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Objective: As the prevalence of diabetes steadily increases, the burden of diabetic kidney disease (DKD) is also intensifying. In response, we have utilized a 10-year diabetes cohort from our medical center to train machine learning-based models for predicting DKD and interpreting relevant factors. Methods: Employing a large dataset from 73,101 hospitalized type 2 diabetes patients at The First Affiliated Hospital of Zhengzhou University, we analyzed demographic and medication data. Machine learning models, including XGBoost, CatBoost, LightGBM, Random Forest, AdaBoost, GBDT (gradient boosting decision tree), and SGD (stochastic gradient descent), were trained on these data, focusing on interpretability by SHAP. SHAP explains the output of the models by assigning an importance value to each feature for a particular prediction, enabling a clear understanding of how individual features influence the prediction outcomes. Results: The XGBoost model achieved an area under the curve (AUC) of 0.95 and an area under the precision-recall curve (AUPR) of 0.76, while CatBoost recorded an AUC of 0.97 and an AUPR of 0.84. These results underscore the effectiveness of these models in predicting DKD in patients with type 2 diabetes. Conclusions: This study provides a comprehensive approach for predicting DKD in patients with type 2 diabetes, employing machine learning techniques. The findings are crucial for the early detection and intervention of DKD, offering a roadmap for future research and healthcare strategies in diabetes management. Additionally, the presence of non-diabetic kidney diseases and diabetes with complications was identified as significant factors in the development of DKD.
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Acute kidney injury (AKI) is a major public health problem worldwide that still lacks effective treatments. Recent studies have suggested that ferroptosis is a key mediator of AKI due to its activation of lipid peroxidation. Therefore, we hypothesized that antiferroptosis agents might be a novel potential therapeutic strategy for AKI. Herein, we demonstrated that liquiritigenin (LG), an active ingredient of liquorice, improves renal function by inhibiting vitamin K epoxide reductase complex subunit 1 (VKORC1)-mediated ferroptosis, both in vivo and in vitro. In a folic acid-induced murine AKI model, after a single pre-treatment intravenous injection, LG markedly alleviated the loss of renal function through suppressing ferroptosis induced by iron accumulation. LG prevented mitochondrial morphological changes and upregulated glutathione and glutathione peroxidase 4 levels, while downregulating malonaldehyde and divalent iron levels. An in vitro RNA-sequence analysis suggested that the protective role of LG may involve upregulation of VKORC1. Moreover, knockdown of VKORC1 diminished the renal protective and antiferroptosis roles of LG. Collectively, our findings demonstrated that LG protected against AKI by inhibiting VKORC1-mediated ferroptosis. This suggests that inhibiting ferroptosis might be a novel therapeutic approach in the future.
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Lesión Renal Aguda , Modelos Animales de Enfermedad , Ferroptosis , Flavanonas , Vitamina K Epóxido Reductasas , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/prevención & control , Animales , Flavanonas/farmacología , Ferroptosis/efectos de los fármacos , Masculino , Vitamina K Epóxido Reductasas/genética , Glycyrrhiza/química , Ratones , Ratones Endogámicos C57BL , Fitoterapia , Hierro/metabolismo , HumanosRESUMEN
PURPOSE: The extent of tumor regression varies widely among locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME). The purpose of this retrospectively study is to assess prognostic factors in LARC patients with NCRT, and further to analyze survival outcomes in patients with different tumor regression grades (TRGs). METHODS: This study includes LARC patients who underwent NCRT and TME at our institution. We retrospectively analyzed the clinicopathological characteristics and survival of all patients, and performed subgroup analysis for patients with different TRGs. Survival differences were compared using the Kaplan-Meier method and the log rank test. Additionally, a multiple Cox proportional hazard model was used to identify independent prognostic factors. RESULTS: The study included 393 patients, with 21.1%, 26.5%, 45.5%, and 6.9% achieving TRG 0, TRG 1, TRG 2, and TRG 3, respectively. The overall survival (OS) rate and disease-free survival (DFS) rate for all patients were 89.4% and 70.7%, respectively. Patients who achieved TRG 0-3 had different 5-year OS rates (96.9%, 91.1%, 85.2%, and 68.8%, P = 0.001) and 5-year DFS rates (80.8%, 72.4%, 67.0%, 55.8%, P = 0.031), respectively. Multivariate analyses showed that the neoadjuvant rectal (NAR) score was an independent prognostic indicator for both overall survival (OS) (HR = 4.040, 95% CI = 1.792-9.111, P = 0.001) and disease-free survival (DFS) (HR = 1.971, 95% CI = 1.478-2.628, P Ë 0.001). In the subgroup analyses, the NAR score was found to be associated with DFS in patients with TRG 1 and TRG 2. After conducting multivariate analysis, it was found that ypT stage was a significant predictor of DFS for TRG 1 patients (HR = 4.384, 95% CI = 1.721-11.168, P = 0.002). On the other hand, ypN stage was identified as the dominant prognostic indicator of DFS for TRG 2 patients (HR = 2.795, 95% CI = 1.535-5.091, P = 0.001). However, none of these characteristics was found to be correlated with survival in patients with TRG 0 or TRG 3. CONCLUSION: NAR score, in particular, appears to be the most powerful prognostic factor. It is important to consider various prognostic predictors for patients with different TRGs.
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Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Supervivencia sin Enfermedad , Adulto , Quimioradioterapia , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis MultivarianteRESUMEN
The mechanisms underlying the complex correlation between immunoglobulin A nephropathy (IgAN) and inflammatory bowel disease (IBD) remain unclear. This study aimed to identify the optimal cross-talk genes, potential pathways, and mutual immune-infiltrating microenvironments between IBD and IgAN to elucidate the linkage between patients with IBD and IgAN. The IgAN and IBD datasets were obtained from the Gene Expression Omnibus (GEO). Three algorithms, CIBERSORTx, ssGSEA, and xCell, were used to evaluate the similarities in the infiltrating microenvironment between the two diseases. Weighted gene co-expression network analysis (WGCNA) was implemented in the IBD dataset to identify the major immune infiltration modules, and the Boruta algorithm, RFE algorithm, and LASSO regression were applied to filter the cross-talk genes. Next, multiple machine learning models were applied to confirm the optimal cross-talk genes. Finally, the relevant findings were validated using histology and immunohistochemistry analysis of IBD mice. Immune infiltration analysis showed no significant differences between IBD and IgAN samples in most immune cells. The three algorithms identified 10 diagnostic genes, MAPK3, NFKB1, FDX1, EPHX2, SYNPO, KDF1, METTL7A, RIDA, HSDL2, and RIPK2; FDX1 and NFKB1 were enhanced in the kidney of IBD mice. Kyoto Encyclopedia of Genes and Genomes analysis showed 15 mutual pathways between the two diseases, with lipid metabolism playing a vital role in the cross-talk. Our findings offer insights into the shared immune mechanisms of IgAN and IBD. These common pathways, diagnostic cross-talk genes, and cell-mediated abnormal immunity may inform further experimental studies.
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Glomerulonefritis por IGA , Enfermedades Inflamatorias del Intestino , Humanos , Animales , Ratones , Glomerulonefritis por IGA/genética , Riñón , Algoritmos , Perfilación de la Expresión Génica , Enfermedades Inflamatorias del Intestino/genética , Hidroxiesteroide Deshidrogenasas , ProteínasRESUMEN
Background: This study aimed to establish and validate a prognostic model based on immune-related genes (IRGPM) for predicting disease-free survival (DFS) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy, and to elucidate the immune profiles associated with different prognostic outcomes. Methods: Transcriptomic and clinical data were sourced from the Gene Expression Omnibus (GEO) database and the West China Hospital database. We focused on genes from the RNA immune-oncology panel. The elastic net approach was employed to pinpoint immune-related genes significantly impacting DFS. We developed the IRGPM for rectal cancer using the random forest technique. Based on the IRGPM, we calculated prognostic risk scores to categorize patients into high-risk and low-risk groups. Comparative analysis of immune characteristics between these groups was conducted. Results: In this study, 407 LARC samples were analyzed. The elastic net identified a signature of 20 immune-related genes, forming the basis of the IRGPM. Kaplan-Meier survival analysis revealed a lower 5-year DFS in the high-risk group compared to the low-risk group. The receiver operating characteristic (ROC) curve affirmed the model's robust predictive capability. Validation of the model was performed in the GSE190826 cohort and our institution's cohort. Gene expression differences between high-risk and low-risk groups predominantly related to cytokine-cytokine receptor interactions. Notably, the low-risk group exhibited higher immune scores. Further analysis indicated a greater presence of activated B cells, activated CD8 T cells, central memory CD8 T cells, macrophages, T follicular helper cells, and type 2 helper cells in the low-risk group. Additionally, immune checkpoint analysis revealed elevated PDCD1 expression in the low-risk group. Conclusions: The IRGPM, developed through random forest and elastic net methodologies, demonstrates potential in distinguishing DFS among LARC patients receiving standard treatment. Notably, the low-risk group, as defined by the IRGPM, showed enhanced activation of adaptive immune responses within the tumor microenvironment.
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AIM: Cannabinoid receptors are components of the endocannabinoid system that affect various physiological functions. We aim to investigate the effect of cannabinoid receptor modulation on kidney disease. METHODS: PubMed, Web of Science databases, and EMBASE were searched. Articles selection, data extraction and quality assessment were independently performed by two investigators. The SYRCLE's RoB tool was used to assess the risk of study bias, and pooled SMD using a random-effect model and 95% CIs were calculated. Subgroup analyses were conducted in preselected subgroups, and publication bias was evaluated. We compared the effects of CB1 and CB2 antagonists and/or knockout and agonists and/or genetic regulation on renal function, blood glucose levels, body weight, and pathological damage-related indicators in different models of chronic and acute kidney injury. RESULTS: The blockade or knockout of CB1 could significantly reduce blood urea nitrogen [SMD,- 1.67 (95% CI - 2.27 to - 1.07)], serum creatinine [SMD, - 1.88 (95% CI - 2.91 to - 0.85)], and albuminuria [SMD, - 1.60 (95% CI - 2.16 to - 1.04)] in renal dysfunction animals compared with the control group. The activation of CB2 group could significantly reduce serum creatinine [SMD, - 0.97 (95% CI - 1.83 to - 0.11)] and albuminuria [SMD, - 2.43 (95% CI - 4.63 to - 0.23)] in renal dysfunction animals compared with the control group. CONCLUSIONS: The results suggest that targeting cannabinoid receptors, particularly CB1 antagonists and CB2 agonists, can improve kidney function and reduce inflammatory responses, exerting a renal protective effect and maintaining therapeutic potential in various types of kidney disease.
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Background: Diabetic retinopathy (DR) is a risk factor for diabetic kidney disease (DKD). Whether the duration, especially the short-term duration, of DR is associated with the development and progression of DKD remains unclear. Materials and Methods: A retrospective study and two-sample Mendelian randomization (MR) analysis were conducted. Kidney disease was defined by the urinary albumin-to-creatinine ratio (ACR) and the estimated glomerular filtration rate (eGFR). DR was diagnosed by an expert ophthalmologist by using a digital fundus camera. Binary and ordinal logistic regression analyses were performed. A restricted cubic spline was utilized to detect nonlinear associations. Summary statistics for DR- and DKD-associated single-nuclear polymorphisms (SNPs) were extracted from the FinnGen and the UK Biobank consortia. Results: A total of 2674 patients with type 2 diabetes mellitus (T2DM) and type 2 diabetic kidney disease (T2DKD) were included. The prevalence and mean duration of DR increased with elevation of ACR and decline in eGFR. Renal function was significantly reduced in patients with DR in the fifth year of life. Binary and ordinal logistic regression showed that each 1-year increase in DR duration was associated with a 19% risk increase in the development of DKD, 16% in the elevation of ACR, and 21% in the decline of renal function. MR estimates indicated that DR was causally associated with DKD development, with an odds ratio of 2.89. Conclusions: DR and the duration of DR were independent risk factors for the development and progression of DKD. The short-term duration of DR may be associated with DKD development. DR had a statistically significant effect on DKD.
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BACKGROUND: Diabetic nephropathy (DN) is a common systemic microvascular complication of diabetes and a leading cause of chronic kidney disease worldwide. Urinary extracellular vesicles (uEVs), which are natural nanoscale vesicles that protect RNA from degradation, have the potential to serve as an invasive diagnostic biomarker for DN. METHODS: We enrolled 24 participants, including twelve with renal biopsy-proven T2DN and twelve with T2DM, and isolated uEVs using ultracentrifugation. We performed microarrays for mRNAs, lncRNAs, and circRNAs in parallel, and Next-Generation Sequencing for miRNAs. Differentially expressed RNAs (DE-RNAs) were subjected to CIBERSORTx, ssGSEA analysis, GO enrichment, PPI network analysis, and construction of the lncRNA/circRNA-miRNA-mRNA regulatory network. Candidate genes and potential biomarker RNAs were validated using databases and machine learning models. RESULTS: A total of 1684 mRNAs, 126 lncRNAs, 123 circRNAs and 66 miRNAs were found in uEVs in T2DN samples compared with T2DM. CIBERSORTx revealed the involvement of uEVs in immune activity and ssGSEA explored possible cell or tissue sources of uEVs. A ceRNA co-expression and regulation relationship network was constructed. Candidate genes MYO1C and SP100 mRNA were confirmed to be expressed in the kidney using Nephroseq database, scRNA-seq dataset, and Human Protein Atlas database. We further selected 2 circRNAs, 2 miRNAs, and 2 lncRNAs from WGCNAs and ceRNAs and demonstrated their efficacy as potential diagnostic biomarkers for T2DN using machine learning algorithms. CONCLUSIONS: This study reported, for the first time, the whole-transcriptome genetic resources found in urine extracellular vesicles of T2DN patients. The results provide additional support for the possible interactions, and regulators between RNAs from uEVs themselves and as potential biomarkers in DN.
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Persistent room temperature phosphorescent materials with unique mechanical properties and robust optical properties have great potential in flexible electronics and photonics. However, developing such materials remains a formidable challenge. Here, we present highly stretchable, lightweight, and multicolored persistent luminescence elastomers, produced by incorporating ionic room temperature phosphorescent polymers and polyvinyl alcohol into a polydimethylsiloxane matrix. These prepared elastomers exhibit high optical transparency in daylight and emit bright persistent luminescence after the removal of 365 nm excitation. The homogeneous distribution of polymers within the matrix has been confirmed by confocal fluorescence microscopy, scanning electron microscopy, and atomic force microscopy. Mechanical property investigations revealed that the prepared persistent luminescence elastomers possess satisfactory stretchability. Impressively, these elastomers maintain robust optical properties even under extensive and repeated mechanical deformations, a characteristic previously unprecedented. These fantastic features make these persistent luminescence elastomers ideal candidates for potential applications in wearable devices, flexible displays, and anti-counterfeiting.
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Acute kidney injury (AKI) is a prevalent pathological condition that is characterized by a precipitous decline in renal function. In recent years, a growing body of studies have demonstrated that renal maladaptation following AKI results in chronic kidney disease (CKD). Therefore, targeting the transition of AKI to CKD displays excellent therapeutic potential. However, the mechanism of AKI to CKD is mediated by multifactor, and there is still a lack of effective treatments. Ferroptosis, a novel nonapoptotic form of cell death, is believed to have a role in the AKI to CKD progression. In this study, we retrospectively examined the history and characteristics of ferroptosis, summarized ferroptosis's research progress in AKI and CKD, and discussed how ferroptosis participates in regulating the pathological mechanism in the progression of AKI to CKD. Furthermore, we highlighted the limitations of present research and projected the future evolution of ferroptosis. We hope this work will provide clues for further studies of ferroptosis in AKI to CKD and contribute to the study of effective therapeutic targets to prevent the progression of kidney diseases.
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Lesión Renal Aguda , Ferroptosis , Insuficiencia Renal Crónica , Humanos , Ferroptosis/genética , Estudios Retrospectivos , Insuficiencia Renal Crónica/patología , Lesión Renal Aguda/metabolismo , Riñón/patologíaRESUMEN
[This corrects the article DOI: 10.3389/fendo.2023.1081543.].
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Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are recommended for type 2 diabetes mellitus patients with impaired renal function, but the actual situation of SGLT2i using is unclear. Therefore, in this real-world study, we analyzed the treatment scheme and clinical characteristics of SGLT2i in patients with diabetic kidney disease (DKD). We included DKD patients hospitalized in the First Affiliated Hospital of Zhengzhou University from October 2017 to March 2020. The Apriori algorithm of association rules was used to analysis treatment scheme prescribing SGLT2i and other different combinations of hypoglycemic drugs. SGLT2i was used in 781 (12.3%) of 6336 DKD patients, both number and proportion of patients using SGLT2i increased from 2017 to 2020 (1.9% to 33%). Nighty-eight percent of all DKD patients using SGLT2i were combined with other glucose-lowering agents, and insulin, metformin and alpha-glucosidase inhibitors are most commonly used in combination with hypoglycemic drugs. Multivariate analysis showed that compared with non-SGLT2i group, patients using SGLT2i were associated with younger age, higher BMI, higher HbA1c, preserved kidney function, dyslipidemia and combined with ACEI/ARB and statins. In this real-world study, use of SGLT2i in DKD patients is still low. Most patients performed younger age and in the early stages of chronic kidney disease with poor glycemic control. Clinical inertia should be overcome to fully exert the cardiorenal protective effects of SGLT2 inhibitors, with attention to rational drug use.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa/uso terapéutico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , SodioRESUMEN
Background: Peritonitis is considered as one of the most serious complications that cause hospitalization in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). There is limited evidence on the impact of the parathyroid hormone (PTH) on the first peritoneal dialysis (PD)-associated peritonitis episode. We aimed to investigate the influence of serum intact parathyroid hormone (iPTH) on peritonitis in patients undergoing PD. Methods: This was a retrospective cohort study. Patients undergoing initial CAPD from a single center in China were enrolled. The baseline characteristics and clinical information were recorded. The primary outcome of interest was the occurrence of the first PD-associated peritonitis episode. Five Cox proportional hazard models were constructed in each group set. In group set 1, all participants were divided into three subgroups by tertiles of the serum concentration of iPTH; in group set 2, all participants were divided into three subgroups based on the serum concentration of iPTH with 150 pg/ml interval (<150, 150-300, and >300 pg/ml). Hazard ratios and 95% confidence intervals (CIs) were calculated for each model. The multivariate linear regression analysis elimination procedure assessed the association between the clinical characteristics at baseline and the iPTH levels. Restricted cubic spline models were constructed, and stratified analyses were also conducted. Results: A total of 582 patients undergoing initial PD (40% women; mean age, 45.1 ± 11.5 years) from a single center in China were recruited. The median follow-up duration was 25.3 months. Multivariate Cox regression analysis showed that, in the fully adjusted model, a higher serum iPTH level (tertile 3, iPTH >300 pg/ml) was significantly associated with a higher risk of PD-associated peritonitis at 3 years [tertile 3: hazard ratio (HR) = 1.53, 95%CI = 1.03-2.55, p = 0.03; iPTH > 300 pg/ml: HR = 1.57, 95%CI = 1.08-2.27, p = 0.02]. The hazard ratio for every 100 pg/ml increase in serum iPTH level was 1.12 (95%CI = 1.05-1.20, p < 0.01) in the total cohort when treating iPTH as a continuous variable. Conclusions: An elevated iPTH level was significantly associated with an increased risk of peritonitis in patients undergoing CAPD.
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Diálisis Peritoneal Ambulatoria Continua , Peritonitis , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Diálisis Peritoneal Ambulatoria Continua/métodos , Estudios Retrospectivos , Peritonitis/epidemiología , Peritonitis/etiología , Peritonitis/terapia , Hormona Paratiroidea , Modelos de Riesgos ProporcionalesRESUMEN
Organic room-temperature phosphorescent (RTP) materials exhibiting reversible changes in optical properties upon exposure to external stimuli have shown great potential in diverse optoelectronic fields. Particularly, dynamic manipulation of response behaviors for such materials is of fundamental significance, but it remains a formidable challenge. Herein, a series of RTP polymers were prepared by incorporating phosphorescent rotors into polymer backbone, and these materials show color-tunable persistent luminescence upon excitation at different wavelengths. Experimental results and theoretical calculations revealed that the various molecular conformations of monomers are responsible for the excitation wavelength-dependent (Ex-De) RTP behavior. Impressively, after gaining insights into the underlying mechanism, dynamic control of Ex-De RTP behavior was achieved through thermal energy driven molecular rotations of monomers. Eventually, we demonstrate the practical applications of these amorphous polymers in anti-counterfeiting areas. These findings open new opportunities for the control of response behaviors of smart-responsive RTP materials through external stimuli rather than conventional covalent modification method.
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Chronic cerebral hypoperfusion (CCH) is one of the main pathophysiological markers of cognitive impairment in central nervous system diseases. Mitochondria are cores of energy generation and information process. Mitochondrial dysfunction is the key upstream factors of CCH induced neurovascular pathology. Increasing studies explored the molecular mechanisms of mitochondrial dysfunction and self-repair for effective targets to improve CCH-related cognitive impairment. The clinical efficacy of Chinese herbal medicine in the treatment of CCH induced cognitive impairment is definite. Existed evidences from pharmacological studies have further proved that, Chinese herbal medicine could improve mitochondrial dysfunction and neurovascular pathology after CCH by preventing calcium overload, reducing oxidative stress damage, enhancing antioxidant capacity, inhibiting mitochondria-related apoptosis pathway, promoting mitochondrial biogenesis and preventing excessive activation of mitophagy. Besides, CCH mediated mitochondrial dysfunction is one of the fundamental causes for neurodegeneration pathology aggravation. Chinese herbal medicine also has great potential therapeutic value in combating neurodegenerative diseases by targeting mitochondrial dysfunction.
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Colorectal cancer (CRC) is one of the most lethal and common malignancies in the world. Chemotherapy has been the conventional treatment for metastatic CRC (mCRC) patients. However, the effects of chemotherapy have been unsatisfactory. With the advent of targeted therapy, the survival of patients with CRC have been prolonged. Over the past 20 years, targeted therapy for CRC has achieved substantial progress. However, targeted therapy has the same challenge of drug resistance as chemotherapy. Consequently, exploring the resistance mechanism and finding strategies to address the resistance to targeted therapy, along with searching for novel effective regimens, is a constant challenge in the mCRC treatment, and it is also a hot research topic. In this review, we focus on the current status on resistance to existing targeted therapies in mCRC and discuss future developments.
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Antineoplásicos , Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Neoplasias Colorrectales/patología , Neoplasias del Colon/tratamiento farmacológico , Terapia Molecular DirigidaRESUMEN
BACKGROUND: RNA methylation is a widely known post-transcriptional regulation which exists in many cancer and immune system diseases. However, the potential role and crosstalk of five types RNA methylation regulators in diabetic nephropathy (DN) and immune microenvironment remain unclear. METHODS: The mRNA expression of 37 RNA modification regulators and RNA modification regulators related genes were identified in 112 samples from 5 Gene Expression Omnibus datasets. Nonnegative Matrix Factorization clustering method was performed to determine RNA modification patterns. The ssGSEA algorithms and the expression of human leukocyte antigen were employed to assess the immune microenvironment characteristics. Risk model based on differentially expression genes responsible for the modification regulators was constructed to evaluate its predictive capability in DN patients. Furthermore, the results were validated by using immunofluorescence co-localizations and protein experiments in vitro. RESULTS: We found 24 RNA methylation regulators were significant differently expressed in glomeruli in DN group compared with control group. Four methylation-related genes and six RNA regulators were introduced into riskScore model using univariate Logistic regression and integrated LASSO regression, which could precisely distinguish the DN and healthy individuals. Group with high-risk score was associated with high immune infiltration. Three distinct RNA modification patterns were identified, which has significant differences in immune microenvironment, biological pathway and eGFR. Validation analyses showed the METTL3, ADAR1, DNMT1 were upregulated whereas YTHDC1 was downregulated in DN podocyte cell lines comparing with cells cultured by the normal glucose. CONCLUSION: Our study reveals that RNA methylation regulators and immune infiltration regulation play critical roles in the pathogenesis of DN. The bioinformatic analyses combine with verification in vitro could provide robust evidence for identification of predictive RNA methylation regulators in DN.
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Diabetes Mellitus , Nefropatías Diabéticas , Humanos , Metilación , Nefropatías Diabéticas/genética , ARN , Algoritmos , Línea Celular , MetiltransferasasRESUMEN
Background: Growing evidence indicates that non-alcoholic fatty liver disease (NAFLD) is related to the occurrence and development of diabetic nephropathy (DN). This bioinformatics study aimed to explore optimal crosstalk genes and related pathways between NAFLD and DN. Methods: Gene expression profiles were downloaded from Gene Expression Omnibus. CIBERSORT algorithm was employed to analyze the similarity of infiltrating immunocytes between the two diseases. Protein-protein interaction (PPI) co-expression network and functional enrichment analysis were conducted based on the identification of common differentially expressed genes (DEGs). Least absolute shrinkage and selection operator (LASSO) regression and Boruta algorithm were implemented to initially screen crosstalk genes. Machine learning models, including support vector machine, random forest model, and generalized linear model, were utilized to further identify the optimal crosstalk genes between DN and NAFLD. An integrated network containing crosstalk genes, transcription factors, and associated pathways was developed. Results: Four gene expression datasets, including GSE66676 and GSE48452 for NAFLD and GSE30122 and GSE1009 for DN, were involved in this study. There were 80 common DEGs between the two diseases in total. The PPI network built with the 80 common genes included 77 nodes and 83 edges. Ten optimal crosstalk genes were selected by LASSO regression and Boruta algorithm, including CD36, WIPI1, CBX7, FCN1, SLC35D2, CP, ZDHHC3, PTPN3, LPL, and SPP1. Among these genes, LPL and SPP1 were the most significant according to NAFLD-transcription factor network. Five hundred twenty-nine nodes and 1,113 edges comprised the PPI network of activated pathway-gene. In addition, 14 common pathways of these two diseases were recognized using Gene Ontology (GO) analysis; among them, regulation of the lipid metabolic process is closely related to both two diseases. Conclusions: This study offers hints that NAFLD and DN have a common pathogenesis, and LPL and SPP1 are the most relevant crosstalk genes. Based on the common pathways and optimal crosstalk genes, our proposal carried out further research to disclose the etiology and pathology between the two diseases.
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Diabetes Mellitus , Nefropatías Diabéticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Perfilación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Enfermedad del Hígado Graso no Alcohólico/genética , Factores de Transcripción/genéticaRESUMEN
Chronic hepatitis B is one of the common infectious diseases in the world, with a wide epidemic range and strong contagiousness, which is difficult to completely eradicate. From July 2020 to April 2022, 142 patients with hepatitis B who were admitted to tertiary hospitals were selected and randomly divided into 2 cases, with 71 cases per case. The control group adopts a conventional model, and the observation group implements a nursing model based on the control group. The management capacity and quality of life before and after the two groups of care were compared. 94 patients with chronic hepatitis B who were admitted to the hospital from July 2020 to April 2022 were selected, and 47 cases were divided into the control group and observation group according to the admission time. The control group is given a conventional model, and the observation group is given a nursing model on the basis of the control group. Both groups of patients observed anxiety self-assessment scale (SAS), depression self-assessment scale (SDS), short life span scale (SF-36) scores, and treatment conditions before and after the intervention, to explore the application of nursing model in the management of hepatitis B patients in tertiary hospitals and its impact on patient quality of life. Based on study's precare outcomes, there was no statistically significant difference between the self-administered scale (PIH) score and the quality of life measurement summary scale (QOL-BREF) score (P > 0.05) between the two groups. After one month of care, both groups had lower PIH scores than before care, and QOL-BREF scores were higher than before care (P < 0.05). After one month of treatment, the PIH score of the observation group was significantly reduced, and the QOL-BREF score after one month of treatment was significantly higher than that of the control group (P < 0.05). The SAS and SDS scores in the observation group were lower than those in the control group, and the quality of life scores and treatment compliance were higher than those in the control group, and the difference was statistically significant (P < 0.05). Conclusions. The nursing model can effectively improve the management and quality of life of hepatitis B patients. It also had a significant positive effect on the therapeutic capacity and quality of life of patients with hepatitis B and improved patient compliance behavior and quality of life.
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Hepatitis B Crónica , Calidad de Vida , Hepatitis B Crónica/terapia , Humanos , Centros de Atención TerciariaRESUMEN
Multiple myeloma is a hematologic tumor characterized by clonal proliferation of plasma cells.The development of novel agents and immunotherapy have substantially improved the prognosis of multiple myeloma,with an expectable median survival beyond ten years.Therefore,there is an urgent need to improve the management of this disease.Health management is effective in controlling chronic diseases and full-cycle management should be implemented from the early to the end stage of the disease.Implanting the full-cycle concept into the health management of multiple myeloma will guide and standardize the advances in this field.This review focuses on the full-cycle concept of multiple myeloma and the corresponding application of health management at each stage of the cycle.