Objective:To investigate the effects of ginkgolide B on neurological function recovery and the Wnt/β-catenin pathway after ischemic stroke in mice.Methods:Fifty-five C57/BL6 mice were selected, of which 10 mice were kept as the sham group and the remaining 45 mice were constructed as the ischemic stroke model. There were 40 mice who finally completed the modeling, and then they were randomly divided into the blank control group (GB0w), short-course administration group (GB1w), long-term administration group (GB2w), and long-term administration+antagonist group (GB2w+PRI-724), with 10 mice in each group. There was no drug intervention after MCAO in GB0w. The mice in GB1w were given ginkgolide B (10 mg/kg) 0.1 ml within 1 week after MCAO; in GB2w were given ginkgolide B (10 mg/kg) 0.1 ml within 2 weeks after MCAO; and in GB2w+PRI-724 were nasally fed ginkgolide B (10 mg/kg) 0.1 ml within 2 weeks after MCAO; and selective antagonist PRI-724 was given 3 h before administration of ginkgolide B on days 8 to 14. Neurological function scores, walking on rotor bar test scores, expression of transforming growth factor-β1 (TGF-β1), fibroblast growth factor 4 (FGF4), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), Wnt, β-catenin, and glycogen synthase kinase-3β (GSK-3β) were compared among the groups.Results:Compared with the sham group, the expressions of MDA, TNF-α, IL-6, FGF4, and GSK-3β in GB0w, GB1w, GB2w, and GB2w+ PRI-724 were increased, and the expressions of GSH-Px, SOD, TGF-β1, β-catenin, and Wnt were decreased (all P < 0.001). Compared with GB0w, the expressions of SOD, GSH-Px, TGF-β1, Wnt, and β-catenin were increased in GB1w, GB2w, and GB2w+PRI-724, and the expressions of MDA, TNF-α, IL-6, FGF4, and GSK-3β were decreased (all P < 0.001). Compared with GB1w, the expressions of GSH-Px, SOD, TGF-β 1, Wnt, and β-catenin were increased in GB2w and GB2w+PRI-724, and the expressions of IL-6, TNF-α, MDA, FGF4, and GSK-3β were decreased (all P < 0.001). Compared with GB2w, the neural function score, walking on the stick test score, and expressions of IL-6, TNF-α, FGF4, MDA, and GSK-3β were increased in GB2w+PRI-724, while the expressions of GSH-Px, TGF-β1, SOD, Wnt, and β-catenin were decreased (all P < 0.001). Conclusions:Ginkgolide B can effectively improve the neurological function of ischemic stroke mice and may be related to the Wnt/β-catenin pathway.

Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L⁻¹ NaAsO₂ model group (NaAsO₂), 50 mg·L⁻¹ NaAsO₂+10 mg·kg⁻¹ GBE intervene group (NaAsO₂+GBE), and 10 mg·kg⁻¹ GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L⁻¹ NaAsO₂, or given intraperitoneal injection of normal saline containing 10 mg·kg⁻¹ GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L⁻¹ NaAsO₂ group (NaAsO₂), 8 μmol·L⁻¹ NaAsO₂ + 200 mg·L⁻¹ GBE intervene group (NaAsO₂+GBE), and 200 mg·L⁻¹ GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO₂ group exhibited an elevated blood glucose compared to the control group, and the NaAsO₂+GBE group showed a decreased blood glucose compared to the NaAsO₂ group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO₂ group and NaAsO₂+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO₂ groups compared to the control groups, which was alleviated in the NaAsO₂+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO₂+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.

ObjectiveTo investigate the regulatory effects of Ginkgolide B on the biological characteristics of brain T cells and their interactions with glial cells during the recovery phase of ischemic stroke in mice. Methods36 adult C57BL/6 mice were randomly assigned to three groups: sham-operated group (Sham group), control group (PBS group), and Ginkgolide B treatment group (GB group). The Sham group underwent only sham surgeries, whereas the PBS and GB groups were subjected to a middle cerebral artery occlusion (MCAO) model using the filament method, followed by intranasal administration of an equivalent volume of either PBS or Ginkgolide B solution for 14 days post-injury. Neurological function changes were evaluated in all three groups using the rotarod test and a neurological scoring system. On day 15, single-cell sequencing was performed on fresh tissues from the brain injury areas, surrounding cortex, corpus callosum, and striatum of mice in the PBS and GB group to assess the biological characteristics of T cells and their subpopulations, and further explore the interactions and mechanisms among T cells, microglia, and oligodendrocytes. ResultsCompared with the Sham group, both PBS and GB group exhibited significant improvements in neurological scores and reduced pre-fall motor durations (P < 0.001). Compared with the PBS group, the GB group showed a downward trend in neurological scores and an upward trend in pre-fall motor durations on days 5, 10, and 15 post-ischemic brain injury, with a significant increase in pre-fall motor duration on day 15 (P < 0.05). Compared with the PBS group, the GB group exhibited a significant increase in T cell proliferative activity in the brain 15 days post brain injury (P < 0.05). The number of proliferative T cells and the levels of lipid metabolism were significantly elevated (P < 0.05), and there was a significant increase in extracellular matrix remodeling in all T cells (P < 0.05). Additionally, the interactions between T cells and both microglia and oligodendrocytes, as well as among the microglia themselves and between microglia and oligodendrocytes, were significantly enhanced in the GB group. This was primarily evident in the strengthened interactions between CD74 and macrophage migration inhibitory factor (MIF), as well as colony stimulating factor 1 receptor (CSF1R) and colony stimulating factor 1 (CSF1) (P < 0.05). However, the inflammatory levels of T cells showed no significant differences compared with the PBS group. ConclusionA mouse model of ischemic stroke can be successfully established by MCAO operation. Ginkgolide B may promote neurological recovery post-brain injury in mice by modulating the biological characteristics of T cells within the brain and their interactions with glial cells.

Objective To investigate the effect of acupuncture at Yangming meridian combined with modified Buyang Huanwu Decoction on hemiplegia,hemorheology and neurotrophic factors in pa-tients with cerebral infarction differentiated as type of Qi deficiency and blood stasis.Methods A to-tal of 84 hospitalized patients with cerebral infarction differentiated as type of Qi deficiency and blood stasis from March 2018 to June 2023 were selected as research objects,and they were randomly divid-ed into observation group and control group,with 42 cases in each group.The control group was con-ducted with acupuncture and routine treatment,while the observation group was conducted with modi-fied Buyang Huanwu Decoction on the basis of the control group.Clinical efficacy after 2 weeks of treatment as well as the scores of main symptoms,neurological function,limb function,hemorheologi-cal indicators and levels of neurotrophic factors before and after treatment were compared between two groups.Results After 2 weeks of treatment,the total effective rate of the observation group was sig-nificantly higher than that of the control group(P＜0.05);after treatment,the scores of symptoms such as hemiplegia,deviated mouth and awkward speech in both groups decreased significantly when compared to those before treatment,and these scores in the observation group were significantly lower than those in the control group(P＜0.05).After treatment,the score of the National Institutes of Health Stroke Scale(NIHSS)in both groups decreased significantly when compared to that before treat-ment,and the score in the observation group was significantly lower than that in the control group(P＜0.05);the score of the Motor Function Assessment Scale(Fugl-Meyer)after treatment in both groups was significantly higher than that before treatment,and the observation group was significant-ly higher than that in the control group(P＜0.05).After treatment,the plasma viscosity,red blood cell aggregation index,whole blood high shear viscosity and whole blood low shear viscosity in both groups decreased significantly when compared to those before treatment,and these indexes in the observation group were significantly lower than those in the control group(P＜0.05).After treatment,the levels of serum brain derived neurotrophic factor(BDNF),nerve growth factor(NGF)and glial cell line-derived neurotrophic factor(GDNF)in both groups increased significant-ly when compared to those before treatment,and the levels of these indexes in the observation group were significantly higher than those in the control group(P＜0.05).Conclusion Acupuncture at Yangming meridian combined with modified Buyang Huanwu Decoction can enhance the therapeutic effect for patients with cerebral infarction differentiated as type of Qi deficiency and blood stasis,im-prove clinical symptoms,repair nerve damage,and promote the recovery of limb function.

Objective To investigate the effect of acupuncture at Yangming meridian combined with modified Buyang Huanwu Decoction on hemiplegia,hemorheology and neurotrophic factors in pa-tients with cerebral infarction differentiated as type of Qi deficiency and blood stasis.Methods A to-tal of 84 hospitalized patients with cerebral infarction differentiated as type of Qi deficiency and blood stasis from March 2018 to June 2023 were selected as research objects,and they were randomly divid-ed into observation group and control group,with 42 cases in each group.The control group was con-ducted with acupuncture and routine treatment,while the observation group was conducted with modi-fied Buyang Huanwu Decoction on the basis of the control group.Clinical efficacy after 2 weeks of treatment as well as the scores of main symptoms,neurological function,limb function,hemorheologi-cal indicators and levels of neurotrophic factors before and after treatment were compared between two groups.Results After 2 weeks of treatment,the total effective rate of the observation group was sig-nificantly higher than that of the control group(P＜0.05);after treatment,the scores of symptoms such as hemiplegia,deviated mouth and awkward speech in both groups decreased significantly when compared to those before treatment,and these scores in the observation group were significantly lower than those in the control group(P＜0.05).After treatment,the score of the National Institutes of Health Stroke Scale(NIHSS)in both groups decreased significantly when compared to that before treat-ment,and the score in the observation group was significantly lower than that in the control group(P＜0.05);the score of the Motor Function Assessment Scale(Fugl-Meyer)after treatment in both groups was significantly higher than that before treatment,and the observation group was significant-ly higher than that in the control group(P＜0.05).After treatment,the plasma viscosity,red blood cell aggregation index,whole blood high shear viscosity and whole blood low shear viscosity in both groups decreased significantly when compared to those before treatment,and these indexes in the observation group were significantly lower than those in the control group(P＜0.05).After treatment,the levels of serum brain derived neurotrophic factor(BDNF),nerve growth factor(NGF)and glial cell line-derived neurotrophic factor(GDNF)in both groups increased significant-ly when compared to those before treatment,and the levels of these indexes in the observation group were significantly higher than those in the control group(P＜0.05).Conclusion Acupuncture at Yangming meridian combined with modified Buyang Huanwu Decoction can enhance the therapeutic effect for patients with cerebral infarction differentiated as type of Qi deficiency and blood stasis,im-prove clinical symptoms,repair nerve damage,and promote the recovery of limb function.

[Abstract] Objective: To investigate the short-term clinical efficacy and safety of intraperitoneal perfusion of natural killer (NK) cells in the treatment of ovarian cancer with ascites. Methods: The clinical data of 15 ovarian cancer patients with ascites effusion, who received NK cell perfusion in the Qinhuai Medical District of the General Hospital of Eastern Theater Command from November 2016 to January 2019, were analyzed. The peripheral blood was collected to isolate the peripheral blood mononuclear cells, and to further obtain the NK cells after culture. NK cell suspension was intraperitoneally perfused into the abdominal cavity (no less than 2×109 cells/ time). The volume of peritoneal effusion, the level of serum tumor marker CA-125, the level of serum cytokines IL-2, INF-γ and TNF-α as well as the changes in peripheral blood lymphocyte subsets were detected before and after the treatment; Moreover, the clinical efficacy and adverse reactions were observed. Results: The effective rate of intraperitoneal perfusion of NK cells was 66.7%, and there were no obvious treatment-related adverse reactions. Compared with before treatment, the serum tumor marker CA-125 level significantly decreased after treatment (P<0.05), and the levels of IL-15, IFN-γ and TNF-α increased significantly (P<0.05 or P<0.01), while there was no significant changes in peripheral blood lymphocyte subsets (all P>0.05). Conclusion: Intraperitoneal infusion of NK cells in the treatment of ovarian cancer associated peritoneal effusion has a good short-term clinical efficacy with little adverse reactions, which is a promising method for the treatment of cancerous peritoneal effusion.

Objective: To explore the significance of minimal residual disease (MRD) in predicting prognosis and guiding therapy of adults with Philadelphia-chromosome negative acute lymphoblastic leukemia (Ph^- ALL) in high-risk. Methods: Data of newly diagnosed adults with Ph^- ALL in high-risk who achieved CR were reviewed. Variables associated with outcome were identified by COX regression model and Landmark analysis. Results: A total of 177 patients, 99 (56%) cases male with a median age of 40 years (range, 16-65 years) were included in this study. Of them, 95 (54%) patients received allo-HSCT in CR₁. Multivariate analyses showed that MRD negativity after the first cycle of consolidation (HR=0.52, 95%CI 0.30-0.89, P=0.017) and achieving CR within 4 weeks (HR=0.43, 95%CI 0.24-0.79, P=0.006) were the factors significantly-associated with longer DFS, and allo-HSCT was associated with both longer DFS (HR=0.13, 95%CI 0.08-0.22, P<0.001) and OS (HR=0.24, 95%CI 0.15-0.41, P<0.001) . Landmark analysis was performed on 121 patients, of 85 patients achieving MRD negativity after the first cycle of consolidation, multivariate analyses showed that MRD negativity after the third cycle of consolidation was significantly-associated with longer DFS (HR=0.18, 95%CI 0.05-0.64, P=0.008) and OS (HR=0.14, 95%CI 0.04-0.50, P=0.003) . For the patients achieving MRD negativity after both the first and the third cycles of consolidation, the 3-year DFS rate in the allo-HSCT cohort had a higher trend compared with that in the chemotherapy cohort (75.2% vs 51.3%, P=0.082) , however, the 3-year OS rates in the 2 cohorts were similar (72.7% vs 68.7%, P=0.992) . In those with MRD positivity after the first and/or the third cycle of consolidation, 3-year DFS (64.8% vs 33.3%, P=0.006) and OS (77.0% vs 33.3%, P=0.028) rates in the allo-HSCT cohort were significantly higher than those in the chemotherapy cohort, and similar to those in the cohort achieving MRD negativity after both the first and the third cycles of consolidation and receiving allo-HSCT. Conclusions MRD negativity after the first cycle of consolidation was a predictor for better outcome in adults with Ph^- ALL in high-risk. The survival advantage of the allo-HSCT cohort was not pronounced compared with that in the chemotherapy cohort even in those with high-risk features but achieving MDR negativity after both the first and third cycles of consolidation. However, allo-HSCT could be a good option for the patients with MRD positivity after the first and/or the third cycle of consolidation.

Objective To investigate the treatment strategy of operation in torcular herophili meningiomas.Methods Retrospectively analyzed the treatment strategy of operation and follow-up data of 16 cases torcular herophili meningiomas patients.Results Grade Ⅰ resection was 9 cases,grade Ⅱ resection was 5 cases,grade Ⅳ resection was 2 cases.One patient appeared transverse thrombosis in postoperative.Followed up for 26-61 months,all patients had no recurrence.Conclusion By detailed preoperative evaluation,selection of appropriate operative approach,reasonable treatment of venous sinus adhesion tumor,supplemented by the necessary radiotherapy,can reduce the risk of operation and recurrence rate to torcular herophili meningiomas.

Objective To investigate the feasibility of using low Kv,low iodine contrast Agent concentration (dual low)CT scan techniques in Coronary CTA (CCTA).Methods Seventy-six patients undergoing CCTA were divided into Group A and Group B , randomly.Group A (38 patients)was the dual-low group,which was scanned with tube voltage of 100 kVp,and injected with iso-osmolarity contrast agent visipaque 270 (270 mg I/mL),with iterative reconstruction technique (ASIR 40%).Group B (38 pa-tients)was scanned with 120 kVp,and low osmolarity contrast agent omnipaque 350 (350 mg I/mL)and FBP reconstruction,The images are assessed double-blindly by two experienced radiologists.Five ROIs were placed onto the ascending root of aorta (AO), left main artery(LM),left anterior descending (LAD),left circumflex artery(LCX),right coronary artery (RCA),and the image qualities are evaluated objectively using CT values,noise,signal noise ratio (SNR),contrast noise ratio (CNR),and compared sta-tistically using Paired t-test.The radiation dosages,such as CTDIvol,DLP and ED were also recorded and compared with Paired t-test.Results CTDIvol,DLP and ED of Group A (dual low)decreased 35.7%,38.6% and 38.6% respectively compared with Group B,the iodine intake decreased 22.9%.While the image qualities of the two groups were not significantly different,all images are good enough for diagnosis,with Group A slightly better than Group B in radiologists’scores.Conclusion Voltage 100 kVp, combined with low contrast agent concentration of 270 mg I/mL can fully satisfy the diagnostics need in CCTA,and significantly lower both the radiation dosage and iodine intake.

The compound excipient containing sodium stearyl fumarate and plasdone S-630 was prepared by applying spray drying method. The basic physical properties of compound excipient were studied by solubility test, scanning electron microscope, differential scanning calorimeter, X-ray diffraction and Fourier transform infra-red spectroscopy. The effect of compound excipient on moisture absorption and ferulic acid in vitro dissolution of spray drying power of angelica were investigated. The results showed that the chemical constituents of compound excipient did not change before and after spray drying. The water soluble compound excipient can improve significantly moisture absorption and has application prospect.