Pathological and High Resolution CT Findings in Churg-Strauss Syndrome

Objective To investigate the Churg-Strauss syndrome (CSS) associated lung involvement,concentrating on clinical characteristics,pathological findings of lung involvements,response to treatment,and prognosis.Methods We retrospectively analyzed the characters of the clinical manifestations,thin-section CT and pathological findings of CSS.The study involved 16 patients.Clinical data were obtained by chart review.All patients underwent transbronchial lung biopsy (TBLB).Six of them underwent surgical lung biopsy as well.Results The patients included 7 men and 9 women,aged from 14 to 61 years (median,47.5 years).Extrathoracic organs involved included nervous system (7/16) and skin (5/16).Respiratory symptoms included cough (12/16),exertional dyspnea (11/16),hemoptysis (4/16),and chest pain (3/16).CT findings included bilateral ground-glass opacities (12/16),bilateral patchy opacities (12/16),and centrilobular nodules (6/16).The pathological findings of TBLB demonstrated increased eosinophils (3/16),vasculitis (3/16),and interstitial pneumonia (16/16).The pathological findings of surgical lung biopsy of 6 cases showed necrotizing vasculitis in 4 cases,capillaries in 5,eosinophilic pneumonia in 3,granulomas in 2,and airway abnormalities in 3.All patients improved in symptoms after therapy during the study period (range,3 to 51 months;median,15 months).Conclusions Asthma may be present in CSS patient when there is bronchial involvement.Ground-glass opacities and consolidation seen on high-resolution CT reflect the presence of eosinophilic pneumonia,vasculitis,and pulmonary alveolar hemorrhage.TBLB has significant limitations for the diagnosis of CSS.Early diagnosis and therapy can result in satisfactory prognosis.

Prevalence of Anti-endothelial Cell Antibodies in Patients with Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases

Objective To investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations. Methods AECAs in sera of 39 CTD patients with PAH,22 CTD patients without PAH,and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated. Results The prevalence of AECAs was 82.1% in CTD patients with PAH,72.7% in CTD patients without PAH,and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%,P<0.05). In CTD patients with PAH,anti-75 kD AECA was more frequently detected in those with Raynaud’s phenomenon or with positive anti-RNP antibody. Conclusion AECAs could be frequently detected in CTD patients with or without PAH,while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.

Mitochondrial carnitine palmitoyl transferase-Ⅱ inactivity aggravates lipid accumulation in rat hepatocarcinogenesis

AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, pre-cancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-Ⅱ alterations were analyzed by immunohistochemistry, and compared with CPT-Ⅱ specific concentration(μg/mg protein). Levels of total cholesterol(Tch), triglyceride(TG), and aminotransferases [alanine aminotransferase(ALT), aspartate aminotransferase(AST)] were determined by the routine methods.RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls(P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher(4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-Ⅱ in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-Ⅱ levels in the cancer group than in any of the other groups(P < 0.05).CONCLUSION Low CPT-Ⅱ expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.

Abnormal expression of HMGB-3 is significantly associated with malignant transformation of hepatocytes

AIM To explore the relationship between dynamic expression of high mobility group box-3(HMGB3) and malignant transformation of hepatocytes.METHODS Expression of HMGB family proteins were observed in rat hepatocarcinogenesis models induced with 2-acetylaminofluorene. Alterations of HMGB3 were analyzed at the m RNA level by reverse transcription-quantitative polymerase chain reaction(RT-q PCR) and at the protein level by immunohistochemistry or Western blotting. HMGB3 in human liver cancer tissues were evaluated using bioinformatics databases from GEO, TCGA, and Oncomine. A specific HMGB3-sh RNA was used to knockdown HMGB3 expression in order to investigate its effects on proliferation and cell cycle in vitro and in vivo.RESULTS Elevated HMGB3 levels were first reported in hepatocarcinogenesis, with increasing expression from normal liver to cancer. Bioinformatic databases showed that HMGB3 expression in hepatocellular carcinoma tissues was significantly higher than that in normal liver tissues. Higher HMGB3 expression was discovered in liver cancer cells compared with LO2 cells in vitro. According to gene set enrichment analysis, HMGB3 m RNA levels were correlated with cell cycle and DNA replication pathways. Knocking down HMGB3 by specific sh RNA significantly inhibited proliferation of Hep G2 cells by cell cycle arrest and downregulating DNA replication related genes(cyclin B1, FEN1, and PCNA) at the m RNA and protein level. Furthermore, silencing HMGB3 significantly inhibited xenograft tumor growth(measured by Ki67) in vivo.CONCLUSION HMGB3 is involved in malignant transformation of hepatocytes and could be a useful biomarker for diagnosis and a potential target for therapy of liver cancer.

Dynamic expression of hepatic GP73 mRNA and protein and circulating GP73 during hepatocytes malignant transformation

Background:Hepatic Golgi protein-73(GP73)expression is related to hepatocellular carcinoma(HCC)progression.The aim of this study was to investigate the dynamic expression of GP73 mRNA and protein during hepatocytes malignant transformation.Methods:Human GP73 expressions in 88 HCC tissues and their self-control surrounding tissues were examined by immunohistochemistry,and survival time of HCC patients was evaluated by the Kaplan-Meier method.HCC model of Sprague-Dawley rats was made by diet containing 2-fluorenylacetamide.The rats were divided into the control,hepatocyte degeneration,precanceration,and HCC groups to observe GP73 protein and mRNA alterations during hepatocytes malignant transformation.Results:The GP73 expression was significantly higher in the cancerous tissues than that in the surrounding tissues,with shorter survival time,and the positive rates of GP73 protein in human HCC tissues were 53.3%at stage I,84.0%at stage II,84.6%at stage III,and 60.0%at stage IV,respectively.The positive rates of hepatic GP73 protein and mRNA in the rat models were none in the control group,66.7%and 44.4%in the hepatocytes degeneration group,88.9%and 77.8%in the hepatocytes precanceration group,and 100%in the HCC group,respectively.There was a positive correlation(r=0.91,P<0.01)between hepatic GP73 and serum GP73 during rat hepatocytes malignant transformation.Conclusions:Abnormal GP73 expression may be a sensitive and valuable biomarker in hepatocarcinogensis.

EVALUATION OF INTERNATIONAL CLASSIFICATION CRITERIA (2002) FOR PRIMARY SJGREN'S SYNDROME IN CHINESE PATIENTS

Objective To evaluate the sensitivity and specificity of international classification criteria (2002) for primary Sjgren’s syndrome (pSS) and the role of lower lip biopsy in diagnosis of pSS in Chinese patients. Methods Patients who were diagnosed by the experts/rheumatologists as pSS during 1990-2002 from the Depart- ment of Rheumatology, Peking Union Medical College Hospital were retrospectively collected as experimental group. Patients who were diagnosed as non-pSS connective tissue diseases or non-connective tissue diseases served as control group. Those with a history of head-neck radiation, hepatitis C virus infection, AIDS, lymphoma, sarcoidosis, graft versus host disease (GVHD), and anti-acetylcholine drug use were exempted. Both groups were required to complete question- naires about symptoms such as dry eyes and dry mouth, and complete the objective tests of keratoconjunctivitis and xero- stomia including Schirmer test, corneal staining, unstimulated salivary flow, sialography, lower lip biopsy, and antinuclear antibodies (including anti-SSA/SSB antibodies) test. Results A total of 330 pSS patients were included in experimental group and 185 non-pSS patients in control group. The mean age of both groups matched (47.8 ± 10.9 years vs. 46.2 ± 13.6 years, P > 0.05). The sensitivities of the criteria in pSS patients with lower lip biopsy and in pSS patients without lower lip biopsy were 89.2% and 87.2%, respectively; the overall sensitivity was 88.5%. The specificity was 97.3%. A total of 11.3% pSS patients with negative anti-SSA/SSB anti- bodies were diagnosed as pSS by lower lip biopsy. Conclusion The international classification criteria (2002) for pSS is feasible in Chinese patients. It has high sensitivity and specificity, and may serve as diagnosis criteria in routine clinical practice.

Alteration of oncogenic IGF-II gene methylation status associates with hepatocyte malignant transformation

Background: Oncogenic insulin-like growth factor-II(IGF-II) is overexpressed in hepatocellular carcinoma(HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its molecular mechanism in HCC progression. Methods: IGF-II alterations were observed in rat hepatocarcinogenesis models induced by 2-acetylaminofluorene. Liver IGF-II expression was compared by immunohistochemistry or tissue IGF-II specific concentration(nmol/mg protein). Status of human IGF-II promoter 3(P3) or rat IGF-II P2 CpG site methylation was amplified by methylation-specific polymerase chain reaction(MSP). Serum IGF-II levels were quantitatively detected by an enzyme-linked immunosorbent assay. Results: The levels of hepatic IGF-II expression were significantly elevated in the HCC group( P < 0.001). The unmethylation rate of IGF-II P3 CpG sites was 100% in the HCC-, 52.5% in the paracancerous-, and none(0%) in the distal noncancerous-tissues. Abnormal IGF-II expression was related to differentiation degree, tumor invasion, and positive HBV-DNA(all P < 0.001), with a negative correlation between P3 methylation degree and IGF-II expression. There was a positive correlation between liver IGF-II specific concentration and circulating IGF-II level( r = 0.97, P < 0.001). Significantly negative correlation was found between IGF-II P2 CpG site methylation and circulating IGF-II( r s =-0.89, P < 0.001) or liver IGF-II level( r s =-0.84, P < 0.001). Conclusions: The increase of serum IGF-II and the alteration of oncogenic gene IGF-II methylation may be biomarkers for HCC diagnosis and DNA methylation may be the therapeutic target of HCC.

Induction of Endothelial Cell Apoptosis by Anti-alpha-enolase Antibody

Objective To assess the prevalence of anti-alpha-enolase antibody in systemic autoimmune diseases in Chinese patients and its role in endothelial cell apoptosis.Methods The reactivity of anti-alpha-enolase antibody in a variety of autoimmune disorders in Chinese patients was evaluated by dot blot assay.Endothelial cell apoptosis was investigated by in vitro incubation of endothelial cells with IgG purified from anti-alpha-enolase antibody-positive sera,with or without pre-incubation with recombinant alpha-enolase.Results Anti-alpha-enolase antibody was prevalent in different systemic autoimmune diseases with relatively high reactivity in Chinese patients.In vitro incubation of endothelial cells with IgG containing anti-alpha-enolase antibody induced apoptosis in a time-and dose-dependent manner.Apoptosis was partly inhibited by pre-incubation of the endothelial cells with recombinant alpha-enolase.Conclusions Our data suggest that alpha-enolase is a common auto-antigen recognized by anti-endothelial cell antibodies in connective tissue disease.Interaction between alpha-enolase and its autoantibody plays a role in endothelial cell apoptosis.Changes other than cell killing may contribute to the pathogenesis of endothelial damage and microvascular lesions.

Abnormal CD44 activation of hepatocytes with nonalcoholic fatty accumulation in rat hepatocarcinogenesis

BACKGROUND Prevalence of nonalcoholic fatty liver disease(NAFLD)is rapidly increasing,and NAFLD has become one of the most common chronic liver diseases worldwide.With abnormal CD44 activation,the severe form of NAFLD can progress to liver cirrhosis and hepatocellular carcinoma(HCC).Thus,the molecular mechanism of CD44 in NAFLD needs to be identified.AIM To investigate the relationship between CD44 activation and malignant transformation of rat hepatocytes under nonalcoholic lipid accumulation.METHODS Sprague-Dawley rats were fed a high-fat(HF)for 12 wk to entice NAFLD and then with HF plus 2-fluorenylacetamide(0.05%)to induce HCC.Rats were sacrificed every 2 wk,and subsequently divided into the groups based on liver pathological examination(hematoxylin and eosin staining):NAFLD,denaturation,precancerosis,HCC,and control.Liver CD44 mRNA was detected by OneArray.Liver fat as assessed by Oil red O staining or CD44 by immunohistochemical assay was compared with their integral optic density.Serum CD44,alanine aminotransferase,aspartate aminotransferase,triglyceride,total cholesterol,and AFP levels were quantitatively tested.RESULTS Elevated CD44 was first reported in hepatocarcinogenesis,with increasing expression from NAFLD to HCC at the protein or mRNA level.The CD44 integral optic density values were significantly different between the control group and the NAFLD(t=25.433,P<0.001),denaturation(t=48.822,P<0.001),precancerosis(t=27.751,P<0.001),and HCC(t=16.239,P<0.001)groups,respectively.Hepatic CD44 can be secreted into the blood,and serum CD44 levels in HCC or precancerous rats were significantly higher(P<0.001)than those in any of the other rats.Positive correlations were found between liver CD44 and CD44 mRNA(rs=0.373,P=0.043)and serum CD44(rs=0.541,P=0.002)and between liver CD44 mRNA and serum CD44(rs=0.507,P=0.004).Moreover,significant correlations were found between liver CD44 and liver AFP(rs=0.572,P=0.001),between serum CD44 and serum AFP(rs=0.608,P<0.001),and between CD44 mRNA and AFP mRNA(rs=0.370,P=0.044).CONCLUSION The data suggested that increasing CD44 expression is associated with the malignant transformation of hepatocytes in NAFLD.

Chemosensitization of HepG2 cells by suppression of NF-κB/p65 gene transcription with specific-si RNA

AIM: To investigate small interfering RNA(si RNA)-mediated inhibition of nuclear factor-kappa B(NF-κB) activation and multidrug-resistant(MDR) phenotype formation in human Hep G2 cells. METHODS: Total RNA was extracted from human Hep G2 or LO2 cells. NF-κB/p65 m RNA was amplified by nested reverse transcription polymerase chain reaction and confirmed by sequencing. NF-κB/p65 was analyzed by immunohistochemistry. Specific-si RNA was transfected to Hep G2 cells to knock down NF-κB/p65 expression. The effects on cell proliferation, survival, and apoptosis were assessed, and the level of NF-κB/p65 or P-glycoprotein(P-gp) was quantitatively analyzed by enzyme-linked immunosorbent assay.RESULTS: Hep G2 cells express NF-κB/p65 and express relatively less phosphorylated p65(P-p65) and little P-gp. After treatment of Hep G2 cells with different doses of doxorubicin, the expression of NF-κB/p65, P-p65, and especially P-gp were dose-dependently upregulated. After Hep G2 cells were transfected with NF-κB/p65 si RNA(100 nmol/L), the expression of NF-κB/p65, P-p65, and P-gp were downregulatedsignificantly and dose-dependently. The viability of Hep G2 cells was decreased to 23% in the combination NF-κB/p65 si RNA(100 nmol/L) and doxorubicin(0.5 μmol/L) group and 47% in the doxorubicin(0.5 μmol/L) group(t = 7.043, P < 0.001). CONCLUSION: Knockdown of NF-κB/p65 with si RNA is an effective strategy for inhibiting Hep G2 cell growth by downregulating P-gp expression associated chemosensitization and apoptosis induction.

Oncogenic tuftelin 1 as a potential molecular-targeted for inhibiting hepatocellular carcinoma growth

BACKGROUND Abnormal tuftelin 1(TUFT1)has been reported in multiple cancers and exhibits oncogenic roles in tumor progression.However,limited data are available on the relationship between TUFT1 and hepatocellular carcinoma(HCC),and the exact biological mechanism of TUFT1 is still poorly understood in HCC.AIM To investigate TUFT1 expression in HCC and how interfering TUFT1 transcription affects HCC growth.METHODS TUFT1 in HCC and non-HCC tissues based on databases of the Cancer Genome Atlas and Oncomine were analyzed,and TUFT1 in human HCC tissues on microarray were detected by immunohistochemistry for clinicopathological features,overall survival,and disease-free survival.HCC cells were transfected with constructed vectors of TUFT1 that interfere or over-express TUFT1 for analyzing the biological behaviors of HCC cells.Proliferation,invasion,migration,and apoptosis of cells were detected by cell counting kit-8,scratch assay,transwell tests,and flow cytometry and confirmed by Western blotting,respectively.RESULTS Abnormal TUFT1 levels in databases expressed in HCC at messenger RNA(mRNA)level and HCC tissues were mainly located in cytoplasm and membrane.The level of TUFT1 expression in the HCC group was significantly higher(χ2=18.563,P<0.001)than that in the non-cancerous group,closely related to clinical staging,size,vascular invasion of tumor,hepatitis B e-antigen positive,and ascites(P<0.01)of HCC patients,and negatively to HCC patients’overall survival and disease-free survival(P<0.001).After interfering with TUFT1 transcription at mRNA level in the MHCC-97H cells by the specific TUFT1-short hairpin RNA,cell proliferation,invasion,and metastasis were significantly inhibited with increasing apoptosis rate.In contrast,proliferation,invasion,and migration were significantly enhanced after over-expression of TUFT1 mRNA in Hep3B cells in vitro.CONCLUSION Oncogenic TUFT1 was associated with the progression of HCC and could be a potential molecular-target for inhibiting HCC growth.

Expression of hepatic Wnt5a and its clinicopathological features in patients with hepatocellular carcinoma

Backgroud： Wingless-type MMTV integration site family member 5a （Wnt5a） is involved in carcinogenesis.However, little data are available in Wnt5a signaling with hepatocellular carcinoma （HCC）. In thepresent study, we investigated the expression of hepatic Wnt5a in HCC and the role of Wnt5a in HCCprogression and outcome.

EVALUATION OF EFFICACY AND SAFETY OF DIACEREIN IN KNEE OSTEOARTHRITIS IN CHINESE PATIENTS

Objective To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). Methods A total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen for this 17-week, randomized, double-dummy, diclofenac sodium-controlled trial, with diacerein dosage of 100 mg/d and diclofenac sodium of 75mg/d. Efficacy and safety of both drugs were evaluated. Results Totally 106 patients in the diacerein group and 107 patients in the diclofenac group were considered qualified for the evaluation. After 12 weeks of treatment, the total effective rates of patients/physicians’ overall assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2%, respectively (P>0.05). The primary efficacy parameter [visual analog scale (VAS) assessment of pain on 20 metres walking] and the secondary efficacy parameters [tenderness on palpation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-item Short-Form (SF-36) Health Survey] significantly improved compared with baseline in both groups (P<0.05). In the follow-up period, there were no obvious changes in above parameters in diacerein group. However, in diclofenac group, pain on 20 metres walking, tenderness on palpation, and WOMAC became aggravated after withdrawing the drug for 4 weeks (P<0.05). Moreover, the consumption of paracetamol was significantly lower in diacerein group than in diclofenac group during follow-up (P<0.001). The incidences of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group, respectively. Mild-to-moderate gastrointestinal disorders were the most frequent adverse events. Conclusions Diacerein is as effective as diclofenac sodium in treating patients with knee OA. Furthermore, it has better extended effect and a good safety profile. It is generally well tolerated and has no severe adverse effect.

Nd(vers)_(3)/Al(i-Bu)_(2)H/AlEt_(3)/EASC体系催化丁二烯/异戊二烯及丁二烯/异戊二烯/月桂烯共聚合的研究

采用新癸酸钕(Nd(vers)_(3))/氢化二异丁基铝(Al(i-Bu)2H)/三乙基铝(AlEt3)/乙基倍半氯化铝(EASC)体系催化丁二烯(Bd)/异戊二烯(Ip)及Bd/Ip/月桂烯(My)共聚合.所得丁戊共聚物组成与催化剂用量无关,单体的投料量与共聚物中此单体的含量几乎呈线性关系;用示差扫描量热仪(DSC)测得共聚物只有一个玻璃化转变,共聚物中Ip含量与其玻璃化转变温度(T_(g))呈良好的线性关系.采用Fineman-Ross方法计算竞聚率得到r_(1)=1.04,r_(2)=1.18,Kelen-Tüdos法计算竞聚率得到r_(1)=1.33,r_(2)=1.59;r_(1),r_(2)均接近于1,说明在此催化体系下反应可以得到无规的丁戊共聚物.利用核磁碳谱对共聚物的序列结构进行了分析和归属,采用Bernoulli模型和一级Markov模型验证共聚物的序列结构,通过比较数均序列长度,一级Markov模型计算得到的序列长度与核磁计算的实际值更接近.Bd/Ip/My三元共聚合时,所得共聚物中My单元含量随着投料比的增加而增加,其DSC曲线上只有一个玻璃化转变,Tg值随着My含量的增加而稍增加.

Constitutive Modeling for Flow Behaviors of Superaustenitic Stainless Steel S32654 during Hot Deformation

Hot deformation behavior of superaustenitic stainless steel S32654 was investigated with hot compression tests at temperatures of 950-1250 C and strain rates of 0. 001-10 s-1. Above 1150 ℃, with strain rate lower than 0.1 s -1 , the flow curves exhibit nearly steady state behavior, while at higher strain rate, continuous flow softening occurs. To provide a precise prediction of flow behavior for the alloy, the constitutive modeling considering effect of strain was derived on the basis of the obtained experimental data and constitutive relationship which incorporated Ar- rhenius term and hyperbolic sine type equation. The material constants α, n, Q and lnA are found to be functions of the strain and can be fitted employing eighth-order polynomial. The developed constitutive model can be employed to describe the deformation behavior of superaustenitic stainless steel S32654.

Selenium-induced Changes in Activities of Antioxidant Enzymes and Content of Photosynthetic Pigments in Spirulina platensis

Spirulina platensis exposed to various selenium （Se） concentrations （0, 10, 20, 40, 80, 150, 175, 200, 250 mg/L） accumulated high amounts of Se in a dose- and time-dependent manner. Under low Se concentrations （〈150 mg/L）, Se induced increases in biomass concentration, content of photosynthetic pigments, and activities of glutathione peroxidase （GPX）, superoxide dismutase （SOD）, catalase （CAT） and Gua-dep peroxidases （POD）, which indicates that antioxidant enzymes play an important role in protecting cells from Se stress. Higher Se concentrations （≥175 mg/L） led to higher Se accumulation and increases in activities of GPX, SOD, CAT and POD, but also induced lipid peroxidation （LPO） coupled with potassium leakage and decreases in biomass concentration and contents of photosynthetic pigment. The results indicate that increases in activities of the antioxidant enzymes were not sufficient to protect cell membranes against Se stress. Time-dependent variations in the activities of antioxidant enzymes, contents of chlorophyll a and carotenoid and the LPO level were also investigated under representative Se concentrations of 40 and 200mg/L. Opposite variation trends between SOD-CAT activities, and GPX-POD-APX activities were observed during the growth cycles. The results showed that the prevention of damage to cell membranes of S. platensis cells could be achieved by cooperative effects of SOD-CAT and GPX-POD-APX enzymes. This study concludes that S. platensis possessed tolerance to Se and could protect itself from phytotoxicity induced by Se by altering various metabolic processes.

Contribution and underlying mechanisms of CXCR4 overexpression in patients with systemic lupus erythematosus

Aberrant expression of CXCR4 has been indicated to play a role in the pathogenesis of systemic lupus erythematosus(SLE),but the mechanism of CXCR4 dysregulation in SLE is unclear.This study is aimed to explore the clinical significance and possible mechanisms of abnormal CXCR4 expression on B cells from patients with untreated SLE.Expression of CXCR4 on peripheral B cells was determined by flow cytometry and western blotting.Freshly isolated B cells were cultured with exogenous interleukin 21(IL-21)in the presence or absence of CD40 ligand(CD40L)plus anti-IgM antibody(aIgM),and changes in CXCR4 expression were detected.Involvement of phosphatidylinositol 3 kinase(PI3K)/Akt and Janus kinase/Signal transducer and activator of transcription(JAK/STAT)signaling pathways was assessed by adding blocking agents Ly294002 and AG490.Since CD63 is reported to mediate endosomal recruitment of CXCR4 and BCL6 is capable of silencing CD63 gene transcription,we also measured BCL6 and CD63 gene transcription with real-time PCR.It was shown that CXCR4 expression on B cells was significantly upregulated in SLE patients,especially in those with lupus nephritis,and was positively correlated with SLE Disease Activity Index scores and negatively with the serum complement 3 levels(Po0.05).Downregulation of CXCR4 by IL-21 was intact.In contrast,a similar effect of aIgM plus CD40L in downregulating CXCR4 expression was defective in SLE patients but was restored by co-stimulation with IL-21 in vitro.Both Ly294002 and AG490 promoted downregulation of surface CXCR4 expression on B cells from SLE patients(P=0.078 and P=0.064).Furthermore,B cells from SLE patients exhibited diminished CD63 mRNA and enhanced BCL6 mRNA expression(both Po0.05).To sum up,CXCR4 was overexpressed on SLE B cells,positively correlating with disease activity and kidney involvement.Overactivation of the PI3K/Akt and JAK/STAT pathways as well as defective CD63 synthesis may contribute to CXCR4 dysregulation in SLE.

Effect of Precipitation on Hot Deformation Behavior and Processing Maps of Nickel-Base UNS N10276 Alloy

The hot deformation characteristics and processing maps of aged nickel-base UNS N10276 alloy were inves- tigated and compared with those of solution-treated UNS N10276 alloy at temperatures of 950-1250 ℃ and strain rates between 0.01 and 10 s-1. The dominant precipitated phase in the aged alloy was identified as topologically close-packed （TCP） # phase enriched in Mo and Ni. The precipitates present in the UNS N10276 alloy could significantly facilitate flow softening after peak stress at temperatures lower than 1150 ℃ and strain rates higher than 0.01 s-1. Processing maps at true strains of 0.1-0.9 were developed using the dynamic materials model and experimental flow stress data. Although aging treatment slightly shrank the suitable hot working window of this alloy, the aged alloy showed higher peak efficiencies of power dissipation and smaller unstable regions in comparison with solution-treated alloy. Furthermore, aging treatment eliminated the instability region of processing maps at true strains of 0.2-0.5. The precipitated phase promoted dynamic recrystallization （DRX） by the particle-stimulated nucleation （PSN） mechanism, which resulted in the larger fraction of DRX as well as finer and more uniform grain structure in the aged alloy specimens compared to the solution-treated alloy.

Effects of Carbon Content on Mechanical Properties of Inconel 718 Alloy

For improving the service performance of Inconel 718 alloy, especially used as a corrosion-resistant alloy for special environment, the microstructure and mechanical property of different carbon-containing Inconel 718 alloys were investigated by the Thermo-Calc software and experiments. The experimental results indicated that the mor- phology, distribution and types of carbides mainly existing in the form of MC＇were hardly influenced by solution treatment at 1050 ℃ for 1 h. The precipitation amount and particle size of carbides decreased with the decrease of carbon content, which was the main reason resulting in the increase of ductility and toughness. In addition, moving dislocation could be restrained by the precipitation of carbides. Therefore, the strength could benefit from the precip- itation strengthening of carbides when the precipitation of γ′/γ″ phase was not influenced by the precipitation of carbides.

Grain Growth Behavior of Inconel 625 Superalloy

The grain growth（GG）behavior of Inconel 625 superalloy was studied in the temperature range of 900-1 250 ℃and holding time range of 10-80 min.Microstructures of the alloy were characterized by optical metallography,scanning electron microscopy（SEM）and transmission electron microscopy（TEM）.Grains grew obviously with either increasing temperature or extending holding time at temperatures above 1 050℃.However,at temperatures lower than 1 050 ℃,the GG was sluggish due to the pinning effect of carbide particles on grain boundary（GB）.Threshold temperature for transition from mixed grain structure to uniform one was considered to be around 1 100℃.Once the temperatures surpassed 1 200℃,an instant increase in the grain size occurred showing no dependence on holding time.TEM analysis showed that the dominant second phase formed heterogeneously on the GB was M6 C,which significantly impeded grain growth.On the basis of experimental data,the mathematical model of GG was established,which can describe GG behavior of Inconel 625 alloy during solution treatment（ST）at 1 100-1 250 ℃.The activation energy for GG of Inconel 625 alloy was 207.3kJ,which suggested that the GG of Inconel 625 alloy was controlled by the process of GB diffusion.