Objective To investigate the effects and underlying mechanisms of a spray prepared from exosomes derived from M2 macrophages induced by interleukin-4 （IL-4） and tantalum particles （Ta） on the healing of pressure ulcers. Methods Bone marrow-derived macrophages were polarized into M2 macrophages using IL-4 or Ta, and exosomes （Exo-IL-4/Exo-Ta） were extracted. The regulatory effects of Exo-IL-4/Exo-Ta on M1 macrophage phenotypes and fibroblast matrix secretion were evaluated in vitro. Proteomic analysis was conducted to explore the biological processes and regulatory networks associated with Exo-Ta. A rat pressure ulcer model was used to assess the effects of Exo-IL-4/Exo-Ta spray on wound healing rate, inflammatory cell infiltration, and collagen deposition. Results In vitro, Exo-IL-4/Exo-Ta induced the polarization of M1 macrophages to M2 macrophages, reduced the secretion of pro-inflammatory factors, and promoted the expression of anti-inflammatory substances. Additionally, Exo-IL-4/Exo-Ta enhanced the production of collagen and fibronectin in fibroblasts. Proteomic analysis revealed that Exo-Ta primarily participated in biological processes such as energy metabolism and macromolecule biosynthesis. In vivo, Exo-IL-4/Exo-Ta spray accelerated wound healing, reduced inflammatory infiltration, and improved tissue remodeling in the rat pressure ulcer model. Conclusion Exosome sprays derived from M2 macrophages could accelerate pressure ulcer healing by modulating inflammation and promoting tissue regeneration, which demonstrated excellent clinical application potential.

Objective:To investigate the prognostic value of molecular subtypes in patients with resected invasive breast cancer.Methods:Between 2015 and 2018 7 869 patients with invasive breast cancer after undergoing surgery were included in this analysis. Breast cancer was classified into four subtypes according to the status of hormone receptor (HR) and HER2: HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. Kaplan-Meier curves and COX regression were used to compare disease-free survival (DFS) and overall survival (OS) among different subtypes.Results:The 5-year DFS and OS were 86.30% and 94.29%, respectively. Proportions of HR+/HER2-、HR+/HER2+、HR-/HER2+ and HR-/HER2- were 52.9%、17.5%、14.1%和15.5%, respectively. The 5-year DFS of HR+/HER2- subtype (88.12%) was higher than HR+/HER2+ (84.67%, P=0.026), HR-/HER2+ (84.19%, P<0.001) and HR-/HER2- (83.70%, P<0.001). The 5-year OS of HR+/HER2- (95.38%) was not different from HR+/HER2+ (95.17%, P=0.187), while it was higher than that of HR-/HER2+ (92.26%, P<0.001) and HR-/HER2- (91.69%, P<0.001). Subtype was still a significant factor regarding DFS and OS in multivariable analyses adjusting for age, sex, stage, Ki67, types and time of surgery. The DFS ( P=0.257) and OS ( P=0.511) was not different between HR-/HER2+与HR+/HER2- subtypes, while HR-/HER2+ and HR-/HER2- patients had worse DFS ( P<0.05) and OS ( P<0.05) than that with HR+/HER2-. Conclusions:Molecular subtype is a significant independent prognostic factor for DFS and OS in operable invasive breast cancer. HR+ subtypes have better prognosis compared with HR- subtypes. The DFS and OS were not different between HR+/HER2- and HR+/HER2+, or between HR-/HER2+ and HR-/HER2-.

Objective:To evaluate the clinical value of tissue doppler imaging Tei index in evaluating the degree of myocardial injury, right cardiac function after neonatal asphyxia.Methods:From March 2018 to May 2019, 62 cases of neonatal asphyxia hospitalized in the undergraduate department of Yiwu Central Hospital were classified as asphyxia group.According to Apgar score of birth, they were further divided into 41 cases of mild asphyxia group, 21 cases of severe asphyxia group.And 30 healthy full-term neonates delivered in our Hospital during the same period were selected as normal control group.The Newborn's Tei index, as well as the different severity asphyxia neonatal serum myocardial injury indicators[amino terminal brain natriuretic peptide(NT-proBNP), troponin(cTn-Ⅰ), creatine kinase isoenzyme(CK-MB), lactate dehydrogenase(LDH)], ultrasonic right heart function parameters[right ventricular ejection fraction(RVEF), E, A value and E/A ratio] were compared.Pearson test was used to evaluate the correlation between Tei index, myocardial injury indicators and right cardiac function parameters in neonatal asphyxia cases.Results:The Tei index of the asphyxiation group was (0.38±0.05), which was higher than (0.27±0.04) of the control group ( t=10.521, P<0.05), and the Tei index of the severe asphyxiation group was (0.43±0.06), which was higher than (0.34±0.05) of the mild asphyxiation group ( t=6.264, P<0.05). In neonatal asphyxia cases, the NT-proBNP, cTnI, CK-MB, LDH levels in the severe asphyxia group were (1 164.27±231.64)ng/L, (0.33±0.05)μg/L, (27.11±3.65)U/L, (298.20±37.57)U/L, respectively, which were higher than those in the mild asphyxia group [(590.38±73.91)ng/L, (0.25±0.04)μg/L, (18.36±2.34)U/L, (200.71±24.39)U/L] ( t=14.576, 6.839, 11.463, 12.338, all P<0.05). The ultrasonic RVEF level, E/A ratio in the severe asphyxia group were (52.94±6.10)%, (0.94±0.11), respectively, which were lower than those in the mild asphyxia group [(56.83±5.97)%, (1.02±0.13)] ( t=2.411, 2.547, all P<0.05). Correlation analysis found that Tei index was positively correlated with NT-proBNP, cTn-Ⅰ, CK-MB, LDH levels, and negatively correlated with RVEF level, and positively correlated with E/A ratio in neonatal asphyxia cases( r=0.745, 0.598, 0.703, 0.665, -0.711, -0.692, all P<0.05). Conclusion:Abnormal increasing of Tei index in neonatal asphyxia cases can objectively reflect the extent of myocardial injury and right heart function decline in children.

Objectives: To examine the expression of the long coding RNA GSTM3TV2 in pancreatic cancer tissues and to examine its role and mechanism in chemoresistance of pancreatic cancer cells. Methods: The expression of lncRNA GSTM3TV2 in 15 pancreatic cancer specimens and corresponding adjacent to cancer tissue samples diagnosed by Department of Pathology, Peking Union Medical College Hospital was detected by real-time PCR.And the expressions of GSTM3TV2 in pancreatic cancer cell AsPC-1, BxPC-3, MIAPaCa-2, PanC-1, SU86.86, T3M4, and chemoresistant cells AsPC-1/GR and MIAPaCa-2/GR, and human pancreatic nestin-expressing cells hTERT-HPNE were detected. Pancreatic cancer cell lines were transfected with GSTM3TV2-pcDNA3.1(+)in order to get cells with GSTM3TV2 overexpression.GSTM3TV2-siRNA was transfected into pancreatic cancer cells to knock down GSTM3TV2. The cell chemoresistance was measured by CCK-8 and flow cytometry assay when incubated with nab-paclitaxel. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of GSTM3TV2 on chemoresistance of tumor growth in nude mice.Western blot assay was also performed to detect the molecular mechanism of chemoresistance of GSTM3TV2. Results: Comparing toadjacent tissues(0.084±0.019), GSTM3TV2 expression was significantly upregulated in the pancreatic cancer tissues(0.493±0.084) (t=5.146, P<0.05). GSTM3TV2 expression were higher in the chemotherapy resistance pancreatic cancer cells AsPC-1/GR(210.799±19.788) and MIAPaCa-2/GR(122.408±23.419) than that in the AsPC-1(3.793±0.615) and the MIAPaCa-2(5.179±1.095)(t=21.800,P<0.05;t=-18.490,P<0.05). The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing GSTM3TV2 group ((1 059.609±102.498)mm³) was significantly larger than that in the control group((566.414±81.087) mm³) by treated with nab-paclitaxel(t=4.230,P<0.05).Meanwhile, GSTM3TV2 could promote the expression of Cyclin D1, CDK6, Cyclin E1, Vimentin, N-cadherin, ZEB1, Snail and Slug; but decrease cleaved caspase-3, cleaved PARP in pancreatic cancer cells. Conclusions The expression level of GSTM3TV2 in pancreatic canceris higher than that in paired adjacent tissues. GSTM3TV2 may act as an oncogene to promote chemoresistance in pancreatic cancer through regulation of cell proliferation, apoptosis, and epithelial-mesenchymal transition.

Objective To evaluate the drug-eluting-beads (DEB)-TACE as down-stage therapy for hepatocellular carcinoma before liver transplantation.Methods Inclusion criteria:the hepatocellular carcinoma exceeding the standard of Milan criteria.From Jan 2016 to Jan 2018,30 patients received DEB-TACE as down-stage therapy for hepatocellular carcinoma before liver transplantation.4 weeks after DEB-TACE,the imaging examination was performed.The patients who received the liver transplantation,the pathological conditions were recorded and the tumor free survival of the patients was followed up.Results 30 patients received 30 times DEB-TACE successfully.76.7％ (23/30) patients was down-staged to meet UCSF criteria,53.3％ (16/30) patients was down-staged to meet Milan criteria.13 patients had being given liver transplantation,pathology showed that DEB-TACE achieved complete necrosis in 30.8 ％ (4/13)cases.No significant treatment related complications were observed.After liver transplantation 12 patients are alive with no tumor recurrence.The tumor recurrence rate after liver transplantation was 7.7％.Conclusion DEB-TACE is safe and effective as down-stage therapy for hepatocellular carcinoma before liver transplantation.

Objective To evaluate the value of DEB-TACE before liver transplantation for hepatocellular carcinoma patients.Methods From Jan.2016 to Jan.2018,23 patients received DEB-TACE before liver transplantation for hepatocellular carcinoma were induced.Complications evaluation was followed up after interventional therapy.4 weeks after the intervention,the imaging examination was performed to examine the tumor response rate depond on mRECIST,the pathological conditions and tumor free survival were studied in the patients who received liver transplantation.Results The achievement ration of operation was 100％ in 23 patients.23 patients received 24 times successfully,1 patient received DEB-TACE twice,and the remaining 22 patients received DEB-TACE once.No serious complications occurred.Eighteen patients (78.3％,18/23) had postembolic syndrome after interventional therapy,mainly fever and pain.Four weeks after DEB-TACE,the complete response rate was 47.8％ (11/23),partial response rate was 30.4％ (7/23),disease stability rate was 21.7％ (5/23).All the 23 patients were included in the waiting list for transplantation.Among them,15 cases received liver transplantation.Pathological results showed that the total necrosis rate was 53.3％ (8/15),and the tumour necrosis rate in 4 of them was less than 50％.The average tumour necrosis rate of the neoplasm was 75.0％.The 15 patients who received liver transplantation were alive with no tumor recurrence.Conclusion DEB-TACE is a safe and effective treatment for patients suffered from hepatocellular carcinoma in waiting for liver transplantation.However,due to the short time of DEBs in China,further research is needed.

Objectives To examine the expression of the long coding RNA GSTM3TV2 in pancreatic cancer tissues and to examine its role and mechanism in chemoresistance of pancreatic cancer cells. Methods The expression of lncRNA GSTM3TV2 in 15 pancreatic cancer specimens and corresponding adjacent to cancer tissue samples diagnosed by Department of Pathology, Peking Union Medical College Hospital was detected by real?time PCR.And the expressions of GSTM3TV2 in pancreatic cancer cell AsPC?1,BxPC?3,MIAPaCa?2,PanC?1,SU86.86,T3M4,and chemoresistant cells AsPC?1/GR and MIAPaCa?2/GR, and human pancreatic nestin?expressing cells hTERT?HPNE were detected. Pancreatic cancer cell lines were transfected with GSTM3TV2?pcDNA3.1(+)in order to get cells with GSTM3TV2 overexpression.GSTM3TV2?siRNA was transfected into pancreatic cancer cells to knock down GSTM3TV2. The cell chemoresistance was measured by CCK?8 and flow cytometry assay when incubated with nab?paclitaxel. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of GSTM3TV2 on chemoresistance of tumor growth in nude mice.Western blot assay was also performed to detect the molecular mechanism of chemoresistance of GSTM3TV2. Results Comparing toadjacent tissues(0.084 ± 0.019), GSTM3TV2 expression was significantly upregulated in the pancreatic cancer tissues(0.493 ± 0.084) (t=5.146, P<0.05). GSTM3TV2 expression were higher in the chemotherapy resistance pancreatic cancer cells AsPC?1/GR(210.799±19.788) and MIAPaCa?2/GR(122.408±23.419) than that in the AsPC?1(3.793±0.615) and the MIAPaCa?2(5.179±1.095)(t=21.800,P<0.05;t=-18.490,P<0.05). The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing GSTM3TV2 group ((1 059.609±102.498)mm3) was significantly larger than that in the control group((566.414±81.087) mm3) by treated with nab?paclitaxel(t=4.230,P<0.05).Meanwhile,GSTM3TV2 could promote the expression of Cyclin D1, CDK6, Cyclin E1, Vimentin, N?cadherin, ZEB1, Snail and Slug; but decrease cleaved caspase?3,cleaved PARP in pancreatic cancer cells.Conclusions The expression level of GSTM3TV2 in pancreatic canceris higher than that in paired adjacent tissues. GSTM3TV2 may act as an oncogene to promote chemoresistance in pancreatic cancer through regulation of cell proliferation,apoptosis, and epithelial?mesenchymal transition.

Objectives To examine the expression of the long coding RNA GSTM3TV2 in pancreatic cancer tissues and to examine its role and mechanism in chemoresistance of pancreatic cancer cells. Methods The expression of lncRNA GSTM3TV2 in 15 pancreatic cancer specimens and corresponding adjacent to cancer tissue samples diagnosed by Department of Pathology, Peking Union Medical College Hospital was detected by real?time PCR.And the expressions of GSTM3TV2 in pancreatic cancer cell AsPC?1,BxPC?3,MIAPaCa?2,PanC?1,SU86.86,T3M4,and chemoresistant cells AsPC?1/GR and MIAPaCa?2/GR, and human pancreatic nestin?expressing cells hTERT?HPNE were detected. Pancreatic cancer cell lines were transfected with GSTM3TV2?pcDNA3.1(+)in order to get cells with GSTM3TV2 overexpression.GSTM3TV2?siRNA was transfected into pancreatic cancer cells to knock down GSTM3TV2. The cell chemoresistance was measured by CCK?8 and flow cytometry assay when incubated with nab?paclitaxel. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of GSTM3TV2 on chemoresistance of tumor growth in nude mice.Western blot assay was also performed to detect the molecular mechanism of chemoresistance of GSTM3TV2. Results Comparing toadjacent tissues(0.084 ± 0.019), GSTM3TV2 expression was significantly upregulated in the pancreatic cancer tissues(0.493 ± 0.084) (t=5.146, P<0.05). GSTM3TV2 expression were higher in the chemotherapy resistance pancreatic cancer cells AsPC?1/GR(210.799±19.788) and MIAPaCa?2/GR(122.408±23.419) than that in the AsPC?1(3.793±0.615) and the MIAPaCa?2(5.179±1.095)(t=21.800,P<0.05;t=-18.490,P<0.05). The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing GSTM3TV2 group ((1 059.609±102.498)mm3) was significantly larger than that in the control group((566.414±81.087) mm3) by treated with nab?paclitaxel(t=4.230,P<0.05).Meanwhile,GSTM3TV2 could promote the expression of Cyclin D1, CDK6, Cyclin E1, Vimentin, N?cadherin, ZEB1, Snail and Slug; but decrease cleaved caspase?3,cleaved PARP in pancreatic cancer cells.Conclusions The expression level of GSTM3TV2 in pancreatic canceris higher than that in paired adjacent tissues. GSTM3TV2 may act as an oncogene to promote chemoresistance in pancreatic cancer through regulation of cell proliferation,apoptosis, and epithelial?mesenchymal transition.

Objective: To explore the role of targeted ultrasound contrast agent in the evaluation of angiogenesis in papillary thyroid carcinoma (PTC) in nude mice by constructing platelet derived growth factor receptor α (PDGFRα)-targeted ultrasound contrast agents, and to explore the effect of platelet derived growth factor (PDGF) on angiogenesis in PTC. Methods: PDGFRα-targeted ultrasound contrast agents were constructed through biotin-avidin linkage, and blank micro-bubbles were served as control group. After the siRNA-PDGF BCPAP cell line was established, well prepared BCPAP cells or siRNA-PDGF-BCPAP cells were injected subcutaneously into the back of male BABL/C nude mice. The growth of the tumors was observed closely. All tumors of the normal group and the siRNA-PDGF group were examined by PDGFRα-targeted ultrasound contrast agents or blank micro-bubbles, and the dynamic images were analyzed quantitatively by QontraXt software.All mice were sacrificed after ultrasonography. Microvessels density (MVD) in the tumors was counted by CD31 staining and the expressions of vascular endothelial growth factor(VEGF) and PDGF were detected by Western Blot. Results: PTCs in nude mice were enhanced well by PDGFRα-targeted ultrasound contrast agent or blank micro-bubbles. The peak of tumors in siRNA-PDGF group was significantly lower than that in the normal group [(43.085±13.244)% vs (57.428±10.952)%, P=0.004]; MVD of the siRNA-PDGF group was significantly less than that of the normal group [(23.200±6.017)strips/view vs (35.000±8.456)strips/view, P=0.012]. The protein expression of PDGF and VEGF in siRNA-PDGF group were significantly lower than those in the normal group, respectively (0.142±0.058 vs 0.269±0.102, P=0.002; 0.096±0.036 vs 0.158±0.072, P=0.016). Conclusions PDGF plays an important role in angiogenesis of PTC, it maybe a new ultrasound molecular imaging method for monitoring tumor angiogenesis.

Objective: To investigate the expression of KLK7 in pancreatic cancer and its clinical significance. Methods: Immunohistochemistry was used to detect the expression of KLK7 protein in pancreatic cancer tissue microarray with 92 samples. Statistical analysis of the relationship between KLK7 and clinicopathological characteristics was finished. Pancreatic cancer cell lines were infected with lentiviuses in order to get cells with KLK7 stable overexpression.KLK7-siRNA was transfected into pancreatic cancer cells to knock down KLK7.Cell proliferation and chemosensitivity were detected by CCK-8 assay; Cell invasion and migration abilities were detected by Transwell assay. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of KLK7 on tumor growth in nude mice. Data were statistically analyzed by rank sum test, χ² test and Logistic regression analysis. Results: The expression level of KLK7 in pancreatic cancer tissues was higher than that in paired adjacent tissues (P<0.05). KLK7 expression was correlated with vascular invasion(χ²=7.535, P<0.05). Further univariate and multivariate analysis showed that KLK7 expression was an independent risk factor for vascular invasion of pancreatic cancer(χ²=7.535, P<0.05). The overexpression of KLK7 in pancreatic cancer cell lines BxPC-3 and CFPAC can increase their proliferation abilities, reduce the chemosensitivity and promote their migration and invasion behaviour; The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing KLK7 group was significantly larger than that in the control group (t=4.479, P<0.05). The group of overexpressing KLK7 showed greater tumor weight than the control group(t=2.831, P<0.05). Conclusions The expression level of KLK7 in pancreatic ductal adenocarcinoma was higher than that in paired adjacent tissues and it is an independent risk factor for vascular invasion of pancreatic cancer.KLK7 can promote the proliferation of pancreatic cancer cells, reduce the chemosensitivity and increase the invasion and migration of pancreatic cancer cells.