Red blood cell distribution width as a predictor of mortality and poor functional outcome after acute ischemic stroke: a meta-analysis and meta-regression.

BACKGROUND: This study aimed to review evidence on the ability of red cell distribution width (RDW) to predict mortality and poor functional outcomes after acute ischemic stroke (AIS). METHODS: Databases of PubMed, CENTRAL, Scopus, Embase, and Web of Science were searched online from inception to 25th Jul 2023 for all studies reporting the association between RDW and outcomes as adjusted ratios. A random-effects meta-analysis was done. Meta-regression was conducted using multiple moderators. RESULTS: 15 studies with 14,968 patients were included. Meta-analysis found that RDW, both as a categorical variable (OR: 2.10 95% CI: 1.74, 2.55 I2 = 42%) and continuous variable OR: 1.16 95% CI: 1.05, 1.28 I2 = 64%) was a significant predictor of mortality after AIS. Age and number of hypertensives were found to be significant moderators in the meta-regression. Also, high RDW, as a categorical variable (OR: 1.68 95% CI: 1.20, 2.35 I2 = 84%), was associated with significantly higher odds of poor functional outcomes after AIS, but not as a continuous variable (OR: 1.07 95% CI: 0.99, 1.16 I2 = 61%). Meta-regression showed that the association was stronger in small sample-sized studies. CONCLUSION: RDW can be a useful, readily available, and cost-effective biomarker to rapidly stratify AIS patients at risk of poor outcomes. High RDW was consistently associated with an increased risk of mortality after AIS, however, its ability to predict poor functional outcomes needs to be verified by further studies.

Responses of bacterial and three sub-microeukaryote communities in the water of white shrimp Penaeus vannamei aquaculture ponds in two polyculture models.

Polyculture operations in freshwater aquaculture ponds can disrupt microbial communities. High-throughput sequencing was used to assess the impact of polyculture operations on bacterial and three sub-microeukaryote communities (fungi, zooplankton, and eukaryotic phytoplankton) in Penaeus vannamei aquaculture ponds containing oriental river prawns and giant freshwater prawns, respectively. The results showed that the bacterial community was less sensitive than the microeukaryote communities to both the polyculture activity and environmental variations. The polyculture of giant freshwater prawns rather than oriental river prawns was the primary factor affecting the beta diversity of the three sub-microeukaryote communities. This may be due to the larger biomass of the polyculture varieties of giant freshwater prawns compared with oriental river prawns. The polyculture activity of giant freshwater prawns with a higher density and that of oriental river prawns with a lower density increased the stochasticity of the community assembly of the three sub-microeukaryote communities. It also affected the topological properties of the microbial communities, including greater correlations between ecosystem elements, and reducing the correlations among zooplanktons. The eukaryotic phytoplankton was the only microbial community that could also be explained by nutrient variation (mainly the total nitrogen). This highlights the potential role of the eukaryotic phytoplankton as a suitable indicator of the effects of nutrient input into ecosystems.

Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels.

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.

Development of nomograms to predict therapeutic response and prognosis of non-small cell lung cancer patients treated with anti-PD-1 antibody.

BACKGROUND: Anti-programmed death-1 (PD-1) antibody changed the treatment of non-small cell lung cancer (NSCLC), however, reliable predictive markers were lacking. We aimed to explore factors associated with response and survival, and develop predictive models. METHODS: This multicenter retrospective study included a training cohort (n = 92) and validation cohort (n = 111) with NSCLC patients received anti-PD-1 antibody monotherapy in eight Chinese hospitals, and a control cohort (n = 124) with NSCLC patients received chemotherapy. Logistic and Cox models were used to identify factors associated with response and survival respectively. Nomograms were developed based on significant factors, and evaluated by Concordance-index (C-index), area under the curve (AUC) and calibration curve. RESULT: In training cohort, smoking history (P = 0.027) and higher absolute lymphocyte count (P = 0.038) were associated with response. Female (P < 0.001), age ≥ 65 years (P = 0.004) and higher lactate dehydrogenase (LDH, P < 0.001) were associated with shorter progression-free survival (PFS). Higher LDH (P < 0.001) and derived neutrophil-to-lymphocyte ratio (P = 0.035) were associated with poorer overall survival (OS). While these factors were nonsignificant in chemotherapy cohort. Three nomograms to predict response at 6-week after treatment, PFS and OS at 6-, 12- and 18-months were developed, and validated in validation cohort. The C-indices of each nomogram in both cohorts were as follow (training vs validation): 0.706 vs 0.701; 0.728 vs 0.701; 0.741 vs 0.709; respectively. AUC showed a good discriminative ability. Calibration curves demonstrated a consistence between actual results and predictions. CONCLUSION: We developed predictive nomograms based on easily available factors to help clinicians early assess response and prognosis for NSCLC patients received anti-PD-1 antibody.

Hepatitis B virus X (HBx) play an anti-apoptosis role in hepatic progenitor cells by activating Wnt/ß-catenin pathway.

Increasing evidence has shown that normal stem cells may act as cancer-initiating cells and contribute to the development and progression of cancer. HBx has a close relationship with hepatocellular carcinoma, however, the role of HBx in hepatic progenitor cells (HPCs) is poorly understood. In this study, we sought to determine the role of HBx in regulating HPCs apoptosis and the underlying molecular mechanism(s) using HPCs derived from mouse fetal liver. The apoptotic ratio of HPCs infected with adenovirus-expressing HBx (Ad-HBx) was examined using flow cytometry. Results showed that the Ad-HBx treatment led to substantially decreased apoptotic ratio of HPCs, as confirmed by the Hoechst 33342 staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). Possible alterations of relative proteins were examined using Western blot and real-time PCR assays. The HBx expression in HPCs increased the expression levels of Bcl2 and Mcl1 while decreasing the expression levels of Bax and cleaved caspase-9 and -3. In addition, the mRNA and protein expression levels of ß-catenin were both increased. The ß-catenin protein were mainly accumulated in cytoplasm and tended to transfer into cell nucleus after Ad-HBx treatment. The over-expression of ß-catenin decreased the apoptotic ratio of HPCs and inhibited the expression of cleaved caspase-9 and -3 while blocking ß-catenin expression resulted in the opposite results. Taken together, our results strongly suggested that the HBx protein may inhibits apoptosis of hepatic progenitor cells, at least in part by activating the WNT/ß-catenin pathway. This provided a new insight into the molecular mechanism of HBx-mediated live carcinogenesis.

Improving consumer stickiness in livestream e-commerce: A mixed-methods study.

With the continuous development and improvement of Internet media technologies in China, the influence of livestream e-commerce is becoming increasingly prominent, and an increasing number of people are engaging in consumption activities in this field. It is important to study consumer stickiness in livestream e-commerce to promote economic structure adjustment and innovation-driven development. Therefore, in this study, we adopted the expectation confirmation theory (ECT) as the theoretical framework and analyzed the ECT and stickiness. The study considered satisfaction as the previous influencing factor of user and consumer stickiness, replaced the continuance intention in the expectation confirmation model with consumer stickiness as the explanatory variable, introduced the variable of perceived playfulness as the value perception after user experience, and established a consumer stickiness factors model. A total of 262 valid questionnaires were collected in this study, and SmartPLS analysis along with interviews were used to justify the limitations of data analysis. The results of the study demonstrated a significant effect of perceived usefulness and confirmation on satisfaction, a significant effect of confirmation on perceived usefulness, a significant effect of satisfaction on stickiness, and a significant effect of confirmation on perceived playfulness. Based on findings from the data analysis and interviews, we further proposed rationalized recommendations, and aimed to provide some theoretical guidance for future research on live streaming.

Synthesis and biological evaluation of furoxan-based nitric oxide-releasing derivatives of glycyrrhetinic acid as anti-hepatocellular carcinoma agents.

A series of novel furoxan-based nitric oxide (NO)-releasing derivatives of glycyrrhetinic acid (GA) were designed, synthesized, and evaluated for their in vitro cytotoxicity against human hepatocellular carcinoma (HCC) and non-tumor liver cells. Five furoxan/GA hybrids, 7b-d, 7f, and 7g, displayed potent cytotoxicity against HCC cells (IC(50): 0.25-1.10 µM against BEL-7402 cells and 1.32-6.78 µM against HepG2 cells), but had a little effect on the growth of LO2 cells, indicating that these compounds had selective cytotoxicity against HCC cells. Furthermore, these compounds produced high concentrations of NO in HCC cells, but low in LO2 cells and treatment with hemoglobin partially reduced the cytotoxicity of the hybrid in HCC cells. Apparently, the high concentrations of NO produced by NO donor moieties and the bioactivity of GA synergistically contribute to the cytotoxicity, but the NO is a major player against HCC cells in vitro. Potentially, our findings may aid in the design of new chemotherapeutic reagents for the intervention of human HCC at clinic.

Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis.

Impairment of glucose (Glu) uptake and storage by skeletal muscle is a prime risk factor for the development of metabolic diseases. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a highly abundant RNA-binding protein that has been implicated in diverse cellular functions. The aim of this study was to investigate the function of hnRNP A1 on muscle tissue insulin sensitivity and systemic Glu homeostasis. Our results showed that conditional deletion of hnRNP A1 in the muscle gave rise to a severe insulin resistance phenotype in mice fed a high-fat diet (HFD). Conditional knockout mice fed a HFD showed exacerbated obesity, insulin resistance, and hepatic steatosis. In vitro interference of hnRNP A1 in C2C12 myotubes impaired insulin signal transduction and inhibited Glu uptake, whereas hnRNP A1 overexpression in C2C12 myotubes protected against insulin resistance induced by supraphysiological concentrations of insulin. The expression and stability of glycogen synthase (gys1) mRNA were also decreased in the absence of hnRNP A1. Mechanistically, hnRNP A1 interacted with gys1 and stabilized its mRNA, thereby promoting glycogen synthesis and maintaining the insulin sensitivity in muscle tissue. Taken together, our findings are the first to show that reduced expression of hnRNP A1 in skeletal muscle affects the metabolic properties and systemic insulin sensitivity by inhibiting glycogen synthesis.

Inhibition of AIM2 inflammasome-mediated pyroptosis by Andrographolide contributes to amelioration of radiation-induced lung inflammation and fibrosis.

Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy, whereas no effective interventions are available. Andrographolide, an active component extracted from Andrographis paniculate, is prescribed as a treatment for upper respiratory tract infection. Here we report the potential radioprotective effect and mechanism of Andrographolide on RILI. C57BL/6 mice were exposed to 18 Gy of whole thorax irradiation, followed by intraperitoneal injection of Andrographolide every other day for 4 weeks. Andrographolide significantly ameliorated radiation-induced lung tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine release in the early phase and progressive fibrosis in the late phase. Moreover, Andrographolide markedly hampered radiation-induced activation of the AIM2 inflammasome and pyroptosis in vivo. Furthermore, bone marrow-derived macrophages (BMDMs) were exposed to 8 Gy of X-ray radiation in vitro and Andrographolide significantly inhibited AIM2 inflammasome mediated-pyroptosis in BMDMs. Mechanistically, Andrographolide effectively prevented AIM2 from translocating into the nucleus to sense DNA damage induced by radiation or chemotherapeutic agents in BMDMs. Taken together, Andrographolide ameliorates RILI by suppressing AIM2 inflammasome mediated-pyroptosis in macrophage, identifying Andrographolide as a novel potential protective agent for RILI.

Axonal sprouting into the denervated spinal cord and synaptic and postsynaptic protein expression in the spinal cord after transplantation of bone marrow stromal cell in stroke rats.

We investigated whether compensatory reinnervation in the corticospinal tract (CST) and the corticorubral tract (CRT) is enhanced by the administration of bone marrow stromal cells (BMSCs) after experimental stroke. Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion (MCAo). Phosphate-buffered saline (PBS, control, n=7) or 3x10(6) BMSCs in PBS (n=8) were injected into a tail vein at 1 day postischemia. The CST of the left sensorimotor cortices was labeled with DiI 2 days prior to MCAo. Functional recovery was measured. Rats were sacrificed at 28 days after MCAo. The brain and spinal cord were removed and processed for vibratome sections for laser-scanning confocal analysis and paraffin sections for immunohistochemistry. Normal rats (n=4) exhibited a predominantly unilateral pattern of innervation of CST and CRT axons. After stroke, bilateral innervation occurred through axonal sprouting of the uninjured CRT and CST. Administration of BMSCs significantly increased the axonal restructuring on the de-afferented red nucleus and the denervated spinal motoneurons (p<0.05). BMSC treatment also significantly increased synaptic proteins in the denervated motoneurons. These results were highly correlated with improved functional outcome after stroke (r>0.81, p<0.01). We conclude that the transplantation of BMSCs enhances axonal sprouting and rewiring into the denervated spinal cord which may facilitate functional recovery after focal cerebral ischemia.

NMDA receptor and iNOS are involved in the effects of ginsenoside Rg1 on hippocampal neurogenesis in ischemic gerbils.

OBJECTIVE: Transient global ischemia increases neurogenesis in the dentate gyrus of adult rodents and this may have a functional relevance. The aim of the present study was to explore the possible mechanisms underlying the effects of ginsenoside Rg1 on hippocampal neurogenesis in adult gerbils suffered from global ischemia. METHODS: Experimental groups include: Group 1: sham operation; Group 2: sham operation + MK-801 (3 mg/kg); Group 3: ischemia only; Group 4: ischemia + MK-801; Group 5: ischemia + Rg1 (5 mg/kg); Group 6: ischemia + Rg1 + MK-801. At the tenth day after ischemia, six gerbils from Groups 1, 3 and 5 were killed and the activity of inducible nitric oxide synthase (iNOS) in the cortex and hippocampus was measured. The rest animals were given bromodeoxyuridine (BrdU, 50 mg/kg) every 4 hours for 12 hours at the tenth day after ischemia and perfused 24 hours after the last injection of BrdU. Immunohistochemistry was performed to identify proliferating cells in the dentate gyrus. RESULTS: Ginsenoside Rg1 increased the magnitude of ischemia induced proliferation of hippocampal progenitor cells and enhanced the activity of iNOS in both the hippocampus and cortex. Systematic injection of MK-801 completely blocked the proliferation increasing effect of Rg1. CONCLUSION: Ginsenoside Rg1 increases neurogenesis after transient global ischemia. The mechanisms underlying this effect may involve activation of iNOS activity and N-methyl-D-aspartate (NMDA) receptors in the brain.

Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis.

Aberrant activation of NLRP3 inflammasome has an important function in the pathogenesis of various inflammatory diseases. Although many components and mediators of inflammasome activation have been identified, how NLRP3 inflammasome is regulated to prevent excessive inflammation is unclear. Here we show NLRP3 inflammasome stimulators trigger Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) translocation to the mitochondria, to interact with and dephosphorylate adenine nucleotide translocase 1 (ANT1), a central molecule controlling mitochondrial permeability transition. This mechanism prevents collapse of mitochondrial membrane potential and the subsequent release of mitochondrial DNA and reactive oxygen species, thus preventing hyperactivation of NLRP3 inflammasome. Ablation or inhibition of SHP2 in macrophages causes intensified NLRP3 activation, overproduction of proinflammatory cytokines IL-1ß and IL-18, and increased sensitivity to peritonitis. Collectively, our data highlight that, by inhibiting ANT1 and mitochondrial dysfunction, SHP2 orchestrates an intrinsic regulatory loop to limit excessive NLRP3 inflammasome activation.

T lymphocyte SHP2-deficiency triggers anti-tumor immunity to inhibit colitis-associated cancer in mice.

Nonresolving inflammation is involved in the initiation and progression process of tumorigenesis. Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) is known to inhibit acute inflammation but its role in chronic inflammation-associated cancer remains unclear. The role of SHP2 in T cells in dextran sulfate sodium (DSS)-induced colitis and azoxymethane-DSS-induced colitis-associated carcinogenesis was examined using SHP2CD4-/- conditional knockout mice. SHP2 deficiency in T cells aggravated colitis with increased level of pro-inflammatory cytokines including IFN-γ and IL-17A. In contrast, the SHP2CD4-/- mice developed much fewer and smaller tumors than wild type mice with higher level of IFN-γ and enhanced cytotoxicity of CD8+ T cells in the tumor and peritumoral areas. At the molecular level, STAT1 was hyper-phosphorylated in T cells lacking SHP2, which may account for the increased Th1 differentiation and IFN-γ secretion. IFN-γ neutralization or IFN-γ receptor knockout but not IL-17A neutralization, abrogated the anti-tumor effect of SHP2 knockout with lowered levels of perforin 1, FasL and granzyme B. Finally, the expression of granzyme B was negatively correlated with the malignancy of colon cancer in human patients. In conclusion, these findings suggest a new strategy to treat colitis-associated cancer via targeting SHP2.

[Role of NO signal in ABA-induced phenolic acids accumulation in Salvia miltiorrhiza hairy roots].

To investigate roles of nitric oxide (NO) signal in accumulations of phenolic acids in abscisic.acid (ABA)-induced Salvia miltiorrhiza hairy roots, S. miltiorrhiza hairy roots were treated with different concentrations of sodium nitroprusside (SNP)-an exogenous NO donor, for 6 days, and contents of phenolic acids in the hairy roots are determined. Then with treatment of ABA and NO scavenger (2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylimidazoline-1- oxyl-3-oxide, c-PTIO) or NO synthase inhibitor (NG-nitro-L-arginine methyl ester, L-NAME), contents of phenolic acids and expression levels of three key genes involved in phenolic acids biosynthesis were detected. Phenolic acids production in S. miltiorrhiza hairy roots was most significantly improved by 100 µmoL/L SNP. Contents of RA and salvianolic acid B increased by 3 and 4 folds. ABA significantly improved transcript levels of PAL (phenylalanine ammonia lyase), TAT (tyrosine aminotransferase) and RAS (rosmarinic acid synthase), and increased phenolic acids accumulations. However, with treatments of ABA+c-PTIO or ABA+L-NAME, accumulations of phenolic acids and expression levels of the three key genes were significantly inhibited. Both NO and ABA can increase accumulations of phenolic acids in S. miltiorrhiza hairy roots. NO signal probably mediates the ABA-induced phenolic acids production.

Structural analysis and optimization of NK(1) receptor antagonists through modulation of atropisomer interconversion properties.

We have previously described a series of antagonists that showed high potency and selectivity for the NK(1) receptor. However, these compounds also had the undesirable property of existing as a mixture of interconverting rotational isomers. Here we show that alteration of the 2-naphthyl substituent can modulate the rate of isomer exchange. Comparisons of the NK(1) receptor affinity for the various conformational forms has facilitated the development of a detailed NK(1) pharmacophore model.

Design, synthesis, and SAR of tachykinin antagonists: modulation of balance in NK(1)/NK(2) receptor antagonist activity.

Through optimization of compounds based on the dual NK(1)/NK(2) antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK(1) and NK(2) potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK(1) potency and thus afforded NK(1) preferential antagonists. Alterations of the piperidine region could then increase NK(2) potency to restore dual NK(1)/NK(2) selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK(1)/NK(2) antagonists, and the third is an NK(1) preferential antagonist. In this paper, the factors affecting the balance of NK(1) and NK(2) selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.

Ginsenoside Rg1 increases ischemia-induced cell proliferation and survival in the dentate gyrus of adult gerbils.

The dentate gyrus is one of the few areas of the mammalian brain where new neurons are continuously produced in adulthood. Recent studies demonstrated that dentate neurogenesis increased after transient global ischemia and it is suggested that the increased neurogenesis contributes to the recovery of hippocampal function. In the present study, adult Mongolian gerbils were chronically treated with ginsenoside Rg1 after ischemia, and the proliferation of cells in the dentate gyrus was examined. It was proved that bromodeoxyuridine (BrdU)-labeled cells in the dentate gyrus were significantly enhanced in number following Rg1 treatment after 6 min global ischemia. In addition, the number of surviving BrdU-positive cells 40 days after ischemia also increased markedly in the Rg1 group. This suggests that ginsenoside Rg1 delivered to the brain well after stroke may have therapeutic benefits.

Ginsenoside Rg1 promotes proliferation of hippocampal progenitor cells.

Neural progenitor cells (NPCs) exist not only in the developing brain, but also in certain areas in adult brain in mammals. Recent studies suggest that promoting neurogenesis in adult mammals might provide a therapeutic way to cure age-related neurodegenerative diseases. So, it will be of great value to find out drugs that can increase the proliferation and/or differentiation ability of neural progenitors. The present study investigated the influence of ginsenoside Rg1, an active ingredient of Panax ginseng C.A. Meyer, on proliferation ability of rodent hippocampal progenitor cells both in vitro and in vivo. Incubation of NPCs with ginsenoside Rg1 resulted in significant increase in absorbency value, 3H-thymidine incorporation and the number of proliferating progenitor cell spheres; In addition, 2 weeks Rg1 administration (i.p.) led to marked enhancement of the number of dividing cells in the hippocampus of adult mice. These findings suggest that ginsenoside Rg1 is involved in the regulation of proliferation of hippocampal progenitor cells and this effect may serve as one of the elementary mechanisms underlying its nootropic and anti-aging actions.

[Culture of neural stem cells from cerebral cortex of rat embryo and effects of drugs on the proliferation ability of stem cells].

AIM: To establish culture procedures of neural stem cells from embryonic rat brain, determine their stem-cell characteristics and observe the effects of several compounds on their proliferation ability. METHODS: Firstly, a stem cell culture system was set up from embryonic rat cortex. The cells were identified as neural stem cells through immunocytochemistry, in which antibodies to neural stem cell specific protein and markers of mature neural cells were used. Then, by using MTT assay, the survival rate of neurospheres incubated with various concentrations of ginsenoside Rg1, (-)-clausenamide and salvianolic acid A were observed. Furthermore, the effect of these drugs was measured with 3[H] thymidine incorporation assay. RESULTS: In this study, a culture model of neural stem cell was successfully set up. In this model, primary cells from E16-18 rat cortex were dissected out, and cultured as floating neurospheres. The results of immunocytochemistry showed that nestin was expressed by the majority of cells within the sphere. After growing for 8 days in differentiation medium, cells from a single neurosphere were shown to differentiate into 3 main kinds of neural cells: neurons, astrocytes and oligodendrocytes. MTT assay revealed that the three drugs all enhanced the survival rate of neural stem cells, but 3[H] thymidine incorporation assay suggested that only Rg1 significantly accelerated the proliferation rate. CONCLUSION: One culture model of neural stem cell was set up successfully. Meanwhile, several drugs were found to increase the proliferation and/or survival rate of neural stem cells. It has been demonstrated that neural stem cells exist in adult mammalian brains. So, these drugs may become promising candidates for the therapy of neurodegenerative diseases; such as Alzheimer's disease and Parkinson's disease.