Objective To observe the effects of doxazosin on the expression of type Ⅰ and type Ⅲ collagen fiber in autoantibodies against α1-adrenergic receptors (α1-AA) positive diabetic rats,and to investigate the protective mechanism of doxazosin on cardiomyopathy of diabetic rats.Methods After establishment of diabetes model with streptozocin,diabetic rats were randomly divided into diabetic group (group A,n =10),doxazosin treated group (group B,n =10),α1-AA mediated group (group C,n =8),α1-AA plus doxazosin treated group (group D,n =8).Group C and group D were injected α1-AA (100 μg/100 g) by caudal vein at 0,4,8,12,and 16 weeks.Doxazosin (0.36 mg · kg-1 · d-1) was administered by lavage for 16 weeks in group B and group D,and other groups were given the same volume of saline every day.Expressions of type Ⅰ and type Ⅲ collagen fibers in myocardium of left ventricle were detected by immunohistochemical staining.Pathological changes in the myocardium were observed by both light and electron microscopes.Changes in collagen fiber in myocardium were detected by Van Gieson staining.Results Among various groups,there was no significant difference in blood glucose levels (P ＞ 0.05).After the intervention of doxazosin,body weight in group B and group D was greater than that of group A and group C (P＜0.05 or P＜0.01).Expression of type Ⅰ and type Ⅲ collagen fibers in myocardium in group D was lower than that in group C (P＜0.05).Expression of type Ⅰ and type Ⅲ collagen fibers in group B was lower than that in group A (P＜0.05) as well.Myocardial pathological changes in group C were most serious,showing reduced mitochondrial,vacuolar degeneration,and interstitial collagen hyperplasia.Cardiomyopathy in group D and group B was less marked as compared with that in group C and group A,respectively.Myocardial collagen fiber in group C was significantly increased and showed poor alignment.Compared with group C,myocardial collagen deposition in group D was obviously reduced.Conclusions Doxazosin may suppress type Ⅰ and type Ⅲ collagen expressions in myocardium of α1-AA mediated diabetic rats,resulting in alleviation of myocardial fibrosis and protection of myocardium in diabetic rats.

Objective To evaluate the gene therapeutic effects of guinea pigs model with immune -mediated inner ear disease(IMIED)after locally injection of bone -marrow mesenchymal stem cells(BMSCs) decorated by in-terleukin-4 gene .Methods Guinea pigs were immunized with keyhole limpet hemocyanin (KLH) and caused 55 animal models ,divided into five groups ,each group with 11 animals :groupA(BMSCs carrier) ,group B(BMSCs emp-ty -carrier control group) ,group C(recombinent lentivirus IL -4 gene) ,group D(lentivirus empty -carrier control group) ,group E(simulation operation control group) .Groups were all injected with the corresponding suspension (20 μl)[includs BMSCs ceas of (1 .5~2 .0) × 106 ,the concentration of (entivirus) is 0 .5 × 108 pfu] by the scala tympani window into the inner ear .The fluorography immunohistochemistry test and enzyme immunohistochemistry test for the situation of IL -4 gene express and productive protein distribution in inner ear .Auditory functions and the KLH level of guinea pigs blood were monitored respectively by auditory brainstem responses (ABRs) and ELISA test .Results The threshold of ABR wave Ⅲ decreased in group A ,group B and group C .The result were more significant in group A and group B than that in group C ,but results in group A was more prominent (P<0 .05) . The results of immunohistochemistry test showed that fluorescence positive BMSCs mainly scattered in scala tymani and scala vestibule .The microscope results showed that for the group A ,B and C ,there were only few foccule and red and white blood cells in scala tympani floc ,but for group D and group E ,with different levels of labyrinthine hy-drops and some mononuclear cells around the spiral ganglion and small blood vessels .Conclusion Restructuring lentiviral vector with IL -4 gene can be successfully transfected into BMSCs in vitro ,compared to inplangting into inner ear in scala tympani approach ,the cells can migrate and generate gene product of IL -4 ,to significantly im-prove the auditory functions and inflammatory reaction of inner ear disease ,and BMSCs can be used as a carrier to migrate to the damaged part with therapeutic gene .

Objective To observe the effect of CYP4F2(rs2108622)polymorphism on the dose of warfarin in old patients(65 to 75 years old)who were treated with atrial fibrillation.Methods Sixty cases of old patients with atrial fibrillation were enrolled in the study.All the subjects had taken warfarin for 3 months,and the international normalized ratio(INR)maintained between 1.6 and 2.5.And the CYP4F2(rs2108622)variant were detected by PCR.Results The patients with CYP4F2(rs2108622)allele C/C scored significantly lower warfarin dose than patients with variant allele C/T and T/T (P < 0.05 ).Conclusion CYP4F2 (rs2108622)gene polymorphism have been related with warfarin dose in old patients.

Objective:To explore significance of brain natriuretic peptide (BNP)and N terminal pro brain natriuretic peptide (NT-proBNP)for diagnosis of acute respiratory distress syndrome and its guidance of treatment.Methods:A total of 124 cases with definite organic heart disease and sudden respiratory distress syndrome (measurement group) received measurement of BNP and NT-proBNP to judge whether they suffered from heart failure or not.Another 110 patients with acute respiratory distress syndrome but no receiving BNP and NT-proBNP measurement were en-rolled as no measurement control group.Relevant data,including diagnosis time,length of hospital stay,hospitali-zation cost and mortality rate etc,were collected in all patients.Results:Compared with no measurement control group,there were significant reductions in diagnosis time [(24.2±6.4)min vs.(16.3±5.2)min],length of hospi-tal stay [(12.5±3.5)d vs.(8.5±4.5)d]and mortality rate (8.18% vs.4.84%)in measurement group,P<0.05 all;there was no significant difference in mean hospitalization cost between two groups (P>0.05).Conclusion:Measurement of brain natriuretic peptide and N terminal pro brain natriuretic peptide possesses important value for early diagnosis,elevating therapeutic effect and improving prognosis in patients with acute respiratory distress syn-drome.

Objective:To study the diagnosis value of Transcranial Doppler ultrasound for intracranial artery stenosis in patients with cerebral infarction.Methods:A total of 140 patients with acute cerebral infarction,transient ischemic attack and posterior circulation ischemic attack in Department of Neurology,Xinjiang cardiovascular and cerebrovascular disease hospital from October 2014 to October 2016 were selected as research object,CT angiography (CTA) and TCD detection were performed in all patients.Used CTA examination results as the gold standard,the detection results of intracranial artery stenosis in two groups were compared,the diagnostic value of TCD and the diagnostic results of TCD to the degree of bilateral middle cerebral artery (MCA) stenosis were analyzed.Results:CTA diagnosis showed that 140 patients had a total of 105 patients with intracranial artery stenosis,in the anterior and posterior circulation vessel of 1155 intracranial segments,CTA detection showed that 249 vessels were narrow,TCD detection showed that 236 vessels were narrow.Com-pared with CTA,TCD was better in the diagnosis of patients (Kappa value＞0.75).The diagnostic sensitivity and positive predictive value of TCD for MCA were the highest,which were 91.26％ and 93.07％,the consistency was the best (Kappa value =0.917).CTA detection showed that 210 MCA vessels had 103 stenoses,mild stenosis 17,moderate stenosis 41,severe stenosis 45,TCD detection showed that the stenosis was 101,mild stenosis 16,moderate stenosis 40,severe stenosis 45.The Kappa test showed that the diagnostic results of TCD to the degree ofMCA stenosis was better consistency compared with CTA (Kappa value=0.884.Conclusion:TCD has a high diagnostic value for cerebral artery stenosis in patients with cerebral infarction,and it is consistent with the diagnosis of CTA.

Objective:To investigate the efficacy and safety of three-dimensional navigation template assisted osteotomy for fracture malunion of lateral condyle of humerus in children.Methods:Eighteen children with ma-lunion of fracture of lateral condyle of humerus were treated in Southern Medical University Third Affiliated Hospital from August 2012 to December 2019 and analyzed retrospectively.Among them, 12 cases were treated with routine ope-ration: according to CT reconstruction and empirical osteotomy during the operation, the location of deformity was analyzed.Six cases were treated with navigation template assisted osteotomy: according to the CT data of bilateral elbow joints, a three-dimensional bone model was established, and the coronal and sagittal deformities of the distal humerus were evaluated by comparing the images of the distal humerus of the affected side with the distal humerus of the healthy side, so as to determine the best plane of osteotomy and the target position of reduction.The preoperative simulation was carried out on the computer, and the osteotomy navigation template and reduction navigation template were designed.The navigation template was printed out with a 3D printer.During the operation, the osteotomy was corrected with the assistance of navigation template, and the broken end of osteotomy was fixed with hollow screw and fixed with 80 degree flexion plaster.The X-ray films of the two groups were reexamined regularly after operation.The amount of intraoperative blood loss, operation time, incidence of postoperative complications (necrosis of humeral head and trochlea, delayed ulnar nerve paralysis, and bone nonunion) and the recovery of flexion and the extension function of elbow joint were observed in the 2 groups.Results:The elbow joint activity of all children basically returned to normal, the orthopedic site of osteotomy achieved bony healing, and the orthopedic effects were satisfactory.All the 18 cases were followed up for 6-24 months (mean 15 months). According to the postoperative Dhillon score, the navigation template group was excellent in 1 case and better in 5 cases, while in the routine group, 11 cases were batter and 1 case was fair.There were no significant differences in Dhillon score between the 2 groups after operation ( P>0.05). There were no significant differences in the range of the motion of elbow joint between the 2 groups ( P>0.05). In the comparison of operation time and intraoperative blood loss, the navigation template group [(200.0±24.2) min, (85.0±10.9) mL]was better than the routine group[(232.0±20.1) min, (139.1±18.3) mL](all P<0.001). Conclusions:The application of three-dimensional humerus reconstruction and mirror image contrast to evaluate the distal humerus deformity of the affected side, and the design of osteotomy and reduction navigation template auxiliary operation can restore the normal anatomical structure of elbow joint to the greatest extent.Accurate correction, and the function of elbow joint recover well after operation, which optimizes the operation procedure, improves the safety and effectiveness of the operation.

Objective To explore the application of tissue-explant technique in culturing rat submandibular gland cell(RSGC)and the characteristics of RSGC.Methods RSGCs were cultured using tissue-explant technique.The cells were purified by enzymatic digestion and differential adhesion.The cell phenotype was identified by cytokeratin-8 immunohistochemical staining.Cellular morphology was observed and photographed under inverted microscope.The cell viability and growth were determined by a double-staining procedure using FDA-PI and MTT assay,respectively.Results Cytokeratin-8 was positive stained in the immunohistochemical staining.The cell viability was more than 95%.The cell growth curve showed that RSGCs were in logarithmic phase since day 5.Conclusion Tissue-explant technique is an easy way to purify plentiful RSGC with normal functions,and it can be used in further research of tissue engineering of submandibular gland.

Objective To investigate the effect of Glycyrrhizin combined with puerarin on serum Leptin and insulin resistance in non-alcoholic fatty liver disease(NAFLD) patients.Methods One hundred and twenty patients with NAFLD were randomized into 4 groups,which were control group,compound Glycyrrhizin group,puerarin group,combined group,and each group was 30 cases.Patients in control group were received the regular liver protecting therapy including vitamins,amino acids,glucurolactone,in compound Glycyrrhizin group were given 60 ml compound glycyrrhizin solution (iv),in puerarin group were given puerarin at dose of 400 mg by intravenous infusion,and in combined group were given both compound glycyrrhizin and puerarin combination.All treatment period was 4 weeks.The levels of serum serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),total cholesterol (TC),triglyceride (TG),leptin (LP),fasting blood glucose (FBG) and insulin(INS) were measured,and the insulin resistance index(IRI) was calculated.The liver CT image of patients were performed by Germany Siemens dual source CT instrument.Results The levels of serum ALT,AST,TC,TG,LP and IRI in control group at before and after treatment were ((83.08 ± 115.68) U/L vs.(43.32 ±11.72) U/L,(52.12±15.62) U/Lvs.(36.08 ±7.28) U/L,(6.20±1.30) mmol/Lvs.(5.60 ±0.70) mmol/L,(2.70 ±0.50) mmol/L vs.(2.10 ±0.40) mmol/L,(14.63 ±3.26) μg/L vs.(7.61 ± 2.46) μg/L,(7.9 ± 1.8) vs.(7.0 ± 1.2)),and the difference were statistically significant (t =12.828,4.244,16.648,21.442,3.341,16.152 respectively,P ＜ 0.01).The levels of serum ALT,AST,TC,TG,LP and IRI in compound glycyrrhizin group after treatment were ((43.28 ± 11.06) U/L,(37.28 ± 7.22) U/L,(5.70± 0.80) mmol/L,(2.20 ± 0.50) mmol/L,(7.89 ± 2.26) μg/L,(7.1 ± 1.6) respectively,significant different from before treatment ((83.06 ± 14.38) U/L,(51.68 ± 15.48) U/L,(6.30 ± 1.50) mmol/L,(2.60 ± 0.40) mmol/L,(15.13 ± 3.87) μg/L,(7.8 ± 2.2) respectively,t =8.893,4.225,16.520,24.708,6.353,21.137 respectively,P ＜ 0.01).The levels of serum ALT,AST,TC,TG,LP and ISI in puerarin group after treatment were (44.26 ± 9.68) U/L,(36.86 ± 6.88) U/L,(5.60 ± 0.70) mmol/L,(2.26 ± 0.48) mmol/L,(6.89 ± 2.18) μg/L,(7.0 ± 1.8) respectively,significant different from that before treatment ((82.68±14.36) U/L,(50.06±15.23) U/L,(6.20±1.60) mmol/L,(2.70±0.52) mmol/L,(15.68 ±3.26)μg/L,(7.7 ±2.8) respectively,t =7.087,8.138,18.159,7.244,7.470,32.283 respectively,P ＜ 0.01).The levels of serum ALT,AST,TC,TG,LP and ISI in combined treatment group after treatment were (22.28 ± 9.38)U/L,(28.48 ± 9.06) U/L,(5.00 ± 0.60) mmol/L,(1.70 ± 0.40) mmol/L,(4.63 ± 2.36) μg/L,(6.20± 1.6) respectively,significantly different from that before treatment ((84.62 ± 14.88) U/L,(49.12 ± 16.56)U/L,(5.70 ± 1.60) mmol/L,(2.78 ± 0.50) mmol/L,(14.78 ± 3.68) μg/L,(7.6 ± 2.1),t =14.255,11.272,8.371,9.941,8.102,37.626,P ＜ 0.01).The levels of serum ALT,AST,TC,TG,LP and ISI of patient were no significant difference before treatment,but after treatment,these indexes in combined therapy group were the lowest among 4 groups (P ＜ 0.05).And there were no significant difference among control group,compound glycyrrhizin group,puerarin group (P ＞ 0.05).Conclusion Compound glycyrrhizin combined with puerarin is proved to be an effect treatment method for NAFLD through decreasing serum leptin,improving insulin resistance.

Background and purpose:In the process of gastric cancer development, cytothesis and apoptosis, and endoplasmic reticulum stress (ERS) are very important pathological processes. Glucose regulated protein 78 (GRP78) and phosphorylated form of extracellular signal-regulated protein kinase (pERK) play important roles in it. This study aimed to investigate the expression of GRP78 and pERK in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis, and the role of GRP78 and pERK in the development of gastric adenocarcinoma. Methods:Gastric adenocarcinoma, chronic atrophic gastritis and superifcial gastritis tissues in 60 cases respectively were employed in the study. We chose 25 fresh tissue samples from each group, and the level of GRP78 and pERK mRNA in different tissues were detected by RT-PCR assay. The expressions of GRP78 and pERK in different parafifn samples were detected using immunohistochemistry assay. In addition, the relationships between GRP78 and pERK expression and age, gender, differentiation, invasion, disease stage, and lymphoid node metastasis were analyzed. Results: The expression level of GRP78 and pERK mRNA in gastric adenocarcinoma(1.26±0.18, 2.35±0.36) were significantly higher than chronic atrophic gastritis (0.89±0.25, 1.18±0.25) and superficial gastritis (0.29±0.09, 0.68±0.10, P<0.01). The positive ratio of GRP78 expression in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis were 78.3%, 46.6%, 6.7%. The positive ratios of pERK expression were 88.3%, 43.3%, 5.0%, respectively. The GRP78 and pERK expression in different tissues were signiifcantly different (P<0.01). GRP78 and pERK expression were positively correlated with differentiation, disease stage and lymph node metastasis. There was a positive correlation between the gene and protein expression of GRP78 and pERK with a Pearson correlation value of 0.307 and 0.368, respectively. Both univariate and multivariate analysis revealed that GRP78 was related to the prognosis of gastric adenocarcinoma. Conclusion:GRP78 and pERK may play an important role in the transition of normal gastric cells to malignant cells. The expression of these two genes enhances tumor progression. Overexpression of GRP78 and pERK is significantly correlated with poor prognosis in patients with gastric adenocarcinoma. The determination of the expression of GRP78 and pERK might be helpful for the prevention, early diagnosis of gastric carcinoma. Particularly, GRP78 is valuable for the judgement of prognosis, and might be a new target for the treatment of gastric adenocarcinoma.

Background and purpose:Metastatic colorectal cancer (mCRC) patients with K-ras mutation won’t benefit in the anti-epidermal growth factor receptor (EGFR) treatments. Thus K-ras mutation analysis is mandatory before this treatment. There is controversy that K-ras mutation analysis should be performed on primaries or related metastases. The aim of our study was to evaluate the concordance of K-ras status between primary and related metastases tumors, thus investigate the validity and rigorousness of clinical K-ras testing. Methods:Seventy-six patients with confirmed mCRC treated in Fudan University Shanghai Cancer Center were enrolled. After DNA extraction and PCR amplification, tumor specimens with paired primary tumors and related metastatic sites were put into sequencing analysis. And the K-ras mutation status in exon 2 was assessed. Results: K-ras mutation was detected in 31 out of 76 primary tumours (40.8%) and also 40.8%of the metastatic sites. But discordance was found between primary tumor and metastasis in 15 cases (19.7%):8 primary tumors had a K-ras mutation with a wild-type metastasis, meanwhile 7 primary tumors were wild type with a K-ras-mutated metastasis. Conclusion:Our study indicated that quite a few mCRC cases have different K-ras status between primary tumors and related metastatic sites, and it’s not very rigorous to choose the anti-EGFR treatments merely according to the primary tumor-K-ras mutation.Further study and consultation are needed on this problem.