Reliability and validity of Chinese version of a tool to assess the quality of life in idiopathic pulmonary fibrosis in patients with interstitial lung disease

Objective:This paper aims to determine the reliability and validity of the Chinese version of a tool that assesses the quality of life in idiopathic pulmonary fibrosis(cATAQ-IPF)in patients with interstitial lung disease(ILD).Methods:We used the process of scale introduction to establish cATAQ-IPF.The content validity of the scale was evaluated by six experts.A total of 92 patients with ILD completed the cATAQ-IPF,St.George's respiratory questionnaire(SGRQ),and The Medical Research Council dyspnoea scale at the baseline,and 15 patients completed cATAQ-IPF at the follow-up period 2 weeks later.Thus,yielding data were used to assess various psychometric properties of cATAQ-IPE Intraclass correlation coefficient(ICC),Cronbach'sαcoefficient,content validity index(CVI),item-level CVI(I-CVI),Pearson's coefficients,criterion-relation validity,and known-group validity were used for data analysis.Results:The cATAQ-IPF showed excellent test-retest reliability(ICC=0.95),except for the therapy domain(Cronbach'sα=0.60)and acceptable internal consistency(Cronbach'sα=0.96 for the total).The scale-level CVI was 0.80,and the I-CVI was in the range of 0.78-1.00.The total cATAQ-IPF score was strongly correlated with the SGRQ total score(r=0.71,P<0.01).The cATAQ-IPF score of patients with ILD was 250.74±47.39,and that of patients with IPF was 287.90±22.56.Patients with IPF possessed considerable impairments in health-related quality of life according to the cATAQ-IPF score(t=4.94,P<0.01).Conclusions:The cATAQ-IPF is a reliable and valid instrument for the evaluation of quality of life of Chinese patients with various forms of ILD.

Mechanisms of the alternative activation of macrophages and non-coding RNAs in the development of radiation-induced lung fibrosis

Radiation-induced lung fibrosis(RILF) is a common side effect of thoracic irradiation therapy and leads to high mortality rates after cancer treatment. Radiation injury induces inflammatory M1 macrophage polarization leading to radiation pneumonitis, the first stage of RILF progression. Fibrosis occurs due to the transition of M1 macrophages to the anti-inflammatory pro-fibrotic M2 phenotype, and the resulting imbalance of macrophage regulated inflammatory signaling. Non-coding RNA signaling has been shown to play a large role in the regulation of the M2 mediated signaling pathways that are associated with the development and progression of fibrosis. While many studies show the link between M2 macrophages and fibrosis, there are only a few that explore their distinct role and the regulation of their signaling by non-coding RNA in RILF. In this review we summarize the current body of knowledge describing the roles of M2 macrophages in RILF, with an emphasis on the expression and functions of non-coding RNAs.

Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene a4 hydrolase and blocking LTB4 biosynthesis

OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a potential strategy for the treatment of ALI or IPF,we identified potent inhibitors of Leukotriene A4 hydrolase(LTA4H),a key enzyme in the biosynthesis of LTB4.METHODS In this study,we identified two known histone deacetylase(HDAC)inhibitors,suberanilohydroxamic acid(SAHA)and its analogue 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide(M344),as effective inhibitors of LTA4H using enzymatic assay,thermofluor assay,and X-ray crystallographic investigation.We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay.A murine experimental model of ALI was induced by lipopolysaccharide(LPS)inhalation.Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA.We next examined m RNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using q RT-PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA.We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin(BLM)-induced IPF model.RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H,significantly decrease LTB4 levels in neutrophil,and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose.CONCLUSION Collectively,SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.

Research progress of renal interstitial fibrosis

Renal interstitial fibrosis （RIF） is a common pathological process of chronic kidney disease that progresses toend-stage renal failure. The degree of RIF is closely related to renal function. The study of the pathogenesis of renalinterstitial fibrosis, exploration of effective prevention measures to delay the progress of end stage renal disease andprolong the life of patients is significant. The pathology of RIF has complicated extracellular and intercellularmechanisms, involving many cells and cytokines, resulting in an incomplete mechanistic understanding of thedisease. Finding effective herbs or herbal extracts for prevention and treatment of RIF is crucial because currentmedical approaches do not reliably slow or reverse RIF. The research progress of RIF in recent years issummarized as follows.

Pre-Lung transplant reflux testing demonstrates high prevalence of gastroesophageal reflux in cystic fibrosis and reduces chronic rejection risk

BACKGROUND Gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic rejection.GER is common in cystic fibrosis(CF),but factors influencing the likelihood of pre-transplant pH testing,and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown.AIM To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF.METHODS This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant.Patients with pretransplant anti-reflux surgery were excluded.Baseline characteristics(age at transplantation,gender,race,body mass index),self-reported GER symptoms prior to transplantation,and pre-transplant cardiopulmonary testing results,were recorded.Reflux testing consisted of either 24-h pH-or combined multichannel intraluminal impedance and pH monitoring.Post-transplant care included a standard immunosuppressive regimen,and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients.The primary outcome of chronic lung allograft dysfunction(CLAD)was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria.Statistical analysis was performed with Fisher’s exact test to assess differences between cohorts,and time-to-event Cox proportional hazards modeling.RESULTS After applying inclusion and exclusion criteria,a total of 60 patients were included in the study.Among all CF patients,41(68.3%)completed reflux monitoring as part of pre-lung transplant evaluation.Objective evidence of pathologic reflux,defined as acid exposure time>4%,was found in 24 subjects,representing 58%of the tested group.CF patients with pre-transplant reflux testing were older(35.8 vs 30.1 years,P=0.01)and more commonly reported typical esophageal reflux symptoms(53.7%vs 26.3%,P=0.06)compared to those without reflux testing.Other patient demographics and baseline cardiopulmonary function did not significantly differ between CF subjects with and without pre-transplant reflux testing.Patients with CF were less likely to undergo pre-transplant reflux testing compared to other pulmonary diagnoses(68%vs 85%,P=0.003).There was a decreased risk of CLAD in patients with CF who underwent reflux testing compared to those who did not,after controlling for confounders(Cox Hazard Ratio 0.26;95%CI:0.08-0.92).CONCLUSION Pre-transplant reflux testing revealed high prevalence of pathologic reflux in CF patients and was associated with decreased risk of CLAD.Systematic reflux testing may enhance outcomes in this patient population.

Exploring the mechanism of Qinghaobiejiatang in treating renal interstitial fibrosis based on network pharmacology

To explore the potential mechanism of the classic ancient prescription Qinghaobiejiatang(QHBJT)in treating renal interstitial fibrosis.Methods:Obtain the active ingredients of Qinghao(Artemisiae annuae herba),Biejia(Trionycis carapax),Dihuang(Rehmanniae radix),Zhimu(Anemarrhenae rhizoma),and Mudanpi(Moutan cortex)through TCMSP and TCMID databases.Collect disease targets through the GENECARDS database.Use Venny2.1.0 platform to draw Venn diagrams to map drugs and disease targets.Import the key targets into Cytoscape 3.7.2 software to draw a network diagram of“drugs-active ingredients-diseases-key targets”.The STRING11.0 database was used to construct the key target protein interaction network diagram.Use R language for Gene ontology function and kyoto encyclopedia of genes and genomes pathway enrichment analysis.Results:A total of 317 active ingredients were obtained through screening,involving 166 targets,and 102 active ingredients related to disease targets,mainly involved in the regulation of key targets such as FOS,IL6,MTOR,MAPK8,RELA,CCND1,TP53,EGFR,and CASP3 signal pathways related to viral infection,tumor-related,apoptosis,signal transduction,fluid shear stress and atherosclerosis play a synergistic role in the treatment of renal fibrosis.Conclusion:The effect mechanism of QHBJT in treating renal interstitial fibrosis is related to inflammation,oxidative stress,hypoxia,apoptosis,pathological activation and damage of renal tubular epithelial cells mediated by the above pathways.

Mechanisms of renal interstitial fibrosis: cross-talk between mitophagy and NLRP3 inflammasome

Renal interstitial fibrosis(RIF)is the main pathological basis leading to end-stage renal disease,and is closely related to the prognosis of patients with kidney disease.Increasing evidence as shown that mitophagy and NLRP3 inflammasome play important roles in the pathogenesis of RIF.Studies suggest that inhibiting NLRP3 inflammasome by activating mitophagy can prevent and alleviate RIF.This review summarizes role played by cross-talk between mitophagy and NLRP3 inflammasome in promoting RIF,so as to offer new perspectives on more effective slow the progression of renal diseases and fibrosis prevention.

Visual Analysis of Knowledge Map of Traditional Chinese Medicine in Prevention and Treatment of Pulmonary Interstitial Fibrosis Based on CiteSpace

Objective: To analyze the relevant research literature on the prevention and treatment of pulmonary interstitial fibrosis with traditional Chinese medicine (TCM), understand the current research status, hot spots and future development trend in this field, and provide basis and feasible suggestions for further research in this field. Methods: The journal literatures related to the prevention and treatment of pulmonary interstitial fibrosis with TCM in recent 20 years in CNKI database were searched and passed through CiteSpace 5.8.R3 generates the knowledge map of relevant literature authors, document issuing institutions and keywords, and makes visual analysis. Results: A total of 1,576 documents were included, and the annual number of documents showed a fluctuating upward trend, forming a relatively stable research team represented by authors such as LYU Xiaodong, PANG Lijian and LIU Chuang;According to the atlas of document issuing institutions, Shandong University of Traditional Chinese Medicine and its affiliated hospitals ranked first in the number of documents issued, and the cooperation between institutions is dominated by the University of traditional Chinese medicine and its affiliated hospitals;Keyword cluster analysis shows that a large number of studies have been carried out in the field of etiology and pathogenesis, TCM compound, clinic and experiment. Conclusion: The research on the prevention and treatment of pulmonary interstitial fibrosis with TCM has a high degree of attention, but the cooperation network between the research authors and institutions needs to be strengthened. The research on the pathogenesis and improving the quality of life of patients is the trend of development in the future.

Effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rats

Objective:To observe effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rate.Methods:A total of 75 SD rate were randomly divided into A,B,C,D,E groups with 15 in each group.Rats in group A served as the control group received just only but tissue separation without modeling operation,while model of unilateral ureteral obstruction(UUO) was established in B,C,D,E groups.Rats in A,B group were given saline lavage placebo treatment,while rats in C,D,E groups were given dianunonium glycyrrhizinate and alprostadil injection.Five rats were sacrificed 1,2,3 weeks after modeling,serum creatinine level of femoral venous blood was determined.Transforming growth factor- β1(TCF- β1) and concentration of connective tissue growth factor(CTGF) were also detected by using ELISA.Line renal interstitial tissue was taken after HE staining,renal interstitial TGF- β1 and CTGF expression were detected by using immunohistochemical method.Results:Serum creatinine levels of B,C,D,E group at different time points in were significantly higher than that of group A(P<0.05);serum creatinine levels in group B were significantly higher than that of C,D,E group at each time point(P<0.05).Serum creatinine level of Croup E was significantly lower than C,D group after 2,3 weeks(P<0.05).Rate in A group at each time point showed no significant changes in TGF- β1 and CREA concentration in serum and kidney tissues(P>0.05);while serum and kidney tissue TGF- β1,concentration of CREA.expression of rats in B,C,D,E groups showed a gradual increasing trend over time.TCF- β1 and CREF of Group B in serum and kidney tissues at each time point were significantly higher than that of the other groups(P<0.05).TCF- β1 and CREF of Group E in serum and kidney tissues at each time point were significantly lower than that of B,C,D group at all time points in serum and kidney tissues(P<0.05).Conclusions:Alprostadil combined with diammonium glycyrrhizinate can significantly lower the expression of TGF- β1 and CTGF in serum and tissues of SD rat with renal interstitial fibrosis,thus inhibit rat renal interstitial fibrosis process.It has synergy protective effect.

Effects of Losartan on Cell Apoptosis and Expression of Caspase-3 and JNK Proteins in Kidney Tissue in Renal Interstitial Fibrosis Rats

[Objectives]To investigate the effects of losartan on cell apoptosis and the expression of caspase-3 and JNK proteins in kidney tissue in the adenine-induced renal fibrosis rats.[Methods]Thirty Wistar rats were randomly divided into three groups:control group(n=10),model group(n=10)and losartan group(n=10).The rats in the control group received saline,while those in the model group and losartan group both received adenine by gavage,for 21 d.After the renal interstitial fibrosis model was established,the rats in the losartan group were treated with losartan[10 mg/(kg·d)],while the rats in the control group and the model group rats were administered with the same amount of saline.The course of treatment was 30 d.Finally,the renal function,blood urea nitrogen(BUN),serum creatinine(Scr),creatinine clearance rate(Ccr)and the pathological morphology of the rats were detected.The apoptosis of renal tubular epithelial cells was tested by TUNEL.The caspase-3 and JNK protein expression was tested by Western blotting.[Results]After administering adenine for 21 d,the BUN,24 MTP and kidney/body weight in the model group were increased,significantly higher than the control group(P<0.01),and the Ccr was remarkably decreased(P<0.01),signifying that the renal interstitial fibrosis model was successfully built.After treating with losartan for 30 d,the Scr,BUN,and 24 MTP were significantly decreased(P<0.01),and the Ccr was significantly increased in the losartan group(P<0.01).In addition,in comparison to the model group,renal tubular epithelial apoptosis was decreased and caspase-3 and JNK expression was downregulated in the losartan group(P<0.05).[Conclusions]Losartan can reduce the adenine-induced elevation of Scr,BUN and 24 hMPT,increase Ccr,improve general condition of renal interstitial fibrosis in rats and ameliorate the progression of chronic kidney failure(CKD).The effectiveness of losartan is probably due to its ability to regulate caspase-3,JNK protein expression and attenuate renal cell apoptosis.

Applications of lung clearance index in monitoring children with cystic fibrosis

A sensitive, reproducible and feasible measure of lung function for monitoring the respiratory health is a prerequisite for the optimization of management of the patients with cystic fibrosis(CF). Spirometry has been considered the method of choice, although it is applicable only in children older than 6 years of age, as good cooperation is necessary for its proper performance. However, over the last15 years, scientific interest in gas dilution techniques and particularly in multiple breath wash out(MBW) method has been revived. The most commonly reported index of MBW is lung clearance index(LCI). The aim of this review is to present the most recent developments in the application of LCI as a monitoring index of respiratory status of CF patients. LCI is a sensitive and reproducible marker of ventilation inhomogeneity. It is more sensitive than spirometry and, unlike spirometry; it can be performed across the whole pediatric age range. Since it is dependent on body size, until at least the age of 6 years, the relative and not the absolute changes are more appropriate for providing clinically meaningful conclusion on ventilation inhomogeneity. Until now, MBW has been mainly used as a research tool. Based on the currently available data LCI cannot safely predict high-resolution computed tomography findings in children with CF, especially in infants. It can be used as an end-point measure for the assessment of beneficial effect of interventions. However, its utility as an outcome measure for the efficacy of therapeutic interventions seems to be dependent on the pathophysiologic mechanisms that underlie each intervention. It seems that more studies,especially longitudinal ones, are required in order to fully clarify the clinical usefulness of LCI, not only in the research setting, but also in every day practice of CF clinic.

Unique interstitial miRNA signature drives fibrosis in a murine model of autosomal dominant polycystic kidney disease

AIM To delineate changes in miRNA expression localized to the peri-cystic local microenvironment(PLM) in an orthologous mouse model of autosomal dominant polycystic kidney disease(ADPKD)(mcwPkd1^(nl/nl)).METHODS We profiled miRNA expression in the whole kidney and laser captured microdissection(LCM) samples from PLM in mcwPkd1^(nl/nl)kidneys with Qiagen miScript 384 HC miRNA PCR arrays. The three times points used are:(1) post-natal(PN) day 21, before the development of trichrome-positive areas;(2) PN28, the earliest sign of trichrome staining; and(3) PN42 following the development of progressive fibrosis. PN21 served as appropriate controls and as the reference time point for comparison of miRNA expression profiles.RESULTS LCM samples revealed three temporally upregulated miRNAs [2 to 2.75-fold at PN28 and 2.5 to 4-fold(P ≤ 0.05) at PN42] and four temporally downregulated miRNAs [2 to 2.75 fold at PN28 and 2.75 to 5-fold(P ≤ 0.05) at PN42]. Expression of twenty-six miRNAs showed no change until PN42 [six decreased(2.25 to 3.5-fold)(P ≤ 0.05) and 20 increased(2 to 4-fold)(P ≤ 0.05)]. Many critical miRNA changes seen in the LCM samples from PLM were not seen in the contralateral whole kidney.CONCLUSION Precise sampling with LCM identifies miRNA changes that occur with the initiation and progression of renal interstitial fibrosis(RIF). Identification of the target proteins regulated by these miRNAs will provide new insight into the process of fibrosis and identify unique therapeutic targets to prevent or slow the development and progression of RIF in ADPKD.

Multicenter cooperative observational study of idiopathic pulmonary fibrosis with non-small cell lung cancer

AIM: To research the natural course of idiopathic pulmonary fibrosis(IPF) with advanced non-small cell lung cancer(NSCLC) and the association between acuteMETHODS: From May 2007 through April 2011, 17 CT naive patients with IPF and advanced NSCLC were enrolled. Patients were classified into best supportive care(BSC) group or CT group based on the patient's preference. Patients in the CT group received carboplatin(CBDCA)(AUC 5-6) plus paclitaxel(PTX)(175-200 mg/m2) on day 1 of each 21-d cycle as first-line therapy.RESULTS: All patients but one chose the CT group. In the CT group, the objective response rate was 38%. The most frequent toxicity ≥ grade 3 was neutropenia(88%). Two patients(12.5%) developed AE-IPF. The median progression-free survival, the median survival time and the 1-year survival rate were 4.1 mo, 8.7 mo and 35%, respectively. Second-line CT-related AE and CT-unrelated AE occurred in 2 and 3 patients(1: BSC group; 2: CT group), respectively. Seven(41%) of all patients developed AE-IPF throughout the clinical course, and 6 of 7 patients with AE-IPF died within one month.CONCLUSION: The incidence of AE-IPF was higher among IPF patients with advanced NSCLC than among those without NSCLC. CBDCA plus PTX regimen was tolerable and effective. However, AE-IPF has a fatal toxicity with or without CT in IPF patients with advanced NSCLC.

Progress in drug delivery system for fibrosis therapy

Fibrosis is a necessary process in the progression of chronic disease to cirrhosis or even cancer,which is a serious disease threatening human health.Recent studies have shown that the early treatment of fibrosis is turning point and particularly important.Therefore,how to reverse fibrosis has become the focus and research hotspot in recent years.So far,the considerable progress has been made in the development of effective anti-fibrosis drugs and targeted drug delivery.Moreover,the existing research results will lay the foundation for more breakthrough delivery systems to achieve better anti-fibrosis effects.Herein,this review summaries anti-fibrosis delivery systems focused on three major organ fibrotic diseases such as liver,pulmonary,and renal fibrosis accompanied by the elaboration of relevant pathological mechanisms,which will provide inspiration and guidance for the design of fibrosis drugs and therapeutic systems in the future.

Intervening Effect of Sodium Aescinate on Pulmonary Fibrosis in Rats with Acute Lung Injury

[Objectives] The aim was to investigate the intervening effect of sodium aescinate on pulmonary fibrosis in rats with acute lung injury( ALI). [Methods] The rats were randomly divided into normal group,model group and sodium aescinate group. The rat model of ALI was induced by administration of oleic acid. The rats in the sodium aescinate group were intravenously injected with sodium aescinate according to the amount of 4 mg/kg for 14 consecutive d. Then,11 rats were selected randomly from each group and slaughtered on Day 1 and Day 14,respectively after last administration. The body mass index,arterial partial pressure of oxygen( PaO_2),oxygenation index( PaO_2/FiO_2),lung index,wet/dry mass ratio of lung,serum IL-1β,TNF-α,PC Ⅲ and TGF-β1 levels of the rats were analyzed. [Results]No significant differences were found in body mass index,lung index or lung wet/dry mass ratio among different groups. Compared with the model group,the PaO_2 and PaO_2/FiO_2 ratio increased significantly( P < 0. 05),the serum IL-1β,TNF-α,PC Ⅲ and TGF-β1 levels declined significantly( P <0. 05),the lung histopathological damage was reduced,and the semi-quantitative histological score( IQA) of damaged lung tissue decreased significantly( P < 0. 01). [Conclusions]Sodium aescinate can reduce the levels of inflammatory factors in rats with ALI,with certain intervening on pulmonary effect.

Effects of Manshenkangning Prescription on Adenine-induced Renal Interstitial Fibrosis in Rats

[Objectives]To study the protective effects of Manshenkangning Prescription on adenine-induced renal interstitial fibrosis in rats,and explore the possible mechanism.[Methods]Sixty Wistar male rats were divided into normal group,model group,control group(administered with 10 mg/(kg·d)losartan)and high,medium and low dose experimental groups(30,15,7.5 mg/(kg·d)Manshenkangning).The rat models of renal interstitial fibrosis were induced by intragastric administration of adenine(250 mg/(kg·d)).After 2 h,the above drugs were administered intragastrically for 21 consecutive days and the administration time was 30 consecutive days.Serum creatinine(SCr),blood urea nitrogen(BUN),24 h urinary protein(24 h MTP)and glomerular filtration rate(eGFR)were measured by biochemical method;renal histopathological changes were observed by hematoxylin-eosin(HE)staining.Renal collagen deposition in rats was observed by Masson staining.[Results]The SCr in model group and the high,medium and low dose experimental groups were(340.00±22.99),(176.80±18.60),(234.75±13.59),(266.11±14.78)μmol/L,and BUN were(23.74±2.51),(14.53±2.25),(18.78±0.88),(18.90±2.14)mmol/L;24 h MTP were(675.86±74.58),(323.81±41.83),(438.84±34.69),(493.76±37.04)mg/d;eGFR were(19.30±2.48),(49.96±10.95),(32.61±10.75),(27.18±5.98)mL/min,and the difference was statistically significant compared with the normal group(all P<0.05).HE staining and Masson staining showed that compared with normal group,the renal interstitial lesions in model group were severe and the renal interstitial collagen material was deposited in a large amount.The renal interstitial tubule injury was relieved and the renal interstitial collagen deposition was reduced in experimental groups.And the difference was statistically significant(all P<0.01).[Conclusions]Manshenkangning can significantly protect the kidney against the progress of interstitial fibrosis in rats.Its possible mechanism is to regulate the activity of SIRT1 and inhibit the expression of COX-2 in order to resist the inflammatory reaction of kidney and improve the ability of anti-oxidative stress of kidney,thus delaying the occurrence and development of chronic renal failure.

Kidney tissue targeted metabolic profiling of renal interstitial fibrosis rats induced by unilateral ureteral obstruction using NMR

Aim Renal interstitial fibrosis （RIF） is a common final pathological process in the progression of kid- hey disease. To investigate the pathogenesis of RIF and offer invaluable instructions for diagnosis and therapy treat- 1 ment of RIF. Method： H NMR based-metabolomics study on targeted kidney tissue of RIF rats induced by uni- lateral ureteral obstruction was conducted combined with multivariate data analysis to characterize the alteration of endogenous metabolites and elucidate the molecular mechanism of RIF. Results The combination of a variety of statistical methods was used to screen out 14 potential significantly changed metabolites, including increased levels of lactate, methionine, aspartate, allantoin, uracil, 3-HB and decreased levels of TMAO, leucine, valine, lysine, adenosine, adenine, tyrosine and phenylalanine in the left kidney of UUO rats, compared with SO rats. To gain ad- ditional insight about the relationship between metabolites, they were mapped to KEGG IDs and built compound network by Metscape reflecting the complex pathology and providing evidence for the involvement of such processes as altered amino acid metabolism, adenine metabolism, energy metabolism, osmolyte change and induced oxidative stress. In addition, we have explored the morphology and size, calculated the degree of fibrosis based on altered differential metabolites, and speculated the probable causes of moderate RIF of contralateral kidneys to help to un- derstand the disease, which was also supported by serum biochemistry and kidney histopathology results. In addi- tion, the correlation analysis of the pathological parameters （ clinical chemistry, histological and immunohistochem- istry results） with the significantly changed differential metabolites responsible for the cluster （different groups） was also performed. Conclusion Our work shows that target tissue metabolomics analysis can be used as a power-ful tool to gain a better understanding of the mechanism of the disease and provide a novel insight in the pathogene- sis of RIF.

IL13-induced lung fibrosis in meconium aspiration

We demonstrated previously that inflammatory cy-tokines TNF, IL-1, IL-6 and IL-8 are signifi-cantly expressed in meconium-instilled lungs. Capto-pril was a strong inhibitor of meconium-induced lung injury, inflammation and apoptosis and reduces lung alveolar and airway epithelial cell damage. Presently we demonstrate that IL-13 expression in the me-conium aspiration syndrome (MAS). IL-13 was maximally expressed 8 hrs after meconium instilla-tion. It was previously described that IL-13 plays a major role in degradation of airway epithelial cells and inducing of lung fibrosis by activating collagen production that is a major point in identification of lung fibrosis. We also showed that Captopril treat-ment significantly inhibits IL-13 expression in the lungs. We believe it reduces meconium-induced lung injury and has a therapeutic effect on histological and biochemical functions of the lungs and possibly pulmonary fibrosis. Captopril treatment significantly reduced the number of neuprophils and macrophages which express IL13 and levels of other inflammatory cytokines after meconium instillation. Selective neu-tralization of IL-13 ameliorated lung injury, airway hyper responsiveness, eosinophil recruitment and mucus overproduction.

Effect of sodium ferulate in combined with atorvastatin on the renal interstitial fibrosis and inflammatory cytokines in patients with diabetic nephropathy

Objective:To explore the effect of sodium ferulate in combined with atorvastatin on the renal interstitial fibrosis and inflammatory cytokines in patients with diabetic nephropathy (DN). Methods: A total of 111 patients with DN who were admitted in our hospital from January, 2016 to April, 2017 were included in the study and randomized into the observation group and the control 1 and 2 group with 37 cases in each group. The patients in the control group were given routine blood sugar reducing, blood pressure reducing, and high quality low protein diet. On the above basis, the patients in the control 2 group were orally administrated with atorvastatin before sleep (20 mg). On the basis of treatments in the control 1 group, the patients in the observation group were given sodium ferulate (0.3 g) + 0.9% NaCl (250 mL), ivdrip, 1 time/d, and administrated with atorvastatin before sleep (20 mg). The fasting peripheral venous blood before and after treatment in the three groups was collected. The glycse oxidase (GOD) method was used to detect FPG. ELISA was used to detect SCr, TGF-β, AngⅡ, CTGF, hs-CRP, TNF-α, and IL-6. RIA was used to detect BUN and 24hUAER. The strengthened chemiluminescence immunoassay was used to detect CⅣ and PCⅢ. MAP was recorded. Results: FPG, MAP, BUN, 24hUAER, and SCr after treatment in the control 2 group were significantly lower than those in the control 1 group. FPG, MAP, BUN, 24hUAER, and SCr after treatment in the observation group were significantly lower than those in the control 2 group. AngⅡ, TGF-β, CTGF, PCⅢ, and CⅣ after treatment in the control 2 group were significantly lower than those in the control 1 group. AngⅡ, TGF-β, CTGF, PCⅢ, and CⅣ after treatment in the observation group were significantly lower than those in the control 2 group. TNF-α, IL-6, and hs-CRP after treatments in the control 2 group were significantly lower than those in the control 1 group. TNF-α, IL-6, and hs-CRP after treatment in the observation group were significantly lower than those in the control 2 group.Conclusions:The sodium ferulate in combined with atorvastatin can effectively improve the renal function in patients with DN, alleviate the systemic inflammatory reaction, and delay the renal interstitial fibrosis speed.