Objective To explore the interventional mechanism of Bufei Yishen formula on chronic obstructive pulmonary disease from pathway level.Methods Macrophage inflammatory model was established by LPS stimulation.Based on gene set enrichment analysis(GSEA)method,macrophage inflammation related pathways were screened,and normalized enrichment score(NES)was used to identify pathways that were reversed by traditional Chinese medicine treatment,revealing the interventional mechanism of Bufei Yishen formula and its compatibility.Results The NES of Bufei Yishen formula was-1377.23,among which the NES of Bushen compatibility was-485.07,that of Huoxue was-351.86,Huatan was-303.71,and Yiqi was-236.59.There were 213 significantly disturbed pathways reversed after the intervention of Bufei Yishen formula,among which there were 184 reversed pathways for Huoxue compatibility,147 reversed pathways for Bushen,134 reversed pathways for Huatan,133 reversed pathways for Yiqi,and the reversal rate was 75.41%,60.25%,54.92%,54.51%,respectively.90 pathways,including TGF-β production,were significantly reversed in the four compatibilities.Positive regulation of cytokine production involved in inflammatory response etc were specifically reversed pathways for compatibility.Conclusion The intensity of Bufei Yishen formula that reversed macrophage-inflammatory related pathways was in order of Bushen,Huoxue,Huatan and Yiqi compatibility.And the number of pathways that could be reversed by the compatibility of Bufei Yishen formula was Huoxue,Bushen,Huatan and Yiqi.Bufei Yishen formula could regulate the common and specific reversal pathways of the compatibilities to intervene the inflammatory response.

AIM:To establish a mouse model of pulmonary fibrosis induced by multiple intratracheal instilla-tions of bleomycin(BLM).METHODS:C57BL/6J mice were randomly divided into five groups:control group(n=5),multiple high-dose BLM(BLM-MH)group(n=10),multiple medium-dose BLM(BLM-MM)group(n=8),multiple low-dose BLM(BLM-ML)group(n=7),and single medium-dose BLM(BLM-SM)group(n=6).The pulmonary fibrosis mod-el was induced by single or multiple intratracheal instillations of BLM.Survival curves were plotted at day 56,and lung tis-sue was collected for lung coefficient calculation.Pathological changes in lung tissue were assessed using hematoxylin-eo-sin(H&E)staining and Masson staining.Indicators of lung fibrosis,such as hydroxyproline(HYP),were measured.Dif-ferentially expressed genes in patients with IPF were screened using the GEO database,and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis was performed to identify pathways associated with IPF.Western blot was used to detect changes in these pathways in the lung tissues of the model mice.RESULTS:The survival rates were 50%in the BLM-MH group and 87.5%in the BLM-MM group,with no deaths in other groups.Compared with the control group,the BLM-MH and BLM-MM groups showed significantly increased lung coefficients(P＜0.05),lung tissue dam-age,inflammation levels,degree of pulmonary fibrosis(P＜0.05 or P＜0.01),and HYP content.The BLM-MH and BLM-MM groups,compared with the BLM-SM group,showed significantly elevated levels of inflammation,fibrosis,and HYP content(P＜0.05 or P＜0.01).GEO database and KEGG enrichment analysis revealed that the extracellular matrix-recep-tor interaction pathway(ECM-RIP)may be involved in IPF development.The expression levels of ECM-RIP pathway-re-lated proteins,such as phosphorylated focal adhesion kinase(p-FAK)and phosphorylated Src protein(p-Src),were in-creased in the lung tissues of the model mice compared with the control group.Compared with the BLM-SM group,the BLM-MH group exhibited significant increases in the protein levels of p-FAK and p-Src in the lung tissue(P＜0.05).CONCLUSION:The murine model of pulmonary fibrosis established through repeated intratracheal instillations of BLM effectively mimics the pathological characteristics of the disease,providing a valuable experimental model for the investiga-tion of idiopathic pulmonary fibrosis pathogenesis and for the development of therapeutic agents.

AIM:To establish a mouse model of pulmonary fibrosis induced by multiple intratracheal instilla-tions of bleomycin(BLM).METHODS:C57BL/6J mice were randomly divided into five groups:control group(n=5),multiple high-dose BLM(BLM-MH)group(n=10),multiple medium-dose BLM(BLM-MM)group(n=8),multiple low-dose BLM(BLM-ML)group(n=7),and single medium-dose BLM(BLM-SM)group(n=6).The pulmonary fibrosis mod-el was induced by single or multiple intratracheal instillations of BLM.Survival curves were plotted at day 56,and lung tis-sue was collected for lung coefficient calculation.Pathological changes in lung tissue were assessed using hematoxylin-eo-sin(H&E)staining and Masson staining.Indicators of lung fibrosis,such as hydroxyproline(HYP),were measured.Dif-ferentially expressed genes in patients with IPF were screened using the GEO database,and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis was performed to identify pathways associated with IPF.Western blot was used to detect changes in these pathways in the lung tissues of the model mice.RESULTS:The survival rates were 50%in the BLM-MH group and 87.5%in the BLM-MM group,with no deaths in other groups.Compared with the control group,the BLM-MH and BLM-MM groups showed significantly increased lung coefficients(P＜0.05),lung tissue dam-age,inflammation levels,degree of pulmonary fibrosis(P＜0.05 or P＜0.01),and HYP content.The BLM-MH and BLM-MM groups,compared with the BLM-SM group,showed significantly elevated levels of inflammation,fibrosis,and HYP content(P＜0.05 or P＜0.01).GEO database and KEGG enrichment analysis revealed that the extracellular matrix-recep-tor interaction pathway(ECM-RIP)may be involved in IPF development.The expression levels of ECM-RIP pathway-re-lated proteins,such as phosphorylated focal adhesion kinase(p-FAK)and phosphorylated Src protein(p-Src),were in-creased in the lung tissues of the model mice compared with the control group.Compared with the BLM-SM group,the BLM-MH group exhibited significant increases in the protein levels of p-FAK and p-Src in the lung tissue(P＜0.05).CONCLUSION:The murine model of pulmonary fibrosis established through repeated intratracheal instillations of BLM effectively mimics the pathological characteristics of the disease,providing a valuable experimental model for the investiga-tion of idiopathic pulmonary fibrosis pathogenesis and for the development of therapeutic agents.

Objective: To investigate the prognostic value of pretreatment albumin to globulin ratio(AGR)in prostate cancer(Pca)patients treated with maximal androgen blockade(MAB). Methods: Clinical and pathological data of 210 Pca patients who underwent MAB as first-line therapy between January 2013 and June 2018 were retrospectively analyzed.The ages of patients in our cohort ranged from 61 to 90 years, with a mean of(77.0±6.5)years.According to the cut-off point for AGR calculated by the receiver-operating curve analysis, patients were categorized into two groups: the high-AGR group and the low-AGR group.Clinical and pathological features were compared between the groups.Independent factors affecting prognosis were analyzed by using univariate and multivariate analysis. Results: The median follow-up duration was 44.0 months.Of the 210 patients, 99 cases had castration resistance, 100 patients(47.6%)had disease progression and 67 patients(31.8%)died.The cut-off point for AGR calculated by the receiver-operating curve analysis was 1.56.There were 103 cases in the low-AGR group(AGR<1.56)and 107 cases in the high-AGR group(AGR≥1.56). Univariate analysis revealed that the progression-free survival(PFS), cancer-specific survival(CSS)and overall survival(OS)were lower in the low-AGR group than in the high-AGR group[1.773(1.298~2.442), 1.948(1.220~3.213), 1.965(1.217~2.996), all P<0.05]. Multivariate Cox regression analysis showed that Gleason score, regional lymph nodes and bone metastases and AGR were independent prognostic factors for PFS(P=0.007, 0.040 and 0.022, P=0.031), CSS(P=0.003, 0.035 and 0.041, P=0.009)and OS(P=0.003, 0.026 and 0.023, P=0.002). Conclusions Pretreatment AGR<1.56 is an independent predictor for poor prognosis in Pca patients treated with MAB.

Objective:To investigate the expressions of TGF-β1,survivin and caspase-3 in hepatolithiasis-associated intrahepatic cholangiocarcinoma(ICC)tissue and their clinical significance.Methods:The expressions of TGF-β1,survivin and caspase-3 in intrahepatic bile duct specimens from 52 patients with intrahepatic stones and concomitant ICC(tumor group)and 30 patients with intrahepatic stones and chronic inflammation(inflammation group)as well as 30 specimens of normal intrahepatic bile duct were determined by immunohistochemical staining.The relations of the three factors with the clinicopathologic characteristics and prognosis of ICC patients were analyzed.Results:In tumor group,inflammation group and normal group,the positive expression rates TGF-β1 and survivin presented a successively decreasing order,while the positive expression rates of caspase-3 showed a successively increasing order(all P<0.05);in ICC tissue,the expressions of TGF-β1 and survivin showed a positive correlation(r=0.917,P<0.01),and both had a negative correlation with that of caspase-3(r=-0.890,P<0.01;r=-0.894,P<0.01).the results of univariate and multivariate analyses showed that TGF-β1,survivin and caspase-3 were independent influential factors for the prognosis of patients with hepatolithiasis-associated ICC(all P<0.05);the survival rates of patients with positive TGF-β1 or survivin expression were significantly reduced compared with respective negative ones(χ2=13.192,P=0.001;χ2=10.536,P=0.002),and the survival rate of patients with positive caspase-3 expression was significantly higher than those with its negative expression(χ2=5.469,P=0.023).Conclusion:The expressions of TGF-β1,survivin and caspase-3 are abnormal in hepatolithiasis-associated ICC tissue,and they may probably be jointly involved in the occurrence and development of this condition.

Objective:To investigate the expressions of TGF-β1,survivin and caspase-3 in hepatolithiasis-associated intrahepatic cholangiocarcinoma(ICC)tissue and their clinical significance.Methods:The expressions of TGF-β1,survivin and caspase-3 in intrahepatic bile duct specimens from 52 patients with intrahepatic stones and concomitant ICC(tumor group)and 30 patients with intrahepatic stones and chronic inflammation(inflammation group)as well as 30 specimens of normal intrahepatic bile duct were determined by immunohistochemical staining.The relations of the three factors with the clinicopathologic characteristics and prognosis of ICC patients were analyzed.Results:In tumor group,inflammation group and normal group,the positive expression rates TGF-β1 and survivin presented a successively decreasing order,while the positive expression rates of caspase-3 showed a successively increasing order(all P<0.05);in ICC tissue,the expressions of TGF-β1 and survivin showed a positive correlation(r=0.917,P<0.01),and both had a negative correlation with that of caspase-3(r=-0.890,P<0.01;r=-0.894,P<0.01).the results of univariate and multivariate analyses showed that TGF-β1,survivin and caspase-3 were independent influential factors for the prognosis of patients with hepatolithiasis-associated ICC(all P<0.05);the survival rates of patients with positive TGF-β1 or survivin expression were significantly reduced compared with respective negative ones(χ2=13.192,P=0.001;χ2=10.536,P=0.002),and the survival rate of patients with positive caspase-3 expression was significantly higher than those with its negative expression(χ2=5.469,P=0.023).Conclusion:The expressions of TGF-β1,survivin and caspase-3 are abnormal in hepatolithiasis-associated ICC tissue,and they may probably be jointly involved in the occurrence and development of this condition.

ObjectiveTo explore the clinical effect of testicular artery-sparing microscopic varicocelectomy (MV) in combination with Qilin Pills (QL) in the treatment of bilateral varicocele-induced oligoasthenospermia.

METHODSSixty patients with bilateral varicocele-induced oligoasthenospermia were randomly assigned to receive MV (n=30) or MV+QL (n=30), those in the latter group treated with oral QL for 12 weeks postoperatively. At 4, 8, and 12 weeks after operation, we compared the semen volume, sperm concentration, sperm motility, the levels of serum Inh B, luteinizing hormone (LH) and total testosterone (TT), and the testosterone secretion index (TSI) between the two groups.

RESULTSAfter surgery, all the patients showed disappearance of varicocele symptoms, remarkably improved semen volume, sperm concentration, sperm motility, serum Inh B and TT levels, TSI, decreased LH and FSH (P<0.01). At 12 weeks after treatment, statistically significant differences were found between the MV and MV+QL groups in Inh B (138.96±22.26 vs 129.54±22.23) ng/L, LH (3.17±0.12 vs 3.59±0.11) IU/L, TT (13.98±3.02 vs 12.68±3.12) nmol/L, and TSI (4.41±0.53 vs 3.53±0.51) nmol/ IU (P<0.05). The pregnancy rate was significantly higher in the MV+QL than in the MV group (73.4% vs 36.6%, P<0.05).

CONCLUSIONSTesticular artery-sparing microscopic varicocelectomy combined with Qilin Pills is an effective strategy for the treatment of bilateral varicocele-induced oligoasthenospermia by significantly improving the semen quality of the patient.

Objective To study the significance of the prognosis assessment by acute physiology and chronic health evaluation (APACHE Ⅱ ),sequential organ failure assessment (SOFA) score,clinical pulmonary infection score(CPIS) and multiple organ dysfunction syndrome (MODS) score in the patients of ventilator-associated pneumonia (VAP). Methods The clinical data of 68 cases with VAP in the ICU or RICU were studied. APACHE Ⅱ , SOFA and MODS scores on admission and APACHE Ⅱ , SOFA, CPIS and MODS scores on the first 24-hour of VAP diagnosis were recorded. The area under the receiver operating characteristic curve(AUROC ) and Logistic regression were used to estimate the prognostic ability by the four kinds of scoring systems. Results The APACHE Ⅱ , CPIS, MODS and SOFA scores on the first 24-hour of VAP diagnosis were significantly higher in non-survivors than those in survivors. AUROC of APACHE Ⅱ ,SOFA,MODS and CPIS respectively were 0.80,0.75,0.73,0.71. Logistic regression analysis showed that only APACHE Ⅱ＞ 18 scores on the first 24-hour of VAP diagnosis was an independent predictor of the mortality (OR: 5.7,95% CI: 1.9 - 20.0, P = 0.013). Conclusion The APACHE Ⅱ on the first 24-hour of VAP diagnosis may be a useful index in predicting progress of patients with VAP.

Objective To analyze the MRI characteristics of hematospermia seminal vesiculitis(HSV) and evaluate the diagnostic value of MRI in HSV. Methods The MRI parameters of 25 HSV patients underwent magnetic resonance imaging(MRI) imaging with SE T 1WI(TR/TE 558/14ms), Flash 2D water excitement(TR/TE 18.5/5.2ms), TSE T 2WI(TR/TE 4000/99ms) and fat suppression sequences were retrospectively analyzed. Results The bilateral seminal vesicles in all 25 patients with HSV enlarged. On SE T1-weighted images, intraseminal vesicle hemorrhage appeared as high signal intensity, which appeared more bright on Flash 2D water excitement sequence. The hypointensive duct wall of seminal vesicles could be clearly seen because of hyperintensive hemorrhage. On TSE T2-weighted images, intraseminal vesicle hemorrhage appeared as relatively lower signal intensity, and the duct wall of seminal vesicles could not clearly be depicted for being covered with relatively hypointensive hemorrhage. Conclusion Hematospermia seminal vesiculitis could be identified by MRI, and MRI was the best imaging method for examining hematospermia seminal vesiculitis.

Objective To study the value of CT and MRI in diagnosis of Caroli disease. Methods CT and MR findings in 10 patients with histologically proved Caroli disease were retrospectively reviewed. All the patients underwent both liver plane CT and contrast-enhanced CT. Five of 10 patients underwent MR imaging with Flash 2D T_1WI(TR/TE 148/4ms), True Fisp T_2WI(TR/TE 5.8/2.9ms) and MRCP(TR/TE 1120/86ms) sequences. Results The imaging paremeters of Caroli disease were multiple saccular/columnar dilatation of intrahepatic biliary ducts and communication with each other, which only partly were depicted at CT, however, all imaging findings were depicted at MRI True Fisp and MRCP without contrast-enhanced scanning. Of 10 patients, 4 cases were type Ⅰ of Caroli disease with hepatolith, but without hepatic cirrhosis and portal hypertention; 6 cases type Ⅱ,all complicated with hepatic cirrhosis and portal hypertension. Of 6 patients with type Ⅱ Caroli disease, 4 cases had not hepatolith, and 2 cases had hepatolith. Of 10 patients, 3 cases had bilateral sponge kidney. Conclusion Caroli disease could be identified by CT or MRI, but MRI was superior to CT in depicting Caroli disease.