Analysis of m6A-regulated genes and subtype classification in lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is the most common and severe clinical manifestation of systemic lupus erythematosus (SLE). N6-methyladenosine (m6A) is a reversible RNA modification and has been implicated in various biological processes. However, the roles of m6A regulators in LN are not fully demonstrated. METHODS: We downloaded the kidney tissue transcriptome dataset of LN patients and normal controls from the GEO database and extracted the expression levels of m6A regulators. We constructed and compared Random Forest (RF) and Support Vector Machine (SVM) models, and subsequently selected featured genes to develop nomogram models. The m6A subtypes were identified based on significantly differentially expressed m6A regulators, and the m6A gene subtypes were identified based on m6A-associated differential genes, and the two m6A modification patterns were comprehensively evaluated. RESULTS: We obtained the GSE32591 and GSE112943 datasets from the GEO database, including 78 LN samples and 36 normal control samples. We extracted the expression levels of 20 m6A regulators. By RF analysis we identified 7 characteristic m6A regulators and constructed nomogramh models with these 7 genes. We identified two m6A subtypes based on these seven important m6A regulators, and the immune cell infiltration levels of the two subtype clusters were significantly different. We identified two more m6A gene subtypes based on m6A-associated DEGs. We calculated the m6A scores using the principal component analysis (PCA) algorithm and found that the m6A scores of m6A cluster A and gene cluster A were lower than those of m6A cluster B and gene cluster B. In addition, we found that the levels of inflammatory factors were also significantly different between m6A clusters and gene clusters. CONCLUSION: This study confirms that m6A regulators are involved in the LN process through different modes of action and provide new diagnostic and therapeutic targets for LN.

Clinicopathological characteristics and outcomes of PLA2R related idiopathic membranous nephropathy in patients with seronegative PLA2R antibodies.

BACKGROUND: Idiopathic membranous nephropathy (IMN) with deposits of phospholipase A2 receptor (PLA2R) antigen in glomerular tissue (GAg+) but no circulating serum PLA2R antibody (SAb-) has been reported. However, little is known about the clinicopathological characteristics and prognosis of this subtype. METHODS: A total of 74 IMN patients with GAg + identified by kidney biopsy were enrolled in this study. We categorized patients into two groups based on the presence or absence of serum PLA2R antibody. Data on clinical features, pathological features, and outcomes were collected. Kaplan-Meier analysis of complete remission (CR) and partial remission (PR) comparing SAb-/GAg + and SAb+/GAg + patients. Cox proportional hazards models was used to examine factors associated with CR and PR. RESULTS: Among 74 IMN patients, 14 were SAb-/GAg+. Compared with SAb+/GAg + patients, SAb-/GAg + patients presented with higher levels of albumin, lower levels of cholesterol and low density lipoprotein cholesterol (all p < .01), but similar pathological manifestations of kidney biopsy. Multivariate logistic analyses indicated that low albumin (0.79 [95%CI: 0.66-0.95], p = .01) and high cholesterol (1.81 [95%CI: 1.02-3.19], p = .04) were correlated with seropositivity of PLA2R antibody. SAb-/GAg + patients exhibited a significantly higher probability of CR (p = .03) than patients who were SAb+/GAg+. However, no difference was found in the PR rate. Cox regression analyses showed that compared to SAb+/GAg + patients, SAb-/GAg + was more predictive of complete remission (4.28 [95%CI: 1.01-18.17], p = .04). CONCLUSION: IMN with PLA2R staining on kidney biopsy but without serum PLA2R antibody has milder clinical manifestations and a better prognosis.

The impact of palliative care education and training program on the resident physicians.

BACKGROUND: Due to the advancements in medicine coupled with the aging population, palliative care has become widely needed. In many countries, medical students are trained in palliative care in their postgraduate courses. However, palliative care education is not available as an independent course or standardized training for residents in China. METHODS: This parallel randomized controlled trial was conducted in the Department of Internal Medicine, Beijing Chao-yang Hospital, Capital Medical University, between June 2016 and August 2017. The aim of the study was to explore the impact of the palliative care education and training program on 72 residents who were trained in standardization and were randomly divided into experimental and control groups at the ratio 1:1. The experimental group received resident physician standardized training and palliative care training program, while the control group received only standardized training. Standardized training included training in humanistic medical skills. The two groups were tested after training. A questionnaire survey was carried out to analyze the effect of palliative care education in humanistic medical skills. RESULTS: The total score of humanistic medical skills assessment of residents in the experimental group was higher compared to the control group (82.92±8.39 vs. 77.36±7.41, t =2.978, P=0.004). The experimental group performed better in terms of medical skills and the ability to care for dying patients. CONCLUSIONS: Palliative care education and training program should be required for residents as it is very useful. The purpose of palliative care education is to translate the knowledge in practice, truly implement the idea of palliative care, and relieve patients of terminal discomfort. The educational promotion of palliative care is of great value in China.

Main Risk Factors Related to Activities of Daily Living in Non-Dialysis Patients with Chronic Kidney Disease Stage 3-5: A Case-Control Study.

INTRODUCTION: Elderly people are at increased risk of falls, disability and death due to reduced functional reserve, decline in multiple systems functions, which affects their activities of daily living (ADL) and eventually develop into frailty. The ADL assessment is conducive to early detection to avoid further serious situations. Previous studies on patients' activities of daily living with chronic kidney disease (CKD) are mainly focused on dialysis patients. Little information is available on non-dialysis patients. PATIENTS AND METHODS: A total of 303 elderly patients with CKD stage 3-5 who were admitted to our hospital were selected. ADL evaluation was performed on patients at admission, with Barthel index (BI) as the evaluation tool. They were divided into two groups based on BI (≥60 and <60). Demographic information, lifestyle and clinical profile were collected. The risk factors related to ADL were analyzed by univariate and multivariate models. RESULTS: The data of 303 patients enrolled in this study were analyzed. The average age of patients was 84.48± 7.14 years and 62.05% were male. There were 88 patients (29.04%) in BI <60 group and 215 patients (70.96%) in the BI ≥60 group. The average age of subjects in the two groups was 87.47 ± 5.85 years and 83.26± 7.28 years, respectively. On univariate analysis, ADL impairment was associated with many factors, such as age, body mass index, blood lipid, heart rate, smoking history, Charlson comorbidity index (CCI), hemoglobin, serum albumin, BNP, eGFR, etc. Multivariate logistic regression showed that age (OR 1.08, 95% CI 1.00-1.17, P=0.0390), Charlson comorbidity index (OR 4.75, 95% CI 1.17-19.30, P=0.0295), and serum albumin (OR 0.80, 95% CI 0.70-0.92, P=0.0012) were the independent risk factors of ADL impairment. CONCLUSION: Decline of ADL in CKD patients was independently correlated with age, Charlson comorbidity index and serum albumin. ADL and its influential factors in the elderly CKD patients deserve further attention.

Simultaneous occurrence of splenic diffuse large B cell lymphoma and gastrointestinal stromal tumor in the stomach: a case report.

BACKGROUND: Although the primary malignant spleen tumor is relatively rare, lymphoma is the most common splenic malignancy. It can have quite different clinical manifestations that usually lead to relatively poor outcomes, and thus early and accurate diagnosis are of utmost importance. CASE PRESENTATION: The present study reports a case of a 67-year-old female with high fever, abnormal spleen (diagnosed by PET/CT) and no obvious lymph node enlargement. After being subjected to splenectomy, the patient was diagnosed with splenic diffuse large B cell lymphoma coexisting with gastrointestinal stromal tumor in the stomach. CONCLUSIONS: To our knowledge, splenic lymphoma accompanied by gastrointestinal stromal tumor in the stomach is rarely reported. This case report discusses the diagnosis and case management of a patient referring to the existing literature.

The expression of microRNA-23a regulates acute myocardial infarction in patients and in vitro through targeting PTEN.

Cardiovascular disease is responsible for one of the highest rates of fatality worldwide. The present study investigated the presence and influence of microRNA (miRNA)-23a in the regulation of acute myocardial infarction (AMI). A total of 6 patients with AMI and 6 normal volunteers without myocardial disease were included, and blood samples were taken to analyze the expression of miRNA­23a by reverse transcription­quantitative polymerase chain reaction. miRNA­23a expression in patients with AMI was downregulated compared with the normal group. In H9C2 cells treated with H2O2, upregulation of miRNA­23a expression increased the superoxide dismutase, glutathione and catalase activity levels, and suppressed the malonaldehyde activity level, as determined by ELISA. Western blot analysis and a caspase­3 substrate assay demonstrated that upregulation of miRNA­23a expression suppressed the Bcl­2­associated X (Bax)/Bcl­2 protein expression ratio, caspase­3 activity level and tumor suppressor p53 (p53) protein expression in H2O2­induced H9C2 cells. Furthermore, downregulation of phosphatase and tensin homolog (PTEN), by the PTEN inhibitor bpV(HOpic), increased miRNA­23a expression and suppressed the Bax/Bcl­2 protein expression ratio, caspase­3 activity level and p53 protein expression in H2O2­induced H9C2 cells. Therefore, the results of the present study indicate that the expression of miRNA­23a may regulate AMI through targeting PTEN in patients and in vitro, and PTEN/miRNA­23a may therefore be potential targets for the clinical treatment of AMI.

Interleukin-13 promotes expression of Alix to compromise renal tubular epithelial barrier function.

The epithelial barrier dysfunction plays a critical role in a number of kidney diseases. The mechanism is unclear. Alix is a protein involving in protein degradation in epithelial cells. This study aims to investigate that interleukin (IL)-13 inhibits Alix to compromise the kidney epithelial barrier function. In this study, the murine collecting duct cell line (M-1) was cultured in Transwell inserts to investigate the significance of Alix in compromising the epithelial barrier functions. T cell (Teff cells) proliferation assay was employed to assess the antigenicity of ovalbumin (OVA) that was transported across the M-1 monolayer barrier. The results showed that M-1 cells express Alix. Exposure to interleukin (IL)-13 markedly decreased the expression of Alix in M-1 cells, which compromised the M-1 monolayer barrier functions by showing the increases in the permeability to OVA. Over-expression of Alix abolished the IL-13-induced M-1 monolayer barrier dysfunction. Knockdown of Alix significantly increased M-1 monolayer permeability. The OVA collected from the Transwell basal chambers induced the OVA-specific T cell proliferation. We conclude that IL-13 compromises M-1 epithelial barrier functions via inhibiting Alix expression.