One of the common hallmark lesions of Alzheimer's disease (AD) brains is neurofibrillary tangles(NFTs), which are composed of phosphorylated tau protein (p-tau).NFTs are also a defining feature of other neurodegenerative disorders and have recently been identified in the patients suffering from chronic traumatic encephalopathy (CTE).Tau protein pathological change is the etiological factor of AD and CTE after traumatic brain injury (TBI), and CIS p-tau is an early driving factor of neurodegeneration after brain injury.CIS p-tau can induce tau protein pathology, and the detection of CIS p-tau in human may provide new diagnostic methods and prognostic measures.Furthermore, the individualized cis p-tau antibody could ultimately be developed as a new treatment for AD, TBI and CTE.This article reviews the mechanism of tau protein in TBI and neurodegeneration, the formation of CIS P-tau protein, the role of cistauosis and the progress of CIS p-tau antibody therapy.

Objective To investigate the expression of mRNAs for cholesterol side chain cleavage enzyme (p450 scc), 17?-hydroxylase / C17-20 lyase (P450 C17) and 3?-hydroxysteroid dehydrogenase (3?-HSD) in frontal cortex, amygdala, hippocampus, striatum and midbrain of morphine dependence rats.Methods Twenty-one male SD rats were randomly divided into 3 groups with 7 animals in each group: (1) control group (group C) ; (2) morphine dependence group (group D) and (3) morphine withdrawal group (group W). In group D and W the animals were given intraperitoneally increasing doses of morphine starting from 5 mg?kg-1 to 10, 15, 20, 30, 40 and 50 mg?kg-1 twice a day for 7 days. In group C the animals were given normal saline instead of morphine. In group C and D the animals were decapitated 1 h after last injection. In group W naloxone 2 mg?kg-1 was given 1h after last morphine injection, then the animals were decapitated 30 min after withdrawal symptoms were observed. The brains were immediately removed and the frontal cortex, amygdala, hippocampus, striatum and midbrain were separated. The expression of mRNAs for the three steroidogenic enzymes in the different brain regions of rats were determined by RT-PCR.Results The expression of P450scc mRNA in striatum and 3?-HSD mRNA in amygdala, striatum and frontal cortex decreased in group D compared with group C. The expression of 3?-HSD mRNA increased in morphine withdrawal group compared with group D.Conclusion The gene expression of steroidogenic enzymes decreases in some brain regions of morphine dependence rats, suggesting that endogenous neurosteroids might be involved in morphine dependence.

AIM: To evaluate the safety and efficacy of loteprednol for controlling of ocular inflammation. METHODS: Data from 8 relevant monographs were retrieved by means of computerized and manual search. The combined analysis of the data was assessed in terms of clinical and statistical criteria, and the data were extracted and synthesized by using the statistical techniques of meta-analysis. Treatment effects and safety of loteprednol were through counting as risk difference between treatment and control groups. The estimates of pooled risk differences were computed according to a random-effects model. RESULTS: A total of 1 660 patients were included in this meta-analysis. Pooled risk differences of intraocular pressure elevation were 1 % (95 % CI, -1 %, 3 %) compared with placebo, -5 % (95 % CI, -9 %, 0 %) compared with prednisolone, respectively. Compared with placebo, pooled risk differences of inflammation improvement were: 31 % (95 % CI, 22 %, 40 %) of postoperative inflammation, 28 % (95 % CI, 19 %, 37 %) of seasonal allergic conjunctivitis, and 26 % (95 % CI, 18 %, 35 %) of giant papillary conjunctivitis, respectively. Compared with prednisolone, pooled risk differences of inflammation improvement of acute anterior uveitis was -15 % (95 % CI, -25 %, -4 %). CONCLUSION: Loteprednol is a safe and effective corticosteroid in controlling ocular inflammation such as postoperative inflammation, seasonal allergic conjunctivitis, giant papillary conjunctivitis, and acute anterior uveitis.

Objective The difference of the equivalent IOL powers before and after LASIK was calculated by using the Haigis-L formula and Sirius ray-tracing respectively.And study the correlation be-tween the intraocular lens power and the myopic before laser in situ keratomileusis.Methods Ninety-one patients undergoing myopic laser in situ keratomileusis were enrolled, they were divided into 3 groups ac-cording to myopic diopter, group I (-1.00D~-3.00D) 13cases, group II( -3.25D and -6.00D)60 cases, group III(-6.25D~-10.0D)18 cases.The equivalent IOL power before and after LASIK will be calculated using Haigis-L formula and Sirius ray-tracing.The data were analyzed using SPSS20.0.Results 80.2%of the cases calculated using Haigis-L formula were within ±0.50D of the predicted refraction , 94.5%were within ±1.00D, and 100%within ±1.50D.also, within ±0.50D of the predicted refrac-tion 13cases(100%),51cases(85%),9cases(50%) in group I, II, III respectively.74.7% of the eyes calculated using Sirius ray-tracing were within ±0.50D of the predicted refraction , 89.0%were within ± 1.00D, and 100%within ±1.50D.within ±0.50D of the predicted refraction 12cases(92.3%),48cases (80%),8cases(44.4%) in group I, II, III respectively.Conclusions Sirius ray-tracing and Haigis-L formula can calculate IOL power accurately in eyes with prior myopic LASIK, with no need for preoperative data.and there is positive correlation between the intraocular lens power aberration and the myopic diopter before LASIK.

Objective: To investigate the effects of the exogenous testosterone propionate on apoptosis of rat germ cells and the mechanisms thereof. Methods: Thirty 35-day-old male SD rats were randomly divided into experimental group and the control group. The rats in experimental group were injected (i.m.) testosterone propionate and the control group with an equal volume of saline. By using terminal deoxynueleotidy transferase nediated dUTP nick-end labeling (TUNEL), flow cytometry (FCM), radioimmunoassay (RIA) and electron microscopy, the quantity and quality of apoptosis of germ cells were evaluated. Results:(1) Compared with the control, the apoptotic number of rat germ cells was increased in the experimental group, especially the primary spermatocyte. The apoptotie rate was 11.3% detected by FCM in experimental group,while 3.6% in the control group (P ＜ 0.01). (2) The percentages of 1C were 21.8% in experimental group and 33.8% in control group (P ＜ 0.01).The percentages of 2C were 52.6% in experimental group and 37.1% in control group (P ＜ 0.01). (3) The serum levels of testosterone were (3 486.8±333.3) ng/L in experimental group and (846.9±167.5) ng/L in control group (P ＜ 0.01). The serum levels of follicle-stimulating hormone (FSH) were (2.5±0.8) IU/L in experimental group and (5.2±1.7) IU/L in control group (P ＜0.01). Conclusion: The exogenous testosterone propionate might induce apoptosis of germ cells by retroinhibition of the hypothalamie-pituitary-gonadal axis, thus having contraceptive effects.

Background Transscleral diode laser cyclophotocoagulation (TDCP) was used to later stage of glaucoma in the past.However,the indications of TDCP are expanding gradually over time and there are more and more reports about its application in different stages and different types of glaucoma.Objective This study was to compare the clinical efficacy of TDCP and trabeculectomy for primary acute angle-closure glaucoma (PAACG) with persistent ocular hypertension.Methods Ninety-five PAACG patients with persistent ocular hypertension were retrospectively analyzed.The patients were divided into TDGP group (62 eyes of 56 cases) and trabeculectomy group (44 eyes of 39 cases) based on the difference of treating fashions.The clinical outcomes were compared between the two groups with the evaluating indexes of visual acuity,intraocular pressure (IOP) before and 1 week,3 months and the end of following-up as well as the number of drug used and the re-treatment.Results The demography was matched between the two groups (all at P＞0.05).The number of eyes with visual improvement was significantly different among the groups (x2 =30.927,P =0.002) in the TDCP group.Compared with before treatment,the number of visual improvement in 1 week after treatment was significantly raised (x2 =16.778,P =0.002).No significant differences were seen in the eye number of visual improvement in various timepoints after treatment (all at P＞0.008).Also,the eye number of visual improvement was significantly different among the different timepoints (x2 =44.345,P＜0.001),and statistically significant change was found between the preoperation and postoperative 1 week (x2 =23.725,P＜0.001).However,there were no significant differences in the eye number of visual improvement in various timepoints after operation each other (all at P＞0.008).The IOP was insignificantly altered among the groups at various timepoints (Fgroup =3.836,P =0.053),but the change was significantly different over time (Ftime =757.078,P＜0.001).The postoperative IOP was significantly higher than that of preoperation in both groups (all at P＜0.001).The proportion of eyes using lowering-IOP drugs was 48.4％ in the TDCP group,and that in the trabeculectomy group was 27.3％,showing a significant difference between them (x2 =4.796,P =0.029).The retherapy was performed in 20 eyes (32.3％) and 2 eyes (4.5％) in the TDCP group and the trabeculectomy group,respectively.Conclusions The short-term lowing-IOP effecacy of TDCP is similar to trabeculectomy,but the longterm lowing-IOP efficacy of TDCP is not good.Compared with the trabeculectomy,TDCP shows more simple operation,less time-consuming during the surgery and milder tissue damage,but the eyes continuing to use anti-glaucomatous drugs or re-therapy are increased.

BACKGROUND:The mechanism and effect of glycogen synthase kinase 3β(GSK-3β) in the differentiation of cardiac stem cel s into cardiomyocytes are stil unclear, although GSK-3βis closely related to the life activities of cel s.
OBJECTIVE:To investigate the changes of GSK-3βexpression in the treatment of myocardial infarction in rats undergoing cardiac stem cel transplantation.
METHODS:The isolation and culture of cardiac stem cel s were performed in 10 neonatal rats. Lentivirus overexpressing GSK-3βor LacZ (control) was constructed and transferred into cardiac stem cel s. Animal model of myocardial infarction was made in 30 Sprague-Dawley rats. Six weeks after model preparation, rat models were assigned into GSK-3β, LacZ or PBS group. GSK-3βor LacZ overexpressing cardiac stem cel solution or PBS in equal volume was injected into the rat myocardium, respectively. Four weeks after transplantation, the cardiac function and myocardial col agen production in rats were detected and compared.
RESULTS AND CONCLUSION:Compared with the other two groups, the left ventricular ejection fraction was significantly higher, and the left ventricular end diastolic diameter was significantly lower in the GSK-3βgroup (P<0.05). Hydroxyproline content, type I col agen mRNA, and type III col agen mRNA expression were significantly lower in the GSK-3βgroup than the other two groups (P<0.05). Findings from Masson staining showed that the content of blue-stained col agen was significantly lower in the GSK-3βgroup than the LacZ group. Moreover, lowest myocardial infarction size was found in the GSK-3βgroup (P<0.05). Al these experimental findings show that GSK-3 overexpression plays a positive role in promoting the therapeutic effect of cardiac stem cel transplantation.

AIM:To elucidate the molecular mechanisms of lipoic acid (LA) on redox regulation and digestive function in intestine of C57BL/6 mice fed high fat diet (HFD).METHODS:C57BL/6 mice were randomly assigned to one of three groups (n=8). The control group consumed an ordinary diet. The other two experimental groups were fed with a high fat diet,high fat plus 0.1% LA. After 6 weeks,the activities of digestive enzymes were examined. In order to evaluate the antioxidant status of the mice,superoxide dismutase (SOD),malondialdehyde (MDA),total antioxidant capacity (TAC) and reactive oxygen species (ROS) in intestinal homogenate were measured. To investigate the molecular mechanisms underlying the effects of LA,the gene expression profiles in intestine were examined using the GeneChip microarray system.RESULTS:A depressed antioxidant defense system,accompanied by digestive and absorptive function impairment,was observed in HFD-fed mice. These changes were partially restored in the LA-treated group. DNA microarray analysis of intestine showed that LA ingestion up-regulated the expression of genes related to free-radical scavenger enzymes,digestive enzymes and transporters.CONCLUSION:Treatment with LA improves redox homeostasis and the function of intestine in mice fed HFD. The mechanism may involve preventing oxidative stress by scavenging ROS directly and increasing those of free-radical scavenger enzymes gene expression indirectly.

Aim To investigate the modulation effects of NaHS on arterial vasodilatation functions of renal hy-pertensive rats .Methods Two-kidney , one-c lip ( 2K1C ) renovascular hypertension was induced .Rats were randomly divided into four group:sham group , two-kidney one-clip model ( 2K1C ) group, 2KIC +NaSH( H2 S donor ) group, PPG group.The systolic blood pressure ( SBP ) was measured before the opera-tion and each week after the operation .The carotid ar-tery was collected for morphometric parameters ( outer radius, wall thickness, the radio of wall thickness to outer radius) and the tension of the carotid artery was observed with the isolated artery ring technique .Immu-nohistochemistry was used to determine the protein ex-pression of eNOS , ET-1 protein in carotid artery .Re-sults The blood pressure of 2K1C group and PPG group was higher than that of sham group ( P<0.05) . Compared with 2K1C group,the blood pressure and the rat arteria carotis communis of the radio of wall thick-ness to outer radius of 2K1C+NaHS group decreased significantly , while the relaxation of carotid artery to ACh in NaHS group increased .According to the immu-nohistochemistry results , eNOS expression was upregu-lated while ET-1 was downregulated in 2K1C +NaHS group as compared with 2K1C group.Conclusions Chronical administration of NaHS can decrease blood pressure in renovasocular hypertensive rats .The anti-hypertensive effect of H 2 S maybe associated with im-provement of the arterial functions .

AIM To investigate if morphine addiction and relapse to morphine-seeking is related to the change in neurosteroid levels in the brain of rats. METHODS Rats were injected ip morphine (5 mg·kg-1·d-1, 18:00-20:00) and trained in conditioned place preference (CPP) box, once daily for 10 d. CPP test was performed 24 h after the last training. After discontinuation of training for 7 d for CPP extinction, then intermittent and inescapable foot-shock (FS, 0.5 mA, 0.5 s on, 40 s off, 15 min) was applied to rats as the priming stimuli for relapse. CPP test was performed 2 h after FS. When CPP test finished, rats were decapitated and the levels of neurosteroids were analyzed using gas chromatography/mass spectrometry. RESULTS CPP was established when rats were injected morphine and trained for 10 d. At the same time, the levels of pregnenolone and allopregnanolone in the brain tissues of rats were significantly increased. When CPP was reinstated in morphine-treated rats by FS-stress after 7 d CPP extinction, the levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate were significantly increased. CONCLUSIONThe development of morphine addiction and relapse may be related to endogenous neurosteroids in rat brain tissues.