OBJECTIVES: To explore the mechanism that mediate the therapeutic effect of quercetin on heart failure. METHODS: We searched the TCMSP and Swiss ADME databases for the therapeutic targets of quercetin and retrieved heart failure targets from the Genecards and OMIM databases. The intersecting targets were analyzed with GO and KEGG pathway analysis using DAVID database, and the key genes were identified via PPI analysis. Molecular docking between the core targets and quercetin was performed using PyMOL and AutoDock Tools. In a heart failure model established in H9C2 cardiomyocytes by treatment with isoproterenol, the effect of quercetin on the expressions of the MAPK signaling pathway was tested. RESULTS: A total of 60 intersecting targets were identified. Enrichment analysis revealed that quercetin may inhibit heart failure through the MAPK signaling pathway. The core genes, including AMPK3 and BCL-2, were identified as potential key regulators in quercetin-mediated improvement of heart failure. Cellular experiments demonstrated that quercetin significantly reduced isoproterenol-induced apoptosis of cardiomyocytes in a dose-dependent manner and obviously decreased the Bax/Bcl-2 ratio and the expression levels of caspase-3, ERK and p38 in the cells. CONCLUSIONS Quercetin improves heart failure possibly by inhibiting cardiomyocyte apoptosis through the MAPK signaling pathway.
Quercetin/pharmacology* ; Myocytes, Cardiac/drug effects* ; Heart Failure/metabolism* ; Apoptosis/drug effects* ; MAP Kinase Signaling System/drug effects* ; Rats ; Animals ; Isoproterenol

OBJECTIVES: To evaluate the protective effect of Bufei Yishen Formula (BYF) against cigarette smoke extract (CSE)-induced injuries in human bronchial epithelial BEAS-2B cells and explore the underlying mechanism. METHODS: BEAS-2B cells exposed to CSE were treated with normal rat serum, BYF-medicated rat serum at low or high doses, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor), PDTC combined with high-dose BYF-medicated serum, or S-carbomethyloysteine (S-CMC, as the positive control). CCK-8 assay was used to determine the optimal concentration and treatment time of CSE, BYF-medicated serum and S-CMC. The treated cells were examined for inflammatory factor levels in the supernatant and cellular expressions of MUC5AC and MUC5B using ELISA, cell ultrastructural changes with transmission electron microscopy, and cell apoptosis rate using flow cytometry. The expression levels of TLR4/NF‑κB pathway-associated mRNAs and proteins were determined by qRT-PCR and Western blotting. RESULTS: CSE exposure significantly increased secretions of IL-1β, IL-6 and TNF-α, mRNA and protein expressions of MUC5AC and MUC5B, and early and total apoptosis rates in BEAS-2B cells, where the presence of apoptotic bodies was detected. CSE also significantly enhanced the mRNA and protein expressions of TLR4, I-κB, and NF-κB and reduced mRNA and protein expressions of AQP5. Treatments of the CSE-exposed cells with BYF-medicated serum, PDTC and S-CMC all significantly lowered inflammatory factor levels, MUC5AC and MUC5B expressions, and early and total cell apoptosis rates, and partly reversed the changes in cellular ultrastructure and mRNA and protein expressions of the TLR4/NF-κB pathway, and the effects were the most conspicuous following the combined treatment with high-dose BYF-medicated serum and PDTC. CONCLUSIONS BYF can inhibit cell apoptosis, inflammation and mucus hypersecretion in CSE-induced BEAS-2B cells by inhibiting the TLR4/NF-κB signaling pathway.
Humans ; Epithelial Cells/cytology* ; Drugs, Chinese Herbal/pharmacology* ; NF-kappa B/metabolism* ; Bronchi/cytology* ; Smoke/adverse effects* ; Apoptosis/drug effects* ; Mucin 5AC/metabolism* ; Cell Line ; Toll-Like Receptor 4/metabolism* ; Mucin-5B/metabolism* ; Signal Transduction/drug effects* ; Nicotiana ; Rats ; Thiocarbamates/pharmacology* ; Animals

Objective To investigate the roles of three Tiao-Bu Fei-Shen Traditional Chinese Medicine(TCM)therapies in improving airway mucus hypersecretion in rats with stable chronic obstructive pulmonary disease(COPD).Methods Ninety rats were divided randomly into nine groups:control(Control)group,model(COPD)group,Bu-Fei Jian-Pi Formula(BJF)group,Bu-Fei Yi-Shen Formula(BYF)group,Yi-Qi Zi-Shen Formula(YZF)group,ERK1/2 inhibitor(PD98059)group,Bu-Fei Jian-Pi combined with inhibitor(BJF+PD98059)group,Bu-Fei Yi-Shen combined with inhibitor(BYF+PD98059)group,and Yi-Qi Zi-Shen combined with inhibitor(YZF+PD98059)group.A rat model of COPD was established by exposing rats to cigarette smoke followed by repeated bacterial infection from weeks 1～8.From weeks 9～16,rats in the control and COPD groups were given 2 mL normal saline,rats in the BJF,BYF,and YZF groups were given the three Tiao-Bu Fei-Shen formulas by gavage,and rats in the PD98059,BJF+PD98059,BYF+PD98059,and YZF+PD98059 groups were given PD98059 by intraperitoneal injection for 7 days at the 16th week.Lung function tests were conducted after 16 weeks and lung tissue morphology,lung water content,inflammatory cell count in bronchoalveolar lavage fluid,and serum levels of inflammatory factors were also assessed.Goblet cell proportion was determined by Alcian blue-periodic acid-Schiff staining,and Muc5AC and Muc5B expression levels were detected by immunohistochemistry.mRNA expression levels of ERK1,ERK2,ENaC,CFTR,and AQP5 were detected by polymerase chain reaction and protein expression levels of ERK1/2 and P-ERK1/2 in lung tissue were determined by Western Blot.Results TV,MV,FVC,FEV0.1,FEV0.1/FVC were significantly decreased(P＜0.01)in COPD rats compared with those in the control group.Lung pathology revealed alveolar disorder,massive fracture of the alveolar wall,and severe shrinkage/thickening of the airway wall accompanied by extensive infiltration of inflammatory cells.Lung tissue water content was significantly increased in COPD rats(P＜0.01),while the proportion of macrophages in BALF was significantly reduced(P＜0.01)and the proportions of neutrophils and lymphocytes were significantly increased(P＜0.01).Serum levels of TNF-α and IL-1β were significantly increased in COPD rats(P＜0.05,P＜0.01).The percentage of goblet cells and expression levels of Muc5AC and Muc5B in airway epithelial cells were significantly increased(P＜0.01),mRNA expression levels of ERK1,ERK2,and ENaC in lung tissue were significantly elevated(P＜0.01),while mRNA expression levels of CFTR and AQP5 were significantly decreased(P＜0.01)in COPD rats compared with levels in the control group.The expression of P-ERK1/2,ERK1/2 in lung tissue was significantly increased(P＜0.01)Rats in the treatment groups demonstrated improvements in the above indicators(P＜0.05,P＜0.01)compared with the COPD group,the groups receiving the three Tiao-Bu Fei-Shen formulas combined with PD98059 showing superior efficacy compared with the single treatment groups(P＜0.05,P＜0.01).Conclusions The three tested Tiao-Bu Fei-Shen therapies can ameliorate airway mucus hypersecretion in COPD rats by inhibiting the ERK1/2 signaling pathway.

Objective Study on mechanism of Xuanfei Jiedu Formula in treating multi-drug resistant Pseudomonas aeruginosa pneumonia.Methods Except the Control group,the MDR-PA(9×108 CFU/mL,0.5 mL)pneumonia rat model was established by tracheal intubation,and an un-modeled control group was used.After successful modeling,rats were randomly divided into model group,XFJDF-low dose group,XFJDF-medium dose group,XFJDF-high dose group and IPM group,with 12 animals in each group;In addition to the blank group and the model group,the remaining drug administration groups were collectively referred to as the intervention treatment group.One day after modeling,the XFJDF-low dose,XFJDF-medium dose,and XFJDF-high dose groups were given the corresponding doses by gavage.The imipenem and cilastatin group was given Imipenem intraperitoneal injection,and the control and model groups were given saline gavage twice a day for 7 days.The rats'general status,body weight changes,and wet-dry weight ratio(W/D)of the lung tissue were observed.Hematoxylin-eosin staining was used to observe the pathological changes to the lung tissue of rats in each group under a light microscope.The serum levels of IL-1β,TGF-β,TNF-α,and IL-6 were detected by enzyme immunosorbent assay.Serum GSH content and MPO activity of rats were detected by colorimetry.The serum content of MDA was detected by TBA method.The total antioxidant capacity(T-AOC)was detected by kit method.The protein levels of TLR4,Myd88,and NF-κBp65 in lung tissues were determined by immunohistochemistry.The mRNA and protein levels of TLR4,Myd88,and NF-κBp65 in the lung tissues of each group were detected by qPCR and Western Blot.Results Compared with the control group,the model groups had delayed responses,increased respiratory frequency,increased respiratory noise,and appeared to have different degrees of chills,as well as decreased diet and water intake and decreased body weight.The W/D of lung tissue was significantly increased(P＜0.01),and a large number of inflammatory cells had infiltrated the alveolar cavity and around the lung bronchus.Some alveolar walls were fractured and fused to form air cavities,with inflammatory exudation,pulmonary interstitial thickening,and local lung fiber formation.The serum levels of IL-1β,TNF-α,TGF-β,and IL-6 were significantly increased(P＜0.01),MDA content was increased,MPO activity was enhanced,GSH content and T-AOC capacity were decreased(P＜0.01),and the mRNA and protein levels of TLR4,Myd88,and NF-κBp65 in lung tissue were significantly increased(P＜0.01).Compared with the model groups,the intervention group and the treatment group showed improvements in the above indexes(P＜0.05,P＜0.01),and the Xuanfei Jiedu Formula high-dose group and IPM group had the most significant improvements(P＜0.05,P＜0.01).Conclusions Xuanfei Jiedu can significantly improve the general state,body weight,lung tissue W/D,and lung tissue pathology,and the reduce inflammation and oxidative stress,of MDR-PA rats.The mechanism may be related to its inhibition of the expression of TLR4/Myd88/NF-κB pathway proteins in lung tissue.

Objective To explore the action of Bufei Jianpi formula(BJF)on mitochondrial damage to skeletal muscle in chronic obstructive pulmonary disease(COPD)rats via its regulation of the IRS-1/PI3K signaling axis.Methods 60 SPF SD rats were randomly divided into Control group,Model group(COPD stable stage group),aminophylline(Am)group,BJF group,pioglitazone(PIO)group and BJF+PIO group,with 10 rats per group.A stable COPD rat model was established via forced smoking and Klebsiella pneumoniae nasal drip method.Samples were taken from the 9th week to the end of the 20th week,and the weight of the rats was measured every week.Routine sectioning and HE staining were performed on lung and skeletal muscle tissue,and corresponding pathological changes were observed under a light microscope.The lung function of the rats was observed by whole-body plethysmography in weeks 0,8,and 20,including tidal VT,PEF,and EF50.The mRNA expression of IRS-1,leptin,PGC1-α,and PI3K in rat skeletal muscle was detected by qPCR.The expression of PGC-1α,TFAM,IRS-1,PI3K,AKT,p-AKT,and leptin in rat skeletal muscle tissue was detected by Western blot.Results The Model group,but not the Control group,showed a large number of inflammatory cells infiltrating the alveolar interstitium and bronchus,indicative of lung disease;some alveolar walls had broken and fused to form air cavities,and fiber networks were destroyed.After drug treatment,the rats showed improved alveolar wall and fiber network integrity and reduced inflammatory cell infiltration in the bronchus,especially those in the BJF and Am groups.In the drug treatment groups,the skeletal muscle pathology of each group showed improved spatial arrangement,the atrophy and fracturing of muscle fibers were ameliorated to different degrees,and cytoplasmic staining of muscle cells was uneven,and the BJF group showed the most significant effects.Compared with the Control group,the Model group's PEF,VT,and EF50 significantly decreased from week 8(P＜0.01),while the BJF,BJF+PIO and Am groups had significantly increased PEF and EF50(P＜0.01).Compared with Control group,the Model group's mRNA and protein expression levels of IRS-1,PGC-1α,and PI3K were significantly decreased(P＜0.05,P＜0.01),the level of leptin was significantly increased(P＜0.01).Compared with the Model group,the mRNA and protein expressions of IRS-1,PGC-1α and PI3K in the BJF group were significantly increased(P＜0.05,P＜0.01),and the mRNA expression of IRS-1 in the PIO group was significantly increased(P＜0.01).The BJF+PIO group's mRNA levels of PGC-1α(P＜0.01)and mRNA and protein levels of IRS-1 and PI3K were significantly increased(P＜0.05,P＜0.01).The mRNA and protein expression levels of PI3K in the Am group were significantly increased(P＜0.01).The expression levels of leptin mRNA were significantly decreased in the four treatment groups(P＜0.01),and the expression of leptin protein was significantly decreased in all treatment groups except the Am group(P＜0.01).Compared with the Control group,the Model group's quadriceps femoris tissue showed a significant decrease in TFAM and p-AKT expression.TFAM and p-AKT expression in all the treatment groups showed an increasing trend,but the difference was not statistically significant(P＞0.05).Conclusions By regulating the IRS-1/PI3K signaling axis,Bufei Jiempi reduces mitochondrial damage to skeletal muscle,increases the expression of PGC-1α and mitochondrial transcription factor TFAM,enhances mitochondrial biosynthesis,and reduces pathological damage to lung and skeletal muscle tissue.

Objective? To explore the clinical application of information technology in the multidisciplinary chain management of surgical patient handover, in order to reduce the safety hazard in the process of surgical patient handover. Methods? In the contemporary controlled study, 300 patients were selected as the control group from February to July 2017 by cluster sampling, and 303 patients were selected as experimental group from February to July 2018. Traditional sectional handover method was adopted in the control group, to managed the patients＇ handover from each section. In the experimental group, based on the information communication platform between the surgery room and relevant clinical departments, by clinical electronic documents chain transfer method, quality inspection and supervision information feedback technology, to achieve shared decision and improvement of patients handover problems, we built the multidisciplinary management pattern. The two groups were compared for statistical difference from six aspects:the rate of acceptance specification, the accuracy of identity verification method, the rate of operation labeling verification, the accuracy of inventory of items, the evaluation of pipeline patency, and the evaluation of skin condition at the compression site. Results? The rate of standard delivery of surgical patient handover increased from 49.33% to 92.08% in the two groups. The experimental group was better than the control group in the rate of correct delivery of handover from the following five aspects: identity recognition, indication of surgical site, inventory of articles carried, unobstructed pipeline and skin state of the pressure site with statistical significance (P＜ 0.01). Conclusions? The multidisciplinary chain management model of surgical patient handover supported by information technology is effective in clinical application, which can significantly reduce the risk of hazard in patient handover and is worthy of clinical promotion.

Objective To evaluate the effectiveness of nutritional support in the treatment of primary chylous reflux obstacle caused by primary lymphatic dysplasia among infants and investigate the effects of the essential components of therapeutic formula milk in treating this disease.Methods Seven infants,who were diagnosed at Beijing Shijitan Hospital between 2012 and 2014 with primary chylous reflux obstacle and aged (8.9±4.6) months at the onset,were retrospectively analyzed to evaluate effectiveness of the nutrition support and prognosis of the disease.Results After personalized enteral nutrition support (using proteins,short peptides and medium-chain triglyceride) of (8.3±2.8) months,heights and weights of all the seven infants were kept between the 3rd and 97th percentile lines,and the growth curve showed onward and upward trend.Their plasma albumin levels reached (43.7±4.4) g/L.The infants defecated 1-2 times a day and the texture of feces was formed and soft with yellow color.Conclusion Clinical symptoms and physical signs of the seven infants were improved after nutrition support,which contributed to the recovery.

Objective To investigate the clinical features of invasive pneumococcal disease(IPD) in pediatric intensive care unit(PICU) and to analyze outcomes,so as to provide evidence for early and reasonable diagnosis and treatment as well as to improvement of prognosis.Methods A retrospective study was conducted at a research center for IPD in PICU in Beijing Children's Hospital from January 2013 to April 2016.Clinical data of children with IPD were collected and analyzed.All specimens were for bacteria culture,isolation,strain identification and drug sensitivity test.At the same time,the quellung test was used to identify serotypes of the streptococcus pneumoniae.Results A total of 30 children meeting inclusion criteria were included,19 male and 11 female.The median age was 1.5 years (range 3 months to 7.5 years).The Pediatric Critical Illness Scores (PCIS) were 72 (64,82) scores.There were 13 cases whose Glasgow Coma Scores (GCS) were below 15 scores.The 28-day mortality rate was 36.7％ (11/30 cases).Among death cases,there were 7 cases of purulent meningitis,3 cases of septicemia and 1 case of purulent pleurisy.The onset age,peripheral blood leucocytes count,PCIS and GCS of death group were significantly lower than those of survival group (all P ＜ 0.05).The mortality rate of children complicated with septic shock was significantly higher than that of children without septic shock [75.0％ (6/8 cases) vs 22.7 ％ (5/22 cases),P ＜ 0.05].The most common serotypes were 19F and 19A.The coverage rate of pneumococcal conjugate vaccine 13 was 96.7％.The percentage of penicillin nonsusceptible streptococcus pneumoniae was 73.3％,and the percentage of penicillin resistant streptococcus pneumoniae was 53.3％,and multi-drug resistant was 90％.Conclusions The mortality rate of IPD in PICU is high,and the main serotypes were 19F and 19A.Most patients of death group were less than 2 years old.Peripheral blood white blood cell count,PCIS and GCS were significantly reduced,and more complicated with septic shock.Vaccination of pneumococcal conjugate vaccine 13 for children less than 2 years old may reduce the incidence of IPD.

Objective To describe the clinical characteristics of acute lower respiratory tract infection (ALRTI)caused by human coronavirus (HCoV)in children.Methods Three thousand five hundred and three hospi-talized children diagnosed with ALRTI in Beijing Children′s Hospital from March 2007 to February 201 3 were re-viewed.Nasopharyngeal aspirate(NPA)specimen was collected from each patient.Reverse transcription (RT)-poly-merase chain reaction(PCR)methods were applied to detect common respiratory viruses including respiratory syncytial virus (RSV),rhinovirus (RV),parainfluenza virus (PIV)type 1 -4,influenza virus type A and B (IFA,IFB),adeno-virus (AdV),enterovirus (EV),HCoV,human metapneumovirus (hMPV)and human bocavirus (HBoV).Serum anti-bodies of mycoplasma and sputum bacterial culture were also detected.Only HCoV positive patients were analyzed in this study.Results Eleven of 3 503 patients were proved as HCoV -positive in NPA specimens.Of the 1 1 children,8 cases were male and 3 cases were female (2.71 .0).The median age was 3 months.The clinical symptoms of HCoV infection included cough (1 1 /1 1 cases,1 00.0%),wheezing (1 0 /1 1 cases,90.9%),fever (6 /1 1 cases,54.5%)and poor appetite (7 /1 1 cases,63.6%).Wheezing (8 /1 1 cases,72.7%)and moist rale in inspiratory phase (5 /1 1 ca-ses,45.4%)could be heard.Most patient′s chest X -ray showed bronchopneumonia.Full blood count displayed that leukocyte was in the normal range.Conclusions Respiratory tract infection with HCoV -positive will be easier to spread to ALRTI,especially in infants less than 1 year old.The symptoms include fever,cough and wheezing,but poor appetite and diarrhea can also be detected.

OBJECTIVETo investigate human coronaviruses (HCoVs) infection in children with acute lower respiratory tract infection(ALRTI)and to explore the clinical features of ALRTI caused by HCoVs in children.

METHODTotally 4 371 children with clinical diagnosis of ALRTI during the period from March 2007 to February 2015 seen in Beijing Children's Hospital were recruited into this study. Patients were divided into 4 groups by age, including 1 890 cases in < 1 year group, 788 cases in 1-3 years group, 553 cases in 3-6 years group, 1140 cases in ≥6 years group. One nasopharyngeal aspirate specimen was collected from each patient. RT-PCR methods were applied to detect 9 common respiratory viruses including HCoVs (including HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1), respiratory syncytial virus (RSV) and so on. Clinical features of ALRTI with single HCoVs infection were analyzed and compared with hospitalized ALRTI cases with single RSV infection in the same period.

RESULT(1) Totally 2 895 cases were positive for at least one virus in this study in 4 371 ALRTI patients (positive rate 66.23%), in which 147 cases were positive for HCoVs infection (positive rate 3.36%). (2) Positive rates of HCoVs in each year from 2007 to 2014 were 6.11%, 3.79%, 4.69%, 4.31%, 2.38% 2.10%, 0.77% and 2.65%, respectively. The mean positive rates of HCoVs for each month from January to December were 2.53%, 2.12%, 3.63%, 6.68%, 1.53%, 3.77%, 3.92%, 3.00%, 2.15%, 5.26%, 3.01% and 2.80%. (3) Detection results of each subtypes of HCoVs in total 4 371 pediatric ALRTI patients were: 48 cases positive for HCoV-OC43(1.10%), 32 cases positive for HCoV-229E(0.73%), 25 cases positive for HCoV-NL63 (0.57%), 27 cases positive for HCoV-HKU1 (0.62%). (4) Positive rates of HCoVs infection in <1 year group, 1-3 years group, 3-6 years group and ≥ 6 years group were 4.13%, 5.08%, 2.71% and 1.23%, respectively. There were significant differences in positive rates of HCoV among groups (χ² = 27.218, P<0.01). (5) There were 16 hospitalized cases with single infection of HCoVs in this study, of which 12 cases were diagnosed as bronchopneumonia, 3 cases developed acute laryngeal obstruction, 2 cases had acute bronchial asthma attack. Common clinical manifestations included cough (14 cases), gasping (13 cases), dyspnea (9 cases), fever (6 cases), hoarseness (4 cases), laryngeal stridor (4 cases) and abnormality on chest X-ray (including fuzzy lung texture, patchy shadow and consolidation) (12 cases). (6) There were no significant differences in the incidence of clinical manifestations (including cough, gasping, dyspnea, fever and abnormality on chest X-ray), complications (including respiratory failure, myocardial damage, and acute bronchial asthma attack) and mechanical ventilation between hospitalized ALRTI patients with single HCoV infection and 193 patients with single RSV infection in the same period.

CONCLUSIONHCoVs are pathogens of ALRTI in children, The overall positive rate of HCoVs was 3.36% in this study. The clinical manifestations and severity of ALRTI caused by single HCoVs was comparable to that of ALRTI with single RSV infection in children.

Acute Disease ; Beijing ; Child ; Child, Preschool ; Coronavirus ; Coronavirus Infections ; epidemiology ; Humans ; Incidence ; Infant ; Respiratory Syncytial Virus Infections ; epidemiology ; Respiratory Syncytial Viruses ; Respiratory Tract Infections ; epidemiology ; virology