Hepacivirus ; Hepatitis C ; complications ; epidemiology ; Humans ; Lichen Planus, Oral ; complications ; epidemiology ; virology

OBJECTIVETo investigate the effects of total flavonoids of propolis (TFP) on apoptosis of myocardial cells of chronic heart failure and its possible mechanism in rats.

METHODSSix male SD rats were randomly selected as normal control group, the remaining rats were made as chronic heart failure (CHF) model by intraperitoneal injection of adriamycin. The rats in the successful model were randomly divided into five groups (n = 6): CHF group, total flavonoids of propolis low dose group (LD group), total flavonoids of propolis middle dose group (MD group), total flavonoids of propolis high dose group (HD group), digoxin group (DIG group). After six week treatment, cardiac function indexes of rats were recorded by signal acquisition system; brain natriuretic peptide (BNP), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) content in plasma were detected; Myocardial morphological changes and collagen fiber hyperplasia by HE and Masson staining were observed; Myocardial apoptosis was detected with TUNEL method and protein connexin 43(P-Cx43) expression was detected by Western blot method.

RESULTSCompared with NC group, left ventricular systolic pressure(LVSP) and maximal rise/fall velocity of left ventriculad pressure (± dP/dt(max)) absolute value in CHF group were significantly lowered (P < 0.01) while left ventricular end diastolic pressure (LVEDP) was increased significantly (P < 0.01); Contents of plasma BNP, cTnI, TNF-α and IL-6 in the CHF group were significantly improved (P < 0.01). Compared with CHF group, LVSP, ± dP/dt(max) absolute value in MD and HD groups were increased (P < 0.05), and LVEDP was significantly lowered (P < 0.01); LVEDP in LD group was significantly lowered (P < 0.01), changes in LVSP and ± dp/dt(max) absolue value were not obvious (P > 0.05). BNP, cTnI, TNF-α and IL-6 contents in MD and HD groups were significantly reduced (P < 0.01), but those plasma indicator changes were not obvious in LD group (P > 0.05). Western blot showed that P-Cx43 expression in CHF group was significantly higher than that in NC group (P < 0.01) and that in all TFP treatment groups it was decreased compared with CHF group (P < 0.05, P < 0.01), among which pairwise comparisons also showed differences (P < 0.05), myocardial apoptosis index (%)(22.62 ± 3.39) in CHF group was higher than that in NC group( 1.12 ± 0.24) (P < 0.01); compared with CHF group, the apoptosis index of myocardial cells (%) in LD,MD and HD groups, (15.79 + 2.8), (9.28 + 2.1) and (4.73 + 1.14) respectively, were significantly lower than those in the CHF group( P < 0.01). The expression level of P-Cx43 positively correlated with the apoptotic index (r = 0. 861, P < 0.01).

CONCLUSIONTotal flavonaids of propolis have inhibitory effect on apoptosis of myocardial cells of chronic heart failure induced by adriamycin in rats, and the mechanism may be closely related to the regulation of Cx43 expression, especially the regulatory phosphorylation status.

Animals ; Apoptosis ; Chronic Disease ; Connexin 43 ; metabolism ; Disease Models, Animal ; Doxorubicin ; adverse effects ; Flavonoids ; pharmacology ; Heart Failure ; drug therapy ; Interleukin-6 ; blood ; Male ; Myocardium ; pathology ; Myocytes, Cardiac ; drug effects ; Natriuretic Peptide, Brain ; blood ; Phosphorylation ; Propolis ; chemistry ; Rats ; Rats, Sprague-Dawley ; Troponin I ; blood ; Tumor Necrosis Factor-alpha ; blood

Objective To investigate the clinical features and risk factors of recurrent communityacquired pneumonia (CAP) in elderly patients.Methods Clinical data of elderly CAP patients admitted to the first affiliated hospital of Sun Yat-Sen university from January 2012 to December 2014 were analyzed retrospectively,including 48 cases of recurrent CAP and 299 cases of non-recurrent CAP.The clinical features were compared between two groups,and the risk factors of recurrent CAP were assessed with logistic regression analysis.Results No significant differences were observed between the two groups in age,sex,smoking,drinking,average hospital stays and total hospitalization expenses (all P ＞ 0.05).In the recurrent pneumonia group,the chronic obstructive pulmonary diseases [54.2％ (26/48) vs.35.5％ (106/299),χ2 =6.146,P=0.013],diabetes [41.7％ (20/48) vs.19.7％ (59/299),χ2 =11.317,P=0.001],the clinical symptoms include cough [79.2％ (38/48) vs.58.5％ (175/299),χ2 =7.432,P =0.006],sputum [70.8％ (34/48) vs.54.5％ (163/299),χ2 =4.488,P =0.034],fever [64.4％ (31/48) vs.40.8％(122/299),χ2 =9.488,P =0.002],poor appetite [52.1％ (25/48) vs.33.1％ (99/299),χ2 =6.483,P =0.011],choking cough [8.3％ (4/48) vs.2.7％ (8/299),χ2 =3.966,P =0.046],poor spirit [45.8％ (22/48) vs.28.4％ (85/299),χ2 =5.875,P =0.015],bilateral lung lesions [41.7％ (20/48)vs.28.8％ (68/299),χ2 =7.825,P =0.005],the complication of respiratory failure [31.3 ％ (15/48) vs.14.7％ (44/299),χ2 =8.012,P =0.005] were higher than those in non-recurrent group.Logistic regression revealed that chronic obstructive pulmonary disease (OR =2.607,95％ CI:1.268-5.358,P =0.009),diabetes (OR =2.948,95％ CI:1.457-5.966,P =0.003) and the history of respiratory failure (0R=2.778,95％CI:1.264-6.108,P=0.011) were risk factors of recurrent CAP.Conclusions Elderly patients with recurrent CAP has a higher rate of cough,sputum and fever,and the scope of lung lesions is broader.Chronic obstructive pulmonary disease,diabetes and the history of respiratory failure are the independent risk factors for recurrent CAP in the elderly.

Objective To reveal evolution characteristics and antigenic epitope variabilities of hemagglutinin (HA) gene of H3N2 viruses in Guangdong during 2014-2015.Methods The HA gene nucleotide sequence of influenza H3N2 virus isolated during 2014-2015 in Guangdong Province was selected by spatial-temporal distribution.The HA gene nucleotide sequences were compared with global HA genes downloaded from GenBank and GISAID and the gene nucleotide mutations were analyzed.The phylogenetic tree and the entropy chart were conducted.Results Compared with HA gene of vaccine strain A/Texas/50/2012,the substitutions of 25 amino acid sites occurred in the HA gene of the 17 Guangdong strains during 2014 to 2015.The epitope A,B,D and E of the HA1 gene developed mutations,which involved 11 amino acid sites.One glycosylation site deletion occurred in A/Guangdong/ 55/2015 in virtue of the N38K site mutation.The high mutation site was at 175 with entropy value of 1.16.The 363 site might be the positive selection while the 368 and 425 sites might be the negative selection sites by comprehensive evaluation of the screening results of the single likelihood ancestor countincy (SLAC),fixed effects likelihood (FEL) and internal fixed-effects likelihood (IFEL) model.Conclusions The mutations emerge in the epitopes A,B,D and E of HA gene of the Guangdong H3N2 stains.Evolution at 363 site is positive selection while those at 368 and 425 sites are negative selection.The mutation accumulation might lead to the epidemic of influenza H3N2.

Background A main cause of visual impairment in proliferative diabetic retinopathy (PDR) is vitreous hemorrhage and retinal detachment due to contraction of fibrovascular membrane.To explore the pathogenic mechanism of fibrovascular membrane is a new target for the prevention and management of PDR.Objective This study was to determine the change in expression of vascular endothelial growth factor (VEGF),connective tissue growth factor(CTGF) and pigment epithelium derived factor(PEDF) in the proliferative membranes of patients with PDR after intravitreal injection of avastin,an anti-VEGF agent.Methods This study was approved by the Medical Ethic Committee of Tianjin Medical College,and written informed consent was obtained from each patient before enrollment.A prospective randomized-controlled study was designed.Twenty-six eyes of 24 patients with PDR scheduled for surgery were enrolled from January to June,2008 in Tianjin Medical College Eye Hospital.The patients were randomized into the simple vitrectomy group and avastin injection combined with vitrectomy group,with matched gender,age and disease duration.1.25 mg (0.05 ml) of avastin was intravitreally injected prior to surgery,and vitrectomy was performed 10 days after injection in the avastin injection combined with vitrectomy group,and only vitrectomy was given in the simple vitrectomy group.Preretinal membrane was collected during the surgery.Expression of VEGF,CTGF and PEDF in the preretinal membranes was assayed by immunochemistry.Results VEGF,CTGF and PEDF were expressed in the cytoplasm.The rate of VEGF expression in the preretinal membranes was 30.77％ in the avastin injection combined with vitrectomy group,showing a significant reduction in comparison with the simple vitrectomy group(100.00％)(U =4.000,P＜0.01).The rate of expression CTGF was remarkable elevated in the avastin injection combined with vitrectomy group compared with the simple vitrectomy group (92.31％ vs.62.54％)(U=7.500,P=0.048).However,no significant difference was found in the expression rate of PEDF between the two groups(100.00％ vs.92.31％) (U =65.500,P =0.299).Conclusions The results suggest that intravitreal injection of anti-VEGF drugs resulted in the decrease of VEGF expression and increased CTGF expression in proliferative membranes from patients with PDR.

Background Doxycycline is a broad spectrum antibiotic,and it is frequently used in the treatment of ocular surface diseases.Objective The purpose of the present study was to investigate the effect of doxycycline on the inhibition of cell proliferation in bovine corneal myofibroblasts in vitro and assess its contribution to ocular surface repairing mechanism.Methods Six fresh bovine corneas were collected.The corneal stromal layer was isolated by two-step method of 1.0 g/L and 2.0 g/L collegenase-1.Isolated cells were plated at mantaryay culture flask in 10％ FBS of RPMI-1640.Vimentin and alpha-smooth muscle actin (α-SMA) organization were evaluated by immunocytochemistry,and the cells with influoresccence staining for vimentin and α-SMA were identified as the corneal myofibroblasts.Doxycycline at the concentrations of 10,20,40,60,80 mg/L was added to the medium,respectively,in different concentrations of doxycycline groups.Dexamethasone (120 mg/L)was used in the same way in the positive control group,and no drug was used in the negative control group.Cell proliferation was evaluated by MTT and the cell cycle was analyzed by BD FACScan flow cytometer assay 24 hours and 48 hours after addition of any drug.Results The cells grew well and showed the positive response for vimentin and α-SMA.MTT assay showed that the A570values of bovine corneal myofibroblasts were gradually declined with the increase of the concentration of doxycycline and lapse of active time,showing statistically significant difference (Fconcentration =1233.778,P＜0.001 ; Ftime =227.564,P ＜ 0.001).And the difference between the two factors was also statistically significant (Ftime*concentration =51.656,P＜0.001).Flow cytometry cell cycle analysis showed that 24 hours after 10,20,40,60,80 mg/L doxycycline treated,the perentage of of corneal myofibroblast cell in G0-G1 phase was 82.85％,84.36％,85.18％,87.12 ％ and 89.31％,showing significant increase in comparison with 63.89％ of the negative control group (all P＜0.05),and that of 40 mg/L doxycycline group was near the positive control group.Forty-eight hours after 10,20,40,60,80 mg/L doxycycline treated,the perentage of of corneal myofibroblast cell in G0-G1 phase was 82.78％,86.15％,88.23％,89.57％,93.00％,with significant increase in comparison with 70.17％ of the negative control group (all P ＜ 0.01),and that of 40 mg/L doxycycline group was near the positive control group.Conclusions The growth of the bovine corneal myofibroblasts is inhibited by doxycycline in time-and dosedependent manner in the range from 10 mg/L to 80 mg/L,and 40 mg/L of doxycycline has an obviously inhibitory action as 120 mg/L dexamethasone.

Local focal adhesion kinase (FAK) is a non-receptor intracellular tyrosine kinase that plays an important role in tumor initiation, development, metastasis and invasion, and is considered to be an important target for the development of antineoplastic drugs. It has both kinase-dependent and non-kinase-dependent scaffolding functions. However, traditional small molecular inhibitors can only inhibit its kinase-dependent activity, so it is difficult to target the kinase-independent scaffolding function. Therefore, there is an urgent need for novel strategies to enhance FAK targeting to lay the foundation for determining the druggability and discovery of FAK inhibitors. Proteolysis targeting chimera (PROTAC) is a new drug development strategy that can recruit E3 ligase to specifically ubiquitinylate target proteins for degradation through the proteasome system. The unique mechanism of action of the PROTAC system could be used to target and degrade the FAK protein, thus eliminating the scaffolding function of FAK. In this review, FAK protein, the signaling pathway, and small molecule inhibitors are briefly described, and the latest research progress in targeting the degradation of FAK using PROTAC technology is summarized.

Objective: To observe the effect of overexpression of miRNA200a (miR-200a) recombinant lentivirus on the expression of Wnt/β-catenin signaling pathway in mouse lung epithelial cell line MLE-12 induced by silica (SiO₂) . Methods: The mice were divided into SiO₂ control group (SiO₂) , virus control group (SiO₂+Lv-NC) group and overexpressing miR-200a virus group (SiO₂+Lv-miR-200a). The expression of β-catenin, MMP2, MMP9, TCF-4 and Cyclin D1 mRNA and protein were detected by realtime-PCR and western blot after incubating cells for 18 h stimulating at the final concentration of 200 μg/ml of SiO₂. Results: The expression of miR-200a in MLE-12 cells of SiO₂+Lv-miR-200 a group was significantly higher than that in SiO₂ group and SiO₂+Lv-NC group. The mRNA and protein expression of β-catenin, MMP2, MMP9, TCF-4 and Cyclin D1 in MLE-12 cells of SiO₂+Lv-miR-200a group were significantly lower than those in SiO₂ group and SiO₂+Lv-NC group (P<0.05) . Conclusion Overexpression of miR-200a can inhibit the expression of related genes of Wnt/β-catenin signaling pathway in silica-induced mouse lung epithelial cells.

Objective: To provide scientific evidence for the prevention and control measures of acute and chronic occupational poisoning by analyzing the epidemiological and occupational characteristics of occupational chemical poisoning cases reported in Tianjin city during 2006-2015. Methods: In September 2016, based on the China Disease Control and Prevention Information System, a database of occupational poisoning cases in Tianjin from 2006 to 2015 was established. The epidemiological characteristics of occupational poisoning were analyzed including three distributions firstly, and then the occupational characteristics were analyzed such as length of service, industry distribution and source of poison. Results: There were 174 occupational poisoning patients in Tianjin from 2006 to 2015, including 16 cases of acute poisoning (9.20%) and 158 cases of chronic poisoning (90.8%) , and the proportion of occupational poisoning cases reported in Binhai New Area is the highest. The number of reported cases of chronic occupational poisoning shows a downward trend. Occupational poisoning cases are concentrated mainly in the age of 40-60 years and length of service of 10-20 years. The high incidence of occupational poisoning mainly exists in the chemical raw materials and chemical manufacturing industry and general, professional equipment manufacturing industry. Acute poisoning was mainly by asphyxial gas (50.00%) , and chronic poisoning was mainly by organic solvent (43.67%) . Conclusion The distribution of occupational poisoning cases in diverse toxic types and regions in Tianjin are quite different. The occupational safety precautions of the chemical raw materials and chemical products manufacturing and occupational poisoning control work in Binhai new area should be strengthened to reduce the occurrence of occupational poisoning.

Objective: To investigate the influence of depression symtoms and related occupational stress on workers in chip manufacturing industry. Methods: By using cluster sampling method, 2 251workers in electronic manufacturing industry were selected as study subjects in July-December 2016. The simple Occupational Stress Questionnnaire and The Chinese version of Effort-reword imbalance questionnaire (ERI) Questionnnaire were used to investigate and evaluate their job demand-control-support questionnaire (JDC) and ERI Occupational stress stiuation respctively. Depression symptoms were measured by the depression module of the patient health questionnaire (PHQ-9) . Results: Among the 2 251 workers, 77.03% workers were found high level of depression symptom.486 workers were the highest level depression.1 248 workers were the higher level depression. The scores of depression symptoms in the related influceing factors JDC and ERI occupational stress were different (P<0.05) . The multivariate logistic analysis results indicated the main positve factors of depression were above college degree, more than 1 years of working age and high input (P<0.05) . The main protective factors of depression were non migrant workers and high return (P<0.05) . Conclusion The rate of depression of workers is relatively higher in chip manufacturing factory. Enterprises should pay special attention to workers who were above college degree, more than 1 years of working age and high input, ERI occupational stress.