Objective To investigate the effect of Ophiopogonin D on lipopolysaccharide(LPS)-induced apoptosis of alveolar epithelial cells by regulating the interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods A549 AT Ⅱ cells cultured in vitro were randomly divided into four groups:control group,LPS group,LPS+Ophiopogonin D group,LPS+Ophiopogonin D+colivelin(JAK2/STAT3 signal activator)group,except for the control group,and cells in all other groups were established injury models while being grouped with Ophiopogonin D and colivelin for treatment.Cell counting kit-8(CCK-8)experiment and flow cytometry were applied to detect cell proliferation and apoptosis in each group;Western blotting was applied to detect the expression of IL-6/JAK2/STAT3 signaling pathway proteins of cells in each group.Results The apoptosis rates of A549 cells in control group,LPS group,LPS+Ophiopogonin D group and LPS+Ophiopogonin D+colivelin group were(2.52±0.73)％,(52.43±4.14)％,(1.67±0.52)％and(47.94±3.43)％;IL-6 protein levels were 0.14±0.03,0.49±0.05,0.17±0.04 and 0.45±0.06,and p-JAK2/JAK2 protein levels were 0.17±0.04,0.64±0.08,0.19±0.06 and 0.61±0.07;p-STAT3/STAT3 protein levels were 0.20±0.06,0.69±0.10,0.22±0.07 and 0.65±0.09;the apoptosis rates of AT Ⅱ cells were(3.01±0.69)％,(55.16±3.94)％,(2.35±0.71)％and(50.28±3.78)％;the levels of IL-6 protein were 0.11±0.03,0.87±0.13,0.19±0.04 and 0.84±0.12;the p-JAK2/JAK2 protein levels were 0.13±0.04,0.56±0.08,0.15±0.03 and 0.53±0.07;p-STAT3/STAT3 protein levels were 0.30±0.08,0.79±0.14,0.33±0.09 and 0.75±0.13.The above indexes:control group,LPS+Ophiopogonin D group compared with LPS group,LPS+Ophiopogonin D+colivelin group compared with LPS+Ophiopogonin D group,the differences were statistically significant(all P＜0.05).Conclusion Ophiopogonin D can reduce LPS induced inflammation and oxidative stress levels by inhibiting the activation of IL-6/JAK2/STAT3 signaling pathway,ultimately reducing LPS-induced apoptosis of alveolar epithelial cells.

Depressive disorder is manifested as emotional and physical abnormality. Theoretically, the governor vessel is distributed along the spine, related to the brain and communicated with five zang and six fu organs. It is the key meridian for understanding the various symptoms of depressive disorder. Depressive disorder is caused by dysfunction, stagnation or emptiness of the governor vessel, resulting in malnutrition of the brain. In clinical diagnosis and treatment, based on the theory of the governor vessel, the etiology and pathogenesis are analyzed in the patients with depressive disorder. In order to achieve harmonizing mutually the mental and physical conditions, acupuncture is delivered to adjust the spirit and physical state, moving cupping is to regulate the governor vessel, tuina manipulation is to promote meridians and collaterals and physical exercise is to coordinate the body and the spirit.
Humans ; Acupuncture Therapy/methods* ; Meridians ; Acupuncture ; Brain ; Depressive Disorder ; Acupuncture Points

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Objective: To investigate the acute and long-term outcome of catheter ablation for the treatment of ventricular tachycardia (VT) in patients with arrhythmogenic left ventricular cardiomyopathy (ALVC). Methods: This retrospective, cross-sectional study enrolled ALVC patients undergoing radiofrequency ablation for the treatment of VT at the First Affiliated Hospital of Nanjing Medical University from January 2011 to December 2018 and collected their clinical characteristics and intraoperative electrophysiological examination. Patients were followed up every 6 months after radiofrequency ablation until August 2021. Echocardiographic results and VT recurrence post radiofrequency ablation were analysed. Results: Totally 12 patients were enrolled (mean age: (42±15) years, 11 males(11/12)). The mean of left ventricular end diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) were (51±5)mm and (65±5)%, respectively. Twelve VTs were induced in 10 patients during the electrophysiological study, and the mean tachycardia cycle length was (293±65) ms. Three-dimensional substrate mapping revealed the diseased area at endocardial site in one patient, at epicardial sites in the other 11 patients (involved endocardial sites in 2 cases) with the basal part near the mitral annulus being the predilection for the substrate (10/11). After the catheter ablation at the endocardial and epicardial sites respectively, the complete procedure endpoint was achieved in all patients (VT cannot be induced post ablation). The median follow-up time was 65 (25, 123) months. One patient was lost to follow-up, and the other 11 patients survived without VT. No significant cardiac function deterioration was detected by the echocardiographic examination ((51±5)mm vs. (52±5)mm, P>0.05 for LVDd, (65±5)% vs. (60±6)%, P>0.05 for LVEF) at the end of follow-up. Conclusion: After radiofrequency ablation, the complete procedure endpoint is achieved in ALVC patients, and the catheter ablation provides long-term ventricular tachycardia control during the long-term follow-up.
Adult ; Cardiomyopathies ; Catheter Ablation ; Cross-Sectional Studies ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pericardium/surgery* ; Recurrence ; Retrospective Studies ; Stroke Volume ; Tachycardia, Ventricular/surgery* ; Treatment Outcome ; Ventricular Function, Left

OBJECTIVE: To explore the mechanism of F.nucleatum-induced pyroptosis in macrophages and the regulatory role of inflammasomes. METHODS: Lactate dehydrogenase (LDH) cytotoxicity assay and Hoechst 33342/PI double fluorescence staining were used to analyze cytolysis in F.nucleatum-infected macrophage RAW264.7 cells.The expressions of pyroptosis-related proteins caspase-1, GSDMD and IL-1β were determined using Western blotting.Inflammasome activation in the cells was analyzed by detecting the mRNA expressions of NLRP3, NLRC4, AIM2, and NLRP1 with qRT-PCR.RNA interference technique was used to knock down the key molecules involved in pyroptosis regulation in the macrophages, and the pyroptosis and necrosis rates of the cells following F.nucleatum infection were examined. RESULTS: The results of LDH cytotoxicity assay and double-fluorescence staining showed that F.nucleatum infection caused swelling and lytic cell death in RAW264.7 cells.F.nucleatum infection resulted in the activation of caspase-1 and GSDMD and upregulated IL-1β expression in a multiplicity of infection (MOI)-and time-dependent manner (P < 0.05).qRT-PCR revealed significantly increased expression of NLRC4 mRNA in the macrophages after F.nucleatum infection (P < 0.05).NLRC4 silencing by siRNA strongly inhibited the activation of caspase-1/GSDMD pathway and reduced cell death (P < 0.05) and IL-1β expression in F.nucleatum-infected cells. CONCLUSION NLRC4 inflammasome drives caspase-1/GSDMD-mediated pyroptosis and inflammatory signaling in F.nucleatum-infected macrophages, suggesting the potential of NLRC4 inflammasome as a therapeutic target for F.nucleatum infections.
Pyroptosis/genetics* ; Inflammasomes/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Macrophages/metabolism* ; RNA, Messenger/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*

OBJECTIVE: To investigate the effect and mechanism of acupoint injection with 0.1% vitamin C+vitamin B complex solution (V_C+V_BCo) at "Tiantu" (CV 22), "Quchi" (LI 11) and "Zusanli" (ST 36) in mouse model of pneumonia induced by influenza A virus (A/PR/8/34 [H1N1], PR8). METHODS: Sixty male ICR mice were randomized into 6 groups, i.e. control group, model group, acupoint injection group, intraperitoneal injection group, non-target point group and ribavirin group, 10 mice in each one. Except the control group, the pneumonia models were induced by slow nasal dripping PR8 virus in the other groups. On the 2nd day of experiment, V_C+V_BCo solution, 40 μL was injected at "Tiantu" (CV 22), "Quchi" (LI 11, left) and "Zusanli" (ST 36, left) in the acupoint injection group; V_C+V_BCo solution, 120 μL was injected intraperitoneally in the intraperitoneal injection group; V_C+V_BCo solution, 40 μL was injected at non-target acupoints (0.5 cm away from "Tiantu" [CV 22] to the left side, "Quchi" [LI 11, left] and "Zusanli" [ST 36, left]) in the non-target point group; and ribavirin solution, 120 μL was injected intraperitoneally in the ribavirin group. The intervention was delivered once daily, for consecutive 7 days. Three parallel experiments were undertaken. The mean death rate and survival time were assessed in each group, the body mass and lung index were compared among groups. Using HE staining, the morphology of lung tissue was observed; and with real-time fluorescence quantitative PCR, viral load in lung tissue was detected. The concentrations of inflammatory factors (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, IL-10) were detected in lung tissue of each group using ELISA; and those of oxidative stress markers (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], malondialdehyde [MDA]) were detected with chemiluminescence method. RESULTS: Compared with the control group, the body mass was decreased and lung index was increased in the model group (P<0.01). In comparison with the model group, body mass was increased in the acupoint injection group (P<0.05), lung index was reduced in the acupoint injection group the and ribavirin group (P<0.05); the mean death rate was decreased and the mean survival time prolonged in the mice of the acupoint injection group (P<0.01, P<0.05); and the mean death rate was reduced in the mice of the ribavirin group (P<0.05). In the model group, the alveolar structure was not integral, the alveolar septum was thickened, inflammatory cells were infiltrated and red blood cells exudated seriously (P<0.01). Compared with the model group, in the acupoint injection group and the ribavirin group, the alveolar structure was integral, the thickened alveolar septum was alleviated; and the infiltration of inflammatory cells and the exudation of red blood cells were reduced remarkably. The viral load was reduced in the mice of the ribavirin group when compared with the model group (P<0.01). Compared with the control group, the concentrations of TNF-α, IL-1β and MDA in lung tissue were increased and those of IL-10, SOD and GSH-Px were reduced in the model group (P<0.01). In the acupoint injection group and the ribavirin group, the concentrations of TNF-α, IL-1β and MDA were reduced in lung tissue and those of IL-10, SOD and GSH-Px were increased (P<0.05, P<0.01) when compared with the model group. CONCLUSION Acupoint injection with V_C+V_BCo solution may alleviate inflammatory responses and oxidative stress in lung tissue of the PR8-induced pneumonia mice, improve survival rate and prolong the survival time in the case of no effect of the viral load.
Acupuncture Points ; Animals ; Influenza A Virus, H1N1 Subtype ; Influenza A virus ; Interleukin-10 ; Male ; Mice ; Mice, Inbred ICR ; Pneumonia ; Ribavirin/therapeutic use* ; Superoxide Dismutase ; Tumor Necrosis Factor-alpha

High-throughput transcriptome sequencing was used to study the mechanism of Shenling Baizhu Powder(SLBZP) in the alleviation of the dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) in mice. The mouse model of DDS-induced UC was treated with SLBZP by gavage. The changes in general state, disease activity index(DAI), and colon length were observed. The hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissues of mice. Enzyme-linked immunosorbent assay(ELISA) was used to determine the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, IL-6, IL-4, and IL-10 in the serum and tissues of mice. The differentially expressed genes in the control group, the model group, and the SLBZP group were analyzed by high-throughput transcriptome sequencing, and the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were conducted on the differentially expressed genes. The results showed that after intragastric administration of SLBZP, the symptoms of diarrhea and bloody stool were improved, and the disease active index(DAI) score was reduced. SLBZP effectively reduced the inflammatory cell infiltration and goblet cell loss in the colonic mucosal tissue, reduced the levels of TNF-α, IL-1β, IL-6 in the serum and colon tissue, and increased the levels of IL-4 and IL-10 in the serum and colon tissue. There were 25 differential genes in SLBZP vs the model group, which were significantly enriched in immune response, immune system process, immunoglobulin production, and other biological processes. KEGG pathway analysis showed that the differential genes were enriched in signaling pathways such as neomycin, kanamycin, and gentamicin biosynthesis, cytokine-cytokine receptor interaction, primary immunodeficiency, and IgA synthesis of the intestinal immune network. This study shows that SLBZP may alleviate UC through immune regulation.
Animals ; Mice ; Colitis, Ulcerative/genetics* ; Colon ; Dextran Sulfate/adverse effects* ; Disease Models, Animal ; Interleukin-10/genetics* ; Interleukin-4/genetics* ; Interleukin-6/genetics* ; Mice, Inbred C57BL ; Powders ; Transcriptome ; Tumor Necrosis Factor-alpha/metabolism* ; Drugs, Chinese Herbal/therapeutic use*

Objective: To analyze the mortality level and tendency of road traffic injury in Shandong province from 2012 to 2020. Methods: Based on the data of road traffic deaths from the cause of death registration system in Shandong province from 2012 to 2020, the mortality rates of road traffic injury were calculated by sex, age, area, and injury type. The mortality was standardized based on the age structure of the Chinese population in the sixth Population Census in 2010. The annual percent change (APC) and average annual percent change (AAPC) of the mortalities and the standarized mortalities were calculated by using Joinpoint regression model, and the trends were also examined. Results: In 2020, the crude mortality of road traffic injury in Shandong Province was 15.58/100 000, and the standardized mortality was 12.90/100 000. From 2012 to 2020, the standardized mortality of road traffic injury in Shandong province showed a downward trend with AAPC of -5.4%. The standardized mortality of middle-south mountain areas, male and children aged 0-14 years in Shandong showed a significantly decreasing trend with AAPC of -6.8%, -6.1% and -6.0%, respectively. The standardized mortality of people aged 65 years and over did not decrease significantly, but the number of deaths increased significantly by 50.96% in 2020 (5 780 cases), compared with those in 2012 (3 829 cases). The standardized mortality of pedestrian and motorcyclists decreased significantly with AAPC of -7.5% and -6.7%, respectively. There was no significant change in the standardized mortality among people who rode motor vehicles or bicycles. Conclusion: From 2012 to 2020, the standardized mortality of road traffic injury in Shandong Province showed an obvious downward trend, but the standardized mortality of people aged 65 years and over did not decrease significantly. In the future, it is still necessary to take government-led, multi-sectoral collaboration, with a focus on comprehensive preventive measures, to further reduce road traffic injury mortality.
Accidents, Traffic ; Asian People ; Child ; Government ; Humans ; Male ; Mortality ; Motor Vehicles

Objective:To explore the potential molecular mechanism of Nelumbinis Plumula alkaloids （NAPs） in the prevention and treatment of non-small cell lung cancer （NSCLC） based on network pharmacology and cell experiment. Method:The main active components of NAPs were obtained by searching Traditional Chinese Medicine System Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and their main targets were predicted and analyzed by employing Swiss Target Prediction. The main target genes of NSCLC were retrieved from GeneCards， Online Mendelian Inheritance in Man （OMIM） and DrugBank databases. The resulting common targets were imported into STRING platform for constructing the protein-protein interaction （PPI） network， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis based on Database for Annotation， Visualization， and Integrated Discovery （DAVID）. The NAPs-common target -pathway network was constructed by Cytoscape 3.7.1. After NSCLC cell line A549 was treated with isoliensinine， the cell morphology was observed under an inverted fluorescence microscope. The effect of isoliensinine on A549 vitality was detected by cell counting kit-8 （CCK-8） assay and the target protein changes were verified by Western blot. Result:The main active components for NAPs against NSCLC were lysicamine， liensinine， and isoliensinine. The phosphatidylinositol-3-kinase-protein kinase B （PI3K-AKT）， RAS-related protein 1 （Rap1）， epidermal growth factor family of receptor tyrosine kinases （ErbBs）， and hypoxia inducible factor-1 （HIF-1） pathways were mainly involved for binding adenosine triphosphate （ATP） and regulating protein kinase activity. The main targets included protein kinase B-1 （AKT1）， alpha catalytic subunit of phosphoinositol-3-kinase （PIK3CA）， cyclin-dependent kinase 2 （CDK2）， mitogen-activated protein kinase-1 （MAPK1）， epidermal growth factor receptor （EGFR）， adenosine triphosphate-binding cassette B1 （ABCB1）， mammalian target of rapamycin （mTOR）， tyrosine kinase （Src）， Janus kinase 1 （JAK1）， and G1-phase-specific gene cyclin-D₁ （CCND1）. The in vitro cell experiment also revealed that isoliensinine down-regulated the expression of phosphorylated AKT （p-AKT） and phosphorylated mTOR （p-mTOR） in a concentration- and time-dependent manner and inhibited the growth of A549 cells. Conclusion:NAPs exert the preventive and therapeutic effects against NSCLC through multiple components， multiple targets， and multiple pathways， especially the PI3K-AKT pathway.