[Urinary protein and renal pathological features in children with immunoglobulin A vasculitis with nephritis and hypercoagulability]. / 儿童IgAè¡€ç®¡ç‚Žè‚¾ç‚Žä¼´é«˜å‡çŠ¶æ€çš„å°¿è›‹ç™½å’Œè‚¾è„ç— ç†ç‰¹å¾åˆ†æž.

OBJECTIVES: To study the association of hypercoagulability with urinary protein and renal pathological damage in children with immunoglobulin A vasculitis with nephritis (IgAVN). METHODS: Based on the results of coagulation function, 349 children with IgAVN were divided into a hypercoagulability group consisting of 52 children and a non-hypercoagulability group consisting of 297 children. Urinary protein and renal pathological features were compared between the two groups, and the factors influencing the formation of hypercoagulability in children with IgAVN were analyzed. RESULTS: Compared with the non-hypercoagulability group, the hypercoagulability group had significantly higher levels of urinary erythrocyte count, 24-hour urinary protein, urinary protein/creatinine, urinary immunoglobulin G/creatinine, and urinary N-acetyl-ß-D-glucosaminidase (P<0.05). The hypercoagulability group also had a significantly higher proportion of children with a renal pathological grade of III-IV, diffuse mesangial proliferation, capillary endothelial cell proliferation, or >25% crescent formation (P<0.05). The multivariate logistic regression analysis showed that capillary endothelial cell proliferation and glomerular crescent formation >25% were associated with the formation of hypercoagulability in children with IgAVN (P<0.05). CONCLUSIONS: The renal injury in IgAVN children with hypercoagulability is more severe, with greater than 25% crescent formation and increased proliferation of glomerular endothelial cells being important contributing factors that exacerbate the hypercoagulable state in IgAVN.

Urinary matrix metalloproteinase-7 is a sensitive biomarker to evaluate renal tubular injury in patients with minimal change disease and focal segmental glomerulosclerosis.

Objective: To explore the advantages of urinary matrix metalloproteinase-7 (MMP-7) in evaluating renal tubular injury in minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients compared with urinary cystatin C (CysC) and retinol-binding protein (RBP). Methods: Serum and urine samples were collected from 20 healthy volunteers, and 40 MCD and 20 FSGS patients. Serum and urinary MMP-7 levels were measured by enzyme-linked immunosorbent assay. Urinary total protein, CysC and RBP levels were measured by automatic specific protein analyzer and compared with urinary creatinine level for calibration. The renal tissue serial sections were stained by MMP-7 immunohistochemistry and periodic acid-Schiff. Results: Under light microscopy, MMP-7 granular weak positive expression was showed sporadically in the cytoplasm of a few renal tubular epithelial cells without obvious morphological changes in MCD patients, and MMP-7-positive expression was observed in the cytoplasm of some renal tubular epithelial cells in FSGS patients. There was no significant difference in serum MMP-7 level among the three groups. Compared with the control group, the urinary MMP-7 level in MCD patients was higher, but urinary CysC and RBP levels were not increased significantly. Compared with the control group and MCD patients, urinary MMP-7, CysC and RBP levels in FSGS patients were upregulated significantly. Conclusions: Urinary MMP-7 could not only evaluate the mild renal tubular epithelial cells injury in MCD patients with massive proteinuria, but also evaluate the continuous renal tubular epithelial cells injury in FSGS patients.

Preclinical characterization of the novel anti-SIRPα antibody BR105 that targets the myeloid immune checkpoint.

BACKGROUND: The CD47-SIRPα pathway acts as an important myeloid cell immune checkpoint and targeting the CD47/SIRPα axis represents a promising strategy to promote antitumor immunity. Several CD47-targeting agents show encouraging early activity in clinical trials. However, due to ubiquitous expression of CD47, the antigen sink and hematologic toxicity, such as anemia and thrombocytopenia, are main problems for developing CD47-targeting therapies. Considering the limited expression of SIRPα, targeting SIRPα is an alternative approach to block the CD47-SIRPα pathway, which may result in differential efficacy and safety profiles. METHODS: SIRPα-targeting antibody BR105 was generated by hybridoma fusion and following humanization. BR105 was characterized for binding to human SIRPα alleles and blockade of the interaction with CD47. The functional activity was determined in in vitro phagocytosis assays by using human macrophages. The effect of BR105 on human T cell activation was studied using an OKT3-induced T-cell proliferation assay and an allogeneic mixed lymphocyte reaction. Human SIRPα-humanized immunodeficient mice were used in cancer models for evaluating the in vivo antitumor efficacy of BR105. Safety was addressed in a repeat-dose toxicity study in cynomolgus monkeys, and toxicokinetic analysis was further evaluated. RESULTS: BR105 shows broad binding activity across various SIRPα variants, and potently blocks the interaction of SIRPα and CD47. In vitro functional assays demonstrated that BR105 synergizes with therapeutic antibodies to promote phagocytosis of tumor cells. Moreover, the combination of BR105 and therapeutic antibody significantly inhibits tumor growth in a xenograft tumor model. Although BR105 may slightly bind to SIRPγ, it does not inhibit T cell activation, unlike other non-selective SIRPα-targeting antibody and CD47-targeting agents. Toxicity studies in non-human primates show that BR105 is well tolerated with no treatment-related adverse effects noted. CONCLUSIONS: The novel and differentiated SIRPα-targeting antibody, BR105, was discovered and displays promising antitumor efficacy in vitro and in vivo. BR105 has a favorable safety profile and shows no adverse effects on T cell functionality. These data support further clinical development of BR105, especially as a therapeutic agent to enhance efficacy when used in combination with tumor-targeting antibodies or antibodies that target other immune checkpoints.

[An introduction of different positioning tests of benign paroxysmal positional vertigo and their clinical values].

OBJECTIVE: To explore the clinical value of different positioning tests for different benign paroxysmal positional vertigo (BPPV). METHOD: This research applies Dix-Hallpike test and Side-lying test for PC-BPPV, Roll test and WRW test for HC-BPPV, Dix-Hallpike test, Side-lying test and Rahko T maneuvers for SC-BPPV. Six hundred and thirteen cases, who were tested with different positioning tests in the sequence of firstly PC-BPPV then HC-BPPV and finally SC-BPPV, were randomly divided into 2 groups. The order of positioning tests for PC-BPPV and HC-BPPV in the two groups was reversed. RESULT: There's no significant difference between the detection rate of Dix-Hallpike test and Side-lying test for PC-BPPV (P > 0.05). Similarly, there's no difference in statistics between the detection rate of Roll test and WRW test for HC-BPPV (P > 0.05). However, the detection rate of Rahko T maneuver was higher than the other two tests for SC-BPPV and the differences were statistically significant (P < 0.05). The detection rates of different positioning tests for PC-BPPV and HC-BPPV between the two groups were not different in statistics (P > 0.05), which implies that the different order had no effect on the sensitivity of each positioning test. CONCLUSION: Dix-Hallpike test is recommended as the first choice for PC-BPPV for its more efficient stimulus to the posterior semicircular canal, and Side-lying test is recommended as a prior choice to the patients with suspected PC-BPPV but unable to receive Dix-Hallpike test because of its similar sensitivity and more convenient manipulation. The detection rate of Both Roll test and WRW test were higher than 90% and there's no significant difference between the two tests. In addition, Roll test is easier to perform and helpful for the therapy, so its considered as the preferred test for HC-BPPV with WRW test as the supplement test. Nevertheless, for SC-BPPV the sensitivity of Rahko T maneuver was higher than that of the other two tests, so it can be used to confirm the suspected SC-BPPV patients detected or missed diagnosed by the two other tests. To avoid misdiagnosis or missed diagnosis, the judgment of affected semicircular canal is determined not only by positioning test but also by the feature of nystagmus.