[Recommendations for the diagnosis and treatment of IgG4-related disease in China].

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition characterized by tumefactive lesions in multi-organs. It is a novel entity presented by variable manifestations. In recent years, there has been progress toward recognizing IgG4-RD. However, the diagnosis and treatment of IgG4-RD still present challenges due to insufficient experience. To address this, the Chinese Rheumatology Association has developed standardized guidelines for the diagnosis and treatment of IgG4-RD based on domestic and international experience. These guidelines aim to enhance the understanding and management of IgG4-RD, ultimately improving the prognosis for patients with IgG4-RD.

[Retrospective study of diagnosis and treatment of renal oncocytoma].

OBJECTIVE: To summarize the experience of diagnosis and surgical treatment of renal oncocytoma, and to evaluate the surgical results based on follow-up results, in order to find the best strategy. METHODS: In the study, 21 cases with renal oncocytoma from December 2003 to April 2016 in Peking University Third Hospital were retrospectively analyzed, including 4 males, and 17 females, with 10 cases on the right side and 11 cases on the left side. Their age was between 15 to 80 years (average: 58 years). Ultrasound or CT examination after admission was conducted. Ultrasound examination showed solid nodules. CT manifestations were solid masses with enhancement, and the tumor size was between 1.5 cm to 6.5 cm (average: 3.3 cm). Of the 21 cases, 9 were located in the middle of kidney, 7 were located in the upper pole, and 5 were located in the lower pole. After preoperative examination, according to the size and location of the tumor, laparoscopic partial nephrectomy or laparoscopic nephrectomy was performed, respectively. RESULTS: All the operations were successful, in which 17 cases underwent laparoscopic partial nephrectomy (including 3 cases which were converted to open surgery), and 4 cases underwent laparoscopic radical nephrectomy. The operation time ranged from 75 to 274 min (mean: 144 min), and the blood loss ranged from 10 to 1 000 mL (mean: 115 mL). The postoperative hospital stay time ranged from 6 to 13 d (average: 8.2 d). The pathological results were all renal oncocytoma. In the study, 17 cases were followed up while 4 cases were lost to follow-up. The follow-up time ranged from 12 to 175 months (mean: 44 months). One case died in 20 months after operation with unknown reason, and there were no recurrence or metastasis in the other 16 cases. CONCLUSION: Renal oncocytoma is a benign tumor with good prognosis. Enhanced CT is an effective diagnostic method in assistant examination, but it is difficult to differentiate clear cell carcinoma only from the naked eye. It is worthwhile to measure CT value at different stages of the tumor by picture archiving and communication systems (PACS), and to compare with CT value of adjacent kidney tissue may improve the diagnostic efficiency of CT. Laparoscopic surgery is an effective treatment for renal oncocytoma. We recommend laparoscopic partial nephrectomy for the patients with renal oncocytoma as the best choice if conditions permit.

Clinical outcomes and predictive relapse factors of IgG4-related disease following treatment: a long-term cohort study.

OBJECTIVES: The aim of this study was to investigate the predictive factors for relapse of IgG4-related disease (IgG4-RD) and observe the long-term clinical outcomes in patients with IgG4-RD. METHODS: We included in the present analysis 122 patients who were newly diagnosed with IgG4-RD, treated with glucocorticoid (GC) monotherapy or GC and immunosuppressant combination therapy, and followed for at least 3 years. Clinical relapse, response and side effects were recorded. RESULTS: The cumulative relapse rates of patients in this study were 10.66%, 22.95% and 27.87% at 12, 24 and 36 months, respectively. Complete drug withdrawal was an independent risk factor for disease relapse. Higher serum IgG4 concentrations, involvement of more organs, higher IgG4 RI scores and elevation of eosinophils at baseline were closely associated with disease relapse. Re-elevation of serum IgG4 concentrations and low GC maintenance dosage during the follow-up period were significantly associated with clinical relapse. The GC dosage should be more than 6.25 mg day-1 as monotherapy during the maintenance stage; moreover, combining with immunosuppressants can reduce the GC dosage. Adding GC or immunosuppressants for patients with re-elevation of serum IgG4 levels could prevent later disease relapse. No serious complications were noted during long-term follow-up. CONCLUSIONS: The combination of GC with immunosuppressants was more effective than GC monotherapy during the steroid tapering and maintenance stages. Higher serum IgG4 levels, involvement of more organs, higher IgG4 RI scores, history of allergy, eosinophil elevation at baseline, re-elevation of serum IgG4 levels and lower GC maintenance dosage at follow-up might be predictive of relapse.

[The effect of Cathepsin S in primary biliary cholangitis].

Objective: To explore the effect of cathepsin (Cat) S in primary biliary cholangitis (PBC). Methods: The serum of PBC patients and Hepatitis B virus (HBV) patients were collected in Peking Union Medical College Hospital from August 2016 to July 2017 and the liver tissue of PBC were collected from March 2010 to July 2013. Indirect enzyme-linked immunosorbent assay (ELISA) was used to detect the serum concentrations of total-and pro-Cat S respectively in 24 PBC patients, 24 Hepatitis B patients and 24 healthy controls. The relation between the serum levels of Cat S and cholestasis biochemical indexes and the serum levels of immunoglobulin (Ig) M, G were analyzed. Immunofluorescence analysis of liver tissue was performed to detect macrophage infiltration and Cat S expression. The data was analyzed by student's t-test, spearman correlation analysis, and receiver operating characteristic (ROC) curve was used to obtain an optimal cutoff value. Results: The serum levels of total-Cat S, pro-Cat S and active-Cat S in PBC group were significantly higher than those in healthy controls and HBV controls (P<0.05). There was a correlation between serum total-Cat S and ALP and GGT in patients with PBC (P<0.05). There was a moderate correlation between pro-Cat S and ALP and GGT (P<0.05) and total Cat S was associated with IgG (P<0.05). The area under ROC curve (AUC) of total-Cat S, pro-Cat S and active-Cat S was 0.85(P<0.01), 0.65(P<0.05) and 0.77(P<0.01), respectively. The optimal cut-off value was 11.30、7.81 and 5.93 pg/L, respectively, with the sensitivity of 0.81, 0.53 and 0.53 and specificity of 0.82, 0.81 and 0.96. Liver tissue immunofluorescence revealed macrophage infiltration in the liver of PBC patients. The average percentage of macrophages and Cat S co-expressed cells in mononuclear cells was 23.77%. Conclusion: The expression of Cat S in serum of patients with PBC is significantly higher than that of healthy controls and HBV patients, and is related to IgG and serum ALP, r-GT levels. Liver tissue macrophages were co-expressed with Cat S. Cat S may participate in the process of antigen presentation in the pathogenesis of PBC.

[Related factors of diabetic nephropathy in patients with type 1 diabetes mellitus].

Objective: To analyze the related factors of diabetic nephropathy in inpatients with type 1 diabetes mellitus (T1DM). Methods: A total of 300 patients with T1DM who were treated in the Department of Endocrinology of Anhui Provincial Hospital between 2014 and 2016 were analyzed retrospectively. All the patients were divided into two groups according to their urine albumin-to-creatinine ratio: non-diabetic nephropathy group (n=193) and diabetic nephropathy group (n=107). Multivariate logistic regression analysis was adopted to analyze the factors related to diabetic nephropathy in T1DM, including the age, diabetic duration, body mass index (BMI) and glycosylated hemoglobin (HbA1c) of the two groups. Results: Age, diabetes duration, HbA1c, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, triglyceride and uric acid (UA) of diabetic nephropathy group were higher than those of non-diabetic nephropathy group (all P<0.05). The total bilirubin, hemoglobin (Hb) and albumin in non-diabetic nephropathy group were higher than those in diabetic nephropathy group (P<0.05). The proportion of women in diabetic nephropathy group was higher than non-diabetic nephropathy group (62.6% vs 42.0%, P=0.001). Multivariate logistic regression analysis showed that diabetes duration (OR=2.142, 95% CI: 1.011-4.539), HbA1c (OR=1.262, 95% CI: 1.090-1.462), DBP (OR=1.048, 95% CI: 1.001-1.096), UA (OR=1.005, 95% CI: 1.001-1.009) and Hb (OR=0.952, 95% CI: 0.929-0.975) were independent related factors for diabetic nephropathy. Conclusions: Positive controlling of blood pressure, blood glucose, hyperuricemia and correcting anemia may reduce the incidence of diabetic nephropathy in T1DM patients.

Use of real-time, label-free analysis in revealing low-affinity binding to blood group antigens by Helicobacter pylori.

Infectious diseases are often initiated by microbial adherence that is mediated by the binding of attachment molecules, termed adhesins, to cell surface receptors on host cells. We present an experimental system, oblique-incidence reflectivity difference (OI-RD) microscopy, which allows the detection of novel, low-affinity microbial attachment mechanisms that may be essential for infectious processes. OI-RD microscopy was used to analyze direct binding of the oncopathogen, Helicobacter pylori ( H. pylori ) to immobilized glycoconjugates in real time with no need for labeling tags. The results suggest the presence of additional Lewis b blood group antigen (Le(b)) binding adhesins that have not been detected previously. OI-RD microscopy also confirmed the high-affinity binding of H. pylori outer-membrane protein BabA to Le(b). The OI-RD microscopy method is broadly applicable to real-time characterization of intact microbial binding to host receptors and offers new strategies to elucidate the molecular interactions of infectious agents with human host cells.

Macromolecular scaffolds for immobilizing small molecule microarrays in label-free detection of protein-ligand interactions on solid support.

We explored two macromolecular scaffolds, bovine serum albumin (BSA) and polyvinyl alcohol (PVA), as chemically complementary platforms for immobilizing small molecule compounds on functionalized glass slides. We conjugated biotin molecules to BSA and amine-derivatized PVA and subsequently immobilized the conjugates on epoxy-functionalized glass slides through reaction of free amine residues on BSA and PVA with surface-bound epoxy groups. We studied binding reactions of such immobilized small molecule targets with solution-phase protein probes using an oblique-incidence reflectivity difference scanning optical microscope. The results showed that both BSA and amine-derivatized PVA were effective and efficient as carriers of small molecules with NHS residues and fluoric residues and for immobilization on epoxy-coated solid surfaces. A significant fraction of the conjugated small molecules retain their innate chemical activity.

Effect of fluorescently labeling protein probes on kinetics of protein-ligand reactions.

We studied the effect of fluorescently labeling proteins on protein-ligand reactions. Unlabeled ligands (streptavidin-binding peptides and rabbit immunoglobulin G (IgG) as antigen targets) are immobilized on epoxy-functionalized glass slides. Unlabeled and Cy3-labeled protein probes from the same batch (streptavidin and goat antibodies) subsequently react with the surface-immobilized targets. By monitoring in situ the surface mass density change using an oblique-incidence reflectivity difference scanning microscope (a label-free detector), we measured k(on) and k(off) for streptavidin-peptide reactions and antibody-antigen reaction. We found that (1) equilibrium dissociation constants, defined as K(D) = k(off)/k(on), for streptavidin-peptide reactions increases by a factor of 3-4 when the solution-phase streptavidin is labeled with Cy3 dye and (2) K(D) for reactions of solution-phase goat anti-rabbit antibodies with rabbit IgG targets also change significantly when the goat antibodies are labeled with Cy3 dye.

Excitation and detection of surface-plasmon polariton waves on Cu(111) with gratings of rare gas monolayers.

We excited surface-plasmon polariton waves (SPPWs) on Cu(111) by coupling optical beams with adsorbed xenon gratings. The SPPWs's excitation causes a resonancelike dip in the angle-resolved reflectivity difference measurement. From the resonance we determined optical constants epsilonCu(633 nm)=-9.53+i0.142 and epsilonCu(780 nm)=-13.44+i0.18. The grating-coupled SPPWs can be used to study mass transport on thin films.

A novel high-throughput scanning microscope for label-free detection of protein and small-molecule chemical microarrays.

We describe a novel scanning optical microscope based on a polarization-modulated nulling ellipsometry. The new microscope employs a combination of scanning mirror and sample translation and thus enables high-throughput label-free detection of biomolecular microarrays with more than 10 000 protein or small-molecule targets. For illustration, we show the image of a 2760-spot protein microarray on a functionalized glass slide obtained with such a microscope. The new scanning microscope is also capable of determining, in parallel, the real-time binding kinetics of multiple molecular species under aqueous conditions.

Effective-substrate theory for optical reflection from a layered substrate.

We show that reflection of a monochromatic light from a semi-infinite medium covered with a stack of layered media is equivalent to that from an effective "semi-infinite medium" characterized by two distinctive optical dielectric constants for the s-polarized and p-polarized components, respectively. Such an effective-substrate approach simplifies the analysis of ellipsometry measurements of a wide range of surface-bound processes including thin film growth and surface-bound reactions.