OBJECTIVE To deeply explore the in vivo pharmacodynamic substance basis of Zhigancao Decoction,a classic tradi-tional Chinese medicine formula,and provide scientific evidence for its rational application and development in modern clinical practice.METHODS Wistar rats were treated with 12.15 g·kg-1 Zhigancao Decoction by gavage.Rat plasma samples were collect-ed at 10 time points(5,15,30,60,120,240,360,480,600 and 720 min after administration)and rat heart(atrial and ventricu-lar)tissue samples were collected at 12 h after administration.Components in the plasma and heart samples were qualitatively identi-fied by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF/MS),and the distri-bution characteristics of Zhigancao Decoction in vivo were analyzed.At the same time,the time-concentration curve of the prototype components and metabolites in Zhigancao Decoction was drawn to observe the changes of blood drug concentration.RESULTS A total of 11 prototype components(Ajugol,Nicotiflorin,Isoschaftoside,4-Hydroxycinnamic acid,Rehmapicrogenin,4-Hydroxybenzoic acid,4′,7-Dihydroxyflavone,Calycosin,3′,4′,7-Trihydroxyflavone,Pinellic acid,Truxillic acid)and 7 metabolites were identified from the plasma samples of Zhigancao Decoction,mainly including flavonoids(flavonoids glycosides),organic acids,and iridoid glyco-sides,etc.Additionally,6 prototype components(Ajugol,Isoschaftoside,Rehmapicrogenin,4′,7-Dihydroxyflavone,Liquiritigenin,3′,4′,7-Trihydroxyflavone)and 3 metabolites were identified from the cardiac samples(the atrium and the ventricle showed the same results).The metabolic pathways mainly involved Phase Ⅰ metabolism and glucuronidation.CONCLUSION The prototype compo-nents and metabolites in plasma and heart tissue of Zhigancao Decoction is preliminarily determined,providing a reference for analyzing the active components of Zhigancao Decoction in heart tissue.

OBJECTIVE To deeply explore the in vivo pharmacodynamic substance basis of Zhigancao Decoction,a classic tradi-tional Chinese medicine formula,and provide scientific evidence for its rational application and development in modern clinical practice.METHODS Wistar rats were treated with 12.15 g·kg-1 Zhigancao Decoction by gavage.Rat plasma samples were collect-ed at 10 time points(5,15,30,60,120,240,360,480,600 and 720 min after administration)and rat heart(atrial and ventricu-lar)tissue samples were collected at 12 h after administration.Components in the plasma and heart samples were qualitatively identi-fied by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF/MS),and the distri-bution characteristics of Zhigancao Decoction in vivo were analyzed.At the same time,the time-concentration curve of the prototype components and metabolites in Zhigancao Decoction was drawn to observe the changes of blood drug concentration.RESULTS A total of 11 prototype components(Ajugol,Nicotiflorin,Isoschaftoside,4-Hydroxycinnamic acid,Rehmapicrogenin,4-Hydroxybenzoic acid,4′,7-Dihydroxyflavone,Calycosin,3′,4′,7-Trihydroxyflavone,Pinellic acid,Truxillic acid)and 7 metabolites were identified from the plasma samples of Zhigancao Decoction,mainly including flavonoids(flavonoids glycosides),organic acids,and iridoid glyco-sides,etc.Additionally,6 prototype components(Ajugol,Isoschaftoside,Rehmapicrogenin,4′,7-Dihydroxyflavone,Liquiritigenin,3′,4′,7-Trihydroxyflavone)and 3 metabolites were identified from the cardiac samples(the atrium and the ventricle showed the same results).The metabolic pathways mainly involved Phase Ⅰ metabolism and glucuronidation.CONCLUSION The prototype compo-nents and metabolites in plasma and heart tissue of Zhigancao Decoction is preliminarily determined,providing a reference for analyzing the active components of Zhigancao Decoction in heart tissue.

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

Objective To evaluate the efficacy and safety of transcatheter hepatic arterial chemoembolization (TACE) combined with CT guided radiofrequency ablation (RFA) for primary liver cancer in the caudate lobe.Methods Sixteen patients with primary liver cancer in the caudate lobe were treated with combination therapy of TACE and RFA.Complet ablation rate,overall and recurrence-free survival,and complications were evaluated.Results A total of 15 cases achieved complet ablation,complet ablation rate was 93.75％ (15/16).Recurrence-free survival time was 19.35 months,overall survival time was 44.62 months.Overall survival rates were 88.23％,66.65％ and 33.18％ at 1,3,5 years after therapy,respectively.Conclusion TACE combined with RFA is a safe and useful therapeutic option for treatment of primary liver cancer in the caudate lobe.

Objective To investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with CT-guided thermal ablation (radiofrequency ablation or microwave ablation) in treating intrahepatic cholangiocarcinoma.Methods The clinical data of 14 patients with pathologicallyproved intrahepatic cholangiocarcinoma,who were admitted to authors' hospital during the period from September 2009 to July 2013 to receive TACE with subsequent radiofrequency ablation (RFA) or microwave ablation (MWA),were retrospectively analyzed.A total of 18 lesions were detected in the 14 patients.The maximal diameter of the lesion (or the sum of maximal diameters if there were multiple lesions) ranged from 2.2 cm to 7.2 cm (mean 4.2±1.4 cm).After TACE,the lesion's complete ablation rate,surgical complications,tumor-free survival time and overall survival time were evaluated.Results Complete ablation was obtained in 15 lesions (83.3％,15/18).The incidence of moderate complications was 6.2％,and no severe complications or death occurred.After the treatment,the patients were followed up for 6-14 months,with a mean of (16.0±10.3) months.At the end of follow-up,6 patients (42.9％,6/14) died.The median tumor-free survival time in patients whose lesions obtained complete ablation was 17 months.The median survival time of all patients was 20 months.The 1-,2-and 3-year overall survival rates were 82.5％,41.3％ and 20.6％ respectively.Conclusion TACE combined with thermal ablation can be regarded as one of the treatment options for intrahepatic cholangiocarcinoma.

Purpose To investigate the expression and clinical significance of Foxp3 ( cell surface marker of regulatroy T) mRNA and its protein in endometrial carcinomas and normal endometrial tissues. Methods Real-time fluorescence quantitative PCR and immuno-histochemical SP methods were used to detect the expressions of mRNA and protein in tumor tissue of 84 cases of endometrial carcino-mas and 40 cases of normal endometrial tissue, then to analyze the relationship between Foxp3 gene and clinical pathological character-istics of endometrial carcinoma specimens, such as differentiation, FIGO stage. Results Foxp3 mRNA and it′s protein expression of endometrial carcinomas were significantly higher than that of normal endometrial tissues. There were significantly relationships between Foxp3 mRNA expression and FIGO stage of endometrial cancer, Foxp3 mRNA expressions of III+IV stage was higher than that ofⅠ+Ⅱ stage endometrial carcinoma (P<0. 05). But the relationship between Foxp3 expression and differentiation degree reached differ-ent conclusions in the two detection methods. By immunohistochemistry the expression of Foxp3 protein was correlation with histological differentiation grade (rs =0. 72, P <0. 01). In poorly differentiated endometrial carcinoma Foxp3 + cell number was significantly higher than that in well differentiated endometrial carcinoma. By detection of real-time fluorescence quantitative PCR method, Foxp3 mRNA expression was not correlated with tumor grade (rs =0. 01, P=0. 35). Conclusion Foxp3 in endometrial carcinomas are high expressions. Immunohistochemical method has more clinical value than real-time fluorescence quantitative PCR test results. Foxp3 may be involved in the regulation of the development of endometrial cancers.

OBJECTIVETo evaluate the long-term clinical outcomes of fractional flow reserve (FFR)-guided versus intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) for intermediate coronary lesions.

METHODSA total of 226 patients with 293 intermediate coronary artery lesions (stenosis of 40%-70%) confirmed by coronary angiography were randomized into 3 groups to undergo PCI for a minimal lumen cross sectional area (MLA)<4 mm(2) (IVUS group, 98 lesions) or for a FFR<0.80 (FFR group, 101 lesions), or to receive standard medical treatment (medication group, 94 lesions). The primary outcome was major adverse cardiac events including death, myocardial infarction, and ischemia-driven target vessel revascularization at 1 year after the index procedure.

RESULTSThe baseline percent diameter stenosis and lesion length were similar between the 3 groups, but more patients in IVUS group than in FFR group received PCI (P<0.001). No significant difference was found in the incidence of major adverse cardiac events between the 3 groups (P=0.182).

CONCLUSIONBoth FFR- and IVUS-guided PCI strategy for intermediate coronary artery disease are associated with favorable outcomes, but IVUS-guided PCI based on the single index of MLA can increase the rate of revascularization therapy.

Coronary Angiography ; Coronary Artery Disease ; surgery ; Fractional Flow Reserve, Myocardial ; Humans ; Myocardial Infarction ; Percutaneous Coronary Intervention

OBJECTIVETo investigate the frequency of USP6 gene rearrangement in nodular fasciitis (NF) and to evaluate its clinical application.

METHODSTwenty nine cases of previously diagnosed NF were screened for the presence of the USP6 gene rearrangement by interphase fluorescence-in-situ hybridization (FISH) on formalin-fixed paraffin-embedded tissue. Fifteen of these cases, which had available tissue, were also analysed for MYH9-USP6 fusion transcripts by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSTwenty four of the 29 cases (83%) were positive for the USP6 gene rearrangement by interphase FISH. The 15 cases with RT-PCR showed the following results: 11 positive, one deletion and three negative for USP6 gene rearrangement. Of these 15 cases, eight (8/15) showed MYH9-USP6 fusion transcript by RT-PCR. Of these eight cases, seven were positive for USP6 gene rearrangement and one showed USP6 deletion by FISH.

CONCLUSIONSUSP6 gene rearrangement is a recurrent genetic event in NF. It is a valuable ancillary tool for the pathological diagnosis of these lesions.

Fasciitis ; genetics ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Interphase ; Proto-Oncogene Proteins ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic ; Ubiquitin Thiolesterase ; genetics

Objective To evaluate the long-term clinical outcomes of fractional flow reserve (FFR)-guided versus intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) for intermediate coronary lesions. Methods A total of 226 patients with 293 intermediate coronary artery lesions (stenosis of 40%-70%) confirmed by coronary angiography were randomized into 3 groups to undergo PCI for a minimal lumen cross sectional area (MLA)<4 mm2 (IVUS group, 98 lesions) or for a FFR<0.80 (FFR group, 101 lesions), or to receive standard medical treatment (medication group, 94 lesions). The primary outcome was major adverse cardiac events including death, myocardial infarction, and ischemia- driven target vessel revascularization at 1 year after the index procedure. Results The baseline percent diameter stenosis and lesion length were similar between the 3 groups, but more patients in IVUS group than in FFR group received PCI (P<0.001). No significant difference was found in the incidence of major adverse cardiac events between the 3 groups (P=0.182). Conclusions Both FFR-and IVUS-guided PCI strategy for intermediate coronary artery disease are associated with favorable outcomes, but IVUS-guided PCI based on the single index of MLA can increase the rate of revascularization therapy.

Objective To evaluate the long-term clinical outcomes of fractional flow reserve (FFR)-guided versus intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) for intermediate coronary lesions. Methods A total of 226 patients with 293 intermediate coronary artery lesions (stenosis of 40%-70%) confirmed by coronary angiography were randomized into 3 groups to undergo PCI for a minimal lumen cross sectional area (MLA)<4 mm2 (IVUS group, 98 lesions) or for a FFR<0.80 (FFR group, 101 lesions), or to receive standard medical treatment (medication group, 94 lesions). The primary outcome was major adverse cardiac events including death, myocardial infarction, and ischemia- driven target vessel revascularization at 1 year after the index procedure. Results The baseline percent diameter stenosis and lesion length were similar between the 3 groups, but more patients in IVUS group than in FFR group received PCI (P<0.001). No significant difference was found in the incidence of major adverse cardiac events between the 3 groups (P=0.182). Conclusions Both FFR-and IVUS-guided PCI strategy for intermediate coronary artery disease are associated with favorable outcomes, but IVUS-guided PCI based on the single index of MLA can increase the rate of revascularization therapy.