The Significance of Crescents on the Clinical Features and Outcomes of Primary Immunoglobin A Nephropathy.

Background: It is still controversial whether the proportion of crescents below 50% can be an independent predictive risk factor for poor prognosis in IgAN patients. We reported the significance of different proportions of crescents on the clinical features and the cut-off value of crescents in predicting the occurrence of end-stage kidney disease (ESKD) in patients with IgAN. Methods: We retrospectively analyzed biopsy-proven primary IgAN patients in Sichuan Provincial People's Hospital from 2007 to 2019. The patients were divided into 5 groups on the basis of crescent proportion as follows: 0 (n = 647), < 10% (n = 221), 10 to 24% (n = 272), 25 to 49% (n = 80), and ≥50% (n = 22). The primary endpoint was defined as ESKD, and the secondary endpoint was the combined renal endpoint (≥50% reduction in eGFR or ESKD). A validation cohort of 346 patients were enrolled from Affiliated Hospital of Southwest Medical University. Cox regression model and Kaplan-Meier survival analysis were performed. Results: A total of 1242 eligible patients with biopsy-proven IgAN were recorded in the database, compared with the non-crescent group, patients in the crescent group had lower levels of hemoglobin (Hb) and albumin (Alb), higher levels of blood urea nitrogen (BUN), 24h urinary protein and hematuria, a higher proportion of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), and tubular atrophy/interstitial fibrosis (T1/T2) (p < 0.05). A higher crescent proportion was associated with lower levels of Hb, ALB, eGFR and serum IgG (p < 0.05), higher levels of SCr, BUN, increasing amounts of 24 h urinary protein, increasing proportion of M1 and E1, and increasing severity of interstitial inflammatory infiltration. During the median follow-up of 43 months (range 6-151), 63 individuals (7.0%) reached the primary outcome of ESKD and 99 patients (11.1%) reached the combined renal endpoint. 34(7.5%), 21 (13.3%), 24(12.2%), 14(21.5%) and 6(31.6%) patients reached the combined renal endpoint in the above five groups in crescents 0, <10%, 10∼24%, 25∼49% and ≥50%, respectively. A total of 274(62.6%) cases in the crescent group and 254 (55.7%) cases in the non-crescent group received immunosuppressive therapy. Multivariate Cox regression showed that crescents ≥50% was an independent risk factor for the progression of ESKD (p = 0.003) and crescents ≥25% was an independent risk factor for the combined renal endpoint(p < 0.001). The receiver operating characteristic curve showed that IgAN patients with crescents ≥43.7% had a higher risk of ESKD, even with immunosuppressants (Sensitivity = 75.7%,specificity = 89.6%,p < 0.001). This discovery cohort and the validation cohort further confirmed that patients with crescents <43.7% had better renal prognosis than those with crescents ≥43.7% in the whole group and those with immunosuppressants (p < 0.001). Conclusion: IgAN patients with crescents had more severe clinicopathological features and poorer prognosis. Crescents ≥50% was an independent risk factor for the progression of ESKD and crescents ≥25% was an independent risk factor for ≥50% reduction in eGFR or ESKD in treated and untreated IgAN patients. Crescents ≥43.7% was an independent risk factor for ESKD in those with immunosuppressants.

HLA-DQB1 and HLA-DRB1 expression is associated with disease severity in IgAN.

BACKGROUND: Several genome-wide association studies have found that HLA class II histocompatibility antigen, DQ beta1 (HLA-DQB1) and HLA class II histocompatibility antigen, DR beta1 (HLA-DRB1) were associated with immunoglobulin A nephropathy (IgAN). However, few studies have explored the association between HLA-DQB1 and HLA-DRB1 expression and IgAN. This is the first study to investigate the relationship between HLA-DQB1 and HLA-DRB1 expression and clinical pathological characteristics. METHODS: A total of 113 patients with biopsy-proven IgAN and 71 healthy control patients participated in this study. HLA-DQB1 and HLA-DRB1 expression in peripheral blood lymphocytes was measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and flow cytometry. Serum galactose-deficient IgA1 (Gd-IgA1) level was measured by an enzyme-linked immunosorbent assay kit. The clinical and histopathological data of patients with IgAN were collected at the time of renal biopsy. Pearson's or Spearman's correlation coefficients were used to analyze the correlation between the expression of HLA-DQB1 and HLA-DRB1 mRNA and protein and the clinical pathological features of IgAN. RESULTS: HLA-DQB1 and HLA-DRB1 messenger ribonucleic acid expression was decreased in IgAN patients compared to healthy control patients (P<0.01). HLA-DQB1 and HLA-DRB1 protein expression was significantly lower in IgAN patients than healthy control patients (P<0.05). HLA-DQB1 and HLA-DRB1 protein expression was positively correlated with 24-h urinary protein excretion (P<0.05). HLA-DRB1 protein expression was negatively correlated with renal function as measured by an estimated glomerular filtration rate (P<0.05). HLA-DRB1 protein expression was higher in patients with crescentic IgAN than patients without crescent formation (P<0.05). CONCLUSIONS: Our study found the expression of HLA-DQB1, HLA-DRB1 were associated with the disease severity of IgAN and abnormal HLA-DQB1 and HLA-DRB1 expression may aggravate the progression of IgAN. We intend to gather further follow-up data to explore the effects of HLA-DQB1 and HLA-DRB1 expression on the prognosis of IgAN.

Biosynthetic Pathway for Ethyl Butyrate Production in Saccharomyces cerevisiae.

Ethyl butyrate is one of the most important flavor substances in Chinese Baijiu and is also an ingredient in various daily-use chemical essences and food flavorings. In this study, to produce ethyl butyrate, we first introduced a butyryl-CoA synthesis pathway into Saccharomyces cerevisiae. Subsequently, three different alcohol acyltransferases, SAAT, VAAT, and CmAAT, were separately introduced into S. cerevisiae to catalyze the reaction of butyryl-CoA with ethanol to produce ethyl butyrate, and the results showed that strain EBS with SAAT produced the most ethyl butyrate (20.06 ± 2.23 mg/L). Furthermore, as the reaction catalyzed by Bcd to produce butyryl-CoA from crotonyl-CoA is a rate-limiting step, we replaced Bcd with Ter, and the modified strain EST produced 77.33 ± 4.79 mg/L ethyl butyrate. Finally, the copy numbers of Ter and SAAT were further increased, and the resulting modified strain EST-dST produced 99.65 ± 7.32 mg/L ethyl butyrate.

Primary thymic mucosa-associated lymphoid tissue lymphoma complicated with renal amyloidosis: A first case report.

INTRODUCTION: Primary mucosa-associated lymphoid tissue (MALT) lymphomas originating in thymus is rare. And, there have been few reports of patients with MALT coexisting with amyloidosis. As far as we know, this was the first case report on MALT lymphoma associated with renal amyloidosis. PATIENT CONCERNS: A 57-year-old man presented with nephrotic syndrome. Further workup revealed IgM-Lambda type monoclonal gammopathy. Bone marrow biopsy showed 8% clonal plasma cells. Renal biopsy confirmed the diagnosis of Lambda light chain AL amyloidosis. positron emission tomography/computed tomography showed thymic lesions which upon biopsy were diagnosed as MALT lymphoma of the thymus. DIAGNOSIS: Primary thymic MALT lymphoma complicated with renal amyloidosis. INTERVENTIONS: The patient underwent surgical resection of the thymus mass and 2 courses of chemotherapy. OUTCOMES: Follow-up data showed that the patient survived 18 months after surgical excision and chemotherapy. CONCLUSION: The case highlights the importance of screening for malignancy in patients with renal amyloidosis.

Saccharomyces cerevisiae proteinase A excretion and wine making.

Proteinase A (PrA), the major protease in Saccharomyces cerevisiae, plays an essential role in zymogen activation, sporulation, and other physiological processes in vivo. The extracellular secretion of PrA often occurs during alcoholic fermentation, especially in the later stages when the yeast cells are under stress conditions, and affects the quality and safety of fermented products. Thus, the mechanism underlying PrA excretion must be explored to improve the quality and safety of fermented products. This paper briefly introduces the structure and physiological function of PrA. Two transport routes of PrA, namely, the Golgi-to-vacuole pathway and the constitutive Golgi-to-plasma membrane pathway, are also discussed. Moreover, the research history and developments on the mechanism of extracellular PrA secretion are described. In addition, it is briefly discussed that calcium homeostasis plays an important role in the secretory pathway of proteins, implying that the regulation of PrA delivery to the plasma membrane requires the involvement of calcium ion. Finally, this review focuses on the effects of PrA excretion on wine making (including Chinese rice wine, grape wine, and beer brewage) and presents strategies to control PrA excretion.