Objective:To investigate the effects of the novel oral edaravone(EDA)on rats with diabetic encepha-lopathy(DE).Methods:The network pharmacology research methodology was employed to elucidate the mechanism of action of oral EDA in the treatment of diabetes mellitus,identify intersecting targets,and conduct initial validation of these findings in vivo.Thirty male SD rats were randomly assigned to three groups:A normal control(control)group,a diabetic encephalopathy DE(DE)group,and an oral edaravone treatment(DE+EDA)group.Diabetic encephalop-athy was induced in both the DE and DE+EDA groups using the streptozotocin(STZ)method.After successful model-ing,the DE+EDA group received oral administration of EDA,while the other two groups were administered equal doses of saline as controls.Serum samples were examined for lipid release rate,and the protein expression levels of oxidative stress factor 3-nitrotyrosine(3-NT)and apoptotic factor cysteinyl aspartate specific proteinase-3(caspase-3)in brain tissues were detected by Western blot.Brain samples were stained with HE staining to observe the pathological changes.Histopathological changes were observed through hematoxylin-eosin(HE)staining.Results:Network pharmacological analysis yielded 27 core targets,and functional annotation of gene bioprocesses showed that the intersecting targets were mainly enriched in response to oxidative stress and neuronal apoptosis.Serum-related lipid assay showed that the DE+EDA group had significantly improved lipid metabolism disorders compared with the DE group.Additionally,expression levels of 3-NT and caspase-3 were significantly higher in the DE group when compared with controls(P＜0.05);How-ever,both markers exhibited a significant decrease within the DE+EDA treatment cohort as opposed to their counter-parts in the DE group(P＜0.05).HE staining showed that in DE group the cellular arrangement was disordered,the cells were shrunk with intact plasma membrane,and the nuclei were condensed showing karyopyknosis,fragmented and dissolved.Compared with the DE group,the brain tissue in the DE+EDA group was relatively dense and neatly ar-ranged,and the cell karyopyknosis,fragmentation and lysis were significantly improved.Conclusion:Both network pharmacology and in vivo experiments provide preliminary evidence that oral EDA reduces damage in diabetic encepha-lopathy rats.

Objective:To investigate the effects of the novel oral edaravone(EDA)on rats with diabetic encepha-lopathy(DE).Methods:The network pharmacology research methodology was employed to elucidate the mechanism of action of oral EDA in the treatment of diabetes mellitus,identify intersecting targets,and conduct initial validation of these findings in vivo.Thirty male SD rats were randomly assigned to three groups:A normal control(control)group,a diabetic encephalopathy DE(DE)group,and an oral edaravone treatment(DE+EDA)group.Diabetic encephalop-athy was induced in both the DE and DE+EDA groups using the streptozotocin(STZ)method.After successful model-ing,the DE+EDA group received oral administration of EDA,while the other two groups were administered equal doses of saline as controls.Serum samples were examined for lipid release rate,and the protein expression levels of oxidative stress factor 3-nitrotyrosine(3-NT)and apoptotic factor cysteinyl aspartate specific proteinase-3(caspase-3)in brain tissues were detected by Western blot.Brain samples were stained with HE staining to observe the pathological changes.Histopathological changes were observed through hematoxylin-eosin(HE)staining.Results:Network pharmacological analysis yielded 27 core targets,and functional annotation of gene bioprocesses showed that the intersecting targets were mainly enriched in response to oxidative stress and neuronal apoptosis.Serum-related lipid assay showed that the DE+EDA group had significantly improved lipid metabolism disorders compared with the DE group.Additionally,expression levels of 3-NT and caspase-3 were significantly higher in the DE group when compared with controls(P＜0.05);How-ever,both markers exhibited a significant decrease within the DE+EDA treatment cohort as opposed to their counter-parts in the DE group(P＜0.05).HE staining showed that in DE group the cellular arrangement was disordered,the cells were shrunk with intact plasma membrane,and the nuclei were condensed showing karyopyknosis,fragmented and dissolved.Compared with the DE group,the brain tissue in the DE+EDA group was relatively dense and neatly ar-ranged,and the cell karyopyknosis,fragmentation and lysis were significantly improved.Conclusion:Both network pharmacology and in vivo experiments provide preliminary evidence that oral EDA reduces damage in diabetic encepha-lopathy rats.

Objective To explore the effect of Sufu on lung adenocarcinoma by observing its mutation and the changes in Gli1 transcription after its mutation.Methods cBioPortal for Cancer Genomics was used to obtain the mutation status of Sufu in lung cancer.Four Sufu single base mutation vectors were constructed and transfected into lung adenocarcinoma cell lines A549 and H1975 to establish cells with Sufu overexpression and knockout.Wounding healing assay was employed to determine the effect of Sufu on cell migration,and RT-qPCR,immunofluorescence assay and dual luciferase reporter gene assay were utilized to explore the changes in Gli1 transcription after Sufu mutation.Results cBioPortal data showed that the mutation rate of Sufu in lung cancer was 11.76％in squamous cell carcinoma(2/17),0.96％in adenocarcinoma(6/625),1.01％in small cell lung cancer(4/396),and 0.69％in non-small cell lung cancer(77/11 227).The median survival of lung cancer patients was significantly decreased in those with Sufu mutation than those without(38.00 vs 54.34 months,HR=1.943,P＜0.05).A549 cells were sensitive to Sufu knockout,and it resulted in significant increase of the transcription level of Gli1(P＜0.05).Overexpression of Sufu inhibited cell migration ability in both A549 and H1975 cells(P＜0.05).Sufu mutation had no significant influence on the location of Gli1 in the cells.The Sufu-T411M mutation up-regulated the the transcription level of Gli1(P＜0.05).Conclusion Sufu has an inhibitory effect on lung adenocarcinoma metastasis,and can be regarded as a potential target for lung adenocarcinoma metastasis.

Aim To explore the role and mechanism of the effective ingredients of Scutellariae Radix in improving the fibrosis of diabetes cardiomyopathy(DCM).Methods The technology platform of Chinese medicine system pharmacology(TCMSP)and the small molecule drug target prediction(Swiss Target Prediction)platform were used to excavate the active components of Scutellariae Radix and the target of its response.DCM related disease gene targets were screened using GeneCards,Disgene,UniPort and OMIM databases,and intersecting genes were imported into the String 11.5 database to construct a drug-disease-protein interaction network diagram.Cytoscape 3.9.1 software was a-dopted to visualize the key target network.Metascape platform was used to explore the molecular targets of Scutellariae Radix effective ingredients against DCM,and draw pathway maps through the KEGG database.H9c2 and AC16 cardio-myocytes were stimulated with 5.5 mmol/L D-glucose as the normal glucose control group,35 mmol/L D-glucose as the high glucose group,and 10 μmol/L Baicalin was used for intervention.The levels of TGF-β1,collagen Ⅰ(COL Ⅰ)and collagen Ⅲ(CO LⅢ)mRNA were detected by RT-qPCR,and the expression of Smad2/3,p-Smad2/3,COL Ⅰ and COL Ⅲprotein were detected by Western blot,TGF-β1 level in supernatant was assessed by ELISA.Results Through the a-bove platform,a total of 33 effective ingredients including Baicalin,441 core targets,and 1 884 DCM disease genes were retrieved,150 core genes for treating DCM with Scutellariae Radix were obtained.The drug-disease interacted genes such as TGF-β1,TP53,MMP-9 and IL-6 were obtained through String PPI,KEGG signaling pathways such as MAPK and PI3K/Akt were enriched.In vitro experiments showed high glucose stimulation of H9c2 and AC16 cardiomyocytes led to upregulation of TGF-β1,COL Ⅰ and COL Ⅲ mRNA levels,p-Smad2/3,COL Ⅰ and COL Ⅲ protein levels,and signifi-cantly increased the content of TGF-β1 in the supernatant,while Baicalin weakened its expression.Conclusion The active ingredients of Scutellariae Radix exert anti DCM effects through multiple targets,among which Baicalin inhibits TGF-β1/Smad signaling to improve high glucose induced cardiomyocyte fibrosis and plays a protective role in DCM.

Objective To approach the significance of changes of percutaneous-arterial blood carbon dioxide partial pressure difference [P(tc-a)CO2] in liquid resuscitation of patients with septic shock. Methods One hundred and sixty-eight patients with septic shock admitted and treated in the Department of Intensive Care Unit (ICU) of Quzhou People's Hospital from January 2015 to January 2018 were enrolled, and after early goal-directed therapy (EGDT) for 6 hours, according to central venous oxygen saturation (ScvO2) and lactate clearance (LC), they were divided into ScvO2 and LC achievement group (ScvO2 ≥ 0.7 and LC≥10%), ScvO2 achievement group (ScvO2 ≥ 0.7 and LC < 10%), LC achievement group (ScvO2 < 0.7 and LC≥10%), and un-achievement group (ScvO2 < 0.7 and LC < 10%). The mechanical ventilation time, ICU hospitalization time, 28-day mortality, P(tc-a)CO2 etc. were compared among the four groups; the receiver operating characteristic curve (ROC) was used to evaluate the predictive value of P(tc-a)CO2 for 28-day prognosis in patients with septic shock. Results The trends of mechanical ventilation time, ICU hospitalization time, and 28-day mortality were all ScvO2 and LC achievement group < LC achievement group < ScvO2 achievement group < un-achievement group [the mechanical ventilation times (days) were respectively 6.12±2.59, 8.43±3.24, 11.78±4.12, 13.03±4.75, ICU hospitalization times (days) were 10.31±2.32, 13.85±3.56, 16.41±3.83, 18.52±4.05, and 28-day mortality rates were 28.85% (15/52), 40.91% (18/44), 51.28% (20/39), 69.70% (23/33)] and the differences among the four groups were statistically significant (all P < 0.05). After 6 hours of EGDT, the heart rate (HR), lactate (Lac), and P(tc-a)CO2 were lower than those before fluid resuscitation, but the mean arterial pressure (MAP), central venous pressure (CVP), and ScvO2 were higher than those before fluid resuscitation among four groups. Except CVP, the differences of other indicators compared among the ScvO2 and LC achievement group, ScvO2 achievement group, LC achievement group and un-achievement group were statistically significant (all P < 0.05). After 6 hours of EGDT, HR, Lac, P(tc-a)CO2 in ScvO2 and LC achievement group, ScvO2 achievement group and LC achievement group were significantly lower than those in the un-achievement group [HR (bpm): 89.05±29.43, 98.82±30.21, 94.33±28.64 vs. 112.85±32.74, Lac (mmol/L): 2.97±1.95, 3.87±2.32, 2.69±1.52 vs. 4.17±2.44, P(tc-a)CO2 (mmHg, 1 mmHg = 0133 kPa): 7.18±4.61, 12.61±5.34, 9.71±4.11 vs. 16.56±10.19], MAP and ScvO2 were significantly higher than those of the un-achievement group [MAP (mmHg): 88.05±21.67, 77.33±18.56, 83.11±19.71 vs. 70.32±18.79, ScvO2: 0.76±0.14, 0.75±0.16, 0.67±0.14 vs. 0.63±0.18, all P < 0.05]. The P(tc-a)CO2 of 28 days survivors were significantly lower than that of the deaths among four groups (mmHg: 5.78±2.27 vs. 14.14±3.65, 7.07±2.81 vs. 15.06±4.11, 6.35±2.09 vs. 14.94±4.06, 7.93±3.81 vs. 18.34±4.63, all P < 0.05). When P(tc-a)CO2 > 7.24 mmHg predicted 28-day mortality in ScvO2 and LC achievement group, the sensitivity was 89.29%, specificity was 91.45%, and the area under ROC curve (AUC) was 0.86; when P(tc-a)CO2 > 9.46 mmHg predicted 28-day mortality in LC achievement group, the sensitivity was 88.72%, specificity was 85.83% and AUC was 0.91; when P(tc-a)CO2 >12.05 mmHg predicted 28-day mortality in ScvO2 achievement group, the sensitivity was 82.79%, specificity was 86.90% and AUC was 0.79; when P(tc-a)CO2 > 16.22 mmHg predicted 28-day mortality in un-achievement group, the sensitivity was 73.35%, specificity was 80.68% and AUC was 0.68. Conclusion P(tc-a)CO2 can be used as an indicator to evaluate fluid resuscitation effect and prognosis in patients with septic shock.

Objective To analyze the pathologically confirmed pulmonary Actinomycosis in the 11 patients in focusing on clinical features and mis-diagnostic reasons so as to improve physicians' awareness of this rare disease and reduce the misdiagnosis.Methods We retrospectively reviewed the medical records of 11 cases with pathologically confirmed pulmonary Actinomycosis during January 2003-August 2015.The clinical data and main causes of misdiagnosis in these cases were collected and analyzed.Results The study included 11 patients with a mean age of(53.0 ± 11.6.0)years.Among the 11 cases,8 (72.7 ％) patients had complications,6 (54.5 ％) were current or ex-smokers.Main clinical manifestations of 11 cases were cough(11/11,100.0 ％),sputum(11/11,100.0 ％),hemoptysis (7/11,63.6％),chest pain(6/11,54.5％)and fever(3/11,27.3％).Ten patients presented with one lobe of lung lesions,including 4 patients in the lower lobe and 3 in the upper lobe of the left lung,2 in the upper lobe and 1 in the lower lobe of the right lung.While,the remained one case presented with lesion locating in right main bronchus.Iconography often presented as pulmonary mass shadow,consolidation shadow,spicule sign,lobulation sign,hilar and/or mediastinal lymphadenopathy and pleural effusion.Vacuolar lesions were observed in some of the focuses.Flexible bronchoscopy was performed in 8 (72.7％)patients.Among them,7 patients showed mucosal swelling and congestion,luminal occlusion with purulence secretion,2 cases with polypoid neoplasm.Initial misdiagnosis rate were 100％ (11/11),among which 7 cases were misdiagnosed as lung cancer,2 cases as fungus infection,and 1 case as pulmonary tuberculosis and 1 case as pneumonia,respectively.All patients were definitely diagnosed by biopsy finding an evidence of hyphae of Actinomycosis in lung tissue specimens.The definitive diagnosis was made by CT-guided percutaneous lung biopsy in 4 cases,by transbronchial lung biopsy (TBLB)in 5 cases and by thoracotomy or video-assisted thoracoscopic surgery(VATS) in 1 case respectively.Actinomycosis in most patients was cured with high-dose penicillin administration over a prolonged period.Conclusions The diagnosis of pulmonary Actinomycosis remains challenging via its non-specific clinical symptoms and iconography features,and the presence of comorbidity may further increase the difficulty and complexity of diagnosis,leading to delaying-or mistaking-diagnosis.Obtaining positively pathological specimens is diagnostic key.Transbronchial lung biopsy through a bronchoscope and CT-guided percutaneous needle biopsy are the priority methods.

Objective To investigate the activation of nuclear factor-B (NF-B)and hypoxia-inducible factor-1 (HIF-1)in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods Subjects were classified into mild-to-moderate OSHAS group (n = 16), severe OSAHS group (n = 14) and the matched control group (n=30). Gene and protein expressions of NF-B and HIF-1 were measured by RT-PCR, Western blot in peripheral blood mononuclear cells (PBMC). Results NF-κB p65 mRNA and NF-κB p65 protein,HIF-1α mRNA and HIF-1α protein in PBMC were significantly higher in severe OSAHS group than those in mild–to-moderate group and control group (P<0.01). But there were no significant difference in NF-κB p65 mRNA and NF-κB p65 protein between mild-to-moderate group and control group (P=0.068, P=0.254 respectively). Only gene (P<0.05) not the protein (P=0.777) of HIF-1αwas higher in mild-to-moderate as compared with control group. Both NF-κB p65 mRNA and HIF-1αmRNA were positively correlated with AHI (r=0.493, P=0.006, r=0.508, P=0.004), while negatively correlated with nighttime lowest blood oxygen saturation (LSaO2)(r=-0.488, P=0.006, r=-0.46, P=0.011). There was a positive correlation between NF-κB p65 protein level and AHI (r=0.669, P<0.001). HIF-1αprotein level was positively correlated with AHI, ODI (r=0.628, P=0.001;r=0.480, P=0.018). There were positive correlations between NF-κBp65mRNA and HIF-1αmRNA (r=0.543, P=0.002), NF-κBp65 and HIF-1αprotein respectively (r=0.716, P<0.001). Conclusions As the gene and protein of NF-κB and HIF-1 were up-regulated in patients with OSAHS, and also positively correlated with the severity of sickness. We conclude that both NF-κB and HIF-1 were involed in the pathogenesis of OSAHS.

A 69-year-old man with fever,pulmonary nodules,joint pain and superficial lymphadenopathy was admitted to our hospital.The patient had a history of ten year hypertension.She smoked a pack of cigarettes daily for forty years and quitted for fifteen years.Family history of coronary heart disease,diabetes,cancer or other diseases was negative.Chest CT showed a nodule in the left lung lower lobe.Percutaneous lung biopsy revealed a large number of atypical B cell proliferation and infiltration which involved the vessel wall.The atypical B-cell phenotype and genotype was EBERs (+),CD20 (+),CD30 (+),CD15 (-).The patient was diagnosed as pulmonary lymphomatoid granulomatosis (LYG),an angiodestructive and angioinvasive lymphoproliferative disorder which is an Epstein-Barr virus associated B cell disorder with reactive T lymphocytes.The patient received six courses of chemotherapy.In this rare case,misdiagnosis of LYG often occurred due to the complex clinical presentation and non-specific imaging.Percutaneous or open lung biopsy is the main choice in the diagnosis of LYG.

Objective To evaluate the influence of nuclear factor (NF)-κB activation in peripheral blood mononuclear cells (PBMCs) on vascular inflammation in elderly patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods The 40 elderly subjects (≥65years old) were classed into control, mild, moderate and severe groups (n = 10, respectively)according to polysomnography (PSG). After PSG, the samples of peripheral venous blood were collected, and PBMCs were isolated. Nuclear protein was extracted and NF-κB was measured by Western blotting. ELISA was applied to measure the levels of TNF-α and IL-6 in serum. Blood samples from 10 cases (moderate 5 and severe 5) were measured again after four weeks of continuous positive airway pressure (CPAP) treatment. Results The expression of NF-κB in PBMCs and the concentration of TNF-α in serum were significantly increased in severe and moderate OSAHS patients compared with controls (P＜0. 05). The NF-κB expression was positively correlated with AHI (r=0. 617, P＜ 0. 001) and TNF-α concentration (r = 0. 498, P＜ 0. 001 ), negatively correlated with LSaO2 (r= -0. 548, P＜0. 001), and not correlated with IL-6 concentration (r=0. 365, P=0. 201).The CPAP treatment could significantly inhibit NF-κB activation in PBMCs and reduce TNF-αexcretion (P＜0.05, respectively). Conclusions PBMCs may play an important role in vascular endothelial injury through NF-κB expression and TNF-α excretion in elderly OSAHS patients, which is closely associated with the severity of the syndrome and night hypoxemia. CPAP treatment can inhibit the pathophysiologic process effectively.

Atherosclerosis is a kind of complex progressive inflammation.Exposure to atherogenic risk factors,particularly OxLDL,induces the activity of BKCa in endothelial cell,monocyte/macrophage(M?),vascular smooth muscle cell,platelet and other cells to activate,which precipitates dysfunction of the cells and therefore contributes to the development of atherosclerosis.This article briefly reviews the reseach progress in BKCa participating in the development of atherosclerosis.