Targeting a cryptic allosteric site of SIRT6 with small-molecule inhibitors that inhibit the migration of pancreatic cancer cells

SIRT6 belongs to the conserved NAD+-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD+. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC50 of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Teaching method of the basic ability of acupuncture in training the manipulation skills in / 中国针灸

Through checking the ancient books and the articles at the modern times and combining the disciplinary characteristics of techniques of acupuncture and moxibustion, the training of manipulation skills was discussed. It is proposed that during the teaching of the techniques of acupuncture and moxibustion, the most basic ability of needling technique should be trained in the first place. This ability includes the ability of spiritual cultivation, the ability of tactile perception and the specific training for the needling techniques. The ability of spiritual cultivation refers to the consciousness concentration to the patient when providing acupuncture, which may promotes and conducts to the affected area. The ability of tactile perception refers to the different feelings of different tissues under the hands before and after acupuncture, the perception to the different needling sensations corresponding to the chief complains of patients as well as the different body responses after acupuncture. In order to ensure the better learning results, the specific manipulations of needling techniques should be provided accordingly on the base of these basic training skills of acupuncture.

Multiple factor analysis of depression in community-dwelling elderly residents in Beijing :A cross-sectional study / 中华老年医学杂志

Objective To investigate the mental states of the community-dwelling elderly in Beijing ,and to explore their relationship with depression using multivariate analysis ,in order to provide evidence for strategies to prevent depression in the elderly. Methods A total of 400 community elderly residents in Chaoyang District of Beijing were recruited in this cross-sectional study. The mental states of older adults were assessed by using the Zung Self-Rating Depression Scale(SDS) ,the Medical Outcomes Study(Mos)36-item Short Form Health Survey (SF-36) ,and the Social Support Rating Scale(SSRS).The correlations of the mental state with demographic data ,quality of life and social support were examined via multivariate analysis. Results Of 400 questionnaires ,364 were valid.Depression occurred in 64 older adults ,and the detection rate was 17.6% (64/364).Multivariate linear regression analysis showed that depression was closely correlated with age ( P = 0.049 ) , physiological function(P=0.009) ,vitality(P=0.028) ,mental health(P＜0.001) ,self-reported health transition(P=0.003) ,objective support(P=0.001)and subjective support(P=0.001)in community-dwelling elderly residents in Beijing.Bivariate Logistic regression analysis showed that five factors , including vitality (OR = 0.595 ,P= 0.036 ) ,mental health (OR = 0.548 ,P = 0.021 ) ,self-reported health transition(OR=1.597 ,P= 0.048) ,objective support (OR= 0.524 ,P= 0.018)and subjective support(OR=1.787 ,P=0.027) ,were influencing factors for depression in the elderly.Self-reported health transition and subjective support had the greatest impact on depression in the elderly . Conclusions Critical approaches to preventing depression in the elderly include a focus on the mental health and social needs as well as measures to enhance self-confidence in the health of these individuals.

Clinical features of tuberculosis in patients with systemic lupus erythematosus / 实用医学杂志

Objective To describe the characteristics and risk factors for Mycobacterium tuberculosis (TB)infection in patients with systemic lupus erythematosus(SLE).Methods A retrospective analysis was per-formed. Results Among our sample of 784 hospitalized patients,42(5.4%)were diagnosed with TB infection. Seventeen were pulmonary TB,11 were pulmonary and extra-pulmonary TB and 14 were extra-pulmonary TB.hest X-rays showed Abnormal chest imaging was observed in 34 cases,among which,19 were multi-lobar involvements and 9 were single-lobe involvements. Logistic regression multivariate analysis indicated that anemia and the daily mean dose of glucocorticoid(GC)were associated with TB. Conclusions Manifestations of TB in SLE patients were atypical.Anemia and the daily mean dose of GC were associated with TB.

High frequency ultrasound expression of abdominal wall endometriomas and diagnostic value / 中国基层医药

Objective To explore the character and clinical value of high frequency ultrasound in diagnosing abdominal wall endometriomas .Methods The characteristics of the ultrosonographic images in 32 cases with abdomi-nal wall endometriomas by operation and pathology were analyzed retrospectively .Results A total of 33 lesions, including 1 case of multiple (2 lesions),the rest of the 31 cases were single,mostly in the original abdominal incision place or incision side subcutaneous soft tissue ,1 case away from the incision ,located in the inguinal region .26 lesions was located in the subcutaneous fat and 6 lesion in the rectus abdominis muscle .All of the lesions hadn't capsule and were irregular in shape .The internal echo behaved low echo and on homogenous mostly ,one or more small anechoic lacunae could be seen on sonography .CDFI according to Adler semi -quantitative method classification ,25 lesions was 0 level (no blood flow signal),7 lesions for I level (edge had a small amount of pitting,short rod blood flow signal),Pulse doppler performance for low -speed and high-resistance characteristics.Conclusion Combining with the history and clinical performance , high frequency ultrasonography in abdominal wall endometriosis can be made relatively clear diagnosis,surgery of positioning has a guiding significance ,which can be used as the disease choice examination method.

Effects of Acupuncture in Patients with Mild or Moderate Depression Treated with Paroxetine Hydrochloride / 中国中医药信息杂志

Objective To observe the clinical efficacy and reverse reactions of acupuncture combined with paroxetine hydrochloride in the treatment of mild or moderate depression. Methods The patients with mild or moderate depression (n=73) were randomly divided into control group (treated with paroxetine hydrochloride,n=33) and observation group (treated with acupuncture and paroxetine hydrochloride,n=40). The therapeutic course lasted for 6 weeks. The total score changes of Hamilton Depression Scale (HAMD) were observed before treatment and treated for 1, 2, 4 and 6 weeks. Rating Scale for Side Effects (SERS) was evaluated before treatment and treated for 2, 4, 6 weeks.Results The total effective rate of clinical efficacy in the observation group was 78.95% (30/38) and the control group was 68.75% (22/32), without significant difference between the two groups (P>0.05). The scores of HAMD decreased 4, 6 weeks after the treatment in the control group and 2, 4, 6 week after the treatment in the observation group compared with those in the same group before the treatment (P<0.05,P<0.01). There was a significant difference in HAMD scores between two groups after the treatment for 4 weeks (P<0.05). The scores of SERS showed a significant difference 4, 6 weeks after the treatment between the two groups (P<0.05).Conclusion Acupuncture can improve the curative effect of paroxetine hydrochloride and decrease its side effects in the treatment of depression.

Farnesoid X receptor up-regulates thyrotropin embryonic factor and at-tenuates pathological injury of Con A-induced hepatitis / 中国病理生理杂志

[ABSTRACT]AIM:ToobservehowfarnesoidXreceptor(FXR)functionedinconcanavalinA(ConA)-induced hepatitis (CIH) and the regulation of FXR-thyrotropin embryonic factor (TEF) pathway.METHODS:C57BL/6 mice were injected with Con A to induce hepatitis .The expression of FXR and TEF in the liver specimens was determined by qRT-PCR and Western blotting .The concentrations of serum ALT/AST and inflammatory cytokines IFN-γ, TNF-α, IL-4 and IL-2 in the blood samples were tested after Con A injection .RESULTS:FXR was down-regulated in CIH mice .TEF was up-regula-ted when FXR was activated by chenodeoxycholic acid (CDCA).Activation of FXR reduced the levels of aminotransferases and inflammatory cytokines IFN-γ, TNF-α, IL-4 and IL-2 in the CIH mice induced by Con A injection .CONCLUSION:FXR activation attenuates CIH mouse liver injury and reduces inflammatory cytokines .FXR activation results in TEF up-regu-lation.The FXR-TEF pathway may play a protective role in autoimmune hepatitis .

A preliminary study on understanding the multiple physiological parameters during sleep in light of traditional Chinese medicine / 国际生物医学工程杂志

Objective This study aimed to understand the continuous physiological parameters during sleep under the guidance of Chinese medical theory and clinical practice and to establish the method to diagnose the physical and mental status by analyzing nocturnal sleep data.Methods More than 2000 subjects were recruited in the nocturnal sleep examination using the micro-movement sensitive mattress sleep monitoring system.Based on the analysis of the sleep indices and nocturnal physiological parameters combined with clinical data,a hypothesis was put forward that sleep cycle could reflect the circulation status of qi and blood,as well as some preliminary exploration on revealing the status of qi,blood,yin and yang.Results Sleep structure could reflect the status of qi and blood circulation in different meridians according to the traditional Chinese time unit.Sleep structure and sleep cycle could show corresponding changes if there is morbidity in some meridian,zang-viscera and fu-viscera.Heart rate,respiration rate and other physiological parameters could reflect the alternative predominance of yin and yang.Conclusion Interpreting the physiological parameters during sleep could be a supplementary diagnosis method for Chinese medicine syndrome differentiation.

A multicenter study of fracture in patients with rheumatoid arthritis in China / 中华风湿病学杂志

ObjectiveTo examine the clinical features of fractures and related risk factors in patients with rheumatoid arthritis(RA) in China.MethodsSix hundred and eighty-one RA patients were randomly selected from department of rheumatology of 18 hospitals of China.Data were obtained from the questionnaire,including age,sex,disease duration,the involvement of joints,treatment regimen,features of fractures etc.The possible risk factors of fracture in patients with RA were analyzed with a multi-variate Logistic regression analysis.Results① In 681 RA patients of the survey,48 patients had 54 fractures,and the incidence of fractures was about 8％.② Fractures occurred at various sites.Foot/ankle,femur,spine and wrist were the mostfrequent sites.③ The Logistic regression analysis showed that several factors increased the risk of fracture in RA patients,including long disease duration (OR:1.245,95％CI:0.987-1.570,P=0.065),male gender(OR:0.433,95％CI:0.199-0.942,P=0.035),more deformed joints(OR:1.042,95％CI:1.006-1.079,P=0.023),family history of RA (OR:2.201,95％CI:0.984-4.923,P=0.055),and high scores of SF-36(OR:1.017,95％CI:1.002-1.033,P=0.028).④ According to the degree of correlation from strong to weak,the risk factors of fracture were disease duration,SF-36,sex,number of deformed joints and family history of rheumatoid arthritis.ConclusionThe incidence of fracture is high in patients with rheumatoid arthritis.Several factors could increase the risk of fractures in RA patients,including long disease duration,male gender,more deformed joints,and family history of RA.In order to prevent the occurrence of fractures,cautions should be taken to prevent the development of fractures and treat the disease aggressively to suppress the disease activity of RA.

Efficacy of triple therapy and sequential therapy in the eradication of Helicobacter pylori in patients receiving long-term non-steroidal anti-inflammatory drugs treatment / 中华消化杂志

Objective To explore the efficacy of triple therapy and sequential therapy in the eradication of Helicobacter pylori (Hp) in patients receiving long-term non-steroidal antiinflammatory drugs (NSAID) treatment.Methods Patients receiving long-term NSAID treatment were enrolled in this study.Patients diagnosed as Hp infection were divided into triple therapy and sequential therapy groups.The patients in triple therapy group received omeprazole,clarithromycin and amoxicillin theray for 10 days.The patients in sequential group received esomeprazole with amoxicillin for five days,and then esomeprazole with clarithromycin and metronidazole for another five days.All patients were given mucosal protective therapy as maintenance treatment after eradication therapy and followed up for 12 weeks.Patients underwent endoscopy examination and Hp testing before and after follow-up.Hp eradication rates were compared with the intention-to-treat (ITT) and per protocol (PP) analysis.Results According to ITT analysis,the eradication rates of Hp in triple therapy group and sequential therapy group were 78.4 ％ (40/51) and 80.0 ％ (40/50) respectively,there was no significant difference between these two groups (x2 =0.038,P=0.846).According to PP analysis,the eradication rates of Hp in triple therapy group and sequential therapy group were 84.4％ (38/45) and 87.0％ (40/46) respectively,there was no significant difference between these two groups either (x2=0.117,P=0.732).Conclusion There was no significant difference in Hp eradication between triple therapy and sequential therapy in patients receiving long-term NSAID treatment.

A multicenter study of costs of drugs in rheumatoid arthritis in China / 中华风湿病学杂志

Objective To describe the distribution of medication costs of rheumatoid arthritis patients, and to analyze the factors that may affect the costs. Methods Data were obtained from a 12-month retrospective investigation of patients with rheumatoid arthritis (RA) across China. Department of Rheuma-tology of 18 hospitals were randomly selected. The data about their social conditions, clinical conditions, medications associated with RA such as disease-modifying antirheumatic drugs (DMARDs), non -steroidal anti -inflammtory drugs (NSAIDs), steroids, biologic agents were collected, and the costs of drugs were calculated. A non-parameter test and multivariate logistic regression analysis were performed. Results Six hundred and forty six patients were enrolled into the study, 435 completed data were chosen for analysis. The results demonstrated that the average costs per patient for medications in the past year was 8018 . The total medication costs were further subdivided into the following parts: DMARDs, (represented 20% of the total costs), biologic drugs (49%), NSAIDs (4%), herbal drugs (22%), steroids (1%). Data analysis showed that patients with higher education and higher incomes, with medical insurance,better health function status and outpatients paid more on DMARDs. Extra-articular manifestations increased the odds of the high-cost group (OR: 2.180, 95%CI: 1.335～3.558, P=0.002), while poor health function status increased the probability of paying high costs (OR: 1.373, 95%CI: 1.012～1.863, P=0.041). Conclusion High medication costs in RA do exist in RA patients. The costs of medication is associated with health function status and the presence of extra-articular manifestations.

Clinical survey on gastroduodenal damages induced by nonsteroidal anti-inflammatory drugs / 中华消化杂志

Objective To investigate the prevalence and the risk factors of gastroduodenal damages induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Methods One hundred and eighty-four patients who were prescribed NSA1Ds for long time in rheumatology and cardiovascular clinics were enrolled. Clinical data such as age, sex, medication history and body mass index were recorded. The lesions were estimated by endoscopy and the specimens were tested for Helicobacter pylori (H. pylori) infection. Results Peptic ulcer was found in 63 (34. 24%) patients including gastric ulcer in 22, duodenal ulcer in 34 and compound ulcer in 7. The endoscopic examination showed that 57 out of 121 patients without peptic ulcer had ≥3 erosive lesions. Logistic regression analysis revealed that H. pylori infection was important risk factor that induced the peptic ulcer in those who were taking NSAIDs for long time (OR = 13. 86, 95% CI: 6. 53 ～ 29. 43). The incidence of gastroduodenal damage was similar in patients taking NSAIDs and low dose aspirin (OR =0.45,95CI:0.16～ 1.28). Conclusions NSAIDs may cause gastroduodenal damages in long-term users and H. pylori infection was an important risk factor. The effect of low dose aspirin on gastroduodenal damages is as same as NSAIDs.

A multicenter,random,open,parallel controlled study on the efficacy and safety of ibuprofen arginate in treating rheumatoid arthritis and knee osteoarthritis / 中华风湿病学杂志

Objective To compare the clinical efficacy of ibuprofen arginate,a new nonsteroidal antiinflammatory drug,with that of ibuprofen,in patients with rheumatoid arthritis or knee osteoarthritis and to evaluate the safety and tolerability of ibuprofen argihate.Methods This is a muhicenter,random,open,active comparator-controlled,parallel clinical trail in which 171 patients with rheumatoid arthritis or knee osteoarthritis were enrolled.Patients were randomized to 2 groups:400 mg of ibuprofen arginate three times daily and 400 mg of ibuprofen three times daily respectively.Clinical efficacy and safety were evaluated after 4-week treatment.Results Ibuprofen arginate,at dosages of 400 mg three times daily,had shown significant efficacy in relieving pain,tenderness and swelling of joints and there was no significant difference when compared to that of ibuprofen.There was no difference in clinical adverse effects between the two groups and no serious adverse effects were repofled.But ibuprofen arginate could initiate effectiveness more rapidly than ibuprofen in both rheumatoid arthritisand osteoarthritis patients.Conclusion Ibuprofen arginate has the same clinical efficacy and safety profiles as itmprofen in treating rheumatoid arthritis and osteoarthritis.However,its onset is more rapid than ibuprofen.

Clinical analysis of the relevance between adult-onset Still's disease and macrophage activation syndrome / 中华风湿病学杂志

Objective To explore the relationship between Adult-onset Still's disease (AOSD) and macrophage activation syndrome (MAS). Methods A total of 78 patients with AOSD who had completed medical information were included in this study. Eleven patients who were diagnosed as rheumatic disease associated hemophagocytic syndrome among 26 patients who had hemophagocytic syndrome with histological evidence consisted of the MAS group. Clinical and laboratory data were analyzed in 78 patients with AOSD and 11 patients with MAS. Results Among 78 cases of AOSD, 9 patients (12%) could be diagnosed as MAS but didn't have hemophagocytic histological evidence. In the 11 MAS cases with hemophagocytic phenomenon, 6 patients fulfilled the diagnostic criteria of AOSD, 2 cases with panniculitis, 1 case with SLE, 1 case of dermatomyositis and 1 case of systemic vasculitis. Logistic analysis showed that splenomegaly (OR =2.13, 95%CI=1.11-3.42), leukopenia (OR=3.57, 95%CI=2.30～4.86), anaemia (OR=0.85, 95%CI=1.03～2.76), thrombocytopenia (OR=2.98, 95%CI=1.17-4.30) and hypertriglyceridemia (OR=1.66, 95%CI=1.02～2.74) were associated with development of MAS in AOSD. Conclusion The development of MAS in AOSD patient is frequent and hemophagocytic histological evidence could be found in severe cases. When splenomegaly and hypocytomsis present in AOSD patients, bone marrow examination should be done and the level of triglyceride and fibrinogen and activity of NK cells should be measured for early diagnosis.

Etanercept combined with methotrexate in the induction and maintenance therapy of hip joint lesion of ankylosing spondylitis / 中华风湿病学杂志

Objective To explore the efficacy of tumor necrosis factor inhibitor in hip joint lesion of ankylosing spondylids (AS). Methods Eight-six patients with hip joint lesion of ankylosing spondylitis were Enrolled in this study. The treatment protocol was: ①Etanercept 25 mg was suncutaneously injected twice a week in the first two months and once a week in the following two months. Then it was injected once every oth-er two weeks in the last two months of the study period.②Methotrexate 15 mg was administered orally or in-travenously once a week.③NSAIDs and prednisone were stopped when symptoms sunsides. Results Twenty-eight cases (33%) stopped NSAIDs because of the disappearance of symptoms in 2 weeks after starting of the study. Forty-three (50%) stopped NSAIDs with in 8 weeks and 36 cases (42%) in them stopped NSAIDs and prednisone. During the 9th and 16th week, etanercept was used once a week and 49 cases (60%) stopped NSAIDs and prednisone. During the 17th and 24th week, etanercept was used once every two weeks, and 38 cases (44%) stopped NSAIDs and prednisone and their disease was stable. Hip Functional Scores of patients were elevated significantly at 2, 4 and 6 months after the treatment (p<0.05) BASDAI and BASFI decreased, and the difference was significant when compared to those before the treatment (P<0.05). For the 19 cases with hip joint synovitis and hydrarthrosis in MRI image but without obvious change in pelvic plain films, syn-ovitis of 11 cases disappeared and 4 cases improved significantly. In 84 hip joints with grade Ⅱ or Ⅲ changes, 13 joints improved for one grade, 16 joints had improvement but less than one grade, and 49 joints had no radiological changes. Conclusion Etanercept, when combined with methotrexate, is effective in treat-ing hip joint lesion of ankylosing spondylitis. The dosage of etanercept can be tapered after the disease is un-der control.

Correlation between serum anti-C1q antibodies and renal pathological characteristic in patients with lupus nephritis / 中华风湿病学杂志

Objective To analyze the correlation between serum anti-C1q antibody (anti-C1q Ab)and renal pathological characteristic,disease activity as well as some laboratory tests in patients with lupus nephritis (LN).Methods Serum anti-C1q antibodies were detected by enzyme-linked immunosorbant assay ELISA) in 120 patients with systemic lupus nephritis (SLE),which included 60 LN patients and 60 non-LN patients.Renal biopsy was conduted in all LN patients.The relationships between serum anti-C1q Ab level and renal pathohistology,lupus nephritis activity,as well as some laboratory parameters were analyzed.Results The mean level of serum anti-C1q Ab in LN patients was (89+26) U/ml,significantly higher than that of nonLN patients (57±23) U/ml (P＜0.01).Twelve cases of renal biopsies were classified as WHO Class Ⅱ,fourteen cases Class Ⅲ,eighteen cases Class Ⅳ,and sixteen cases Class Ⅴ.Significant difference of serum anti-C1q Ab level between each class was found by ANOVA test,and serum anti-C1q Ab level of Class Ⅳ was the highest (P＜0.01).Renal biopsies showed a positive correlation between serum anti-C1q Ab level and activity index of renal pathohistology (P＜0.01).Renal deposition of C1q was related with the level of serum anti-C1q Ab.Serum anti-C1q Ab level was positively correlated with proteinuria (P＜0.01),and negatively correlated with levels of C3 and C4 (P＜0.01).Mean level of serum anti-C1q antibody in SLE patients with positive antidsDNA was higher than that in the patients with negative anti-dsDNA (P＜0.01).Conclusion Serum antiC1q Ab level is significantly associated with lupus nephritis activity and renal pathohistology.It is a useful marker to predict renal lesion and disease activity in lupus nephritis.

Compatible Stability of Ceftriaxone Sodium with Calcium-containing Solutions / 中国药房

OBJECTIVE:To study the compatible stability of Ceftriaxone Sodium with Compound Sodium Chloride Injection or Sodium Lactate Ringer's Injection and study the compatible stability of the simulated in vivo peak concentration of ceftriaxone sodium with instant high concentration of calcium gluconate ion injection. METHODS: The concentration of Ceftriaxone Sodium in the mixture was determined by HPLC,meanwhile,the changes of the mixture in appearance,pH value,and the insoluble particles at room temperature were observed. RESULTS: At 0～2 hours,the mixture of Ceftriaxone Sodium and Compound Sodium Chloride Injection was clear in appearance;however,at 2 hours,it was white cloudy macroscopically,and its pH valued increased,ceftriaxone sodium content decreased and insoluble particles increased. The ceftriaxone sodium content reduced when mixed with sodium lactate ringer's injection. After mixing of simulated in vivo peak concentration of ceftriaxone sodium with instant high concentration of calcium gluconate ion injection,the appearance of the mixture was stable but the concentration of Ceftriaxone Sodium reduced slightly. CONCLUSION: Ceftriaxone Sodium can't be used in combination with Compound Sodium Chloride Injection or Sodium Lactate Ringer's Injection. Whether it is suitable to infuse calcium gluconate when ceftriaxone sodium (iv gtt) reached peak concentration remains to be confirmed in future study.

Activiation of NF-AT and AP-1 in peripheral blood mononuclear cell in patients with systemic lupus erythematosus / 中国免疫学杂志

Objective:To detect the activation of NF AT and AP 1 in peripheral blood mononuclear cells(PBMCs) in patients with systemic lupus erythematosus and investigate their relationship with serum ANA,anti dsDNA antibody,ESR,CRP and C 3.Methods:Activation of NF AT and AP 1 were detected by electrophoretic mobility shift assay(EMSA).Results:①Activation of NF AT in PBMC in active and inactive SLE patients was increased when compared with normal controls,respectively,and the activation of NF AT in active patients was higher than that of inactive ones.②Elevated activation of AP 1 in PBMC in active SLE patients was found as compared with normal controls,and there was no significant difference in activation of AP 1 between inactive patients and normal control.③Activation of NF AT in SLE patients with positive anti dsDNA antibody was higher than that of patients with negative anti dsDNA antibody,and there was not different positively in AP 1 activation between above two patient groups.④Activation of NF AT in PBMC was related positively with CRP and SLEDAI,respectively,but no correlation with ESR,ANA,C 3.There was no relation between the activation of AP 1 and above clinical parameters.Conclusion:The abnormal expression of NF AT and AP 1 indicates disturbed intracellular signaling in SLE,which is suggested that alternations in activation of transcription factors may contribute to the pathogenesis of SLE.Activation of NF AT may be used as a predicator of SLE disease activity.

Expression of B lymphocyte stimulator in peripheral blood mononuclear cells in individuals with SLE and effect of dexamethasone on its expression / 中国病理生理杂志

AIM: To determine the expression of membrane-bound B lymphocyte stimulator((BLyS)) and its mRNA in peripheral blood mononuclear cells(PBMCs) from individuals with systemic lupus erythematosus(SLE),and to investigate the effect of dexamethasone on(BLyS) expression.METHODS: PBMCs were obtained from 25 individuals with SLE(mean age of 31.40?14.23) and 20 female healthy volunteers(mean age of 28.20?10.36).They were randomized into dexamethasone((1 ?mol/L)) group and media group.PBMCs were gathered at 0,6,12 and 24 h for(BLyS) mRNA assessment using reverse transcription-PCR(RT-PCR).PBMCs were also collected at 72 h for membrane-bound(BLyS) protein detection using flow cytometry(FACS) and direct immunofluorescence.RESULTS:(1) The expression of(BLyS) mRNA and membrane-bound protein were significantly higher in PBMCs from individuals with SLE than that in PBMCs from healthy controls(0.40?0.18 vs 0.27?0.20,P

Activation of Akt signal pathway cascades in kidney tissue in murine chronic graft-versus-host disease lupus nephritis and its regulation by prednisone / 中国病理生理杂志

AIM: To examine whether Akt signal pathway proteins, including Akt, NF-?B and I?B?, are activated in kidney tissue of murine chronic graft-versus -host disease (GvHD) lupus nephritis in vivo , and whether prednisone suppres ses activation of them. METHODS: Akt activity and phosphorylated I?B? were detected by Weste rn-blot. Activation of NF-?B was detected by electropheretic mobilit y shift assay (EMSA). RESULTS: Activity of Akt, NF-?B and phosp horylated I?B ? were significantly increased in kidney tissue of murine chronic graft-versus -ho st disease (GvHD) in 8th week and 12th week after monocell injection, respective ly. However, they were no significant elevation in 16th week, when compared with controls. Prednisone treatment significantly prevented the increase in serum an ti-dsDNA antibody level, urinary protein excretion and glomerular cell prolif eration in GvHD mice, indicating the beneficial effects of prednisone on t his model. Prednisone also significantly suppressed the increase in the activities o f glomerular Akt, NF-?B and phosphorylated I?B?. CONCLUSION: T his study provides t he first evidence of marked increase in glomerular Akt-NF-?B signal pathway act ivities in murine chronic graft-versus-host disease lupus nephritis. The benefic ial effect of prednisone on this lupus nephritis model may be partially mediated by the suppression of abnormal Akt- NF-?B activation.