Background and purpose:Members of the serine protease inhibitor(SERPIN)family can influence tumorigenesis,progression,and prognosis by modulating processes such as apoptosis,invasion,metastasis,and angiogenesis in tumor cells.However,their role in pancreatic cancer remains unclear.This study aimed to investigate the impact of high expression of serine protease inhibitor A3(SERPINA3)on the proliferation,apoptosis,migration,and chemoresistance of pancreatic cancer cells and its mechanism.Methods:This study analyzed the SERPINA3 expression levels in the normal pancreatic ductal epithelial cell line hTERT-HPNE and pancreatic cancer cell lines SW1990,Capan-1,PANC-1,and ASPC-1 by real-time reverse transcription quantitative polymerase chain reaction(qRT-PCR).We established gemcitabine-resistant pancreatic cancer cell lines PANC-1/R and ASPC-1/R,and used qRT-PCR assay and cell counting kit-8(CCK-8)to determine the SERPINA3 expression levels in the constructed resistant cell lines and their parental sensitive cell lines,as well as the differences in their chemosensitivity to gemcitabine.We constructed the SERPINA3-knockdown cell line si-SERPINA with siRNA,and the negative control group si-SERPINA#NC with siRNA negative control.We used MDA assay,CCK-8 assay,EdU cell proliferation assay,transwell migration assay,matrigel invasion assay,scratch assay,and apoptotic assay to respectively detect the lipid oxidation levels,proliferation,migration,invasion,wound-healing ability,and the influence on apoptosis of the gemcitabine-resistant pancreatic cancer cells in the si-SERPINA group and the si-SERPINA#NC group.Results:Compared with normal pancreatic ductal epithelial cells hTERT-HPNE,the expression level of SERPINA3 in various pancreatic cancer cell lines was significantly increased(P＜0.05).mRNA and protein expression levels of SERPINA3 in PANC-1/R and ASPC-1/R were significantly increased compared with those in parent cells(P＜0.001).When SERPINA3 was knocked down in PANC-1/R and ASPC-1/R cells,the survival rate of the cells under different concentrations of gemcitabine chemotherapy decreased,and MDA detected that the lipid oxidation level was increased(P＜0.001).In addition,the proliferation rate of PANC-1/R and ASPC-1/R cell lines with SERPINA3 knockout,the number of migrating/invading cells and the healing rate of scratch test were significantly decreased(P＜0.01),and flow cytometry demonstrated that the number of apoptotic cells was increased(P＜0.05).These results suggest that SERPINA3 knockdown can inhibit the proliferation,migration,invasion and wound healing ability of gemcitabine-resistant pancreatic cancer cells,and promote the apoptosis of these resistant cells.Conclusion:SERPINA3 overexpression was found in various pancreatic cancer cells.SERPINA3 overexpression promoted malignant progression and chemotherapy resistance of pancreatic cancer,and interference with SERPINA3 expression promoted ferroptosis and enhanced chemotherapy sensitivity of gemcitabine-resistant pancreatic cancer cells.

Background and purpose:Members of the serine protease inhibitor(SERPIN)family can influence tumorigenesis,progression,and prognosis by modulating processes such as apoptosis,invasion,metastasis,and angiogenesis in tumor cells.However,their role in pancreatic cancer remains unclear.This study aimed to investigate the impact of high expression of serine protease inhibitor A3(SERPINA3)on the proliferation,apoptosis,migration,and chemoresistance of pancreatic cancer cells and its mechanism.Methods:This study analyzed the SERPINA3 expression levels in the normal pancreatic ductal epithelial cell line hTERT-HPNE and pancreatic cancer cell lines SW1990,Capan-1,PANC-1,and ASPC-1 by real-time reverse transcription quantitative polymerase chain reaction(qRT-PCR).We established gemcitabine-resistant pancreatic cancer cell lines PANC-1/R and ASPC-1/R,and used qRT-PCR assay and cell counting kit-8(CCK-8)to determine the SERPINA3 expression levels in the constructed resistant cell lines and their parental sensitive cell lines,as well as the differences in their chemosensitivity to gemcitabine.We constructed the SERPINA3-knockdown cell line si-SERPINA with siRNA,and the negative control group si-SERPINA#NC with siRNA negative control.We used MDA assay,CCK-8 assay,EdU cell proliferation assay,transwell migration assay,matrigel invasion assay,scratch assay,and apoptotic assay to respectively detect the lipid oxidation levels,proliferation,migration,invasion,wound-healing ability,and the influence on apoptosis of the gemcitabine-resistant pancreatic cancer cells in the si-SERPINA group and the si-SERPINA#NC group.Results:Compared with normal pancreatic ductal epithelial cells hTERT-HPNE,the expression level of SERPINA3 in various pancreatic cancer cell lines was significantly increased(P＜0.05).mRNA and protein expression levels of SERPINA3 in PANC-1/R and ASPC-1/R were significantly increased compared with those in parent cells(P＜0.001).When SERPINA3 was knocked down in PANC-1/R and ASPC-1/R cells,the survival rate of the cells under different concentrations of gemcitabine chemotherapy decreased,and MDA detected that the lipid oxidation level was increased(P＜0.001).In addition,the proliferation rate of PANC-1/R and ASPC-1/R cell lines with SERPINA3 knockout,the number of migrating/invading cells and the healing rate of scratch test were significantly decreased(P＜0.01),and flow cytometry demonstrated that the number of apoptotic cells was increased(P＜0.05).These results suggest that SERPINA3 knockdown can inhibit the proliferation,migration,invasion and wound healing ability of gemcitabine-resistant pancreatic cancer cells,and promote the apoptosis of these resistant cells.Conclusion:SERPINA3 overexpression was found in various pancreatic cancer cells.SERPINA3 overexpression promoted malignant progression and chemotherapy resistance of pancreatic cancer,and interference with SERPINA3 expression promoted ferroptosis and enhanced chemotherapy sensitivity of gemcitabine-resistant pancreatic cancer cells.

Breast cancer is the most common malignancy in women,which not only brings serious harm to female health but also substantially increased the burden of social medical care.Therefore it is necessary to adopt effective treatment strategies to control the social harm caused by cancer.Radiotherapy plays a critical role in the adjunctive therapy of breast cancer,which significantly reduces the risk of local recurrence and improves the long-term survival of breast cancer patients.In recent years,intraoperative radiotherapy has become a research hotspot in breast conserving surgery treatment,and is gradually applied in clinic with the advantage of mild side effect and shortening the patients′later treatment time.

Objective:To assess the effect of rosiglitazone on inflammation in peritoneal dialysis patients. Methods:Fifty patients undergoing continuous ambulatory peritoneal dialysis were collected in our hospital. The treatment group was assigned to receive regular peritoneal dialysis and rosiglitazone 4mg once daily while the control group was received regular peritoneal dialysis for 12 weeks. Such serum examinations as fasting blood glucose (FBG), glycosylated hemoglobin A1c, haemoglobin, serum total cholesterol, high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol, triglycerides and high sensitivity C reactive protein (hs-CRP) were measured, tumor necrosis factorα(TNF-α) and interleukin-6 (IL-6) levels were measured by ELISA, and homeostasis model as-sessment of insulin resistance( HOMA-IR) was also evaluated before and after the treatment. Results:After the 12-week treatment by rosiglitazone, the levels of FPG, HOMA-IR, hs-CRP, TNF-αand IL-6 were declined significantly(P<0. 05), and the level of HDL-C was increased significantly(P<0. 05). Conclusion: Rosiglitazone shows significant anti-inflammatory, insulin resistance improve-ment and anti-lipidemic effects in peritoneal dialysis patients.

Objective To investigate the influence of microbleeds on the onset and development of different types of stroke. Methods According to stroke subtypes, 163 patients were classified into lacunar infarction (n= 56), transient iscbemia attach (n=31), atherothrombotic infarction (n=37), intracerebral hemorrhage (n=39), and control groups (n=43). Suaceptibility-weighted imaging , T1WI, T2WI and diffusion-weighted imaging were performed with 3.0 T system to observe cerebral microbleed and infarction. Results The incidence and the number of micrehleeds were significantly greater in patients with intracerebral hemorrhage (75.6% and 14.5±11.6, re-spectively),then lacunar infarction and therothrombetic infarction atherothrombotic infarction [(55.3% and 8.1± 3.4), (37.8% and 4.5±2.6)] and the incidence and the number of microhleeds in above groups are higher than transient ischemia attach (9.7% and 0.3±0.1), and controls (9.3% and 0.2±0.1) (P<0.01). There was a correlation between the number of microbleeds and the severity of lacunar infarction, aslo a correlation between the number of microbleeds and the number of intracerebral hemorrahages (r=0.402, P<0.001). Conclusion Microb-leeds are closely associated with stroke, which may indicate more advanced microangiopathy and higher risk of bleeding.