Guided by the pathogenesis of"structure-activity imbalance of lung collaterals",this paper proposes that structure-activity imbalance of lung collaterals is the initial factor of idiopathic pulmonary fibrosis(IPF)and elucidates the pathogenesis of abnormal changes in biomechanical properties of IPF.It is postulated that the changes of biomechanical properties of lung tissue are closely related to the injury of lung qi collaterals,the abnormal mechanical stress are closely related to the injury of lung blood collaterals,and the biomechanical response of intrapulmonary resident cells is closely related to the structure-activity imbalance of lung collaterals,which ultimately leading to abnormal increase in lung tissue stiffness and progressive scarring formation in lung tissue.Integrating traditional pathogenesis concepts with microscopic pathological changes,and the in-depth exploration of the correlation between the structure-activity imbalance of lung collaterals and the biomechanical properties of IPF can provide direction for exploring IPF medical-engineering cross research,which are of great significance for enriching the syndrome and treatment system of lung collateral diseases.

Idiopathic pulmonary fibrosis （IPF） can be classified as pulmonary collateral disease，and its pathogenesis is mainly characterized by the loss of Qi meridian nourishment，the loss of Yin meridian nourishment，and the formation of blood stasis in the blood vessels. Qi Yin deficiency is the pathological basis that runs through IPF，and obstruction of meridians and collaterals is a key element in the development of the disease. The dysfunction of "spleen being in charge of the defensive function" is closely related to the formation of the pathological pattern of "lung deficiency and collateral stasis" in IPF. The term "spleen being in charge of the defensive function" originated from the Yellow Emperor's Inner Canon. If the spleen is healthy，the Qi will be filled with vitality. Positive energy is stored inside，evil cannot be dried up. Its concept is quite similar to the immune defense function in modern medicine. If the principle of "spleen being in charge of the defensive function" is lost，the key structure and function of the IPF alveolar epithelial barrier may be abnormal，and it can interact with various innate immune cells to promote inflammation and fibrosis processes. Therefore，this article explains the imbalance of immune homeostasis in IPF alveolar epithelium from two aspects：the barrier function of alveolar epithelial cells（AECs） and their interaction with innate immune cells. And based on the theory of "spleen being in charge of the defensive function"，using traditional Chinese medicine for strengthening the spleen and nourishing Qi to treat IPF from the perspective of the spleen. This not only strengthens the scientific connotation of "spleen being in charge of the defensive function" in the pathogenesis of IPF，but also provides new research directions and ideas for its future clinical prevention and treatment.

Guided by the pathogenesis of"structure-activity imbalance of lung collaterals",this paper proposes that structure-activity imbalance of lung collaterals is the initial factor of idiopathic pulmonary fibrosis(IPF)and elucidates the pathogenesis of abnormal changes in biomechanical properties of IPF.It is postulated that the changes of biomechanical properties of lung tissue are closely related to the injury of lung qi collaterals,the abnormal mechanical stress are closely related to the injury of lung blood collaterals,and the biomechanical response of intrapulmonary resident cells is closely related to the structure-activity imbalance of lung collaterals,which ultimately leading to abnormal increase in lung tissue stiffness and progressive scarring formation in lung tissue.Integrating traditional pathogenesis concepts with microscopic pathological changes,and the in-depth exploration of the correlation between the structure-activity imbalance of lung collaterals and the biomechanical properties of IPF can provide direction for exploring IPF medical-engineering cross research,which are of great significance for enriching the syndrome and treatment system of lung collateral diseases.

Objective To explore the biological basis of different diseases with the same syndrome for pulmonary related comorbidities(pulmonary hypertension,obstructive sleep apnea syndrome,chronic obstructive pulmonary disease,lung cancer)in idiopathic pulmonary fibrosis(IPF)through genomic bioinformatics analysis.Methods GSE110147,GSE113439,GSE135917,GSE106986 and GSE118370 datasets were downloaded as research subjects.The differential genes between each disease group and the control group were screened.Cytoscape 3.10.0 software was used for topology analysis to screen core genes.OmicShare was used to perform GO and KEGG pathway enrichment analyses on core genes.Results A total of 23 core genes related to IPF was obtained.GO enrichment analysis showed that core genes were mainly enriched in biological processes such as cellular process,metabolic process,biological regulation/biological process,developmental process,localization,response to stimulus,immune system process and signaling;in cellular components such as cellular anatomical entity and protein-containing complex;in molecular functions such as binding,catalytic activity,structural molecule activity,molecular adaptor activity,molecular function regulator and transcription regulator activity.KEGG pathway enrichment analysis showed that core genes were mainly enriched in ribosome biogenesis in eukaryotes,AGE-RAGE signaling pathway in diabetic complications,Th17 cell differentiation,JAK-STAT signaling pathway,RNA polymerase,neutrophil extracellular trap formation.Conclusion Using genomic bioinformatics analysis to explore the core genes and signaling pathways of pulmonary related comorbidities in IPF can reveal the mechanism of different diseases with the same syndrome for pulmonary related comorbidities in IPF to a certain extent.

Purpose: It is well known that congenital diaphragmatic hernia (CDH) in infants impacts pulmonary function rehabilitation after surgery. However, the risk factors of postoperative pulmonary function are still unclear. In this research, we analyzed the potential risk factors of postoperative pulmonary function in CDH patients in order to improve the clinical management of CDH patients. Methods: Thirty-three cases CDH infants followed were enrolled from November 2016 to September 2018. Clinical data were reviewed. Tidal breathing pulmonary function testing was performed after surgery. Correlation between pulmonary function and clinical characteristics was evaluated using multivariate analysis of variance. Results: Pulmonary dysfunction was detected in 87.9% patients (29 of 33). The defect size was found to be significantly larger in patients with obstructed and mixed ventilatory disorders (P = 0.001). Diagnosis of gestational age (GA) was also significantly earlier compared to restrictive ventilatory disorders (P = 0.001). Larger defect size, and earlier prenatal diagnosis of GA were detected in severe obstructive ventilatory disorders (P = 0.007, P = 0.001, retrospectively). Conclusion Most patients had various degrees of pulmonary dysfunction after surgery. Patients with larger defect size and earlier diagnosis time might be vulnerable to severe obstructive and mixed ventilatory disorders.

BACKGROUND/AIMS: Interstitial cells of Cajal (ICC) and their special calcium-activated chloride channel, anoctamin-1 (ANO1) play pivotal roles in regulating colonic transit. This study is designed to investigate the role of ICC and the ANO1 channel in colonic transit disorder in dextran sodium sulfate (DSS)-treated colitis mice. METHODS: Colonic transit experiment, colonic migrating motor complexes (CMMCs), smooth muscle spontaneous contractile experiments, intracellular electrical recordings, western blotting analysis, and quantitative polymerase chain reaction were applied in this study. RESULTS: The mRNA and protein expressions of c-KIT and ANO1 channels were significantly decreased in the colons of DSS-colitis mice. The colonic artificial fecal-pellet transit experiment in vitro was significantly delayed in DSS-colitis mice. The CMMCs and smooth muscle spontaneous contractions were significantly decreased by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), an ANO1 channel blocker, and NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of nitric oxide synthase activity, in DSS-colitis mice compared with that of control mice. Intracellular electrical recordings showed that the amplitude of NPPB-induced hyperpolarization was more positive in DSS-colitis mice. The electric field stimulation-elicited nitric-dependent slow inhibitory junctional potentials were also more positive in DSS-colitis mice than those of control mice. CONCLUSION: The results suggest that colonic transit disorder is mediated via downregulation of the nitric oxide/ICC/ANO1 signalling pathway in DSS-colitis mice.
Animals ; Blotting, Western ; Chloride Channels ; Colitis ; Colon ; Dextrans ; Down-Regulation ; In Vitro Techniques ; Interstitial Cells of Cajal ; Mice ; Muscle, Smooth ; Myoelectric Complex, Migrating ; NG-Nitroarginine Methyl Ester ; Nitric Oxide Synthase ; Polymerase Chain Reaction ; RNA, Messenger ; Sodium

BACKGROUND/AIMS: Interstitial cells play important roles in gastrointestinal (GI) neuro-smooth muscle transmission. The underlying mechanisms of colonic dysmotility have not been well illustrated. We established a partial colon obstruction (PCO) mouse model to investigate the changes of interstitial cells and the correlation with colonic motility. METHODS: Western blot technique was employed to observe the protein expressions of Kit, platelet-derived growth factor receptor-α (Pdgfra), Ca²⁺-activated Cl⁻ (Ano1) channels, and small conductance Ca²⁺- activated K⁺ (SK) channels. Colonic migrating motor complexes (CMMCs) and isometric force measurements were employed in control mice and PCO mice. RESULTS: PCO mice showed distended abdomen and feces excretion was significantly reduced. Anatomically, the colon above the obstructive silicone ring was obviously dilated. Kit and Ano1 proteins in the colonic smooth muscle layer of the PCO colons were significantly decreased, while the expression of Pdgfra and SK3 proteins were significantly increased. The effects of a nitric oxide synthase inhibitor (L-NAME) and an Ano1 channel inhibitor (NPPB) on CMMC and colonic spontaneous contractions were decreased in the proximal and distal colons of PCO mice. The SK agonist, CyPPA and antagonist, apamin in PCO mice showed more effect to the CMMCs and colonic smooth muscle contractions. CONCLUSIONS: Colonic transit disorder may be due to the downregulation of the Kit and Ano1 channels and the upregulation of SK3 channels in platelet-derived growth factor receptor-α positive (PDGFRα⁺) cells. The imbalance between interstitial cells of Cajal-Ano1 and PDGFRα-SK3 distribution might be a potential reason for the colonic dysmotility.
Abdomen ; Animals ; Apamin ; Blotting, Western ; Chloride Channels ; Colon ; Down-Regulation ; Feces ; Interstitial Cells of Cajal ; Mice ; Muscle, Smooth ; Myoelectric Complex, Migrating ; Nitric Oxide Synthase ; Platelet-Derived Growth Factor ; Silicon ; Silicones ; Small-Conductance Calcium-Activated Potassium Channels ; Up-Regulation

Objective To analyze the value of the potential risk factors on predicting primary graft dysfunction (PGD) after bilateral lung transplantation for the patients with idiopathic pulmonary fibrosis (IPF).Methods A retrospective study was conducted. Fifty-eight patients with IPF who underwent the bilateral lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from June 2014 to March 2017 were enrolled. The grade 3 PGD happened within 72 hours after transplantation was taken as the outcome event, and these patients were divided into PGD and non-PGD groups. The age, gender, body mass index (BMI), underlying disease, and N-terminal-probrain natriuretic peptide (NT-proBNP) before operation, pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), and mean pulmonary artery pressure (mPAP) before and after operation, duration of operation, the volume of blood transfusion during operation and postoperation, the use of extracorporeal membrane oxygenation (ECMO) during the operation, blood purification treatment after operation, and shock within 3 days after operation were recorded. The differences of parameters mentioned above between the two groups were compared. The predictive factors of PGD were searched by binary logistic regression analysis, and the receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of preoperative PADP for grade 3 PGD after transplantation.Results Among 58 patients who underwent the bilateral lung transplantation, 52 patients were enrolled. The rest patients were excluded because of incomplete clinical data. There were 17 patients in the PGDgroup, with a mortality rate of 47.06%. The non-PGD group included 35 patients with a mortality rate of 8.57%. PADP and mPAP ahead of operation, the dosage of red cells suspension after the operation, and the total amount of blood transfusion during and after the operation in PGD group were significantly higher than those in non-PGD group [PADP ahead of operation (mmHg, 1 mmHg = 0.133 kPa): 33.7±10.5 vs. 25.3±10.1, mPAP ahead of operation (mmHg): 40.4±14.1 vs. 32.8±11.1, the dosage of red cells suspension after the operation (mL): 700 (300, 1500) vs. 300 (300, 500), the total amount of blood transfusion during and after the operation (mL): 2250 (1850, 4275) vs. 1800 (1550, 2800)], with statistically significant differences (all P < 0.05). There were no significant differences in age, gender, BMI, underlying disease, NT-proBNP before operation, PASP before and after operation, PADP and mPAP after operation, duration of operation, amount of plasma and red cells suspension as well as total amount of blood transfusion during operation, plasma amount and total amount of blood transfusion after operation, amount of plasma and red cells suspension during and after operation, use of ECMO during operation, blood purification treatment after operation, and shock after operation between the two groups (all P > 0.05). It was shown by binary logistic regression analysis that the preoperative PADP was the independent risk factor of grade 3 PGD after lung transplantation [odds ratio (OR) = 1.084, 95% confidence interval (95%CI) = 1.016-1.156,P = 0.015]. It was shown by ROC curve that the area under the ROC curve (AUC) of the PADP before operation for predicting the grade 3 PGD after lung transplantation was 0.728. When the cut-off value was 36 mmHg, the sensitivity was 47.1%, and the specificity was 91.4%.Conclusions Compared with the non-PGD group, the patients with higher preoperative PADP were more common in the PGD group, and the patients in the PGD group were more likely to be characterized by grade 3 PGD after lung transplantation. The preoperative PADP was an effective predictor of grade 3 PGD after lung transplantation.

Objective To investigate the pathogen distribution and drug resistance condition in patients after lung transplantation so as to guide the reasonable use of antibiotics.Methods The clinical specimens from 242 lung transplantation patients in Wuxi People's Hospital between Jan.2010 to Dec.2016 were retrospectively analyzed.Among the 242 patients,182 were males and 60 were females with the average age of (52 ± 15) years old.Automatic analysis instrument VITEK-2 was applied for pathogen detection and K-B method was used to test drug resistance.Results From 2373specimens,1005 strains of pathogens were isolated and the detection rate was 42.35％ (1005/2373),in which gram-negative bacteria accounted for 81.79％ (822/1005).The specimens mainly resulted from sputum (76.19 ％) and bronchoalveolar lavage (19.76 ％).Among those strains,acinetobacter baumannii (28.76％),pseudomonas aeruginosa (16.62％),klebsiella pneumonia (14.33％),escherichia coli (5.57％) and Stenotrophomonas maltophilia (4.88％) ranked the top five species.Acinetobacter baumannii strains were highly resistant to most of antibiotic agents,with the drug resistant rate from 59.52％ to 100％,except cefperazone-sulbactam (＜ 50％).Pseudomonas aeruginosa strains were highly resistant to cefazolin,ceftriaxone,cefotetan,ampicillin,ampicillinsulbactam with the resistance rate of 80.24％-98.80％,while compared to other anibiotics with the resistance rate less than 50％.Stenotrophomonas maltophilia strains with intrinsic drug resistance to imipenem were sensitive to trimethoprim-sulfamethoxazole,cefperazone-sulbactam,piperacillintazobactam,levofloxacin,ciprofloxacin with the drug resistance rate of 12.24％,14.29％,32.65％,16.33％ and 18.37％ respectively.Klebsiella Klebsiella pneumoniae and escherichia coli,whose resistant rate to ceftazidime,cefperazone-sulbactam,piperacillin-tazobactam,aztreonam,amikacin and tobramycin was all less than 50％,were highly sensitive to imipenem,with the resistance rate of 24.31％ and 7.14％ respectively.Gram-positive bacteria were accounted for 9.35％,mainly Staphylococcus aureus,Staphylococcus haemolyticus and Staphylococcus epidemics,and drug resistant rate of them to vancomycin was all less than 20.00％.Fungi were accounted for 8.86％,mainly Candida albicans and Filamentous fungi,whose drug resistance rate to 5 antifungal drugs was less than 20.00％.The drug resistance rate of C.glabrata strains and C.krusei strains to fluconazole was 80.00％ and 100.00％,respectively.Conclusion The incidence of gram-negative bacteria infection and multiple bacterial strain infection in patients after lung transplantation is very high and the nonfermentation bacteria are highly resistant to multiple antibiotics.So,the rational antibiotics' use inclinical practice should be based on drug sensitivity results in order to improve the lung transplant recipients' survival rate.

AIM: To explore the effect of Shenshuai Capsule on renal functio n, NO and TNF-? in CRF rat's blood. METHODS: Wister rats were fed with adenine to establish the chronic renal insufficiency anemia model, and then they were divided into three groups and fed with Shenshuai Capsule (high or low dosage) and Niaoduqing proup, respec tively. Kidney function index and the levels of NO and TNF-? in blood of CR F rats were measured. RESULTS: The comparison of renal function between the treatment gro up (high dosage) and the Niaoduqing group were significantly different respectiv ely. At the same time, Shenshuai Capsule can increase the NO of CRF rat's blood and reduce the TNF-?. CONCLUSION: Shenshuai Capsule can improve renal function of CRF rat , simultaneously raise the NO of CRF rat's blood and reduce the TNF-?. The lat ter may be one of the mechanism of action that Shunshuai Capsule can delay the r enal failure.