Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a higher incidence in males, but the association of sex with survival remains controversial. This study aimed to examine the effect of sex on HCC survival and its association with age. METHODS: Among 33,238 patients with HCC from 12 Chinese tertiary hospitals, 4175 patients who underwent curative-intent hepatectomy or ablation were analyzed. Cancer-specific survival (CSS) was analyzed using Cox regression and Kaplan-Meier methods. Two propensity score methods and multiple mediation analysis were applied to mitigate confounding. To explore the effect of estrogen, a candidate sex-specific factor that changes with age, female participants' history of estrogen use, and survival were analyzed. RESULTS: There were 3321 males and 854 females included. A sex-related disparity of CSS was present and showed a typical age-dependent pattern: a female survival advantage over males appeared at the perimenopausal age of 45 to 54 years (hazard risk [HR], 0.77; 5-year CSS, 85.7% vs 70.6%; P = .018), peaked at the early postmenopausal age of 55 to 59 years (HR, 0.57; 5-year CSS, 89.8% vs 73.5%; P = .015), and was not present in the premenopausal (<45 y) and late postmenopausal groups (≥60 y). Consistent patterns were observed in patients after either ablation or hepatectomy. These results were sustained with propensity score analyses. Confounding or mediation effects accounted for only 19.5% of sex survival disparity. Female estrogen users had significantly longer CSS than nonusers (HR, 0.74; 5-year CSS, 79.6% vs 72.5%; P = .038). CONCLUSIONS: A female survival advantage in HCC depends on age, and this may be associated with age-dependent, sex-specific factors.

Safety and efficacy of microwave ablation for the treatment of low-risk papillary thyroid microcarcinoma: a prospective multicenter study.

OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.

Congo Red-Derived Carbon Dots: Simultaneously as Fluorescence Probe for Protein Aggregates, Inhibitor for Protein Aggregation, and Scavenger of Free Radicals.

The pathological aggregation of some proteins is claimed to be highly related to several human diseases, such as ß-amyloid 1-42 (Aß42 ) to Alzheimer's disease (AD), islet amyloid polypeptide, and insulin to type 2 diabetes mellitus. Therefore, it is in desperate need to develop effective methods for detection of protein aggregates and inhibition of abnormal aggregation. Herein, to construct all-in-one probe with both diagnosis and treatment potentials for protein aggregation diseases, Congo red (CR), a classical staining reagent with red fluorescence signal output for protein aggregates, is deliberately adopted to react with three different reductive carbon sources and ammonium persulfate to generate three CR-derived carbon dots (CDs). The obtained CDs exhibit the capabilities of turn-on red fluorescence imaging of protein aggregates, and/or inhibition of protein aggregation as well as scavenging of free radicals. Among them, CA-CDs, using citric acid as the reductive carbon source, demonstrate the superiority to the other two studied CDs in integrating all of these functions, and particularly exert excellent cytoprotection effect against toxic Aß42 species, possessing tremendous potential in diagnosis and treatment of AD for future study. The present study paves a new way to develop all-in-one CDs for the protein disease research.

Period-Dependent Survival Benefit of Percutaneous Microwave Ablation for Hepatocellular Carcinoma: A 12-Year Real-World, Multicentric Experience.

Introduction: Although microwave ablation (MWA) is a promising technique for hepatocellular carcinoma (HCC) treatment, its 10-year efficacy is unknown. Objective: The objective of the study was to assess whether the advances in MWA for HCC translated into a real-world survival benefit. Methods: This retrospective study included 2,354 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 to B from 5 hospitals, with at least 2 years of follow-up for all the patients. Recurrence and survival were analyzed using the Kaplan-Meier method with time-period stratification. Results: A total of 5,326 HCCs (mean diameter, 2.9 cm ± 1.2) underwent 4,051 sessions of MWA with a median follow-up of 61.3 (0.6-169.5 range) months during 3 periods (2007-2010, 2011-2014, and 2015-2018). Technical success was achieved in 5,194 (97.5%) tumors with significant improvement over time, especially for >3.0-cm HCC (p < 0.001). Local tumor progression (LTP) showed no period-dependent advance, with >3.0-cm HCC and perivascular location being the risk factors for LTP. The median intrahepatic metastasis time was 27.6 (95% confidence interval [CI]: 25.2-28.8) months, with 5- and 10-year occurrence rates of 68.8% and 79.4%, respectively. The 5- and 10-year overall survivals were 63.9% and 41.1%, respectively, and BCLC stage 0, A, and all B patients showed an observable survival improvement over time (p < 0.001). The median disease-free survival time increased from 19.4 (95% CI: 16.5-22.6) months in 2007-2010 to 28.1 (95% CI: 25.9-32.3) months in 2015-2018. The improved survival for early recurrent (≤2 years) patients was period-dependent, as verified by Cox regression analyses. The major complications rate per procedure was 3.0% (122/4,051). Conclusions: These real-world data show that MWA provided an upward trend in survival for HCC patients with BCLC stage 0-B over a 12-year follow-up period. An encouraging clear survival benefit in early recurrent patients was also observed.

A multicenter 10-year oncologic outcome of ultrasound-guided percutaneous microwave ablation of clinical T1 renal cell carcinoma: will it stand the test of time?

OBJECTIVES: We updated the experience on percutaneous microwave ablation for renal cell carcinoma with five-center data and long-term follow-up. METHODS: This retrospective study reviewed the T1N0M0 renal cell carcinoma patients who underwent microwave ablation between April 2006 and December 2019. Clinicopathological and procedural data were collected. Technical effectiveness and complications were assessed, and the Kaplan-Meier method was used for cancer-specific survival, disease-free survival, overall survival, and local neoplastic process analyses. RESULTS: A total of 323 consecutive patients (mean age, 62.9 years ± 14.0) with 371 biopsy-proved tumors (mean diameter, 2.9 cm ± 1.2) were enrolled, and 42.6% of the tumors were located adjacent to collecting system/bowel and technical effectiveness was achieved in 360 (97.0%) tumors. For 275 cT1a patients, during median follow-up time of 66.0 months (IQR, 58.4-73.6), 10-year local neoplastic processes, cancer-specific survival, disease-free survival, and overall survival rates were 1.9%, 87.4%, 71.8, and 67.5%, respectively. For 48 cT1b patients, during the median follow-up time of 30.4 months (IQR, 17.7-44.8), 5-year local tumor progression, cancer-specific survival, disease-free survival, and overall survival rates were 11.3%, 91.4%, 69.1, and 89.2%, respectively. Major complications showed no differences between cT1a (3.5%) and cT1b (6.9%) patients (p = 0.28). A clinical risk stratification system was developed based on multivariable model to predict DFS and CSS with c-indexes of 0.78 (95% CI: 0.71-0.85) and 0.77 (95% CI: 0.65-0.90), respectively. CONCLUSIONS: With matured follow-up at five institutions, ultrasound-guided percutaneous microwave ablation is a reliable treatment option for cT1a renal cell carcinoma even in dangerous location and appears to be promising for cT1b tumors. KEY POINTS: • To our knowledge, this is the first multicenter cohort of long-term oncologic outcomes with percutaneous MWA of cT1 RCC. • The predicting model we developed is accurate to predict the long-term DFS and CSS, which can help to provide a better MWA prognostication over routinely available clinical information. • The available evidence shows that microwave ablation of clinical stage T1 RCC is safe and reliable with promising long-term oncologic outcomes, especially for cT1a RCC with excellent 10-year results.

Structural elucidation and antidiabetic activity of fucosylated chondroitin sulfate from sea cucumber Stichopus japonicas.

A fucosylated chondroitin sulfate was isolated from the body wall of sea cucumber Stichopus japonicus (FCSsj), whose structure was characterized by NMR spectroscopy and HILIC-FTMS. At the ratio of 1.00:0.26:0.65, three fucosyl residues were found: 2,4-disulfated-fucose (Fuc2,4S), 4-sulfated-fucose (Fuc4S) and 3,4-disulfated-fucose (Fuc3,4S), which were only linked to the O-3 of glucuronic acid residues (GlcA). Besides mono-fucosyl moieties, di-fucosyl branches, namely Fuc2,4Sα(1→3)Fuc4S, were also found to be attached to the O-3 of GlcA. The antidiabetic activity of FCSsj was evaluated using glucosamine induced insulin resistant (IR) Hep G2 cells in vitro. It was found that FCSsj significantly promoted the glucose uptake and glucose consumption of IR-Hep G2 cells in a dose-dependent manner, and could alleviate the cell damage. Furthermore, FCSsj could promote the glycogen synthesis in the glucosamine-induced IR-Hep G2 cells. These results provided a supplement for studying the antidiabetic activity of FCSsj.

Application of marine natural products in drug research.

New diseases are emerging as the environment changes, so drug manufacturers are always on the lookout for new resources to develop effective and safe drugs. In recent years, many bioactive substances have been produced in the marine environment, which represents an alternative resource for new drugs used to combat major diseases such as cancer or inflammation. Many marine-derived medicinal substances are in preclinical or early stage of clinical development, and some marine drugs have been put on the market, such as ET743 (Yondelis®). This review presents the sources, activities, mechanisms of action and syntheses of bioactive substances based on marine natural products in clinical trials and on the market, which is helpful to understand the progress of drug research by application of marine natural products.

Highly efficient removal of silver nanoparticles by sponge-like hierarchically porous thiourea-formaldehyde resin from Water.

With the increasing production and rapid market penetration as well as the confirmation of the toxic effects, silver nanoparticles (AgNPs) are one kind of newly emerging environmental contaminants of high concern. It is urgent to develop the efficient method to remove them from the environment. In this study, the sponge-like hierarchically porous thiourea-formaldehyde (TF) resin rich with nitrogen and sulfur was for the first time proposed as the adsorbent to achieve this goal. With enormous interconnected layer structure and plentiful macropores, the porous TF resin provided abundant available interaction sites and fast mass transfer to adsorb citrate stabilized AgNPs (citrate-AgNPs). Fast adsorption rate and high adsorption capacity (2478 mg/g) were obtained based on the electrostatic and metal-ligand interactions. Heterogeneous aggregation and simultaneous adsorption contributed to this removal process. Furthermore, with the assistance of NaCl, the porous TF resin exhibited largely enhanced removal efficiency towards citrate-AgNPs up to 98.7 % in 5 min, possibly due to the co-operation of adsorption and coagulation. This study proposed a promising adsorbent to remove AgNPs and provided a referential strategy to design highly efficient adsorbents for removal of nanoparticles.

Structure-based discovery of novel 4-(2-fluorophenoxy)quinoline derivatives as c-Met inhibitors using isocyanide-involved multicomponent reactions.

The c-Met kinase has emerged as a promising target for the development of small molecule antitumor agents because of its close relationship with the progression of many human cancers, poor clinical outcomes and even drug resistance. In this study, two novel series of 6,7-disubstitued-4-(2-fluorophenoxy)quinoline derivatives containing α-acyloxycarboxamide or α-acylaminoamide scaffolds were designed, synthesized, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (H460, HT-29, MKN-45, and MDA-MB-231). Most of the target compounds exhibited moderate to significant potency and possessed selectivity for H460 and HT-29 cancer cell lines. The preliminary structure-activity relationships indicated that α-acyloxycarboxamide or α-acylaminoamide as 5-atom linker contributed to the antitumor potency. Among these compounds, compound 10m (c-Met IC50 = 2.43 nM, a multitarget tyrosine kinase inhibitor) exhibited the most potent inhibitory activities against H460, HT-29 and MDA-MB-231 cell lines with IC50 of 0.14 ± 0.03 µM, 0.20 ± 0.02 µM and 0.42 ± 0.03 µM, which were 1.7-, 1.3- and 1.6-fold more active than foretinib, respectively. In addition, concentration-dependent assay and time-dependent assay indicated compound 10m can inhibit the proliferation of H460 cell in a time and concentration dependent manner. Moreover, docking studies revealed the common mode of interaction with the c-Met binding site, suggesting that 10m is a potential candidate for cancer therapy deserving further study.

Release of antidiabetic peptides from Stichopus japonicas by simulated gastrointestinal digestion.

Sea cucumber (Stichopus japonicus) is a high-protein food with the potential to release certain peptides through enzymolysis. This work is to explore the characteristics of peptides released from Stichopus japonicus protein in the process of digestion. Hydrolysates were obtained by gastrointestinal digestion and fractioned to <3, 3-10, 10-30 and >30 kDa fractions. Fifty-eight peptides from <3 kDa fraction were characterized using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hydrolysates could improve glucose uptake of 3 T3-L1 cells and high insulin-induced insulin-resistant Hep G2 cells. Molecular docking showed that the released peptides had similar binding mode with anagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor. The <3 kDa fraction in gastro and intestinal digestion showed the greatest DPP-IV inhibitory potency (IC50 0.51 and 0.52 mg/mL, respectively). The results indicated that sea cucumber could be used as a functional food to release antidiabetic peptides through gastrointestinal digestion.

Contralateral seventh cervical nerve transfer can affect the pennation angle of the lower limb in spastic hemiplegia patients: An observational case series study.

INTRODUCTION: We previously reported transferring seventh cervical (C7) nerve from unaffected side to affected side in patients with spastic hemiplegia due to chronic cerebral injury, to improve function and reduce spasticity of paralyzed upper limb. In the clinics, some patients also reported changes of spasticity in their lower limb, which could not be detected by routine physical examinations. Pennation angle of muscle can indirectly reflect the condition of spasticity. The purpose of this study was to evaluate whether this upper limb procedure may affect spasticity of lower limb, using ultrasonography to detect changes of muscle pennation angle (PA). METHODS: Twelve spastic hemiplegia patients due to cerebral injury including stroke, cerebral palsy, and traumatic brain injury, who underwent C7 nerve transfer procedure, participated in this study. B-mode ultrasonography was used to measure PA of the gastrocnemius medialis (GM) muscle at rest preoperatively and postoperatively. The plantar load distribution of the lower limbs was evaluated using a Zebris FDM platform preoperatively and postoperatively. RESULTS: The PA of the GM was significantly smaller on the affected side than that of unaffected side before surgery. On the affected side, the postoperative PA was significantly larger than preoperative PA. On the unaffected side, the postoperative PA was not significantly different compared to preoperative PA. The postoperative plantar load distribution of the affected forefoot was significantly smaller than preoperative load distribution, which was consistent with ultrasonography results. CONCLUSIONS: This study indicates that C7 nerve transfer surgery for improving upper limb function can also affect muscle properties of lower limb in spastic hemiplegia patients, which reveals a link between the upper and lower limbs. The interlimb interactions should be considered in rehabilitation physiotherapy, and the regular pattern and mechanism need to be further studied.

Neuroprotection and CD131/GDNF/AKT Pathway of Carbamylated Erythropoietin in Hypoxic Neurons.

Carbamylated erythropoietin (CEPO), an EPO derivative, is attracting widespread interest due to neuroprotective effects without erythropoiesis. However, little is known about molecular mechanisms behind CEPO-mediated neuroprotection. In primary neurons with oxygen-glucose deprivation (OGD) and mice with hypoxia-reoxygenation, the neuroprotection and possible molecular mechanism of CEPO were performed by immunohistochemistry and immunocytochemistry, Western blot, RT-PCR, and ELISA. The comparisons were analyzed by ANOVA followed by unpaired two-tailed Student's t test. Both CEPO and EPO showed the neuroprotective effects in OGD model and hypoxic brain. CEPO did not trigger JAK-2 but activated AKT through glial cell line-derived neurotrophic factor (GDNF). It has been shown that CEPO acts upon a heteroreceptor complex comprising both the EPO receptor and the common ß receptor subunit (ßcR, also known as CD131). The blockage of CD131 reduced CEPO-mediated GDNF production, while GFR receptor blockage and GDNF neutralization inhibited CEPO-induced neurogenesis. Addition of GDNF to cultured neurons increased phosphorylation of AKT. CEPO protects neurons possible through the CD131/GDNF/AKT pathway.

Effectiveness of ultrasound-guided percutaneous microwave ablation for symptomatic uterine fibroids: a multicentre study in China.

PURPOSE: To evaluate the clinical efficacy of ultrasound-guided percutaneous microwave ablation (PMWA) therapy for symptomatic uterine fibroids in a multicentre study. MATERIALS AND METHODS: Patients with symptomatic uterine fibroids who underwent PMWA at multiple treatment centres in China between January 2013 and August 2015 were prospectively studied to compare the reduction rate of uterine fibroids, haemoglobin level and uterine fibroid symptom and health-related quality of life questionnaire (UFS-QOL) scores before and at 3, 6 and 12 months after ablation. RESULTS: A total of 311 patients (405 leiomyomas) from eight treatment centres underwent the treatment (age, 29-55 years; mean ± SD, 41 ± 5.11 years). The mean diameter of the myomas ranged from 2.03 to 12.50 cm (mean, 5.10 ± 1.28 cm) and the volume ranged from 4.40 to 1022.14 cm3 (mean, 95.01 ± 70.29 cm3). Forty-eight myomas were identified as FIGO type 1/2 fibroids, 256 as type 3/4 fibroids and 101 as type 5/6 fibroids. The mean ablation rate was 86.6% (54.0-100%). The mean reduction rate was 63.5%, 78.5% and 86.7% at 3, 6 and 12 months posttreatment, respectively. The haemoglobin level increased significantly from 88.84 ± 9.31 g/L before treatment to 107.14 ± 13.32, 116.05 ± 7.66 and 117.79 ± 6.51 g/L at 3, 6 and 12 months posttreatment, respectively (p = .000). The symptom severity score (SSS) and health-related quality of life (HRQL) scores were also significantly improved posttreatment compared with before treatment (p = .000). CONCLUSION: PMWA is an effective, minimally invasive treatment for symptomatic leiomyomas that can significantly improve the quality of life of patients.

Midterm results of percutaneous microwave ablation under ultrasound guidance versus retroperitoneal laparoscopic radial nephrectomy for small renal cell carcinoma.

Laparoscopic radial nephrectomy (LRN) and microwave ablation (MWA) are optional treatment for renal cell carcinoma (RCC). However, the comparative study with two techniques remains lacking. The aim of this study was to evaluate midterm results of MWA vs. LRN in patients with small RCC. A total of 426 patients with ≤ 4 cm RCC were included from April 2006 to October 2012. Ninety-eight patients underwent MWA and 328 patients LRN. The survival, recurrence, and renal function changes were compared between two treatments. Although overall survival after MWA (82.6% at 5 years) was lower than those after LRN (98.6% at 5 years, p = 0.0004), the RCC-related survival (97% at 5 years) was comparable to those following LRN (98% at 5 years, p = 0.38). One local tumor progress occurred at 32 months after MWA and none after LRN. The major complication rates were comparable between two techniques (1.7% in MWA vs. 1.5% in LRN, p = 0.75), but MWA showed less renal function damage than LRN (p < 0.0001). The multivariate analysis showed the presence of postablation extrarenal metastasis may become a predictor of the oncologic outcome (p = 0.059) and treatment modality had no influence (p = 0.965). This study demonstrates that MWA and LRN provide comparable results in small RCC outcomes.

The lack of CD131 and the inhibition of Neuro-2a growth by carbamylated erythropoietin.

Recombinant human erythropoietin (EPO), a glycohormone, is one of the leading biopharmaceutical products, while carbamylated erythropoietin (CEPO), an EPO derivative, is attracting widespread interest due to its neuroprotective effects without erythropoiesis in several cells and animal models. However, exogenous EPO promotes an angiogenic response from tumor cells and is associated with tumor growth, but knowledge of CEPO on tumor growth is lacking. Here we show that CEPO, but not EPO, inhibited Neuro-2a growth and viability. As expected, CEPO--unlike EPO--did not activate JAK-2 either in primary neurons or in Neuro-2a cells. Interestingly, CEPO did not induce GDNF expression and subsequent AKT activation in Neuro-2a cells. Before CEPO/EPO treatment, glial cell line-derived neurotrophic factor (GDNF) neutralization and GFR receptor blocking decreased the viability of EPO-treated Neuro-2a cells but did not influence CEPO-treated Neuro-2a cells. As compared to primary neurons, the expression of CD131, as a receptor complex binding to CEPO, is almost lacking in Neuro-2a cells. In BABL/C-nu mice, CEPO did not promote the growth of Neuro-2a cells nor extended the survival time compared to mice treated with EPO. The results indicate that CEPO did not promote tumor growth because of lower expression of CD131 and subsequent dysfunction of CD131/GDNF/AKT pathway in Neuro-2a cells, revealing its therapeutic potential in future clinical application.

Local tumour progression after ultrasound-guided microwave ablation of liver malignancies: risk factors analysis of 2529 tumours.

OBJECTIVES: To identify the incidence and risk factors that predict local tumour progression (LTP) after ultrasound-guided percutaneous microwave ablation (MWA) of liver malignancies. MATERIALS AND METHODS: One thousand two hundred and nine patients with 2,529 malignant nodules (mean size 2.8 ± 1.4 cm, range 0.9-8.0 cm) were treated by MWA between July 2005 and December 2012. The influence of 11 factors on the risk of LTP was assessed. Univariate Kaplan-Meier and Cox proportional hazard models were used for statistical analysis. RESULTS: The overall LTP was 4.2 % per tumour and 8.6 % per patient with a median follow-up of 20.3 months. LTP per tumour was 4.3 % for primary liver cancer and 4.1 % for metastases (p = 0.32). The survival of LTP and free-LTP patients at 1, 3, and 5 years was 92.4 %, 71.6 %, and 45.1 %, respectively, and 92.9 %, 70.1 %, and 52.4 %, respectively (p = 0.93). By univariate analysis, tumour location, size and ablation time were significant risk factors of LTP. Multivariate analysis identified tumour size (>3.0 cm) to be the only independent predictor of LTP. CONCLUSIONS: MWA of liver malignancies achieves a relatively low-incidence LTP, although LTP risk significantly increases if tumour size >3.0 cm. The technique seems to be appropriate even for patients with a tumour at a risk location. KEY POINTS: • Microwave ablation of liver malignancies achieves a low incidence local tumour progression. • LTP risk significantly increases if the tumour size is >3.0 cm. • MWA seems to be appropriate even for patients with a tumour at a risk location.

TSPO-specific ligand vinpocetine exerts a neuroprotective effect by suppressing microglial inflammation.

Vinpocetine has long been used for cerebrovascular disorders and cognitive impairment. Based on the evidence that the translocator protein (TSPO, 18 kDa) was expressed in activated microglia, while Vinpocetine was able to bind TSPO, we explored the role of Vinpocetine on microglia treated with lipopolysaccharide (LPS) and oxygen-glucose deprivation (OGD) in vitro. Our results show that both LPS and OGD induced the up-regulation of TSPO expression on BV-2 microglia by RT-PCR, western blot and immunocytochemistry. Vinpocetine inhibited the production of nitrite oxide and inflammatory factors such as interleukin-1ß (IL-1ß), IL-6 and tumour necrosis factor-α (TNF-α) in BV-2 microglia, in which cells were treated with LPS or exposed to OGD, regardless of the time Vinpocetine was added. Next, we measured cell death-related molecules Akt, Junk and p38 as well as inflammation-related molecules nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). Vinpocetine did not change cell death-related molecules, but inhibited the expression of NF-κB and AP-1 in LPS-stimulated microglia, indicating that Vinpocetine has an anti-inflammatory effect by partly targeting NF-κB/AP-1. Next, conditioned medium from Vinpocetine-treated microglia protected from primary neurons. As compared with in vitro, the administration of Vinpocetine in hypoxic mice also inhibited inflammatory molecules, indicating that Vinpocetine as a unique anti-inflammatory agent may be beneficial for the treatment of neuroinflammatory diseases.