1.Advances in Study on Intestinal Apical Sodium-dependent Bile Acid Transporter and Related Diseases
Chinese Journal of Gastroenterology 2015;(4):244-247
Bile acids play critical roles in the solubilization and absorption of lipids. The ileal apical sodium-dependent bile acid transporter( ASBT)located at the enterocyte brush border is responsible for the reuptake of bile acids and the maintenance of bile acid homeostasis. Recently,great success has been made in understanding the relationship between ASBT and intestinal inflammation,tumorigenesis,secretion,motility,sensation,gut microbiota,and gut-liver axis in addition to its expression regulation,which implicates ASBT as a contributor of some gastrointestinal diseases and a promising new therapeutic target for these diseases. In this review article,the advances in study on above-mentioned issues were summarized.
2.Protective effects of rapamycin induced autophagy on acute kidney injury induced by sepsis
Rui WANG ; Xiaoying GONG ; Hanyu QIN ; Guofu LI
Chinese Critical Care Medicine 2016;28(10):927-932
Objective To investigate the protective effect of autophagy inducer rapamycin on acute kidney injury (AKI) induced by sepsis. Methods Twenty-four Sprague-Dawley (SD) male rats were randomly divided into sham group, caecal ligation and puncture (CLP) model group, and rapamycin treatment group (Rap treatment group), with 8 rats in each group. The septic AKI model was reproduced by CLP in rats, and rats in sham group were given appendix isolation without ligation and puncture. The rats in Rap treatment group were given 1.6 mg rapamycin by intraperitoneal injection immediately after model reproduction, and the rats in CLP model group were injected with an equal amount of normal saline. The rats in all groups were sacrificed after collecting peripheral blood specimen at 24 hours after model reproduction, and the levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were determined. The pathomorphology change in renal tissue was observed under light microscope after periodic acid Schiff (PAS) staining. Real-time polymerase chain reaction (real-time PCR, RT-PCR) was used to determine the mRNA expressions of renal tubular autophagy related molecules Atg-5 and Beclin-1. Western Blot was used to detect the expressions of renal tubular autophagy associated protein microtubule labeled protein 1 light chain 3-Ⅱ (LC3-Ⅱ) and Beclin-1 as well as apoptosis protein cytochrome C (Cyt C), Bax and Bcl-2. TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to determine the renal tubular epithelial cell apoptosis. Results Rapamycin could alleviate pathomorphology changes in rats with septic AKI, and decrease the levels of BUN and SCr. Compared with sham group, the expressions of Atg-5, Beclin-1 and LC3-Ⅱ in CLP model group were significantly increased [Atg-5 mRNA (2-ΔΔCt): 2.34±0.04 vs. 1.00±0.03, Beclin-1 mRNA (2-ΔΔCt): 1.40±0.02 vs. 1.00±0.03, LC3-Ⅱ protein (gray value): 0.82±0.03 vs. 0.45±0.04, Beclin-1 protein (gray value): 0.59±0.06 vs. 0.29±0.03, all P < 0.01]. Rapamycin could further up-regulate the expressions of Atg-5, Beclin-1, and LC3 Ⅱ [Atg-5 mRNA (2-ΔΔCt): 3.28±0.19 vs. 2.34±0.04, Beclin-1 mRNA (2-ΔΔCt): 2.38±0.08 vs. 1.40±0.02, LC3-Ⅱ protein (gray value): 1.11±0.07 vs. 0.82±0.03, Beclin-1 protein (gray value): 0.85±0.05 vs. 0.59±0.06, all P < 0.01]. Compared with sham group, the apoptotic cells in CLP model group were increased significantly [(34.49±10.45)% vs. (2.78±1.40)%, P < 0.01], Cyt C and Bax protein expressions were significantly up-regulated (gray value: 0.87±0.02 vs. 0.46±0.03, 1.20±0.06 vs. 0.46±0.01, both P < 0.01), and Bcl-2 expression was significantly down-regulated (gray value: 0.64±0.02 vs. 1.33±0.09, P < 0.01). Rapamycin could effectively inhibit cell apoptosis [(15.44±5.50)% vs. (34.49±10.45)%, P < 0.01] and the protein expressions of Cyt C and Bax (gray value: 0.72±0.03 vs. 0.87±0.02, 0.84±0.03 vs. 1.20±0.06, both P < 0.01), and up-regulate the protein expression of Bcl-2 (gray value: 0.77±0.04 vs. 0.64±0.02, P < 0.01). Conclusion The protective effect of rapamycin on renal tissue of rat with AKI induced by sepsis was depended on cell apoptosis inhibition through inducing and promoting cell autophagy.
3.The application and research progress of nuclear medicine in digestive diseases
Hanyu ZHANG ; Di WU ; Guoxing WANG ; Chunsheng LI
Journal of Chinese Physician 2021;23(1):150-154
Nuclear medicine can not only display the anatomical structure of organs or lesions, but also provide the information of blood flow, function, metabolism and receptor density of organs and lesions in digestive system . It is not only complementary to computer tomography (CT) and magnetic resonance imaging (MRI) in organic diseases of digestive system, but aslo has unique clinical value in functional diseases of digestive system.
4.Preliminary results of a phase Ⅱ prospective clinical study of early-stage nasal NK/T-cell lymphoma with extended involved-field intensity-modulated radiotherapy
Shaoqing NIU ; Yujing ZHANG ; Ge WEN ; Yiyang LI ; Lingling FENG ; Hanyu WANG ; Bixiu WEN
Chinese Journal of Radiation Oncology 2015;(4):377-381
Objective To investigate the feasibility of the scheme of target volume delineation with extended involved?field intensity?modulated radiotherapy (IMRT) for patients with early?stage nasal NK/ T?cell lymphoma (NC?NKTL). Methods Twenty?one patients with stage IE?IIE NC?NKTL were treated with short?course chemotherapy combined with radiotherapy from 2011 to 2013. The majority of patients received the GELOX regimen. All patients received extended involved?field IMRT with a dose of 54?? 6 Gy in 26 fractions for gross tumor volume, 50?? 7 Gy in 26 fractions for high?risk clinical target volume (CTV), and 45?? 5 Gy in 26 fractions for low?risk CTV. The dose distribution, short?term treatment outcomes, and adverse reactions were analyzed. Results The 2?year sample size was 12. The 2?year follow?up rate was 100%. The 2?year local control rate ( LRC) was 100%. The 2?year overall and progression?free survival rates were 90?? 5% and 90?? 5%, respectively. The median coverage rates of planning target volumes with 90% of the prescribed doses of 54?? 6 Gy, 50?? 7 Gy, and 45?? 5 Gy were 99?? 8%, 99?? 6%, and 99?? 7%, respectively. No grade 3 or 4 adverse reactions were observed in patients. Conclusions The scheme of target volume delineation and dose configuration in our study not only achieves excellent target volume coverage, but also reduces adverse reactions in patients, which achieves a 2?year LRC ideal for patients with early?stage NC?NKTL.
5.Characteristics of Thromboelastography in Patients with Advanced Pregnancy Complicated with Severe Preeclampsia
Jia JIA ; Qiaoni YANG ; Zifang ZHAO ; Hanyu QIN ; Qiushi WANG ; Bin ZANG
Journal of China Medical University 2016;45(12):1105-1109
Objective To analysis the characteristics of thromboelastography and coagulation test in patients with advanced pregnancy combined with severe preeclampsia. Methods A retrospective single?center study was conducted. 35 patients with advanced pregnancy combined with se?vere preeclampsia who were admitted to hospital from January 2012 to December 2014 were analyzed compared to 43 third trimester patients with?out any complication. All the patients were treated based on the routine strategy. Blood sample were taken from the middle elbow vein to test blood cell count,serum biochemistry test,routine coagulation test and thromboelastography. All the results,including R,K,CI,α?angle and MA value, were compared between two groups. Analysis was performed to evaluate the correlation between all parameters of TEG and coagulation test. Re?sults There was no statistical significance between two groups in age ,prothrombin time and activated partial prothrombin time. In the severe pre?eclampsia group,the R value of TEG was increased(5.21±1.20 min vs 6.19±1.55 min,t=-3.144,P=0.002),α?angel was decreased(64.43°± 7.90° vs 60.37°±7.09°,t=2.367,P=0.02),and CI was decreased(0.81±2.27 vs-0.37±1.82,t=2.495,P=0.015). In blood cell count test,the platelets count was decreased in severe preeclampsia group[(217.48±65.68)×109/L vs(166.65±61.39)×109/L,t=3.500,P=0.001]. In routine coagulation test,only thrombin clotting time was increased in severe preeclampsia group(14.59±0.51 s vs 15.28±0.97 s,F=-3.800,P<0.001). In serum biochemistry test,the albumin was decreased in severe preeclampsia group(34.75±3.90 g/L vs 28.77±4.05 g/L,t=6.632,P<0.001),while serum urea nitrogen was increased(2.78±0.87 mmol/L vs 5.98±8.07 mmol/L,F=-2.333,P=0.026). In correlation analysis,thrombin clot?ting time had relationship between R(r=0.290,P=0.010),CI(r=-0.257,P=0.023)andα?angle(r=-0.243,P=0.032). Platelets count cor?related with CI(r=0.383,P=0.001),K(r=-0.409,P<0.001),α?angle(r=0.375,P=0.001)and MA(r=0.512,P<0.001). Conclusion For those who suffered from severe preeclampsia patients with advanced pregnancy,low coagulation function occurs in most of the patients com?pared to those patients without any complications. Thromboelastography may be helpful for those who have high risk factors ,especially with low platelets count and increased thrombin clotting time ,so as to reduce the incidence of bleeding or thromboembolic diseases.
6.Expression of HIF-1? in rat's radiation-induced oral mucositis
Chongjin FENG ; Junbing GUO ; Hongwei JIANG ; Chunyang LI ; Bin CHENG ; Yong CHEN ; Hanyu WANG ; Huijun LI
Chinese Journal of Pathophysiology 1989;0(06):-
AIM: To detect the mRNA and protein level of HIF-1 alpha in the tissues of rat's radiated mucosa. METHODS: The left buccal mucosa was irradiated and excised. The right buccal mucosa was excised to serve as own control tissue. The mRNA of HIF-1 alpha was determined by using the semi quantitative RT-PCR. SABC method was employed to immunostain and to elucidate the localization, intensity and distribution of HIF-1 alpha protein.RESULTS: A Sprague-Dawley rat's model of radiation-induced oral mucositis (ROM) was successfully established. The results of RT-PCR indicated that the left buccal mucosa expressed HIF-1 alpha mRNA while the right buccal mucosa did not or seldom expressed it. Immunohistochemical analysis of HIF-1 alpha demonstrated that the left side mucosa expressed HIF-1 alpha protein.CONCLUSION: The mucosa of ROM expresses the mRNA and protein of HIF-1 alpha. The expressions of HIF-1 alpha are correlated with the severity of ROM.
7.Pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone hydrochloride.
Caixia WANG ; Chunlei LI ; Xi ZHAO ; Hanyu YANG ; Na WEI ; Yanhui LI ; Li ZHANG ; Lan ZHANG
Acta Pharmaceutica Sinica 2010;45(12):1565-9
This study is to compare the pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone (Mit-lipo) and free mitoxantrone (Mit-free). The antineoplastic effect of Mit-lipo was evaluated on PC-3 human xenograft tumor model after repeated intravenous injection at dose levels of 1, 2 and 4 mg x kg(-1). The pharmacokinetic study of Mit-lipo and Mit-free was performed on dogs following a single intravenous injection. The tissue distribution of Mit-lipo and Mit-free was observed on S-180 bearing mice after a single intravenous injection. (1) Pharmacodynamics: Mit-lipo dose-dependently inhibited PC-3 tumor growth at a dose ranging from 1 to 4 mg x kg(-1). The antitumor effect studies showed that Mit-lipo significantly improved the therapeutic effect in comparison with free drug. (2) Pharmacokinetics: in comparison with Mit-free, the AUC and t(1/2) values of Mit-lipo at the same dose level were higher than those of Mit-free in Beagle dogs. The results showed that Mit-lipo had long circulation characteristics. (3) Tissue distribution in S-180 bearing mice: compared to Mit-free, Mit-lipo preferentially accumulated into tumor zones instead of normal tissues. Tumor AUC in Mit-lipo treated animals was 8.7 fold higher than that in mice treated with the same dose of Mit-free. The Cmax values of Mit-lipo in heart, kidney, lung, spleen and intestinal tissue in Mit-lipo were 30.2%, 161.6%, 20.2%, 27.9% and 78.3% lower than those of Mit-free, respectively. The pharmacokinetics and tissue distribution of Mit-lipo changed obviously, thus increasing therapeutic effect and improving drug therapeutic index.
8.Tendency of quality of life in patients with nasopharyngeal carcinoma treated with conventional radiotherapy
Weiwei XIAO ; Taixiang LU ; Jiaxin LI ; Qing LIU ; Chong ZHAO ; Fei HAN ; Hanyu WANG
Chinese Journal of Radiation Oncology 2010;19(2):87-91
Objective To investigate the tendency of quality of life in patients with nasopharyngeal carcinoma (NPC) treated with conventional radiotherapy. Methods Quality of life in NPC patients was assessed using FACT-H&N and NPC-QOL Patients were divided into nine groups according to the treatment period :before treatment group, 0 -20 Gy group, 20 -50 Gy group, > 50 Gy group, 0 -6 months after treatment group, 6 - 12 mouths group, 1 -2 years group, 2 -3 years group and 3 -5 years group. Scores of FACT-H&N and NPC-QOL were compared between the either two groups. Results 450 NPC patients were assessed. The total score of FACT-H&N decreased during the treatment and then increased six months after the treatment. The tendencies of physical and functional well-being were similar. The social/family and emotional well-being did not change significantly along with the treatment but the scores of head and neck well-being and NPC-QOL decreased obviously. Xerotomia was aggravated from the initiation of treatment and became the most severe at 6 - 12 months after treatment. 50% - 60% of the patients with disease-free reported severe xerotomia at 3 -5 years after radiotherapy. Incidence of severe trismus increased up to 14% at 3 -5 years after treatment. Conclusions Quality of life of NPC patients with conventional radiotherapy deteriorates during the treatment period, but recovers to the normal level six months after the treatment. Xerotomia and trismus can affect the quality of life of NPC patients.
9.Outcomes and prognostic factors in patients with primary bone lymphoma
Ge WEN ; Hanyu WANG ; Yujing ZHANG ; Ling CAI ; Yong YANG ; Yunfei XIA ; Xunxing GUAN ; Mengzhong LIU
Chinese Journal of Radiation Oncology 2011;20(4):313-316
Objective To retrospectively analyze the treatment results and prognostic factors in patients with primary bone lymphomas (PBL).Methods Thirty-one patients with PBL treated between April 1994 and May 2009 at Sun Yat-sen University Cancer Center were analyzed.All patients were diagnosed by pathology.Twenty-two patients had stage Ⅰ E, 4 patients had stage Ⅱ E and 5 patients had stage ⅣE diseases.One patient was treated with surgical resection alone, 1 patient with radiotherapy (RT) alone, 2 patients with chemotherapy (CT) alone and 4 patients with resection followed by chemotherapy.The remaining 23 patients received CT combined with RT.The median radiation dose was 50 Gy.Results The median follow-up time was 45.2 months.The follow-up rate was 83.9%.Nine patients had a follow-up time of 10 years.The 5-year and 10-year overall survival rates were 92% and 92%, respectively.The 5-year and 10-year disease-free survival rates were 79% and 70%, respectively.In the group who received non-combined chemoradiotherapy, the complete response rate was 50%, the incidence of progression or recurrence was 2/8 and the median recurrence time was 6.8 months.In the group who received combined chemoradiotherapy, the complete response rate was 65%, the incidence of progression or recurrence was 13% and the median recurrence time was 39.1 months.In univariate analyses, favorable prognostic factors for survival included age≤50 years (χ2=5.32,P=0.021) and ECOG PS score 0-1(χ2=5.48,P=0.019).Favorable prognostic factors for DFS included IPI score≤1(χ2=7.81,P=0.005) and ECOG PS score 0-1(χ2=18.70,P=0.000).Conclusions Treatment results of patients with PBL can be generally well.CT combined with RT appears to be the treatment of choice.RT dose ≥40 Gy is safe and feasible.Younger age and better performance status are associated with a better outcome.
10.Influence of intensity-modulated radiotherapy on tumor regression in nasopharyngeal carcinoma
Fei HAN ; Weiwei XIAO ; Hanyu WANG ; Ying HUANG ; Meiling DENG ; Chong ZHAO ; Taixiang LU
Chinese Journal of Radiological Medicine and Protection 2012;32(2):204-206
Objective To retrospectively analyze the influence of intensity-modulated radiotherapy (IMRT) on tumor regression in primary nasopharyngeal carcinoma (NPC).Methods 272 patients with NPC received radical radiotherapy alone,196 by IMRT with a total treatment time of 6 weeks,and 76 by bilateral field conventional radiotherapy (CRT) with the total treatment timc of 7 weeks.Results By the end of radiotherapy,the primary tumor and neck lymph node residual rates of the IMRT group were 36.7% and 44.2%,respectively,both significantly higher than those of the GRT group (21.1% and 26.6%,x2 =6.15,3.99,P < 0.05).Three months after the radiotherapy,residual lesions were observed at the nasopharynx or neck lymph nodes in 12 of the IMRT group,with a residual rate of 6.1%,not significantly different from that of the CRT group (9.2%,7/76).The 12 residual lesions of the IMRT group all vanished completely 4 -9 months after the radiotherapy.Conclusions There is an obvious difference in regressive mode between IMRT and CRT technique in NPC treatment.At the end of IMRT,the tumor residual rate is slightly increased.However,the delivered dose of gross tumor volume (GTV) is sufficient,and the boost dose should not be delivered indiscreetly.