Rheumatoid arthritis(RA) is an autoimmune disease(AID) characterized by arthrosynovitis.Cytokines are involved in the whole course of the disease.Such important cytokines as TNF-? and IL-1? play a key role in the proliferation of synovial cells and progression of inflammation,and,therefore,have been taken as clinical therapeutic targets for RA in the recent years.The blocking agent of TNF-? or IL-1? is effective for only a few patients and the increasing adverse events it causes,such as infection and malignancy,are arousing more and more concern.The abnormal expression and imbalance of interleukin-6(IL-6) are closely associated with RA.IL-6 is an important regulatory factor for the pathogenesis of RA,and the blocking agent may be applied to the treatment of the disease.

Objective To evaluate the efficacy and safety of different doses of prednisone combined with cyclosporine A(CSA) on the treatment of idiopathic membranous nephropathy (IMN). Methods The data of 64 patients with nephrotic syndrome (NS) diagnosed as IMN by renal biopsy were retrospectively analyzed. Median follow?up time was 10 (7, 19) months. The subjects were divided into 2 groups according to different prednisone dosage. Thirty?two cases were in the low?dose group:prednisone 0.15 mg·kg-1·d-1+CSA, and 32 cases in the moderate?dose group:prednisone 0.4?0.5 mg· kg-1·d-1+CSA. Clinical and laboratory data were collected at baseline, 1, 3, and 6 months after treatment. During follow?up, cumulative recurrence rate and adverse reactions after treatment were recorded. Results Serum albumin (sALB) were significantly increased and 24 h urinary protein (24hUP) significantly decreased after treatment for 1, 3, 6 months compared with baseline data in the two groups. Serum creatine (Scr) increased after treatment with time. The elevation of sALB and the reduction of 24hUP in the moderate?dose group were higher than that of low?dose group at 6 months after treatment (P<0.05). The effective rate of the low?dose and moderate?dose group was 65.6% and 87.5% at 6 months after treatment, respectively (χ2=4.267, P=0.039). Comparison of different doses of CSA in two groups at 6 months after treatment, in low?dose group: the effective rates of CSA<3 mg· kg-1·d-1 and >3 mg·kg-1·d-1 subgroup were 76.5% and 53.3%, respectively (P=0.296); In moderate?dose group:the effective rates of CSA<3 mg·kg-1·d-1 and>3 mg·kg-1·d-1 subgroup were 89.5%and 84.6%, respectively (P=0.077); there were similar effects in patients treated with different dose CSA in the two groups. About 20.4% of the total patients relapsed when followed up for 18 months (low dose group vs moderate?dose group: 9.5% vs 28.6%, P=0.136), which most occurred after prednisone withdrawal or during the reduction of cyclosporine. Renal function decreased in 57.8% patients (low dose group vs moderate?dose group:50%vs 65.6%), mainly in the elderly (9/11) and the long course of treatment of CSA. There was no significant difference on adverse reactions between the two groups (P>0.05). Renal function in patients with high Scr or high blood trough concentration of cyclosporine was difficult to fully recover. Conclusions Remission rate is lower in low?dose prednisone combined with cyclosporine than the moderate?dose group in the treatment of IMN for 6 months. The recurrence rate of IMN or the incidence of adverse reactions are similar between the two groups. Induction therapy of IMN with cyclosporin<3 mg·kg-1·d-1 is safe and effective. The incidence of renal function reduction in the elderly is high, and the renal function is difficult to restore in patients with Scr exceeding normal upper limits.

Aim To investigate the time-dependent effect of insulin on the expression of SREBP-1(sterol regulatory element binding protein-1),FAS(fat acid synthase)and lipid droplet formation in HKC cells(human renal proximal tubular epithelial cells line).MethodsHKC cells were respectively treated with 100 nmol·L~(-1) insulin for 0,2,4,6,12 h and 24 h.The analysis of SREBP-1 and FAS mRNA was performed by RT-PCR and the expression of SREBP-1 protein was detected by Western blot and immunocytochemistry.Furthermore,Oil Red O staining was used to determine cellular lipid droplet formation.ResultsCompared with HKC cells of 0 h group,there was no difference of SREBP-1 and FAS mRNA in HKC cells of 2 h group.However,the expression of SREBP-1 and FAS mRNA was significantly increased in HKC cells of 4,6 h and 12 h group.Further,the most expression of SREBP-1 and FAS mRNA was at 6 h group and was respectively increased by 3.578 and 4.272 times compared with 0 h group.The results of Western blot showed that the precursor and mature segments of SREBP-1 protein in 4,6 h and 12 h group HKC cells were increased and those of 6 h group HKC cells were the highest and about 4.106 and 5.167 times than those of 0 h group HKC cells.Immunocytochemistry presented the result that SREBP-1 protein was located in the plasma and the expression of 4,6 h and 12 h group HKC cells was significantly higher than that of 0,2 h and 24 h group HKC cells.The result of Oil Red O staining showed that lipid droplet markedly deposited in 6 h group HKC cells,contrarily,no lipid droplet was found in HKC cells of other groups.ConclusionAbove results suggested that insulin up-regulated SREBP-1 and FAS in time-dependent manner that led to cellular lipid droplet deposit,which may play an important role in the pathogenesis of renal lipid accumulation in metabolism syndrome.

Aim To investigate the effects of irbesartan on Wnt/β-catenin signaling pathway in tubular epithelial-mesenchymal transition(EMT)in HKCs induced by high-glucose.Methods Human kidney proximal tubular epithelial cell line(HKCs)cultured in vitro was divided into four groups:normal-glucose group,mannitol control group,high-glucose group and high-glucose plus irbesartan group.Immunocytochemistry staining was used to observe the expression of β-catenin;the protein expression of Wnt4,β-catenin,E-cadherin and α-SMA was assessed by Western blot;Wnt4 and β-catenin mRNA were detected by reverse transcription-polymerase chain reaction(RT-PCR).Results Compared with normal-glucose and mannitol control group,both the protein and the mRNA of Wnt4 were up-regulated in HKCs stimulated by high-glucose.α-SMA expression significantly increased but E-cadherin decreased in HG group.The cytoplastic and nuclear fraction of β-catenin enhanced with highglucose stimulation.But no difference of the total protein and mRNA of β-catenin was observed between highglucose-treatment and control groups.Highglucose induced Wnt4 and β-catenin expression in a time-dependent manner,both peaking at 24 h.Irbesartan reduced the promotional effect of HG on Wnt4 and α-SMA expression,and nuclear translocation of β-catenin.HG-mediated inhibition of E-cadherin was also restored by irbesartan.Conclusion These data supported a functional role for Wnt/β-catenin signaling pathway during epithelial-mesenchymal transition of HKCs induced by high glucose and suggested that irbesartan might reverse tubular EMT by regulating activity of Wnt/β-catenin pathway.

Purpose To investigate the role of PTEN in podocyte injury in patients with diabetic nephropathy ( DN) . Methods Uri-nary samples from 30 patients with DN and 10 healthy volunteers were collected to detect the level of PCX by ELISA. Renal biopsies were reviewed to observe the morphological changes. All patients with DN were divided into three groups by glomerular lesion. The ex-pression of p-Akt and PTEN in glomeruli was detected by immunohistochemistry. Results The levels of PCX in the urine were signifi-cantly higher in patients with DN compared with those in healthy volunteers, and gradually increased along with glomerular lesion aggra-vating. The expression of p-Akt and PTEN increased in patients with DN compared with healthy volunteers. Although the expression of p-Akt and PTEN decreased with the aggravation of glomerular lesion, they were still higher than that in volunteers. There were obvious-ly positive correlation between the level of PCX and 24-h urinary protein and negative correlation between the level of PCX and the ex-pression level of p-Akt and PTEN. Conclusion PTEN down-regulation may be associated with podocyte injury in DN, which may be associated with the phosphorylation of Akt.

Multiple myeloma is common in the older population and is treated mainly with chemotherapy. However, chemotherapy-related side effects imitate the clinical manifestations of Sheehan's syndrome, which leads to misdiagnosis and missed diagnosis, particularly for older patients without a clear history of postpartum hemorrhage. Therefore, when older women with malignant myelomas show refractory hyponatremia and gastrointestinal disorders while under chemotherapy, a diagnosis of Sheehan's syndrome should be considered. The early detection of the disorder will guarantee timely individualized treatment.

Objective To discuss the clinical application value of Omaha system-based targeting nursing care for patients with hepatocellular carcinoma (HCC) who were treated with transcatheter arterial chemoembolization (TACE).Methods A total of 60 advanced HCC patients,who were planned to receive TACE,were prospectively and randomly divided into the control group (n=30) and the observation group (n=30).Routine nursing mode was adopted for the patients in the control group,while Omaha system nursing model was employed for the patients in the observation group.The patients of the observation group were evaluated with Omaha system at the time of admission,the key common problems were screened out and targeted nursing measures were employed.Meanwhile,on the days of admission and discharge all the patients of both groups were asked to fill in the forms of Hamilton depression scale (HAMD-17),Hamilton anxiety scale (HAMA),social support rating scale (SSQ) and numerical pain rating scale (NRS);and the degrees of depression,anxiety,social support and pain were respectively assessed.Results Both nursing modes could improve the degrees of depression and anxiety as well as the social support system of HCC patients,but the curative effect of these two aspects in the observation group were obviously better than those in the control group (P＜0.05).No statistically significant difference in the improvement of pain degree existed between the two nursing models,but Omaha system-based targeting nursing mode could alleviate the patient's pain to a certain extent.Conclusion For patients with advanced HCC,Omaha system-based targeting nursing care can alleviate the patient's negative emotion and promote the patients to establish effective social support system,this nursing mode is superior to conventional nursing mode.Therefore,Omaha system-based targeting nursing has great application potential in clinical practice.

Objective: To examine the impact of heat waves and cold spells on the incidence of hemorrhagic stroke, so as to provide insights into prevention of hemorrhagic stroke. Methods: Data pertaining to the incidence of hemorrhagic stroke in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance, and the meteorological data during the period from 2015 to 2019 were captured from National Meteorological Information Center of China. The air quality index (AQI) was collected from the National Daily Report of Urban Air Quality in China. Heat wave was defined as the highest daily temperature that was no less than the 90th percentile (P90), P92.5, P95 and P97.5 of the highest daily temperature in the warm season for at least 2, 3 or 4 days, and cold spell was defined as the lowest daily temperature that was no more than the P10, P7.5, P5 and P2.5 of the lowest daily temperature in the cold season for at least 2, 3 or 4 days. The effect of heat waves and cold spells on the incidence of hemorrhagic stroke was evaluated using a generalized additive model and described with relative risk (RR) and its 95%CI. Results: A total of 8 844 case with first-onset hemorrhagic stroke were recorded in Zibo City from 2015 to 2019. The lowest daily temperature that was no more than P10, P7.5 or P5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 or P7.5 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.187, 95%CI: 1.031-1.366; highest RR=1.242, 95%CI: 1.042-1.480), and after adjusting the effect of daily mean temperature, the lowest daily temperature that was no more than P10 or P7.5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.236, 95%CI: 1.009-1.513; highest RR=1.274, 95%CI: 1.023-1.585). However, there was no significant association between heat waves and the risk of hemorrhagic stroke. Conclusion Cold spells may increase the risk of hemorrhagic stroke, while no significant association is examined between heat waves and the risk of hemorrhagic stroke.

ObjectiveToll-like receptors (TLRs) play important role in the progression and tumor immunity of some types of cancer,some research have demonstrated that agonist of TLR3 can trigger apoptosis of cancers.This study was proposed to investigate if Poly(I:C),the specific agonist of TLR3,could impact proliferation or apoptosis of progressive breast cancer cells MDA-MB-231,and to investigate the primary mechanism of the function.MethodsExpression of TLR1-10 mRNA was detected by quantitative real-time reverse transcription-polymerase chain reaction.Cell Counting Kit-8 was used to determine the inhibitory effect of Poly(I:C) on proliferation of MDA-MB-231 cells.Cell apoptosis was assayed by flow cytometry with V-FITC/PI staining.Results First,the toll-like receptors 1-10 were all expressed on MDA-MB-231 cells,while the expression level of TLR8 was lower than that of others.Second,according to the CCK-8,the proliferation of MDA-MB-231 cells was inhibited,but the apoptosis was not affected on the basis of Apoptosis Kit.At last,the mRNA expression of TNF-α、IFN-β and IFN-γ were elevated approximately 20 times after Poly(I:C) stimulation for 6 hours.ConclusionMDA-MB-231 cells express all toll-like receptors on mRNA level,and TLR8 was expressed lower than others.The stimulation of TLR3 with Poly(I:C) can inhibit the proliferation of MDA-MB-231,but had no effect on apoptosis.TNF-α、IFN-β and IFN-γ maybe participate in this process.

Objective To evaluated intra-articular injection of TNF-α inhibitors into the sacroiliac joint as an effective and viable alternative. Methods Sixteen patients with documented ankylosing spondylitis (AS), without steroids or disease modifying anti-rheumatic drugs (DMARDs) were performed CT-guided intra-articular injections of etanercept (TNF-α antagonist) at week 0, 4 and 8 (25 mg per dose). Similarly, 20 patients with AS in the control group received systemic etanercept therapy at a dose of 50 mg per week for 8 weeks. All patients were followed up clinically and evaluated periodically. Pathological features of sacroiliitis were observed with light microscopy and immunohistochemistry. Expression of cytokines in joint biopsy samples was estimated by RT-PCR. Image changes of sacroiliitis were observed by SPECT/CT and MRI. Ttest, t'tesr and χ2 Fisher's test were selected. Results All the 16 patients who received intra-articular etanercept, the mean value of radiological nuclide decrease of the SIJ ROI (region of interest) in the SPECT improved significantly after 8 weeks treatment [(1.38±0.16 vs 1.45±0.14) P<0.05] . Bone marrow edema and fat deposition in MRI were relieved significantly after 8 weeks (P<0.05). In 8 patients the expression of TNF-α and TGF-β mRNA in joint tissue decreased significantly after 8 weeks [(0.89±0.06, 0.84±0.05) vs (l.08± 0.19, 1.13±0.33) (P<0.05)]. The occurrence of gynonitis, enthesitis, chondritis, subehondral bony plate destruction, bone marrow inflammation and inflammatory cell index also decreased significantly (P<0.05). Participants given intra-articular injection showed significant clinical improvement after 8 weeks and 12 weeks treatment(P<0.01 ) in BASDAI score [(32±13) mm]. Conclusion This study has shown that intra-articular injection of etanercept in SIJ can improve joint function and quality of life. It has a satisfactory safety profile and is cost effective. This mode of treatment is most beneficial in local arthropathy of recent onset and in those patients who do not tolerate systemic etanercept therapy.