Objective To study the effect of vitexin inhibiting Ras homology C(RhoC)/Rho-associated kinase(ROCK)signaling on lung inflammation and airway remodeling in rats with chronic obstructive pulmonary disease.Methods SD rats were divided into control group,model group(chronic obstructive pulmonary disease model),experimental-L group(chronic obstructive pulmonary disease model,1.5 mg·kg-1 vitexin treatment),experimental-M group(chronic obstructive pulmonary disease model,3.0 mg·kg-1 vitexin treatment),experimental-H group(chronic obstructive pulmonary disease model,6.0 mg·kg-1 vitexin treatment),experimental-H+LPA group(chronic obstructive pulmonary disease mode,6.0 mg·kg-1 vitexin,lysophosphatidic acid 1 mg treatment),Western blot detection of RhoC protein expression,detection of pulmonary function indexes in rats,hematoxylin-eosin staining to observe lung histopathology,and evaluation of airway inflammation in rats score,airway smooth muscle thickness,enzyme-linked immunosorbent assay method to detect interleukin-6(IL-6)content in bronchoalveolar lavage fluid,immunohistochemistry to detect basic fibroblast growth factor(bFGF)in lung tissue.Results The expression levels of RhoC protein in the control group,model group,experimental-H group,and experimental-H+LPA group were 0.25±0.02,0.71±0.09,0.31±0.03,0.47±0.04;forced vital capacity(FVC)were(8.25±0.62),(4.12±0.24),(7.21±0.54),(6.44±0.52)mL;inflammation score were 0.52±0.04,2.54±0.15,1.23±0.11,1.79±0.32;smooth muscle thickness were(19.28±1.52),(28.43±1.74),(19.45±1.18),(25.85±1.57)μm;IL-6 content were(2.40±0.08),(5.67±0.44),(2.85±0.23),(4.01±0.29)ng·L-1;bFGF protein expression were 0.19±0.02,0.52±0.05,0.24±0.02,0.43±0.05.There were statistically significant differences in the above indicators between the model group and the control group,between the experimental-H group and the model group,and between the experimental-H+LPA group and the experimental-H group(all P＜0.05).Conclusion Vitexin inhibits RhoC/Rock signaling to improve lung inflammation and airway remodeling in chronic obstructive pulmonary disease rats.

Aim To explore the inhibitory effect of lenvatinib plus fluvastatin on liver transplantation tumor in mice and the mechanism.Methods Mouse model of subcutaneous liver cancer was used.Single agent of lenvatinib, single agent of fluvastatin, a combination of lenvatinib and fluvastatin and control solvent were given to four groups of mice.Tumor volume was measured.Immunohistochemistry was used to examine proliferation of tumor cells.Tunel was employed to detect the cell apoptosis.qRT-PCR and immunohistochemistry were used to measure the expression of TLR4.Western blot was employed to determine β-catenin expression.Rescue experiment was done using human hepatoma cells cultured in vitro.Results Treatment with both lenvatinib and fluvastatin significantly suppressed tumor growth in nude mice.Combined treatment significantly decreased the expressions of PNCA and increased apoptosis in tumor cells.Mechanically combined treatment synergistically suppressed the mRNA and protein expression of TLR4 which further inhibited the expression of β-catenin in hepatoma cells.Conclusions A combination of lenvatinib and fluvastatin synergistically inhibits tumor growth and promotes tumor cell apoptosis.The combination treatment significantly inhibits TLR4/β-catenin signaling pathway.

Objective: To explore the expression of Runt-related transcription factor 1 (RUNX1) in nasal polyps (NPs) tissues and the potential role on apoptosis of primary human nasal epithelial cells (pHNECs) in NPs. Methods: The expression level of RUNX1 in NPs tissues was determined by Western blot (WB) and immunohistochemical staining (IHC). In vitro, TNF-α (20 ng/ml) was used to stimulate pHNECs to establish the apoptosis injury model. Hoechst staining was performed to observe pHNECs apoptosis by kit. Subsequently, quantitative real-time PCR (qRT-PCR) and WB were utilized to detect the expression of apoptosis-related proteins B-cell lymphoma-2 (BCL-2), BCL2-associated X (BAX) and cysteinyl aspartate specific proteinase-3 (Caspase-3) to assess the level of apoptosis. The plasmid of sh-RUNX1-6 was transfected into the pHNECs apoptosis model, then the effect of RUNX1 silence on apoptosis was evaluated by WB and flow cytometry. Statistical analysis was performed by the SPSS 19.0 and GraphPad Prism5 software. Results: The expression of RUNX1 in NPs tissue was significantly higher than that in inferior turbinates, and the difference was statistically significant (0.274±0.042 vs 0.110±0.027, t=9.675, P<0.05). Compared with the inferior turbinates, BAX and Caspase-3 expressions were increased whereas BCL-2 was decreased in NPs, and the differences were statistically significant (BAX 0.346±0.032 vs 0.302±0.037, Caspase-3 0.228±0.061 vs 0.158±0.065, BCL-2 0.090±0.047 vs 0.276±0.057, t value was 2.680, 2.361 and 7.575, respectively, all P<0.05). The expression levels of RUNX1 and apoptosis in pHNECs increased in a time-dependent manner after TNF-α exposure (P<0.05). Plasmid of sh-RUNX1-6 transfected silenced the expression of RUNX1 in pHNECs treated by TNF-α. After silencing RUNX1 in pHNECs apoptosis model, the protein levels of BAX and Caspase-3 were decreased, while the expression of BCL-2 was increased, the rate of apoptosis was decreased (P<0.05). Conclusions: RUNX1 is increased in NPs. Silencing RUNX1 can inhibit the apoptosis and reduce cell inflammatory damage of pHNECs induced by TNF-α.
Apoptosis ; Core Binding Factor Alpha 2 Subunit/genetics* ; Epithelial Cells ; Humans ; Nasal Polyps ; Turbinates

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

OBJECTIVETo establish the intrauterine growth curves of neonates in Shenzhen, China and to investigate the intrauterine growth of neonates in Shenzhen.

METHODSCross-sectional cluster sampling was performed for an on-the-spot investigation of 16 887 neonates (9 418 males and 7 469 females) with a gestational age of 27-42 weeks who were born in two hospitals in Shenzhen from April 2013 to September 2015. The Lambda Mu Sigma (LMS) method was used for the curve fitting of body weight, body length, head circumference, chest circumference, and crown-rump length.

RESULTSThe 3rd-97th percentile intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length were plotted for the neonates with a gestational age of 27-42 weeks who were divided into three groups (male, female, and mixed). The male neonates had significantly higher curves for the five indices than the female counterparts. The pattern and changing trend of body weight curves of these neonates were basically consistent with those in China Neonatal Network.

CONCLUSIONSThe percentile intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length in neonates with a gestational age of 27-42 weeks in Shenzhen which has been established can provide a reference for clinical practice in the department of neonatology.

Body Height ; Body Weight ; Cross-Sectional Studies ; Crown-Rump Length ; Female ; Fetal Development ; physiology ; Gestational Age ; Head ; anatomy & histology ; Humans ; Infant, Newborn ; Male ; Thorax ; anatomy & histology

To exert pharmacological effects, no matter therapeutic effect or toxic/side effect, it's necessary to achieve enough plasma concentration. Chinese medical compounds, which contain various ingredients, influence the metabolism of some active ingredients through the interaction of ingredients to improve curative effects or reduce toxic/side effects. Pharmacokinetics can be used to explore how Chinese medical compounds influence the in vivo metabolism of some active ingredients to achieve better curative effects.
Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; Humans

OBJECTIVETo establish height-weight indices in newborns of different gestational ages and to provide reference data for evaluation of intrauterine fetal growth.

METHODSThe weight, height, crown-rump length, head circumference, and chest circumference of 8 357 newborns were measured in Maternal and Child Health Care Hospital of Bao'an District of shenzhen between 2005 and 2006, with the method of fact-finding investigation with cross-sectional cluster sampling, to establish the height-weight indices in newborns of different gestational ages.

RESULTSFive gender-specific height-weight indices (Quetelet Index, QI; Kaup Index, KI; Rohrer Index, RI; Livi Index, LI; Polock Index, PI) in newborns of different gestational ages (28-44 weeks of gestation) in three different groups (boys+girls, boys, and girls) were established in Shenzhen, China, and were expressed as mean gestational weeks±SD. The five indices above all increased with increasing gestational age, and the highest values appeared at 41-43 gestational weeks, suggesting that body density and enrichment degree increased constantly with increasing gestational age. Three indices (QI, KI and PI) were higher in boys than in girls (P<0.05).

CONCLUSIONSWith the increasing gestational age, the body density and enrichment degree of newborns increase, and the enrichment degree in boys is better than that in girls.

Body Height ; Body Weight ; Cross-Sectional Studies ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Male ; Sex Characteristics

BACKGROUNDNurr1 plays an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons, and it is a potential target for Parkinson's disease (PD). Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs), but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.

METHODSThe mRNA levels of Nurr1 in PBMC of four subgroups of 362 PD patients and 193 healthy controls (HCs) using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurr1 expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level.

RESULTSThe relative Nurr1 mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments (de novo) (P < 0.001) and HC groups (P < 0.010), respectively. Furthermore, the increase in Nurr1 mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurr1 mRNA expression level in PBMC. In vitro, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurr1 mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively (P < 0.001).

CONCLUSIONSDA agonists can induce Nurr1 expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.

Adult ; Aged ; Aged, 80 and over ; Dopamine Agonists ; therapeutic use ; Female ; Humans ; Leukocytes, Mononuclear ; drug effects ; metabolism ; Male ; Middle Aged ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; genetics ; Parkinson Disease ; drug therapy ; genetics ; RNA, Messenger ; genetics ; Young Adult

OBJECTIVETo investigate the clinical value of the expression of glucose regulated protein 78 (GRP78) for assessment of severity, chemoresistance and prognosis in patients with gastric adenocarcinoma ( GC) .

METHODSA cohort of 237 patients with gastric cancer was included in this study. 160 patients of them were treated by D2 radical gastrectomy and adjuvant chemotherapy. The GRP78 expression was detected by immunohistochemistry and 80 patients of them were tested in vitro for cancer chemosensitivity by ATP-tumor chemosensitivity assay (ATP-TCA). In addition, the relationships were analyzed between GRP78 and age, gender, tumor differentiation, invasion, disease stage, lymph node metastasis and chemoresistance as well as disease-free survival (DFS).

RESULTSThe positive rate of GRP78 expression in the gastric adenocarcinoma was 68.8% before the initiation of chemotherapy. The positive GRP78 expression was significantly correlated with tumor invasion depth, poor differentiation, TNM stages, and lymph node metastasis (all P < 0.05), not correlated with gender and age, and high GRP78 expression was associated with the chemoresistance of the gastric cancer cells to chemotherapeutic agents. Negative GRP78 expression was associated with higher sensitivity to both drugs and regimens. The DFS of GRP78-positive group and GRP78-negative group was (53.6 ± 0.9) months and (38.3 ± 0.8) months, respectively (P = 0.041). Interestingly, subgroup analysis revealed that the DFS in GRP78-negative and-positive patients treated with taxane-containing chemotherapy was (58.6 ± 2.6) months and (49.1 ± 2.7) months, respectively, but the difference was statistically not significant (P = 0.111). In contrast, in the subset of GRP78-negative and- positive patients treated with taxane-containing regimens, the DFS was (45.5 ± 1.9) months and (35.1 ± 2.2) months, respectively, showing a significant difference (P = 0.038). In the group of patients with positive GRP78 expression, the patients treated with taxane-containing chemotherapy had a longer DFS [(49.1 ± 2.7) months] than those without that treatment [(35.1 ± 2.2) months], showing a significant difference (P = 0.017). Univariate analysis revealed that DFS was correlated with histological grade, GRP78 expression and lymph node metastasis (all P < 0.05). Multivariate analysis showed that GRP78 expression and TNM staging were independent influencing factors for gastric cancer (both P < 0.05).

CONCLUSIONSThe results of our study suggest that GRP78 may be a novel biomarker for assessment of malignant degree and prediction of chemoresistance in gastric cancer, and may be helpful to chemotherapy planning and prognosis prediction in patients with gastric cancer.

Adenocarcinoma ; drug therapy ; metabolism ; pathology ; surgery ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Bridged-Ring Compounds ; administration & dosage ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Female ; Gastrectomy ; Heat-Shock Proteins ; metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Taxoids ; administration & dosage

OBJECTIVETo investigate the epidemic characteristics and pathogenic spectrum of community acquired pneumonia (CAP) in Guangzhou from 2009 to 2012.

METHOD14 major comprehensive hospitals were selected from 11 districts as sentinel hospitals for CAP cases surveillance, including 18 982 223 in total during the 4 years. The characteristics of pathogenic spectrum of CAP were stratified and analyzed by year, age and season.

RESULTS18 982 223 cases were included in the surveillance from year 2009 to 2012, in which 56 618 cases were CAP. The number of CAP cases increased from 8677 in year 2009 to 19 947 in year 2012 in Guangzhou; while the percentage of visits for CAP raised from 0.22% (8677/3 893 800) to 0.41% (19 947/4 839 766). The difference showed statistical significance (χ(2) = 2693.00, P < 0.05). Among the hospitalized CAP cases, 66.05% (10 954/16 585) were aged ≤ 5 years old or > 66 years old. The percentage of cases infected by a single pathogen was 88.11% (14 613/16 585), while co-infected cases accounted for 4.17% (691/16 585). Bacteria accounted for the largest proportion of 65.25% (10 821/16 585) as a single pathogen, followed by mycoplasma 13.54% (2245/16 585), virus 9.01% (1494/16 585) and chlamydia 0.32% (53/16 585). The proportion of virus infection was increasing from 4.74% to 11.64%. The difference showed statistical significance (χ(2) = 135.32, P < 0.05). Bacteria infection was the leading causes for CAP cases in all age groups; however the percentage increased with the increasing of ages. The rate of bacterial infection was increased from 48.35% (2993/6191) among children aged ≤ 5 years old to 81.31% (3873/4763) among adults aged over 65 years (χ(2) = 1632.00, P < 0.05). The rate of atypical pathogens (mycoplasma, chlamydia) for children ( ≤ 15 years old) (25.99%, 1805/6945) was higher than that for adults aged ≥ 16 years old (5.12%, 494/9640) (χ(2) = 2.11, P < 0.05). The effect from season on the pathogenic spectrum was not observed.433 hospitalized CAP cases were dead from 2009 to 2012. Case fatality rate was highest among people aged over 65 years old (4.70%, 224/4763) and lowest among children aged between 6 to 15 years old (0.27%, 2/754).

CONCLUSIONThe incidence of community acquired pneumonia was rising in Guangzhou from 2009 to 2012. Bacteria was the dominant pathogen. Children and old people were the high-risk population of community acquired pneumonia; while co-infection was still at low level.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Community-Acquired Infections ; epidemiology ; microbiology ; Female ; Humans ; Infant ; Male ; Middle Aged ; Pneumonia ; epidemiology ; microbiology ; Sentinel Surveillance ; Young Adult