Objective To explore the roles of transcription factor E26 transformation-specific 1(ETS1)and F-box protein 45(FBXO45)in invasion and metastasis in hepatocellular carcinoma cells and the potential molecular mechanism.Methods Jaspar,hTFtarget and Cistrome transcription factor database prediction websites were used to predict the transcription factors of FBXO45.According to the intersection of the predicted results of each database,the expression of FBXO45 was detected after the candidate transcription factors were knockdown in HCCLM3 and Huh7 liver cancer cells,respectively.The most significant influence on FBXO45 expression was selected for further analysis,and chromatin immunoprecipitation assay(ChIP)was used to verify the binding to the FBXO45 promoter.Finally,the potential transcription factor of FBXO45 was identified.The effect of ETS1 overexpression on invasion and migration in HCCLM3 and Huh7 cells was detected by Transwell assay,and the expression levels of epithelial-mesenchymal transition(EMT)pathway proteins were detected by Western blot assay.The effects of FBXO45 knockdown on the invasion and migration under the condition of overexpression of ETS1 were also studied.Results Intersection of FBXO45 transcription factors identified 3 candidate transcription factors,ETS1,SPI1 and YY1.When the 3 transcription factors were knocked down in HCCLM3 and Huh7 cells,respectively,ETS1 knockdown significantly reduced the expression of FBXO45.According to the analysis of The Cancer Genome Atlas(TCGA)data and the Gene Expression Omnibus(GEO)data,the expression levels of ETS1 and FBXO45 were significantly positively correlated(R=0.31,P<0.000 1;R=0.40,P=0.021 9).ChIP suggested that ETS1 could specifically bind to FBXO45 promoter sequence to regulate its expression,confirming that ETS1 was a potential transcription factor of FBXO45.After overexpression of ETS1 in HCCLM3 and Huh7 cells,the invasion and migration abilities of cells were significantly enhanced,and the expression of N-cadherin and Snail was up-regulated(P<0.01).In addition,in the case of ETS1 overexpression,FBXO45 knockdown significantly inhibited the invasion and migration(P<0.01).Conclusion ETS1 activates the transcription of FBXO45 and leads its high expression,which enhances the invasion and migration of HCC cells via EMT pathway and promotes the progression of hepatocellular carcinoma.

Objective:To investigate the value of dual-energy CT parameters in the evaluation of pathological grade of pancreatic ductal adenocarcinoma.Methods:80 cases of pancreatic ductal adenocarcinoma confirmed by pathology were retrospectively analyzed and divided into high grade group (36 cases) and low grade group (44 cases) according to their differentiation degree. All 80 patients underwent SOMATOM Force DECT for arterial phase (AP) and pancreatic phase (PP) scanning, and measured dual-energy parameters including dual-phase iodine concentration (IC AP, IC PP) in tumors and normal pancreatic parenchyma, pancreatic phase and arterial phase iodine concentration difference (ICD PP-AP) in tumors, dual-phase iodine uptake ratio (IUR AP, IUR PP) , dual-phase tumor/normal pancreatic parenchyma fat fraction ratio, and dual-phase slope of energy spectrum curve. Differences between two groups were compared by two independent sample t-test or Mann-Whitney U test or chi-square test. The multivariate logistic regression model was used to analyze the influencing factors of pathological grading of PDAC. Results:There were statistically significant differences in gender, age, aspect ratio, positive lymph node, fat fraction ratio in pancreatic phase between the two groups ( P< 0.05) . The multivariate logistic regression analysis showed that fat fraction ratio in pancreatic phase ( OR=1.781, 95% CI 1.127-2.814, P=0.013) , positive lymph node ( OR=4.870, 95% CI 1.488-15.938, P=0.009) , aspect ratio ( OR=0.019, 95% CI 0.001-0.437, P=0.013) were independent factors influencing the pathologic grade of PDAC. Conclusion:Parameters of dual-energy CT are valuable in the evaluation of pathological grading of PDAC.

Objective:To investigate the value of dual-energy CT parameters in the evaluation of pathological grade of pancreatic ductal adenocarcinoma.Methods:80 cases of pancreatic ductal adenocarcinoma confirmed by pathology were retrospectively analyzed and divided into high grade group (36 cases) and low grade group (44 cases) according to their differentiation degree. All 80 patients underwent SOMATOM Force DECT for arterial phase (AP) and pancreatic phase (PP) scanning, and measured dual-energy parameters including dual-phase iodine concentration (IC AP, IC PP) in tumors and normal pancreatic parenchyma, pancreatic phase and arterial phase iodine concentration difference (ICD PP-AP) in tumors, dual-phase iodine uptake ratio (IUR AP, IUR PP) , dual-phase tumor/normal pancreatic parenchyma fat fraction ratio, and dual-phase slope of energy spectrum curve. Differences between two groups were compared by two independent sample t-test or Mann-Whitney U test or chi-square test. The multivariate logistic regression model was used to analyze the influencing factors of pathological grading of PDAC. Results:There were statistically significant differences in gender, age, aspect ratio, positive lymph node, fat fraction ratio in pancreatic phase between the two groups ( P< 0.05) . The multivariate logistic regression analysis showed that fat fraction ratio in pancreatic phase ( OR=1.781, 95% CI 1.127-2.814, P=0.013) , positive lymph node ( OR=4.870, 95% CI 1.488-15.938, P=0.009) , aspect ratio ( OR=0.019, 95% CI 0.001-0.437, P=0.013) were independent factors influencing the pathologic grade of PDAC. Conclusion:Parameters of dual-energy CT are valuable in the evaluation of pathological grading of PDAC.

The identification of pathogenic antigens in membranous nephropathy (MN) is a hot topic in the research field of kidney diseases. In recent years, the widespread application of mass spectrometry has brought a breakthrough in the identification of MN-pathogenic antigens. As the antigen spectrum continues to be refined, the diagnosis of MN has evolved from morphological level to molecular level. This article reviewed the research progress of currently identified antigens of MN, such as phospholipase A2 receptor (a major pathogenic antigen of primary MN), thrombospondin type 1 domain-containing 7A (a potential tumor-associated antigen), neural epidermal growth factor-like protein 1 (an antigen associated with various secondary factors), semaphorin 3B (an antigen specific to pediatric MN) and so on, and the pathogenic mechanisms and clinical significance of these antigens.

Objective:To investigate the expression of nucleoporin 43 (NUP43) in hepato-cellular carcinoma tissues and its impact on prognosis of patients and proliferation and migration of hepatocellular carcinoma cells.Methods:The retrospective cohort study and experi-mental study were conducted. The clinicopathological data of 102 hepatocellular carcinoma patients who were admitted to The First Affiliated Hospital of Army Medical University from January 2008 to December 2012 were collected. There were 83 males and 19 females, aged 56(range, 19-87)years. The expression of NUP43 in hepatocellular carcinoma tissues was analyzed by immunohistochemical staining. HepG2 and SK-HEP-1 hepatocellular carcinoma cells were cultured in vitro. The Western blot was used to verify the effects of Flag-NUP43 overexpression plasmid in transfected cells. The CCK-8 and cell migration experiments were used to analyze the effect of NUP43 overexpression on HepG2 and SK-HEP-1 hepa-tocellular carcinoma cells. Measurement data of normal distribution were expressed as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data of skewed distribution were represented as M(range). Count data were expressed as absolute numbers, and comparisons between groups was conducted using the paired chi-square test. The Kaplan-Meier method was used to calculate survival time, and Log-rank test was used for survival analysis. The R 4.2.1 software was used to draw survival curves. The COX proportional hazards regre-ssion model was used for univariate and multivariate analyses. Results:(1) Expression of NUP43 in hepatocellular carcinoma and adjacent tissues, and analysis of clinicopathological characteristics of patients with high and low expression of NUP43. Results of immunohistochemical staining showed that NUP43 was mainly expressed in the cytoplasm and nuclear membrane of cells. Of 102 hepatocellular carcinoma tissue samples, there were 49 samples with low expression of NUP43 and 53 samples with high expression of NUP43. Of 102 hepatocellular carcinoma adjacent tissue samples, there were 80 samples with low expression of NUP43 and 22 samples with high expression of NUP43. There was a significant difference in the expression of NUP43 between hepatocellular carcinoma and adjacent tissues ( χ2=16.505, P<0.05). Of 102 hepatocellular carcinoma tissue samples, there were significant differences in tumor diameter, pathological grading, and intrahepatic metastasis between the patients with low expression of NUP43 and the patients with high expression of NUP43 ( χ2=5.104, 23.217, 4.169, P<0.05). (2) Survival of hepatocellular carcinoma patients and prognostic factors analysis. The follow-up time of 102 hepatocellular carcinoma patients was 17.9(range, 0.1-107.9)months. The postoperative 1-, 3-, and 5-year overall survival rates were 79.59%, 53.06% and 34.69% for the patients with low expression of NUP43, versus 52.83%, 18.87%, and 9.43% for the patients with high expre-ssion of NUP43, showing a significant difference between them ( χ2=27.071, P<0.05). Results of multi-variate analysis showed that gender, NUP43 expression, TNM staging, and pathological grading were independent influencing factors for postoperative survival in patients with hepatocellular carcinoma ( hazard ratio=1.846, 2.206, 2.040, 2.177, 95% confidence interval as 1.231-2.768, 1.419-3.429, 1.322-3.148, 1.377-3.254, P<0.05). (3) Effects of NUP43 overexpression on the proliferation and migration of HepG2 and SK-HEP-1 hepatocellular carcinoma cells. Western blot analysis showed that transfection of Flag-NUP43 overexpression plasmid significantly increased the expression of NUP43 in HepG2 and SK-HEP-1 cells. Results of CCK-8 experiment showed that after transfection with the control plasmid and Flag-NUP43 overexpression plasmid, the cell proliferation indices of HepG2 were 0.79±0.07 and 1.47±0.05, respectively, showing a significant difference between them ( t=19.402, P<0.05). After transfection with the control plasmid and Flag-NUP43 overexpression plasmid, the cell proliferation indices of SK-HEP-1 cells were 0.59±0.05 and 0.95±0.05, respectively, showing a significant difference between them ( t=15.753, P<0.05). Results of cell migration experiments showed that after transfection with the control plasmid and Flag-NUP43 overexpression plasmid, the number of cell migrations in HepG2 was 188±8 and 595±13, respectively, showing a significant difference between them ( t=46.192, P<0.05). After transfection with the control plasmid and Flag-NUP43 overexpre-ssion plasmid, the number of cell migrations in SK-HEP-1 cells were 136±10 and 447±20, respectively, showing a significant difference between them ( t=24.721, P<0.05). Conclusions:The expression of NUP43 in hepatocellular carcinoma tissues is significantly higher than that in adjacent tissues. Gender, NUP43 expression, TNM staging, and pathological grading are independent influen-cing factors for postoperative survival of hepatocellular carcinoma patients. Overexpression of NUP43 can significantly promote the proliferation and migration of HepG2 and SK-HEP-1 hepatocellular carcinoma cells.

Objective:To investigate the expression of nucleoporin 43 (NUP43) in hepato-cellular carcinoma tissues and its impact on prognosis of patients and proliferation and migration of hepatocellular carcinoma cells.Methods:The retrospective cohort study and experi-mental study were conducted. The clinicopathological data of 102 hepatocellular carcinoma patients who were admitted to The First Affiliated Hospital of Army Medical University from January 2008 to December 2012 were collected. There were 83 males and 19 females, aged 56(range, 19-87)years. The expression of NUP43 in hepatocellular carcinoma tissues was analyzed by immunohistochemical staining. HepG2 and SK-HEP-1 hepatocellular carcinoma cells were cultured in vitro. The Western blot was used to verify the effects of Flag-NUP43 overexpression plasmid in transfected cells. The CCK-8 and cell migration experiments were used to analyze the effect of NUP43 overexpression on HepG2 and SK-HEP-1 hepa-tocellular carcinoma cells. Measurement data of normal distribution were expressed as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data of skewed distribution were represented as M(range). Count data were expressed as absolute numbers, and comparisons between groups was conducted using the paired chi-square test. The Kaplan-Meier method was used to calculate survival time, and Log-rank test was used for survival analysis. The R 4.2.1 software was used to draw survival curves. The COX proportional hazards regre-ssion model was used for univariate and multivariate analyses. Results:(1) Expression of NUP43 in hepatocellular carcinoma and adjacent tissues, and analysis of clinicopathological characteristics of patients with high and low expression of NUP43. Results of immunohistochemical staining showed that NUP43 was mainly expressed in the cytoplasm and nuclear membrane of cells. Of 102 hepatocellular carcinoma tissue samples, there were 49 samples with low expression of NUP43 and 53 samples with high expression of NUP43. Of 102 hepatocellular carcinoma adjacent tissue samples, there were 80 samples with low expression of NUP43 and 22 samples with high expression of NUP43. There was a significant difference in the expression of NUP43 between hepatocellular carcinoma and adjacent tissues ( χ2=16.505, P<0.05). Of 102 hepatocellular carcinoma tissue samples, there were significant differences in tumor diameter, pathological grading, and intrahepatic metastasis between the patients with low expression of NUP43 and the patients with high expression of NUP43 ( χ2=5.104, 23.217, 4.169, P<0.05). (2) Survival of hepatocellular carcinoma patients and prognostic factors analysis. The follow-up time of 102 hepatocellular carcinoma patients was 17.9(range, 0.1-107.9)months. The postoperative 1-, 3-, and 5-year overall survival rates were 79.59%, 53.06% and 34.69% for the patients with low expression of NUP43, versus 52.83%, 18.87%, and 9.43% for the patients with high expre-ssion of NUP43, showing a significant difference between them ( χ2=27.071, P<0.05). Results of multi-variate analysis showed that gender, NUP43 expression, TNM staging, and pathological grading were independent influencing factors for postoperative survival in patients with hepatocellular carcinoma ( hazard ratio=1.846, 2.206, 2.040, 2.177, 95% confidence interval as 1.231-2.768, 1.419-3.429, 1.322-3.148, 1.377-3.254, P<0.05). (3) Effects of NUP43 overexpression on the proliferation and migration of HepG2 and SK-HEP-1 hepatocellular carcinoma cells. Western blot analysis showed that transfection of Flag-NUP43 overexpression plasmid significantly increased the expression of NUP43 in HepG2 and SK-HEP-1 cells. Results of CCK-8 experiment showed that after transfection with the control plasmid and Flag-NUP43 overexpression plasmid, the cell proliferation indices of HepG2 were 0.79±0.07 and 1.47±0.05, respectively, showing a significant difference between them ( t=19.402, P<0.05). After transfection with the control plasmid and Flag-NUP43 overexpression plasmid, the cell proliferation indices of SK-HEP-1 cells were 0.59±0.05 and 0.95±0.05, respectively, showing a significant difference between them ( t=15.753, P<0.05). Results of cell migration experiments showed that after transfection with the control plasmid and Flag-NUP43 overexpression plasmid, the number of cell migrations in HepG2 was 188±8 and 595±13, respectively, showing a significant difference between them ( t=46.192, P<0.05). After transfection with the control plasmid and Flag-NUP43 overexpre-ssion plasmid, the number of cell migrations in SK-HEP-1 cells were 136±10 and 447±20, respectively, showing a significant difference between them ( t=24.721, P<0.05). Conclusions:The expression of NUP43 in hepatocellular carcinoma tissues is significantly higher than that in adjacent tissues. Gender, NUP43 expression, TNM staging, and pathological grading are independent influen-cing factors for postoperative survival of hepatocellular carcinoma patients. Overexpression of NUP43 can significantly promote the proliferation and migration of HepG2 and SK-HEP-1 hepatocellular carcinoma cells.

Objective:To investigate the effect of treadmill training on spasticity and the expression of potassium chloride co-transporter 2 (KCC2) after blocking BDNF-TrkB signaling pathway in rats with incomplete spinal cord injury (SCI).Methods:Forty female Sprague-Dawley rats were randomly divided into a sham-operation group (Sham group), an SCI+ phosphate-buffered saline group (SCI/PBS group), an SCI-treadmill training+ PBS group (SCI-TT/PBS group), an SCI/TrkB-IgG group and an SCI-TT/TrkB-IgG group. All of the rats underwent 1 week of intrathecal catheterization, and then T 10 incomplete SCI was induced. In the Sham group the spinal cord was only exposed. Seven days later, BDNF-TrkB signaling was blocked in the SCI/TrkB-IgG and SCI-TT/TrkB-IgG groups using the TrkB-IgG. The remaining three groups were controls treated with PBS. The SCI-TT/PBS and SCI-TT/TrkB-IgG groups began exercising 7 days after the SCI and continued for 4 weeks. The spasticity in their hind limbs was assessed using the Asworth assessment and H reflex (H-max/M-max ratio). The expression of KCC2 in the distal spinal cord was detected using western blotting and immunohistochemistry. Results:After the SCI the average Ashworth spasticity grades of the four SCI groups increased significantly compared with the Sham group. The average Ashworth spasticity grade of the SCI-TT/PBS group was significantly lower than those of the SCI/PBS and SCI/TrkB-IgG groups in the 3rd through the 5th week, and the SCI-TT/PBS group′s average grade was significantly less than that of the SCI-TT/TrkB-IgG group after 4 weeks. Within 5 weeks the average H-max/M-max ratio of the Sham group remained unchanged, significantly lower than the other 4 groups′ averages. There was no significant difference in the H-max/M-max ratio among the 4 groups of injured rats within 2 weeks after the SCI, but after 3-5 weeks the average H-max/M-max ratio of the SCI-TT/PBS group was significantly lower than those of the SCI/PBS, SCI/TrkB-IgG and SCI-TT/TrkB-IgG groups. At the 4th and 5th week the average H-max/M-max ratio in the SCI-TT/TrkB-IgG group was significantly lower than that in the SCITrkB-IgG group. And after 5 weeks the average expression of KCC2 in the anterior horn of the injured spinal cord was significantly lower in the 4 SCI groups than in the Sham group. Exercise significantly increased the expression of KCC2 in the SCI-TT/PBS group, and its immune intensity and relative optical density were significantly higher than those in the SCI/PBS, SCI/TrkB-IgG and SCI-TT/TrkB-IgG groups. However, there was no significant difference between the SCI/TrkB-IgG group and the SCI-TT/TrkB-IgG group.Conclusions:Treadmill training can improve spasticity after incomplete SCI and the expression of KCC2 in the distal spinal cord, at least in rats.

Objective To report the spontaneous remission and induced remission of phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) in adults,as well as to explore the potential prognostic factors.Methods A total of 120 patients with IMN in Huashan Hospital during 2012 and 2017 were enrolled and their clinical data were collected.Results PLA2R-associated IMN patients accounted for 89.2％ of the IMN patients.Spontaneous remission occurred in 35.5％ of PLA2R-associated IMN patients.The patients with higher serum albumin and lower level of PLA2R antibody were more likely to achieve spontaneous remission (both P ＜ 0.05).Multivariate logistic regression analysis showed that male was an independent risk factor for spontaneous remission in PLA2R-associated IMN patients (OR=0.060,95％CI 0.007-0.493,P=0.009),while higher serum albumin at baseline (OR=1.480,95％ CI 1.144-1.932,P=0.004) and the improvement of serum albumin after 3 months' non-immunosuppressive treatment (OR=2.040,95％CI 1.322-3.151,P=0.001) were independent protective factors for spontaneous remission.About 42.1％ PLA2R-associated IMN patients had received immunosuppressive therapy,with induced remission rate being 70.7％.High serum albumin before treatment was an independent protective factor for induced remission (OR=1.268,95％ CI 1.014-1.585,P=0.038).Conclusions PLA2R-associated IMN accounts for most of the IMN patients,with a spontaneous remission rate of 35.5％,during the follow-up period,which is even higher in patients with higher baseline serum albumin and lower PLA2R antibody titer.Induced remission rate is 70.7％ in patients in need of immunosuppresants.The serum albumin level may be helpful in predicting spontaneous remission and response to immunosuppressive therapy.

Exercise plays a critical role in non-drug treatment of diabetes .However,exercise-associated hypoglycemia (EAH) restrains diabetic patients from exercising .Till now,the underlying mechanism of exercise-associated hypoglycemia is unclear .Here we reviewed studies on pathogenesis of exercise-associated hypoglycemia in diabetes,in order to provide references and ideas for further studies in EAH .

The academic origin of homogeny of spleen and pancreas is explained from the aspect of Chinese medicine.The authors think spleen faihng to spread essence is the basic pathogenesis to diabetes mellitus.Spleen function of spreading essence is impaired.Thus essence of water and grain could not be spread in the whole body but amass sugar-turbidity,which manifests high blood sugar.Differentiating diabetes mellitus from the viewpoint of spleen,invigorating spleen and benefiting Qi could help spleen to ascend clear.Invigorating spleen-yin and clearing endogenous heat are used.The liver and kidney should be considered.The methods of dissipating phlegm and activating blood circulation could be combined.The treating idea of treating spleen is treating pancreas should be used in preventing and treating diabetes mellitus.