High Levels of Heat Shock Protein 47 in the Aqueous Humor of Patients with Acute Primary Angle Closure.

INTRODUCTION: Acute primary angle closure (APAC) is often characterized by acute elevation of intraocular pressure (IOP) accompanied by severe ocular and systemic symptoms. Excessive collagen accumulation, which can be caused by upregulated heat shock protein 47 (HSP47) expression, can produce scarring in rat conjunctival blebs. Meanwhile, the presence of HSP47 in human aqueous humor and its levels are yet to be determined. METHODS: We examined 32 consecutive patients with APAC and 16 age-matched participants without APAC scheduled for cataract surgery who were enrolled as a control group. Aqueous humor samples were collected from all subjects at the time of surgery and compared between the subjects with and without APAC. RESULTS: The levels of HSP47 in the aqueous humor of patients with APAC (1,210.4 ± 450.2 pg/mL) were found to be significantly increased (P = 0.001) compared with those in the control group (863.4 ± 240.0 pg/mL). Notably, the levels of HSP47 negatively correlated with the age of patients with APAC (P = 0.023). CONCLUSION: HSP47 was upregulated in the aqueous humor of patients with APAC and may play a role in scarring after trabeculectomy for APAC.

Comparison Study of ASCO and TOAST Classification System in Chinese Minor Stroke Patients.

BACKGROUND: Precise subtype classification based on underlying pathophysiology is important to prevent recurrent attack in minor stroke patients. A newly developed Atherosclerosis, Small vessel disease, Cardiac source, Others (ASCO) phenotypic classification system aims to characterize patients using different grades of evidence for stroke subtypes. However, this system has not been specifically applied to minor stroke population. In our study, the impact of using the newer ASCO criteria on minor stroke etiologies was investigated, and compared with that of Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. METHODS: Consecutive patients with minor ischemic stroke (NIHSS ≤3) were assessed and subtyped by the ASCO and TOAST systems. Stroke etiologies were presented and compared. The McNemar test and k statistic were used to analyze the difference and concordance between the 2 algorithms, respectively. RESULTS: A total of 604 first-ever minor stroke patients were analyzed in the present study. Using TOAST classification, large artery atherosclerosis was the most frequent subtype (281, 46.5%), followed by small artery occlusion category (165, 27.3%). When ASCO was applied, 37 different profiles of stroke etiologies were identified. Using grade 1 of evidence, atherosclerosis (A1) was the most frequent subtype (308, 51.0%), followed by small vessel disease (S1, 178, 29.5%). Under consideration of grades 1 and 2, 239 (39.6%) patients were classified into more than 1 category. The ASCO system revealed determined etiologies in 104 of the 137 patients classified to cause undetermined subtype by TOAST classification. Good to very good accordance was observed between ASCO grade 1 and TOAST schemes across etiologic subtypes (κ = 0.719-0.832) except cause undetermined category (κ = 0.470). CONCLUSION: Application of ASCO decreased the proportion of patients assigned to cause undermined category compared to TOAST system. Comprehensive characteristics of ASCO system might be helpful in the personalized therapy or secondary prevention for individual patients in the future.

[Association between acid reflux and esophageal dysmotility in patients with gastroesophageal reflux disease].

OBJECTIVE: To investigate the association between esophageal motility and acid reflux in patients with gastroesophageal reflux disease (GERD). METHODS: A total of 94 patients with typical reflux symptoms such as heartburn, regurgitation and chest pain, whose score (Sc) of reflux diagnostic questionnaire (RDQ) was greater than or equal to 12 were enrolled in the study. Each participant was evaluated by upper gastrointestinal endoscopy, high resolution manometry (HRM) of esophagus and 24 h esophageal pH monitoring. The participants were divided into groups of reflux esophagitis (RE) and non-erosive reflux disease (NERD) on the basis of endoscopy findings. The 24 h esophageal pH monitoring categorized participants into physiologic reflux (pH) and pathologic reflux (pH+). The characteristics of esophageal motility and acid reflux were compared between the two groups of participants. RESULTS: Lower but non-significant differences (P > 0.05) were found in pressure of lower esophageal sphincter (LESP), length of lower esophageal sphincter (LESL), esophageal contraction amplitude (CA), distal contractile integral (DCI) and effective peristalsis proportion (EPP) in the participants in the RE group compared with those in the NERD group. Participants in the RE group had significantly higher prevalence of reduced LESP (63.0% vs. 31.7%, P < 0.01) and hiatus hernia (HH) (37.0% vs. 14.3%, P < 0.05) than those in the NERD group, pH+ was more prevalent in the RE group than in the NERD group (63.0% vs. 17.5%, P < 0.01). Indicators of 24 h esophageal pH monitoring were significantly higher in participants in the RE group compared with those in the NERD group (P < 0.05). Participants with pH+ had significantly lower LESP, CA and higher HH and prevalence of reduced LESP compared with those with pH (P < 0.05). LESL, DCI and EPP were lower in those with pH+ compared with those with pH-, but without statistical significance (P > 0.05). CONCLUSION: RE is closely associated with acid reflux and hiatus hernia. Esophageal dysmotility is more likely to appear in patients with pH+. The interaction of acid reflux and esophageal dysmotility may play a role in GERD.

Bone marrow mesenchymal stem cells ameliorate hepatic ischemia/reperfusion injuries via inactivation of the MEK/ERK signaling pathway in rats.

BACKGROUND: Primary graft dysfunction or nonfunction after liver transplantation, which is usually caused by ischemia/reperfusion injury (IRI), is a serious clinical problem. Although bone marrow mesenchymal stem cells (MSCs) have shown great potential in cell therapy for IRI in several organs, the mechanism(s) by which MSCs offer protection is unclear. METHODS: In the present study, we injected MSCs systemically via the tail vein in the rat model of 70% hepatic IRI and measured the biochemical and pathologic alterations to evaluate the therapeutic effect of MSC transplantation. Concurrently, H(2)O(2) was used in vitro to mimic oxidative injury and to induce apoptosis in the human normal liver cell line LO2 to evaluate the protective effects of mesenchymal stem cell conditioned medium (MSC-CM) on LO2 cells. RESULTS: The systemic infusion of MSCs led to a significant prevention of liver enzyme release and an improvement in the histology of the acutely injured liver. In vitro assays demonstrated that MSC-CM promoted hepatocyte proliferation and had a direct inhibitory effect on hepatocyte apoptosis induced by H(2)O(2). In addition, we demonstrated that the prevention of MEK/ERK pathway activation played a pivotal role in the protection. CONCLUSIONS: These data suggest that MSC may represent a potential therapeutic strategy to alleviate hepatic ischemia/reperfusion injuries after liver transplantation via inactivation of the MEK/ERK signaling pathway.

The clinical value of serum hepatic parenchyma cell volume-normalized hepatitis B surface antigen levels in hepatitis B e antigen -positive and -negative chronic hepatitis B patients.

BACKGROUND: While serum hepatitis B surface antigens (HBsAg) play an important role in the diagnosis and assessment of treatment results of hepatitis B virus (HBV) infections, it remains unclear whether HBsAg levels normalized to hepatic parenchymal cell volume (HPCV) is a superior indicator of disease state. This study compared the absolute and HPCV-normalized serum HBsAg levels in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with chronic hepatitis B (CHB). METHODS: Patients admitted to our institution with CHB were retrospectively included and categorized into the HBeAg-positive and HBeAg-negative groups. HPCV was calculated based on pathological examination of liver biopsy specimens and theory of sphere geometry. The difference between HBsAg levels and HBsAg normalized to HPCV, and also correlation between HBsAg levels and liver inflammation and fibrosis was analyzed. RESULTS: Absolute HBsAg levels (P=0.004), but not HPCV-normalized HBsAg levels (P=0.071) were significantly higher in HBeAg-positive patients compared to HBeAg-negative patients. In HBeAg-positive CHB patients, absolute HBsAg levels were positively correlated with liver inflammation grade (R=0.285, P=0.001) and hepatic fibrosis stage (R=0.351, P<0.001), as were HPCV-normalized HBsAg levels (R=0.640 and 0.742, both, P<0.001). However, in HBeAg-negative CHB patients, only HPCV-normalized HBsAg level were correlated with liver inflammation grade and hepatic fibrosis stage (R=0.640 and 0.785, both, P<0.001). CONCLUSIONS: HPCV-normalized serum HBsAg levels, rather than absolute HBsAg levels, were positively correlated with liver inflammation grade and hepatic fibrosis stage in both HBeAg-positive and HBeAg-negative CHB patients. Thus, HPCV-normalized HBsAg levels may more accurately reflect the pathological progress of CHB patients compared to absolute HBsAg levels.

Hyperinsulinemia-induced KLF5 mediates endothelial angiogenic dysfunction in diabetic endothelial cells.

Reduced expression of endothelial nitric oxide synthase (eNOS) is a hallmark of endothelial dysfunction in diabetes, which predisposes diabetic patients to numerous cardiovascular complications including blunted angiogenesis. The Krüppel-like factor (KLF) five has been implicated as a central regulator of cardiovascular remodeling, but its role in endothelial cells (ECs) remains poorly understood. We show here that expression of endothelial KLF5 was significantly increased in the ECs from mouse diabetes mellitus type 2 (T2DM) model, when compared to non-diabetic or T1DM mouse. KLF5 up-regulation by insulin was dependent on activation of multiple pathways, including mammalian target of rapamycin, oxidative stress and Protein kinase C pathways. Hyperinsulinemia-induced KLF5 inhibited endothelial function and migration, and thereby compromised in vitro and in vivo angiogenesis. Mechanistically, KLF5 acted in concert with the MTA1 coregulator to negatively regulate NOS3 transcription, thereby leading to the diminished eNOS levels in ECs. Conversely, potentiation of cGMP content (the essential downstream effector of eNOS signaling) by pharmacological approaches successfully rescued the endothelial proliferation and in vitro tube formation, in the HUVECs overexpressing the exogenous KLF5. Collectively, the available data suggest that the augmentation of endothelial KLF5 expression by hyperinsulinemia may represent a novel mechanism for negatively regulating eNOS expression, and may thus help to explain for the T2DM-related endothelial dysfunction at the transcriptional level.

Traditional Chinese medicine (Xiaoai Jiedu Decoction) as an adjuvant treatment for prevention new colorectal adenomatous polyp occurrence in post-polypectomy: Study protocol for a randomized controlled trial.

BACKGROUND: Colorectal Adenomatous Polyp (CAP) was one precursor of colorectal cancer (CRC) and having a high chance of developing into CRC. There was a lack of conclusive chemoprevention evidences to prevention new CAP occurrence in post-polypectomy. Xiaoai Jiedu Decoction, Chinese National Medical Professor (Zhou Zhongying)'s experience formula, has been used to treat new CAP occurrence in post-polypectomy from the 20th century in China. However, clinical research of Xiaoai Jiedu Decoction in the treatment of CAP recurrence was lack. We design this study to evaluate the efficacy and safety of Xiaoai Jiedu Decoction in the treatment of new CAP occurrence in post-polypectomy on colonoscopy. METHODS/DESIGN: A randomized, controlled, blind and multicenter trial to evaluate the efficacy and safety of Xiaoai Jiedu Decoction is proposed. CAP patients (after complete polypectomy under colonoscopy) will be randomly assigned into Xiaoai Jiedu Decoction group and Xiaoai Jiedu Decoction mimetic agent group. Patients will receive 6-course treatments and a 2-year follow-up. Follow-up colonoscopy will be anticipated to perform in 1 and 2 years after the baseline examinations. The primary outcome measure is the new CAP occurrence in 1 and 2 years. The secondary outcome measure is the occurrence of advanced adenoma in 1 and 2 years. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Xiaoai Jiedu Decoction as an adjuvant treatment for new CAP occurrence in post-polypectomy. TRIAL REGISTRATION: NCT03616444.

Diagnostic ability of ganglion cell complex thickness to detect glaucoma in high myopia eyes by Fourier domain optical coherence tomography.

AIM: To evaluate the ability of macular ganglion cell complex (GCC) thickness using Fourier domain optical coherence tomography (FD-OCT) to detect glaucoma in highly myopic eyes. METHODS: Cross-sectional study. A total of 114 participants, consecutively were enrolled. Macular GCC thickness and peripapillary retinal nerve fiber layer (RNFL) thickness were obtained with RTVue FD-OCT. Receiver operating characteristics curves were constructed for each measurement parameter, and areas under the curves (AUCs) were compared. RESULTS: Both the average GCC and average RNFL thickness showed negative correlations with axial length (rGCC=-0.404, P=0.001; rRNFL=-0.561, P<0.001). The largest AUCs from GCC, and RNFL parameters were 0.968 [global loss volume (GLV)], and 0.855 (average RNFL), respectively. GLV was significantly better for detecting high myopic glaucoma than average RNFL (P<0.001). CONCLUSION: Macular GCC thickness has higher diagnostic power than peripapillary RNFL thickness to discriminate glaucoma patients from non-glaucoma subjects in high myopia.

[Effect of oxidative stress on periprosthetic osteolysis induced by TCP wear particles in mouse calvaria and its mechanism].

OBJECTIVE: To explore the effect of oxidative stress on periprosthetic osteolysis induced by TCP wear particles in mouse calvaria and its mechanism. METHODS: Thirty-six male ICR mice were randomly divided into three groups (n=12):sham group, TCP wear particles (TCP) group and N-acetyl-L-cysteine (NAC) group. Aperiprosthetic osteolysis model in mouse was established by implanting 30 mg of TCP wear particles onto the surface of bilateral parietal bones following removal of the periosteum. On the 2nd day post-operation, NAC (1.0 mg/kg) was locally injected to the calvarium under the periosteum every other day for 2 weeks. Then, all the mice were sacrificed to obtain blood and the calvaria. Periprosthetic osteolysis in the mouse calvaria was observed by tartrate resistant acid phosphatase (TRAP) staining; serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), interleukin-6 (IL-6); total anti-oxidation capacity (T-AOC) and superoxide dismutase (SOD) activity were examined by ELISA and chemical colorimetry, respectively; protein levels of glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phospho-PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α) and phospho-eIF2α (p-eIF2α) in periprosthetic bone tissue were detected by Western blot. RESULTS: Compared with sham group, serum levels of TNF-α, IL-1ß and IL-6, and osteolysis area were increased obviously in TCP group (P<0.05), and serum level of T-AOC and SOD activity were decreased significantly in TCP group (P<0.05), GRP78 expression, the ratio of p-PERK and PERK, p-eIF2α and eIF2α in the mouse calvaria of TCP group were up-regulated markedly. Compared with TCP group, serum levels of TNF-α, IL-1ß and IL-6, and osteolysis area were decreased markedly in NAC group (P<0.05), serum level of T-AOC and SOD activity were increased obviously in NAC group (P<0.05), and GRP78 expression, the ratio of p-PERK/PERK and p-eIF2α/eIF2α were obviously down-regulated. CONCLUSIONS: Inhibition of oxidative stress can prevent periprosthetic osteolysis induced by TCP wear particles, which may be mediated by inactivation of PERK/eIF2α signaling pathway.

[The linkage disequilibrium of four loci in hepatic lipase promoter gene of cerebral infarction patients in Shanghai].

OBJECTIVE: To investigate the single nucleotide polymorphism (SNP), the distribution of their haplotypes and linkage disequilibrium of hepatic lipase (HL) gene promoter 250G/A, 514C/T, 710T/C and 763A/G in cerebral infarction patients of Shanghai. METHODS: Peripheral blood sample were collected from 133 patients with cerebral infarction and 112 healthy controls in Shanghai. The HL gene polymorphism was analyzed by polymerase chain reaction- restriction fragment length polymorphism. RESULTS: There were statistically significant differences in genotype and allele frequencies between the healthy controls and the patients with cerebral infarction in -250G/A and -514C/T genotypes and allele frequencies (all P < 0.05). However, there were no significant differences in genotype and allele frequencies in -710T/C and -763A/G between the healthy controls and the patients with cerebral infarction (all P > 0.05). Besides, there was a strong linkage disequilibrium between -250G/A and -514C/T, -710T/C, and -763A/G respectively, between -514C/T and -710T/C and -763A/G respectively, and between -710T/C and -763A/G. When the haplotypes were -250G/-514C, -250G/-710C, -250G/-763G, -514C/-710C, and 514C/-763G respectively, the frequencies in the cerebral infarction group were significantly lower than that in the healthy controls. When the haplotype was -250A/-514T, -250A/-710T, -250A/-710C, -250A/-763G, -514T/-710C, -514T/-763G, and -710T/-763G respectively, the frequencies in the cerebral infarction group were significantly higher than those in the healthy controls. CONCLUSION: There are significant haplotypes and linkage disequilibrium among the four SNPs of HL gene in the cerebral infarction patients of Shanghai. The haplotypes GC, GG, and CC lower the incidence rate of cerebral infarction, while the haplotypes AT, AC, AG, TC, and TG increase the incidence rate of cerebral infarction.

Diabetes mellitus is associated with late-onset post-stroke depression.

OBJECTIVE: To explore the associated factors of late-onset post-stroke depression (PSD). METHODS: A total of 251 patients with acute ischemic stroke were recruited. The evaluation of depression was performed 2 weeks after ischemia. 206 patients showing no depression in 2 weeks were followed up. They were divided into late-onset PSD group and non-depressed group by clinical interview with Hamilton depression scale score 3 months after stroke. On the first day following hospitalization, the clinical data including age, gender, educational level and vascular risk factors were recorded. The severity, etiological subtype and location of stroke were evaluated. The inflammatory mediators, glucose and lipid levels were recorded on the day of admission. The association between clinical factors and late-onset PSD was explored by logistic regression analysis. The ROC analysis was performed to evaluate the predicting power of the clinical factors. RESULTS: 187 of 206 patients completed the assessment 3 months after stroke. 19 (10.16%) patients were diagnosed as late onset PSD. Diabetes mellitus was an independent risk factor for late-onset PSD (OR 2.675, p = 0.047). ROC analysis demonstrated that glucose and HbA1C could predict late-onset PSD with specificity of 84.4%. LIMITATIONS: The sample of our study was small. The results should be further confirmed in a larger cohort of patients with acute ischemic stroke. CONCLUSIONS: The acute ischemic stroke patients with diabetes mellitus were more tendered to suffer late-onset PSD.

[Effects of absorption enhancers on intestinal absorption of lumbrokinase].

AIM: To explore the intestinal absorption characteristics of lumbrokinase (YJM-I) in the absence or presence of various absorption enhancers and to find the optimum intestinal site for YJM-I absorption. METHODS: The absorption kinetics and absorption intestinal sites for YJM-I absorption were investigated with the method of diffusion cell in vitro, duodenum bolus injection, recirculating perfusion and in situ duodenum perfusion in vivo. RESULTS: YJM-I could be transported into blood and kept its biological activity across intestinal endothelial membrane after administration via duodenum site, whereas with lower bioavailability. Some of the absorption enhancers were shown good enhancement effects on intestinal absorption of YJM-I in vitro and in situ experiments. The order of enhanced efficiencies of various enhancers on duodenum, ileum and jejunum in vitro permeation experiments were shown as follows: 1% chitosan > 1% SDCh > 1% Na2EDTA > 1% SDS > 1% sodium caprylate > 1% poloxamer > 1% HP-beta-CD. The order of enhanced efficiencies of various enhancers on duodenum absorption of YJM-I in vivo were as follows: 2.5% SDCh > 2.5% Na2EDTA > 2.0% chitosan > 2.5% SDS > 2.5% sodium caprylate > 2.5% Poloxamer > 2.5% HP-beta-CD. CONCLUSION: The results indicated that the absorption of YJM-I could be enhanced by various enhancers, and duodenum was the optimum absorption site of YJM-I. Furthermore, bio-adhesive chitosan might be a potential enhancer of intestinal YJM-I absorption.

Cooperative effect of silicon and other alloying elements on creep resistance of titanium alloys: insight from first-principles calculations.

Creep resistance is one of the key properties of titanium (Ti) alloys for high temperature applications such as in aero engines and gas turbines. It has been widely recognized that moderate addition of Si, especially when added together with some other elements (X), e.g., Mo, significantly improves the creep resistance of Ti alloys. To provide some fundamental understandings on such a cooperative effect, the interactions between Si and X in both hexagonal close-packed α and body-centered cubic ß phases are systematically investigated by using a first-principles method. We show that the transition metal (TM) atoms with the number of d electrons (Nd) from 3 to 7 are attractive to Si in α phase whereas those with Nd > 8 and simple metal (SM) alloying atoms are repulsive to Si. All the alloying atoms repel Si in the ß phase except for the ones with fewer d electrons than Ti. The electronic structure origin underlying the Si-X interaction is discussed based on the calculated electronic density of states and Bader charge. Our calculations suggest that the beneficial X-Si cooperative effect on the creep resistance is attributable to the strong X-Si attraction.

Lentivirus-Mediated Overexpression of MicroRNA-210 Improves Long-Term Outcomes after Focal Cerebral Ischemia in Mice.

AIMS: MicroRNAs play an important role in the pathogenesis of ischemic brain injury and in the repair process during postischemic condition. However, the key miRNAs and their function in these processes remain unclear. METHODS: Circulating blood MicroRNAs profiles were examined in the ischemic stroke patients. The predicted network of difference was analyzed by ingenuity pathway analysis. The key MicroRNAs were selected, and the function was further studied in a mouse ischemia model. The predicted downstream target was confirmed. RESULTS: We found that 24 MicroRNAs were differently expressed in stroke patients compared to the control (P < 0.05). Bioinformatic analysis showed a MicroRNAs regulated network with the highest score in the stroke cascade, which was consisted of 10 MicroRNAs including key hypoxia-related miR-210 and its predicted downstream target brain derived neurotrophic factor (BDNF). Lentivirus-mediated miR-210 overexpression enhanced the microvessel density and the number of neural progenitor cells in the ischemic mouse brain (P < 0.05) and improved neurobehavioral outcomes in the ischemic mouse (P < 0.05). MiR-210 upregulation increased mBDNF/proBDNF protein expression in the normal and ischemic mouse brain. The dual-luciferase reporter assay identified that BDNF was the direct target of miR-210. CONCLUSION: MiR-210 is a crucial ischemic stroke-associated MicroRNAs and a potential target for the stroke therapy.

Genotype CC of rs1800947 in the C-reactive protein gene may increase susceptibility to colorectal cancer: a meta-analysis.

BACKGROUND: Single nucleotide polymorphisms of C-reactive protein (CRP) have been shown to be related to circulating CRP level, risk and prognosis in cancer patients. However, accumulating evidence of rs1800947 involvement in risk of cancer is inconsistent. Thus, a meta-analysis was performed to obtain a more precise relationship. MATERIALS AND METHODS: The pooled odds ratio (OR) and its 95% confidence interval were assessed in 10 eligible articles with 12 studies containing 5,601 cancer cases and 8,669 cancer-free controls. RESULTS: No significant association was observed overall and in subgroups in comparison of genotype GC vs GG (PH=0.847, OR=0.939, 95%CI=0.810-1.087), GC/CC vs GG (PH=0.941, OR=1.021, 95%CI=0.901-1.157) and allele C vs G (PH=0.933, OR=1.026, 95%CI=0.909-1.159). However, statistically significance was evident in comparison of genotype CC vs GG in cancer risk (PH=0.586, OR=2.854, 95%CI= 1.413-5.763), especially in colorectal cancer (PH=0.481, OR=4.527, 95%CI= 1.664- 12.315). CONCLUSIONS: Genotype CC of rs1800947 in the CRP gene is strongly associated with increased cancer risk, particularly in colorectal cancer.

The protective role of Tongxinluo on blood-brain barrier after ischemia-reperfusion brain injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL), a renowned traditional Chinese medicine, consists of several different kinds of ingredients and has been widely used to treat myocardial infarction and ischemic stroke. However, the underlying neuroprotective mechanisms are not fully understood. AIM OF THE STUDY: We focus on the effect of TXL on blood-brain barrier (BBB) including edema formation and tight junction (TJ) protein rearrangement, and inflammatory response after transient middle cerebral artery occlusion (tMCAO). We further explore the protective mechanism of TXL on ischemia-induced BBB damage. MATERIALS AND METHODS: Adult CD1 male mice (n=168) were randomly divided into TXL pre-treatment group, TXL pre-post treatment group, TXL post-treatment group, control group and sham group. Mice in TXL pre-treatment group were given TXL solution by 1g/kg/day orally for 7 days before tMCAO. Mice in pre-post treatment group were continuously given TXL 7 days before and 14 days after tMCAO. Mice in TXL post-treatment group were given TXL solution immediately after tMCAO. Rotarod test and neurological severity scores were evaluated at 1-14 days following tMCAO. Brains were harvested for examining infarct volume, edema formation, and immunofluorescent staining at 1 and 3 days after tMCAO. Cytokines IL-6, IL-1ß and TNF-α mRNA expression, and BBB permeability were further examined by RT-PCR and immunostaining. RESULTS: TXL pre-post treatment improved neurobehavioral outcomes and reduced infarct volume compared to the control (p<0.05). Meanwhile, hemispheric swelling, Evans blue and IgG protein extravasation reduced, while TJ protein expression up-regulated in pre-post treatment group (p<0.05). Further study indicated that infarct volume was smaller and BBB damage was less severe in TXL pre-post treatment group compared to TXL pre-treatment alone. It was noted that fewer myeloperoxidase (MPO) positive cells and less cytokines IL-6, IL-1ß and TNF-α expression in pre-post treatment group compared to the control group (p<0.05). CONCLUSIONS: TXL pre-treatment and pre-post treatment effectively protected the brain from BBB disruption via alleviating inflammatory response. Moreover, pre-post treatment has better outcomes, suggesting that continuous administration of TXL before and throughout ischemia period is necessary because of multiple functions of TXL.