Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

BACKGROUND:In the initial stage of multiple sclerosis,central immune cells activate and release a large number of inflammatory factors,causing white matter demyelination and even involving gray matter neurons.The equilibrium of differentiation between different subsets of CD4+ T cells plays an important role in the progression of experimental autoimmune encephalomyelitis.The previous results of the research group showed that the active ingredient astragalus glycoprotein in astragalus can regulate the immune response in experimental autoimmune encephalomyelitis mice,and whether it has a regulatory effect on the differentiation of T cell subsets has not been determined. OBJECTIVE:To explore the therapeutic effects and immune regulatory mechanisms of astragaloside IV on experimental autoimmune encephalomyelitis mice. METHODS:Female C57BL/6 mice were divided into the normal control group,experimental autoimmune encephalomyelitis disease model group,and astragaloside IV treatment group(n=8 per group).Myelin oligodendrocyte glycoprotein peptides 35-55 were used for experimental autoimmune encephalomyelitis model induction in the last two groups.On day 10 to 28 after immunization,the astragaloside IV treatment group was treated with 40 mg/kg per day astragaloside IV intragastrically.Body weight and clinical scores of mice in each group were recorded from the immunization day to the 28th day.On the 28th day after immunization,the mouse spinal cord was taken and made into frozen sections for hematoxylin-eosin staining and Lux fast blue staining to observe pathological changes in the spinal cord.Percentage of splenic T cell subsets was detected using flow cytometry.Western blot assay was used to determine the protein expression of interferon-γ,interleukin-17 and interleukin-6 in the spinal cord.Levels of interferon-γ,interleukin-17,interleukin-6 and interleukin-4 in supernatants of cultured splenocytes were determined by ELISA. RESULTS AND CONCLUSION:(1)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could reduce the degree of weight loss in experimental autoimmune encephalomyelitis mice(P<0.05),ameliorate clinical symptoms(P<0.05),inhibit the infiltration of inflammatory cells and alleviate myelin loss(P<0.01,P<0.05).(2)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could inhibit the proportion of CD4+T cell subsets expressing interferon-γ(P<0.001)and interleukin-17(P<0.001),but increase percentages of CD4+ interleukin-10+(P<0.001)and CD4+ transforming growth factor-β+(P<0.01)T cell subsets.(3)Astragaloside IV could inhibit the expression of interferon-γ(P<0.05,P<0.01),interleukin-17(P<0.05,P<0.05),and interleukin-6(P<0.05,P<0.05)in the spinal cord and spleen,and up-regulate the expression of interleukin-4(P<0.01)in spleen.(4)These findings confirm that astragaloside IV alleviates clinical symptoms in experimental autoimmune encephalomyelitis mice,which may be related to regulating the splenic T cell subsets,therefore,inhibiting the infiltration of inflammatory cells into the center and reducing the demyelination.

OBJECTIVE To explore the independent risk factors of voriconazole （VCZ）-related liver injury in elderly patients with hypoproteinemia. METHODS Elderly patients with invasive fungal infection and hypoproteinemia who were hospitalized in the respiratory intensive care unit of our hospital and treated with VCZ from August 2020 to July 2023 were selected. They were divided into group A （liver injury group） and group B （non-liver injury group） based on whether the liver injury occurred after using VCZ. Pearson correlation analysis was used to analyze the correlation between minimum concentration （cmin） of VCZ and inflammatory factor[C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）]， as well as liver function [alanine transaminase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBIL）]； univariate analysis was performed by using χ 2 test； Logistic regression analysis was used to analyze the independent risk factors affecting the occurrence of liver injury. RESULTS A total of 320 patients were included in the study， of whom 56 developed liver injury， with an incidence of 17.50%. The VCZ cmin in group A was significantly higher than group B （P＝ 0.021）. CRP， PCT， IL-6， and TBIL were correlated with VCZ cmin （P＜0.05）. CRP， PCT， IL-6， and TBIL had a significant impact on VCZ cmin （P＜0.05）. VCZ cmin， PCT， and TBIL were independent risk factors for liver injury （P＜0.05）. The patients with VCZ cmin≥3.76 mg/L had a significantly increased risk of liver injury. CONCLUSIONS VCZ cmin， PCT， and TBIL are independent risk factors for the occurrence of liver injury in elderly patients with hypoproteinemia. For patients with high PCT and TBIL， VCZ cmin and liver function should be closely monitored during VCZ treatment to reduce the risk of liver injury.

BACKGROUND:Astrocytes play an important role in the pathology of central nervous system diseases.The phenotypic and functional changes in astrocytes suggest that it may be an effective therapeutic target for central nervous system diseases.Our previous studies have confirmed that astragaloside can inhibit the lipopolysaccharide-induced astrocyte inflammatory response.Whether astragaloside can regulate the phenotype and function of astrocytes through Notch-1 and its downstream signaling pathway remains unclear. OBJECTIVE:To explore the effect of astragaloside on astrocyte activation and inflammatory response induced by inflammation and its possible mechanism. METHODS:Cerebral cortex astrocytes derived from neonatal C57BL/6 mouse were cultured in vitro.CCK-8 assay was used to determine the optimum concentration of astragaloside and Notch active inhibitor DAPT.The astrocytes were divided into five groups:PBS group,lipopolysaccharide group,lipopolysaccharide + astragaloside group,lipopolysaccharide + DAPT group and lipopolysaccharide + DAPT + astragaloside group.The secretion level of inflammatory factors was detected by ELISA,and the level of nitric oxide was detected by Griess method.The astrocytes and splenic mononuclear cells were co-cultured in Transwell chamber to observe the migration of CD4T cells.The expression of astrocyte activation marker GFAP,A1 marker C3 and A2 marker S100A10 as well as Notch 1 and Jag-1 was detected by immunofluorescence staining.The expressions of CFB,C3,S100A10,PTX3,Notch-1,Jag-1,and Hes were detected by western blot assay. RESULTS AND CONCLUSION:(1)According to the results of CCK8 assay,the final concentration of astragaloside was selected as 25 μmol/L and the final concentration of DAPT was 50 μmol/L for follow-up experiments.(2)Compared with PBS group,interleukin-6,interleukin-12 and nitric oxide secretion levels in the lipopolysaccharide group were significantly increased(P<0.05,P<0.05,P<0.01).Compared with the lipopolysaccharide group,interleukin-6(all P<0.05),interleukin-12(P>0.05,P<0.05,P<0.05)and nitric oxide(P<0.05,P<0.01,P<0.01)secretion significantly reduced in the lipopolysaccharide + astragaloside group,lipopolysaccharide +DAPT group,lipopolysaccharide + DAPT + astragaloside group.(3)Compared with the PBS group,the expression of GFAP that is the marker of activated astrocytes and the migration of CD4 T cells were significantly increased in the lipopolysaccharide group(P<0.01).Compared with the lipopolysaccharide group,astrocyte activation was significantly inhibited and CD4 T cell migration was significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group(P<0.05,P<0.05,P<0.01).(4)Compared with the PBS group,the expressions of A1 markers C3 and CFB in the lipopolysaccharide group were increased(P<0.01,P<0.05),and the expressions of A2 markers S100A10 and PTX3 were decreased(P<0.01,P<0.05).Compared with the lipopolysaccharide group,C3(all P<0.01)and CFB(both P<0.05)were significantly reduced and S100A10(all P<0.01)and PTX3(P<0.05,P<0.05 and P>0.05)were increased in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(5)Compared with the PBS group,the expressions of Jag-1,Notch-1 and Hes in the lipopolysaccharide group were significantly increased(all P<0.01).Compared with the lipopolysaccharide group,the expressions of Jag-1(all P<0.01),Notch-1(all P<0.01)and Hes(P<0.05,P<0.01 and P<0.01)were significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(6)The results indicate that astragaloside can promote the transformation of astrocytes from A1 to A2 by regulating Notch-1 signaling pathway,reduce the secretion of inflammatory factors and the migration of CD4 T cells,and thus inhibit astrocyte activation and inflammatory response.

Objective To observe the value of transesophageal echocardiography(TEE)for guiding left atrial appendage closure(LAAC)with LAmbre occluder.Methods Data of 40 non-valvular atrial fibrillation(NVAF)patients who underwent LA AC with LAmbre occluder were retrospectively analyzed.CT angiography(CTA)before treatment,TEE and digital subtraction angiography(DSA)findings during LAAC were comparatively observed,and the correlations of the anchor area diameter and left atrial appendage opening diameter measured with the above three as well as occluder size were analyzed,and TEE and DSA for evaluating peri-device leak(PDL)were compared.Results LAAC were successfully performed with LAmbre occlude in all 40 cases.The diameter of the fixed umbrella was positively correlated with anchor area diameter measured with CTA,TEE and DSA(r=0.79,0.82,0.91,all P＜0.01),of occlusion umbrella was positively correlated with left atrial appendage opening diameter measured with CTA,TEE and DSA(r=0.56,0.89,0.86,all P＜0.01).Immediately after the release of occluder in LAAC,PDL occurred in 16 cases and were detected with both TEE and DSA,while in the rest 24 cases no PDL was found with neither TEE nor DSA.Conclusion TEE had comparable value to DSA for guiding LAAC using LAmbre occluder.

Objective: To explore the intervention effect of different intensity of classroom physical exercise on cardiorespiratory fitness and executive function of Tibetan first grade students at high altitude, so as to provide reference for improving the level of cardiorespiratory fitness and executive function of Tibetan adolescents. Methods: From September to December 2020, 184 Tibetan students from five first grade classes in a middle school in Lhasa, Tibet, were randomly assigned into a control group (81 students in two classes) and an intervention group (103 students in three classes). Both groups followed the same teaching programme, but the intervention group received 36 sessions of moderate to high intensity classroom physical activity, one session per day, Monday,Wednesday and Friday, for 12 weeks. Before and after the intervention, cardiorespiratory fitness and executive function were tested by 20m round trip running and Flanker s experimental paradigm, 2-back s experimental paradigm, and More odd shifting experimental paradigm for inhibitory control, refreshing memory, and switching flexibility, and the results were analysed by analysis of covariance (ANCOVA) to compare the results of the pre and post intervention periods. Results: The maximum oxygen uptake (VO 2max ) of Tibetan first grade students in the intervention group increased by 2.25 mL/(kg〖WW）〗·〖WW(〗min) compared with the control group after the intervention ( t =-3.89, P <0.01); the response time of the inhibitory function was reduced by 4.40 ms, that of the refreshing function by 196.06 ms, and that of the switching function by 92.72 ms in the intervention group compared with the control group ( t =2.98, 4.82 ,3.21, P <0.05). Conclusion The 12 week moderate to high intensity classroom physical activity intervention has different degrees of improvement effects on cardiorespiratory fitness and executive function in Tibetan adolescents.

Objective:To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) .Methods:From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis.Results:①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five na?ve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days vs 228 days, P<0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . Conclusions:There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Objective:To explore mechanism of Fasudil reducing Aβ1-42 induced BV2 cell injury based on NLRP3 inflamma-some.Methods:BV2 cells were divided into:normal control group,Aβ stimulation group,Aβ+Fasudil intervention group,Aβ+MCC950(NLRP3 inhibitor)intervention group.Cell morphology was observed under microscope.Cell activity was determined of by CCK8.NO release was measured by Griess.NLRP3,caspase 1 and IL-18 expressions were detected by immunofluorescence staining.NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were detected by Western blot.Results:Compared with normal control group,BV2 cells in Aβ stimulation group were activated and showed amoeba-like shape,cell activity was decreased,NO production was increased,NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were increased.Fasudil intervention and MCC950 intervention inhibited cell injury induced by Aβ1-42 in which BV2 cell morphology tended to be normal,cell activity was increased,while produc-tion of NO was reduced,and NLRP3,ASC,caspase 1,IL-1β and IL-18 expressions were down-regulated,there was no significant difference between Fasudil intervention group and MCC950 intervention group.Conclusion:Fasudil may alleviate Aβ1-42 induced BV2 cell injury and inflammatory reaction by inhibiting NLRP3 inflammasome activation.

BACKGROUND: Tri-ponderal mass index (TMI) has been reported to be a more accurate estimate of body fat than body mass index (BMI). This study aims to compare the effectiveness of TMI and BMI in identifying hypertension, dyslipidemia, impaired fasting glucose (IFG), abdominal obesity, and clustered cardio-metabolic risk factors (CMRFs) in 3- to 17-year-old children. METHODS: A total of 1587 children aged 3 to 17 years were included. Logistic regression was used to evaluate correlations between BMI and TMI. Area under the curves (AUCs) were used to compare discriminative capability among indicators. BMI was converted to BMI- z scores, and accuracy was compared by false-positive rate, false-negative rate, and total misclassification rate. RESULTS: Among children aged 3 to 17 years, the mean TMI was 13.57 ± 2.50 kg/m 3 for boys and 13.3 ± 2.33 kg/m 3 for girls. Odds ratios (ORs) of TMI for hypertension, dyslipidemia, abdominal obesity, and clustered CMRFs ranged from 1.13 to 3.15, higher than BMI, whose ORs ranged from 1.08 to 2.98. AUCs showed similar ability of TMI (AUC: 0.83) and BMI (AUC: 0.85) in identifying clustered CMRFs. For abdominal obesity and hypertension, the AUC of TMI was 0.92 and 0.64, respectively, which was significantly better than that of BMI, 0.85 and 0.61. AUCs of TMI for dyslipidemia and IFG were 0.58 and 0.49. When 85th and 95th of TMI were set as thresholds, total misclassification rates of TMI for clustered CMRFs ranged from 6.5% to 16.4%, which was not significantly different from that of BMI- z scores standardized according to World Health Organization criteria. CONCLUSIONS TMI was found to have equal or even better effectiveness in comparison with BMI in identifying hypertension, abdominal obesity, and clustered CMRFs TMI was more stable than BMI in 3- to 17-year-old children, while it failed to identify dyslipidemia and IFG. It is worth considering the use of TMI for screening CMRFs in children and adolescents.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Body Mass Index ; Dyslipidemias ; East Asian People ; Hypertension ; Obesity, Abdominal ; Pediatric Obesity/diagnosis* ; Cardiometabolic Risk Factors