Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of Toxicodendron vernicifluum, a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an in vitro 3D oxygen-glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor-β treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF.

Objective To evaluate the protective effect of epigallocatechin gallate (EGCG) on lipopolysaccharide (LPS) -induced acute kidney injury (AKI) in rats and its underlying mechanisms. Methods Sprague-Dawley rats were randomly divided into the Sham group, AKI group, EGCG group and TLR4 group (n = 10 each). To establish the rat model of endotoxemia, serum creatinine (Cr) and urea nitrogen (BUN) levels were detected by biochemical assays; serum interlukin (IL) -6, IL-1β, IL-10, and TNF-α levels were detected by ELISA; kidney histopathology was examined by hematoxylin and eosin (HE) staining method; and expression of TLR4, Myd88 and nuclear factor-kappa B (NF-κB) in rat kidneys at both protein and mRNA levels was detected by Western blotting and qRT-PCR, respectively.Results Kidney injury increased significantly in AKI group compared to the sham group. Serum Cr, BUN, IL-6, IL-1β, and TNF-α levels significantly increased whereas IL-10 levels significantly decreased in AKI group compared to the sham group. Expression levels of TLR4, Myd88, and NF-κB also significantly increased at both protein and mRNA levels in AKI group compared to the sham group. Treatment with EGCG prior to induction of LPS-mediated AKI conferred protection against AKI by significantly reducing the expression of inflammatory markers such as, TLR4, Myd88, and NF-κB. Given TLR4 inhibitor based on this, the protective effect of EGCG on AKI was via inhibition of the TLR4/Myd88/NF-κB pathway. Conclusion EGCG exhibited a protective effect against LPS-induced AKI by inhibiting the activation of TLR4/Myd88/NF-κB pathway.

Objective To investigate the effects of Epigallocatechin gallate (EGCG) on cardiac protection in diabetic rats and the expression of TGF-1/Smad3 signaling pathway. Methods The influence of clean level 40 SD rats, weight 200-220 g, divided into four random groups:control (Sham) group, diabetic cardiomyopathy model (DC) group, EGCG group, and metformin positive control group (Met).Post 8 weeks of high-fat-diet administration, the rats were injected intraperitoneally with STZ to establish the diabetes cardiomyopathy model. Upon successful model establishment, the EGCG group was intraperitoneally injected with EGCG and the cardiac function of the rats was measured after 28 days of drug administration. Then, the pathological results of the myocardial tissue were analyzed. Triglyceride (TG), total cholesterol (TC), glycosylated hemoglobin (HbA1 c), and blood glucose (FBG) concentrations were also measured. Further, the concentrations of superoxide dismutases (SOD), malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GPX) in serum were measured by ELISA. The expression of TGF-β1 and Smad3 in kidney tissues of the rats was measured by Western blotting analysis. Results EGCG could reduce the glucose, lipid, and MDA levels in the blood of the diabetic rats, enhance cardiac systolic and diastolic functions, inhibit TGF-β1 and Smad3 protein expression, enhance the activity of SOD, CAT and GPX, and reduce myocardial tissue fibrosis. Conclusion EGCG can protect diabetic rat hearts by improving metabolic disorder, and its mechanism may be related to the oxidative-stress mediated by the TGF-β1/Smad3 signaling pathway.

Objective: To explore the safety of liver transplantation recipients with Rh blood group mismatchming. Methods: From May 2005 to December 2018, 1 546 cases of liver transplantation in our hospital were retrospectively analyzed. Among these cases, 5 cases of Rh blood group mismatched were Rh(-) recipients receiving Rh(+ ) donor liver. For each Rh blood group mismatched liver transplantation, 5 patients received the same Rh blood group liver allograft were matched according to a certain principle and were defined as Rh-mismatch group and Rh-match group respectively. The serum alanine aminotransferase (ALT), aspartate aminotransferase(AST)and creatinine(SCr)were compared between two groups at Days 7 & 14 post-operation. Serum total bilirubin(TB), gamma-glutamyl transpeptidase(GGT)were compared between two groups at Month 1, 6 & 12 post-operation. Hemoglobin (Hb)were compared between two groups Month 1, 3 & 6 post-operation. The rates of infection, vascular complications and acute rejection was also compared. Indirect antiglobulin test (IAT)was used for detecting the production of anti-RhD antibody in patients in Rh-mismatch group at Month 1, 6 & 12 post-operation. Results: At the mentioned time, no significant inter-group difference existed in serum ALT, AST, SCr, TB, GGT and blood Hb levels(all P>0.05); Also, no significant difference existed in the incidence of infection, vascular complications or acute rejection(all P>0.05). In Rhmismatch group, 4 recipients received Rh(+ )RBC transfusion during perioperative period and no hemolytic anemia occurred after operation. Rh(D) antibody was negative at all timepoints. Conclusions Taking into account the rarity of Rh-negative blood group in Chinese, it is safe and feasible to carry out Rh blood group mismatched liver transplantation when donor or recipient with the same Rh blood group is not available.

Objective To summarize our experience in the diagnosis and treatment of hepatic epithelioid angiomyolipoma (HEAML),with the aim to reduce the future misdiagnosis rate.Methods The PubMed,Medline,China Science Periodical Database (CSPD),and VIP Databases were searched from January 2000 to March 2018 on all reports on HEAML.Results There were 409 cases of HEAML in 97 reports.The ratio of men to women was 1∶4.84.The age ranged from 12 to 80 years and the median age was 44 years.61.9％ of patients (205/331) were asymptomatic,while 34.7％ (115/331) had upper or right upper quadrant abdominal discomfort.Some patients presented with abdominal mass,gastrointestinal reaction,low grade fever or weight loss.The clinical symptoms in 78 patients were not mentioned in the reports.The misdiagnostic rate of HEAML was as high as 40.3％ (165/409).The imaging findings of HEAML were nonspecific.Ultrasound,CT and MRI scan usually showed contrast enhancement in the arterial phase.Most lesions were accompanied by central vessels with early drainage veins.The enhanced scans showed varied characteristics.The ratios of fast wash-in and fast wash-out,to fast wash-in and slow wash-out,and to delayed enhancement were roughly 4∶ 5∶ 1.A definitive diagnosis of HEAML is based on the pathological findings of epithelioid cells in the lesions and the expressions of HMB45,SMA,Melan-A and Actin on immunohistochemical staining.HEAML had a relatively low malignant rate of 3.9％.Surgical resection was the main treatment for HEAML.Conclusion HEAML was a rare and easily misdiagnosed disease.,which could be diagnosed by taking into account the clinical course,imaging,pathological and immunohistochemical findings.HEAML.

Objective To understand the life quality status of freshmen in higher medical colleges,and discuss the factors influencing the quality of life,in order to improve their life quality,and put forward the countermeasures and suggestions.Methods We randomly selected a higher medical colleges and universities in Yunnan,the grade one students were investigated with SF-36 scale investigation,the data were analyzed by t test and multiple linear regression analysis.Results The quality of life scores (PCS,MCS) of freshmen in this medical college are lower than the national norm,the segmentation in the field of eight only GH is higher than the national norm,and the RP,BP,VT,RE are lower than the national norm.There are six factors into the regression equation of the quality of life:health,insomnia,life pressure,communicating with people,life rule.Conclusions The QOL of freshmen in higher medical colleges and universities is low,relevant departments should be caused to take seriously.To improve the QOL,the government,society,school,personal must make joint efforts in many ways,and take targeted measures.

The aim of this paper is to explore the prevention of rabbit postoperative abdominal cavity adhesion with poly (lactic-co-glycotic acid) (PLGA) membrane and the mechanism of this prevention function. Sixty-six Japanese white rabbits were randomly divided into normal control group, model control group and PLGA membrane group. The rabbits were treated with multifactor methods to establish the postoperative abdominal cavity adhesion models except for those in the normal control group. PLGA membrane was used to cover the wounds of rabbits in the PLGA membrane group and nothing covered the wounds of rabbits in the model control group. The hematologic parameters, liver and kidney functions and fibrinogen contents were detected at different time. The rabbit were sacrificed 1, 2, 4, 6, 12 weeks after the operations, respectively. The adhesions were graded blindly, and Masson staining and immunohistochemistry methods were used to observe the proliferation of collagen fiber and the expression of transforming growth factor β1 (TGF-β1) on the cecal tissues, respectively. The grade of abdominal cavity adhesion showed that the PLGA membrane-treated group was significant lower than that in the model control group, and it has no influence on liver and kidney function and hematologic parameters. But the fibrinogen content and the number of white blood cell in the PLGA membrane group were significant lower than those of model control group 1 week and 2 weeks after operation, respectively. The density of collagen fiber and optical density of TGF-β1 in the PLGA membrane group were significant lower than those of model control group. The results demonstrated that PLGA membrane could be effective in preventing the abdominal adhesions in rabbits, and it was mostly involved in the reducing of fibrinogen exudation, and inhibited the proliferation of collagen fiber and over-expression of TGF-β1.
Abdominal Cavity ; surgery ; Animals ; Collagen ; metabolism ; Lactic Acid ; Polyglycolic Acid ; Rabbits ; Tissue Adhesions ; prevention & control ; Transforming Growth Factor beta1 ; metabolism

Objective To evaluate the changes in the expression of aquaporin-8 (AQP8) in intestinal mucosa in pigs with hemorrhagic shock.Methods Sixteen Bama miniature pigs,weighing 22-25 kg,were equally and randomly divided into sham operation group (group S) and hemorrhagic shock group (group HS).The animals were fasted for 8 h before operation.The animals were anesthetized with propofol 3 mg/kg injected via the auricular vein,and tracheostomized and mechanically ventilated.In group S,the femoral artery and internal jugular vein were only cannulated.In group HS,the femoral artery and internal jugular vein were cannulated for blood pressure and mean arterial pressure monitoring and blood sampling.Hemorrhagic shock was then induced by removing 40 percent of blood volume over 15 min.Before anesthesia (T0),and at 30 min and 1.0,1.5,2.0,3.0 and 4.0 h after the end of blood-letting (T1.6),blood samples were collected for determination of serum D-lactate and intestinal fatty acid binding protein (I-FABP) concentrations.After blood sampling at T6,the pigs were sacrificed,and intestinal specimens were obtained for microscopic examination and for determination of AQP8 cotent in intestinal mucosa (by ELISA).The water content of intestines was calculated by wet/dry weight ratio.Results Compared with group S,the serum D-lactate concentrations at T2-6,I-FABP concentrations at T1-6,and water content of intestines were significantly increased,and the cotent of AQP8 was up-regulated at T6 in group HS.No changes were found in the intestinal mucosa in group S.In group HS,severe damage to the intestinal mucosa was found,and bleeding,inflammatory cell infiltration,and epithelial cell necrosis were observed.Conclusion The mechanism of hemorrhagic shock-caused damage to intestines is related to up-regulated expression of AQP8 in intestinal mucosa in pigs.

OBJECTIVETo investigate the effects of PLGA absorbable membrane in prevention of postoperative abdominal adhesion in rabbits.

METHODS66 Japanese white rabbits were randomly divided into three groups: the normal control group n = 6, model control group n = 30 and PLGA group n = 30. Rabbits were received multifactor methods to establish postoperative abdominal adhesion models except for normal control group. The cecum wound was covered PLGA membrane in the PLGA group. At postoperative 1, 2, 4, 6 and 12 weeks, the abdominal cavities were reopened and the adhesive severity was graded blindly, and the hydroxyproline level in cecum tissue was measured and the cecum histopathology was observed.

RESULTS(1) the degree of adhesion and hydroxyproline level in model control group were significantly higher than those of normal control group (P < 0.05, P < 0.01), while the degree of adhesion and hydroxyproline level in PLGA group were significantly lower than those of model control group (P < 0.05). (2) HE staining showed that cecum serosa had obviously inflammatory cell infiltration and fibroblast proliferation, while PLGA could inhibit fibroblast proliferation and reduce the inflammatory cell infiltration and collagen.

CONCLUSIONPLGA absorbable membrane can inhibit fibroblast proliferation and collagen to prevent the experimental postoperative peritoneal adhesions.

Abdominal Cavity ; pathology ; Animals ; Cell Proliferation ; Collagen ; analysis ; Fibroblasts ; cytology ; Lactic Acid ; chemistry ; Membranes, Artificial ; Polyglycolic Acid ; chemistry ; Postoperative Complications ; prevention & control ; Rabbits ; Tissue Adhesions ; prevention & control

Objective To evaluate the effect of dexmedetomidine on lung injury induced by renal ischemia/reperfusion (l/R) in rats.Methods Healthy male Sprague-Dawley rats,aged 4-5 months,weighing 250-300 g,were randomized into 4 groups (n =10 each) using a random number table:sham operation group (group S); group I/R; dexmedetomidine pretreatment group (group D1) and dexmedetomidine postconditioning group (group D2).Renal I/R was induced by right nephrectomy and occlusion of the left kidney for 45 min followed by reperfusion in animals anesthetized with intraperitoneal chloral hydrate.In group D1,dexmedetomidine was infused intravenously starting from 30 min before ischemia until beginning of ischemia.In group D2,starting from onset of reperfusion until 30 min of reperfusion,dexmedetomidine was infused intravenously for 10 min at a rate of 1 μg· kg-1 · h-1,and then infused for 20 min at 0.5 μg· kg-1 · h 1.Blood samples were collected at 6 h of reperfusion to determine serum creatinine,blood urea nitrogen,interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-α (TNF-α) concentrations,and IL-1β,IL-6 and TNF-α concentrations in broncho-alveolar lavage fluid (BALF).Lungs were removed for microscopic examination and for determination of wet/dry lung weight ratio.Results Compared with group S,wet/dry lung weight ratio,serum creatinine and blood urea nitrogen concentrations,and IL-1β,TNF-α and IL-6 concentrations in serum and BALF were significantly increased in the other three groups (P ＜ 0.05).The parameters mentioned above were significantly lower in D1 and D2 groups than in I/R group (P ＜ 0.05).Microscopic examination showed that the pathological changes were significantly attenuated in D1 and D2 groups as compared with I/R group.Conclusion Both dexmedetomidine pretreatment and postconditioning can attenuate lung injury induced by renal I/R and inhibition of inflammatory responses is involved in the mechanism.