Objective:This study aims to investigate the behavioral changes, gut microbiota alterations, and short-chain fatty acid levels in mice with chronic dizocilpine (MK-801) administration and to evaluate the correlation between gut microbiota and its metabolites with schizophrenia-like behaviors.Methods:This study was conducted from March to September 2024, involving 24 male C57BL/6 mice aged 6 to 8 weeks, purchased from the Guangdong Provincial Medical Laboratory Animal Center. The mice were randomly divided into a control group and a model group using a random number table method. The model group mice were intraperitoneally injected with MK-801 (0.6 mg/kg) for 14 days, while the control group mice were intraperitoneally injected with an equal amount of normal saline for 14 days. After modeling, behavioral performance was assessed using the open field test (OFT), novel object recognition test (NOR), forced swimming test (FST), tail suspension test (TST), elevated plus maze test (EPM), and prepulse inhibition test (PPI). Additionally, mouse feces were collected for 16S rRNA sequencing to analyze the composition of gut microbiota. The gas chromatography-tandem mass spectrometry (GC-MS/MS) was applied to detect the levels of short-chain fatty acids quantitatively. Between-group comparisons of behavioral data were performed using an independent samples t-test or repeated measures ANOVA with adjusted Bonferroni or corrected Greenhouse-Geisser. Between-group comparisons of gut microbiota composition were conducted using an independent samples t-test or the Mann-Whitney U test. Between-group comparisons of short-chain fatty acids were performed using an independent samples t-test. The correlations among behavioral indicators, gut microbiota composition, and short-chain fatty acids were analyzed using Spearman′s rank correlation. Results:(1) Behavioral experiments showed that the model group mice exhibited significantly prolonged immobility times in the FST and TST ( t=-4.84, -2.54; P<0.05), significantly reduced exploration frequency and time in the open arms of the EPM ( t=3.31, 2.48; P<0.05), significantly lower PPI at 76 dB, 79 dB, and 85 dB ( F=23.28, 10.65, 17.82; P<0.05), and a significantly reduced NOR index ( t=2.90, P<0.05) compared to the control group, indicating successful modeling. (2)16S rRNA sequencing revealed that, compared with the control group, the model group exhibited significantly lower relative abundances of Actinobacteriota, Coriobacteriia, Coriobacteriales, and Ileibacterium( Z=-3.10--2.04, all P<0.05). Conversely, the relative abundances of Tannerellaceae, Rikenellaceae, Alistipes, Bacteroides, Intestinimonas, Parabacteroides, Unclassified_f_Prevotellaceae, and unclassified_f_Erysipelotrichaceae significantly increased ( Z=-3.78--2.04; all P<0.05). (3)GC-MS/MS analysis showed that the concentrations of acetic acid and butyric acid in the feces of the model group were significantly lower compared to the control group ( t=2.66, 2.10; P<0.05). (4)Spearman correlation analysis with FDR correction (Benjamini-Hochberg method) revealed that Actinobacteriota significantly positively correlated with the open-arm exploration frequency in the EPM ( r=0.69, Q<0.05), whereas unclassified_f_Erysipelotrichaceae significantly negatively correlated with this measure ( r=-0.66, Q<0.05). Additionally, Bacteroides and Intestinimonas were significantly negatively correlated with PPI at 85 dB ( r=-0.71, -0.63; Q<0.05).Conversely, Ileibacterium demonstrated a significant positive correlation with PPI at 85 dB ( r=0.64, Q<0.05). Conclusion:Alterations in gut microbiota and SCAFs may be associated with MK-801-induced schizophrenia-like behaviors.

Objective:This study aims to investigate the behavioral changes, gut microbiota alterations, and short-chain fatty acid levels in mice with chronic dizocilpine (MK-801) administration and to evaluate the correlation between gut microbiota and its metabolites with schizophrenia-like behaviors.Methods:This study was conducted from March to September 2024, involving 24 male C57BL/6 mice aged 6 to 8 weeks, purchased from the Guangdong Provincial Medical Laboratory Animal Center. The mice were randomly divided into a control group and a model group using a random number table method. The model group mice were intraperitoneally injected with MK-801 (0.6 mg/kg) for 14 days, while the control group mice were intraperitoneally injected with an equal amount of normal saline for 14 days. After modeling, behavioral performance was assessed using the open field test (OFT), novel object recognition test (NOR), forced swimming test (FST), tail suspension test (TST), elevated plus maze test (EPM), and prepulse inhibition test (PPI). Additionally, mouse feces were collected for 16S rRNA sequencing to analyze the composition of gut microbiota. The gas chromatography-tandem mass spectrometry (GC-MS/MS) was applied to detect the levels of short-chain fatty acids quantitatively. Between-group comparisons of behavioral data were performed using an independent samples t-test or repeated measures ANOVA with adjusted Bonferroni or corrected Greenhouse-Geisser. Between-group comparisons of gut microbiota composition were conducted using an independent samples t-test or the Mann-Whitney U test. Between-group comparisons of short-chain fatty acids were performed using an independent samples t-test. The correlations among behavioral indicators, gut microbiota composition, and short-chain fatty acids were analyzed using Spearman′s rank correlation. Results:(1) Behavioral experiments showed that the model group mice exhibited significantly prolonged immobility times in the FST and TST ( t=-4.84, -2.54; P<0.05), significantly reduced exploration frequency and time in the open arms of the EPM ( t=3.31, 2.48; P<0.05), significantly lower PPI at 76 dB, 79 dB, and 85 dB ( F=23.28, 10.65, 17.82; P<0.05), and a significantly reduced NOR index ( t=2.90, P<0.05) compared to the control group, indicating successful modeling. (2)16S rRNA sequencing revealed that, compared with the control group, the model group exhibited significantly lower relative abundances of Actinobacteriota, Coriobacteriia, Coriobacteriales, and Ileibacterium( Z=-3.10--2.04, all P<0.05). Conversely, the relative abundances of Tannerellaceae, Rikenellaceae, Alistipes, Bacteroides, Intestinimonas, Parabacteroides, Unclassified_f_Prevotellaceae, and unclassified_f_Erysipelotrichaceae significantly increased ( Z=-3.78--2.04; all P<0.05). (3)GC-MS/MS analysis showed that the concentrations of acetic acid and butyric acid in the feces of the model group were significantly lower compared to the control group ( t=2.66, 2.10; P<0.05). (4)Spearman correlation analysis with FDR correction (Benjamini-Hochberg method) revealed that Actinobacteriota significantly positively correlated with the open-arm exploration frequency in the EPM ( r=0.69, Q<0.05), whereas unclassified_f_Erysipelotrichaceae significantly negatively correlated with this measure ( r=-0.66, Q<0.05). Additionally, Bacteroides and Intestinimonas were significantly negatively correlated with PPI at 85 dB ( r=-0.71, -0.63; Q<0.05).Conversely, Ileibacterium demonstrated a significant positive correlation with PPI at 85 dB ( r=0.64, Q<0.05). Conclusion:Alterations in gut microbiota and SCAFs may be associated with MK-801-induced schizophrenia-like behaviors.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

OBJECTIVE: To investigate the effects of resveratrol (Res) on aging of marrow mesenchymal stem cells (MSCs), and to explore its mechanism. METHODS: MSCs were isolated from young SD rats and cultured in vitro. The optimal D-gal concentration for induction of MSCs senescence was determined. Then MSCs were randomly divided into four groups, namely the control group, 10μmol/L, 50μmol/L and 100μmol/L Res groups. After the cells were treated with different concentration of Res for 48 h, the senescence-associated changes were examined with senescence-associated-β-galactosidase (SA-β-gal) staining; the expression of p53, p16 and γ-H2AX was evaluated by Western blot. The total active oxygen species (ROS) level was determined by flow cytometry with DCFH-DA staining. In order to assess the effect of Res on the mitochondrial function, MitoSox Red staining was used to detect mitochondrial ROS levels in each group, mitochondrial membrane potential was detected by JC-1 assay, mPTP method was used to detect mitochondrial membrane channel opening level, and Western blot was used to detect the expression level of cytoplasmic cytochrome C (Cyt-C). RESULTS D-gal 10 and 50 g/L significantly increased the number of SA-β-gal positive cells and the level of mitochondrial ROS (all P<0.01). Therefore, 10 g/L D-gal was used to induce the senescence of MSCs in subsequent experiment. Compared with the control group, the number of SA-β-gal positive cells in Res groups significantly decreased (all P<0.01), the expression of p53, p16 and γ-H2AX decreased, and the total and mitochondrial ROS level also decreased (all P<0.01). Moreover, mitochondrial membrane potential, open level of mitochondrial membrane channels and the levels of cytoplasm Cyt-C in the Res treatment groups decreased compared with the control group (P<0.05 or P<0.01). CONCLUSIONS Resveratrol can protect the mitochondrial function of MSCs, and effectively delay the MSC senescence.

Objective To observe the clinical efficacy of moxibustion in treating perimenopausal syndrome (PMS).Method Totally 108 PMS patients of yang deficiency or yin deficiency constitution were randomized into a treatment group of 56 cases and a control group of 52 cases. The treatment group was intervened by moxibustion, while the control group was by medication. The modified Kupperman Index (KI), Hamilton Anxiety Scale (HAMA), Symptom Checklist-90 (SCL-90), and Self-rating Depression Scale (SDS) were observed before and after treatment for comparison.Result The KI score, HAMA score, SCL-90 total score, and SDS score were significantly changed in both groups after intervention (P<0.01,P<0.05). After treatment, the KI score, HAMA score, SCL-90 total score, and SDS score in the treatment group were significantly different from that in the control group (P<0.01,P<0.05).Conclusion Moxibustion is effective in treating PMS, and it can improve the anxiety and depression symptoms of the patients.

OBJECTIVE:To establish a HPLC method for the content determination of the principal agent in Ligustrazine Phosphate for injection.METHODS:Ligustrazine Phosphate was separated on Zorbax Extend C18(150mm?4.6mm,5?m).The mobile phase consisted of methanol-water(3∶2).A UV-detector at 295nm was used.RESULTS:The linear range of Ligustrazine Phosphate was 0.21～3.00mg?mL-1(r=0.999 9).The average recovery was 100.1%(RSD=0.93%,n=9).CONCLUSION:This method is simple,accurate,sensitive and reproducible,and it can be applied to the quality control of Ligustrazine Phosphate for injection.

Objective To evaluate the effect and safety of trans-arterial chemotherapy embolization (TACE) in the treatment of primary hepatic carcinoma ( PHC ) with portal vein tumor thrombus. Methods There were 83 PHC patients complicated with portal vein tumor thrombus, age ranging from 29 to 76 years. Fifty-three cases underwent TACE ( Group A) , 30 receiving trans-arterial chemotherapy infusion only (TAI, Group B). Results The survival rate in group A at 6,12,24 and 36 months was 97. 8% , 85.2%,45.8% and 4.4%, respectively, significantly higher than that in group B (37. 6% ,5. 3% ,0,0, P