AIM:To investigate the effect of ginkgo leaf extract on oxidative stress and haemodynamics of diabetic nephropathy(DN).METHODS:The patients of DN were divided into ginkgo leaf extract treatment group and control group.The changes of serum superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and hemorheology indexes were observed.RESULTS:Before treatment,serum SOD,GSH-Px,MDA and hemorheology indexes had no significant difference between ginkgo leaf extract treatment group and control group.After treatment,the serum levels of T-SOD and GSH-Px were increased;the level of MDA,hemorheology indexes,erythrocyte aggregation index and platelet aggregation rate were decreased significantly in ginkgo leaf extract treatment group compared with those in control group(P

Objective To optimize the spray pelletization technology for Compound Jiakang Tablets.Methods The experiment was performed by orthogonal design,and the inspection criteria key were granule uniformity,granule size and the content of astragaloside IV,combined with the granule hygroscopic velocity.Results The optimal spray pelletization parameters were as follows:the frequency of main fan was(35.0?5)Hz,atomizational pressure was 0.1 mPa,the rate of spray was 1.2 Hz,the density of extract was 1.20 g/mL.Conclusion The granules made by this technology are uniform,burly,stable,and are beneficial for pressing into tablet.

Objective To observe how different measuring methods of corneal curvature produce affect postoperative corneal a-stigmatism correction after implantation of TORIC artificial lens .Methods To measure 4 teams of age-related cataract patients complicated with regular astigmatism of more than 1 .0D by the procedure of manual keratometer ,IOL Master ,auto keratometer and Pentacam respectively .The Toric artificial lenses were precisely placed in appropriate position in phacoemulsification surgery .We observed the uncorrected visual acuity (UCVA) ,best corrected visual acuity (BCVA) in 1D ,1W ,1M ,3M before and after the sur-gery ,corneal astigmatism after the surgery ,as well as anticipated and consequent residual astigmatism .Results The variance analy-sis of absolute-value deviation between anticipated residual astigmatism (ARA) and best corrected visual acuity (BCVA) is P<0 .0001 ,the above difference was statistically significant ;we consider that the astigmatic deviation measured by the four methods is different ;besides the deviation of paired comparison results between Master-team (0 .322) and auto-team (0 .242) ,auto-team and manual-team (0 .218) ,manual-team and Pentacam-team(0 .107) is more than 0 .05 and not statistically significant ,all the remaining paired comparison results are statistically significant ,(P<0 .05) ,the Pentacam-team (0 .082) is the minimum deviation ,while the IOL Master-team (0 .422) is the maximum one .Conclusion The measuring result to estimate the exact value of Acrysof Toric IOL by Pentacam is more accurate than by other methods .

Objective To evaluated diagnosis yield of cytological and histological analysis of endoscopic ultrasound guided fine needle aspiration (EUS-FNA).Methods A total of 43 patients who were clinically diagnosed as having mediastinal lesions,retroperitoneal lesions or pancreatic lesions by CT were recruited to the study.EUS-FNA was performed with standard 22G needle.Specimens were placed in formalin for histological analysis,and residual materials were prepared for cytologic analysis.Results Lesions were located in the mediastinum (n =9),the retroperitoneum (n =1),and pancreas (n =33).Cytologic diagnoses included malignancy (n =22),suspicious malignancy (n =2),atypical cell (n =3),absence of malignancy (n =16).Histologic diagnoses included malignancy (n =30),suspicious malignancy (n =1),sarcoidosis (n =2),chronic inflammation (n =10).The positive rates,sensitivities and accuracies of cytology and histology were 51％,59％,65％ and 74％,81％,84％,respectively.Conclusion The positive rate,sensitivity and accuracy of histology of EUS-FNA is superior to cytology.

This study aims to investigate the effects of fibroblast growth factor 21 (FGF-21) on learning and memory abilities and antioxidant capacity of D-galactose-induced aging mice. Kunming mice (37.1 +/- 0.62) g were randomly divided into normal control group, model group and FGF-21 high, medium and low dose groups (n = 8). Each group was injected in cervical part subcutaneously with D-galactose 180 mg x kg(-1) x d(-1) once a day for 8 weeks. At the same time, FGF-21-treated mice were administered with FGF-21 by giving subcutaneous injection in cervical part at the daily doses of 5, 2 and 1 mg x kg(-1) x d(-1). The normal control group was given with normal saline by subcutaneous injection in cervical part. At seventh week of the experiment, the learning and memory abilities of mice were determined by water maze and jumping stand tests. At the end of the experiment, the mice were sacrificed and the cells damage of hippocampus was observed by HE staining in each group. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and total antioxidant capacity (T-AOC) in the brain of mice were determined. The results showed that different doses of FGF-21 could reduce the time reaching the end (P < 0.01 or P < 0.05) and the number of touching blind side (P < 0.01 or P < 0.05) in the water maze comparing with the model group. It could also prolong the latency time (P < 0.05) and decrease the number of errors (P < 0.01 or P < 0.05) in the step down test. The result of HE staining showed that FGF-21 could significantly reduce brain cell damage in the hippocampus. The ROS and MDA levels of three different doses FGF-21 treatment group reduced significantly than that of the model group [(5.58 +/- 1.07), (7.78 +/- 1.92), (9.03 +/- 1.77) vs (12.75 +/- 2.02) pmol (DCF) x min(-1) x mg(-1), P < 0.01 or P < 0.05], [(2.92 +/- 0.71), (4.21 +/- 0.81), (4.41 +/- 0.97) vs (5.62 +/- 0.63) nmol x mg(-1) (protein), P < 0.01]. Comparing with the model group, the activities of SOD, GPx, CAT and T-AOC of the three different doses FGF-21 treatment groups were also improved in a dose-dependent manner. This study demonstrates that FGF-21 can ameliorate learning and memory abilities of D-galactose induced aging mice, improve the antioxidant abilities in brain tissue and delay brain aging. This finding provides a theoretical support for clinical application of FGF-21 as a novel therapeutics for preventing aging.

Objective A phase Ⅱ trial of anti-programmed death-1 (PD-1) monoclonal antibody CT-011,an anti PD-1 humanized monoclonal antibody combined with rituximab therapy in patients with relapsed follicular lymphoma (FL) were conducted.Methods In order to evaluate the safety and efficacy of CT-011,the impacts of CT-011 on immune cells both from the peripheral blood (PB) samples and tumor microenvironment were examined.PB and core needle biopsies from involved lymph nodes were collected prior to and on day 14 after the first infusion of CT-011.PB mononuclear cells (PBMC) were analyzed by multiparametric flow cytometry to determine various immune cell subsets.Whole genome gene expression profiling (GEP) was performed on core needle biopsies.Results A significant increase in the absolute number of PB immune cells were observed in day 14 samples compared with baseline including total lymphocyte count (P ＜ 0.01),CD+3 T cells (P =0.01),CD+4 T cells (P ＜ 0.01).Comparison of GEP from core needle biopsies obtained pretreatment and day 14 (n =8 pairs) showed up regulation of several genes associated with T cell activation.Conclusion Administration of CT-011 was associated with increase in the numbers of CD+4 T cells and resulted in activation of T cells in the PB and the tumor microenvironment in FL.These results provide insight into the mechanism of action of CT-011 and offer a predictive biomarker for selection of patients for future clinical trials with this class of agents in FL.

To investigate the cell-killing effect and its possible mechanism of rClone30-hDR5 in combination with TRAIL on human hepatic carcinoma (HCC) cell line, first of all, recombinant plasmid pee12.4-hDR5 was introduced into HepG2 cells by liposome transfection. After five rounds of screening by flow cytometry, HepG2 cells expressing high levels of DR5 on cell surface were isolated. The cytotoxicity of TRAIL to selected cells was higher than that of TRAIL to HepG2 cells by MTT method (P < 0.01). The result suggested that the cloned hDR5 gene had biological activity. MTT assay showed that, rClone30- hDR5 in combination with TRAIL more efficiently inhibited the tumor growth of HepG2 cells compared to rClone30-hDR5 or TRAIL in vitro. The results of Annexin V-FITC/PI staining and Quantitative Real-time PCR indicated that rClone30-hDR5 in combination with TRAIL significantly increased the mRNA levels of caspase 3 and caspase 8, and induced the apoptosis of tumor cells. HepG2 cells were infected with rClone30-hDR5 or rClone30 at MOI of 1. The expression of hDR5 on tumor surface increased significantly by rClone30-hDR5 compared to that by rClone30, which contributed to the sensitivity to TRAIL. In conclusion, rClone30-hDR5 in combination with TRAIL has potential application value in cancer treatment.

Objective To evaluate the effect of aminolevulinic acid-based photodynamic therapy (ALA-PDT) on the expression of protein kinase D1 (PKD1) in a cutaneous squamous cell carcinoma cell line A431,and to explore the mechanism underlying ALA-PDT-induced apoptosis of A431 ceils.Methods A431 cells were cultured in vitro,and cell counting kit-8 (CCK-8) assay was performed to select the optimal combination of ALA concentration and PDT dose with the strongest proliferation inhibitory effect.A431 ceils at exponential growth phase were randomly divided into 4 groups:control group receiving no treatment,ALA group treated with ALA solution alone,PDT group treated with PDT alone,and ALA-PDT group treated firstly with ALA solution and then with PDT.After 12-,24-,36-and 48-hour additional culture,CCK-8 assay was conducted to evaluate the cellular proliferation inhibition,and the apoptosis rate at the time point of the strongest proliferation inhibitory effect was measured by flow cytometry.RT-PCR was performed to determine the expression of protein kinase D1 gene (PRKD1) in A431 cells at different time points after the ALA-PDT treatment,and Western blot analysis to measure protein expression of PKD 1 and its phosphorylation at Tyr463 (pTyr463) and Ser916 (pSer916) in A431 cells.Results The combination of ALA at the concentration of 1.5 mmol/L with PDT at an irradiation dose of 2 J/cm2 was optimal due to its strongest proliferation inhibitory effect.After 12-,24-,36-and 48-hour additional culture,there were significant differences in the proliferation inhibition rate among the 4 groups (F =39.56,P ＜ 0.05).At 24 hours after the treatment,the ALA-PDT group showed significantly higher proliferation inhibition rate (46.26％ ± 1.25％) compared with the ALA group (14.65％ ± 0.33％,P ＜ 0.05),PDT group (14.96％ ± 0.68％,P ＜ 0.05) and control group (11.98％ ± 0.32％,P ＜ 0.05),as well as compared with that at 12 hours (P ＜ 0.05).At 24 hours after the treatment,the apoptosis rate significantly differed among the 4 groups (F =16.32,P ＜ 0.05),and the ALA-PDT group showed a significantly higher apoptosis rate (41.92％ ± 3.23％) compared with the control group (4.67％ ± 0.88％,P ＜ 0.05),ALA group (7.02％ ± 1.52％,P ＜ 0.05) and PDT group (8.37％ ± 0.59％,P ＜ 0.05).At 0,6,12,24,36 and 48 hours after the treatment,there were significant differences in the mRNA expression of PRKD 1 among the 4 groups (F =22.24,P ＜ 0.05),and the mRNA expression of PRKD1 at 24 hours was significantly lower than that at 0,6,12 hours (all P ＜ 0.05),but was not significantly different from that at 36 and 48 hours (both P ＞ 0.05).No significant difference in the Ser916-phosphorylated PKD1 expression was found among the 4 groups (F =1.53,P ＞ 0.05),while there were significant differences in the expression of PKD1 and Tyr463-phosphorylated PKD 1 among the 4 groups (F =10.04,8.27,both P ＜ 0.05).Additionally,the ALA-PDT group showed significantly lower expression of PKD 1 and Tyr463-phosphorylated PKD 1 compared with the control group,ALA group and PDT group (all P ＜ 0.05).Conclusion PKD1 may be involved in the photochemical process of A431 cell apoptosis induced by ALA-PDT,and may promote the occurrence of squamous cell carcinoma by Tyr463 phosphorylation.

Objective:To study the efficacy of direct intrahepatic portosystemic shunt (DIPS) in treatment of Budd-Chiari syndrome (BCS).Methods:From January 1, 2015 to June 31, 2017, consecutive patients with BCS who were treated with DIPS at the Department of Interventional Therapy of Beijing Shijitan Hospital, the Liver Disease Research Center of Beijing Friendship Hospital and the General Surgery Department of Beijing Ditan Hospital were retrospectively analyzed. The symptoms, physical signs (including abdominal distension, ascites, pleural effusion, splenomegaly, hepatic encephalopathy) and perioperative laboratory results of these patients were collected and analyzed. Biochemical indicators including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), and portal pressure gradient were compared before and 2 weeks after treatment. The patients were followed up for at least 3 years to assess their clinical symptoms, patency of shunt, oncological status and survival.Results:Of 67 patients with BCS who were included in the study, there were 45 males and 22 females, aged (38.12±23.22) years. The BCS classification of these patients were hepatic vein type ( n=65), including 62 patients with complete hepatic vein obstruction, 3 patients with hepatic vein occlusion due to thrombosis, and 2 patients with mixed hepatic vein and inferior vena cava occlusion. All 67 patients underwent DIPS with 93 stents being implanted. In addition, 43 patients underwent gastric coronary vein embolization, and 2 patients with mixed type of BCS underwent inferior vena cava stenting. The portal pressure gradient decreased from (22.17±9.16) mmHg (1 mmHg=0.133 kPa) to (9.87±4.75) mmHg, the difference was statistically significant ( P<0.05). Abdominal distension was relieved, at one month and ascites completely subsided in 3 months after operation. The liver congestion and swelling were obviously relieved. Comparison of patients 2 weeks after operation and before operation, ALT decreased from (65.28±27.75) U/L to (28.43±13.46)U/L, AST from (68.75±29.23) U/L to (26.92±13.33)U/L, TBil from (175.31±80.48)μmol/L to (45.08±26.54)μmol/L, DBil from (127.55±44.65)μmol/L to (35.12±10.77)μmol/L, and albumin increased from (31.56±7.22) g/L to (44.18±11.36)g/L, the difference was statistically significant (all P<0.05). All patients were followed up for at least 3 years. Shunt stenosis was detected in 5 patients (7.46%) with shunt expansion being performed, variceal bleeding in 2 patients (2.99%), ascites recurrence in 4 patients (5.97%) and hepatic encephalopathy in 2 patients (2.99%). No patients were diagnosed with hepatic cancer, and no patients died. Conclusion:DIPS was efficacious, safe and reliable to that BCS patients. It rapidly reduced portal venous pressure, relieved liver congestion, and restored liver morphology and liver function in these patients.

Objective To investigate the clinical efficacy of transjugular intrahepatie portosystemie shunting (TIPS) for recurrent portal hypertension after liver transplantation.Methods The retrospective crosssectional study was conducted.The clinical data of 15 patients with recurrent portal hypertension after liver transplantation who underwent TIPS in the 9th School of Clinical Medicine between January 2008 to June 2016 were collected.Course of TIPS:the portal vein pressure was measured and varicose veins were embolized after puncture,cannulation and angiography.A balloon catheter with diameter of 7 mm or 8 mm was used to dilate the preshunt channel,and a covered stent or bare stent with a diameter of 7,8 or 10 mm was implanted to establish the shunt channel.Portal vein angiography was performed and the portal vein pressure was measured again.Observation indicators:(1) Surgical situations;(2) changes of portal vein pressure before and after TIPS;(3)follow-up and survival situations.Follow-up using outpatient examination was performed to record clinical symptoms at postoperative 1,3,6 and 12 months.Regular hepatic vascular ultrasonography was done at postoperative 1,3,6 and 12 months to detect patency of shunt.The follow-up period was up to June 2018.Measurement data with normal distribution were represented as (x) ±s and analyzed by the paired t test.Measurement data with skewed distribution were described as M (range).Count data were represented as percentage.Results (1) Surgical situations:all the 15 patients underwent successful TIPS,without any serious complications or death.Stent implantation situation:bare stent,covered stent and bare stent + covered stent were implanted in 4,8 and 3 patients,respectively.Among the 15 patients,7 mm,8 mm and 10 mm diameter shunt channel were established in 4,8 and 3 patients respectively.(2) Changes of portal vein pressure before and after TIPS:portal vein pressure of the 15 patients decreased from (34±8)mmHg (1 mmHg=0.133 kPa) to (21±7)mmHg before and after TIPS,with a statistically significant difference (t =7.07,P＜0.05).Portal vein pressure gradient decreased from (26± 9)mmHg to (12±5)mmHg before and after TIPS,with a statistically significant difference (t=6.43,P＜0.05).(3) Follow-up and survival situations:15 patients were followed up for 24.0-60.0 months,with a median follow-up time of 37.8 months.Main clinical symptoms:of 12 patients with gastrointestinal hemorrhage,3 had gastrointestinal rehemorrhage mainly due to portal vein pressure rising again caused by shunt restenosis or occlusion,9 had no gastrointestinal rehemorrhage.Of 5 patients with portal vein thrombosis,thrombus was disappeared basically in 3 patients and decreased obviously (no effect on blood flow) in 2 patients.Three patients with refractory ascites were effectively improved after TIPS,however,2 of them were recurred at postoperative 5 months.Postoperative restenosis or occlusion of shunt channel:among 15 patients,7 developed restenosis or occlusion of the shunt channel (including 4 with bare stents).Five of them underwent shunt recanalization and another 2 without special clinical symptoms had no treatment.Hepatic encephalopathy:6 of 15 patients including 1 with 7 nun shunt,3 with 8 mm shunt and 2 with 10 mm shunt developed hepatic encephalopathy,of which grade Ⅰ,Ⅱ,Ⅲ,and Ⅳ hepatic encephalopathy wee detected in 2,3,0 and 1 patients,respectively.Survival situations:of the 15 patients,1 died of hepatic failure at postoperative 6 months,3 were performed liver transplantation again at postoperative 3,8 and 14 months,respectively,11 survived more than 2 years with the longest survival time more than 6 years.Conclusion TIPS is safe and effective for recurrent portal hypertension after liver transplantation for patients who have not effective other treatment.