OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

【Objective】 To compare the risk of generalization in patients with ocular myasthenia gravis (OMG) receiving or not receiving immunosuppressive treatment. 【Methods】 The data of patients with OMG registered in Tangdu Hospital of Air Force Military Medical University from January 1, 2015 to May 1, 2019 were reviewed; the patients were divided into treatment group and control group according to whether they had received immunosuppressive treatment. The multivariate Cox proportional hazards regression model analysis was used to compare the risk of generalization between the two groups of patients within 2 years of onset. Sensitivity analysis was used to evaluate the duration of immunosuppressive treatment and the risk of generalization under different immunotherapy regimens. By using stratified analysis, the consistency of the main results across different levels of subgroup factors was evaluated. 【Results】 A total of 702 OMG patients were collected. Of them 367 patients (52.3%) were included in the treatment group, with an average onset age of (50.54±15.1) years, and 159 (43.3%) being female. Another 335 patients (47.7%) were included in the control group, with an average age of (49.1±14.6) years, and 159 ones (47.5%) were female. A total of 28 cases (7.7%) in the treatment group and 106 cases (31.6%) in the control group developed generalization during the observation period. After multivariate-adjusted Cox model analysis, patients who had received immunosuppressive treatment had a significantly lower risk of generalization compared with the control group (HR=0.24; 95% CI: 0.15-0.37; P<0.001). Sensitivity analysis found that the longer the duration of immunosuppression, the lower the risk of generalization (HR=0.88; 95% CI: 0.85-0.91; P<0.001). Stratified analysis showed that immunosuppressive therapy reduced the risk of generalization in different subgroups of patients. 【Conclusion】 Early immunosuppressive treatment can significantly reduce the risk of generalization in patients with OMG.

Objective To investigate the effects of DNA demethylation drugs combined with histone deacetylase in-hibitors on fragile X mental retardation 1 neighbor protein (FMR1NB) expression and its promoter methylation in human oral cancer cells and try to find a strategy of weakening the heterogeneity of FMR1NB expression.Methods Human oral cancer cell lines Cal27 and SCC-9 were treated with decitabine (DAC) , an inhibitor of DNA meth-yltransferase, combined with trichostatin A (TSA) and valproic acid (VPA), inhibitors of histone deacetylase.Then reverse transcription-polymerase chain reaction (RT-PCR) , quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of FMR1 NB and pyrosequencing was used to detect the methylation of FMR1NB promoter.Results Compared with the blank control group, DAC and its combination with TSA and VPA significantly induced the expression of FMR1NB mRNA and protein in Cal27 and SCC-9 cells.Compared with DAC alone group, FMR1NB mRNA expression of each DAC-combined drug groups significantly increased, but FMR1NB protein did not significantly change in Cal27 cells; for SCC-9 cells, except for DAC+TSA group, the mRNA and protein levels of FMR1NB significantly increased in all other groups.In addition, there was no signifi-cant difference in the expression of FMR1 NB mRNA and protein between the three-combined drugs group and two-combined drugs groups.Further methylation assay showed that the methylation level of the overall FMR1NB promot-er and its each CpG site measured were reduced to varying degrees in all treatment groups except for three-combina-tion drug group of SCC-9.Conclusion DAC and its combination with TSA and VPA can enhance the expression of FMR1NB by mediating the demethylation of FMR1NB promoter, wherein the enhanced expression effect of the com-bination of the two drugs is stronger, suggesting that they have the potential to weaken the heterogeneity of FMR1NB expression and improve the immunotherapy effect of oral cancer.

Objective To compare the biomechanical stability of three cross-bridge headless compression screws and lock-ing plates in the fixation of Mason type Ⅲ radial head fractures by finite element method.Methods Using reverse modeling technology,the radial CT data and internal fixation data of a healthy 25-year-old male were imported into the relevant software.Three-dimensional finite element model of 3 cross-bridge headless compression screws and locking plates for Mason Ⅲ radial head fractures were established,and the radial head was loaded with 100 N axial loading.The maximum displacement,maxi-mum Von Mises stress and stress distribution of the two groups were compared.Results The maximum displacements of the three cross-bridge screws group and locking plate group were 0.069 mm and 0.087 mm respectively,and the Von Mises stress peaks were 18.59 MPa and 31.85 MPa respectively.The stress distribution of the three screws group was more uniform.Con-clusion Both internal fixation methods can provide good fixation effect.CoMPared with the locking plate fixation method,the 3 cross-bridge headless compression screws fixation is more stable and the stress distribution is more uniform.

Objective:To study the clinical characteristics and management strategies of patients with chronic obstructive pulmonary disease (COPD) in high-altitude areas.Methods:An observational cross-sectional study was conducted in 79 stable COPD patients who visited the outpatient of Respiratory Medicine at Tibet Autonomous Region People′s Hospital and Peking University Third Hospital from August 3 rd 2020 to November 30 th 2020. Patients were divided into Lhasa group ( n=44) and Beijing group ( n=35). The differences of clinical characteristics including demographic characteristics, risk factors, respiratory symptoms, comorbidities, medications and spirometry were analyzed. Further comparative analysis was conducted on the clinical characteristics of smokers ( n=15) and non-smokers ( n=29) in Lhasa group. Results:The proportion of female patients and biofuel exposure in Lhasa group was significantly higher than Beijing group (56.8% vs 0, 86.4% vs 0, both P<0.001). The proportion of smokers in Lhasa group was significantly lower than Beijing group (34.1% vs 100%, P<0.001). The mean score of COPD assessment test (CAT) in Lhasa group was significantly higher than Beijing group (21.27 vs 9.17, P<0.001). The proportion of acute exacerbations ≥2 in the past year in Lhasa group was significantly higher than Beijing group (31.8% vs 11.4%, P=0.032). The median percentage of forced vital capacity in the first second of predicted value (FEV 1%pred) of patients in Lhasa group was significantly higher than Beijing group (63% vs 38%, P<0.001). The proportion of patients treated by inhaled corticosteroid/long-acting β 2-agonist (ICS/LABA) and inhaled long-acting muscarinic antagonists (LAMA) in Lhasa group was significantly lower than Beijing group (4.5% vs 60.0%, 0 vs 65.7%, both P<0.001). There were no significant differences in CAT score, number of acute exacerbations in the past year and lung function between smokers and non-smokers in Lhasa group. Conclusions:Compared with those patients in Beijing, the majority of patients with COPD living in Lhasa are female, with a low proportion of smokers and a high proportion of biofuel exposure. Although their lung function is better, their respiratory symptoms are more severe with more acute exacerbations in the past year, and most patients do not receive standardized medication.

Objective:To investigate the therapeutic effect difference between first-line treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) and chemotherapy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) rare mutation.Methods:A retrospective case-control study was performed. Data of NSCLC patients with rare EGFR mutation who were treated in Shanxi Province Cancer Hospital from January 2013 to October 2019 were retrospectively analyzed. EGFR mutations in living tissues or blood were detected by using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) before first-line treatment. According to first-line treatment methods,they were divided into EGFR-TKI treatment group and chemotherapy group. Objective remission rate (ORR) and disease control rate (DCR) of both groups were compared. Kaplan-Meier method was used to draw progression-free survival (PFS) and the overall survival (OS) curves. Log-rank test was used for comparison among groups. Single-factor and multi-factor Cox proportional risk models were used to analyze the influencing factors of PFS and OS.Results:A total of 169 patients with EGFR rare mutations were included, and the age [ M (IQR)] was 63 years (12 years); there were 96 cases (56.8%) < 65 years and 73 cases (43.2%) ≥65 years; 70 (41.4%)males and 99 (58.6%) females; 55 cases (32.5%) had EGFR G719X mutation,45 cases (26.6%) had L861Q mutation, 17 cases (10.1%) had S768I mutation, and 52 cases (30.8%) had complex mutation; 55 cases (32.5%) received the first-line chemotherapy and 114 cases (67.5%) received the first-line EGFR-TKI treatment. In the chemotherapy group, ORR was 36.4% (20/55) and DCR was 85.5% (47/55); in EGFR-TKI treatment group, ORR was 72.8% (83/114) and DCR was 90.4% (103/114). The ORR of EGFR-TKI treatment group was higher than that of chemotherapy group ( χ2 = 20.70, P = 0.001), and there was no statistically significant difference in DCR between two groups ( χ2 = 1.76, P = 0.184). Subgroup analysis showed that ORR in EGFR-TKI treatment group with G719X, L861Q and complex mutations was higher than that of the corresponding mutations in chemotherapy group, and the differences were statistically significant (all P < 0.05), while there were no significant differences in DCR among subgroups (all P > 0.05). The median PFS time was 9.7 months (95% CI: 6.0-13.4 months) and 3.8 months (95% CI: 3.1-7.1 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was a statistically significant difference in PFS between the two groups ( P < 0.001). The median OS time was 25.6 months (95% CI: 18.0-37.9 months) and 31.7 months (95% CI: 18.0-42.8 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was no statistically significant difference in OS between the two groups ( P = 0.231). Multivariate Cox regression analysis showed that brain metastasis [with vs. without: HR = 2.306, 95% CI: 1.452-3.661, P < 0.001] and the first-line treatment methods (EGFR-TKI vs. chemotherapy: HR = 0.457, 95% CI:0.317-0.658, P < 0.001) were independent influencing factors for PFS of NSCLC patients with EGFR rare mutation; brain metastasis (with vs. without: HR = 2.087, 95% CI: 1.102-3.953, P = 0.024; unknown vs. without: HR = 2.118,95% CI: 1.274-3.520, P = 0.004) were independent influencing factors for OS of NSCLC patients with EGFR rare mutation. Conclusions:Compared with the first-line chemotherapy, EGFR-TKI first-line treatment could improve objective remission and PFS of NSCLC patients with EGFR rare mutation, while no OS benefit is observed.

Objective:Based on the investigation on the advantages of Traditional Chinese Medicine(TCM)participation in the field of basic public health services,exploring how TCM participates in public health.Methods:It searched for policies related to basic public health services and conducted a questionnaire survey on 2 995 people working in public health-related jobs in Beijing to conduct an empirical study on the advantages of Chinese medicine and the current status of participation.Results:2 982 valid questionnaires were collected,and practitioners in the field of public health services in Beijing had a high level of attention and recognition towards the participation of TCM.TCM is generally considered to have obvious advantages in basic public health services such as responding to epidemics,preventing and treating chronic diseases,and managing the health of Children 0-6 Years and the elderly.However,TCM shows overall shortcomings in emphasis,talent allocation,infrastructure construction,public perception and resource balance.Conclusion:To play the ascendant role and enhance the service capacity of TCM,basic public health services can be further developed by optimizing mechanisms related to the participation of TCM in disease prevention and control,chronic disease management,children's,and elderly health management.Basic public health services can enhance the service capacity of TCM from several aspects such as increasing financial support,strengthening the cultivation and management of TCM talents,and emphasizing grassroots and balanced resource allocation of TCM.

Objective:Based on the investigation on the advantages of Traditional Chinese Medicine(TCM)participation in the field of basic public health services,exploring how TCM participates in public health.Methods:It searched for policies related to basic public health services and conducted a questionnaire survey on 2 995 people working in public health-related jobs in Beijing to conduct an empirical study on the advantages of Chinese medicine and the current status of participation.Results:2 982 valid questionnaires were collected,and practitioners in the field of public health services in Beijing had a high level of attention and recognition towards the participation of TCM.TCM is generally considered to have obvious advantages in basic public health services such as responding to epidemics,preventing and treating chronic diseases,and managing the health of Children 0-6 Years and the elderly.However,TCM shows overall shortcomings in emphasis,talent allocation,infrastructure construction,public perception and resource balance.Conclusion:To play the ascendant role and enhance the service capacity of TCM,basic public health services can be further developed by optimizing mechanisms related to the participation of TCM in disease prevention and control,chronic disease management,children's,and elderly health management.Basic public health services can enhance the service capacity of TCM from several aspects such as increasing financial support,strengthening the cultivation and management of TCM talents,and emphasizing grassroots and balanced resource allocation of TCM.

Objective:Based on the investigation on the advantages of Traditional Chinese Medicine(TCM)participation in the field of basic public health services,exploring how TCM participates in public health.Methods:It searched for policies related to basic public health services and conducted a questionnaire survey on 2 995 people working in public health-related jobs in Beijing to conduct an empirical study on the advantages of Chinese medicine and the current status of participation.Results:2 982 valid questionnaires were collected,and practitioners in the field of public health services in Beijing had a high level of attention and recognition towards the participation of TCM.TCM is generally considered to have obvious advantages in basic public health services such as responding to epidemics,preventing and treating chronic diseases,and managing the health of Children 0-6 Years and the elderly.However,TCM shows overall shortcomings in emphasis,talent allocation,infrastructure construction,public perception and resource balance.Conclusion:To play the ascendant role and enhance the service capacity of TCM,basic public health services can be further developed by optimizing mechanisms related to the participation of TCM in disease prevention and control,chronic disease management,children's,and elderly health management.Basic public health services can enhance the service capacity of TCM from several aspects such as increasing financial support,strengthening the cultivation and management of TCM talents,and emphasizing grassroots and balanced resource allocation of TCM.