OBJECTIVE To explore the effect and mechanism of berberine in ameliorating asthma in mice by regulating glycolysis via the hypoxia inducible factor-1α （HIF-1α）/pyruvate dehydrogenase kinase-1 （PDHK1） pathway.METHODS Mice were randomly divided into blank control group， model group， low- and high-dose berberine groups （100， 200 mg/kg， intragastric administration）， dimethyloxalylglycine （DMOG， HIF-1α agonist） group （2 mg， intranasal instillation）， and berberine+DMOG group （intragastric administration of 200 mg/kg berberine plus intranasal instillation of 2 mg DMOG）， with 12 mice in each group. Except for the blank control group， mice in the remaining groups were subjected to ovalbumin-induced sensitization and challenge to establish the asthma model. During the challenge period， mice were given corresponding drugs or normal saline once a day for 6 consecutive days. At 24 h after the last challenge， pulmonary function and airway reactivity of mice were determined； the content of ovalbumin-specific immunoglobulin E （OVA-sIgE） in serum was detected； inflammatory cells in bronchoalveolar lavage fluid （BALF） were counted； bronchial inflammation and goblet cell hyperplasia were histologically evaluated； the levels of inflammatory cytokines [interleukin-4 （IL-4）， IL-5， IL-13]， contents of glycolytic products [lactic acid， pyruvic acid， adenosine triphosphate （ATP）]， as well as mRNA and protein expressions related to the HIF-1α/PDHK1 pathway in lung tissue were measured.RESULTS Compared with the model group， the low- and high-dose berberine groups exhibited significantly elevated or increased dynamic lung compliance， peak expiratory flow， forced vital capacity （FVC）， forced expiratory volume in 0.1 second （FEV 0.1 ）， and FEV 0.1 /FVC （ P ＜0.05）， accompanied by significantly decreased airway resistance and enhanced pause value （ P ＜0.05）. Moreover， serum OVA-sIgE content， counts of white blood cell， neutrophil， lymphocyte， monocyte， eosinophil and basophil in BALF， scores for bronchial inflammation and goblet cell hyperplasia， levels of pulmonary inflammatory cytokines and contents of glycolytic products， as well as mRNA and protein expressions of HIF-1α， PDHK1， pyruvate kinase M2 and lactate dehydrogenase A were all significantly reduced （ P ＜0.05）. DMOG pretreatment obviously reversed the protective effects of high-dose berberine in asthmatic mice （ P ＜0.05）.CONCLUSIONS Berberine can inhibit the HIF-1α/PDHK1 pathway to decrease glycolytic level， so as to ameliorate airway inflammation and airway hyperresponsiveness in asthmatic mice.

Objective To analyze the risk factors for gestational diabetes mellitus(GDM)in late pregnancy and explore the correlation between inflammatory stress status and pregnancy outcomes in GDM pregnant women.Methods A total of 87 pregnant women with GDM in late pregnancy were se-lected as GDM group,and another 87 pregnant women without GDM during the same period were se-lected as non-GDM group.Univariate analysis was conducted to compare the clinical data between the GDM group and the non-GDM group,and binary Logistic regression analysis was used to explore the risk factors for GDM.Spearman correlation analysis was employed to investigate the correlation between inflammatory stress status and pregnancy outcomes in GDM pregnant women.Results Univariate a-nalysis showed that compared with the non-GDM group,the GDM group had a higher proportion of women who were older,had a weight gain of ≥15 kg during pregnancy,a history of adverse pregnancy outcomes,a family history of diabetes,gestational hypertension,anemia during pregnancy,vaginal candidiasis infection,a preference for sweet foods,and a lower proportion of women engaging in daily exercise for≥1 h(P＜0.05).Binary Logistic regression analysis revealed that older age,weight gain of≥15 kg during pregnancy,history of adverse pregnancy outcomes,family history of diabetes,gesta-tional hypertension,anemia during pregnancy and preference for sweet foods were independent risk factors for GDM in late pregnancy(P＜0.05),while daily exercise for ≥1 h was an independent protective factor(P＜0.05).Compared with pregnant women with adverse pregnancy outcomes,women with favorable pregnancy outcomes had higher levels of C-reactive protein(CRP),lymphocytes(LYM),neutrophils(NEUT),procalcitonin(PCT)and white blood cells(WBC)(P＜0.05).Spearman correlation analysis showed that the levels of inflammatory stress indicators such as CRP,LYM,NEUT,PCT and WBC were positively correlated with the risk of adverse pregnancy outcomes in GDM pregnant women(P＜0.05).Conclusion The incidence of GDM in late pregnancy is asso-ciated with maternal age,weight gain during pregnancy,history of adverse pregnancy outcomes,family history of diabetes,gestational hypertension,anemia during pregnancy,preference for sweet foods and daily exercise time.Moreover,the inflammatory stress status of GDM patients in late preg-nancy is closely related to adverse pregnancy outcomes.

Objective To study the inhibitory effect of Huidu Yinhua powder from the Orthodox Manual of External Medicine on methicillin-resistant Staphylococcus aureus(MRSA),virulence factor α-hemolysin(Hla)activity,and biofilm formation,and to explore the optimal ratios of Huidu Yinhua powder and provide experimental support for its use.Methods The inhibitory effects of Huidu Yinhua powder and the herbs in the formula on USA300 were analyzed by the minimum inhibitory concentration(MIC),minimum bactericidal concentration(MBC),and disk diffusion assay(K-B method).Hemolysis,neutralization,oligomerization,and Western blot assays were used to verify in which form the drug inhibits the activity of virulence factor α-hemolysin(Hla).A biofilm assay was performed to evaluate the inhibitory effect of Huidu Yinhua powder on biofilm.Orthogonal experiments were performed to explore the optimal ratio of Huidu Yinhua powder.Results Huidu Yinhua powder inhibited the MRSA strain with a MIC90 of 64 mg/mL and an MBC of 256 mg/mL with antibacterial circle diameter of(7.50±0.50)mm.Huidu Yinhua powder inhibited Hla activity by inhibiting Hla secretion.The minimum effective concentration(MEC)was 16 mg/mL,and the MEC of biofilm was 8 mg/mL.In Huidu Yinhua powder,honeysuckle and astragalus only affected the hemolytic activity of MRSA and biofilm formation without inhibiting bacterial growth.The hemolytic activity and biofilm of MEC were both 32 mg/mL.Glycyrrhiza had a strong bacterial inhibitory capacity with a MIC90 of 8 mg/mL and biofilm MEC of 1 mg/mL without showing inhibitory hemolytic activity at subinhibitory concentrations.The orthogonal experiment showed that,at a ratio of honeysuckle,astragalus,and glycyrrhiza in Huidu Yinhua powder of 1∶2∶4,the MIC90 was 16 mg/mL,MEC of hemolytic activity was 8 mg/mL and that of biofilm was 4 mg/mL,both of which were the lowest among the nine groups.Conclusions Huidu Yinhua powder affects the hemolytic activity and biofilm formation of MRSA at subinhibitory concentrations with the optimal ratio of honeysuckle,astragalus,and glycyrrhiza being 1∶2∶4.

The field of two-dimensional (2D) nanomaterial-based cancer immunotherapy combines research from multiple subdisciplines of material science, nano-chemistry, in particular nano-biological interactions, immunology, and medicinal chemistry. Most importantly, the "biological identity" of nanomaterials governed by bio-molecular corona in terms of bimolecular types, relative abundance, and conformation at the nanomaterial surface is now believed to influence blood circulation time, bio-distribution, immune response, cellular uptake, and intracellular trafficking. A better understanding of nano-bio interactions can improve utilization of 2D nano-architectures for cancer immunotherapy and immunotheranostics, allowing them to be adapted or modified to treat other immune dysregulation syndromes including autoimmune diseases or inflammation, infection, tissue regeneration, and transplantation. The manuscript reviews the biological interactions and immunotherapeutic applications of 2D nanomaterials, including understanding their interactions with biological molecules of the immune system, summarizes and prospects the applications of 2D nanomaterials in cancer immunotherapy.

Objective:To investigate the normal range of exhaled nitric oxide (FeNO) in 6-18-year-old children in China, so as to provide a data base for the establishment of FeNO standards for Chinese children.Methods:A multi-center study was conducted on 5 949 children aged 6-18 (3 101 males and 2 848 females) in 16 pro-vinces of 7 administrative districts in China.According to the technical standard recommended by American Thoracic Society/European Respiratory Association, FeNO was measured, and the relationship of FeNO with the sex, age, height, weight, body mass index and region was discussed.Results:The geometric mean FeNO value of Chinese children aged 6-18 was 14.1 ppb, and its 95% confidence interval (skewness distribution) was 1.0-38.2 ppb.The geometric mean FeNO values of children aged 6-11 and 12-18 were 13.1 ppb and 15.7 ppb, respectively, and their 95% confidence intervals (skewness distribution) were 1.0-38.1 ppb and 2.0-38.2 ppb.For children at and under 11 years old, FeNO decreased with age, with a mean decline of 1 ppb per year.The multiple linear regression results suggested that there was a significant correlation between FeNO and age for children aged 6-11, and FeNO of children aged 12-18 was significantly correlated with the gender, height, and region(all P<0.01). Conclusions:FeNO values of Chinese children and adolescents in this study are higher than those obtained by the previous study conducted from 2010 to 2012.For children aged 12-18, 16 ppb is recommended as the clinical cut-off point.For children at or under 11 years old, the influence of age on FeNO should be considered, and the cut-off point of FeNO decreases by 1 ppb as the age is reduced by one year.

Objective To investigate the effecs of evidence-based nursing of the treatment with propranolol forthe intractable infantile hemangiomahemangioma. Methods Dividing the children who were treated with propranolol into experimental groups and matched groups randomly according to the random number table each 42 .The experimental group adopted evidence-based care,according to PICO tool description of the problem and combining the results of theresponsibility nurse′s regular follow-up and assessment to come up with evidence-based problems,seeking for high-level evidences,combining the existing conditions of careand having formulated corresponding care norms,contingency plans for adverse reactions,healthy education card,the operation videos and other measures and they are implemented.The control group adopted the routine care procedure.two groups of effects were determined by the Achauer level 4 classification after 12 months of treatment,and evaluating the condition of occur of blood pressure drop ,slow heart beat ,diarrhea, sleepdisorders, hypoglycemia and other adverse reactions in both groups during the process of treatment. Results there was statistical significance in the difference of two groups′Achauer 4 levels. The numbers of Ⅰ, Ⅱ, Ⅲ, and Ⅳ in the two groups were 3, 7, 20, 12, and 11, 15, 11, 5, respectively (t1=1372, t2=2132, P<0.05). The two groups had a statistically significant difference in blood pressure, heart rate, diarrhea, sleep disorder, and low blood sugar response. The numbers of two groups were 12, 2, 3, 6, 1 and 26, 15, 12, 21, 8 respectively (χ2=6.098-12.464, all P<0.05). Conclusions Evidence-based nursing enhances the treatment effectiveness of theintractable infantile hemangioma with propranolol effectively and has preventing the occur of adverse reactions during the process of treatment.

Objective To investigate the trend of C-reactive protein in patients underwent total knee arthroplasty, and to seek the best time to assess the risk of deep vein thrombosis (DVT) in order to guide clinical nursing. Methods A total of 1 316 patients underwent total knee arthroplasty from January 2015 to December 2017 were studied to observe the occurrence of DVT. Patients were divided into DVT group (n=297) and non-DVT group (n=1 019). The C-reactive protein was compared between the two groups before operation, 1 to 7 days and 14 days after operation. Results Within 3 months after operation, the incidence of DVT in total knee arthroplasty patients was 22.57% (297/1 316). Symptomatic DVT occurred in 34 patients during hospitalization and asymptomatic DVT occurred in 263 patients within 3 months after operation. The levels of C-reactive protein in the DVT group were higher than those in the non-DVT group since the 3rd day after operation, and the differences were statistically significant (P＜ 0.05). Conclusions The level of C-reactive protein in patients with DVT is higher than that in patients without DVT. Medical staff should use various measures to prevent DVT, and dynamically observe changes in C-reactive protein to facilitate the early identification of DVT.

BACKGROUND:There is no effective drug for idiopathic pulmonary fibrosis (IPF), because of a lack of the animal model imitating the complete pathogenesis of human IPF. Therefore, it is critical to establish an ideal animal IPF model used for investigating the underlying pathogenesis and developing a kind of effective drug. OBJECTIVE:To establish an animal model that can mimic more characters of human IPF. METHODS:Seventy male C57BL/6 mice were randomly divided into two groups, fol owed by subjected to the intraperitoneal injection of bleomycin (35 mg/kg) on days 1, 4, 8, 11, 15, 18, 22, and 25, twice (group A) or once (group B) a week. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the eighth injection, and the lung tissues were moved used for hematoxylin-eosin, Masson and immunohistochemical stainings. RESULTS AND CONCLUSION:There were various degrees of alveolitis and pulmonary fibrosis in the two groups at different time points after the last injection. The scores of alveolitis and pulmonary fibrosis in the group A began to gradual y increase from the 2nd week and reached the highest level at the 6th-8th weeks until the 10th week. In contrast, the scores of alveolitis and pulmonary fibrosis in the group B peaked at the 2nd week, then fluctuately decreased, and were significantly lower than those in the group A at the 6th week (P<0.05). Immunohistochemistry showed that type I col agen deposition was mainly distributed in the subpleural region, peri-vascular region and alveolar septa, which was consistent with Masson staining findings. The expression levels of transforming growth factorβ1 (TGF-β1) andα-smooth muscle actin (α-SMA) in the regions developing alveolitis and pulmonary fibrosis were significantly increased. In the group A, the expression levels of type I col agen, TGF-β1,α-SMA, and the hydroxyproline content in the lung tissues reached the peak level at 6-8 weeks. However, in the group B, al above indicators reached the highest level at the 2nd week, but gradual y decreased thereafter. At the 4th week, the expression Levels of TGF-β1 andα-SMA in the group B were significantly lower than those in the group A (P<0.05). At the 6th week, the hydroxyproline and type I col agen levels in the group B were significantly lower than those in the group A (P<0.05). In conclusion, the mouse model of pulmonary fibrosis induced by intraperitoneal injection of 35 mg/kg bleomycin twice weekly can be used to mimic the repetitive wound healing process, pathological morphology and cytokine changes of human IPF, which is prone to administration, with better stability and repeatability. This model is of great significance for the study on IPF. Subject headings:Disease Models, Animal;Pulmonary Fibrosis;Bleomycin

Objective To investigate the therapeutic effect of Jianpi Yiqi, Bushen Fenjing combined with oxaliplatin+CF/5-FU on colorectal cancer.MethodsEighty patients with colorectal cancer who were treated in our hospital from January 2014 to December 2015 were randomly divided into observation group(40cases) and control group (40cases).The control group was given oxaliplatin+CF/5-FU treatment, the observation group in the control group based on the application of Spleen Qi, Bushen fill essence treatment, observed before and after treatment of two groups of serum tumor markers, clinical symptoms and living conditions, changes, record adverse reactions.ResultsThe observation effect of 82.50% was significantly higher than that of the control group (62.50%).The QOL score (37.8±5.6) was significantly higher than that of the control group (33.5±3.1) and the adverse reaction rate was 30.00% (P<0.05).The difference between the two groups was significant (P<0.05).ConclusionThe effect of invigorating spleen qi and tonifying siren solution combined with oxaliplatin+CF/5-FU on colorectal cancer can improve the clinical symptoms and improve the quality of life of patients.

Objective To explore the effects of the systematic "three preventions and three positions" nursing on preventing arthritic prosthesis dislocation after total hip arthroplasty (THA) for different diseases. Methods Based on historical control,459 patients who received THA in the orthopedics department of a hospital between January 2012 and December 2013 were selected as a control group. Patients in the control group received conventional nursing as well as health education and perioperative care as per routines. Totally 768 patients who received THA in the same hospital between January 2014 and December 2016 were selected as a treatment group. On the basis of conventional nursing,patients in the treatment group received targeted holistic nursing derived from the systematic "three preventions and three positions" nursing. The incidence of arthritic prosthesis dislocation between the two groups 3 months after THA was then compared.Results The incidence of arthritic prosthesis dislocation of the treatment group was 0.65%,including 1.56% for revision of THA,0.90% for femoral neck fractures,0.64% for osteonecrosis of the femoral head (ONFH),and 0.70% for congenital hip disorder (CHD) patients,while the incidence of arthritic prosthesis dislocation of the control group was 2.18%, which included 33.33% for revision of THA,1.25% for femoral neck fractures,0.70% for ONFH,and 0.70% for CHD patients. The treatment group′s incidence of arthritic prosthesis dislocation was lower than that of the control group (χ2=5.552;P<0.05):The incidence of arthritic prosthesis dislocation of THA revision patients in the treatment group was significantly lower than that of the patients in the control group (χ2=5.485;P<0.05);and the incidence of arthritic prosthesis dislocation among femoral neck fractures,ONFH and CHD patients in the treatment group was lower than the patients in the control group (χ2=0.309,0.743,2.771;P>0.05). Conclusions The systematic "three preventions and three positions" nursing helps to reduce the incidence of arthritic prosthesis dislocation after THA and THA revision,which is worthy of application and expansion.