Objective To study the effect of LDYS-14007 on JAK1-STAT3 signaling pathways.Methods MDA-MB-231 cells were treated with 10μmol,1 nmol LDYS-14007, and 10 μmol Tofacitinib,respectively.Western blot assay was used to determine the expression of JAK1,Phospho-JAK1, STAT3 and Phospho-STAT3.Results The absorbance value was linearly related to the concentration of protein C, The linear equation is A=0.0075C+0.0029, r=0.9976, The linear range of 1.08-5.08 mg/mL, With the increased concentration of LDYS-14007, the amount of Phospho-JAK1, Phospho-STAT3 were all gradually decreased.Conclusion LDYS-14007 leads to the levels of Phospho-JAK1 and Phospho-STAT3 decrease, which inhibits JAK1-STAT3 signaling pathway.LDYS-14007 may play an important role in the treatment of rheumatoid arthritis.

OBJECTIVE:To compare therapeutic efficacies of Shengxuening tablet and Iron sucrose injection for anemia in maintenance hemodialysis(MHD)patients,and their effects on oxidative stress and micro-inflammation state. METHODS:80 pa-tients who had received MHD over half year were assigned into shengxuening group and iron sucrose group with 40 cases in each group. Both groups received MHD 3 times a week,4 h/time,blood flow of 200~300 ml/min;erythropoietin(EPO)was used at a dose of 10 000 IU/time hypodermically in each group. Shengxuening group was additionally given Shengxuening tablet orally,0.5 g/time,tid. Iron sucrose group was given Iron sucrose injection 100 mg 2 h intravenously via dialyser after the beginning of hemo-dialysis,twice a week,received iron treatment every one week until complete the total dose of 1 000 mg,to maintain ferritin be-tween 100~300 μg/L. The levels of Hb,Hct,SF,TSAT,hs-CRP,IL-6,TNF-α,MDA,SOD and GSH-Px were tested in 2 groups before and 12 weeks after the treatment. RESULTS:After 12 weeks of treatment,the levels of Hb,Hct,SF and TSAT in 2 groups were significantly increased,with statistical significance (P<0.01);but there was no statistical significance between 2 groups (P>0.05). Compared with before treatment,the levels of hs-CRP,IL-6,TNF-α and MDA increased significantly in iron sucrose group,while SOD and GSH-Px levels declined significantly,with statistical significance (P<0.01). Above indicators of shengxuening group had no significant change,compared with before treatment;there was statistical significance between 2 groups after treatment(P<0.01). No obvious ADR was found in 2 groups. CONCLUSIONS:Therapeutic efficacy of shengxuening is simi-lar to that of iron sucrose in improving the anemia and iron deficiency status of MHD patients,but doesn't aggravate oxidative stress and micro-inflammation state. It is an safe and effective oral iron supplement drugs.

Objective To investigate the different distribution and expression of mammalian target of rapamycin complex (mTORC) in the kidney of diabetic nephropathy (DN) mice.Methods Fourteen eight-week-old male C57BL/6 mice were assigned to 2 groups: the control group ( n=7 ) and the streptozotocin ( STZ )-induced DN group ( n=7 ) . Blood and urinary variables including glucose , albumin, creatinine and albumin/creatinine ratio were assessed 2 weeks after STZ injection.Hematoxylin-eosin staining was performed for renal pathological analyses .The distributions of mTOR , phosph-ser2448-mTOR(p-mTOR), mTORC1(Raptor), mTORC2(Rictor) and phosph-ser240/244-S6K1 (p-S6K1) were determined by immunofluorescence.The expression levels of mTOR, p-mTOR, mTORC1(Raptor), mTORC2(Rictor), S6K1 and p-S6K1 were detected by Western blotting .Results Two weeks after STZ injection , the diabetic mice developed albuminuria (P<0.01) and renal hypertrophy (P<0.05).The immunofluorescence positive staining for mTOR , Raptor, and Rictor was distributed in the epithelial cells of proximal tubules , glomerular mesangium and capillary loops as well as the medullary collecting ducts of the control mouse kidney .These positive signals increased in the DN mouse kidney ( P<0.05).However, pS6K1 was not detected in the inner medulla of control mouse and p-mTOR was not found in the glomeruli of both control and DN mice .Conclusion mTORC is widely expessed in the mouse kidney and participates in the development of DN , whereas the 2448 serine phosphorylation of mTOR may be not implicated in the hyperglycemia mediated glomerular injury .

A series of andrographolide derivatives with the structure of 12-N-substituted-14-deoxyandrographolide were synthesized from the parent compound andrographolide.Their antitumor activities were preliminarily evaluated on various cancer cell lines and compound 4d stood out due to its potent growth inhibitory effect in comparison with andrographolide.Compound 4d also demonstrated significant antitumor effect on human hepatoma HepG2cells in vitro and on sarcoma 180 (S180) and hepatoma 22(H22)-bearing mice in vivo.Then,the apoptosis induced by compound 4d in HepG2cells was detected by Annexin V/PI double staining assay.Further mechanic study showed that the expression of p53 and Bax was significantly elevated and that of Bcl-2was downregulated in 4d-treated HepG2cells.Collectively,these data suggested that compound 4d had remarkable antitumor effect both in vitro and in vivo and could effectively induce apoptosis via a p53-dependent pathway in HepG2 cells,thus deserving further investigation.

Objective:The occurrence of numerous tumors, particularly classical Hodgkin's lymphoma (CHL), is related with Ep-stein-Barr virus (EBV) infection. However, the incidence of CHL and its association with EBV varies significantly with ethnicity, geo-graphic location, sex, and age. This study investigated the association of EBV infection with CHL in Northern Chinese Han population. Methods:EBV-encoded small RNA (EBER) was detected in 136 cases of CHL through in situ hybridization. Results:A total of 37 cas-es were EBER positive (28%). The mixed cellularity (MC) subtype had the highest positive EBER rate of 49%(23/47;P<0.001), fol-lowed by lymphocyte-rich subtype with 30%(3/10), nodular sclerosis (NS) subtype with 14%(10/73), and 1ymphocyte depletion with 0%(0/2). Our study identified a single age distribution in the third decade. Moreover, NS subtype showed an evident single peak in the third decade. However, MC subtype had a lower peak in the fifth decade. The incidence of EBER showed a bimodal age distribution with two peaks in the first and fifth decades (21.6%and 24.3%, respectively). Conclusion:CHL in Northern Chinese Han population was associated with EBV infection, particularly the MC subtype.

Objective The purpose of study was to investigate the differences in the value of urine acute kidney injury ( AKI) biomarkers in the diagnosis and prognosis of AKI in patients with or without acute respiratory distress syndrome ( ARDS ) . Methods We collected the clinical data about 304 ICU patients, in-cluding 105 ARDS (49 in the lungs and 48 outside the lungs) and 199 non-ARDS cases.Using ELISA, we determined the levels of uN-GAL, uL-FABP, uKIM-1, and uIL-18 in the first 48 hours, compared the clinical data and AKI biomarkers between different groups of patients.We analyzed the differences in the diagnostic value of the AKI biomarkers using the ROC curve and their value in predicting hospital mortality by logistic regression analysis. Results Compared with the patients without AKI, the AKI cases exhibited a signif-icantly increased level of uKIM-1 (1.02 [0.57, 3.01] vs 4.68 [54.74, 270.54], P=0.000) in the ARDS group and that of uL-FABP in the non-ARDS group (102.69 [37.98, 348.09] vs 53.52 [10.86, 141.39], P=0.009).In the ARDS group, the area under the ROC curve (AUC) for the combined efficiency of the four AKI biomarkers was 0.81 (95% CI 0.70-0.92), markedly higher than that of uNGAL (0.57 [95%CI 0.43-0.70]), uL-FABP (0.55 [95%CI 0.39-0.71]), and uIL-18 (0.56 [95%CI 0.40-0.72]) alone (P<0.05), so was the AUC for the combined efficiency of the four biomarkers than that of each biomarker alone in the patients with ARDS in or outside the lungs (P<0.05).The OR value of uKIM-1 for predicting hospital mortality was 1.529 (95%CI 1.148-2.036) in the ARDS group, 1.593 (95%CI 1.070-2.369) in the patients with ARDS in the lungs, and 1.512 (95%CI 1.005-2.274) in those with ARDS outside the lungs. Conclusion There were differences of diagnostic and predictive value of Urine AKI biomarkers have different values in the diagnosis and prognosis of AKI in ARDS and non-ARDS patients and in those with ARDS in or outside the lungs.

Purpose The diagnosis of adult onset Still's disease (AOSD) is usually difficult due to the lack of specific clinical manifestation.This paper summarizes the manifestations of 18F-FDG PET/CT in adult onset Still's disease and investigates the value of PET/CT in diagnosis and differential diagnosis of AOSD.Materials and Methods Fiftyfour patients who was diagnosed as AOSD were selected and underwent 1 8F-fluorodeoxyglueosepositron emission tomography/computed tomography (18F-FDG PET/CT).The clinical features,laboratory examination and the maximum standard uptake value (SUVmax) of liver,spleen,bone marrow,lymph node were collected.Then the main PET/CT manifestations of patients with AOSD,the influence factor of SUVmax and correlation between SUVmax and laboratory indexes were analyzed.Results FDG accumulation occurred mainly in bone marrow (88.89％;SUVmax:3.91 ± 1.16),spleen (79.63％,SUVmax:3.24±0.89) and lymph node (77.78％;SUVmax:3.83± 1.97).FDG accumulation can also occurred in joints,parotid gland,submandibular gland,pleural and other organs.Compared with the nonglucocorticoid group,SUVmax of the spleen,bone marrow and lymph node were significantly decreased in the glucocorticoid group with or without fever (P＜0.05),whereas the SUVmax of liver,spleen,bone marrow and lymph node between the two glucocorticoid groups were not statistically different (P＞0.05).The SUVmax of liver,spleen,bone marrow and lymph node between two groups with or without disease-modifying anti-rheumatic drugs were not statistically different (P＞0.05).Correlation analysis showed that spleen SUVmax and lactate dehydrogenase,bone marrow SUVmax and C reactive protein were weakly correlated (r=0.33 and 0.30,P＜0.05).Conclusion The main manifestations of 18F-FDG PET/CT of AOSD are FDG accumulation in spleen,bone marrow and lymph nodes.Glucocorticoid can reduce the SUVmax.18F-FDG PET/CT can help to rule out malignancy,guide biopsy and assist in definite diagnosis of AOSD.

In this study, the effects of hyperosmolality on the expression of urea transporter A2 (UTA2) and aquaporin 2 (AQP2) were investigated in transfected immortalized mouse medullary collecting duct (mIMCD3) cell line. AQP2-GFP-pCMV6 and UTA2-GFP-pCMV6 plasmids were stably transfected into mIMCD3 cells respectively. Transfected mIMCD3 and control cells were cultured in different hypertonic media, which were made by NaCl alone, urea alone, or an equiosmolar mixture of NaCl and urea. The mRNA and protein expression of AQP2 was elevated by the stimulation of NaCl alone, urea alone and NaCl plus urea in AQP2-mIMCD3 cells; whereas NaCl alone and NaCl plus urea rather than urea alone increased the mRNA and protein expression of UTA2 in UTA2-mIMCD3 cells, and all the expression presented an osmolality-dependent manner. Moreover, the mRNA and protein expression of UTA2 rather than AQP2 was found to be synergistically up-regulated by a combination of NaCl and urea in mIMCD3 cells. It is concluded that NaCl and urea synergistically induce the expression of UTA2 rather than AQP2 in mIMCD3 cells, and hyperosmolality probably mediates the expression of AQP2 and UTA2 through different mechanisms.

Objective To investigate the mechanism of hypoxia regulate osteopontin (OPN) secreting by mature dendritic cells (mDCs). Methods CD14 + cells were enriched using anti-CD14 immunomagnetic beads, for inducing to mDCs, CD14 + cells were cultured with GM-CSF and IL-4 in hypoxia or normoxiain vitro. Concentration of OPN and TGF-β1 in supernatant were detected by sandwich ELISA, OPN mRNA detected by RT-PCR. Approach regulating function of A2 R in expressing of OPN by mDCs by using NECA (surrogate of adenosine), A2R agonist (CGS21680), A2R antagonist (SCH58261) and investigate role of TGF-β1 in this process by using rhTGF-β1 and anti-TGF-β1 Ab. Results Hypoxia inreased the level of OPN and OPN mRNA in mDCs, and this effect could be reversed by A2 R antagonist. Under normoxia,both NECA and A2R agonist (CGS21680) could upregulate the level of OPN and OPN mRNA in mDCs significantly, but this positive effect could be reversed by A2 R antagonist. A2 R played a role in regulating TGF-β1, and confirmed TGF-β1 involved in regulation of OPN by using rhTGF-β1 and anti-TGF-β1 Ab. Conclusion High adenosine induce the generation of TGF-β1 through the A2R on mDCs, and then TGF-β1 raise the OPN secreting by mDCs.

Objective:To evaluate the effectiveness and safety of enhanced recovery after surgery(ERAS)in perioperative period of liver transplantation.Methods:The authors searched systematically domestic and foreign databases to collect researches on applying ERAS for liver transplantation. The retrieval period was from database inception to November 2020. Quality assessment and data extraction were performed by two researchers according to the inclusion criteria. Meta-analysis of postoperative indicators(length of ICU stay, total length of hospital stay, postoperative complications, admission rate & mortality rate)was performed by RevMan 5.3.5 software.Results:3 Three randomized controlled studies (RCTs) and 4 cohort studies were selected with a total of 1 016 patients, including 404 in ERAS group and 612 in conventional group(traditional perioperative management). The results of Meta-analysis revealed that, as compared with control group, length of ICU stay was significantly shorter in ERAS group [weighted mean difference(WMD)=-2.20, 95% CI: -2.43~-1.97, P<0.05]; Total length of hospital stay was significantly shorter in ERAS group [WMD=-5.85, 95% CI: -8.20~-3.49, P<0.05]; The incidence of postoperative complications was significantly shorter in ERAS group [OR=0.61, 95% CI: 0.42~0.88, P<0.05]. However, no inter-group statistically significant differences existed between admission rate or mortality rate( P>0.05). Conclusions:In perioperative period of liver transplantation, using ERAS protocol can shorten length of ICU stay and total length of hospital stay, lower the incidence of postoperative complications and accelerate patient recovery.