Identification of key genes for IgA nephropathy based on machine learning algorithm and correlation analysis of immune cells.

INTRODUCTION: The pathogenesis and progression mechanism of Immunoglobulin A nephropathy (IgAN) is not fully understood. There is a lack of panoramic analysis of IgAN immune cell infiltration and algorithms that are more efficient and accurate for screening key pathogenic genes. METHODS: RNA sequencing (RNA-seq) data sets on IgAN were downloaded from the Gene Expression Omnibus (GEO) database, including GSE93798, GSE35489, and GSE115857. The RNA-seq data set of kidney tissue as control samples were downloaded from the Genotype-Tissue Expression (GTEx) database. Three machine learning algorithms-weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO), and support vector machine-were used to identify the key pathogenic gene sets of the IgAN disease. The ssGSEA method was applied to calculate the immune cell infiltration (ICI) of IgAN samples, whereas the Spearman test was used for correlation analysis. The receiver operator characteristic curve (ROC) was used to evaluate the diagnostic efficacy of key genes. The correlation between the key genes and ICI was analyzed using the Spearman test. RESULTS: A total of 177 genes were screened out as differentially expressed genes (DEGs) for IgAN, including 135 up-regulated genes and 42 down-regulated genes. The DEGs were significantly enriched in the inflammatory- or immune-related pathways (gene sets). Activating transcription factor 3 (AFT3), C-X-C Motif Chemokine Ligand 6 (CXCL6), and v-fos FBJ murine osteosarcoma viral oncogene homolog B (FOSB) were identified using WGCNA, support vector machine, and LASSO algorithms. These three genes revealed good diagnostic efficacy in the training and test cohorts. The CXCL6 expression positively correlated with activated B cells and memory B cells. CONCLUSION: ATF3, FOSB, and CXCL6 genes were identified as potential biomarkers of IgAN. These three genes exhibited good diagnostic efficacy for IgAN. We described the landscape of immune cell infiltration for IgAN. Activated B cells and memory B cells were more highly expressed in the IgAN samples than in the control samples. CXCL6 seems crucial to the pathogenesis of IgAN and may induce IgAN by enriching immune cells. Our study may contribute to developing CXCL6 inhibitors that target B cells for IgAN therapy.

Combination therapy with DHA and BMSCs suppressed podocyte injury and attenuated renal fibrosis by modulating the TGF-ß1/Smad pathway in MN mice.

Artemisinin has immunomodulatory, anti-inflammatory, and antifibrotic effects. Some studies have demonstrated that artemisinins have a protective effect on the kidney. DHA is a derivative of artemisinin and has effects similar to those of artemisinin. Human bone marrow-derived mesenchymal stem cells (BMSCs) accelerate renal repair following acute injury. In the study, we investigated the effects of combination therapy with DHA and BMSCs on membranous nephropathy (MN) mice. The 24-h urinary protein, serum total cholesterol (TC) and triglyceride (TG) levels, and renal histopathology, were measured to evaluate kidney damage. Anti-PLA2R, IgG, and complement 3 (C3) were detected by ELISA. The expression levels of the podocyte injury-related proteins were analyzed by immunohistochemistry. The protein expression levels of α-SMA, ED-1, TGF-ß1, p-Smad2, and p-Smad3 were detected by western blot to analyze renal fibrosis and its regulatory mechanism. Results showed that combination therapy with DHA and BMSCs significantly ameliorated kidney damage in MN model mice by decreasing the levels of 24 h urinary protein, TC and TG. This combination therapy also improved renal histology and reduced the expression of IgG and C3 in the glomerulus. In addition, this combination therapy decreased the expression of podocin and nephrin and relieved renal fibrosis by downregulating α-SMA and ED-1. Furthermore, this combination therapy suppressed TGF-ß1 expression and Smad2/3 phosphorylation. This result (i.e., this combination therapy inhibited the TGF-ß1/Smad pathway) was also supported in vitro. Taken together, combination therapy with DHA and BMSCs ameliorated podocyte injury and renal fibrosis in MN mice by downregulating the TGFß1/Smad pathway.

Development and Application of Global Health Events-Mental Stress Scale for Assessment of Medical Staff's Acute Mental Stress Responses.

Background: Medical workers have been increasingly involved in emergent public health events, which can lead to severe stress. However, no standardized, officially recognized, unified tool exists for mental distress measurement in medical workers who experienced the public health events. Purpose: In the present study, we propose the Global Health Events-Mental Stress Scale (GHE-MSS), as a revised version of the Impact of Event Scale-Revision (IES-R), for assessment of medical workers' acute mental stress responses within one month and their chronic mental stress responses within six months after major health events. Patients and methods: The IES-R was slightly modified, developed, and its reliability and validity were tested using the Delphi survey, primary survey with 115 participants, formal survey with 300 participants, and clinical evaluation with 566 participants. Results: Exploratory factor analysis and confirmatory factor analysis confirmed a promising validity of the scale. The values of Cronbach's alpha coefficient, the Spearman-Brown coefficient, and the retested Cronbach's alpha coefficient of the scale applied for the clinical evaluation were 0.88, 0.87, and 0.98, respectively, which confirmed a good internal consistency and stability. The results of the goodness-of-fit test indicated a good adaptation of the model. A correlation analysis was conducted to assess the correlation between the GHE-MSS and the PCL-C, which had a correlation coefficient of 0.68 (P<0.01). Conclusion: GHE-MSS can be applied with a promising reliability and validity for the assessment of the acute mental stress response of medical workers experiencing public health events. This method can also be used for the screening of mental stress-associated disorders.

[Effect of moxibustion on renal function and hypercoagulable state in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis].

OBJECTIVE: To compare the effect of moxibustion combined with basic treatment and simple basic treatment on the clinical symptoms, renal function and hypercoagulable state in patients with idiopathic membranous nephropathy (IMN) of low to medium risk with spleen-kidney deficiency and blood stasis. METHODS: A total of 60 patients with IMN of low to medium risk with spleen-kidney deficiency and blood stasis were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 1 case dropped off). In the control group, the conventional basic treatment of anti-hypertension, regulating blood lipid and anti-coagulation was adopted. On the basis of the control group, moxibustion was applied at Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, once a day, 5 days a week continuously with 2 day interval. The treatment of 6 months was required in the both groups. Before treatment and 3 and 6 months into treatment, the total TCM syndrome score, the renal function indexes (24-hour urinary protein quantity [UTP], albumin [ALB], urea nitrogen [BUN] and creatinine [Scr]), the blood coagulation indexes (fibrinogen [FIB], D-Dimer [D-D], p-selection and von Willebrand factor [vWF]), total cholesterol (TC) and triacylglycerol (TG) levels were observed, and the therapeutic efficacy was evaluated on 3 and 6 months into treatment in the two groups. RESULTS: The effective rates of 3 and 6 months into treatment were 78.6% (22/28) and 89.3% (25/28) in the observation group, which were higher than 62.1% (18/29) and 75.9% (22/29) in the control group respectively (P<0.05). On 3 and 6 months into treatment, the total TCM syndrome scores were decreased compared before treatment in the both groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). On 3 months into treatment, the levels of UTP, FIB, D-D, P-selection and vWF were decreased (P<0.05), the level of ALB was increased (P<0.05) compared before treatment in the observation group; the levels of UTP and FIB were decreased compared before treatment in the control group (P<0.05); the level of ALB in the observation group was higher than that in the control group (P<0.05), the levels of FIB and vWF in the observation group were lower than those in the control group (P<0.05). On 6 months into treatment, the levels of UTP, FIB, D-D, P-selection, vWF, TC and TG were decreased (P<0.05), the levels of ALB were increased (P<0.05) compared before treatment in the both groups (P<0.05); the levels of UTP, FIB, D-D, P-selection, vWF, TC and TG in the observation group were lower than those in the control group, the level of ALB in the observation group was higher than that in the control group (P<0.05). CONCLUSION: Moxibustion combined with basic treatment can effectively improve the clinical symptoms, renal function and renal microcirculation in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis, the therapeutic effect is superior to the simple basic treatment.

[Correlation between hyponatremia and the severity of coronavirus disease 2019].

OBJECTIVE: To investigate the correlation between hyponatremia and the severity of coronavirus disease 2019 (COVID-19). METHODS: Clinical data of 12 patients with COVID-19 admitted to Shantou Central Hospital from January 23 to February 5 in 2020 were retrospectively analyzed, including gender, age, symptoms, lab test and clinical outcomes, to analyze the change trend of blood Na+ level in the patients with COVID-19. RESULTS: Among the 12 patients with COVID-19, there were 8 males and 4 females with the mean age of (38.0±16.3) years old, most of them were admitted to the hospital with cough and/or fever. All patients had a positive nucleic acid test for 2019 novel coronavirus (2019-nCoV), and were discharged after clinical treatment with oxygen therapy, antiviral, antibacterial, anti-inflammatory, and nutritional support. All patients were of ordinary type when they were admitted to the hospital. Among them, 1 patient turned into a severe case during the course of the disease, and 1 patient showed a tendency to become severe case. It was found that 10 patients without severe conversion had an average blood Na+ of (138.3±1.3) mmol/L at admission, and the lowest blood Na+ during the course of disease was (135.9±3.1) mmol/L. However, 2 patients who became severe and had a tendency to become severe disease (Na+ levels at admission were 140.0 mmol/L and 138.0 mmol/L, respectively) experienced hyponatremia during the course of the disease (the lowest blood Na+ levels were 129.0 mmol/L and 122.0 mmol/L). Further analysis showed that the lower serum Na+ level, the higher level of white blood cell count (WBC) and C-reactive protein (CRP), but serum Na+ level was consistent with the change trend of lymphocytes, suggesting that hyponatremia was closely correlated with severe inflammation reaction. CONCLUSIONS: Serum Na+ showed decreasing tendency during the development of COVID-19, and hyponatremia was closely related to the severity of COVID-19. It was necessary to pay great attention to the change trend of blood Na+ level. However, further research was needed to obtain more reliable conclusions and explorer the pathophysiological mechanisms.