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.Comparison of clinical features and prognosis between patients with early-stage NK/T-cell lymphoma originating from nasal cavity and Waldeyer's ring
Shaoqing NIU ; Yujing ZHANG ; Yong YANG ; Qing XIA ; Ge WEN ; Hanyu WANG ; Yunfei XIA
Chinese Journal of Radiation Oncology 2013;22(5):352-356
Objective To investigate the differences in clinical features and prognosis between patients with stage Ⅰ E-Ⅱ E nasal cavity natural killer (NK)/T-cell lymphoma (NC-NKTL) and Waldeyer's ring NK/T-cell lymphoma (WR-NKTL).Methods A retrospective analysis was performed on 273patients with NK/T lymphoma who were initially treated in our hospital from January 1991 to December 2011.Of these patients,184 had Ann Arbor stage Ⅰ E disease,and 89 had stage Ⅱ E disease;209 had NCNKTL,and 64 had WR-NKTL.A total of 258 patients (94.5%) were first treated with chemotherapy.The majority of patients received CHOP or CHOP-like chemotherapy.The median dose of radiotherapy was 54Gy.Results Compared with NC-NKTL patients,WR-NKTL patients had significantly higher percentages of individuals in stage Ⅱ E and individuals with B symptoms (P <0.05 for both).The overall response rates of the two groups after treatment were similar (88.7% vs 87.9%,P =0.869).The follow-up rate was 96.3%.196 patients were followed up for at least 5 years.The 5-year overall survival (OS) and progression-free survival (PFS) were 52.6% and 41.4%,respectively.The 5-year OS of NC-NKTL patients was nonsignificantly higher than that of WR-NKTL patients (57.0% vs 39.0%,P =0.062),while the 5-year PFS of NC-NKTL patients was significantly higher than that of WR-NKTL patients (46.7% vs 25.8%,P =0.019).Conclusions Patients with early-stage WR-NKTL are more prone to systemic symptoms and cervical lymph node metastasis and have poorer prognosis,as compared with patients with early-stage NC-NKTL,so radiotherapy and prophylactic irradiation should be considered in early stage.
6.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.
7.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.
8.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.
9.Salvage treatment outcome and prognosis of patients with locoregionally recurrent early-stage extranodal NK/T cell lymphoma,nasal type
Qin TONG ; Yanrong LUO ; Yujing ZHANG ; Lingling FENG ; Yiyang LI ; Hanyu WANG ; Yunfei XIA ; Xiaohong AI
Chinese Journal of Radiation Oncology 2017;26(1):45-49
Objective To retrospectively analyze the prognostic factors for locoregionally recurrent early?stage extranodal nasal?type natural killer/T?cell lymphoma ( NKTCL) . Methods A total of 56 patients with early?stage extranodal nasal?type NKTCL, who had locoregional recurrence after initial treatment and then received salvage treatment from 1995 to 2014, were enrolled as subjects. The effects of salvage treatment on the overall survival ( OS) rate were analyzed after initial treatment and recurrence. Univariate and multivariate prognostic analyses were performed on the OS rate after recurrence. Results The median follow?up time was 35. 9 months after initial treatment and 14. 8 months after recurrence. The 3?year OS rate was 73% after initial treatment and 58% after recurrence. Compared with chemotherapy alone, radiotherapy?containing salvage treatment significantly improved the OS rates after initial treatment and recurrence ( P=0. 040, 0. 009 ) , and re?irradiation also significantly improved the OS rates after initial treatment and recurrence (P=0. 018, 0. 019). Most (84%) of the acute and late adverse reactions after re?irradiation were grade 1?2 ones. The univariate and multivariate analyses showed that the Karnofsky Performance Status score, radiotherapy in initial treatment, and radiotherapy in salvage treatment were influencing factors for the OS rate after recurrence. Conclusions Radiotherapy achieves improved survival and tolerable toxicities, making it indispensable in the treatment of locoregionally recurrent extranodal nasal?type NKTCL.
10.Serological evaluation using recombinant 16 ku-38 ku-ESAT-6 protein of mycobacterium tuberculosis
Lijian WU ; Bo ZOU ; Fang NIE ; Hanyu ZHANG ; Meiqiu SUN ; Benzhi JIA ; Xiaoge WANG
Chinese Journal of Postgraduates of Medicine 2011;34(13):7-10
Objective To investigate the diagnostic value of 16 ku-38 ku-ESAT-6 protein in tuberculosis (TB). Methods ELISA was used for measuring the level of recombinant 16 ku-38 ku-ESAT-6 protein in 105 TB patients (TB group,26 patients with smear-positive, 79 patients with smear-negative) and 45 controls (control group, 20 healthy volunteers and 25 subjects with pulmonary diseases other than TB). The value of the antigen for diagnosis of TB in serodiagnosis was assessed, and ROC curve evaluation system was established. Results In control group, the positive rate of anti-recombinant 16 ku-38 ku-ESAT-6 protein and commercialization of TB antibody test kit had significant difference [6.67% (3/45) vs. 51.11% (23/45)](P<0.01);but in TB group, there was no significant difference [59.05%(62/105) vs. 64.76% (68/105)](P>0.05). The optical density value in TB group and control group was 2.22 ± 0.58 and 1.35 ± 0.24,and there was significant difference(t = 6.06,P< 0.01). The sensitivity, specificity, positive predictive value and negative predictive value of the test was 59.05%,93.33%,95.38%,49.41% respectively. Analyzed by ROC curve, the area under the curve was 0.751, the- value of cutoff was 2.52, and sensitivity and specificity was 65.4% and 84.8%. Conclusions Recombinant 16 ku -38 ku -ESAT-6 protein of mycobacterium tuberculosis has higher specificity, and it can significantly distinguish TB and non-TB. So it might be selected as one of diagnosis antigens of TB.