injury model was established in vitro, then the damaged cells were given different interventions and treatment with 0.175, 0.1 mg• mL-1 RC aqueous extract as the test drug, and dexamethasone(Dex) as positive control drug. The optimal test doses of LPS and RC aqueous extract were selected and determined by cell counting kit-8(CCK-8), the cellular apoptosis rate was determined by flow cytometry, TLR4/NF-κB and TLR4/IRF3 signaling pathways and the mRNA level of related inflammatory mediators(TNF-α, IL-1β, IL-6) were detected by RT-PCR, the NF-κB p65 protein expression was analysed by Western blot and immunofluorescence techniques. RESULTS: ①Compared with normal control group, 0.1 mg•mL-1 LPS affected on BRL cells for 24 h, the cell survival rate was decreased significantly(P<0.01), the apoptotic rate increased significantly(P<0.01), the mRNA level of TLR4, NF-κB, IRF3, TNF-α, IL-1β, IL-6 were significantly increased(P<0.01), and the NF-κB p65 protein expression was increased. ②Compared with the model group, 0.1 and 0.175 mg•mL-1 RC affected on LPS-induced BRL cells for 24 h, the survival rate of BRL cells was increased significantly(P<0.05), the apoptotic rate decreased significantly(P<0.01), the mRNA level of TLR4, NF-κB, IRF3, TNF-α, IL-1β, IL-6 and the NF-κB p65 protein expression were decreased significantly(P<0.01). CONCLUSION: Rhizoma Coptis has obviously protective effect on LPS-induced inflammatory injury in rat hepatocytes(BRL), the mechanism of which may be related with inhibiting apoptosis, reducing the release of inflammatory factors such as TNF-α, IL-1β and IL-6, blocking NF-κB p65 protein nuclear translocation, interfering the R4/NF-κB and TLR4/IRF3 signaling pathway.
5.Long-term efficacy of concurrent chemoradiotherapy at different radiotherapy doses in treatment of esophageal carcinoma
Xuejiao REN ; Lan WANG ; Chun HAN ; Boyue DING ; Jing HAN ; Yang YOU
Chinese Journal of Radiation Oncology 2017;26(9):1006-1011
Objective To compare the local control (LC), long-term overall survival (OS), and clinical adverse reactions in esophageal carcinoma patients receiving concurrent chemoradiotherapy at different radiotherapy doses.Methods A total of 373 esophageal carcinoma patients who received concurrent chemoradiotherapy in our hospital during 2004-2013 were included in this retrospective study.These patients were divided into<60 Gy group (n=99), 60 Gy group (n=155), and>60 Gy group (n=119) based on the dose of radiation.The Kaplan-Meier method was used to calculate LC and OS rates;the log-rank test was used for survival comparison and univariate prognostic analysis;the Cox model was used for multivariate prognostic analysis.Results The 3-, 5-, 7-, and 10-year sample sizes were 97,96,56, and 38 in the<60 Gy group, 146,141,72, and 17 in the 60 Gy group, and 118,115,56, and 20 in the>60 Gy group.The 3-, 5-, 7-, and 10-year LC rates were 55.3%, 51.4%, 48.9%, and 48.9% in the<60 Gy group, 65.1%, 60.1%, 55.1%, and 55.1% in the 60 Gy group, and 49.4%, 45.1%, 37.7%, and 37.7%(8-year) in the>60 Gy group (P=0.020).The 3-, 5-, 7-, and 10-year OS rates were 35.4%, 26.1%, 22.0%, and 22.0% in the<60 Gy group, 49.0%, 41.3%, 32.1%, and 28.9% in the 60 Gy group, and 31.1%, 25.2%, 14.5%, and 12.9%(8-year) in the>60 Gy group (P=0.000).The univariate analysis showed that for stage Ⅱ esophageal carcinoma patients with gross tumor volume (GTV) ≤44 cm3, the LC rate was higher in the 60 Gy group than in the<60 Gy group (P=0.040,0.035), and the OS rate was higher in the 60 Gy group than in the other two groups (P=0.001,0.003 and P=0.045,0.006).Similarly, for stage Ⅲ esophageal carcinoma patients with GTV>44 cm3, the LC rate was higher in the 60 Gy than in the>60 Gy group (P=0.011,0.015), and the OS rate was higher in the 60 Gy group than in the other two groups (P=0.045,0.006 and P=0.033,0.002).The incidence rates of acute radiation esophagitis and radiation pneumonia were significantly higher in the>60 Gy group than in the other two group (P=0.007,0.033).Furthermore, the multivariate analysis indicated that radiotherapy dose, T stage, and N stage were independent prognostic factors for esophageal carcinoma (P=0.004,0.008,0.037).Conclusions Concurrent chemoradiotherapy at 60 Gy is most efficacious for patients with esophageal carcinoma, and the radiotherapy dose of>60 Gy significantly increases the incidence of adverse reactions.
6.The development of iodine-123 with MC-50 cyclotron.
Yong Sup SUH ; Seung Tae YANG ; Kown Soo CHUN ; Jong Doo LEE ; Hyon Soo HAN
Korean Journal of Nuclear Medicine 1991;25(2):286-293
No abstract available.
Cyclotrons*
7.A dose study of the late course accelerated hyperfractionation radiotherapy for esophageal carcinoma
Chun HAN ; Xiangran YANG ; Jun WANG ; Guoxin MA ; Aiqin XIAO ; Xin ZHANG
Chinese Journal of Radiation Oncology 2005;0(05):-
Objective To discuss the optimal radiation dose in the treatment of the late course accelerated hyperfractionation(LCAH) radiotherapy for esophageal carcinoma by using two different treatment doses,focusing on the difference of the short term results,local control rates,treatment tolerance and long term survival rates between the two groups.Methods One hundred patients with esophageal carcinoma were randomly divided by the envelope method into two groups:the 60Gy group and the 75Gy group.Patients in 60Gy group received conventional fraction radiation for the first 3 weeks,and then hyperfractionation radiation(1.5Gy per fraction,two fractions a day with 6 hour interval,10 fractions per week) to the total dose of 60Gy/35 fractions/5 weeks.The radiation schedule of the 75Gy group was the same as the 60Gy group: conventional fractionation of radiation for the first 3 weeks and then hyperfractionation radiation for the rest 3 weeks to the total dose of 75Gy/45 fractions/6 weeks.Results There was no significant difference between the two groups in short term results.The 1-,3-,5-year local control rates were 86%,42%,32% in 60Gy group and 88%,52%,48% in 75Gy group,respectively.The 1-,3-,5-year survival rates were 86%,40%, 28% in 60Gy group and 72%,34%,16% in 75Gy group,with no significant difference(P= 0.283).The median survival time was 25 months for the 60Gy group and 19 months for the 75Gy group.Patients suffered from heavy radiation-induced esophagitis in the 75Gy group were significantly more than those in the 60Gy group(28% vs 10%,P= 0.022).But it was similar for patients who died of side effects in the two groups.Conclusions It is not suitable to pursue high dose in treating esophageal carcinoma with late course accelerated hyperfractionation radiotherapy as high incidence of side effects are unadvoidable if the dose is increased without changing the radiation fields and techniques.When escalating the dose to the esophagus,the radiated lung volume as well as the other normal tissues should be first subjected to meticulous and careful consideration.
8.Effects of hypothermia on the liver in a swine model of cardiopulmonary resuscitation
Yi HAN ; Zhen-Ju SONG ; Chao-Yang TONG ; Chun-Sheng LI
World Journal of Emergency Medicine 2013;4(4):298-303
BACKGROUND: The study aimed to explore the effects of hypothermia state induced by 4 oC normal saline (NS) on liver biochemistry, enzymology and morphology after restoration of spontaneous circulation (ROSC) by cardiopulmonary resuscitation (CPR) in swine. METHODS: After 4 minutes of ventricular fibrillation (VF), standard CPR was carried out. Then the survivors were divided into two groups: low temperature group and normal temperature group. The low temperature (LT) group (n=5) received continuously 4 oC NS at the speed of 1.33 mL/kg per minute for 22 minutes, then at the speed lowering to 10 mL/kg per hour. The normal temperature (NT) group (n=5) received NS with normal room temperature at the same speed of the LT group. Hemodynamic status and oxygen metabolism were monitored and the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured in blood samples obtained at baseline and at 10 minutes, 2 hours and 4 hours after ROSC. At 24 hours after ROSC, the animals were killed and the liver was removed to determine the Na+-K+-ATPase and Ca2+-ATPase enzyme activities and histological changes under a light or electron microscope. RESULTS: Core temperature was decreased in the LT group (P<0.05), while HR, MAP and CPP were not significantly decreased (P>0.05) compared with the NT group (P>0.05). The oxygen extraction ratio was lower in the LT group than in the NT group (P<0.05). The serum levels of ALT, AST and LDH increased in both groups but not significantly in the LT group. The enzyme activity of liver ATP was much higher in the LT group (Na+-K+-ATP enzyme: 8.64±3.32 U vs. 3.28±0.71 U; Ca2+-ATP enzyme: 10.92±2.12 U vs. 2.75±0.78 U, P<0.05). The LT group showed less cellular edema, inflammation and few damaged mitochondria as compared with the NT group. CONCLUSION: These data suggested that infusing 4 oC NS continuously after ROSC could quickly lower the core body temperature, while maintaining a stable hemodynamic state and balancing oxygen metabolism, which protect the liver in terms of biochemistry, enzymology and histology after CPR.
9.The study of macrophage colony-stimulating factor in the pathogenesis of spondyloarthropathy
Chun-Hua YANG ; Feng HUANG ; Jie-Ruo GU ; Han-Wei ZHANG ; De-En YU ;
Chinese Journal of Rheumatology 2003;0(12):-
Objective To study the macrophage colony-stimulating factor(M-CSF)expression levels of serum and synovial fluids from patients with spondyloarthropathy(SPA)and its contribution to the pathogen- esis of SpA.Methods Eleven SpA synovial tissue samples were compared to those from peripheral blood mononuclear cells(PBMC)of 10 normal subjects using a 1176 gene array.M-CSF was detected in both serum samples and synovial fluids by enzyme linked immunosorbent assay(ELISA).Two groups of AS subjects were tested.The first group consisted of 41 ankylosing spondylitis(AS)patients who had not been treated with bio- logics.The second group consisted of 13 subjects whose serum samples were collected before and 14 weeks af- ter initiation of infliximab.These were compared to serum samples from 28 normal subjects,and synovial fluid samples from 15 SpA patients.Results Expression of M-CSF could be detected in both serum samples and synovial fluids.The concentration of M-CSF in the group of 41 AS patients not treated with biologics correlated with the Bath Ankylosing Spondylitis Disease Activity Index(BASDAI)values(r=0.41,P=0.004).Treatment of infliximab in AS patients led to a significant decrease in the values of BASDAI(P=0.000 07),but no signif- icant change in the serum M-CSF values.Conclusion M-CSF is a promising candidate for research on the mechanisms of SpA and its signaling on pathway in SpA is different from tumor necrosis factor(TNF)-?,and it may provide new basis for developing new anti-biologics for SpA.
10.Effect of Insulin on D_5 Dopamine Receptor Expression and Function in Renal Proximal Tubule Cells
Jian YANG ; Yu HAN ; He-Fei HUANG ; Duo-Fen HE ; Chun-Yu ZENG ;
Chinese Journal of Hypertension 2007;0(05):-
Objective To investigate the effect of insulin on D_5 dopamine receptor expression and function in renal proximal tubule (RPT).Methods Immortalized RPT cells and D_5 receptor transfected HEK293 (HEK-D_5) cells were used in the study to investigate the effect of insulin on D_5 receptor expression and function,and those effects were compared in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The function of D_5 receptor was determined by measurement of the Na~+-K~+-ATPase activity in HEK-D_5 cells. Results Insulin increased D_5 receptor protein expression in a concentration and time-dependent manner in WKY RPT cells,but not in SHR.The basal level of D_5 receptor expression was higher in WKY cells than that in SHR cells. Stimulation with fenoldopam(D_1-like dopamine receptor agonist) inhibited the Na~+-K~+-ATPase activity;pretreat- ment with insulin increased the inhibitory effect of fenoldopam on Na~+-K~+-ATPase activity in HEK-D_5 cells. Conclusion The abnormal regulation of insulin on D_5 receptor expression and function might be involved in the path- ogenesis of essential hypertension.