Integrated single-cell sequencing, spatial transcriptome sequencing and bulk RNA sequencing highlights the molecular characteristics of parthanatos in gastric cancer.

BACKGROUND: Parthanatos is a novel programmatic form of cell death based on DNA damage and PARP-1 dependency. Nevertheless, its specific role in the context of gastric cancer (GC) remains uncertain. METHODS: In this study, we integrated multi-omics algorithms to investigate the molecular characteristics of parthanatos in GC. A series of bioinformatics algorithms were utilized to explore clinical heterogeneity of GC and further predict the clinical outcomes. RESULTS: Firstly, we conducted a comprehensive analysis of the omics features of parthanatos in various human tumors, including genomic mutations, transcriptome expression, and prognostic relevance. We successfully identified 7 cell types within the GC microenvironment: myeloid cell, epithelial cell, T cell, stromal cell, proliferative cell, B cell, and NK cell. When compared to adjacent non-tumor tissues, single-cell sequencing results from GC tissues revealed elevated scores for the parthanatos pathway across multiple cell types. Spatial transcriptomics, for the first time, unveiled the spatial distribution characteristics of parthanatos signaling. GC patients with different parthanatos signals often exhibited distinct immune microenvironment and metabolic reprogramming features, leading to different clinical outcomes. The integration of parthanatos signaling and clinical indicators enabled the creation of novel survival curves that accurately assess patients' survival times and statuses. CONCLUSIONS: In this study, the molecular characteristics of parthanatos' unicellular and spatial transcriptomics in GC were revealed for the first time. Our model based on parthanatos signals can be used to distinguish individual heterogeneity and predict clinical outcomes in patients with GC.

Hydroxychloroquine Induces Remission for IgA Nephropathy With Mild to Moderate Proteinuria: A Single-Centered Retrospective Analysis.

BACKGROUND: Hydroxychloroquine (HCQ) influences both toll-like receptor (TLR) signaling and leukocyte activation, which are speculated to play a role in the pathogenesis of IgA nephropathy (IgAN). METHODS: This is a single-centered retrospective study involving 426 IgAN patients diagnosed from May 2016 to August 2020. All patients were matched according to a propensity score matching (PSM) to produce three groups: renin-angiotensin-aldosterone system inhibitors (RAASi) group (RAASi only), corticosteroids group (corticosteroids only or combined with RAASi), and HCQ group (HCQ only or combined with RAASi), consisting of 63 patients for each group. RESULTS: After PSM, the median urine protein/creatinine ratio (UPCR) of overall patients was 0.91 g/g, while their median serum creatinine was 87.00 µmol/L. After the median follow-up period of 11.03 months, the total remission rates of the RAASi group, corticosteroids group, and HCQ groups were 49.21% (n = 31), 74.60% (n = 47), and 52.38% (n = 33), respectively (p = 0.017). Thirteen (6.88%) patients experienced a decline in estimated glomerular filtration rate (eGFR) of more than 25% from baseline, including six (9.52%) patients in the RAASi group, three (4.76%) patients in the corticosteroids group, and four (6.35%) patients in HCQ group (p = 0.677). One (1.59%) patient in the HCQ group had blurred vision and continued to use HCQ after ruling out retinal lesions by ophthalmic examination. CONCLUSION: HCQ is effective in inducing remission and well-tolerated in IgAN patients with mild to moderate proteinuria.

The efficacy of rituximab plus belimumab or telitacicept in refractory lupus nephritis.

OBJECTIVE: Lupus nephritis is a severe and common complication of systemic lupus erythematosus (SLE). The pathogenesis of lupus nephritis is characterized by B-cell activation and autoantibody formation. Rituximab and belimumab, as well as telitacicept, target B cells through different mechanisms, potentially exerting a synergistic effect in the treatment of lupus nephritis. This study aims to investigate the efficacy and safety of treatment with rituximab followed by belimumab or telitacicept in the management of refractory lupus nephritis. METHODS: We conducted a single-center, open-label, retrospective study, including 25 patients with refractory lupus nephritis. All patients received combination therapy with rituximab in individualized dosages to achieve peripheral B-cell depletion, and then followed by belimumab or telitacicept. The follow-up period was at least 12 months, and the primary end point was renal remission rate at the last follow-up. RESULTS: During a median follow-up of 19 (13, 29) months, 20 of 25 (80%) patients achieved objective remission (OR), including 19 (76%) patients achieved complete renal response (CRR). After rituximab (712 ± 416mg in average), 18 patients received belimumab and seven patients received telitacicept. In the rituximab plus telitacicept group, all patients achieved CRR; while in the rituximab plus belimumab group, 12 (66.7%) patients achieved CRR and 13 (72.2%) patients achieved OR. The mean SLEDAI-2K score decreased from 15 ± 6 to 6 ± 6, representing an average reduction of 60%. At the last follow-up, 18/25 (72%) had prednisone ≤ 5 mg/d or even discontinued prednisone use. Adverse effects were mainly immunoglobulin deficiency, respiratory tract infection, urinary tract infections, and rash. No death occurred. CONCLUSIONS: Rituximab followed by belimumab or telitacicept may be effective in inducing remission in refractory lupus nephritis, with tolerable adverse effects.

Elevated Urinary IL-6 Predicts the Progression of IgA Nephropathy.

Introduction: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. However, biomarkers for predicting the progression or regression of IgAN remain a clinical challenge. In the present study, we aim to identify promising prognostic markers of IgAN. Methods: Using the cytokine antibody array, we detected serum and urinary levels of 9 common cytokines selected from 23 IgAN-related biomarkers in 32 patients with IgAN and 16 healthy controls. The best biomarkers for distinguishing IgAN patients from healthy controls were identified and confirmed in a multicenter cohort with 222 patients with IgAN and 159 age- and sex-matched healthy controls. Their associations with IgAN progression were further explored in 762 patients with IgAN with a median follow-up of 65 months. Results: Among the 9 candidate markers, urinary interleukin-6 (IL-6) and transforming growth factor-ß1 (TGF-ß1) levels were the best for distinguishing patients with IgAN from healthy controls. In the diagnostic cohort, both urinary IL-6 and TGF-ß1 levels were elevated in patients with IgAN and showed good discriminatory power, with an area under curve (AUC) of 0.9725 (95% confidence interval: 0.9593-0.9858). Elevated urinary IL-6 level was independently and significantly correlated with the high risk of composite renal outcome (hazard ratio per log-transformed IL-6:1.420 [1.139-1.769]), but no statistical significance was observed between urinary TGF-ß1 level and IgAN progression after adjusting for multiple confounders. Conclusions: Elevated urinary IL-6 and TGF-ß1 levels predict the progression of IgAN. Urinary IL-6 is an independent risk factor and a promising noninvasive predictor for IgAN progression.

Validation of the Antineutrophil Cytoplasmic Antibody Renal Risk Score and Modification of the Score in a Chinese Cohort With a Majority of Myeloperoxidase-Positive Patients.

OBJECTIVE: We aimed to validate and modify the renal risk score for antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) in a Chinese cohort with a majority of myeloperoxidase (MPO)-positive patients. METHODS: A total of 285 patients with biopsy-proven AAGN in our center were retrospectively included. Patients were randomly assigned to the development set (n = 201) and the validation set (n = 84). We calculated the renal risk score and analyzed the clinicopathological characteristics and follow-up data. The nomogram was constructed based on the independent prognostic factors identified by the multivariable Cox regression and then compared with the renal risk score. RESULTS: Over a median follow-up period of 41.3 (range 20.0-63.8) months, 84 (29.5%) patients reached end-stage kidney disease (ESKD). In the development set, hypertension (hazard ratio [HR] 2.16, 95% CI 1.08-4.32, P = 0.03), high serum creatinine (HR 1.002, 95% CI 1.001-1.003, P < 0.001), high daily urine protein (HR 1.34, 95% CI 1.15-1.57, P < 0.001), high glomerular sclerosis (HR 13.98, 95% CI 3.50-55.92, P < 0.001), and interstitial fibrosis > 50% (HR 4.18, 95% CI 1.90-9.19, P < 0.001) were independent risk factors for ESKD, and these indicators were included in the nomogram. The C-indices of the nomogram model in the development set, validation set, and all-data set were 0.838 (range 0.785-0.891), 0.794 (range 0.774-0.814), and 0.822 (range 0.775-0.869), respectively, which were higher than those of the renal risk score model, 0.801 (range 0.748-0.854), 0.746 (range 0.654-0.838) and 0.783 (range 0.736-0.830), respectively. The net reclassification improvement and the integrated discrimination improvement further illustrated the higher predictive ability of the nomogram. CONCLUSION: We present a nomogram as a practical tool to predict renal outcomes in Chinese patients with MPO-ANCA glomerulonephritis.

The significance of follow-up serum uric acid levels in predicting all-cause mortality and cardiovascular mortality in peritoneal dialysis patients.

BACKGROUND: This study aimed to analyze the change of serum uric acid (SUA) level post peritoneal dialysis (PD), and the correlation between follow-up SUA and prognosis in patients with PD. METHODS: A total of 1402 patients with PD were evaluated. We graded SUA levels into four grades at baseline, 6 months, 12 months, 18 months, and 24 months post PD, and then compared all-cause mortality and cardiovascular mortality among patients with different SUA grades at each time point. Kaplan-Meier and Cox proportional-hazards regression models were used in the analysis. RESULTS: The SUA levels were 7.97 ± 1.79, 7.12 ± 1.48, 7.05 ± 1.33, 7.01 ± 1.30, and 6.93 ± 1.26 mg/dl at baseline, 6, 12, 18, and 24 months, respectively. There was significant difference on all-cause mortality among patients with PD with different graded SUA levels at 6 months post PD (p = 0.010), and the all-cause mortality was lowest in patients with the grade of 5.65 mg/dl ≤ SUA <7.13 mg/dl. CONCLUSION: SUA level decreased after PD during follow-up. At 6 months post PD, the grade of 5.65 mg/dl ≤ SUA <7.13 mg/dl was appropriate for better patients' survival.

Aortic Stress Activates an Adaptive Program in Thoracic Aortic Smooth Muscle Cells That Maintains Aortic Strength and Protects Against Aneurysm and Dissection in Mice.

BACKGROUND: When aortic cells are under stress, such as increased hemodynamic pressure, they adapt to the environment by modifying their functions, allowing the aorta to maintain its strength. To understand the regulation of this adaptive response, we examined transcriptomic and epigenomic programs in aortic smooth muscle cells (SMCs) during the adaptive response to AngII (angiotensin II) infusion and determined its importance in protecting against aortic aneurysm and dissection (AAD). METHODS: We performed single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) analyses in a mouse model of sporadic AAD induced by AngII infusion. We also examined the direct effects of YAP (yes-associated protein) on the SMC adaptive response in vitro. The role of YAP in AAD development was further evaluated in AngII-infused mice with SMC-specific Yap deletion. RESULTS: In wild-type mice, AngII infusion increased medial thickness in the thoracic aorta. Single-cell RNA sequencing analysis revealed an adaptive response in thoracic SMCs characterized by upregulated genes with roles in wound healing, elastin and collagen production, proliferation, migration, cytoskeleton organization, cell-matrix focal adhesion, and PI3K-PKB/Akt (phosphoinositide-3-kinase-protein kinase B/Akt) and TGF-ß (transforming growth factor beta) signaling. ScATAC-seq analysis showed increased chromatin accessibility at regulatory regions of adaptive genes and revealed the mechanical sensor YAP/transcriptional enhanced associate domains as a top candidate transcription complex driving the expression of these genes (eg, Lox, Col5a2, Tgfb2). In cultured human aortic SMCs, cyclic stretch activated YAP, which directly bound to adaptive gene regulatory regions (eg, Lox) and increased their transcript abundance. SMC-specific Yap deletion in mice compromised this adaptive response in SMCs, leading to an increased AAD incidence. CONCLUSIONS: Aortic stress triggers the systemic epigenetic induction of an adaptive response (eg, wound healing, proliferation, matrix organization) in thoracic aortic SMCs that depends on functional biomechanical signal transduction (eg, YAP signaling). Our study highlights the importance of the adaptive response in maintaining aortic homeostasis and preventing AAD in mice.

Effects of Typical Antimicrobials on Growth Performance, Morphology and Antimicrobial Residues of Mung Bean Sprouts.

Antimicrobials may be used to inhibit the growth of micro-organisms in the cultivation of mung bean sprouts, but the effects on mung bean sprouts are unclear. In the present study, the growth performance, morphology, antimicrobial effect and antimicrobial residues of mung bean sprouts cultivated in typical antimicrobial solutions were investigated. A screening of antimicrobial residues in thick-bud and rootless mung bean sprouts from local markets showed that the positive ratios of chloramphenicol, enrofloxacin, and furazolidone were 2.78%, 22.22%, and 13.89%, respectively. The cultivating experiment indicated that the production of mung bean sprouts in antimicrobial groups was significantly reduced over 96 h (p < 0.05). The bud and root length of mung bean sprouts in enrofloxacin, olaquindox, doxycycline and furazolidone groups were significantly shortened (p < 0.05), which cultivated thick-bud and rootless mung bean sprouts similar to the 6-benzyl-adenine group. Furthermore, linear regression analysis showed average optical density of 450 nm in circulating water and average production had no obvious correlation in mung bean sprouts (p > 0.05). Antimicrobial residues were found in both mung bean sprouts and circulating water. These novel findings reveal that the antimicrobials could cultivate thick-bud and rootless mung bean sprouts due to their toxicity. This study also proposed a new question regarding the abuse of antimicrobials in fast-growing vegetables, which could be a potential food safety issue.

Changes of gut microbiota in diabetic nephropathy and its effect on the progression of kidney injury.

PURPOSE: We aimed to illustrate gut microbiota and short chain fatty acid (SCFA) levels in diabetic nephropathy (DN) patients, and investigate the mechanism of sodium butyrate in diabetic mellitus (DM) rats. METHODS: Gut microbiota and serum SCFA levels were measured by 16S rDNA and GC-MS. After being built by streptozotocin (DM rats), the DM rats were administered 300 mg/kg sodium butyrate for 12 weeks (DM + BU rats). Gut microbiota, serum and fecal butyrate level were measured. RT-PCR, WB and transmission electron microscopy were performed to explore LC3mRNA or LC3B protein expression, and autophagosomes in kidney tissues. AMPK/mTOR protein expression in renal tissue were also measured. RESULTS: The gut microbial dysbiosis was found in DM and DN groups, and some SCFAs-producing bacteria were decreased in DN group. The serum butyrate concentrations were lower in SCFA-DN group compared with SCFA-HC group and SCFA-DM group in the other cohort. Serum butyrate level was positively correlated with eGFR. Sodium butyrate increased serum and fecal butyrate levels, and improved the enlargement of glomerular area and fibronectin and collagen IV expressions in renal tissues in DM + BU rats. The LC3 mRNA, LC3BII/I ratio and number of autophagosomes were increased in renal tissue of DM + BU rats. Higher p-AMPK/AMPK ratio and lower p-mTOR/ mTOR ratio were shown in renal tissue of DM + BU rats compared with DM rats. CONCLUSIONS: We found the decrease in SCFAs-producing bacteria and low SCFAs concentrations in DN patients. Oral butyrate supplementation may improve kidney injury in DM rats, possibly by increasing autophagy via activating AMPK/mTOR pathway.

The survival nomograms for anti-neutrophil cytoplasmic antibody-associated glomerulonephritis patients with a follow-up of more than one year.

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with kidney injury, manifested as ANCA-associated glomerulonephritis (AAGN), often portends a poor prognosis of renal function and life survival in long term. METHODS: A cohort of 339 AAGN patients were enrolled retrospectively. These patients survived and were followed up for at least 12 months after diagnosis in our centre. Multivariate Cox regression analysis and nomogram models were performed to determine the risk factors associated with renal survival and patient survival. RESULTS: The median follow-up time of all 339 patients was 65.2 (IQR 45.1, 91.3) months and the median age was 61(IQR 53, 69) years. In order to analyse the impact of the factors on renal survival, we divided the patients into 2 groups: non-dialysis group (204 patients without dialysis at the final visit) and dialysis group (135 patients with maintaining dialysis). The patients in dialysis group had lower haemoglobin level, lower eGFR level, lower platelets count, more daily urine protein, and higher Birmingham Vasculitis Activity Score (BVAS) at admission than those in non-dialysis group. Multivariate Cox regression revealed that low haemoglobin (HR=0.977, 95%CI 0.965-0.990, p<0.001), low eGFR (HR=0.957, 95%CI 0.941-0.973, p<0.001) and high proteinuria (HR=1.139, 95%CI 1.055-1.230, p=0.001) at admission were independent risk factors for developing maintaining dialysis. A nomogram was established based on the results of multivariate Cox analysis and the internal bootstrap resampling approach showed the C-index of the nomogram was 0.83. Then we divided all patients into death group (n=99) and survival group (n=240). The patients in death group had older age, more hypertension, more chronic lung disease, lower platelets count, lower serum albumin, higher BVAS and lower eGFR at admission than those in survival group. Multivariate Cox regression revealed that the status of maintaining dialysis (HR 3.51, 95% CI 1.91-6.47, p<0.001) and old age (HR 1.07, 95% CI 1.04-1.09, p<0.001) were independent risk factors for all-cause mortality. Again, a nomogram was established and the C-index was 0.74. CONCLUSIONS: We analysed the independent risk factors for maintaining dialysis and all-cause mortality in AAGN patients with a follow-up of more than 12 months. The two proposed nomograms were of predictive value.

Alternative Splicing: A New Cause and Potential Therapeutic Target in Autoimmune Disease.

Alternative splicing (AS) is a complex coordinated transcriptional regulatory mechanism. It affects nearly 95% of all protein-coding genes and occurs in nearly all human organs. Aberrant alternative splicing can lead to various neurological diseases and cancers and is responsible for aging, infection, inflammation, immune and metabolic disorders, and so on. Though aberrant alternative splicing events and their regulatory mechanisms are widely recognized, the association between autoimmune disease and alternative splicing has not been extensively examined. Autoimmune diseases are characterized by the loss of tolerance of the immune system towards self-antigens and organ-specific or systemic inflammation and subsequent tissue damage. In the present review, we summarized the most recent reports on splicing events that occur in the immunopathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and attempted to clarify the role that splicing events play in regulating autoimmune disease progression. We also identified the changes that occur in splicing factor expression. The foregoing information might improve our understanding of autoimmune diseases and help develop new diagnostic and therapeutic tools for them.

Analysis of the dynamic relationship between immune profiles and the clinical features of patients with COVID-19.

BACKGROUND: The novel coronavirus disease (COVID-19) has been declared a global pandemic, with the cumulative number of confirmed cases and deaths exceeding 150 million and 3 million, respectively. Here, we examined the dynamic changes in the immune and clinical features of patients with COVID-19. METHODS: Clinical data of 98 patients with confirmed COVID-19 diagnosis were acquired from electronic medical records and curated. The data were analyzed based on the stage of the admission, deterioration, and convalescence, which included age, sex, severity, disease stages, biochemical indicators, immune cells, inflammatory cytokines, and immunoglobulins. Additionally, temporal changes in the immune response in patients undergoing continuous renal replacement therapy (CRRT) were also examined. RESULTS: Compared to mild stage patients, severe stage patients with COVID-19 exhibited a significant reduction in lymphocyte [23.10 (17.58-33.55) vs. 4.80 (2.95-6.50), P<0.001], monocyte [8.65 (7.28-10.00) vs. 3.45 (2.53-4.58), P<0.001], and NK cell levels [244.00 (150.50-335.00) vs. 59.00 (40.00-101.00), P<0.001] but showed elevated levels of neutrophils [64.90 (56.30-73.70) vs. 90.95 (87.60-93.68), P<0.001], inflammatory cytokines [Interleukin-10, 3.05 (1.37-3.86) vs. 5.94 (3.84-8.35), P=0.001; and tumor necrosis factor-α, 11.50 (6.55-26.45) vs. 12.96 (12.22-36.80), P=0.029], which improved during convalescence. Besides, the number of immune cells-T lymphocytes, B lymphocytes, helper T cells, suppressor T cells, NK cells, and monocytes, except neutrophils-slowly increased in critically ill patients receiving CRRT from 0 to 3 weeks. CONCLUSIONS: Our results indicate that the surveillance of immune cells may contribute to monitoring COVID-19 disease progression, and CRRT is a potential therapeutic strategy to regulate the immune balance in critically ill patients.

Identifying Sequence Variants of 18 Hereditary Ovarian Cancer-Associated Genes in Chinese Epithelial Ovarian Cancer Patients.

OBJECTIVES: The causes of ovarian cancer (OC) have been confirmed to be closely related to genetic factors. Identifying sequence variants of hereditary ovarian cancer (HOC) susceptibility genes can increase clinical surveillance, facilitate early detection, and provide personalized treatment for patients. This study is aimed at investigating the variation frequency of HOC susceptibility genes in the Chinese population and providing information for the etiology and genetics of OC. METHODS: 118 epithelial OC patients were recruited in this clinical study. Variants of 18-gene panel were detected in blood samples by next-generation sequencing (NGS) technology. RESULTS: Overall, 36.44% (43/118) of patients carried at least one pathogenic variant. Among these, BRCA1 pathogenic variants were detected in 31 (26.27%) patients, and 5 (4.24%) patients carried pathogenic variants of BRCA2. Moreover, 27.12% (32/118) of patients carried variants of unknown significance (VUSs). Importantly, we detected eight variants that were not reported previously. CONCLUSIONS: Our study enlarged the spectrum of HOC-associated gene sequence variants in the Chinese population and also proved the necessity of multigene testing in epithelial OC patients. The identification of patients with HOC will allow family members to undergo cascade testing where identification of unaffected carriers can facilitate early detection, risk reduction, or prevention of OC and ultimately improve long-term outcomes.

Case Report: Pathogenic MYH9 c.5797delC Mutation in a Patient With Apparent Thrombocytopenia and Nephropathy.

MYH9-related disease or disorder (MYH9-RD) is an autosomal dominant disease caused by mutations in the MYH9 gene. Mutations in this gene initially affect the hemic system, and other manifestations may evolve with age. Here, we report the case of a 46-year-old Chinese woman with MYH9-RD who was primarily misdiagnosed with idiopathic thrombocytopenia purpura. Exome sequencing of the patient, and the mother and son of the patient revealed a deletion mutation c.5797delC (p. R1933Efs*15) in exon 41 (encoding non-helical tailpiece, NHT) of the MYH9 gene, which consequently led to a frameshift mutation. To the best of our knowledge, this mutation has been reported in Italy once, while the substitution mutation c.5797 C>T is the most frequent mutation. Mutations that affect the NHT region cause thrombocytopenia throughout life; however, our patient presented with a more severe phenotype than previously reported, including thrombocytopenia, inclusion bodies in neutrophils, sensorineural hearing loss, nephropathy, and abnormal liver enzymes. Our goal in the current case is to prevent further progression of renal involvement and to identify other affected members in this family to provide early intervention. This case may raise awareness of MYH9-RD when diagnosing thrombocytopenia and improve our understanding of this condition.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Acute Kidney Injury: Short-Term Recovery Predicts Long-Term Outcome.

Background: Kidney involvement is common in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). It tends to be aggressive, and in some patients, the kidney involvement may reach the criteria of acute kidney injury (AKI). Here, we aim to describe the clinical characteristics of these patients and find risk factors for poor outcomes. Methods: Patients diagnosed with AAV in our hospital from February 2003 to February 2017 were included. Those who reached the KDIGO AKI criteria were reclassified according to the KDIGO AKI stage. The clinical features of these patients were analyzed. Also, according to the variation of serum creatinine 3 months after AKI episode, patients were further divided into two groups: patients whose serum creatinine (Scr) level at the third month decreased by 30% or more from the peak Scr level was classified into G1 and others were classified into G2. Long-term renal and survival outcomes of these patients were analyzed with a Cox model. The renal endpoint was reaching end-stage renal disease (ESRD), and the survival endpoint was death. Nomograms were built based on cox models. Results: Of 141 AAV patients included, during the median follow-up period of 64.0 (IQR 34.8, 85.4) months, 36 (25.5%) patients reached renal endpoints, and 22 (15.6%) patients died. The median renal survival time was 35.9 (IQR 21.3, 72.6) months and the median survival time was 48.4 (IQR 26.8, 82.8) months. Multivariate analysis showed that poor recovery of Scr level at 90 days (P < 0.001, RR = 9.150, 95%CI 4.163-20.113), BVAS score (P = 0.014, RR = 1.110, 95% CI1.021-1.207), and AKI stage 3 (P = 0.012 RR = 3.116, 95%CI 1.278-7.598) were independent risk factors for renal endpoints; poor recovery of Scr level at 90 days (P = 0.010, RR = 3.264, 95%CI 1.326-8.035), BVAS score (P = 0.010, RR = 1.171, 95%CI 1.038-1.320) and age (P = 0.017, RR = 1.046, 95%CI 1.008-1.086) were independent risk factors for all-cause death. The c-index of nomograms is 0.830 for the renal outcome and 0.763 for the survival outcome. Conclusion: KDIGO AKI stage 3 is the risk factor for ESRD in AAV patients with AKI. The BVAS score and level of kidney function recovery at 90 days are the independent risk factors for both ESRD and all-cause death and are of predictive value for the outcome.

Recent advances in analytical techniques for the detection of adulteration and authenticity of bee products - A review.

Bee products have been considered as functional foods for a long time in China because of their wide range of biological activity. China has the largest number of bee colonies and the highest production of bee products in the world. Major bee products include honey, royal jelly, propolis and bee pollen. In recent years, consumption of bee products in China has been increasing due to an increased public awareness of their nutritional and health benefits. With the development of the Chinese economy and the improvement of people's living standards, high-end and gift-oriented products have become more popular and bee products are one of the options. However, the production of bee products cannot increase rapidly in short term and this is a driver for substantial economic-motivated adulteration. This is compounded by globalisation of supply chains which has also resulted in a rise in bee products fraud. These illicit products are eroding market prices and consumer trust, causing significant damage to the beekeeping industry. In order to provide information or solutions for regulators and consumers, in this article, we review he characteristics of bee products in China and the current situation regarding adulteration and authenticity of bee products. Moreover, advances in analytical techniques for detection of adulteration and authenticity of bee products including sensory techniques, DNA methods, isotope ratio mass spectrometry, spectroscopic techniques and mass spectrometry are reviewed. Finally, the applications and limitations of analytical methods in authentication are critically assessed. Suggestions are also put forward for the future management of China's bee products industry.

The risk factors for early mortality and end-stage renal disease in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis: experiences from a single center.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common disease with high mortality. Kidney involvement in AAV commonly performances as ANCA-associated glomerulonephritis (AAGN). We aimed to identify the risk factors for mortality and end-stage renal disease(ESRD) within 6 months since diagnosis in AAGN patients. A total of 350 AAGN patients were enrolled in our center between 2004 and 2017 retrospectively. We analyzed the demographic, clinical and follow-up data. Factors for mortality and ESRD were investigated with univariate and multivariate Cox regression models. The median follow-up time was 60.8 (IQR 31.2, 84.5) months and 40 (11.4%) patients died within the first 6 months. In the multivariate analysis, age ≥ 65 years (HR = 2.245, 95%CI 1.085-4.645, P = 0.029), high leukocyte counts (HR = 1.089, 95%CI 1.015-1.168, P = 0.018), high Birmingham Vasculitis Activity Score (BVAS) (HR = 1.089, 95%CI 1.017-1.165, P = 0.014), infection (HR = 2.023, 95%CI 1.013-4.042, P = 0.046) and low serum albumin (HR = 0.916, 95%CI 0.845-0.992, P = 0.030) were independent risk factors for all-cause mortality in the first 6 months. A total of 95 patients reached ESRD within the first 6 months. The renal survival rate was 72.9% at 6 months. Multivariate analysis showed that high BVAS (HR = 1.198, 95%CI 1.043-1.376, P = 0.011), high daily urine protein (HR = 1.316, 95%CI 1.046-1.656, P = 0.019) and low eGFR (HR = 0.877, 95%CI 0.804-0.957, P = 0.003) were independent risk factors for ESRD. The mortality and ESRD rates were high in the first 6 months for AAGN patients. High disease activity evaluated by BVAS impacted both on patients' survival and renal survival, while over 65 years of age and infection were risk factors for mortality.

Early Detection of Aortic Degeneration in a Mouse Model of Sporadic Aortic Aneurysm and Dissection Using Nanoparticle Contrast-Enhanced Computed Tomography.

[Figure: see text].

Performance of the 2019 EULAR/ACR systemic lupus erythematosus classification criteria in a cohort of patients with biopsy-confirmed lupus nephritis.

OBJECTIVE: To evaluate the performance of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria in a cohort of patients with biopsy-confirmed lupus nephritis (LN) and their renal prognosis. METHODS: Patients with newly diagnosed SLE attending and followed up for >12 months were included. A retrospective review of all patients with renal biopsy fulfilling a consensus expert opinion during 2014 and 2018. Clinical, serological and pathological data were collected and each patient was assigned a high/low criteria scores (HS/LS) group. Survival curves for flare adjusted for multiplicity on renal flares, was applied to the two groups. RESULTS: Applying EULAR/ACR criteria in our cohort of 126 patients, 6 (4.76%) did not meet the criterion, resulting in a sensitivity of 95.24%. The EULAR/ACR criteria scores was positively correlated with SLE disease activity index scores. Additionally, we noticed that a significant difference in clinical and immunological manifestations between HS and LS group. We observed a higher proportions of class Ⅲ or Ⅳ LN and lower proportions of class Ⅱ or V LN (p=0.034) and pathological higher activity index in HS group (p=0.007). Compared with LS groups, patients involved more severe renal damage and achieved higher rate of complete remission in the HS group. The Kaplan-Meier exploratory analyses, adjusted for LN classification, estimated glomerular filtration rate, activity index and chronicity index and induction and maintenance treatments, showed that patients in the HS group had a tendency of higher renal flare risk than that in the LS group (HR=0.21, p=0.04). CONCLUSIONS: The EULAR/ACR criteria performed high sensitivity in identifying SLE in this cohort of biopsy-confirmed LN. Patients with LN with high criteria scores had more extrarenal manifestations, and worse renal prognosis in the short and long terms.

The correlation of anti-ß2-glycoprotein I antibody with complement activation in patients with idiopathic membranous nephropathy.

PURPOSE: This study evaluated the correlation of anti-ß2-glycoprotein I (anti-ß2-GPI) antibodies with complement activation in patients with idiopathic membranous nephropathy (IMN). METHODS: Thirty-two IMN patients with positive anti-ß2-GPI antibody were enrolled, and 32 age- and sex-matched IMN patients with negative anti-ß2-GPI antibody were randomly enrolled as controls. The frozen serum samples of these 64 patients were collected for detection of anti-phospholipase A2 receptor (PLA2R) antibody and the activity of three complement pathways. Paraffin specimens of the kidney tissues of these 64 patients were collected for immunohistochemical staining of C4d. RESULTS: IMN patients with positive anti-ß2-GPI antibody had a significant decline of the residual complement activity of alternative pathway than those with negative anti-ß2-GPI antibody (37.4 ± 21.2% vs 65.7 ± 50.5%, P = 0.021). The positive rate of kidney C4d staining in IMN patients with and without anti-ß2-GPI was 65.6 and 81.2%, with no significant difference (P = 0.257). Patients with and without anti-ß2-GPI had the same positive rate of anti-PLA2R antibody. CONCLUSION: Anti-ß2-GPI antibody was associated with alternative complement activation in patients with IMN.