BACKGROUND: Astragalus membranaceus plays an important role in the adjustment of immunological function. Whether does it have protective effect on neuron in the intervention of acute craniocerebral injury and what is the pathway in effect?OBJECTIVE: To observe the effect of astragalus membranaceus on activity of nitric oxide synthetase after brain injury.DEDIGN: Randomized controlled trial.SETTING: Neurosurgery institute of Lanzhou Military Area Command of Chinese PLA.MATERIALS: This experiment was completed in the Laboratory of Neurosurgery Institute of Lanzhou Military Area Command of Chinese PLA. Fifty-four healthy SD rats were divided randomly into 3 groups: brain injury group( n=24), astragalus membranaceus group( n = 24) and control group( n = 6). Injury and astragalus membranaceus groups were sampled at 4different time points(0.5 hour, 2 hours, 6 hours, and 24 hours) after injury,6 rats were sacrificed at each time point.METHODS: The brain injury and astragalus membranaceus groups were prepared by improved Feeney' s free falling method. Bone windows were opened for the control group, but no brain injury produced. After injury, rats in astragalus membranaceus group were immediately injected 200 mg/kg astragalus membranaceus intraperitoneally rat cerebral injury models were established and the nitric oxide synthetase concentration was tested at different time points.MAIN OUTCOME MEASURES: Activity of nitric oxide synthetase in the brain tissue of rats in each group.RESULTS: All 54 rats entered the final analysis. Nitric oxide synthetase activity in brain injury and astragalus membranaceus groups increased sharply contrasting with control group at 30 minute after injury [ (46.44 ± 13.45),(43.15 ± 12.43), (40. 46 ± 12. 85) nkat/L, P ＜0.05], reaching the peak at 2hours[ (67.49 ± 22.45), (64. 26 ± 19.78) nkat/L, P ＜ 0.01 ], starting to drop from6 hours [(63.46±24. 68), (52.91 ±21.36) nkat/L, P ＜0. 01], and getting to basic level at 24 hours[ (41.23 ± 12. 57), (40.92 ± 12. 25) nkat/L,P ＞ 0.05 ]. In the astragalus membranaceus treated group, nitric oxide synthetase activity dropped at 2 hours and 6 hours after injury contrasting with injury group( P ＜ 0. 05, P ＜ 0. 01 respectively).CONCLUSION: Nitric oxide synthetase activity increases in the injured brain tissue and astragalus membranaceus can protect injured neuron by inhibiting nitric oxide synthetase activity.

Objective: To investigate the effects of complex prescription astragalus mongholicus injection(复方黄芪注射液) on the serum concentrations of neuron-specific enolase(NSE),myelin basic protein(MBP) and S100 protein B(S100B) in cases with acute severe craniocerebral injury.Methods: One hundred and ninety-six patients with acute severe craniocerebral injury were randomly divided into two groups.The treated group was treated with complex prescription astragalus mongholicus injection plus conventional treatments including dehydration,antibiotics,organ functional support,nerve nutrition,prevention of complication,etc;the control group was treated with conventional treatments alone.The concentrations of NSE,MBP and S100B in plasma at admission and at 4,7 and 10 days after treatment were determined;the Glasgow coma score(GCS) at admission and at 1 week and 2 weeks after hospitalization and the Glasgow outcome scale(GOS) after 3 months were compared to observe the long-term efficacy in the patients.Results: After treatment,the concentrations of serum NSE,MBP and S100B in the treatment group were all lower than those in the control group,the differences being significant(NSE(14.62?3.38)?g/L vs.(21.54?5.68) ?g/L,MBP(7.52?1.06) mg/L vs.(10.21?2.01) mg/L,S100B(0.90?0.28) ?g/L vs.(1.20?0.34) ?g/L,all P0.05);the GCSs of the patients at 1 week,2 weeks and GOS at 3 months after treatment in the complex prescription astragalus mongholicus injection group were significantly higher than those in the control group(GCS, 1 week(9.8?2.6)score vs.(7.2?2.1) score,2 weeks(10.6?3.0) score vs.(7.8?2.2) score;GOS,3 months after treatment(4.8?1.0) score vs.(3.6?0.8) score,all P

Objective:To analyze and evaluate the effect of OX40L as a potential adjuvant for H7N9 whole-virion inactivated vaccine (WIV).Methods:Fifty BALB/c mice were randomly divided into five groups and immunized intramuscularly with PBS (control group) and 1.5 μg WIV alone or in combination with 0.6, 1.8 or 3.0 μg Fc-fused OX40L (OX40L/Fc) adjuvant. Three weeks after immunization, IgG, IgG1 and IgG2 titers were measured by ELISA and hemagglutination inhibition (HI) assay. Moreover, the mice were challenged with 50×median lethal dose (LD 50) of homologous virus and the changes in mouse body weight and survival rate were recorded to evaluate the effects of OX40L. Flow cytometry was used to analyze the mechanism of OX40L as an adjuvant 7 d after immunization. Results:Compared with immunization with WIV alone, co-immunization of WIV with OX40L/Fc induced higher antigen-specific IgG in mice. The geometric mean titers (lgGMT) of antibodies induced by 0.6, 1.8 and 3.0 μg OX40L/Fc reached 3.79, 4.40 and 4.20, respectively. WIV combined with OX40L/Fc induced high levels of IgG1 and IgG2a without influencing Th1/Th2 balance. HI antibodies were also higher in WIV+ 1.8 μg OX40L/Fc and WIV+ 3.0 μg OX40L/Fc groups than in WIV group (6.25±0.50 and 5.70±0.97 vs 3.00±0.97, both P<0.05). WIV combined with 1.8 or 3.0 μg OX40L/Fc could protect 80% or 75% of mice against lethal challenge with H7N9 and result in less weight loss as compared with WIV alone. The most effective dose of OX40L/Fc was 1.8 μg. Flow cytometry showed that WIV (0.6, 1.8, 3.0 μg) in combination with OX40L/Fc enhanced the proliferation of T follicular helper cells (Tfh) through promoting the expression of CXCR5 and PD-1 as compared with WIV alone (all P<0.05). Conclusions:This study suggested that OX40L was beneficial to potent antibody responses induced by H7N9 WIV through promoting Tfh cell proliferation.

Objective:To analyze the risk factors for heart failure in patients with hemodialysis, and to construct a nomogram model.Methods:The clinical data of 218 patients with hemodialysis in Xianyang Central Hospital from January 2021 to April 2022 were retrospectively analyzed. Among them, 83 cases developed heart failure (heart failure group), and 135 cases did not develop heart failure (control group). The relevant clinical data were recorded, including age, sex, body mass index, disease duration, concurrent infection, blood calcium, blood phosphorus, soluble CD 146 (sCD 146), soluble growth-stimulated expression gene 2 protein (sST2), N-terminal brain natriuretic peptide precursor (NT-proBNP), time-averaged urea concentration (TACurea), tumor necrosis factor α (TNF-α), blood creatinine and 24 h urine volume. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of each index in predicting heart failure in patients with hemodialysis. Multivariate Logistic regression was used to analyze the independent risk factors of heart failure in patients with hemodialysis. R language software 4.0 "rms" package was used to construct the nomogram model for predicting the heart failure in patients with hemodialysis, the calibration curve was internally validated, and the decision curve was used to evaluate the predictive efficacy of the nomogram model. Results:There were no statistical difference in gender composition, age, body mass index, disease duration, 24 h urine volume and blood creatinine between the two groups ( P>0.05); the rate of concurrent infection, blood phosphorus, sCD 146, sST2, NT-proBNP, TNF-α and TACurea in heart failure group were significantly higher than those in control group: 39.76% (33/83) vs. 8.89% (12/135), (1.53 ± 0.34) mmol/L vs. (1.27 ± 0.24) mmol/L, (43.60 ± 10.24) μmol/L vs. (28.08 ± 7.99) μmol/L, (49.00 ± 9.41) μg/L vs. (34.53 ± 8.05) μg/L, (38.57 ± 6.79) μg/L vs. (29.72 ± 5.64) μg/L, (5.18 ± 0.92) μg/L vs. (4.07 ± 1.13) μg/L and (24.28 ± 4.37) mmol/L vs. (17.96 ± 2.52) mmol/L, the blood calcium was significantly lower than that in control group: (1.95 ± 0.36) mmol/L vs. (2.31 ± 0.39) mmol/L, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the optimal cut-off values of blood calcium, blood phosphorus, sCD 146, sST2, NT-proBNP, TNF-α and TACurea for heart failure in patients with hemodialysis were 2.01 mmol/L, 1.42 mmol/L, 34.15 μmol/L, 40.37 μg/L, 35.37 μg/L, 4.33 μg/L and 20.74 mmol/L. Multivariate Logistic regression analysis result showed that the blood calcium (≤2.01 mmol/L), blood phosphorus (>1.42 mmol/L), sCD 146 (>34.15 μmol/L), sST2 (>40.37 μg/L), NT-proBNP (>35.37 μg/L), TNF-α (>4.33 μg/L) and TACurea (>20.74 mmol/L) were independent risk factors for heart failure in patients with hemodialysis ( OR = 1.183, 1.582, 1.915, 1.105, 1.459, 1.347 and 1.717; 95% CI 1.102 to 1.191, 1.274 to 1.868, 1.716 to 2.105, 1.072 to 1.141, 1.225 to 1.703, 1.132 to 1.574 and 1.482 to 1.935; P<0.05 or <0.01). The blood calcium, blood phosphorus, sCD 146, sST2, NT-proBNP, TNF-α and TACurea were used as predictors to construct a nomogram model for predicting heart failure in patients with hemodialysis. Internal validation result showed that the nomogram model predicted the heart failure with good concordance in patients with hemodialysis (C-index = 0.811, 95% CI 0.675 to 0.948); the nomogram model predicted the heart failure in patients with hemodialysis at a threshold>0.18, provided a net clinical benefit, and all had higher clinical net benefits than blood calcium, blood phosphorus, sCD 146, sST2, NT-proBNP, TNF-α and TACurea. Conclusions:The nomogram model constructed based on blood calcium, blood phosphorus, sCD 146, sST2, NT-proBNP, TNF-α and TACurea has better clinical value in predicting the heart failure in patients with hemodialysis.

Objective To create a recombinant rabies virus overexpressing IL-33 and to clarify the effect of IL-33 overexpression on the phenotypic characteristics of recombinant virus in vitro. Methods The IL-33 gene was obtained and amplified from the brain of a highly virulent strain of rabies infected mouse. It was then inserted between the G and L genes of the parental virus LBNSE genome by reversing genetic manipulation and rescuing a recombinant virus overexpressing IL-33. BSR cells or mouse NA cells were infected with recombinant rabies virus (rLBNSE-IL33) and the parental strain LBNSE. Sequencing and fluorescent antibody virus neutralization assay was employed to detect the stability of recombinant virus at multiplicity of infection=0.01. Viral titres focal forming units (FFU) were detected to plot multi-step growth curves (multiplicity of infection=0.01). Cytotoxicity assay kit was used to detect cellular activity. ELISA was adopted to identify the IL-33 in the supernatant of infected cells of different multiplicity of infection. Results Rescued rLBNSE-IL33 overexpressing IL-33 remained stable for at least 10 consecutive generations and had virus titers of approximately 10⁸ FFU/mL. rLBNSE-IL33 was able to express IL-33 at high levels in a dose-dependent manner, but no high expression of IL-33 was detected in the supernatant of cells infected by LBNSE. Examination of the titers of rLBNSE-IL33 and the parental strain LBNSE in BSR and NA cells over 5 days showed no significant differences and similar kinetic properties in growth. Overexpression of IL-33 had no significant effect on the proliferation and activity of infected cells. Conclusion Overexpression of IL-33 does not significantly affect the phenotypic characteristics of recombinant rabies virus in vitro.
Animals ; Cricetinae ; Mice ; Cell Line ; Interleukin-33/genetics* ; Rabies virus/genetics* ; Phenotype

Pleural mesothelioma （PM） is a rare malignant tumor originating from the pleura. Most patients are already in the advanced stage at the time of diagnosis， resulting in a low overall survival rate. MicroRNA （miRNA）， as key regulators of tumor epigenetic modification， have an intertwined interactive network with PM drug resistance. The mechanisms of drug resistance in PM to chemotherapeutic drugs include increasing drug efflux， reducing drug intake， enhancing DNA repair， and altering drug targets. The mechanisms of resistance to targeted therapy drugs include activating alternative signaling pathways， establishing a favorable tumor microenvironment， and triggering epithelial-mesenchymal transition. MiRNA plays a key part in the aforementioned resistance mechanisms， with some miRNAs promoting the drug sensitivity of cancer cells， while others contribute to increased drug resistance. In light of these key regulatory functions， targeting the dysregulated expression of endogenous miRNAs in the process of resistance formation using miRNA antagonists or miRNA mimics may be an effective therapeutic strategy to reverse drug resistance in PM.