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Icariin (ICA) has a significant capacity to protect against depression and hippocampal injury, but it cannot effectively cross the blood-brain barrier and accumulate in the brain. Therefore, the mechanism by which ICA protects against hippocampal injury in depression remains unclear. In this study, we performed proteomics analysis of cerebrospinal fluid to investigate the mechanism by which ICA prevents dysfunctional hippocampal neurogenesis in depression. A rat model of depression was established through exposure to chronic unpredictable mild stress for 6 weeks, after which 120 mg/kg ICA was administered subcutaneously every day. The results showed that ICA alleviated depressive symptoms, learning and memory dysfunction, dysfunctional neurogenesis, and neuronal loss in the dentate gyrus of rats with depression. Neural stem cells from rat embryonic hippocampi were cultured in media containing 20% cerebrospinal fluid from each group of rats and then treated with 100 μM corticosterone. The addition of cerebrospinal fluid from rats treated with ICA largely prevented the corticosterone-mediated inhibition of neuronal proliferation and differentiation. Fifty-two differentially expressed proteins regulated by chronic unpredictable mild stress and ICA were identified through proteomics analysis of cerebrospinal fluid. These proteins were mainly involved in the ribosome, PI3K-Akt signaling, and interleukin-17 signaling pathways. Parallel reaction monitoring mass spectrometry showed that Rps4x, Rps12, Rps14, Rps19, Hsp90b1, and Hsp90aa1 were up-regulated by chronic unpredictable mild stress and down-regulated by ICA. In contrast, HtrA1 was down-regulated by chronic unpredictable mild stress and up-regulated by ICA. These findings suggest that ICA can prevent depression and dysfunctional hippocampal neurogenesis through regulating the expression of certain proteins found in the cerebrospinal fluid. The study was approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2017.

This study aims to elucidate the underlying mechanism of Erxian Decoction(EXD) against neurogenesis impairment in late-onset depression(LOD) rats based on cerebrospinal fluid(CSF) proteomics. A total of 66 20-21-month-old male Wistar rats were randomized into naturally aged(AGED) group, LOD group, and EXD group. All rats received chronic unpredictable mild stress(CUMS) for 6 weeks for LOD modeling except for the AGED group. During the modeling, EXD group was given EXD(ig, twice a day at 4 g·kg~(-1)) and other groups received equivalent amount of normal saline(ig). After modeling, a series of behavioral tests, such as sucrose preference test(SPT), open-field test(OFT), forced swimming test(FST), and Morris water maze test(MWMT) were performed. Immunofluorescence method was used to detect the number of Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area of each group. High-concentration corticosterone(CORT) was combined with D-galactose(D-gal) to simulate the changes of LOD-related stress and aging and the proliferation and differentiation of primary neural stem cells of hippocampus in each group were observed. Data independent acquisition(DIA)-mass spectrometry(MS) was used to analyze the differential proteins in CSF among groups and bioinformatics analysis was performed to explore the biological functions of the proteins. Behavioral tests showed that sucrose consumption in SPT, total traveling distance in OFT, and times of crossing the platform in MWMT were all reduced(Plt;0.01) and the immobility time in FST was prolonged(Plt;0.01) in the LOD group compared with those in the AGED group, suggesting that LOD rats had developed depression symptoms such as anhedonia, decreased locomotor activity ability, and cognitive dysfunction. Behavioral abnormalities were alleviated(Plt;0.01, Plt;0.05) in the EXD group as compared with those in the LOD group. Immunofluorescence results demonstrated that Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area were fewer(Plt;0.05) in LOD group than in the AGED group, and the positive cells in the EXD group were more(Plt;0.05) than those in the LOD group. In vitro experiment showed that the proliferation and differentiation of primary hippocampal neural stem cells under the CORT+D-gal treatment were reduced(Plt;0.01). The proliferation rate of neural stem cells decreased(Plt;0.05) in CORT+D-gal+LOD-CSF group but increased(Plt;0.01) in CORT+D-gal+EXD-CSF group compared with that in the CORT+D-gal group. A total of 2 620 proteins were identified from rat CSF, with 135 differential proteins between the LOD group and AGED group and 176 between EXD group and LOD group. GDF11, NrCAM, NTRK2, and GhR were related to neurogenesis and 39 differential proteins were regulated by both LOD and EXD. EXD demonstrated obvious anti-LOD effect, as it improved the locomotor activity ability and cognitive function of LOD rats and protected the proliferation and differentiation of hippocampal neural stem cells. EXD exerts anti-LOD effect by regulating the proteins related to neurogenesis in CSF, such as GDF11, NrCAM, NTRK2, and GhR and maintaining hippocampal neurogenesis.

BackgroundHippocampal neurogenesis dysfunction is one of the main pathogenesis of depression. Icariin (ICA) has significant anti-depression and anti-hippocampal damage effects but could not effectively cross the blood-brain-barrier and accumulate in brain. Based on the proteomics of cerebrospinal fluid (CSF), this study aimed to explore the mechanism of ICA against hippocampal neurogenesis dysfunction in depression.MethodsIn vivo, rats were exposed to 6-week CUMS and treated by ICA to observe the effects of ICA on depressive symptoms, cognitive functions, neurogenesis and number of neurons in DG. Tandem mass tag (TMT) proteomics were used to screen the differentially expressed proteins (DEPs) in CSF co-regulated by CUMS and ICA. Parallel reaction monitoring (PRM) was used to validate 10 DEPs that were related to cell proliferation and survival. In vitro, CSF was conducted on primary hippocampal neural stem cells (NSCs) to observe the proliferation and differentiation under high-corticosterone (CORT) concentration.Results It was shown that ICA could alleviate depressive symptoms, learning-memory dysfunction, neurogenesis dysfunction and neuronal loss in DG of depression rats and ICA-CSF could effectively repair the CORT-induced damage. A total of 52 DEPs co-regulated by CUMS and ICA in CSF were screened and mainly involved in ribosome pathway, PI3K-Akt pathway and IL-17 pathway. Rps4x, Rps12, Rps14, Rps19, Hsp90b1, Hsp90aa1 and HtrA1 were validated by PRM.ConclusionsThese findings indicate that to regulate the expression of proteins in CSF may be involved in the effects of ICA against hippocampal neurogenesis dysfunction in depression.

Magnetic nano materials were known as high adsorption properties Nano-structural Ni2.33Fe alloy was successfully prepared by hydrothermal method and was used to remove CrO42- ions from aqueous solution. The results show that the equilibrium adsorption quantity increased with the increase of initial CrO42- concentration and pseudo-second-order kinetic models were successfully used for fitting the kinetic data. Webb Maurice diffusion model shows adsorption was controlled by external mass transfer followed by internal particle diffusion mass transfer. And the fitting degree of the Langmuir isotherm and the experimental data was quite high. And the Freundlich isotherm also fitted well.

This study was performed to investigate the effect of early pressure dressing on the prevention of postoperative subdural effusion secondary to decompressive craniectomy (DC) in patients with severe traumatic brain injury (STBI). Patients with STBI who had undergone DC for refractory increased intracranial pressure between January 2008 and December 2011 (n = 169) were randomly divided into early pressure dressing (n = 82) and control (n = 87) groups. Early pressure dressing with an elastic bandage or general wrapping (control treatment) was applied 7 to 10 days after DC. Patients' age, sex, preoperative Glasgow Coma Scale score, incidence rate of subdural effusion, hospitalization time, and postoperative Glasgow Outcome Scale score were compared between groups. Intracranial pressure was measured immediately before and on the day after pressure dressing. No significant difference in age, sex, preoperative Glasgow Coma Scale score, or postoperative Glasgow Outcome Scale score was observed between groups (P > 0.05). Subdural effusion incidence rates were significantly lower in the early pressure dressing group than those in the control group (χ² = 5.449, P = 0.021), and a larger proportion of patients in the early pressure dressing group was hospitalized for 30 days or less (χ² = 5.245, P = 0.027). Early pressure dressing 7 to 10 days after DC, which is a noninvasive, simple procedure, reduced the incidence rate of subdural effusion and shortened hospitalization time after DC for STBI.

The study aimed to evaluate the levels of serum free kappa (κ) and lambda (λ) light chains in patients with rheumatoid arthritis (RA) as well as exploring the association between serum free κ and λ light chains and activity of RA. For this purpose, healthy individuals and patients with active RA and RA in remission were enrolled, and their serum levels of free κ and λ light chains were measured using rate nephelometry. The diagnostic accuracy of serum free κ and λ light chains was evaluated by receiver operating characteristic curves and 95% confidence intervals for areas under the curve (AUC). The results obtained indicated that the levels of serum free κ and λ light chains in patients with active RA were significantly higher than those of patients in remission and of healthy controls (p

Objective: Resistant strains of Mycoplasma pneumoniae lead to antibiotic inefficacy. The relationship between M pneumoniae 23S rRNA (GenBank: X68422.1) gene mutations and macrolide resistance phenotype has not been fully established, to our knowledge. In this study, we isolated and cultured macrolide-resistant strains of M pneumoniae and tested them for 23S rRNA gene mutations. Methods: Throat swab samples from patients (n = 800) with community-acquired respiratory tract infections were isolated by nested PCR for the molecular identification of clinical isolates. An in vitro drug sensitivity test was performed on clinical isolates for macrolide antibiotic efficacy. The minimum inhibitory concentration (MIC) was used to select resistant strains. Resistant strains of 23S rRNA were sequenced and compared with the sequences of standard macrolidesensitive M129 strains by comparative sequence analysis, focusing the analysis on mutations linked to the drug-resistance phenotype. Results: One hundred M pneumoniae strains were isolated, of which 82 strains were macrolide sensitive and 18 strains were resistant. Mutations were identified in 16 of the 18 macrolide-resistant strains. The following mutations were detected: A2063G, A2064G, C2617G, and A2067G. Of these mutations, A2063G exhibited 14-ring macrolide resistance, A2064G exhibited 14- and 16-ring macrolide resistance, C2617G demonstrated 14- and 15-ring macrolide resistance, and A2067G demonstrated josamycin resistance. Conclusion: M pneumoniae resistance to macrolide antibiotics is a serious clinical issue: our results indicate that 23S rRNA mutations are associated with drug resistance. By analysis of the 23S rRNA mutation and resistance phenotype, our understanding of the clinical drug resistance of M pneumoniae can aid in the rational selection and application of antibiotics for optimal therapeutic treatments.

Background: Liver injury is one of the serious side effects of anti-tuberculosis (TB) drugs. It is controversial whether hepatoprotectant prophylaxis is efficient and safe in anti-TB treatment, so we aimed to assess the efficacy and safety of hepatoprotectant prophylaxis in patients who had received anti-TB treatment. Methods: PubMed, the Cochrane library, Embase, Ovid, Springer link, Wiley, Elsevier, Web of Science, and the Karger Online Journal were systematically searched prior to April 2016 for articles related to hepatoprotectant prophylaxis in the treatment of TB. A meta-analysis was conducted to estimate the effect of hepatoprotective agents on liver function and adverse events (AEs) in patients who had received anti-TB drugs. The primary outcomes were changes in alanine transaminase (ALT) and aspartate transaminase (AST) levels. The other outcomes were drug-induced liver injury (DILI) and AEs. Results: In our review, 6 trials that involved 1,227 patients were included. Our analysis indicated that hepatoprotective agents exerted protective effects on liver function in patients who had received anti-TB drugs (weighted mean difference, WMD = -7.81, 95% CI [-12.26, -3.37], p = 0.0006 [ALT]; WMD = -7.07, 95% CI [-11.43, -2.72], p = 0.001 [AST]) in any age group. However, in the subgroup analysis of treatment duration, the use of hepatoprotective agents was not associated with significant changes in ALT and AST levels after 2 weeks of treatment and exhibited a positive effect on liver function after 4 weeks of treatment. Moreover, the use of hepatoprotectants significantly decreased the number of DILI cases (risk ratio, RR 0.50, 95% CI [0.34-0.73], p = 0.0004). However, the use of hepatoprotectants led to similar AEs in the control groups (RR 1.07, 95% CI [0.82-1.39], p = 0.62). Conclusions: The use of hepatoprotective drugs may prevent liver injury in patients who are receiving anti-TB drugs without any significant AEs 4 weeks after the initiation of hepatoprotective medication.

Background The purpose of this systematic review was to evaluate the effect of magnesium sulfate in the treatment of acute traumatic brain injury. Materials and methods A systematic search of ClinicalTrials.gov, the Cochrane Library database, EMBASE, MEDLINE, Web of Science, and the World Health Organization trial registry, plus manual searches of gray literature, was undertaken in April 2013. Two reviewers independently extracted the data with a predefined data extraction form. RevMan 5 software was used to synthesize data and calculate the risk ratio for mortality with the 95% confidence interval. For the Glasgow Outcome Scale and posttreatment Glasgow Coma Scale data, the weighted mean difference was calculated with the 95% confidence interval. Results A total of 8 randomized controlled trials with a total of 786 patients were included. Meta-analysis showed that there was no significant difference between the groups for mortality. The Glasgow Outcome Scale of the treatment group was higher than that of the control group, although the significance was borderline. The Glasgow Coma Scale score change posttreatment was significantly higher than that of the control. Conclusions The present meta-analysis of existing randomized controlled trials does not identify a significant beneficial effect in the mortality of traumatic brain injury patients; however, it suggests that magnesium sulfate shows a tendency to improve the Glasgow Outcome Scale and Glasgow Coma Scale scores, which is a promising result for traumatic brain injury therapy. Further effort is necessary to explore which subgroup of traumatic brain injury patients could benefit from magnesium sulfate.

To explore effects and possible mechanisms of curcumin on hypoxia induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma cell line HepG2.HepG2 cells were divided to 3 groups, i.e., the normal control group, the CoCl2 group, and the CoCl2 plus 10 micromol/L curcumin group. The proliferation of HepG2 was determined using MTT assay. The migration of HepG2 was detected by wound healing assay.The mRNA expression of hypoxia-inducible factor-1 (HIF-1alpha) was evaluated with real-time RT-PCR. The protein expressions of HIF-1alpha, epithelial-cadherin (E-cadherin), and vimentin were determined using Western blot.Compared with the normal control group, the proliferation and migration of HepG2 cells under CoCl2-induced hypoxia significantly increased, the expression of HIF-1alpha was up-regulated, and the expression of E-cadherin protein was obviously down-regulated, and the expression of vimentin significantly increased (all P0.05). Intervention by curcumin significantly inhibited the proliferation and migration of hypoxic HepG2 cells, and expressions of HIF-1alpha and vimentin decreased, and the expression of E-cadherin was up-regulated, showing statistical difference when compared with those of the CoCl2 group (P0.05). There was no statistical difference in HIF-1alpha mRNA expression among the 3 groups (P0.05).Curcumin could reverse the proliferation and migration of HepG2 cells under CoCl2-induced hypoxia condition, which might be associated with inhibiting up-regulated expressions of HIF-1alpha protein and EMT.

In the title compound, C12H12N2O2, synthesized by ammonolysis of 3-phenylisoxazole-5-carbonyl chloride in dichloromethane, the dihedral angle between the isoxazole ring and the phenyl ring is 14.05 (7)°. In the crystal, centrosymmetrically related molecules are linked into dimers by pairs of C—H...O hydrogen bonds, generating rings of graph-set motif R 2 2(10).

Remote epidural hematoma (REDH) is an uncommon complication of decompressive craniectomy. Remote epidural hematomas of the parietal occiput region have been reported only rarely. We report a unique case of delayed-onset bilateral extensive straddle postsagittal sinus and bilateral lateral sinus parietal occiput REDH after decompressive craniectomy, of which volume was approximately 130 mL, with left deviating midline structures. The patient was immediately taken back to the operating room for evacuation of the REDH via bilateral parietal and occiput craniectomy. Postoperatively, serial computed tomographic scans performed 3 days later showed that the REDH had been completely evacuated. Two months later, the patient regained full consciousness and obtained a near-complete recovery except for right facial paralysis.

The purpose of this systematic review was to evaluate and meta-analyse the current evidence for the use of calcium channel blockers (CCBs) in the treatment of acute traumatic brain injury (TBI) and traumatic subarachnoid haemorrhage (tSAH). A systematic search of clinical trials.gov, Cochrane library databases, EMBASE, MEDLINE, Web of science search and WHO trial registry, plus hand-searching of grey literature, was undertaken in March 2013. Two reviewers independently extracted the data using a pre-defined data extraction form. RevMan 5 software was used to synthesise data and calculate the risk ratio (RR) based on event rates as well as the 95% confidence interval (CI). Finally, nine RCTs with a total of 2182 patients were included. Meta-analysis showed that there was no difference between CCBs and control groups for rates of mortality (n=1337, 5 RCTs, RR 0.93 CI 0.77-1.12). In a subgroup tSAH analysis, the difference was not significant (n=389, 2 RCTs, RR 0.73 CI 0.53-1.02). There were slightly fewer unfavourable outcomes in the treatment group, but the difference was not statistically significant (n=2101, 8 RCTs, RR 0.90 CI 0.76-1.08). In the subgroup tSAH analysis, again, the difference did not reach statistical significance (n=1074, 5 RCTs, RR 0.95 CI 0.73-1.24). It seems that larger, well-designed RCTs are necessary in order to ascertain any clinical benefit CCBs may or may not have for the treatment of acute TBI.

To compare the efficacy and safety of low-dose rituximab combined with different dosage of glucocorticoids for immune thrombocytopenia (ITP).Seventy-four patients (35 male, median age 34 years, range 18-70 years) including 60 newly-diagnosed, 6 persistent, 5 chronic and 3 refractory patients were enrolled in this study, and separated into control (36 cases) and experimental (38 cases) groups according to the dosage of glucocorticoids. Patients in both groups received dexamethasone 40 mg/day on days 1-4, followed by rituximab 100 mg on days 7, 14, 21, 28. The patients in experimental group also received decrements of prednisone 60, 30, 20, 10 mg/day on days 5-7, 8-14, 15-21, 22-28. The initial, long-term efficacy and safety were evaluated.Platelet counts of all patients at day 4 remarkably increased, with the median platelet count from 11(1-26) × 10⁹/L to 84(23-132) × 10⁹/L in control group, and 10(2-20) × 10⁹/L to 80(22-115) × 10⁹/L in experimental group; the platelet counts of patients at day 14 in experimental group [163(19-262) × 10⁹/L] was higher than that of control group [98(18-238) × 10⁹/L] (P0.05). The overall response (OR) rates at day 28 in experimental group (84.21%) was significantly higher than that of control group (66.67%, P = 0.03). There was no significant difference of sustained response (SR) rates in two groups (63.89%vs 65.79%, 58.33%vs 60.53%, P0.05) at six and twelve months follow-up points. Both groups showed similar incidence of adverse events, and no patients discontinued the treatment due to side effects.Low-dose rituximab and glucocorticoids was an effective method for ITP patients, and maintenance treatment with decrements of prednisone contributed to improving earlier CR rate.目的 比较两种糖皮质激素联合小剂量利妥昔单方案治疗成人原发免疫性血小板减少症（ITP）的疗效。方法 74例ITP患者，男35例、女39例，中位年龄34（18～70）岁，新诊断的ITP 60例、持续性ITP 6例、慢性ITP 5例、难治性ITP 3例。按糖皮质激素治疗方案随机分为①对照组（36例）：地塞米松40 mg/d 第1~4天口服； 利妥昔单抗100 mg 第7、14、21、28天静脉滴注。②试验组（38例）：地塞米松40 mg/d 第1~4天口服；泼尼松60 mg/d 第5~7天、30 mg/d 第8~14天、20 mg/d 第15~21天、10 mg/d 第22~28天口服；利妥昔单抗100 mg第7、14、21、28天静脉滴注。观察比较两组患者的近、远期疗效和不良反应情况。结果 治疗第4天，对照组、试验组患者PLT分别由治疗前的11（1～26）×10⁹/L、10（2～20）×10⁹/L升高至84（23～132）×10⁹/L、80（22～115）×10⁹/L；治疗第14天，试验组患者PLT明显高于对照组［163（19～262）×10⁹/L对98（18～238）×10⁹/L，P=0.045］；治疗第28天，试验组患者总有效率高于对照组（84.21%对66.67%，P=0.03）；随访至6、12个月，对照组和试验组患者持续有效率比较，差异无统计学意义（63.89%对65.79%, 58.33%对60.53%, P0.05）。两组患者不良反应均能耐受。结论 大剂量地塞米松后泼尼松维持联合小剂量利妥昔单抗方案治疗ITP早期缓解率优于地塞米松联合小剂量利妥昔单抗方案。

To investigate the expression and clinical significance of CEACAM1 and HBx in HBV related hepatocellular carcinoma.The expression of CEACAM1 and HBx in 81 HBV related hepatocellular carcinoma were detected by immunohistochemistry, and the relationship with clinicopathological features was analyzed. The expression of CEACAM1 in the human normal hepatocyte cell line QZG, HepG2 and HepG2-X were detected by Western blot.The positive rate of CEACAM1 and HBx in 81 HBV related hepatocellular carcinoma tissues were 71.60%(58/81) and 74.07%(60/81) respectively. The expression of CEACAM1 and HBx were correlated with portal vein invasion, nodal metastasis and TNM staging. The expression of CEACAM1 was negative correlated with HBx(r(s);=-0.310, P0.01). CEACAM1 protein was significantly down regulated in HepG2-X than in HepG2-PC and human normal hepatocyte cell line QZG.The higher expression of HBx and lower expression of CEACAM1 are correlated with invasion and metastasis of HBV related hepatocelular carcinoma, CEACAM1 may be a effect molecule in HBV related hepatocarcinogenesis.

To investigate the expression of HBx and COX-2 in hepatitis B virus-related hepatocellular carcinoma, and Its correlation with microangiogenesis and metastasis, and possible mechanism.Immunohistochemistry was used to detect the expression of hepatitis B virus X, cyclooxygenase-2 and CD34 in hepatitis B virus related hepatic carcinoma and 22 non-HBV related hepatic carcinoma tissues. The expression of hepatitis B virus x protein and cyclooxygenase-2 in hepatitis B virus-related hepatocellular carcinoma correlated with microangiogenesis and metastasis was tested by Spearman correlation analysis. The expression of COX-2 in HepG2-X was detected by Western blot and RT-PCR. PGE2 was detected by ELISA in clear supernatant liquid of HepG2-X. Trypan blue exclusion was performed to examine the inhibitory effects of COX-2 selective inhibitor (celecoxib).In Hepatitis B carcinoma tissue, HBx and COX-2 were expressed at high level. The positive rate of COX-2 expression was 88.87% (55/62) in HBx positive expression group, which was significantly higher than that of the positive expression 31.82% (7/22, x2=27.188, P0.01) in HBx negative expression group and 40.91% (9/22, x2=20.453, P0.01) in non-HBV related hepatic carcinoma tissues, but it had no statistical difference (x2=0.393, P=0.531) between the HBx negative expression group and non-HBV related hepatic carcinoma tissue group. The expressions of HBx and COX-2 in metastasis group were higher than that in non-metastasis group (P0.01), MVD in HBx or COX-2 positive expression group was significantly higher than that in negative expression group and non-HBV related hepatic carcinoma tissues (P is less than 0.01). MVD with metastasis was higher than that without metastasis (P0.01) and MVD with portal vein invasion was higher than that without invasion (P0.05). Spearman correlation analysis showed that the expression of COX-2 was significantly correlated with the expression of HBx (Rs=0.568, P0.01). Celecoxib suppressed the growth of both cells in a dose-dependent manner. HepG2-X was significantly susceptible to celecoxib as compared to the HepG2-PC cells. COX-2 protein and mRNA were upregulated in HepG2-X cells than in HepG2-PC. Moreover, PGE2 was upregulated in clear supernatant liquid of HepG2-X than in HepG2-PC.The expressions of HBx and COX-2 were higher in HBV-related hepatocellular carcinoma. COX-2 was significantly correlated with HBx in HCC and it could be a key factor involved in HBx contributed hepatocellular carcinoma's microangiogenesis and metastasis. The possible mechanism of the dual effects might be through HBx, COX-2 and PGE2 pathways in infiltration involved metastasis and microangiogenesis involved metastasis.

Hypoxia inducible factor-1alpha (HIF-1alpha) was well correlated with carcinogenesis and tumor progression in many kinds of cancer. In this study, high expression of HIF-1alpha was found in 37 of the 72 (51.39%) tumor specimens, and significantly correlated with venous invasion and lymphonode invasion. Patients with high expression of HIF-1alpha had a significantly shorter overall survival rate and disease-free survival rate than those with low expression. Multivariate analysis showed high HIF-1alpha expression was a borderline independent factor of overall survival. HIF-1alpha expression was also found to be significantly correlated with the expression of hepatitis B virus X protein (HBx), and over-expressed HBx upregulated HIF-1alpha protein expression in vitro. These results suggested that HIF-1alpha, which was partially regulated by HBx, might be a prognostic marker of HBV-related HCC patients.

To investigate the expressions of hepatitis B virus x protein (HBx) and hypoxia-inducible factor-1alpha (HIF-1alpha) in hepatocellular carcinoma (HCC) tissues and HepG2 cells under normoxic and hypoxic conditions.Immunohistochemistry was used to detect the expressions of HBx and HIF-1alpha in 78 hepatic carcinoma tissues, and their possible relationships were analyzed using SPSS 10.0 statistical software. Immunofluorescence and Western blot were used to investigate the expression of HIF-1alpha in HepG2 and HepG2-X cells under normoxic and hypoxic conditions. Flow cytometric analysis was used to measure reactive oxygen species (ROS) in HepG2 and HepG2-Xd cells under normoxic and hypoxic conditions.The positive rate of HBx in the hepatocellular carcinoma tissues was 74.36% (58/78), while the positive rate of HIF-1alpha was 69.23% (54/78). Under normoxic condition, HIF-1alpha was mainly localized in the cytoplasm and partially translocated into the nuclei of most HepG2-X cells, while under hypoxic condition the expression of HIF-1alpha was positive in the cytoplasm and nuclei of HepG2 and HepG2-X cells. Under normoxic condition the expression of HIF-1alpha was negative in the HepG2 cells while it was positive in HepG2-X cells, but HIF-1alpha was upregulated time-dependently in both HepG2 and HepG2-X cells under hypoxia condition. Furthermore, HepG2-X cells had a higher level of ROS than HepG2 cells under normoxic condition, while under hypoxic condition, the levels of ROS in HepG2 and HepG2-X cells were not significantly different, but the levels of ROS in HepG2 and HepG2-X cells under hypoxia condition were higher than those under normoxia condition.HBx and HIF-1alpha were widely expressed in HCC tissues and there is a positive relationship between them. HIF-1alpha can be upregulated by HBx in HepG2 cells under normoxic and hypoxia conditions. Regulation of HIF-1alpha by HBx in HCC might be via the ROS pathway.