AIM: To investigate the effects of pioglitazone on corneal neovascularization(CNV)induced by alkali burnin rats and on expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF).METHODS: CNV was induced by alkaline burn in rats which were then administered pioglitazone subconjunctivally.Corneal angiogenesis was evaluated and observed with a slit lamp microscope and the VEGF and b-FGF level were determined by immunohistochemistry and Western blot at different intervals.RESULTS: The CNV of the rats was shown two days after alkaline burn, and reached its highest level in 7-10 days. The mean values of the area and length of neovascularization and the VEGF and b-FGF levels in the pioglitazone-treated group were significantly lower than those in the control group at various time.CONCLUSTON: Local application of pioglitazone could remarkably inhibit CNV, probably by means of downregulation of VEGF and b-FGF expression.

OBJECTIVETo investigate the impact of hyperglycemia on the hydrogen sulfide (H2S) signaling pathway in rat penile tissue and its relationship with erectile function.

METHODSTwenty healthy male Sprague Dawley (SD) rats aged 8 weeks were randomly divided into groups A (4-week healthy control), B (4-week diabetes mellitus model), C (6-week healthy control) and D (6-week diabetes mellitus model). The rats in groups B and D were injected intraperitoneally with streptozotocin at 50 mg/kg to induce diabetes mellitus, while those in groups A and C with the same volume of normal saline. The animals were killed at 4 (groups A and B) and 6 weeks (groups C and D) after treatment for measurement of the maximal intracavernous pressure/mean arterial blood pressure (ICP(max)/MAP) by electrostimulation, determination of the H2S concentration in the plasma and penile tissue, and detection of the expressions of cystathionine-beta-synthetase (CBS) and cystathionine-gamma-lyase (CSE) in the penile corpus cavernosum by immunohisto- chemistry and Western blot.

RESULTSWith electrostimulation of the pelvic ganglia at 5V and 7 V, ICP(max)/MAP was significantly reduced in groups B (0.19 +/- 0.03 and 0.29 +/- 0.04) and D (0.14 +/- 0.04 and 0.25 +/- 0.04) as compared with A (0.46 +/- 0.07 and 0.68 +/- 0.09) and C (0.43 +/- 0.07 and 0.65 +/- 0.16) (P < 0.05). No statistically significant differences were found in the level of serum testosterone either between groups A and B ([469.19 +/- 126.46] ng/dl vs [359.08 +/- 60.06] ng/dl, P > 0.05) or between C and D ([470.44 +/- 209.28] ng/dl vs [297.01 +/- 96.58] ng/dl, P > 0.05). Groups B and D showed remarkable reduction in the H2S concentration (P < 0.05) and the expressions of CBS and CSE (P < 0.05) in comparison with A and C, and the CBS and CSE expressions were even more significantly decreased in D than in B (P < 0.05).

CONCLUSIONThe reduced concentration of H2S and decreased expressions of CBS and CSE in the penile corpus cavernosum of the diabetic rats suggested that the H2S signaling pathway might be involved in hyperglycemia-induced erectile dysfunction.

Animals ; Blood Pressure ; physiology ; Cystathionine gamma-Lyase ; metabolism ; Diabetes Mellitus, Experimental ; chemically induced ; metabolism ; Electric Stimulation ; methods ; Erectile Dysfunction ; etiology ; Humans ; Hydrogen Sulfide ; metabolism ; Hyperglycemia ; metabolism ; Lyases ; metabolism ; Male ; Penis ; enzymology ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Testosterone ; metabolism

Objective To establish a pancreatic ?-cell developmet fish model with specific spatial expression patterns.Methods Molecular cloning,microinjection,whole embryo in-situ hybridization(WISH)and fluorescence microscopy in living were used to analyze of ?-cell development through generation of transgenic zebrafish.ResultsScreened and established pancreatic ? cells of transgenic zebrafish,and confirmed the fluorescence protein expression in the same spatiotemporal pattern with endogenous insulin gene to achieve dynamic monitoring islet ?-cell development situation in vivo.Conclusion The pancreatic ? cells of transgenic zebrafish animal model can successfully trace pancreatic ? cell development.

Objective To assess the clinical significance of three-dimensional speckle tracking imaging (3D-STI) in the evaluation of left ventricular myocardial function in breast cancer survivors with postoperative anthracycline-based chemotherapy.Methods A total of 51 breast cancer survivors with postoperative anthracycline-based chemotherapy were recruited and 31 female healthy volunteers as the controls.Conventional echocardiography and 3D-STI derived parameters [including global longitudinal strain (GLS) and global area strain (GAS)] were measured before and at 3 and 6 anthracycline-based chemotherapeutic cycles.The receiver operating characteristics (ROC) curve was constructed to determine optimal sensitivity and specificity of 3ID-STI derived parameters for the prediction of future cardiotoxicity.Results In comparison with the controls and baseline cases,GLS and GAS deteriorated significantly (P ＜ 0.05 for both).No statistical difference in GCS and conventional parameters showed before and after the initiation of chemotherapy (P ＜0.05,respectively).The ROC curves showed that GAS as the best 3D-STI predictor of patients who develop cardiotoxicity during the follow-up.The area under ROC(AUC) of GAS was 0.894,and its optimal cut-off value was-28.4％,with a specificity of 88.0％ and a sensitivity of 82.9％.AUC of GLS was 0.802,and its optimal cut-off value was-14.3％,with a specificity of 62.0％ and a sensitivity of 85.4％.Conclusions Early decreases in GAS and GLS based on 3D-STI may allow the prediction of subsequent cardiotoxic development accurately in breast cancer survivors with postoperative anthracycline-based chemotherapy.

Objective:To evaluate the role of nuclear receptor subfamily 1, group D, member 1/brain and muscle Arnt-like 1(Rev-erbα/Bmal1) signaling pathway in myocardial ischemia-reperfusion (I/R) injury in diabetic rats and its relationship with autophagy.Methods:SPF-grade adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-220 g, were used in this study.Type I diabetes mellitus was induced by intraperitoneal streptozotocin 60 mg/kg.The rats were continuously fed for 8 weeks after successful establishment of the model.Thirty rats with type 1 diabetes mellitus were divided into 3 groups by a random number table method: diabetic sham operation group (DS group, n=6), diabetic myocardial I/R group (DI/R group, n=12) and diabetic myocardial I/R plus Rev-erbα antagonist SR-8278 group (DI/R+ SR group, n=12). Eighteen non-diabetic rats were divided into 2 groups by a random number table method: non-diabetic sham operation group (NS group, n=6) and non-diabetic myocardial I/R group (NI/R group, n=12). The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion in anesthetized rats.SR-8278 2 mg/kg was intravenously injected via the femoral vein at 1 h before ischemia in group DI/R+ SR.Blood samples were collected from the carotid artery immediately after the end of reperfusion for determination of serum troponin I (cTnI), creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) levels (by enzyme-linked immunosorbent assay). Then the rats were sacrificed, and myocardial tissues were obtained for determination of myocardial infarct size (by TTC method), expression of Rev-erbα and Bmal1 mRNA (by real-time polymerase chain reaction) and expression of Rev-erbα, Bmal1, microtubule-associated protein 1 light chain (LC3) Ⅱ and LC3Ⅰ (by Western blot) and for calculation of the ratio of LC3 Ⅱ/LC3Ⅰand the number of autophagosomes (with a transmission electron microscope). Results:Compared with group NS, the percentage of myocardial infarct size, serum levels of cTnI, CK-MB and LDH and the number of autophagosomes were significantly increased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas increased in group NI/R, and serum levels of cTnI, CK-MB and LDH were increased, the number of autophagosomes was decreased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated and the ratio of LC3 Ⅱ/LC3Ⅰwas decreased in group DS ( P<0.05). Compared with group NI/R, the percentage of myocardial infarct size and serum levels of cTnI, CK-MB and LDH were significantly increased, the number of autophagosomes was decreased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas decreased in group DI/R ( P<0.05). Compared with group DS, the percentage of myocardial infarct size, serum levels of cTnI, CK-MB and LDH and the number of autophagosomes were were significantly increased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas increased in group DI/R ( P<0.05). Compared with group DI/R, the percentage of myocardial infarct size, serum levels of cTnI, CK-MB and LDH and the number of autophagosomes were significantly decreased, the expression of Rev-erbα and its mRNA in myocardial tissues was down-regulated, the expression of Bmall and its mRNA was up-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas increased in group DI/R+ SR ( P<0.05). Conclusion:Rev-erbα/BMAL1 signaling pathway is involved in the process of myocardial I/R injury by regulating cell autophagy in diabetic rats.

Objective To study the changes of serum interleukin(IL)-4,IL-12 and correlation with cellular immunity in children with asthma of different stages.Methods Fifty asthmatic children were randomly selected, including 30 cases in attack stage (group A) and 20 cases in remission stage (group R). At the same time, 22 healthy children were studied as normal controls (group N).The levels of IL-12 and IL-4 ,T cells subgroups and erythrocyte immunity were detected.Results 1.Serum IL-12 levels were (24.44? 13.26 ),(42.30?12.65),(44.68?28.28) ng/L in group A, R and N,respectively. There was significant difference in three groups (F=8.92 P

0.05);and there were significant diffe-rences between the final diagnosis and pre-hospitalized diagnosis in all patients with VE(?2=47.08 P

Objective To explore the value of color doppler ultrasonography by bed side in the early diagnosis of HIE in full term neonates.Methods The changes of cerebral parenchymal and cerebral arterial blood stream parameter on 35 cases of neonates clinically diagnosed HIE of mild and moderate degree and 40 cases of normal newborns on the 24,48 and 72 hours after birth were observed by color doppler ultrasonography by bed side.Results 1.The cerebral parenchyma was even echo in normal newborns,but it was maldistributed and reinforced in mild asphyxia neonates and it was more serious in moderate degree.The echo of cerebral parenchyma in mild degree was near normal in 48 hours after birth,while the echo of cerebral parenchyma in moderate degree was still maldistributed and reinforced in 48 and 72 hours after birth.2.There was obvious changes in the cerebral arterial blood stream parameter and hemodynamics of the asphyxia newborns compared with normals.The systolic peak velocity(Vs)and end diastolic velocity(Vd)of the cerebral arteries in mild and moderate degree were obviously lower than that of control group in 24,48 hours after birth(Pa0.05).3.Resistance index(RI)of the cerebral arteries in mild and moderate degree were higher than that of control group in 24,48 hours after birth(Pa0.05).Conclusion Color doppler ultrasonography by bed side is a convenient,noninvasive method for diagnosing HIE.

Objective Hepatic artery (HA) reconstruction is one challenging procedure in pediatric liver transplantation (PLT).Here we review the first 115 microsurgical reconstructions of HA in PLT performed by a single surgeon,aiming to demonstrate the learning curve and the problems encountered.Methods From July 2016 to January 2017,a series of 115 microsurgical reconstructions of HA in PLT for end-stage liver disease were finished by one single surgeon with 4-year liver surgery experience and 2-week microsurgical training.HA reconstruction was performed with an operating microscope (Carl-Zeiss S88).Reconstruction was completed with interrupted sutures with 8-0 or 9-0 Prolene using the double clip for fixation.The blood flow was examined by Doppler scan daily after PLTs in first week and then once in 2nd week and first month for patency.A total of 143 artery anastomoses were performed in 115 PLTs.The age ranged from 3 months to 9 years.Indications for PLT included biliary atresia (105/115),Alagille syndrome (5/115),PFIC (3/115),Caroli disease (1/115),methylmalonicacidemia (1/115) and glycogen storage disease (1/115).Most of the PLTs were living donor liver transplantation (107/115),along with OLT (5/115) and split LT (3/115).Results The diameter of the arteries was mostly less than 2 mm (98/115).Up to date,one HA thrombosis (HAT) occurred at D8 after LT and 4 cases suspected as temporal HA stenosis (HAS) around 2 weeks after LT,which manifested as low velocity (<20 cm/s) and resistance index (<0.50) by Doppler.The HAT case failed in emergent re-anastomosis,but had a spontaneous recanalization at 3 weeks and is now in good condition without biliary problem.All the HAS children recovered to normal flows at first month.All children with HA complications started warfarin upon detection,with a targeted INR between 1.5-2.0.There were 6 deaths in this series including 5 cases of infections and 1 case of graft failure.Learning curve suggested a two phases growth (first 44 cases practicing phase vs.next 71 cases mature phase),which can be attributed to experience accumulation in terms of precise of manipulation,choice of inflow arteries for better match and stronger pulsation,avoidance of length redundant,prevention of kink.All the HAT and HASs happened in practicing phase while outcomes were excellent in mature phase.Moreover,time for each anastomosis was significantly shortened in second phase from 45-70 min to 30-55 min.Conclusion Microsurgical technique is highly safe in pediatric HA reconstruction,especially for very tiny arteries.It is possible to achieve low risk of complications for a new surgeon with adequate experience in liver surgery and microsurgical training.However,more surveillance and timing anticoagulation therapy is required before the mature of microsurgical technique.

Objective: To investigate the survival and individualized therapy of metastatic colorectal cancer (mCRC) patients who achieved a stable disease state after induction chemotherapy. Methods:Data were reviewed from 204 metastatic colorectal cancer pa-tients, who presented a stable disease state after first-line and second-line chemotherapy at Tianjin Medical University Cancer Insti-tute and Hospital. The clinical and pathological characteristics were analyzed. Moreover, we analyzed the significance of maintenance treatment in patients with certain mCRC characteristics. Results:Univariate analysis indicated that the line of chemotherapy, levels of CA724, CEA, and CA19-9, and platelet-to-lymphocyte ratio (PLR) were considered prognostic factors of treatment after induction che-motherapy. According to the multivariate analysis, first-line chemotherapy, as well as low levels of CA19-9 and PLR, with maintenance treatment after the induction chemotherapy was significantly associated with better survival. Among the patients with high levels of PLR, those who underwent maintenance treatment achieved a progression-free survival of 13.43 months (versus 10.63 months in pa-tients from the observation group, P=0.003). Conclusion:The levels of CA19-9 and PLR, and treatment after chemotherapy were signif-icant prognostic factors for mCRC patients who achieved a stable disease state after induction chemotherapy. These patients, especial-ly those with high PLR, could benefit from the maintenance treatment.