Objective To explore the role of JNK signaling pathway in epithelial mesenchymal transition (EMT)process of human alveolar epithelial cells A549 induced by TGF‐β1 in vitro.Methods Human alveolar epithelial cells (A549)cultured in vitro were divided randomly into three groups :normal group ,TGF‐β1 group ( treated by TGF‐β1 with 10 ng/mL)and inhibitor group (treated by 10 ng/mL TGF‐β1 and 20 μmol/L Sp600125).Morphological observation on the cells was performed under light microscope after culturing in 3% serum medium for 72 h. The expression of E‐cadherin (E‐cad ,a epithelial cell marker) ,α‐smooth muscle actin (α‐SMA ,a mesenchymal cell marker)and Collagen fibers Ⅰ(ColⅠ ,a mesenchymal cell marker)were tested by RT‐PCR.The level of JNK phosphorylation (p‐JNK)was detected through Western blot.All experiments were repeated three times at least.Results The normal human alveolar epithelial cells (A549)cultured invitro were arranged closely like peb‐bles.E‐cad expressed at a certain level ,while the expression ofα‐SMA ,ColⅠand p‐JNK was weakly detected.In TGF‐β1 group , the cells were spindle‐shaped ,the expression of E‐cad was reduced ,while the expression ofα‐SMA ,ColⅠand p‐JNK was signifi‐cantly increased 72 h after treatment of TGF‐β1. However ,compared with TGF‐β1 group ,spindle‐shaped cells in the inhibitor group were recovered after 72 h being treated by TGF‐β1 and Sp600125 ,the expression of E‐cad was increased and the expres‐sion levels of α‐SMA ,ColⅠand p‐JNK were significantly decreased 72 h after treatment with TGF‐β1 and Sp600125 in inhibitor group. As compared with normal group ,the shape of the cells in inhibitor group was prolate ,and the expression of E‐cad ,α‐SMA ,ColⅠand p‐JNK was not significantly different.Conclusion JNK signaling pathway is related to the process of EMT of human alveolar epithelial cells induced by TGF‐β1. Sp600125 ,a special inhibitor of JNK ,could validly restrain the process.

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Objective To evaluate the effects of nucleos (t)ide analogues initial treatment on virology and complications in hepatitis B virus (HBV) related decompensated liver cirrhosis.Methods From May 2012 to October 2013,a total of 209 patients with HBV related decompensated liver cirrhosis of 18 hospitals in China were enrolled.According to antiviral medicine taken by them,they were divided into entecavir (ETV) group (n =161),lamivudine (LAM) monotherapy or combined with adefovir (ADV)group (n=48,LAM 22 cases,LAM+ADV 26 cases).During the 12-month follow up period,ChildPugh scores,the level of HBV DNA and complications of liver cirrhosis were documented every three months,the safety evaluation was also carried out.The t-test or chi-square test was performed for statistical analysis.Results In ETV group,before treatment and 12 months after treatment,Child-Pugh scores were 7.91±2.05 and 5.75±1.72,respectively,and the latter was lower than the former (t=10.130,P＜0.01); in LAM alone or combined with ADV group,Child-Pugh scores were 8.08±2.23 and 5.85±1.44,respectively,and the latter was lower than the former (t=5.480,P＜0.01).However there was no significant difference in Child-Pugh scores between the two groups in different time points (both P＞0.05).The undetectable rates of HBV DNA gradually increased along with the treatment period.After 12 months treatment,the undetectable rate of HBV DNA of ETV group was 91.0％ (61/67),and that of LAM alone or combined with ADV group was 87.5％ (35/40),there was no significant difference between the two groups (P＞0.05).Before treatment and 12 months after treatment,the incidences of ascites were 59.4％ (82/138) and 15.0％ (12/80) in ETV group,the latter was lower than the former (x2 =40.740,P＜0.01) ; the incidences of ascites in LAM alone or combined with ADV group were 62.2％ (28/45) and 8.1％ (3/37),and the latter was lower than the former (x2=25.290,P＜ 0.01).After 12 months treatment,the rates of esophageal varices disappearance of ETV group and LAM alone or combined with ADV group were 26.6％ (33/124) and 25.0％ (7/28),accordingly the rates of gastric varices disappearance were 2.5％ (1/40) and 1/19,and the difference was not statistically significant between the two groups (both P＞0.05).There was no significant difference in serum urea nitrogen,serum creatinine and estimated glomerular filtration rates between the two groups before treatment and at different time points after treatment (all P＞0.05).Conclusion The efficacy and safety of ETV and LAM alone or combined with ADV are similar in patients with HBV related decompensated liver cirrhosis,however,the long-term efficacy should be identified by further clinical observation.

Objective To explore the roles of IκBα and TGF-β1 on airway inflammation in rats with chronic bronchitis induced by smoking and study the effects and mechanism of anti-inflammation of pretreatment with ambroxol. Methods Sixty male wistar rats were randomly divided into four groups: Normal dosage group, model group, high dosage group and low dosage group. The rats with chronic bronchitis were established by smoking. For high and low dosage group, rats were pretreated respectively with ambroxol group, rats were pretreated with normal saline through peritoneal injection as much as the low dosage group.After 76 days, the histopathologic changes stained in hemotoxylin and eosin (H. E.) of bronchopulmonary tissues were observed under opticalmicroscope, white cell counts and differential analysis were performed in BALF, the expression of IκBα and TGF-β1 were detected by immunohistochemistry. Results The pathological changes of model group were in consistent with that of chronic bronchitis, but the degrees were significantly reduced in high and low dosage groups. Compared with those in normal group, the white cell count and the neutrophilic granulocyte count of BALF in model group were significantly increased and the macrophagocyte count decreased, and the expression of IκBαwas significantly decreased(t =3.24,3.31,3.29,3.48, P ＜0. 05) and the TGF-β1 significantly increased (P ＜0. 05). Compared with those in the model group, the white cell count and the neutrophilic granulocyte count of BALF in high and low dosage group were significantly decreased and the macrophagocyte count increased, the expression of IκBαwas significantly increased (t =2. 86,2. 97,2. 92,3.52,2.42,2. 88,2. 58,3.48, P ＜0. 05) and the TGF-β1 significantly decreased (P ＜0. 05) . Compared with those in low dosage group, the expression of TGF-β1 was decreased and the expression of IκBαincreased in high dosage group (t =2. 82,3.64, P ＜0. 05). Conclusions Down-regulating the expression of IκBα and up-regulating of TGF-β1 may be involved in the process of airway inflammation in rats with chronic bronchitis induced by smoking. Ambroxol might have better effects on ameliorating airway inflammation by up-regulating the expression of IκBα and down-regulating of TGF-β1.

Objective To analyze the antibiotic resistance of pathogenic bacteria recovered from bronchial secretions by bronchofiberscope in bronchiectasis patients complicated with infection for improving antibacterial therapy. Methods A total of 97 bronchiectasis patients complicated with infection treated in Liyuan Hospital during the period from June 2013 to December 2015 were included in this analysis. The pathogens were recovered from bronchial secretions by bronchofiberscope and subjected to antimicrobial susceptibility testing by Kirby-Bauer disc method. The data were analyzed with WHONET 5.5 software. Results Pathogenic organisms were isolated from 53 (54.6%) of the 97 patients, including 49 (92.4%) strains of gram negative bacilli, mainly Pseudomonas aeruginosa, followed by Acinetobacter baumannii, Klebsiella pneumoniae, 3 (5.7%) strains of?gram?positive?cocci,?specifically?2?strains?of?S. aureus and 1 strain of S. pneumoniae, and 1 (1.9%) strain of Candida albicans. Antimicrobial susceptibility testing showed that most P. aeruginosa isolates (>71.8%) were susceptible to tobramycin, amikacin,cefepime, and aztreonam, but 100% resistant to levofloxacin. More A. baumannii isolates were susceptible to tobramycin and amikacin (both 85.7%), followed by imipenem (>42.9%). More than half (>50%) of the K. pneumoniae isolates were resistant to cefotaxime, gentamycin, ciprofloxacin, and levofloxacin.Conclusions Gram negative bacilli are dominant in the pathogenic organisms recovered from bronchial secretions in bronchiectasis patients complicated with infection. Most of the pathogens are relatively susceptible to tobramycin and amikacin, but resistant to ciprofloxacin?and?levofloxacin.

Objective To evaluate the effects and mechanism of valerian extract treatment on bleomycin-induced pulmonary fibrosis of rats. Methods After healthy Wistar rats(irrespective of sex)were given diethyl ether inhalation anesthesia, giving a single intratracheal instillation of bleomycin at a dose of 5 mg/kg to make a pattern of pulmonary fibrosis. 65 survival rats were randomly divided into four groups: Valerian high-dose groups(n = 16), Valerian low-dose groups(n = 16), Colchicine group(n = 16)and Model group (n = 17).Each group was given a dose of 100 mg/kg valeian extract everyday, a dose of 20 mg/kg valeian extract Valeian extract , a dose of 100μg/kg colchicine and a dose of 10ml/kg after second day. And in each groups, 6 rats were killed on day 7, 10 rats were killed on day 28 after instillation respectively. Rats in control group (n = 8) were instilled with saline intractracheally and saline was given everyday with a dose of 10ml/kg. Control group was killed on day 28. After rats were killed, The right lower pulmonary lobes were harvested for HE-staining, Masson-staining was used to observe the transformation of pulmonary tissue and immunohistochemistry was used to examine transforming growth factor-β1 (TGF-β1) which was analyzed by image analysis system. Results No obvious transformation were found in control group. The alveolitis in valerian and colchicine groups were ameliorated, compared with model group on day 7. The expressions of TGF-β1 in control group were lower than that in model group, and the mean integrated optical densities of TGF-β1 in control group were lower than that in mod-el group(P<0.05). The pulmonary fibrosis in valerian and colchicine group were ameliorated, compared with model group on day 28. The expressions of TGF-β1 in valerian and colchicine group were lower than that in model group. There were no significant differences between the valerian group and the colchicine group. Conclusion Valerian extract could reduce the degree of alveolitis and fibrosis induced by bleo-mycin through suppressing of TGF-β1.

Immune-checkpoint blockers(ICBs)have been well received in a variety of tumors,and the quality of patient life has improved significantly.However,the reasons why not all patients treated with ICBs benefit from lesion control,symptom improvement,and survival time.Many patients are resistant to the first time when they have been using ICBs for a period of time.This is a clinical challenge.This review lists possible causes of primary drug resistance and acquired resistance to ICBs.The primary resistance is associated with several mechanisms,including tumor microenvironment,cancer cells themselves and other related factors.The acquired resistance includes nonclassical immunoprecipitation molecules secondary overexpression,abnormalities of antigen presenting signal pathway and dysfunction of T cell activation killer.Finally,we have described a variety of possible new combination of treatment,including combined radiotherapy and chemotherapy,and combined targeted therapy with other measures.

[ ABSTRACT] AIM:To observe the effects of long-term cigarette smoke exposure on pulmonary vascular remode-ling and the protein expression of transforming growth factor-β1 ( TGF-β1 ) in the rats, and to explore the mechanism. METHODS:SD rats (n=36) were randomly divided into control group, 2-week smoke exposure (S-2W) group and 12-week smoke exposure (S-12W) groups.HE staining andα-smooth muscle actin staining were performed to observe the pul-monary vascular remodeling.The protein expression of proliferating cell nuclear antigen ( PCNA) and TGF-β1 in the pulmo-nary arteries was determined by the method of immunohistochemistry.The mRNA expression of TGF-β1 in the pulmonary arteries was evaluated by RT-qPCR.RESULTS:Compared with control group, ratio of pulmonary vessel wall thickness to vessel diameter ( WT%) and percentage of muscularized vessels were significantly increased in S-2W group and S-12W group ( P<0.01) .Significant increases in the protein expression of PCNA and TGF-β1 in smoke exposure groups were ob-served compared with control group.There was significant difference between 2 model groups (P<0.01).Compared with control group, the mRNA expression of TGF-β1 in pulmonary artery walls obviously increased in smoke exposure groups. There was significantly difference between S-2W and S-12W groups (P<0.05).The mRNA expression of TGF-β1 was positively correlated with pulmonary vascular muscularization, WT% and the protein expression of PCNA.CONCLU-SION:Long-term cigarette smoke exposure results in pulmonary artery remodeling in rats.The possible mechanism is that cigarette smoking exposure induces the over-expression of TGF-β1 at mRNA level in pulmonary vessels and promotes the proliferation of pulmonary vascular smooth muscle cells in rats.

OBJECTIVE:To probe into the status quo,characteristics and influencing factors of ADR cases in our city. METHODS:In the retrospective statistical analysis study,a total of 752 ADR cases reported in Panzhihua Municipal ADR Monitoring Center in 2008 were analyzed and evaluated in respect of patients' age and sex,route of administration,drug varieties,organs and system involved and common countermeasures for ADR,etc. RESULTS:Of the total 752 ADR cases,323 cases of patients aged more than 60 showed the highest proportion(42.95%); 401 cases(53.32%) were caused by intravenous route; 810 kinds of drugs were used,of which antibiotics caused ADR in 317 cases (39.14%); lesions of skin and its appendants were the most common presentations of the ADR,which appeared in 314 cases(36.38%). CONCLUSION:The incidence of ADR relates to the patients' age,routed of administration and frequency of clinical drug use,which should be emphasized in the clinic.

Objective To demonstrate the role of clinical pharmacists in nutritional support for a patient with malignant obstructive jaundice and to provide a reference for the clinical application of nutritional supplements in patients during the perio-perative period.Methods Clinical pharmacists evaluated the nutritional status of an obstructive jaundice patient with nutrition risk screening tool and developed nutrition support programs perioperatively.The daily dose of 30% long-chain fat emulsion 250 ml was replaced with 20% medium/long-chain fat emulsions 250 ml.Oral nutrition support was added.Pharmaceutical care was implemented for the patient during the perioperative period.Results During the perioperative period,parenteral nu-trition support was changed to enteral nutritional support.The patient′s nutritional status and jaundice were improved.The pa-tient recovered well from surgery with no complication.Conclusion Clinical pharmacists work closely with physicians in devel-oping and adjusting nutritional support program to improve the nutritional status and pharmaceutical care for patients.