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.

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 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.

Objective To evaluate the role of nutritional parameters in prognosis,especially in the early and late mortality of hospital-acquired acute kidney injury (AKI) patients.Methods This study was a prospective cohort study conducted in a hospital comprising 1500 beds in Shanghai, China. One hundred ninety-four patients with hospital-acquired AKI, as determined using the RIFLE staging criteria,were enrolled as subjects after obtaining informed consent.Patients with AKI caused by postrenal obstruction,glomerulonephritis,interstitial nephritis or vasculitis were excluded.Nutritional evaluation,including subjective global assessment (SGA),anthropometric and laboratory examination,was conducted. Other laboratory measurements and clinical data were recorded.The primary outcome was early mortality (≤ 7 days) and late mortality (8-28 days) after enrolling into the study. Results AKI patients at enrollment were characterized by a high prevalence of malnutrition as determined by SGA, anthropometric and laboratory examination.Univariate analysis showed that the SGA,the serum levels of prealbumin,cholesterol and total lymphatic cells, and the Maastricht index were significantly different among early mortality,late mortality and survival groups.The serum prealbumin and cholesterol levels in the early death group were significantly lower than those in the survival and late death groups (P＜0.05).Multivariate analysis revealed that SGA,albumin,prealbumin and cholesterol remained independently and significantly associated with early mortality after adjusting for age,sex,dialysis,ventilation,hemoglobin,platelets,bilirubin,and Glasgow coma score.The areas under the receiver operating characteristic curve to predict early mortality for albumin,prealbumin and cholesterol were 0.591,0.736 and 0.603,respectively,with that of prealbumin significantly higher than others (P＜0.05). Conclusion Low levels of serum prealbumin,albumin and cholesterol at enrollment are independtly associated with increased early mortality in hospital-acquired AKI patients.

Objective To elucidate the malnutrition in patients with hospital-acquired acute kidney injury(AKI), and to examine the association betweensubjective global assessment (SGA) and prognosis.Methods Adult patients with hospital-acquired AKI were prospectively enrolled in this cohort study.Nutritional evaluations, including SGA, anthropometric and serum nutritional markers were conducted at enrollment.Overall survival at 90 days among different SGA scores was analyzed using Kaplan-Meier methods, and differences were tested using the log-rank test.The Cox model was used to analyze the relationship between SGA scores and all-cause mortality after adjusting for confounders.Results A total of 170 patients were enrolled.The prevalence of moderate malnutrition(SGA B) and severe malnutrition(SGA C) was 51.8％ and 22.9％ respectively, while patients with normal nutrition(SGA A) accounted for 25.3％.After 90 days follow-up, all-cause mortality was 9.8％ in SGA A group, 34.9％ in SGA B group and 56.8％inSGACgrouprespectively. Afteradjustingforage,sex,dialysis,ventilation, hemoglobin, platelets and bilirubin, the hazard ratio(HR) of 90 days all-cause mortality was 4.0(95％ CI 1.42-11.22, P=0.008) in malnutrition group (SGA B group and SGA C group) compared with SGA A group.The Kaplan-Meier curve also revealed that the worse the SGA score was, the lower the cumulative survival became (P＜0.01).Conclusion SGA score is an independent risk factor for all-cause mortality within 90 days in patients with hospital-acquired acute kidney injury.

Objective To investigate the cortex gray matter configuration in amnestic mild cognitive impairment(aMCI)patients using MRI technology, FMRIB software library(FSL)and Freesurfer software.Methods Twenty aMCI patients and 20 normal control subjects were recruited and studied. They were matched by age, sex and education. All the patients and healthy volunteers underwent MRI scan using SEMENTS trio 3.0 T MRI. The subtile three-dimensional brain images were obtained using high resolution scanning technique. The imaging data was processed and analyzed with FSL and Freesurfer software. The cortex gray matter density and thickness in different brain areas of aMCI patients and normal control subjects were calculated and compared using statistic analysis. Results Compared to that in the controls, cortex gray matter density in the aMCI patients showed remarkable decreases in left frontal lobe, temporal lobe,parietal lobe, and slight decrease in right thalamus, temporal lobe and island lobe; For cortex thickness,aMCI patients showed significant decreases in left anterior cingulate gyrus((2. 19 ±0. 24)mm), inferior parietal lobe((2. 27 ± 0. 15)mm), bilateral parahippocampal gyrus((2. 03 ± 0. 15),(2. 04 ±0. 17)mm), precentral gyrus((2. 20 ± 0. 11),(2. 31 ± 0. 19)mm), postcentral gyrus((1.88 ± 0. 11),(1.82 ± 0. 09)mm), superior frontal gyrus((2. 42 ± 0. 34),(2. 40 ± 0. 28)mm), middle frontal gyrus ((2.31±0.31),(2.33 ±0.29)mm), supramarginal gyrus((2.53 ±0.33),(2.55 ±0.23)mm),temporal pole((3.41 ±0.68),(3.30 ±0.56)mm)and transverse temporal gyrus((2.04 ±0. 12),(2. 01 ± 0. 11)mm; t = 2. 13-3.75, P ＜ 0. 05), no significant changes in the other areas(t = 0. 09-1.88, P ＞ 0. 05). Conclusions Our results suggest that there are significant changes in gray matter configuration in cortex of aMCl patients. The changes of cortical thickness is earlier than the changes of gray matter density.