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Objectives Our study purpose was to detect the distribution of anti-nuclear antibody (ANA) IgG subclasses in patients with systemic lupus erythematosus (SLE) and to evaluate their influence on the inflammatory process in SLE. Methods We determined the serum levels of ANA IgG subclasses from 70 SLE patients, 25 patients with other autoimmune diseases (OAD), and 25 healthy controls using ELISA. The serum level of total ANA IgG and the avidity of ANA IgG, dsDNA IgG, and dsDNA IgG subclasses were analysed by ELISA. Results The results indicated that levels of four ANA IgG subclasses (IgG1, IgG2, IgG3 and IgG4) and total IgG were significantly higher in SLE patients than in OAD patients and healthy controls ( p Conclusions First, we demonstrated that the ANA IgG subclasses were diagnostic tools in SLE patients. Furthermore, HA IgG ANAs might affect the distribution of ANA IgG3 and IgG4. Moreover, ANA IgG3 might play a particular role in the activity of SLE disease and therapy. Therefore, an altered ANA IgG subclass distribution might be a risk factor influencing the inflammatory process in SLE.

Data on long-term tenofovir alafenamide (TAF) therapy for pregnant women with active chronic hepatitis B (CHB) (immune clearance and reactivation phases, currently and previously diagnosed) and their infants are lacking.Pregnant women with active CHB treated with TAF and tenofovir disoproxil fumarate (TDF) were enrolled in this multicenter prospective study, and infants received immunoprophylaxis. The primary outcomes were rates of adverse (safety) events in pregnant women and defects in infants and fetuses. The secondary outcomes were virologic responses in pregnant women, infants' safety, hepatitis B surface antigen (HBsAg) status, and growth conditions.One hundred three and 104 pregnant women were enrolled and 102 and 104 infants were born in the TAF and TDF groups, respectively. In the TAF group, the mean age, gestational age, alanine aminotransferase level, and viral loads at treatment initiation were 29.3 years, 1.3 weeks, 122.2 U/L, and 5.1 logTAF administered throughout or beginning in early pregnancy is generally safe and effective for pregnant women with active CHB and their infants.

Antinuclear antibodies (ANAs) are a serological hallmark of systemic autoimmune rheumatic diseases (SARDs); however, few studies have investigated their post-treatment levels. The mechanism by which ANA titers are upregulated in SARDs remains unclear. We assessed factors associated with the ANA titer after treatment. In this retrospective study, we analyzed the clinical database of Zhongshan Hospital, Medical College of Xiamen. Demographic data and baseline and 12-month post-treatment ANA titers were collected. Bivariate and multivariate analyses were performed to determine the factors associated with the ANA titer. This study identified 31,923 patients who underwent ANA assay for SARDs screening, and a total of 1043 patients were included in the study. Approximately 16% of the patients showed a decrease in the serological ANA titer. Younger patients ( 20) were 3 × more likely to experience such a decrease (P = 0.005) compared to older patients (≥ 60 years). Having a baseline ANA titer 1:10,000 was associated with an increase likelihood of a decrease in the serological ANA titer compared with baseline ANA titer 1:10,000, 1:3200 and 1:1000 (P 0.001). We found that a decrease in the serum ANA titer at 12 months after treatment for SARDs is associated with age and ANA baseline titers.

The aim of our study was to assess the regulatory response of the chemokine CXCL13 in the serum of systemic lupus erythematosus (SLE) patients with disease activity and to evaluate its influence on the inflammatory process in SLE. Serum samples from 97 SLE patients, 49 non-SLE patients (23 patients with other autoimmune diseases and 26 patients with rheumatoid arthritis) and 50 healthy controls were analyzed for the concentration of CXCL13 using ELISA. The results indicated that the serum levels of CXCL13 were significantly higher in SLE patients than in non-SLE patients and healthy controls (p

Two novel Sm(III) complexes, [Sm(3,4-DMBA)3(3,4-DMHBA)(5,5′-DM-2,2′-bipy)]2 (1), [Sm(3-MOBA)3(5,5′-DM-2,2′-bipy)]2 (2) (3,4-dimethylbenzoic acid = 3,4-DMHBA, 3-methoxybenzoic acid = 3-MOHBA and 5,5′-dimethyl-2,2′-bipyridine = 5,5′-DM-2,2′-bipy), have been successfully synthesized and assembled. The crystal structures were determined by single crystal X-ray diffraction. Two complexes were characterized by the elemental analysis, IR, powder X-ray diffraction, thermal gravimetric technology. Because of the different ligands, the structures of the two complexes are very different, especially the structure of the complex 1. Each central Sm(III) ion of complex 1 was coordinated by three deprotonated 3,4-DMBA−,one unprotonated 3,4-DMHBA and one 5,5′-DM-2,2′-bipy, which has rarely been reported before. However each central Sm(III) ion of complex 2 was only coordinated via three deprotonated 3-MOBA− and one 5,5′-DM-2,2′-bipy. In addition, the thermal decomposition mechanism and the three-dimensional infrared accumulation spectra of the evolved gas during the thermal decomposition for two complexes were studied by the simultaneous TG/DSC-FTIR technology. What′s more, the luminescence properties of two complexes were also discussed. Finally, the bacteriostatic activities of two complexes were evaluated against Staphlococcus aureus, Escherichia coli and Candida albicans.

Histone deacetylase 6 (HDAC6) is a potential target for Alzheimer's disease (AD). In this study, a series of novel phenothiazine-, memantine-, and 1,2,3,4-tetrahydro-γ-carboline-based HDAC6 inhibitors with a variety of linker moieties were designed and synthesized. As a hydrochloride salt, the phenothiazine-based hydroxamic acid W5 with a pyridyl-containing linker motif was identified as a high potent and selective HDAC6 inhibitor. It inhibited HDAC6 with an IC50 of 2.54 nM and was more than 290- to 3300-fold selective over other HDAC isoforms. In SH-SY5Y cells, W5 dose-dependently increased the acetylated α-tubulin levels and reduced the hyperphosphorylated tau proteins at Ser396. As an effective metal chelator, W5 inhibited Cu2+-induced Aβ1–42 aggregation and disaggregated Cu2+-Aβ1−42 oligomers, and showed protective effects on the SH-SY5Y cells against Aβ1–42- as well as Cu2+-Aβ1–42 induced cell damages, serving as a potential ligand to target AD metal dyshomeostasis. Moreover, W5 promoted the differentiated neuronal neurite outgrowth, increased the mRNA expression of the recognized neurogenesis markers, GAP43, N-myc, and MAP-2. Therefore, W5 might be a good lead for the development of novel HDAC6 inhibitors targeting multi-facets of AD.

Our aim was to investigate the prevalence value of a high-avidity antinuclear antibody (ANA) of the IgG isotype (HA IgG ANA) compared with that of ANAs of other isotypes in patients with systemic lupus erythematosus (SLE) and to assess the associations of HA IgG ANA with the activity of SLE and lupus nephritis.We retrospectively analyzed clinical and laboratory data from subjects. Blood samples were acquired from 101 SLE patients, 67 patients with other autoimmune diseases, and 65 healthy donors. The levels of HA IgG ANA and other isotype ANAs were measured by indirect immunofluorescence (IIF). The prevalence and diagnosis value of HA IgG ANA and other antibodies in SLE patient were tested. The advantage of HA IgG ANA compared with HA anti-dsDNA antibodies IgG (HA dsDNA IgG) was verified by ELISA. We monitored the relative avidity indexes (RAIs) of HA IgG ANA and HA dsDNA IgG at 3 time points after the start of treatment in the same individuals with SLE.The prevalence of HA IgG ANA was significantly higher in active cases than in inactive cases of SLE and LN, which is consistent with data for IgG ANAs, anti-dsDNA IgG antibodies, low C3 levels, low C4 levels, and anti-C1q antibodies. HA IgG ANA showed moderate sensitivity and specificity (80% and 81.3%) for discriminating active and inactive SLE cases. However, HA IgG ANA showed no significant differences among the different clinical manifestations of SLE. Compared with that of HA dsDNA IgG, the RAI of HA IgG ANA was positively related to SLEDAI scores after treatment at 0, 1, and 3 months (r = 0.6813, p = 0.0026; r = 0.5972, p = 0.0114; r = 0.4817, p = 0.0474).First, we demonstrated that HA IgG ANA was a reliable diagnostic tool in SLE patients. Furthermore, HA IgG ANA was supposed to be more appropriate for identifying the activity of SLE compared with HA dsDNA IgG. In summary, HA IgG ANA may be a new biomarker for diagnosing SLE and identifying SLE activity. Key Points • We first introduced the concept of a "high-avidity IgG ANA (HA IgG ANA)" that could distinguish between the early stage of SLE and SLE that had been active for some time. • The relative avidity indexes (RAIs) of HA IgG ANA and HA dsDNA IgG were presented and applied here to evaluate the avidities of antibodies involved in SLE. • In our study, we confirmed the value of HA IgG ANA in diagnosing SLE. In addition, HA IgG ANA was more appropriate for identifying the activity of SLE than was HA dsDNA IgG. • In conclusion, HA IgG ANA could be a potential biomarker for the assessment of the prognosis of SLE activity.

This study characterizes psychiatric manifestations as a primary symptom of neurosyphilis (NS). Fifty-two of the 169 NS patients presented with psychiatric manifestations, many patients had characteristics of more than one syndrome, including cognitive impairment, personality disorders, delirium, hostility, dysarthria, confusion, disruption of their sleep-wake cycle, fecal and urinary incontinence, dysphoria, paranoia, hallucinations, expansive mood, and mania. Fifty-two patients had positive sera RPR and T. pallidum particle agglutination (TPPA), 75% had positive CSF RPR, 96.2% had positive CSF TPPA, 44.2% had CSF pleocytosis and elevated CSF proteins, and 70.0% had nonspecific, abnormal brain MRIs. These results indicate that NS mimics almost all psychiatric disorders.

Background: The clinical spectrum of neurosyphilis (NS) has changed over time. Objective: To describe the clinical spectrum and characteristics of NS in HIV-negative patients. Methods: A retrospective chart review was performed for 149 in patients with NS. Result: All patients were >25 years old, including 16.8% asymptomatic for NS, 15.4% with syphilitic meningitis, 24.2% with meningovascular NS, 38.9% with general paresis, 4.0% with tabes dorsalis and 0.7% with gummatous NS. The original misdiagnosis rate was 84.6%. All 149 patients had positive serum Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR). The overall positive rates of cerebrospinal fluid RPR (CSF-RPR) and CSF-TPPA were 57.0 and 89.9%, respectively. CSF pleocytosis and elevated CSF protein were found in 40.3% of patients. Nonspecific abnormal brain magnetic resonance imaging and electroencephalography findings were present in 60.4 and 54.8% of NS patients, respectively. Conclusions: NS has various clinical manifestations, laboratory findings and magnetic resonance imaging and electroencephalography findings, but all studies lack specificity. Every patient with neurological or psychiatric symptoms that are without unambiguous causes should have blood tests for syphilis. When serology proves positive, patients should undergo CSF examination.

Background Chemokine ligand 13 (CXCL13) is believed to play a role in the recruitment of B cells in the central nervous system during neuroinflammation. Neurosyphilis is a group of clinical syndromes of the central nervous system caused by Treponema pallidum (T. pallidum) infection. The relationship between CXCL13 and neurosyphilis still needs further study. In our study, CSF and serum CXCL13 concentrations were detected among 40 neurosyphilis patients, 31 syphilis/non-neurosyphilis patients, 26 non-syphilis/other central nervous system diseases patients. Serum CXCL13 concentrations were detected in 49 healthy persons. All enrolled persons were HIV-negative. Receiver operating characteristic (ROC) analysis was performed to determine the threshold value that could distinguish neurosyphilis from syphilis. Results We found that the CSF CXCL13 concentrations and CXCL13 quotient (QCXCL13) were significantly increased in neurosyphilis patients compared to syphilis/non-neurosyphilis (χ2 = 21.802, P

Recent studies showed that two single nucleotide polymorphisms (SNPs) (rs12979860 and rs8099917) near the gene IL28B coding for IFNk3 were associated with the antiviral treatment response of the combination therapy of pegIFN plus RBV. We established the use of tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) for detecting IL28B rs8099917 genotype (T > G) in 56 Chinese chronic hepatitis C patients infected with Hepatitis C Virus (HCV) genotype 1. The new assay showed 98.2% specificity, and was confirmed by direct sequencing. Among the 56 samples, TT genotype and TG genotype accounted for 80.4% (45/56) and 19.6% (11/56), respectively. GG genotype was not found. The proportion of responders in TT group was higher than that in TG group (68.9% vs. 27.3%, p = 0.029). For HCV clinical decision-making, using the new assay, rs8099917 genotyping could provide similar information to rs12979860 genotyping due to a strong association between the two SNPs in Chinese patients. The assay system in this study can be implemented using basic laboratory equipments, making it convenient for clinical and research purposes. 2012 Elsevier B.V. All rights reserved.

To construct a single-chain human anti-EGFR antibody (scFv) and truncated protamine (tP) fusion protein, ScFv/tP, carrying small interfering (si)RNA directed against the heat shock protein Hsp47, a collagen-binding glycoprotein, in order to evaluate the role Hsp47 in apoptosis of hepatic stellate cells.A single chain of the human variable fragment was obtained by phage display and fused with the tP gene and with or without (negative control) the Hsp47 siRNA sequences. Following expression and purification of the scFv/tP fusion protein and the scFv/tPHsp47 siRNA fusion protein, internalization capabilities were tested in isolated human hepatic stellate cells and the QSG-7701 human hepatocyte cells with visualization by immunofluorescent staining. The DNA binding ability of the fusion proteins were verified by gel shift assay.Following ScFv/tP-Hsp47 siRNA fusion protein transfection into the human hepatic stellate cells, the levels of Hsp47 mRNA and protein expression were tested by RT-PCR and Western blotting; in addition, effects of siRNA-mediated silencing of Hsp47 on cell proliferation and apoptosis were analyzed by the cell counting kit (CCK)-8, flow cytometry and Western blot detection of the apoptosis marker poly (ADP-ribose) polymerase (PARP).Indirect immunofluorescence revealed that the ScFv/tP fusion proteins were internalized into human hepatic stellate cells but not into the QSG-7701 cells.The ScFv/tP-Hsp47 siRNA fusion protein caused reduced expression of Hsp47 mRNA and protein expression in the human hepatic stellate cells, as well as increased the cells' apoptosis remarkably.The ScFv/tP fusion protein can be used as a transfection reagent to deliver Hsp47 siRNA into hepatic stellate cells and to mediate apoptosis via blockade of Hsp47 expression.

Egg allergy is associated with diarrhoeal symptoms. However, the mechanism underlying allergic diarrhoea remains unclear.To determine whether egg white-specific IgE antibodies coexist with egg white-specific IgG antibodies in patients with egg allergy featuring diarrhoeal symptoms, and whether there is any relationship between these two antibody types.A total of 89 patients with egg allergy featuring diarrhoeal symptoms (average age, 23.2 years; range, 1-78 years), all of whom tested positive for egg white-specific IgG, were enrolled in this study. The concentration of total IgE, egg white-specific IgE and number of eosinophils in the serum were determined.Among the 89 egg white allergic patients tested, 49 (55.1%) patients showed high reactivity to egg white-specific IgG, 48 (53.9%) patients had elevated serum total IgE levels, and 25 (28.1%) patients had elevated absolute eosinophil numbers. Out of the 89 egg white allergic patients, 25 showed elevated egg white-specific IgE antibody levels. Of the 25 patients who were positive for egg white-specific IgE antibody, 21 presented high sensitive reaction to egg white-specific IgG, three presented moderate sensitive reaction to egg white-specific IgG, and one presented mild sensitive reaction to egg white-specific IgG. A moderate correlation between egg white-specific IgG and egg white-specific IgE, egg white-specific IgG and absolute eosinophil number was found in the egg white allergic patients (r=0.438, P=0.000; r=0.322, P=0.002). Egg white-specific IgE levels varied in different age groups; the egg white-specific IgE concentration of younger patients (age≤18 years, mean rank 54.29) was significantly higher than that of the adult patients (age18 years, mean rank 34.61) (Z=-3.629, P=0.000).Egg white-specific IgE antibody could coexist with egg white-specific IgG antibody in patients suffering from egg white allergy. Aberrant changes in the concentration of egg white-specific IgE antibody were associated with the presence of egg white-specific IgG antibody.

A retrospective chart review was performed to characterize the clinical presentation, the characteristic combination of serologic and cerebrospinal fluid (CSF) abnormalities, and the neuroimaging findings of neurosyphilis (NS) patients who had epileptic seizures alone as an initial presenting symptom. In a 6.75-year period, 169 inpatients with NS were identified at Zhongshan Hospital (from June 2005 to February 2012). We demonstrated that 13 (7.7%) of the 169 NS patients had epileptic seizures alone as an initial presenting feature. Epileptic seizures occurred in NS patients with syphilitic meningitis (2 cases), meningovascular NS (5 cases), and general paresis (6 cases). The types of epileptic seizures included simple partial, complex partial with secondary generalization (including status epilepticus), and generalized seizures (no focal onset reported). Nine of NS patients with only epileptic seizures as primary symptom were misdiagnosed, and the original misdiagnosis was 69.23% (9/13). Ten (10/13, 76.9%) patients had an abnormal magnetic resonance imaging, and 7 (7/13 53.8%) patients had abnormal electroencephalogram recordings. In addition, the sera rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) from all 13 patients were positive. The overall positive rates of the CSF-RPR and CSF-TPPA were 61.5% and 69.2%, respectively. Three patients demonstrated CSF pleocytosis, and 9 patients exhibited elevated CSF protein levels. Therefore, NS with only epileptic seizures at the initial presentation exhibits a lack of specificity. It is recommended that every patient with clinically evident symptoms of epileptic seizures should have a blood test performed for syphilis. When the serology results are positive, all of the patients should undergo a CSF examination to diagnose NS.

To explore the relationship between the single nucleotide polymorphisms (SNPs) of rs12979860 and rs8099917 in IL28B gene and the response to interferon treatment in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B patients.Peripheral blood samples were collected from 82 HBeAg-positive patients with chronic hepatitis B receiving interferon treatment, including 38 with favorable response to the treatment and 44 without response. IL28B gene was amplified from the chromosomal DNA, and rs8099917 SNP was genotyped based on PCR-RLFP and rs12979860 SNP by sequencing.In the responsive patients, the distribution frequencies of TT and TG+GG genotypes and allele G in SNPrs8099917 were 81.6% (31/38), 18.4% (7/38), and 9.2% (7/76), as compared to the frequencies of 97.7% (43/44), 2.3% (1/44), and 1.1% (1/88) in nonresponsive patients, respectively. The frequencies showed significant differences between the responsive and nonresponsive patients (P=0.014 for genotypes and P=0.025 for allele G). The distribution frequencies of CT genotypes and allele T in SNPrs12979860 showed no differences between the responsive and nonresponsive patients (P0.05).rs8099917 SNP is probably associated with the response to interferon treatment in HBeAg-positive patients with chronic hepatitis B, and Allele G may be predictive of the treatment success.

Evidence has shown that the p7, NS2 and NS3 genes affect the outcome of pegylated-IFN-α/ribavirin (PEG-IFN/RBV) combination therapy in different populations with HCV infections. Here, we test the hypothesis that diversity in the p7, NS2 and NS3 genes influences the probability of obtaining either a sustained (SVR) or non-sustained (non-SVR) viral response in Chinese patients with genotype 1b chronic hepatitis C. There were significantly more unique variations in the p7, NS2 and NS3 genes in the sequences from SVR than non-SVR patients. Inter-patient variations related to treatment outcome in NS3 were concentrated in the protease domain. There were no significant differences in the frequency of variations in the core, E1 and E2 proteins between the groups. In conclusion, increased amino acid sequence diversity in the p7, NS2 and NS3 genes is associated with an SVR to PEG-IFN/RBV therapy in Chinese patients with genotype 1b chronic hepatitis C.

To develop a rapid and specific method for hepatitis C virus ( HCV) genotyping using reverse dot blot hybridization technique and investigate the distribution of HCV genotypes and subtypes in Guangdong.The primers and the probes targeting the 5'untranslated region (5'UTR) and core region of HCV genotypes 1b, 2a, 3a, 3b and 6a were designed, and the RT-PCR reverse dot blot hybridization (PCR-RDH) method for HCV genotyping was established. A total of 115 patients with hepatitis C were genotyped using this method, and 38 of them were also genotyped by sequencing and phylogenetic analysis to evaluate the accuracy and specificity of the method.Of the 115 patients, 111 were successfully genotyped to be 1b, 2a, 3a, 3b, 6a and mix-infection of 1b/2a at frequencies of 56.8%, 8.1 %, 3.6%, 5.4%, 25.2% and 0.9% respectively, and all the 15 healthy control samples showed negative results. The accuracy and reliability of the genotyping method of PCR-RDH was confirmed in 38 cases by amplification of HCV core and NS5B regions followed by DNA sequencing and phylogenetic analysis.This method for HCV genotyping, with high reliability and specificity, is suitable for clinical and epidemiological investigations. The prevalence of HCV genotypes 1b and 2a decreases while 1b remains the dominant genotype in Guangdong, where the prevalence of 6a significantly increases as compared with that 10 years ago.

To establish immortalized B lymphoblast cell lines (B-LCLs) from healthy anti-HBs antibody (anti-HBs)-positive volunteers and screen for human anti-HBs and the antibody-secreting cells.The peripheral blood mononuclear cells (PBMC) isolated from 3 healthy volunteers positive for anti-HBs with hepatitis B vaccine boost vaccination were infected with Epstein-Barr virus (EBV) and incubated in the presence of CpG DNA motifs and cyclosporin A (CyA). The anti-HBs in the culture supernatant of the immortalized B-cells was quantified by Architect anti-HBs assay with chemiluminescent microparticle technique. Immunocytochemistry was performed to identify the differentiation of the cell clones expressing anti-HBs.Immortalized B-cell culture was successfully established from the cell clones secreting anti-HBs with EBV infection and CpG DNA stimulation. The titer of anti-HBs in the culture supernatant was at its peak at 3 weeks of cell culture and then decreased gradually. At 3 months of cell culture, the cells still retained the capacity of anti-HBs production as verified by the results of immunocytochemistry for CD20 and CD138.Immortalized B-cell culture secreting anti-HBs from volunteers receiving boost hepatitis B vaccination has been successfully established by modified EBV immortalization technique.