AIM:To investigate whether crocin alleviates right ventricular injury induced by monocrotaline(MCT)in rats with pulmonary arterial hypertension(PAH),and to explore the underlying mechanisms.METHODS:Forty male SD rats were randomly divided into 4 groups:normal group,PAH group,crocin group and sildenafil group,with 10 rats in each group.The rats in PAH,crocin and sildenafil groups received subcutaneous injection of MCT(50 mg/kg)to establish the PAH model.Starting from the day of MCT injection,the rats in crocin group received crocin(200 mg/kg),the rats in sildenafil group received sildenafil(30 mg/kg),and those in PAH and normal groups were orally gavaged with an equal volume of saline once daily.After 4 weeks,measurements of right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),right ventricular hypertrophy index(RVHI)and right ventricular mass index(RVMI)were taken for the rats in each group.Tissue staining was conducted to observe pathological changes in the right ventricle,and the expression levels of inflammatory factors(IL-1β,IL-6 and TNF-α),the p38 MAPK/NF-κB inflammato-ry pathway,CCL2,CCR2,and the macrophage marker CD68 were assessed.RESULTS:Compared with PAH group,the rats in crocin and sildenafil groups exhibited significant reductions in RVSP,mPAP,RVHI and RVMI(P＜0.05).Right ventricular tissue displayed no evident infiltration of inflammatory cells or proliferation of collagen fibers.The down-regulation of the p38 MAPK/NF-κB pathway and inflammatory factors(IL-1β,IL-6 and TNF-α)was significant(P＜0.05).Additionally,the CCL2/CCR2 pathway and the infiltration of CD68+ macrophages were markedly decreased(P＜0.05).CONCLUSION:Crocin effectively mitigates right ventricular damage in MCT-induced PAH rats,with its effica-cy comparable to that of sildenafil at the dosage utilized in this experiment.Some protective mechanisms of crocin may be attributed to its regulatory effects on inflammation.

Collagen, which widely exists in skin, bone, muscle and other tissues, is a major structural protein in mammalian extracellular matrix. It participates in cell proliferation, differentiation, migration and signal transmission, plays an important role in tissue support and repair and exerts a protective effect. Collagen is widely used in tissue engineering, clinical medicine, food industry, packaging materials, cosmetics and medical beauty due to its good biological characteristics. This paper reviews the biological characteristics of collagen and its application in bioengineering research and development in recent years. Finally, we prospect the future application of collagen as a biomimetic material.
Animals ; Collagen/analysis* ; Tissue Engineering/methods* ; Extracellular Matrix/metabolism* ; Biomimetic Materials/chemistry* ; Bone and Bones ; Tissue Scaffolds ; Mammals/metabolism*

Objective:To investigate the clinical efficacy of laparoscopic radical resection of hilar cholangiocarcinoma.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 25 patients with hilar cholangiocarcinoma who were admitted to Henan Provincial People′s Hospital from January 2017 to July 2019 were collected. There were 16 males and 9 females, aged from 51 to 75 years, with a median age of 64 years. All the 25 patients underwent laparoscopic radical resection of hilar cholangiocarcinoma. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up using out-patient examination and telephone interview was performed to detect local recurrence and distant metastasis of patients up to December 2019. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were described as M (range). Count data were described as absolute numbers. Results:(1) Surgical situations: of the 25 patients, 15 patients in Bismuth typeⅠunderwent laparoscopic radical resection of hilar cholangiocarcinoma+ regional lymph node dissection+ Roux-en-Y choledocho-jejunostomy, 2 patients in Bismuth type Ⅱ underwent laparoscopic radical resection of hilar cholangiocarcinoma+ perihilar resection+ regional lymph node dissection+ Roux-en-Y choledochojejunostomy, 2 patients in Bismuth type Ⅲa underwent laparoscopic radical resection of hilar cholangiocarcinoma+ regional lymph node dissection+ right hemihepatectomy+ hepatic caudate labectomy+ Roux-en-Y choledochojejunostomy, 3 patients in Bismuth type Ⅲb underwent laparoscopic radical resection of hilar cholangiocarcinoma+ regional lymph node dissection+ left hemihepatectomy+ hepatic caudate labectomy+ Roux-en-Y choledochojejunostomy, 3 patients in Bismuth type Ⅳ underwent laparoscopic radical resection of hilar cholangiocarcinoma+ regional lymph node dissection+ hepatic caudate labectomy+ Roux-en-Y choledochojejunostomy. The operation time was (388±118)minutes, and volume of intraoperative blood loss was 200 mL(range, 50-2 000 mL). Six patients were treated with blood transfusion intraoperatively. The operation time of 2 patients in Bismuth type Ⅲa was 375 minutes and 465 minutes, and the volume of intraoperative blood loss was 200 mL and 1 000 mL, respectively; 1 case received blood transfusion. The operation time of 3 patients in Bismuth type Ⅲb was 410 minutes, 465 minutes, 501 minutes, and the volume of intraoperative blood loss was 300 mL, 400 mL, 450 mL, respectively; neither had intraoperative blood transfusion. The operation time of 3 patients in Bismuth type Ⅳ was 415 minutes, 560 minutes, 600 minutes, and the volume of intraoperative blood loss was 300 mL, 600 mL, 800 mL, respectively; 1 case had intraoperative blood transfusion. (2) Postoperative situations: of the 25 patients, 4 patients had grade Ⅰ complications, including 2 cases of biliary fistula (1 case in Bismuth type Ⅰ and 1 case in Bismuth type Ⅲa), 1 case of pulmonary infection (Bismuth type Ⅳ), and 1 case of postoperative liver insufficiency (Bismuth type Ⅲa), all of them were improved after conservative treatment. Results of postoperative pathological examination: bile duct adenocarcinoma and high-grade intraepithelial neoplasia were detected in 23 and 2 patients; there were 8 cases with nerve invasion, 3 cases with lymph node metastasis and no vascular thrombus. The duration of hospital stay and hospitalization expenses were 24 days (range, 10-45 days) and 9.4×10 4 yuan [range, (5.3-18.7)×10 4 yuan] for all the 25 patients; the above indicators were 36 days, 45 days, 15.1×10 4 yuan, 18.7×10 4 yuan for the 2 patients in Bismuth type Ⅲa, 15 days, 26 days, 33 days, 7.3×10 4 yuan, 11.5×10 4 yuan, 15.9×10 4 yuan for 3 patients in Bismuth type Ⅲb, 24 days, 39 days, 41 days, 12.1×10 4 yuan, 15.2×10 4 yuan, 16.7×10 4 yuan for the 3 patients in Bismuth type Ⅳ, respectively. (3) Follow-up: 25 patients were followed up for 2-36 months, with a median follow-up of 16 months. Of the 25 patients, 18 had no recurrence or metastasis, 2 patients in Bismuth type Ⅳ had extensive intraperitoneal metastasis, 1 patients in Bismuth type Ⅲa had trocar hole metastasis, and 4 patients died. Conclusions:Laparoscopic radical resection of hilar cholangiocarcinoma is safe and feasible. Surgeries should be selected strictly based on surgical indications and the Bismuth type.

Objective To evaluate the clinical application value of portal vein implantation pump for chemotherapy in patients with intrahepatic cholangiocarcinoma (ICC) after radical surgery.Methods The clinical data of 97 patients with ICC who underwent radical surgery in Henan People's Hospital from June 2012 to June 2016 were retrospectively analyzed.Results Among the 97 patients,14 patients received portal venous pump chemotherapy (portal group),33 patients received peripheral venous chemotherapy (peripheral group),and 50 patients did not receive postoperative chemotherapy (control group).There were no statistically significant differences in gender and age between the three groups.The results of survival analysis indicated that the disease-free survival (DFS) period and overall survival (OS) time in the portal group and the peripheral group were significantly better than that in control group (both P ＜ 0.05).In addition,despite the lack of statistical significance (P ＞ 0.05),for the control of intrahepatic metastasis,portal vein pump chemotherapy was better than that of systemic chemotherapy via peripheral vein,and almost all side effects of chemotherapy in the portal group were lower than those in the peripheral group.Conclusion Portal vein pump chemotherapy can improve the prognosis of intrahepatic bile duct patients,especially for the control of intrahepatic metastasis,and can reduce systemic side effects of chemotherapy.

Objective To evaluate the effects of laparoscopic splenectomy and esophagogastric devascularization(LSPD) vs.open procedure(OSPD) on stress and immune function in patients with portal hypertension due to cirrhosis.Methods From June 2015 to June 2017 a total of 66 patients underwent LSPD or OSPD procedures.Results Plasma cortisol concentration in the LSPD group was lower than that in the OSPD group (Fgroup =18.85,P =0.020).Cortisol concentration in the two groups increased firstly and then decreased with time extension (Ftime =532.08,P =0.000).The level of CD3 +,CD4 +,CD4 +/CD8 + in LSPD group was higher than that in OSPD group,and the level of CD8 + was lower than that in OSPD group (Fgroup =3.55,21.47,154.84,64.29,P ＜ 0.05),the levels of CD3 +,CD4 + and CD4 +/CD8 + in the two groups first decreased and then increased with the extension of time,and the levels of CD8 + increased firstly and then decreased (Ftime =199.22,298.48,864.33,510.23,P ＜ 0.05),the increase range of CD3 +,CD4 +,and CD4 +/CD8 + in LSED group was higher than that in OSPD group (Finteraction =19.27,18.21,79.55,35.21,P ＜ 0.05);there was no statistical significance in the complications such as:rebleeding,thrombosis and splenic fever in the two groups (x2 =0.05,0.67,0.07,0.16,P=0.829,0.413,0.789,0.693).But the postoperative chest/cavity effusion and fever (＞ 38.0 ℃,and ＞ 3 days) is OSPD group is higher than in the LSPD group(x2 =5.49,6.68,P =0.019,0.010).Conclusion LSPD effectively reduces postoperative stress,protects immune function,decreases postoperative pleural and abdominal effusion and fever.

Objective To assess the safety and efficacy of catheter-directed thrombolysis combined with percutaneous transluminal angioplasty (PTA) in treating acute thrombo-embolism of artificial arteriovenous fistula.Methods The clinical data of 64 patients with acute thrombo-embolism of artificial arteriovenous fistula (84 events in total),who were admitted to single medical center during the period from January 2012 to September 2016,were retrospectively analyzed.The diagnosis of acute thrombo-embolism of artificial arteriovenous fistula was confirmed by angiography via femoral approach in all patients.Mechanical thrombectomy of the thrombotic occlusion segment by using common guide wire was carried out first,which was followed by bolus injection of urokinase (125,000-375,000 units);if the thrombus was not completely dissolved the catheter would be retained and the urokinase would be continuously infused with a micro-pump until the thrombus was completely dissolved.Conventional balloon dilatation would be employed when the stenosis of artificial arteriovenous fistula lumen was ＞50％ or the stenosis impeded the performance of dialysis.Kaplan-Meier survival curve was used to estimate the primary and secondary cumulative patency rates after the first intervention.Results Of the 84 interventional procedures,technical success was achieved in 69 procedures (82.1％).A total of 14 conventional balloon dilatation procedures had to be conducted as the fistula was seriously narrowed,and up to 12 procedures (85.7％) were succeeded.The overall clinical success rate was 78.5％ (66/84).During the therapeutic course,bleeding event occurred in 7 procedures (8.3％),including major bleeding (n=3) and minor bleeding (n=4).After the treatment,the 3-,6-,12-,24-month primary and secondary patency rates were 76.1％,63.6％,40.8％,12.5％ and 81.3％,70.8％,47.0％,32.5％respectively.Conclusion For the treatment of acute thrombo-embolism of artificial arteriovenous fistula,catheter-directed thrombolysis is safe and effective,it can assist conventional balloon dilatation therapy to obtain satisfactory therapeutic result for internal fistula stenosis.

Bromodomain and extra-terminal domain(BET)Bromodomain has become a new target for the treatment of cancers and other human disorders. Nowadays,several classes of its potent and selective small-molecule inhibitors have been identified,many of which are in clinical trials. Preclinical and clinical data have shown that BET Bromodomain inhibitors have good prospects. Howev-er,there are potential therapeutic deficiencies,such as drug resistance. At present,attempts are being made to develop BET Bromodo-main inhibitors and degraders based on polypharmacology,combining BET Bromodomain with other targets of different mechanisms. In this paper,small-molecule kinase/BET inhibitors,small-molecule histone deacetylases(HDAC)/BET inhibitors and BET protein degraders are reviewed,which may provide guidance for further research on BET protein.

Recognizing acetyl-lysine of histone is a key process of epigenetic regulation that is mediated by a protein module called bromodomain(BRD). The bromodomain inhibitors of the bromodomains and extra-terminal(BET)family have shown great potential in anti-inflammatory and antiproliferative effects. Through a review of diseases and structures about BET bromodomain, different kinds of inhibitors were analyzed and their structure-activity relationships were summarized. Herenin, the recent advances reported are reviewed for discovering more excellent small molecule inhibitors.

Objective The purpose of this study was to assess the antibacterial effects of hematoporphyrin monomethylether-photodynamic therapy (HMME-PDT) on Enterococcus faecalis within infected simulated lateral canals in vitro with different energy.Methods Simulated lateral canals were prepared on extracted teeth.The specimens were infected with Enterococcus faecalis and then were randomly divided into eight groups.Group A was considered as negative control,its specimens were irrigated with physiological saline.Group B was the positive control,they were irrigated with 5.25％ NaClO.Other groups were incubated with HMME at concentration of 40 μg/ml for 5 min,followed by exposure to light at 532 nm for 120 s with different powers in a spiral pattern.Groups were named C-H,in corresponding with the power 50,60,70,80,90,100 mW.Microbial samples (the dentin chips from simulated lateral canals) were taken before and after the treatments.The survival fractions in each simulated lateral canal was calculated by counting colony-forming units(CFUs).Results 1.The HMME-PDT-treated groups resulted in a significant reduction in the number of E.faecalis in simulated lateral canals compared with the negative controls(P＜0.05).2.The antibacterial effects of group D、E、F、G、H were higher than the NaCl0-irrigated group(P＜0.05).3.The difference of antibacterial effects between the F、G、H groups was in significant(P＞0.05).Conclusion HMME-PDT had significant inhibitive efficacy on Enterococcus faecalis within infected simulated lateral canals and the efficacy was power-depended.It can play the best effect with the power of 80 mW.

Objective To Study the effect of efflux pump-inhibitors(EPI)-Verapamil in photodynamic therapy (PDT) using hematoporphyrin monomethylether (HMME) as photosensitizer on the cariogenic bacteria in dental plaque biofilms.Methods According to the administrator order of the verapamil and photosensitizer in PDT,streptococcus mutans,streptococcus sanguis,eosinophilic lactobacillus and actinomyces viscosus were used to establish the dental plaque biofilm model.The experiment was divided into five groups,group A was incubated with the photosensitizer and verapamil group,group B using verapamil before incubated the photosensitize,group C suing photosensitizer before incubated verapamil,group D with PDT only,group E was control group.After laser treatment,the influence of the dental plaque biofilms was observed by confocal laser scanning microscope.Results As saline-treated group is a group of normal the dental plaque biofilms.In PDT only group,compared with the saline group,red fluorescence increased significantly,the bacteria lose accumulation capacity,and were isolated and scattered in dispersed state.In PDT plus verapamil group,compared with only PDT group,green staining increased,bacterial activity increased.In group B,cells were incubated with verapamil before incubated the photosensitizer group,green staining increased significantly,red fluorescence reduced,indicating live bacteria increased,and bacteria activity was significantly increased.Conclusion PDT is an effective method in eliminating cariogenic bacteria of dental plaque biofilms.Bacterial efflux pump inhibitors can lower HMME-PDT inhibition cariogenic bacteria in dental plaque biofilm,and pre-verapamil administration could significantly inhibit the effect of PDT treatment of dental caries.