rhFGF-21 accelerates corneal epithelial wound healing through the attenuation of oxidative stress and inflammatory mediators in diabetic mice.

Diabetic keratopathy, commonly associated with a hyperactive inflammatory response, is one of the most common eye complications of diabetes. The peptide hormone fibroblast growth factor-21 (FGF-21) has been demonstrated to have anti-inflammatory and antioxidant properties. However, whether administration of recombinant human (rh) FGF-21 can potentially regulate diabetic keratopathy is still unknown. Therefore, in this work, we investigated the role of rhFGF-21 in the modulation of corneal epithelial wound healing, the inflammation response, and oxidative stress using type 1 diabetic mice and high glucose-treated human corneal epithelial cells. Our experimental results indicated that the application of rhFGF-21 contributed to the enhancement of epithelial wound healing. This treatment also led to advancements in tear production and reduction in corneal edema. Moreover, there was a notable reduction in the levels of proinflammatory cytokines such as TNF-α, IL-6, IL-1ß, MCP-1, IFN-γ, MMP-2, and MMP-9 in both diabetic mouse corneal epithelium and human corneal epithelial cells treated with high glucose. Furthermore, we found rhFGF-21 treatment inhibited reactive oxygen species production and increased levels of anti-inflammatory molecules IL-10 and SOD-1, which suggests that FGF-21 has a protective role in diabetic corneal epithelial healing by increasing the antioxidant capacity and reducing the release of inflammatory mediators and matrix metalloproteinases. Therefore, we propose that administration of FGF-21 may represent a potential treatment for diabetic keratopathy.

Integrating carbon dots and gold/silver core-shell nanoparticles to achieve sensitive detection of dopamine with fluorometric/colorimetric dual signal.

Dopamine (DA) is a potent neuromodulator in the brain that affects a wide range of motivated behaviors. Abnormal concentration of DA is related to a variety of diseases. Hence, it is imperative to establish a rapid and precise method for quantifying DA. In this work, we integrate orange-yellow emissive carbon dots (CDs) with target-induced silver deposition on gold nanoparticles (Au NPs), forming gold/silver core-shell nanoparticles (Au@Ag NPs), to construct a fluorometric and colorimetric dual-signal sensor for sensitive detection of DA. Au NPs and silver ions (Ag+) have minimal effect on the fluorescence of CDs. DA can reduce the silver ions to Ag(0) on the surface of the Au NPs to form a silver shell, resulting in the blue-shift of the absorbance peak from 520 to 416 nm, which overlaps with the excitation spectrum of CDs. As a result, the system color turns from pink to orange-yellow, and the fluorescence of CDs is quenched due to the strong inner filter effect. The linear range of the colorimetry is 0.5-18 µM with a limit of detection (LOD) of 0.41 µM, while the linear range for the fluorometry method is 0.5-14 µM with a LOD of 0.021 µM. This method demonstrates notable advantages including a low detection limit, rapid response time, and straightforward operation in practical samples, showing great potential in biomedical analysis.

Dexmedetomidine for prevention of propofol injection pain upon induction of anesthesia: a meta-analysis.

PURPOSE: Propofol injection pain is a very common problem during the induction of general anesthesia. The purpose of this review is to evaluate the effectiveness of dexmedetomidine for the prevention of propofol injection pain so as to provide evidence for future clinical applications. METHODS: PubMed, Embase, Cochrane library, and Google Scholar databases were searched for relevant randomized controlled trials examining the use of dexmedetomidine for the prevention of propofol injection pain. The pooled risk ratio (RR) with corresponding 95% confidence intervals (CI) was calculated employing fixed-effects or random-effects models, depending upon the heterogeneity of the included trials. Because of the wide variety of interventions investigated, three comparisons of studies were established, dexmedetomidine compared with saline, lidocaine, and ketamine. RESULTS: Compared with saline, dexmedetomidine allowed more patients to experience no pain upon propofol injection (RR = 0.26, 95% CI (0.18, 0.38), P < 0.00001). Dexmedetomidine at doses of < 1 µg/kg did not show superiority in relieving propofol injecting pain compared with lidocaine (RR = 1.28, 95% CI (0.82, 2.00), P = 0.04). Dexmedetomidine is less effective than ketamine in reducing pain on propofol injection with a statistically significant P value of < 0.000010 (RR = 1.93, 95% CI (1.51, 2.47)). The report of adverse effects is rare, dexmedetomidine is a safe method to reduce propofol injection pain. CONCLUSION: Pretreatment with dexmedetomidine may be a useful alternative for reducing pain on propofol injection, even though dexmedetomidine is less effective than lidocaine and ketamine.

Inhibition of microRNA-376b Protects Against Renal Interstitial Fibrosis via Inducing Macrophage Autophagy by Upregulating Atg5 in Mice with Chronic Kidney Disease.

BACKGROUND/AIMS: Renal interstitial fibrosis (RIF) is a common feature that facilitates the progression of chronic kidney disease (CKD), and emerging lines of evidence suggest that microRNA-376b (miR-376b) is capable of promoting RIF. In this study, we examined collagen deposition in kidney tissues, the autophagy and mitochondrial reactive oxygen species (ROS) of macrophages, and the apoptosis of kidney fibroblasts (KFBs) after the promotion or suppression of endogenous miR-376b in cultured macrophages and renal fibroblasts obtained from mice with CKD. METHODS: FVB/N mice were prepared to establish a CKD model. A target prediction program and luciferase activity determination were used to confirm that autophagy-related gene 5 (Atg5) was a direct target of miR-376b. Macrophages and KFBs were isolated after the treatment to study the mechanisms and functions of miR-376b in relation to Atg5 in CKD. The autophagy level was determined, and KFB proliferation and apoptosis were assessed through MTT and EdU assays and flow cytometry, respectively. RESULTS: Atg5 was confirmed as a direct target of miR-376b. miR-376b and Atg5 exhibited high and low expression in kidney tissues from mice with CKD. The mice treated with a miR-376b inhibitor exhibited reduced collagen deposition, suppressed interstitial fibrosis, a higher level of autophagy, higher ROS production, enhanced apoptosis, and inhibited proliferation of KFBs, which suggested that the downregulation of miR-376b could exert beneficial effects on CKD through Atg5. CONCLUSION: miR-376b downregulation promotes macrophage autophagy to relieve RIF by negatively regulating Atg5 in mice with CKD. Thus, miR-376b might represent a potential focus of future investigations on treatments for CKD.

Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity.

BACKGROUND: IgA nephropathy (IgAN) is one of the most common forms of idiopathic glomerular diseases and might lead to end-stage kidney disease. Accurate and non-invasive biomarkers for early diagnosis are required for early intervention and consequent therapy for IgAN patients. Because variance in the disease incidence and predisposing genes of IgAN has been detected among different ethnicities, the ethnicity factor should be considered in IgAN biomarker discovery. The differences in the protein profiles and pathological mechanisms of IgAN in patients of Uygur ethnicity need to be clearly illustrated. METHODS: In this study, we used urinary proteomics to discover candidate biomarkers of IgAN in patients of Uygur ethnicity. The urinary proteins from Uygur normal control and Uygur IgAN patients were extracted and analyzed using 2D-LC-MS/MS and isobaric tags for relative and absolute quantitation (iTRAQ) analysis. RESULTS: A total of 277 proteins were found to be differentially represented in Uygur IgAN compared with the respective normal controls. The bioinformatics analysis revealed that the immune response, cell survival, and complement system were activated in Uygur IgAN. Many differentially expressed proteins were found to be related to nephropathy and kidney injuries. Four candidate biomarkers were validated by Western blot, and these results were consistent with the iTRAQ results. ICAM1, TIMP1, SERPINC1 and ADIPOQ were upregulated in Uygur IgAN. Bioinformatic analysis revealed that the increase of ICAM1 and TIMP1 might be caused by IgAN, but the increase of SERPINC1 and ADIPOQ might be caused by proteinuria. SERPINC1 and ICAM1 were identified as the candidate biomarkers with excellent area-under-the-curve (AUC) values (0.84) for distinguishing Uygur IgAN from normal controls. CONCLUSIONS: Using urinary proteomic analysis, we identified several candidate biomarkers for IgAN in patients of Uygur ethnicity. These results will prove helpful for exploring the pathological mechanism of IgAN in patients of Uygur ethnicity and for developing better treatments for these patients.

Analysing the mutational status of adenomatous polyposis coli (APC) gene in breast cancer.

BACKGROUND: Breast cancer is a heterogeneous disorder for which the underlying genetic basis remains unclear. We developed a method for identifying adenomatous polyposis coli (APC) mutations and we evaluated the possible association between APC genetic variants and breast cancer susceptibility. METHODS: Genomic DNA was extracted from tumor and matched peripheral blood samples collected from 89 breast cancer patients and from peripheral blood samples collected from 50 controls. All samples were tested for mutations in exons 1-14 and the mutation cluster region of exon 15 by HRM analysis. All mutations were confirmed by direct DNA sequencing. RESULTS: We identified a new single nucleotide polymorphism (SNP), c.465A>G (K155K), in exon 4 and seven known SNPs: c.573T>C (Y191Y) in exon 5, c.1005A>G (L335L) in exon 9, c.1458T>C (Y486Y) and c.1488A>T (T496T) in exon 11, c.1635G>A (A545A) in exon 13, and c.4479G>A (T1493T) and c.5465T>A (V1822D) in exon 15. The following alterations were found in 2, 1, 2, and 1 patients, respectively: c.465A>G, c.573T>C, c.1005A>G, and c.1488A>T. There was no observed association between breast cancer risk and any of these APC SNPs. CONCLUSIONS: APC mutations occur at a low frequency in Taiwanese breast cancer cases. HRM analysis is a powerful method for the detection of APC mutations in breast.

Epidermal Growth Factor and Intestinal Barrier Function.

Epidermal growth factor (EGF) is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.

Validating the Sensitivity of High-Resolution Melting Analysis for JAK2 V617F Mutation in the Clinical Setting.

BACKGROUND: Janus kinase 2 (JAK2) plays an important role in normal hematopoietic growth factor signaling. The detection of the JAK2 V617F mutation (c.1849GNT, GTC → TTC) is crucial for the diagnosis of myeloproliferative neoplasm (MPN) and has become the essential criteria for diagnosis of MPN by the WHO. High-resolution melt (HRM) curve analysis is a nongel-based, closed-tube method, in which PCR amplification and subsequent analysis are sequentially performed in the well, making it more convenient than other scanning methodologies. METHODS: We evaluated JAK2 V617F mutation by HRM. Twenty-nine patients diagnosed with MPN were examined. We studied the analytical sensitivity of the HRM analysis using real-time polymerase chain reaction (PCR) for identifying the JAK2 V617F mutation. Additionally, the sensitivity of HRM analysis and allele-specific PCR (AS-PCR) assay was compared. RESULTS: The JAK2 V617F mutation was successfully discriminated at an abundance of 6% or above in HRM analysis. Both HRM analysis and AS-PCR showed 100% accuracy with detection limits of 6% and 2.5%, respectively. CONCLUSION: HRM analysis is a fast, simple, reliable, and nonexpensive method for the detection of the JAK2 V617F mutation. However, more validation of the detection limits of HRM analysis should be performed before declaration of the analytic sensitivity of the method.

High-resolution melting analyses for genetic variants in ARID5B and IKZF1 with childhood acute lymphoblastic leukemia susceptibility loci in Taiwan.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL), a heterogeneous disease that includes multiple subtypes is defined by cell lineage and chromosome anomalies. Previous genome-wide association studies have reported several ARID5B and IKZF1 single nucleotide polymorphisms (SNPs) associated with the incidence of ALL. High-resolution melting (HRM) analysis is a rapid and convenient technique to detect SNPs; we thereby detected SNPs in ARID5B and IKZF1 genes. METHODS: We enrolled 79 pediatric ALL patients and 80 healthy controls. Polymorphic variants of IKZF1 (rs6964823, rs4132601, and rs6944602) and ARID5B (rs7073837, rs10740055, and rs7089424) were detected by HRM, and SNPs were analyzed for association with childhood ALL. RESULTS: The distribution of genotype rs7073837 in ARID5B significantly differed between ALL and controls (P=0.046), while those of IKZF1 (rs6964823, rs4132601, and rs6944602) and ARID5B (rs10740055 and rs7089424) did not. We analyzed the association for SNPs with B lineage ALL to find rs7073837 in ARID5B, conferring a higher risk for B lineage ALL (odds ratio, OR=1.70, 95% confidence interval, CI=1.01-2.87, P=0.049). CONCLUSION: HRM is a practical method to detect SNPs in ARID5B and IKZF1 genes. We found that rs7073837 in ARID5B correlated with a risk for childhood B lineage ALL.

Developing tools for identifying employer and employee satisfaction of nursing new graduates in China.

PURPOSE: Researchers developed evaluation tools measuring employment relevant satisfaction for nursing new graduates. The evaluation tools were designed to be relevant to nursing managers who make employment decisions and nursing new graduates who were just employed. METHODS: In-depth interviews and an expert panel were established to review the activities that evaluate the employee and employer satisfaction of nursing new graduates. Based on individual interviews and literature review, evaluation items were selected. A two-round Delphi study was then conducted from September 2008 to May 2009 with a panel of experts from a range of nursing colleges in China. RESULTS: The response rate was 100% and Kendall's W was 0.73 in the second round of Delphi study. After two rounds of Delphi surveys, a list of 5 employee satisfaction items and 4 employer satisfaction items was identified for nursing new graduates. CONCLUSIONS: The findings of this study identified a different but multidimensional set of factors for employment relevant satisfaction, which confirmed the importance of certain fundamental aspects of practice. We developed the evaluation tools to assess the employer and employee satisfaction of nursing new graduates, which provided a database for further study.

Effect of vitamin D supplementation during pregnancy on the Th1/Th2 cell balance of rat offspring.

Vitamin D has important functions in the immune system, and it may suppress the proliferation of T helper (Th) cells and modulate their cytokine production. In this study, we aimed to investigate the effects of maternal supplementation with different doses of vitamin D on the allergy status of the offspring. We gave pregnant female rats a low dose (48000IU/kg, equal to 800IU/d in human) and a high dose (240000IU/kg,equal to 4000IU/d in human) of vitamin D3 intramuscular injection on gestation day (GD)17, and we used an enzyme-linked immunosorbent assay (ELISA) to determine the levels of immune responsive cytokines including IL-4, IgE, and interferon gamma (IFN-gamma) in the offspring. On postnatal day (PND) 21, plasma IL-4 levels were elevated by 10.43% (p < 0.01) in the offspring from the high dose vitamin D3 group compared with the control group. And offspring plasma IL-4 levels in the low dose group decreased by 7.27% (p < 0.05) compared with the control dose group. We found that the offspring of mothers given a low dose of vitamin D3 had a 6.17% (p < 0.01) decrease in their plasma IgE levels compared to control animals, but the high dose of vitamin D3 showed no effect. The serum 25(OH)D3 levels were negatively correlated with the IL-4 (r = -0.561, p < 0.01) and IgE (r = -0.421, p < 0.05) levels of the offspring from the low dose group. In the lung tissues of the offspring of the high dose group, we observed thickening of the alveolar septa and more inflammatory cells compared with the control group and low dose group. Thickened alveolar septa were also found in the lung tissues of the offspring from the control group. We conclude that high dose vitamin D3 maternal supplementation during pregnancy induced an imbalance of Th1 and Th2 cells in their offspring resulting allergic and inflammatory response.

Lacidipine attenuates apoptosis via a caspase-3 dependent pathway in human kidney cells.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalised patients and has a poor prognosis. Therefore, new therapeutic strategies are anticipated. Lacidipine, a novel third-generation dihydropyridine calcium channel blocker, has been demonstrated effective for hypertension. However, its potential effect on renal injury remains unknown. In the present study, an in vitro model of renal ischemia reperfusion (I/R) injury was used to investigate the protective effect and underlying mechanisms of lacidipine on human kidney cell (HKC) apoptosis. METHODS: HKCs were subjected to adenosine triphosphate (ATP) depletion and recovery (0.01 µM AA, depletion for 2 h and recovery for 30 min), with or without lacidipine (1 µM and 10 µM, 24 h), then cell viability and apoptosis were determined using the cell counting kit-8 (CCK-8) assay and Annexin V flow cytometry. The expression of Bcl-2, Bax, and cytochrome c (cyt c) was examined by western blot. RESULTS: Antimycin A (AA) was found to induce apoptosis of HKCs. The proportion of early apoptosis and activity of caspase-3 peaked at 30 min after ATP depletion and recovery and were attenuated by lacidipine. The expression of cyt c and Bax was decreased, while that of Bcl-2 was increased significantly in lacidipine treated group. CONCLUSION: We conclude that lacidipine protects HKCs against apoptosis induced by ATP depletion and recovery by regulating the caspase-3 pathway.

Relationship between polymorphisms in vitamin D metabolism-related genes and the risk of rickets in Han Chinese children.

BACKGROUND: Vitamin D deficiency rickets is common in China. Genetic factors may play an important role in the susceptibility to rickets. Our study aimed to identify the relationship between three vitamin D-related genes (group specific component [GC], cytochrome P450, family 2, subfamily R, polypeptide 1 (CYP2R1), and 7-dehydrocholesterol reductase/nicotinamide-adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) and rickets in Han Chinese children from northeastern China. METHODS: A total of 506 Han children from northeastern China were enrolled in the current study. Twelve SNPs in three candidate genes were genotyped using the SNaPshot assay. Linear regression was used to examine the effect of 12 single-nucleotide polymorphisms (SNPs) on the risk of rickets. RESULTS: In our case-control cohort, six alleles of the 12 SNPs conferred a significantly increased risk of rickets in GC (rs4588 C, P = 0.003, OR: 0.583, 95% CI: 0.412-0.836; rs222020 C, P = 0.009, OR: 1.526, 95% CI: 1.117-2.0985; rs2282679 A, P = 0.010, OR: 0.636, 95% CI: 0.449-0.900; and rs2298849 C, P = 0.001, OR: 1.709, 95% CI: 1.250-2.338) and in CYP2R1 (rs10741657 G, P = 0.019, OR: 1.467, 95% CI: 1.070-2.011; and rs2060793 G, P = 0.023, OR: 0.689, 95% CI: 0.502-0.944). The results remained significant after adjustment for sex and body mass index. We further analyzed the effect of genotypes under three different genetic models. After using Bonferroni's method for multiple corrections, rs4588, rs2282679, and rs2298849 of the GC gene were significantly associated with rickets under the dominant (P =0.003 for rs4588, P =0.024 for rs2282679, and P =0.005 for rs2298849) and additive models (P = 0.006 for rs4588, P = 0.024 for rs2282679, and P = 0.005 for rs2298849). Haplotype analysis showed that the CAT haplotype of the GC gene (P = 0.005) and the GAA haplotype of the CYP2R1 gene (P = 0.026) were associated with susceptibility to rickets. CONCLUSIONS: This case-control study confirmed the strong effect of GC and CYP2R1 loci on rickets in Han children from northeastern China.

Combination therapy with 5-amino-4-imidazolecarboxamide riboside and arsenic trioxide in acute myeloid leukemia cells involving AMPK/TSC2/mTOR pathway.

The aim of this study was to demonstrate the effects of the AMP-activated protein kinase (AMPK) activator 5-amino-4-imidazolecarboxamide riboside (AICAR) in combination with arsenic trioxide (ATO) in acute myeloid leukemia cells and determine its mechanism of action. Cell lines were either exposed to each drug alone or both the drugs simultaneously. Cell proliferation, cell cycle and apoptosis were assessed. Combination index (CI) method was used to calculate the synergistic, additive, or antagonistic effects of these drugs. Western blot technique was used to study the signaling molecules in the AMPK/TSC2/mTOR pathway. Simultaneous exposure of HL-60 cells to AICAR and ATO indicated a synergism (CI < 1), whereas CI on NB4 cells was greater than 1. In HL-60, the change in expression level of each protein was quite significant in the presence of the combination as compared to that induced through any single agent. On the contrary, ATO weakened the effect of AICAR-mediated AMPK activation in NB4 cells. ATO caused a profound decrease in the protein level of PML/RARalpha in NB4 cells after 48 h, but there was no change with AICAR and the combination. The combination of AICAR and ATO produced a synergistic effect in the treatment of HL-60 cells involving AMPK/TSC2/mTOR pathway, and AICAR reduced ATO-mediated apoptotic death on acute promyelocytic leukemia NB4 cells.

Advances in understanding and treating diabetic kidney disease: focus on tubulointerstitial inflammation mechanisms.

Diabetic kidney disease (DKD) is a serious complication of diabetes that can lead to end-stage kidney disease. Despite its significant impact, most research has concentrated on the glomerulus, with little attention paid to the tubulointerstitial region, which accounts for the majority of the kidney volume. DKD's tubulointerstitial lesions are characterized by inflammation, fibrosis, and loss of kidney function, and recent studies indicate that these lesions may occur earlier than glomerular lesions. Evidence has shown that inflammatory mechanisms in the tubulointerstitium play a critical role in the development and progression of these lesions. Apart from the renin-angiotensin-aldosterone blockade, Sodium-Glucose Linked Transporter-2(SGLT-2) inhibitors and new types of mineralocorticoid receptor antagonists have emerged as effective ways to treat DKD. Moreover, researchers have proposed potential targeted therapies, such as inhibiting pro-inflammatory cytokines and modulating T cells and macrophages, among others. These therapies have demonstrated promising results in preclinical studies and clinical trials, suggesting their potential to treat DKD-induced tubulointerstitial lesions effectively. Understanding the immune-inflammatory mechanisms underlying DKD-induced tubulointerstitial lesions and developing targeted therapies could significantly improve the treatment and management of DKD. This review summarizes the latest advances in this field, highlighting the importance of focusing on tubulointerstitial inflammation mechanisms to improve DKD outcomes.

Follicular Helper T Cells and Follicular Regulatory T Cells Involved in Immune Disorders of Idiopathic Membranous Nephropathy.

OBJECTIVES: To investigate the role of follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells in immune disorders of idiopathic membranous nephropathy (IMN). METHODS: Peripheral blood samples of 41 IMN patients and 30 healthy controls were collected. The percentages of B cells, Tfh cells and Tfr cells were determined by flow cytometry, and the concentrations of IL-6, IL-17A, and IL-21 were determined by enzyme linked immunosorbent assay (ELISA). Furthermore, sorted Tfh cells or Tfr cells were co-cultured with B cells in vitro to detect the cell function. RESULTS: B cells, Tfh cells, Tfr cells, Tfr / Tfh ratio, IL-6, IL-17A, and IL-21 were significantly higher in IMN patients compared to controls. IMN patients had reduced percentages of CTLA-4+Tfr cells, increased percentages of PD-1+Tfr cells, and reduced CTLA-4+Tfr / PD-1+Tfr. In the co-culture system, IgG4, lactic acid, IL-6, IL-17A, and IL-21 were higher in Tfh cells derived from IMN patients, while IgG4, lactic acid, IL-6, IL-17A, and IL-21 were lower in Tfr cells derived from healthy patients. CONCLUSIONS: Tfh cells and Tfr cells are involved in immune disorders in IMN. This may be associated with abnormal expression of CTLA-4 and PD-1.

Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy.

The glomerular filtration barrier, comprising the inner layer of capillary fenestrated endothelial cells, outermost podocytes, and the glomerular basement membrane between them, plays a pivotal role in kidney function. Podocytes, terminally differentiated epithelial cells, are challenging to regenerate once injured. They are essential for maintaining the integrity of the glomerular filtration barrier. Damage to podocytes, resulting from intrinsic or extrinsic factors, leads to proteinuria in the early stages and eventually progresses to chronic kidney disease (CKD). Immune-mediated podocyte injury is a primary pathogenic mechanism in proteinuric glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and lupus nephritis with podocyte involvement. An extensive body of evidence indicates that podocytes not only contribute significantly to the maintenance of the glomerular filtration barrier and serve as targets of immune responses but also exhibit immune cell-like characteristics, participating in both innate and adaptive immunity. They play a pivotal role in mediating glomerular injury and represent potential therapeutic targets for CKD. This review aims to systematically elucidate the mechanisms of podocyte immune injury in various podocyte lesions and provide an overview of recent advances in podocyte immunotherapy. It offers valuable insights for a deeper understanding of the role of podocytes in proteinuric glomerular diseases, and the identification of new therapeutic targets, and has significant implications for the future clinical diagnosis and treatment of podocyte-related disorders.

Decision tree-based learning to predict patient controlled analgesia consumption and readjustment.

BACKGROUND: Appropriate postoperative pain management contributes to earlier mobilization, shorter hospitalization, and reduced cost. The under treatment of pain may impede short-term recovery and have a detrimental long-term effect on health. This study focuses on Patient Controlled Analgesia (PCA), which is a delivery system for pain medication. This study proposes and demonstrates how to use machine learning and data mining techniques to predict analgesic requirements and PCA readjustment. METHODS: The sample in this study included 1099 patients. Every patient was described by 280 attributes, including the class attribute. In addition to commonly studied demographic and physiological factors, this study emphasizes attributes related to PCA. We used decision tree-based learning algorithms to predict analgesic consumption and PCA control readjustment based on the first few hours of PCA medications. We also developed a nearest neighbor-based data cleaning method to alleviate the class-imbalance problem in PCA setting readjustment prediction. RESULTS: The prediction accuracies of total analgesic consumption (continuous dose and PCA dose) and PCA analgesic requirement (PCA dose only) by an ensemble of decision trees were 80.9% and 73.1%, respectively. Decision tree-based learning outperformed Artificial Neural Network, Support Vector Machine, Random Forest, Rotation Forest, and Naïve Bayesian classifiers in analgesic consumption prediction. The proposed data cleaning method improved the performance of every learning method in this study of PCA setting readjustment prediction. Comparative analysis identified the informative attributes from the data mining models and compared them with the correlates of analgesic requirement reported in previous works. CONCLUSION: This study presents a real-world application of data mining to anesthesiology. Unlike previous research, this study considers a wider variety of predictive factors, including PCA demands over time. We analyzed PCA patient data and conducted several experiments to evaluate the potential of applying machine-learning algorithms to assist anesthesiologists in PCA administration. Results demonstrate the feasibility of the proposed ensemble approach to postoperative pain management.

Integration of three machine learning algorithms identifies characteristic RNA binding proteins linked with diagnosis, immunity and pyroptosis of IgA nephropathy.

Objective: RNA-binding proteins (RBPs) are essential for most post-transcriptional regulatory events, which exert critical roles in nearly all aspects of cell biology. Here, characteristic RBPs of IgA nephropathy were determined with multiple machine learning algorithms. Methods: Our study included three gene expression datasets of IgA nephropathy (GSE37460, GSE73953, GSE93798). Differential expression of RBPs between IgA nephropathy and normal samples was analyzed via limma, and hub RBPs were determined through MCODE. Afterwards, three machine learning algorithms (LASSO, SVM-RFE, random forest) were integrated to determine characteristic RBPs, which were verified in the Nephroseq database. Immune cell infiltrations were estimated through CIBERSORT. Utilizing ConsensusClusterPlus, IgA nephropathy were classified based on hub RBPs. The potential upstream miRNAs were predicted. Results: Among 388 RBPs with differential expression, 43 hub RBPs were determined. After integration of three machine learning algorithms, three characteristic RBPs were finally identified (DDX27, RCL1, and TFB2M). All of them were down-regulated in IgA nephropathy than normal specimens, with the excellent diagnostic efficacy. Additionally, they were significantly linked to immune cell infiltrations, immune checkpoints, and pyroptosis-relevant genes. Based on hub RBPs, IgA nephropathy was stably classified as two subtypes (cluster 1 and 2). Cluster 1 exhibited the relatively high expression of pyroptosis-relevant genes and characteristic RBPs. MiR-501-3p, miR-760, miR-502-3p, miR-1224-5p, and miR-107 were potential upstream miRNAs of hub RBPs. Conclusion: Collectively, our findings determine three characteristic RBPs in IgA nephropathy and two RBPs-based subtypes, and thus provide a certain basis for further research on the diagnosis and pathogenesis of IgA nephropathy.

Rapid diagnosis of diabetes based on ResNet and Raman spectroscopy.

Diabetes mellitus is a global public health problem, and the epidemic situation in China is particularly serious. The prevalence of the disease has been increasing in recent years, and the number of patients is the highest in the world. Diabetes has become another chronic non-communicable disease that seriously endangers the health of our people after cardiovascular and cerebrovascular diseases and tumors. In this study, urine sample data were collected from 37 diabetic patients and 37 healthy volunteers using Raman spectroscopy. The collected data were preprocessed using an adaptive iterative reweighted penalized least squares (airPLS) algorithm and a polynomial Savitzky-Golay smoothing algorithm. After extracting features using principal component analysis (PCA) dimensionality reduction algorithm, ResNet, support vector machine (SVM) and linear discriminant analysis (LDA) classification models were selected to classify and identify diabetic patients and healthy controls. The results show that ResNet has the best discrimination effect, and the average accuracy, recall and F1-score can reach 84.28%, 86.20% and 84.02% respectively after five cross-validations, and the area under the subject working characteristic (ROC) curve is 0.93. The experimental results show that the model established in this paper is simple to operate, highly accurate and has good reference value for rapid screening of diabetes.