Insulin neuroprotection and the mechanisms / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To analyze the mechanism of neuroprotection of insulin and which blood glucose range was benefit for insulin exerting neuroprotective action.</p><p><b>DATA SOURCES</b>The study is based on the data from PubMed.</p><p><b>STUDY SELECTION</b>Articles were selected with the search terms "insulin", "blood glucose", "neuroprotection", "brain", "glycogen", "cerebral ischemia", "neuronal necrosis", "glutamate", "γ-aminobutyric acid".</p><p><b>RESULTS</b>Insulin has neuroprotection. The mechanisms include the regulation of neurotransmitter, promoting glycogen synthesis, and inhibition of neuronal necrosis and apoptosis. Insulin could play its role in neuroprotection by avoiding hypoglycemia and hyperglycemia.</p><p><b>CONCLUSIONS</b>Intermittent and long-term infusion insulin may be a benefit for patients with ischemic brain damage at blood glucose 6-9 mmol/L.</p>

Clinical study on Bevacizumab for macular edema induced by retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

To evaluate the safety and efficacy of intravitreal bevacizumab injection in patients with macular edema (ME) induced by retinal vein occlusion (RVO). ● METHODS: The records of patients treated with intravitreal injection of 1. 75mg bevacizumab for ME induced by RVO were retrospectively reviewed. All patients were evaluated by complete ophthalmic examination, optical coherence tomography ( OCT) and fundus fluorescein angiography ( FFA ), etc. Best corrected visual acuity (BCVA), intraocular pressure, the change of lens and vitreous, central foveal thickness (CFT) were observed at 1, 2, 3, 6mo after treatment and compared with before treatment. Repeated treatment with intravitreous bevacizumab occurred if there were signs of persistent or recurrent exudation. All the cases were followed up at least 6mo. An intravitreal injection of bevacizumab (1. 75mg) was given at 6wk intervals. ●RESULTS: Fifty patients (56 eyes) with the average of (57±18. 56) years old were included. The mean baseline of BCVA, CFT were (logMAR0. 82±0. 63), (626. 5±178. 0)μm respectively. Although there was no significant decrease in mean CFT at 1wk after injection, the mean BCVA had significant improvement. Followed up at mean 10. 26 ± 5. 87mo, BCVA, CFT showed significant improvements over baseline values. The statistics of CFT at 1, 2, 3mo after injection were significant differences compared with before injection in each of the three groups. CFT at 1, 3, 12mo after injection were (365. 11±23. 212) μ m, (333. 42± 35. 526) μ m, (267. 6 ± 116. 8) μ m, which had a significant difference ( P 0. 05). OCT image showed that after injection macular retinal thickness was becoming thinner. FFA showed that after injection macular fluorescein leakage decreased. BCVA was improved by at least two lines in 48 eyes (86%),remained stable in 8 eyes (14%) at the last visit. A total of 112 injections were performed and the average number of injections was 1. 96 in the group. About 50% of reinjections gained at least two lines of vision improvement at 1wk following the retreatment. There was no serious complications during the treatment. ●CONCLUSlON: lntravitreal injection of bevacizumab can improve visual acuity (VA) of RVO (CRVO and BRVO) in patients with ME, relieve ME, reduce the leakage of CNV, and repeated treatment is better. But a prolonged treatment effect needs further observation. There are no serious ocular and systemic complications occurred in our study.

Clinical observation of bevacizumab (avastin) for treating age - related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the safety and efficacy of intravitreal bevacizumab ( avastin ) injection in patients with exudative age related macular degeneration ( AMD) . METHODS: The records of patients treated with intravitreal injection of 1. 75mg bevacizumab for AMD were retrospectively reviewed. All patients were evaluated by complete ophthalmic examination, optical coherence tomography and fundus fluorescein and/or indocyanine green angiography. Observation was made on the best corrected visual acuity ( BCVA) , intraocular pressure, and the changes of lens, vitreous, central retinal thickness (CFT) and total macular volume (TMV), at 1d, 3d, 7d, 1mo and 6mo after the treatment and then compared with those of pre - operation. Repeated treatment with intravitreous bevacizumab occurred if there were signs of persistent or recurrent exudation. And all cases were followed up at least 6mo. An intravitreal injection of bevacizumab (1. 75mg) was given once every 6wk. RESULTS:All 50 eyes of 48 patients with the average of 58±20. 46 years old were included. The mean baseline of BCVA and CFT were 0. 82±0. 53, and 364. 97±151. 83μm respectively. Although there was no significant decrease in mean CFT and TMV one week after the injection, the mean BCVA had significant improvement. At the last visit of 9. 7mo follow - up, BCVA, CRT and TMV showed significant improvements over baseline values. BCVA was improved by at least two lines in 32 eyes (64%),remained stabilization in 18 eyes (36%) at the last visit. A total of 98 injections were performed and the average number of injections was 1. 98 for each eye in the group. About 50%of re - injections gained at least two lines of vision improvement one week postoperatively. There were no serious adverse events during the treatment. CONCLUSION: Intravitreal bevacizumab ( avastin ) injection for managing CNV due to age-related macular degeneration is safe and few side effects. Intravitreal avastin associated with improvement in visual acuity ( VA ) , which can reduce macular edema and choroidal neovascularization leakage. But a prolonged treatment effect needs further observation.

Molecular mechanism of ORFV intervention strategies based on the UPS of host cell: a review / 病毒学报

In order to compete the antiviral effects of the host cell in the process of infection, ORFV(known as Orf virus) relies on a series of functional genes developed through long-term population evolution, such as interferon resistance genes, Bcl-2 protein genes and cell cycle inhibitor gene and so on, with these weapons this virus is able to effectively counteract immune clearance and immune regulation from a host cell. Concurrently, ORFV also focuses on exploiting signal transduction pathways of the ubiquitin-proteasome system(UPS), circumvents the intracellular signal transduction and CD8+ T activation, for shielding virus particles towards maturation and releasing outside. This review introduced inner link between the UPS of host cell and intervention mechanism by virus, and analyzed the key roles of certains components in UPS, these all together showed the evolution tendency of ORFV that was involved in the designing of inhibition to immune response and for intracellular immune escape upon the selection pressure in host cell infected.

Impact of unilateral acute testicular ischemia on the contralateral testis of rabbits in anesthetic and conscious states / 中华男科学杂志

<p><b>OBJECTIVE</b>To compare the impact of unilateral acute testicular ischemia on the hemodynamics and histology of the contralateral testis of the rabbits under consistent anesthesia with that of the rabbits in the conscious state.</p><p><b>METHODS</b>Forty-two healthy male white rabbits were randomly divided into an anesthetic group (Group A) to receive injection of sodium pentobarbital (PS) and a non-anesthetic group (Group B), each including a control group of 5 animals (A0 and B0), an incomplete testicular ischemia group of 8 (A1 and B1), and a complete testicular ischemia group of 8 (A2 and B2). Testicular ischemia models were constructed by color Doppler ultrasonography. Contrast-enhanced ultrasound (CEUS) was used to observe the perfusion of the contralateral testes before and after ligating and loosening the unilateral spermatic cord in each experimental group. The control animals also underwent CEUS and measurement of the heart rate (HR) and blood pressure (BP) at the corresponding time. Histological structure changes in the contralateral testes of the rabbits were observed in both anesthetic and conscious states.</p><p><b>RESULTS</b>PS anesthesia markedly suppressed the HR and BP of the rabbits. The parameters in Groups of A0, A1 and A2 showed no statistically significant changes after unilateral ligation of the spermatic cord, while Groups B1 and B2 displayed significantly decreased peak-base difference (PBD) and prolonged arrival time (AT) and half time of descending peak intensity (HT). Groups A1, B1 and B2 showed significantly increased PBD and prolonged HT shortly after loosening the spermatic cord. Focal pathological and ultrastructural changes were observed in the contralateral testes of the ischemic rabbits, but no significant difference was found in Johnson's score in comparison with the controls. The apoptotic cells were remarkably increased in Groups A1, B1 and B2.</p><p><b>CONCLUSION</b>Acute testicular ischemia may induce injury to the contralateral testis to some degree, and a reflexive sympathetic response may cause hemodynamic changes in the non-anesthetic state. And the neural and vascular inhibitory effects of anesthesia could make insignificant changes of blood perfusion in the contralateral testis.</p>

Ischemic postconditioning reduces testis ischemia-reperfusion injury in rabbits / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of ischemic postconditioning (IP) against different degrees of testicular ischemia-reperfusion (IR) injury in rabbits.</p><p><b>METHODS</b>Forty-two white male rabbits were equally randomized into 7 groups: a control, 3 IR (R1, R2 and R3), and 3 IP (P1, P2 and P3) groups. Testicular models of different degrees of ischemia were established in the IR and IP groups. Before reperfusion, ultrasonography showed homogeneous echoes with slightly decreased blood flow in R1 and P1, heterogeneous echoes with obviously decreased blood flow in R2 and P2, lamellar or fragmental low echo areas absent of blood flow signals in R3 and P3. Then the IR groups were directly subjected to perfusion, and the IP groups to 3 episodes of 30-second reperfusion followed by 30-second ischemia. All the groups underwent contrast-enhanced ultrasonography (CEUS) before reperfusion and, after 3 days, examined for the contents of malonaldehyde (MDA), superoxide dismutase (SOD) and histology, and observed for the pathological changes of the testicular tissue.</p><p><b>RESULTS</b>Before reperfusion, no significant differences were found in the CEUS parameters beta, time-to- peak (TTP), peak-base intensity (PBD) and half of declining time (DT/2) between R1 and P1, R2 and P2, and R3 and P3 (P>0.05). There were remarkable differences in MDA and SOD between R1 and P1, and R2 and P2 (P<0.05), but not between R3 and P3 (P >0.05). Johnson's score, apoptosis index and ultrastructure showed marked differences between R1 and P1 (P<0.05) but not between R2 and P2, and R3 and P3 (P >0.05).</p><p><b>CONCLUSION</b>IP can attenuate IR-induced testis injury, but the effect varies with the degree of ischemia, and its pathological manifestation differs from the biochemical one.</p>

Ultrasonographic appearance of experimental testicular ischemia and protective effect of allopurinol / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the correlation of the ultrasonographic appearance of different degrees of experimentally induced acute unilateral testicular ischemia with the protective effect of allopurinol.</p><p><b>METHODS</b>Forty-two male white rabbits were equally randomized into 7 groups: sham-operation control, ischemic A, B and C, and treatment D, E and F. Models of different degrees of unilateral testicular ischemia were established in the ischemic and treatment groups under the dynamic observation by color Doppler ultrasound. The ischemic testes showed slightly decreased homogeneous echoes and flow signals in groups A and D, obviously decreased heterogeneous echoes and flow signals in groups B and E, and radial or fragmental low-echo areas and disappearance of flow signals in groups C and F. The ischemic groups received reperfusion after the appearance of the above ultrasonographic changes, while the treatment groups following the intraperitoneal injection of allopurinol at 200 mg/kg. Contrast-enhanced ultrasonography (CEUS) was performed on the bilateral testes before and 3 days after the reperfusion. After 3 days of breeding, the histological changes and malondialdehyde (MDA) contents of the ischemic testes were observed, and the correlation was analyzed between the protective effect of allopurinol and the ultrasonographic appearance of different degrees of acute unilateral testicular ischemia.</p><p><b>RESULTS</b>CEUS showed fast wash-in and fast wash-out in the sham-operation control group, slow wash-in and slow wash-out in groups A and B and extensive central filling defect in group C before the reperfusion. Fast wash-in and slow wash-out were observed in all the ischemic groups 3 days after the reperfusion, most obviously in group C. Groups D, E and F exhibited the same CEUS appearance as A, B and C before and 3 days after the reperfusion. Johnsen's scores were significantly increased in groups D (9.10 +/- 0.23) and E (7.03 +/- 0.20) in comparison with A (8.53 +/- 0.22) and B (5.82 +/- 0.33) (P < 0.05), but with no significant differences between C (2.30 +/- 0.53) and F (2.45 +/- 0.33) (P > 0.05). The rates of apoptosis were significantly decreased in groups D ([1.68 +/- 0.43]%) and E ([12.53 +/- 0.59]%) compared with A ([7.12 +/- 0.84]%) and B ([20.87 +/- 1.59]%) (P < 0.05), but with no significant differences between C ([52.93 +/- 2.62 ]%) and F ([51.23 +/- 2.53 ]%) (P > 0.05). Significant decreases of MDA contents in the ischemic testes were observed in groups D ([0.64 +/- 0.05] nmol/mg prot), E ([1.59 +/- 0.06] nmol/mg prot) and F ([3.10 +/- 0.17] nmol/mg prot) in comparison with A ([1.38 +/- 0.07] nmol/mg prot), B ([2.11 +/- 0.08] nmol/mg prot) and C ([3.25 +/- 0.14] nmol/mg prot) (P < 0.05).</p><p><b>CONCLUSION</b>Allopurinol contributes to the recovery of spermatogenesis when testicular ischemia is sonographically shown to be mild or moderate, but produces no significant effect when it is shown to be severe. Ultrasonography helps to choose the right therapy of testicular torsion and predict spermatogenesis of ischemic testes after reperfusion.</p>

Correlation between sonographic appearance of experimental testicular ischemia and histological changes of the testis after reperfusion / 中华男科学杂志

<p><b>OBJECTIVE</b>To discuss the correlation between sonographic appearance of different degrees of acute unilateral testicular ischemia and histological changes of the testis after reperfusion.</p><p><b>METHODS</b>Thirty-two male rabbits were equally divided into a control (sham operation) group and 3 ischemia groups. Unilateral testicular ischemia models were established under the color Doppler ultrasound (CDU) observation and allocated according to different degrees of ischemia to Group A (with homogeneous echoes and slightly decreased flow signals), B (with heterogeneous echoes and obviously decreased flow signals) and C (with radial or small-shredded low echoes and absence of flow signals). Then contrast-enhanced ultrasonography (CEUS) was performed, followed by reperfusion of the ischemic testes. A month later, the histological changes of the testes were observed and the correlation of the histological changes with the sonographic and CEUS manifestations was analyzed.</p><p><b>RESULTS</b>Concerning the CEUS parameters such as the arrival time (AT), reperfusion rate, time-to-peak (TTP), half descent time (DT/2) of the ischemic testes, Groups A and B showed significant differences from the control group (P < 0.05). The peak-base difference (PBD) was significant in Group B (P < 0.05) but not in A (P > 0.05), and no enhancement was seen in Group C. As for Johnson's scores obtained 1 month later, Group A exhibited no significant difference (8.70 +/- 0.39) (P > 0.05), Group B showed significant difference (6.01 +/- 0.88) (P < 0.05), and Group C extremely significant difference (3.16 +/- 1.05) (P< 0.001) from the control group (9.10 +/- 0.11).</p><p><b>CONCLUSION</b>CEUS is superior to CDU in evaluating the perfusion of testicular ischemia. Sonographic appearances of testicular ischemia are significantly correlated with histological changes of the testis after reperfusion. Ultrasonography helps to predict the spermatogenetic function of ischemic testes after reperfusion.</p>

Effect of fibroblast growth factor 9 on Runx2 gene promoter activity in MC3T3-E1 and C2C12 cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fibroblast growth factor 9 (FGF9), expressed in brain, kidney and developing skeletal tissues, can physiologically inhibit endochondral ossification; but little is known about how FGF9 affects osteoblasts and its detailed regulatory mechanism. Here we examined the effect of FGF9 on the activity of the murine Runt-related transcription factor 2 (Runx2) gene promoter in preosteoblast MC3T3-E1 and premyoblast C2C12 cells.</p><p><b>METHODS</b>Plasmids containing the Runx2 promoter region were transfected into MC3T3-E1 and C2C12 cells and stably transfected cell lines were established. The method of luciferase reporter gene activation was used to examine the effects of FGF9 on the promoter activity.</p><p><b>RESULTS</b>FGF9 (10 ng/ml) increased Runx2 promoter activity in MC3T3-E1 cells. When MC3T3-E1 cells were treated with FGF9 plus the various inhibitors or activator of the intracellular signaling transducation pathways, including 10 micromol/L U0126 (the inhibitor of mitogen-activated protein kinase kinase), 10 micromol/L SB203580 (the inhibitor of p38/mitogen activated protein kinase), or 1 micromol/L C6 ceramide (an activator of mitogen activated protein kinase), the luciferase expression did not change significantly compared with that of the cells treated with FGF9 only. However, when C2C12 cells were treated with 10 ng/ml FGF9, Runx2 gene promoter activity first decreased and then increased over a period of 1 to 5 days. Among the above inhibitors, only U0126 (10 micromol/L) completely blocked the effects of FGF9 on Runx2 gene promoter activity.</p><p><b>CONCLUSIONS</b>Our data showed that FGF9 can affect Runx2 gene promoter activity in MC3T3-E1 and C2C12 cells. The action of FGF9 appears to depend partly on the mitogen-activated protein kinase kinase/mitogen-activated protein kinase pathways in C2C12 cells.</p>