Anticoagulation and Transjugular Intrahepatic Portosystemic Shunt for the Management of Portal Vein Thrombosis in Cirrhosis: A Prospective Observational Study.

INTRODUCTION: Current guidelines recommend anticoagulation as the mainstay of portal vein thrombosis (PVT) treatment in cirrhosis. However, because of the heterogeneity of PVT, anticoagulation alone does not always achieve satisfactory results. This study aimed to prospectively evaluate an individualized management algorithm using a wait-and-see strategy (i.e., no treatment), anticoagulation, and transjugular intrahepatic portosystemic shunt (TIPS) to treat PVT in cirrhosis. METHODS: Between February 2014 and June 2018, 396 consecutive patients with cirrhosis with nonmalignant PVT were prospectively included in a tertiary care center, of which 48 patients (12.1%) were untreated, 63 patients (15.9%) underwent anticoagulation, 88 patients (22.2%) underwent TIPS, and 197 patients (49.8%) received TIPS plus post-TIPS anticoagulation. The decision of treatment option mainly depends on the stage of liver disease (symptomatic portal hypertension or not) and degree and extension of thrombus. RESULTS: During a median 31.7 months of follow-up period, 312 patients (81.3%) achieved partial (n = 25) or complete (n = 287) recanalization, with 9 (3.1%) having rethrombosis, 64 patients (16.2%) developed major bleeding (anticoagulation-related bleeding in 7 [1.8%]), 88 patients (22.2%) developed overt hepatic encephalopathy, and 100 patients (25.3%) died. In multivariate competing risk regression models, TIPS and anticoagulation were associated with a higher probability of recanalization. Long-term anticoagulation using enoxaparin or rivaroxaban rather than warfarin was associated with a decreased risk of rethrombosis and an improved survival, without increasing the risk of bleeding. However, the presence of complete superior mesenteric vein thrombosis was associated with a lower recanalization rate, increased risk of major bleeding, and poor prognosis. DISCUSSION: In patients with cirrhosis with PVT, the individualized treatment algorithm achieves a high-probability recanalization, with low rates of portal hypertensive complications and adverse events.

Sorafenib may enhance antitumour efficacy in hepatocellular carcinoma patients by modulating the proportions and functions of natural killer cells.

Dysfunction of natural killer (NK) cells is associated with poor prognosis in hepatocellular carcinoma (HCC). We explored the phenotypic and functional characteristics of peripheral blood NK cells in HCC patients following sorafenib treatment.Peripheral blood samples were collected from 60 HCC patients in a single centre (2015~2017) and 45 healthy donors. The percentage and cytoplasmic granule production of NK cells were analysed. Subset proportions were evaluated for their associations with the modified Response Evaluation Criteria in Solid Tumors (mRECIST), time to progression, and median overall survival (OS).Compared with baseline, the percentages of total and CD56dimCD16+ NK cells increased after two months of treatment, while the percentage of CD56brightCD16- NK cells decreased, leading to a dramatically reduced ratio of CD56bright and CD56dim NK cells (ratiobri/dim). Patients with low ratiobri/dim exhibited better mRECIST responses and longer median OS than those with high ratiobri/dim. The expression levels of granzyme B and perforin in total NK cells and in both subsets of cells were increased after treatment.This study showed that sorafenib could affect the proportions and functions of peripheral CD56brightCD16- and CD56dimCD16+ NK cells, which was associated with the outcomes including OS of HCC patients.

Tumor Hypervascularity and hand-foot-skin reaction predict better outcomes in combination treatment of TACE and Sorafenib for intermediate hepatocellular carcinoma.

BACKGROUND: To validate the robust predictive values of tumor vascularity and hand-foot-skin reaction (HFSR) in combination treatment of transarterial chemoembolization (TACE) and sorafenib for patients with intermediate hepatocellular carcinoma (HCC), and then select the potential candidates who would survive best from such treatment. METHODS: A total of 132 treatment-naive patients with intermediate HCC undergoing combination therapy of TACE and sorafenib were recruited between January 2010 and December 2014. The tumor vascularity was defined according to digital subtraction angiography (DSA) and HFSR was assessed by the national cancer institute common terminology criteria for adverse events (NCI-CTCAE). The Mann-Whitney U test was used to assess the correlation between vascularity and radiologic response; time to radiologic progression (TTP) and overall survival (OS) were evaluated using Kaplan-Meier techniques and compared by log-rank test; factors associated with them were evaluated using multivariate Cox regression analysis. RESULTS: During a median follow up of 17.3 months, it was revealed that hypervascularity and development of ≥2 grade of HFSR within 60 days after sorafenib initiation were favorable predictors for TTP (HR 0.378, p < 0.001; HR 0.627, p = 0.018) and OS (HR 0.499, p = 0.002; HR 0.555, p = 0.004). The median TTP and OS for patients with both were 12.2 and 29.1 months, which were better than patients with either of them (6.0 months, HR 1.74, p = 0.012; 16.5 months, HR 1.73, p = 0.021), as well as those with neither (2.9 months, HR 3.74, p < 0.001; 11.9 months, HR 3.17, p < 0.001). CONCLUSIONS: Tumor hypervascularity and development of ≥2 grade of HFSR within 60 days were favorable predictive factors for the combination treatment of TACE and sorafenib, with both of which the patients survived longest and might be the potential candidates.

Hand-foot-skin reaction of grade ≥ 2 within sixty days as the optimal clinical marker best help predict survival in sorafenib therapy for HCC.

Background & Aims Sorafenib-related adverse events have been reported as clinical surrogates for treatment response in hepatocellular carcinoma (HCC); however, no consensus has been reached regarding the definition of responders. We evaluated the predictive abilities of different definitions for sorafenib response based on treatment-emergent adverse events, aiming to identify the most discriminatory one as a clinical marker. Methods From January 2010 to December 2014, 435 consecutive HCC patients treated with sorafenib were enrolled. Considering the type, severity and timing of adverse events, twelve different categories of sorafenib response were defined. By comparing their discriminatory abilities for survival, an indicative criterion was defined, the prognostic value of which was evaluated by time-dependent multivariate analysis, validated in various subsets and confirmed by landmark analysis. Results Using concordance (C)-index analysis and time-dependent receiver operating characteristic curves, the development of a hand-foot-skin reaction ≥ grade 2 within 60 days of sorafenib initiation (2HFSR60) showed the highest discriminating value. Based on this criterion, 161 (37.0%) sorafenib responders achieved decreased risk of death by 47% (adjusted HR 0.53, 95%CI 0.43-0.67, P < 0.001) and likelihood of progression by 26% (adjusted HR 0.74, 95%CI 0.58-0.96, P = 0.020) compared with non-responders. Notably, 2HFSR60 remained an effective discriminator among most subgroups and had superior predictive ability to previous definitions, even according to the landmark analysis. Conclusions Our study demonstrated that 2HFSR60, with the best discriminatory ability compared to currently available definitions of sorafenib-related adverse events, could be the optimal clinical marker to identify sorafenib responders with decreased risk of death by half.

Motor Cortex Mapping in Patients With Hepatic Myelopathy After Transjugular Intrahepatic Portosystemic Shunt.

RATIONALE AND OBJECTIVES: As a special movement disorder, hepatic myelopathy (HM) is characterized by spastic paraperesis and may be secondary to transjugular intrahepatic portosystemic shunt (TIPS). The prediction and diagnosis of HM is difficult due to largely unknown neuropathological underpinnings and a lack of specific biomarkers. We aimed to delve into the alterations in motor system of HM patients' brain and their potential clinical implication. MATERIAL AND METHODS: Twenty-three patients with HM and 23 without HM after TIPS and 24 demographically matched healthy controls were enrolled. High-spatial-resolution structural imaging and functional data at rest were acquired. Motor areas were included as seed regions for functional connectivity analysis. Then, we performed brain volume analysis. RESULTS: We found decreased right supplementary motor area (SMA)-seeded functional connectivity with bilateral insula, thalamus and midbrain, left cerebellum and middle temporal gyrus, and right middle cingulate gyrus in HM compared to non-HM patients (p < 0.001). The right insula revealed decreased volume (p < 0.001), and white matter volume reduced in the right corona radiata beneath the right SMA (p < 0.001) in HM relative to non-HM patients. Furthermore, the strength of right SMA-seeded connectivity with insula was positively correlated with folic acid level in HM patients (r = 0.60, p = 0.03), showing an accuracy of 0.87 to distinguish HM from non-HM. CONCLUSION: Our study demonstrates the HM-specific dysconnectivity with an anatomical basis, and its correlation with laboratory findings and diagnostic value. Detecting these abnormalities might help to predict and diagnose post-TIPS HM.

Identification of Herb Pairs in Esophageal Cancer.

BACKGROUND: Chinese herbal medicine (CHM) is used widely to treat various diseases, including cancer. However, effective herb pairs for treating specific cancer types have so far not been identified. Here, we aimed to calculate the survival benefits of herb pairs by cluster analysis, association rules, and survival evaluation in patients with esophageal cancer (EC) treated with CHM. PATIENTS AND METHODS: 59 patients with EC who received 176 prescriptions including 178 types of herbs were enrolled into the study. The herb pairs were identified by both cluster analysis and association rules. Overall survival (OS) was estimated by the Kaplan-Meier method. RESULTS: Eight groups of herb pairs were identified by cluster analysis, and 4 groups of herb pairs were identified by association rules. Of these, 3 groups of herb pairs were identified by both methods. OS estimation showed that the pair of chicken gizzard-membrane/Astragalus was associated with improved survival in patients with EC treated with CHM. CONCLUSION: Patients who received prescriptions containing the pair of chicken gizzard-membrane and Astragalus had improved OS compared with patients who received prescriptions lacking this pair.

mRECIST response combined with sorafenib-related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib.

The mRECIST and dermatologic adverse events (AEs) can be used to assess the patient response to transarterial chemoembolization (TACE) and/or sorafenib for hepatocellular carcinoma (HCC). Here, we aimed to combine the two criteria to stratify the prognosis in patients with unresectable HCC receiving TACE plus sorafenib (TACE-S). In total, 176 consecutive HCC patients treated with TACE-S were enrolled. CT scans and laboratory tests were conducted pretreatment (at baseline, 5-7 days before the TACE-S) and post-treatment (at 1, 2 and 3 months). The radiological response was assessed according to mRECIST. Sorafenib-related AEs were recorded every 2 weeks after oral administration, and patients with dermatologic AEs of Grade 2 or more were defined as dermatologic responders. The earliest time at which mRECIST and dermatologic responses correlated with survival was 2 months after therapy. The mRECIST-dermatologic AE combination assessment stratified patients into three different prognoses; responders on both assessments exhibited the longest median overall survival (OS), followed by responders on one assessment and non-responders on both assessments (30.5, 17.4 and 8.3 months, respectively; p < 0.001). Achieving the highest C-index, the mRECIST-dermatologic AE combination showed better performance in predicting survival than either mRECIST or dermatologic AEs alone. Furthermore, the mRECIST-dermatologic AE combination remained a significant predictor of OS, even when the patients were stratified according to the BCLC stage, ECOG score or alpha-fetoprotein (AFP) value. This study showed that the combination of mRECIST response and dermatologic AEs is superior to either criterion used alone for predicting the survival of HCC patients treated with TACE-S.

The transcriptional activator GaaR of Aspergillus niger is required for release and utilization of d-galacturonic acid from pectin.

We identified the d-galacturonic acid (GA)-responsive transcriptional activator GaaR of the saprotrophic fungus, Aspergillus niger, which was found to be essential for growth on GA and polygalacturonic acid (PGA). Growth of the ΔgaaR strain was reduced on complex pectins. Genome-wide expression analysis showed that GaaR is required for the expression of genes necessary to release GA from PGA and more complex pectins, to transport GA into the cell, and to induce the GA catabolic pathway. Residual growth of ΔgaaR on complex pectins is likely due to the expression of pectinases acting on rhamnogalacturonan and subsequent metabolism of the monosaccharides other than GA.

[Influence on the expression of RHOA and ROCK-II after global cerebral ischemia-reperfusion in hippocampus by shenxiong huayu capsule].

OBJECTIVE: To investigate the effect of Shenxiong Huayu capsule on the expression of hippocampal CA1 recombinant protein A (small GTP binding protein A, RHOA) and ROCK-2 (RHO associated protein kinase-2, ROCK-II). METHODS: Clean SD male rats (n=96), divided into three groups with 32 rats for each group, gavage was applied 7 days before modeling until the morning of the day to put to death. The groups included the normal control group (normal saline), global cerebral ischemia model group (normal saline) and Shenxiong Huayu capsule+global cerebral ischemia group (Shenxiong Huayu capsule 0.048 g/kg, was dissolved in 0.5 mL double distilled water, once a day, orally 0.3 mL/100 g). Modified Pulsinelli four-vessel occlusion model was constructed in global cerebral ischemia model and Shenxiong Huayu treatment groups and at 1, 3, 7, 14 d after successful modeling, water maze learning test was applied to evaluate the memory abilities of different groups, histopathological changes in HE staining, expression and protein content of RHOA and ROCK-II in immunohistochemical staining and Western blot was observed. RESULTS: At each time point, escape latency in model group was prolonged (P<0.05) when compared with that in normal control group, and that in Shenxiong Huayu was shorter (P<0.05) than that of model group, but still longer (P<0.05) than that of normal control group. HE staining showed that, compared with the normal group, model hippocampal CA1 reduced gradually from 1 d to 14 d; an increased survival neurons (P<0.05) in Shenxiong Huayu treatment group at each time points was observed, but still less than that in normal group (P<0.05); immunohistochemistry and Western blot analysis demonstrated that the expression of RHOA and ROCK-II in normal control group was not obvious, in model group was decreased after an initial increasing, and that in Shenxiong Huayu treatment group was lower than that of model group (P<0.05), but still higher than that in normal group (P<0.05). CONCLUSION: Shenxiong Huayu capsule improve neuronal damage induced by global ischemia, decreased the expression of hippocampal CA1 region of RHOA and ROCK-II.

Low awareness of stroke guidelines and preference for Chinese herbs in community physicians: a national survey in China.

BACKGROUND: Physicians' adherence to stroke guidelines is becoming a critical part of public stroke care system. The objective of this national survey was to examine Chinese physicians' awareness of the guidelines in secondary stroke prevention. METHODS: This is a non-commercial and no-incentive internet survey. Respondents were asked to perform a self-examination of 13 questions regarding their stroke practice. Their awareness of stroke guidelines, preference for Chinese traditional herbs (CTH), and patients' expense for stroke treatment were surveyed and compared between physicians from community and from tertiary hospitals using univariate analysis and logistic regression. RESULTS: A total of 8,581 physicians (70.1% from community hospitals) responded to the survey. Only 32.1% physicians considered risk factors control necessary for stroke. For the treatments of symptomatic carotid stenosis, only 10.4% physicians selected carotid endarterectomy and anti-platelet plus controlling stroke risk factors. Only 21.45% physicians selected warfarin anticoagulation for stroke patients with atrial fibrillation. In contrast, a high percentage (64.56%) of physicians had positive attitude towards CTH. Compared with those from tertiary hospitals, community physicians were more likely unaware of the guidelines and preferred CTH. Those who prescribed CTH reported more patients' cost (P<0.001, OR 1.78, 95% CI, 1.55-2.04) than who didn't. CONCLUSIONS: There is a very low awareness of stroke guidelines in Chinese community physicians. A well-organized continuing stroke-guidelines education should be an essential part of public stroke-care system in China. Also, more well-designed clinical trials are required to establish the safety and effectiveness of CTH.

Characterization and bioavailability of tea polyphenol nanoliposome prepared by combining an ethanol injection method with dynamic high-pressure microfluidization.

Tea polyphenols are major polyphenolic substances found in green tea with various biological activities. To overcome their instability toward oxygen and alkaline environments, tea polyphenol nanoliposome (TPN) was prepared by combining an ethanol injection method with dynamic high-pressure microfluidization. Good physicochemical characterizations (entrapment efficiency = 78.5%, particle size = 66.8 nm, polydispersity index = 0.213, and zeta potential = -6.16 mv) of TPN were observed. Compared with tea polyphenol solution, TPN showed equivalent antioxidant activities, indicated by equal DPPH free radical scavenging and slightly lower ferric reducing activities and lower inhibitions against Staphylococcus aureus , Escerhichia coli , Salmonella typhimurium , and Listeria monocytogenes . In addition, a relatively good sustained release property was observed in TPN, with only 29.8% tea polyphenols released from nanoliposome after 24 h of incubation. Moreover, TPN improved the stability of tea polyphenol in alkaline solution. This study expects to provide theories and practice guides for further applications of TPN.

The role of central nervous system on hypoglycemia and the feasibility of the brain theory in traditional Chinese medicine on treatment of diabetes mellitus.

The central nervous system (CNS) plays a key regulatory role in glucose homeostasis. In particular, the brain is important in initiating and coordinating protective counterregulatory responses when blood glucose levels fall. This may due to the metabolic dependency of the CNS on glucose, and protection of food supply to the brain. In healthy subjects, blood glucose is normally maintained within a relatively narrow range. Hypoglycemia in diabetic patients can increase the risk of complications, such as heart disease and diabetic peripheral neuropathy. The clinical research finds that the use of traditional Chinese medicine (TCM) has a positive effect on the treatment of hypoglycemia. Here the authors reviewed the current understanding of sensing and counterregulatory responses to hypoglycemia, and discuss combining traditional Chinese and Western medicine and the theory of iatrogenic hypoglycemia in diabetes treatment. Furthermore, the authors clarify the feasibility of treating hypoglycemia on the basis of TCM theory and CNS and have an insight on its clinical practice.

Assembly of a phospho-molybdic Wells-Dawson-based silver coordination polymer derived from Keggin polyoxoanion cluster.

A 2D Wells-Dawson-based silver(I) coordination polymer was achieved based on silver-Schiff base building blocks and [P(2)Mo(18)O(62)](6-) clusters using AgNO(3), N,N'-bis(furan-2-ylmethylene)hydrazine and Keggin [PMo(12)O(40)](3-) as original materials at room temperature. It is structurally characterized by IR spectroscopy, (31)P NMR, XRPD, thermogravimetric (TG) analyses and X-ray crystallography. The structure of 1 exhibits a novel crystalline 2D coordination polymer constructed by the coordination interaction between the Wells-Dawson polyoxoanion [P(2)Mo(18)O(62)](6-) and Ag-L species. The luminescent property of 1 in the solid state is investigated.

Chemometric resolution of coeluting peaks of eleven antihypertensives from multiple classes in high performance liquid chromatography: a comprehensive research in human serum, health product and Chinese patent medicine samples.

A novel chemometric-assisted high performance liquid chromatography method coupled with diode array detector (HPLC-DAD) was presented for the simultaneous determination of eleven antihypertensives from multiple classes in most concerned matrix systems. With the aid of second-order calibration which enables specific information of analytes to be well extracted, the heavily overlapping profiles between analytes and the coeluting interferences can be successfully separated and thus accurately quantified. A great advantage of the novel strategy lies in the fact that the analysis could be carried out with the same isocratic mobile phase (methanol/KH(2)PO(4): 58:42, v/v, pH 2.60) in a short time regardless of the changes of matrices, such as human serum, health product and Chinese patent medicine. Both qualitative and quantitative results indicate that the hybrid strategy that using HPLC-DAD coupled with second-order chemometric method would be a high performance approach for the purpose of simultaneously quantifying multiple classes of antihypertensives in complex systems. Additionally, the analytical strategy can potentially benefit drug monitoring in both therapeutic research and pharmaceutical quality control. Moreover, the accuracy and reliability of the proposed methodology has been evaluated using several statistical parameters such as root mean squared error of prediction (RMSEP), figures of merit (FOM) and reproducibility of inter-day analysis.

[Protective effect of pretreatment of Salvia miltiorrhiza Bunge. f. alba plasma against oxygen-glucose deprivation-induced injury of cultured rat hippocampal neurons by inhibiting apoptosis].

The present study was to investigate the effect of Salvia miltiorrhiza Bunge. f. alba (SMA) pharmacological pretreatment on apoptosis of cultured hippocampal neurons from neonate rats under oxygen-glucose deprivation (OGD). Cultured hippocampal neurons were randomly divided into five groups (n = 6): normal plasma group, low dose SMA plasma (2.5%) group, middle dose SMA plasma (5%) group, high dose SMA plasma (10%) group and control group. The hippocampal neurons were cultured and treated with plasma from adult Wistar rats intragastrically administered with saline or aqueous extract of SMA. The apoptosis of neurons was induced by glucose-free Earle's solution containing 1 mmol/L Na2S2O4 and labeled by MTT and Annexin V/PI double staining. Moreover, protein expressions of Bcl-2 and Bax were detected by immunofluorescence. The results showed that few apoptotic cells were observed in control group, whereas the number of apoptotic cells was greatly increased in normal plasma group and low dose SMA plasma group. Both middle and high dose SMA plasma could protect cultured hippocampal neurons from apoptosis induced by OGD (P < 0.05). The protective effect of high dose SMA plasma was stronger than that of middle one (P < 0.05). Compared to control, normal plasma and low dose SMA plasma groups, middle and high dose SMA plasma groups both showed significantly higher levels of Bcl-2 (P < 0.05 or 0.01), whereas expressions of Bax was opposite. There were no significant differences of Bcl-2 and Bax expressions between middle and high dose SMA plasma groups. Number of Bcl-2- and Bax-positive cells had similar tendency. Bcl-2/Bax (number of positive cells) ratio was higher in high dose SMA plasma group than those of all the other groups (P < 0.05 or 0.01). These results suggest that pharmacological pretreatment of blood plasma containing middle and high dose SMA could raise viability and inhibit apoptosis of OGD-injured hippocampal neurons by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax.

Assessment of the clinical effect of Chinese medicine therapy combined with psychological intervention for treatment of patients of peri-menopausal syndrome complicated with hyperlipidemia.

OBJECTIVE: To observe the effect of Chinese medicine therapy combined with psychological intervention (combined therapy) on the clinical symptoms and levels of blood lipids and sex hormones of patients of peri-menopausal syndrome complicated with hyperlipidemia. METHODS: With the use of a randomizing digital table method, 185 patients that fit the registration standard were randomly assigned to three groups. The 59 cases in Group A were treated with two Chinese patents, Kunbao Pill and Modified Xiaoyao Pill; the 63 in Group B received psychological intervention alone; and the 63 in Group C were treated with both (the combined therapy), with the treatment course for all six months. The items of observation included: (1) scoring by SCL-90 on eight factors and seven symptoms; (2) scoring on Chinese medicine symptoms by Kupermann scale, including anxiety and bad temper, scorching sense action with sweating, dizziness, tinnitus, soreness and weakness of the loin and knees, palpitation, insomnia, lassitude, weakness, and hyposexuality; (3) blood contents of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apoprotein AI (ApoAI) and B (ApoB); (4) levels of sex hormones, including estradiol (E(2)), progesterone (P), pituitary prolactin (PRL), follicular stimulating hormone (FSH), and), luteinzing hormone (LH) in some randomly selected patients; (5) adverse reaction; and (6) one-year follow-up study on long-term effect. RESULTS: A total of 21 patients (6, 8, and 7 cases in Groups A, B, and C, respectively) dropped out; the drop-out rate was insignificant among groups. (1) The markedly effective rates in Group A, B, and C were 26.42% (14/53), 18.18% (10/55), and 53.57% (30/56), respectively, and the total effective rates in them were 64.15% (34/53), 50.91% (28/55), and 87.50% (49/56), respectively, suggesting the therapeutic efficacy in Group C was significantly better than that in Groups A and B (P<0.01). (2) SCL-90 scoring showed that the total scores decreased significantly after treatment in Group C (P<0.01), but remained unchanged in Groups A and B (P>0.05). (3) Scoring on Chinese medicine symptoms showed the same results as shown by SCL-90 scoring in terms of total scores and individual symptoms, except that menstrual disorder and amenorrhea were unchanged in all three groups (P>0.05). (4) Levels of HDL-C, ApoAI, and E(2) increased and those of TG, TC, LDL-C, ApoB, FSH, and LH decreased after treatment in Group C, reaching near normal levels; similar trends of blood lipids were shown in Group A, but the level of sex hormones was unchanged. In Group B all the above-mentioned indices were unchanged (P>0.05). (5) A one-year follow-up study showed the markedly effective rate and the total effective rate in Group C were higher than those in the other two groups respectively (P<0.01). (6) No adverse reaction was found. CONCLUSION: Chinese medicine therapy combined with psychological intervention could not only improve the nervous symptoms, but also regulate the blood levels of lipids and sex hormones in patients of peri-menopausal syndrome complicated with hyperlipidemia.

Expression of the receptors of VEGF and the influence of extract of Ginkgo biloba after cisternal injection of autologus arterial hemolysate in rats.

The study was aimed to investigate the alterations of vascular endothelial growth factor (VEGF) receptors and the influence of extract of Ginkgo biloba (EGb) after subarachnoid hemorrhage (SAH). Wistar rats were divided into non-SAH, SAH, vehicle, EGb1 (lower dose), and EGb2 (higher dose) groups. Autologus arterial hemolysate was injected into cisterna magna to induce SAH. The non-SAH rats received cisternal injection of saline instead. Rats underwent RT-PCR determination of one of the VEGF receptors flt-1mRNA, and immunohistochemistry for VEGF receptors Flt-1 and Flk-1. The results revealed that there was only slight expression of flt-1mRNA in the brain tissue in non-SAH rats. The expression in SAH group was enhanced 24 hours and 72 hours after cisternal injection. No Flt-1 and Flk-1 positive cell was observed in the brain in non-SAH group. A good few Flt-1 and Flk-1 positive cells were found in cortex and other regions of the brain in SAH group. The expression of flt-1mRNA, Flt-1 and Flk-1 proteins were increased by the use of two doses of EGb. It was concluded that the up-regulated expression of the two kinds of VEGF receptors may be an intrinsic protective mechanism in the process of SAH, which can be enhanced by EGb.