Objective To compare the characteristics of ulcer wound healing in current commonly used C57BL/6J-db/db mouse models of spontaneous gene mutation-induced type 2 diabetes and in C57BL/6J mice with diabetes induced by streptozotocin (STZ), and to provide a basis for related experimental studies on diabetic ulcer in animal models.Methods To establish the mouse models of diabetic ulcer wound, observe the healing time and calculate the wound healing rate at 0, 3, 5, 7, 10, 14 days.Tissue samples were collected at days 7 and 14.HE and Masson staining, and immunohistochemistry (CD31 and PCNA) were used to observe the pathological changes of the wound tissues.Gene expressions of collagen-IIIα, fibronectin and α-SMA were detected by fluorescent quantitative analysis.Results The wound healing time of db/db mice was significantly delayed compared with the STZ mice, which was extended from 16.6±0.8 d to 20.2±1.3 d (P< 0.001).Compared with the STZ group, the growth of granulation tissue in the db/db group was slow, the length of newly formed epithelium was insufficient, the collagen deposition was disordered, and the wound healing was poor.At 7 days, the expression of CD31 and PCNA was significantly lower in the db/db group (P< 0.01), and at 7 and 14 days, the increase of collagen-IIIα and α-SMA genes up-regulation was significantly lower in the db/db group than in the STZ group.Conclusions Both the two types of diabetic mice show delayed wound healing.However, compared with the STZ-induced diabetic mice, the gene mutation db/db mice are more suitable for studies of diabetic ulcer wound healing as regarding the extent of the delay and the degree of difficulty of wound healing.

ObjectiveTo investigate the effect of heme oxygenase-1 (HO-1) on cyclin-dependent kinase 5 (CDK5)-ataxia telangiectasia mutated (ATM)-P53 signal transduction pathway in rat hippocampal neurons subjected to oxygen-glucose deprivation (OGD) injury.MethodsHippocampal neurons of newborn Wistar rats ( ＜ 48 h) were cultured for 7 days in vitro.The primary cultured neurons were randomly divided into 4 groups with 10 wells in each group:control group (group C),OGD (group D),OGD + hemin (HO-1 inducer) group (group D + H ) and OGD + hemin + zinc protoporphyrin ( HO-1 inhibitor) group ( group D + H + T).For OGD experiments,cultures were washed three times in a glucose-free balanced salt solution (BSS).They were then placed in deoxygenated glucose-free medium and sealed under 95％ N2-5％ CO2 in an anaerobic chamber equilibrated to 37°C and 100％ humidity for 45 min.OGD was terminated by replacement of stored medium and by returning the cultures to a standard incubator maintained at 37 ℃ in 95％ air-5％ CO2.The OGD model was established after the neurons were preconditioned with hemin 10 μmol/L for 24 h in group D + H.The OGD model was established after the neurons were preconditioned with hemin 10 μmol/L and zinc protoporphyrin 10 μmol/L for 24 h in group D + H + T.After 24 h of culture,the neuronal viability,apoptosis rate,and expression of HO-1 mRNA and protein,and CDK5,ATM and P53 protein were detected.ResultsCompared with group C,the expression of HO-1 mRNA,and HO-1,CDK5,ATM and P53 protein was up-regulated,the neuronal viability was significantly decreased,and the apoptosis rate was significantly increased in group D (P ＜ 0.01 ).Compared with group D,the expression of HO-1 mRNA and protein was up-regulated,the expression of CDK5,ATM and P53 protein was down-regulated,the neuronal viability was significantly increased,and the apoptosis rate was significanlly decreased in group D + H ( P ＜ 0.01 ).Compared with group D + H,the expression of HO-1 mRNA and protein was down-regulated,the expression of CDK5,ATM and P53 protein was up-regulated,the neuronal viability was significantly decreased,and the apoptosis rate was significantly increased in group D + H + T ( P ＜ 0.01 ).ConclusionHO-1 can inhibit neuronal apoptosis through blocking CDK5-ATM-P53 signal transduction pathway in rat hippocampal neurons subjected to OGD injury.

BACKGROUND:In early experiments, we prepared hydroxyapatite-coated mechanical heart valve embedded with col agen using impulse laser sediment method.
OBJECTIVE:To further analyze the histocompatibility and toxicity of hydroxyapatite-coated mechanical heart valve embedded with col agen.
METHODS:After passage, canine vascular endothelial cellsuspension was inoculated onto the hydroxyapatite-coated mechanical heart valve embedded with col agen. One group was inoculated in 5%CO2, 37 ℃ incubator for 3 weeks static culture, and the other group was inoculated in 5%CO 2 , 37 ℃ incubator for 3 weeks spinner culture. Scanning electron microscope was used to observe cellattachment on the material. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to the proliferative capacity of vascular endothelial cells cultured with the hydroxyapatite-coated mechanical heart valve embedded with col agen.
RESULTS AND CONCLUSION:During the spinner culture, adherent cells were found on the surface of mechanical heart valve, and the cells distributed evenly and confluent at 21 days to cover the surface of the material. The number of adherent cells in the spinner culture was higher than that in the static culture. The cells during the static culture were aggregated and distributed irregularly. The mechanical heart valve exhibited no effects on the proliferation of canine vascular endothelial cells which grew wel . These findings indicate that the hydroxyapatite-coated mechanical heart valve embedded with col agen exert no effect on proliferation of vascular endothelial cells, has no toxicity and has good biocompatibility.

Objective To investigate the effect of transduction of heme oxygenase-1 (HO-1) protein on oxygen-glucose deprivation and restoration (OGD/R)-induced injury to hippocampal neurons in rats.Methods Plasmid 11R-HO-1 was constructed using plasmid pET-21a(+)-p53-11R (plasmid 11R) and 11R-HO-1 fusion protein was identified and collected.Hippocampal neurons obtained from newborn Wistar rats (＜ 48 h) were cultured for 7 days in vitro and then the neurons were randomly divided into 5 groups (n =171 each) using a random number table:OGD/R group,normal saline group (group NS),plasmid 11R group (11R group),300 nmol/L 11R-HO-1 group (H1 group),and 1 500 nmol/L 11R-HO-1 group (H2 group).In NS,11R,H1 and H2 groups,the neurons were incubated for 2 h with 300 nmol/L normal saline,300 nmol/L plasmid 11R,300 nmol/L 11R-HO-1 fusion protein,and 1 500 nmol/L 11R-HO-1 fusion protein,respectively,and then OGD/R was performed.The neurons were incubated in deoxygenated glucose-free DMEM medium and sealed under 5 ％ CO2-95 ％ N2 in an anaerobic chamber equilibrated to 37 ℃ for 45 min.OGD was terminated by replacement of the medium with high glucose DMEM medium and by returning the cultures to a standard incubator maintained at 37 ℃ in 5 ％ CO2-95 ％ air and the neurons were then incubated for 24 h.Immediately after OGD/R was established,the cell survival rate (by MTT assay),apoptosis rate (using TUNEL),and expression of HO-1 and caspase-3 protein (by using Western blot) were measured.Results Compared with group OGD/R,the cell survival rate was significantly increased,the apoptosis rate was decreased,the caspase-3 expression was down-regulated,HO-1 protein expression was up-regulated in H1 and H2 groups (P ＜ 0.05),and no significant change was found in the parameters mentioned above in NS and 11R groups (P ＞ 0.05).Compared with group H1,the cell survival rate was significantly increased,the apoptosis rate was decreased,the caspase-3 expression was down-regulated,and HO-1 protein expression was up-regulated in group H2 (P ＜ 0.05).Conclusion Transduction of HO-1 protein can reduce OGD/R-induced injury to hippocampal neurons of rats.

Object To prepare Heart protecting Musk Pellet (HPMP). Methods The HPMP was prepared by using a centrifugal granulator. The effect of formulation and technology on the yield of pellets was investigated. The optimal conditions of technology were selected by the uniform design. Results The yields of core pellets were affected significantly by the rotating rate of plate, amount of adhesive agent, the added speed of adhesive agent and the conditions of nebulization. The spraying rate of binder solution and feeding rate of powder were found to have significant influences on pelletizing. The process parameters established by the uniform design were as follows: the ratio of fine intermediate product and MCC was 1∶1, the adhesive agent was 3% HPMC solution. The rotating rate of plate was 200 r/min, the blower rate was 10?20 L/min, the rate of air flow was 15 L/min, the spray air pressure was 0 5 MPa, the rotating rate of spray solution pump was 14 r/min and the rotating rate of powder feed machine was 18 r/min. Conclusion Under the optimal conditions, the pellets prepared by using centrifugal granulator have perfect shape and surface characteristics and the yield of 1 000 700 ?m pellets could reach to 90 4%.

Objective:To evaluate the application value of small IT knife pre-cut in assistance to duodenal papillary cannulation compared with conventional guidewire cannulation.Methods:A retrospective analysis was performed on the data of 90 patients with choledocholithiasis including 52 patients with small IT knife pre-cut assisted intubation (small IT knife group) and 38 patients with conventional guidewire intubation (conventional group) in endoscopic retrograde cholangiopancreatography (ERCP) from May 2016 to July 2019 in the digestive endoscopy center of Nanjing Drum Tower Hospital. The basic data, curative effect and complications of the two groups were collected and compared.Results:There was statistically significant difference in gender composition between the small IT knife group and the conventional group ( χ2=5.679, P=0.017), but no significant difference in other baseline data between the two groups (all P>0.05). The median intubation time of the small IT knife group was significantly shorter than that of the conventional group (141.5 s VS 270.0 s, Z=1 268.0, P=0.022). There were no significant differences in the success rate of intubation [98.1% (51/52) VS 94.7% (36/38), χ2=0.760, P=0.571], the incidence of intraoperative bleeding [15.4% (8/52) VS 7.9% (3/38), χ2=1.148, P=0.345], postoperative pancreatitis [5.8% (3/52) VS 7.9% (3/38), χ2=0.159, P=0.694], and postoperative cholangitis [1.9% (1/52) VS 5.3% (2/38), χ2=0.760, P=0.571] between the two groups. No perforation occurred in the two groups. After stratifying according to the operator′s proficiency, the median intubation time was significantly different between the small IT knife expert group and the conventional expert group (116.0 s VS 258.0 s, Z=276.0, P=0.038), while there was no significant difference in the intubation time among other groups (all P>0.05). Conclusion:The small IT knife is safe and effective to pre-cut and assist intubation in ERCP, and it may shorten the intubation time.

OBJECTIVEThis study was about the influence of porcelain thickness on crack at interface.

METHODSThe effect of porcelain thickness on the flaw at the interface between porcelain and metal was studied in three groups with porcelain thickness of 0.5 mm, 1.5 mm and 2.5 mm (metal thickness of 0.5 mm) by means of moire interferometre and interfacial fracture mechanics. The parameter Jc was compared among the three groups and the growing of the flaw was observed.

RESULTSJc and the extreme strength of group with porcelain thickness of 0.5 mm (2.813 N/m and 9.979 N) were lower than those of the groups with porcelain thickness of 1.5 mm and 2.5 mm (5.395 N/m, 19.134 N and 5.429 N/m, 19.256 N). Flaws extend along the interface in the groups with porcelain thickness of 1.5 mm and 0.5 mm.

CONCLUSIONS(1) Fracture resistance of the interface in the groups with porcelain thickness of 1.5 mm and 2.5 mm is similar and it decreases in the group with 0.5 mm thick porcelain. (2) When porcelain is 1.5 mm or 0.5 mm thick, flaws will extend along the interface. When porcelain is 2.5 mm thick, flaws will extend into the porcelain layer.

Objective To investigate the efficacy and safety of endoscopic ultrasound-guided biliary drainage ( EUS-BD ) on obstructive jaundice patients who had failed in the endoscopic retrograde cholangiography ( ERC ) . Methods Seventeen obstructive jaundice patients who underwent EUS-BD at Nanjing Drum Tower Hospital from October 2015 to July 2017 were enrolled in the study. The types of biliary drainage, technical success rate, clinical efficacy, post-procedure adverse events, and follow-up were analyzed. Results EUS-BD was successfully performed in 16 out of 17 patients, with technical success rate of 94. 1％. Operation pathway included 12 EUS-guided hepaticogastrostomy, 2 EUS-guided antegrade stenting, 1 EUS-guided rendezvous, and 1 EUS-guided choledochoduodenostomy. All the 16 patients′bilirubin decreased at different levels after operation, and the clinical success rate was 94. 1％ (16/17). Post-operation complications included 5 cases of cholangitis, 2 of bile leakage, and 1 of pneumoperitoneum and duodenal perforation. The patients were followed up for 14-390 days after procedures. Two patients died of underlying disease one month after operation. Jaundice in another 2 patients worsened during follow-up and were improved after replacement of previous stent. Conclusion EUS-BD has a relatively high technical success rate, and can be considered as an alternative choice for patients with obstructive jaundice after failure of ERC. Operation pathway should be decided according to patient′s condition.

Background and Objective Previous study showed tenecteplase and alteplaxe were equovalent for 30-day mortality in the treatment of acute myocardial infarction. The purpose of this open-label, randomized, multi-center, angiographic trial was to assess the efficacy and safety of tenecteplase compared with alteplase in Chinese patients with acute myocardial infarction. Methods We recruited patients with acute ST-elevation myocardial infarction presenting within 6 hours of symptom onset from October, 2002 to March,2004, in 5 hospitals in Beijing. After giving informed consent, patients were randomly assigned a single-bolus injection of tenecteplase (30-50 mg according to body weight) or front loaded alteplase (100 mg), and underwent coronary angiography at 90 min after starting the study drug. All patients received aspirin and heparin (target activated partial thromboplastin time 50-70 s). The primary efficacy end point was the rate of TIMI grade 3 flow at 90 minutes. Other efficacy end points included TIMI grade 2/3 flow at 90 minutes. Safety end points included all stroke, intracranial hemorrhage (ICH), moderate/severe hemorrhage (except for ICH), all-cause mortality at 30-days, and major non-fatal cardiac events at 30 days. Results Overall 110 patients were eligible for statistical analysis, with 58 patients assigned to receive tenecteplase and 52 patients to alteplase. Tenecteplase produced a rate of TIMI grade 3 flow at 90 minutes after the start of thrombolysis(68.4%) similar to that of alteplase (66.7%, P=1.0); the rates of TIMI grade 2 or 3 were similar for patients treated with tenecteplase versus alteplase (89.5% versus 80.4%, respectively, P=0.278). At 30 days, rates for all strokes were similar for the two groups (5.17% for tenecteplase and 1.92% for alteplase, P=0.62); rates of ICH were 3.45% and 1.92% (tenecteplase and rt-PA,P=1.00) respectively. The rate of moderate/severe hemorrhage was 8.62% with tenecteplase and 5.77% with alteplase (P=0.72); total mortality was almost identical in the two groups (13.8% versus 9.6%, respectively, P=0.565) while the rates of non-fatal cardiac complications were 10.35% and 11.54% (tenecteplase and alteplase, P=1.0). Conclusions The efficacy of a single-bolus, weightadjusted tenecteplase fibrinolytic regimen is equivalent to front-loaded alteplase in terms of the rates of TIMI grade 3 flow, and TIMI 2 or 3 flow, but the 30-day mortality and ICH in both groups was so high that the use of tenecteplase is not permitted in China. These negative safety results might be due to the high rate of percutaneous coronary intervention (PCI) and high dose of bolus heparin and suboptimal concomitant medical therapy during hospitalization, so further studies are needed to confirm the safety for tenecteplase in Chinese patients.

Ovotesticular disorders of sex development is a rare chromosomal gender abnormality disease. MRI has more advantages than ultrasound in showing the location, shape and development of internal genitalia, which is of great significance in diagnosing and judging the types of hermaphroditism. The purpose of this paper is to explore the significance of MRI in clinical diagnosis and differential diagnosis in order to improve the understanding of the disease and the ability of clinical diagnosis and treatment.