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BACKGROUND: Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors. METHODS: A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population. RESULTS: Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported. CONCLUSION: While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.
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Neoplasias de la Mama , Supervivientes de Cáncer , Fatiga , Moxibustión , Humanos , Femenino , Moxibustión/métodos , Moxibustión/efectos adversos , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/terapia , Fatiga/etiología , Fatiga/terapia , Persona de Mediana Edad , Resultado del Tratamiento , Adulto , Calidad de Vida , China/epidemiología , Anciano , Rayos Infrarrojos/uso terapéuticoRESUMEN
The transcription factor Twist1 plays a vital role in normal development in many tissue systems and continues to be important throughout life. However, inappropriate Twist1 activity has been associated with kidney injury and fibrosis, though the underlying mechanisms involved remain incomplete. Here, we explored the role of Twist1 in regulating fibroblast behaviors and the development kidney fibrosis. Initially Twist1 protein and activity was found to be markedly increased within interstitial myofibroblasts in fibrotic kidneys in both humans and rodents. Treatment of rat kidney interstitial fibroblasts with transforming growth factor-ß1 (a profibrotic factor) also induced Twist1 expression in vitro. Gain- and loss-of-function experiments supported that Twist1 signaling was responsible for transforming growth factor-ß1-induced fibroblast activation and fetal bovine serum-induced fibroblast proliferation. Mechanistically, Twist1 protein promoted kidney fibroblast activation by driving the expression of downstream signaling proteins, Prrx1 and TNC. Twist1 directly enhanced binding to the promoter of Prrx1 but not TNC, whereas the promoter of TNC was directly bound by Prrx1. Finally, mice with fibroblast-specific deletion of Twist1 exhibited less Prrx1 and TNC protein abundance, interstitial extracellular matrix deposition and kidney inflammation in both the unilateral ureteral obstruction and ischemic-reperfusion injury-induced kidney fibrotic models. Inhibition of Twist1 signaling with Harmine, a ß-carboline alkaloid, improved extracellular matrix deposition in both injury models. Thus, our results suggest that Twist1 signaling promotes the activation and proliferation of kidney fibroblasts, contributing to the development of interstitial fibrosis, offering a potential therapeutic target for chronic kidney disease.
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BACKGROUND: The prevalence of vascular calcification (VC) in chronic kidney disease (CKD) patients remains substantial, but currently, there are no effective pharmaceutical therapies available. BRCA1/BRCA2-containing complex subunit 36 (BRCC36) has been implicated in osteoblast osteogenic conversion; however, its specific role in VC remains to be fully elucidated. The aim of this study was to investigate the role and underlying mechanisms of BRCC36 in VC. METHODS: The association between BRCC36 expression and VC was examined in radial arteries from patients with CKD, high-adenine-induced CKD mice, and vascular smooth muscle cells (VSMCs). Western blotting, real-time polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to analyse gene expression. Gain- and loss-of-function experiments were performed to comprehensively investigate the effects of BRCC36 on VC. Coimmunoprecipitation and TOPFlash luciferase assays were utilized to further investigate the regulatory effects of BRCC36 on the Wnt/ß-catenin pathway. RESULTS: BRCC36 expression was downregulated in human calcified radial arteries, calcified aortas from CKD mice, and calcified VSMCs. VSMC-specific BRCC36 overexpression alleviated calcium deposition in the vasculature, whereas BRCC36 depletion aggravated VC progression. Furthermore, BRCC36 inhibited the osteogenic differentiation of VSMCs in vitro. Rescue experiments revealed that BRCC36 exerts the protective effects on VC partly by regulating the Wnt/ß-catenin signalling pathway. Mechanistically, BRCC36 inhibited the Wnt/ß-catenin pathway by decreasing the K63-linked ubiquitination of ß-catenin. Additionally, pioglitazone attenuated VC partly through upregulating BRCC36 expression. CONCLUSIONS: Our research results emphasize the critical role of the BRCC36-ß-catenin axis in VC, suggesting that BRCC36 or ß-catenin may be promising therapeutic targets to prevent the progression of VC in CKD patients.
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Ratones Endogámicos C57BL , Insuficiencia Renal Crónica , Ubiquitinación , Calcificación Vascular , Vía de Señalización Wnt , beta Catenina , Calcificación Vascular/metabolismo , Calcificación Vascular/patología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/complicaciones , Animales , beta Catenina/metabolismo , Humanos , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Ratones , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Osteogénesis , Persona de Mediana Edad , Diferenciación CelularRESUMEN
Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed that L. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.
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Lesión Renal Aguda , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Probióticos , Microbioma Gastrointestinal/efectos de los fármacos , Limosilactobacillus reuteri/fisiología , Limosilactobacillus reuteri/metabolismo , Animales , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/metabolismo , Ratones , Lipopolisacáridos/metabolismo , Masculino , Riñón/microbiología , Riñón/metabolismo , Heces/microbiología , Modelos Animales de Enfermedad , Creatinina/sangre , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacosRESUMEN
Objective: To explore the influence of case-based learning (CBL) teaching methods in comparison to the traditional lecture-based learning (LBL) model in clinical teaching of nephrology for master's degree students in clinical medicine. Methods: Clinical medicine master's degree students who were trained in the Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University from December 2015 to December 2021 were selected as the study objects. The selected students were divided into two groups: the LBL group comprised 16 graduate students who received the traditional LBL model from December 2015 to December 2018, and the CBL group comprised 18 graduate students who received the CBL teaching methods from January 2019 to December 2021. Both groups participated in the professional theoretical knowledge assessment, including objective and subjective questions and calculating the total score), and the examination of clinical skills communication ability, preparation of handling materials, anesthesia techniques, operational skills, aseptic techniques, and postoperative management), at the time of discharge from the department. The independent learning ability (self-management ability, information ability, and learning ability) of students of the two groups after teaching was then assessed, and the satisfaction of the two groups with their respective teaching mode (including satisfaction with the teaching format, teaching effectiveness, interest stimulation, independent learning and the improvement of teamwork ability) was assessed by the questionnaire on the degree of satisfaction of the two groups. Results: The assessment scores of professional theoretical knowledge in the CBL group were significantly higher than those in the LBL group in objective questions, subjective questions, and total scores (P1 = .028; P2 = .036; P3 = .041). The CBL group scored higher than the LBL group in the assessment of communication skills, preparation of operative items, anesthesia technique, operative skills, aseptic technique, and postoperative handling skills, but the differences were not statistically significant (P1 = .071; P2 = .260; P3 = .184; P4 = .127; P5 = .352; P6 = .584). The self-management ability, information ability, and learning ability scores of students in the CBL group were significantly higher than those in the LBL group (P1 = .006; P2 = .013; P3 = .003). Students in the CBL group were significantly higher than those in the LBL group in terms of satisfaction with teaching form, teaching effect, interest stimulation, improvement of independent learning ability, and satisfaction with teamwork ability (P1 = .015; P2 = .008; P3 = .010; P4 = .024; P5 = .022). Conclusions: The CBL teaching model can improve and enhance the clinical thinking ability of clinical medicine master's degree students in nephrology, and stimulate their interest in learning. Professional master's degree students have a high degree of satisfaction with the CBL model.
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Medicina Clínica , Nefrología , Humanos , Aprendizaje Basado en Problemas/métodos , Estudiantes , Encuestas y CuestionariosRESUMEN
SIGNIFICANCE STATEMENT: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. However, blockade of IL-1 signaling in AKI has not consistently demonstrated kidney protection. The current murine experiments show that IL-1R1 activation in the proximal tubule exacerbates toxin-induced AKI and cell death through local suppression of apolipoprotein M. By contrast, IL-1R1 activation in endothelial cells ameliorates AKI by restoring VEGFA-dependent endothelial cell viability. Using this information, future delivery strategies can maximize the protective effects of blocking IL-1R1 while mitigating unwanted actions of IL-1R1 manipulation. BACKGROUND: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. IL-1R1 is expressed on some myeloid cell populations and on multiple kidney cell lineages, including tubular and endothelial cells. Pharmacological inhibition of the IL-1R1 does not consistently protect the kidney from injury, suggesting there may be complex, cell-specific effects of IL-1R1 stimulation in AKI. METHODS: To examine expression of IL-1 and IL-1R1 in intrinsic renal versus infiltrating immune cell populations during AKI, we analyzed single-cell RNA sequencing (scRNA-seq) data from kidney tissues of humans with AKI and mice with acute aristolochic acid exposure. We then investigated cell-specific contributions of renal IL-1R1 signaling to AKI using scRNA-seq, RNA microarray, and pharmacological interventions in mice with IL-1R1 deletion restricted to the proximal tubule or endothelium. RESULTS: scRNA-seq analyses demonstrated robust IL-1 expression in myeloid cell populations and low-level IL-1R1 expression in kidney parenchymal cells during toxin-induced AKI. Our genetic studies showed that IL-1R1 activation in the proximal tubule exacerbated toxin-induced AKI and cell death through local suppression of apolipoprotein M. By contrast, IL-1R1 activation in endothelial cells ameliorated aristolochic acid-induced AKI by restoring VEGFA-dependent endothelial cell viability and density. CONCLUSIONS: These data highlight opposing cell-specific effects of IL-1 receptor signaling on AKI after toxin exposure. Disrupting pathways activated by IL-1R1 in the tubule, while preserving those triggered by IL-1R1 activation on endothelial cells, may afford renoprotection exceeding that of global IL-1R1 inhibition while mitigating unwanted actions of IL-1R1 blockade.
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Lesión Renal Aguda , Receptores de Interleucina-1 , Humanos , Ratones , Animales , Receptores de Interleucina-1/genética , Apolipoproteínas M , Células Endoteliales/metabolismo , Lesión Renal Aguda/patología , Ratones Noqueados , Interleucina-1 , Endotelio/metabolismo , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN. METHODS: 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman's correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission. RESULTS: In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766. CONCLUSIONS: FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.
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Biomarcadores , Fibrinógeno , Glomerulonefritis Membranosa , Síndrome Nefrótico , Receptores de Fosfolipasa A2 , Humanos , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Receptores de Fosfolipasa A2/inmunología , Síndrome Nefrótico/sangre , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/complicaciones , Adulto , Biomarcadores/sangre , Fibrinógeno/análisis , Fibrinógeno/metabolismo , Curva ROC , Estudios Retrospectivos , Inducción de Remisión , Resultado del Tratamiento , Inmunosupresores/uso terapéutico , Estimación de Kaplan-Meier , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Factores de RiesgoRESUMEN
The purpose of this study was to investigate the efficacy and safety of a low-dose Rituximab (RTX) regimen driven by peripheral blood B lymphocyte count in the treatment of adult patients with nephrotic syndrome (NS) complicated with acute kidney disease (AKI). We conducted a prospective single-arm study to evaluate the effect of B cells-driven RTX regimen. Patients with NS (MCD, FSGS, MN, IgAN) complicated with AKI fulfilling the inclusion criteria were eligible for this study. Patients were followed up at intervals of 2 months. Student's t-test and Chi-squared test were used to analyze normally distributed continuous variables and non-normally distributed continuous variables, respectively. From August 2018 to January 2022, 23 patients met the inclusion criteria and agreed to participate in the study. 3, 9, and 11 patients were AKI stage 1, 2, and 3, respectively. From baseline to the latest follow-up, 20 patients had complete and partial recovery of renal function. Accompanied by depletion of B cells, significant reduction of urinary protein excretion, serum total cholesterol, and the number of relapses were observed during the 12 months after the first RTX infusion as compared with during the 12 months before RTX injection. The number of patients who maintained steroids and immunosuppressive medications also remarkably decreased. This study indicates that the targets-driven treatment of low-dose RTX can achieve a high remission rate and alleviate the loss of kidney function in treating NS with AKI. The long-term efficacy, side effects, and therapeutic economics of RTX are reasonable.
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Lesión Renal Aguda , Síndrome Nefrótico , Adulto , Humanos , Rituximab/efectos adversos , Síndrome Nefrótico/tratamiento farmacológico , Estudios Prospectivos , Resultado del Tratamiento , Recurrencia , Lesión Renal Aguda/tratamiento farmacológico , Inmunosupresores/uso terapéuticoRESUMEN
Vascular calcification (VC) is a strong predictor of cardiovascular mortality and overall mortality in patients with chronic kidney disease (CKD); however, the molecular mechanisms underlying VC have yet to be elucidated. Here, we report the role of the deubiquitinating enzyme BRCC36 in the process of VC in CKD. We established an in vitro VC model of vascular smooth muscle cells (VSMCs) and an adenine-induced CKD mouse model. The expression of BRCC36 was significantly decreased in both the in vivo and in vitro VC models. Alizarin red staining and calcium content assays showed that BRCC36 overexpression reduced calcium deposition in the presence of calcifying medium, while the contractile protein α-smooth muscle actin (α-SMA) was upregulated and phosphorylated ß-catenin was downregulated. Cell immunofluorescence showed that BRCC36 overexpression also reduced the expression of phosphorylated ß-catenin in the nucleus in the presence of calcifying medium. In addition, coimmunoprecipitation showed that BRCC36 can bind to ß-catenin. These results suggest that BRCC36 can interact with ß-catenin, the main effector protein of the Wnt/ß-catenin pathway, inhibiting the phosphorylation of ß-catenin and negatively regulating the cell signalling pathway, thereby inhibiting VC. This may provide new insights into the molecular mechanisms of VC in the context of CKD.
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BACKGROUND: Urinary ascites represents a scarcely observed pseudo-acute kidney injury in clinical settings. Protracted or missed diagnosis may hold grave ramifications for patient outcomes. CASE PRESENTATION: We reported a case involving an elderly female patient experiencing pseudo-acute kidney injury accompanied by ascites, wherein her renal dysfunction persisted despite medical intervention and hemodialysis. Urinary ascites was identified via a methylene blue test and by contrasting creatinine levels in serum and ascites. This patient's kidney function was multiple typified by a marked elevation in serum creatinine/Cystatin C ratio (> 2 L/dL), potentially serving as a clue for the clinical diagnosis of pseudo-acute kidney injury engendered by urinary ascites. CONCLUSIONS: This case suggested the potential diagnostic value of an asynchronous increase in serum creatinine and serum CysC (or an increased ratio of blood creatinine to blood CysC) in patients with pseudo-acute kidney injury.
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Lesión Renal Aguda , Cistatina C , Humanos , Femenino , Anciano , Ascitis/diagnóstico , Ascitis/etiología , Creatinina , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Diagnóstico ErróneoRESUMEN
Objective: Glomerular basement membrane (GBM) thickening is a typical and essential histopathological characteristic for the diagnosis of primary membranous nephropathy (PMN). The present study aimed to explore the relationship between GBM thickness and treatment response in PMN patients.Methods: A total of 128 patients with nephrotic syndrome concurrent with PMN were studied. The highest GBM thickness was measured from at least five glomerular capillary loops using an electron microscope, and the mean value was obtained. Patients were categorized into three groups according to the tertiles of GBM thickness as follows: Group 1 (GBM thickness ≤ 1100 nm, n = 48), Group 2 (1100 nm < GBM thickness ≤ 1300 nm, n = 40), Group 3 (GBM thickness >1300 nm, n = 40). Clinicopathological features and treatment response were compared among the three groups. The associations of GBM thickness with complete remission (CR) were assessed by Cox proportional hazard analyses and a cubic spline curve.Results: During a median follow-up period of 25.80 months, 69 (53.9%) patients achieved CR. Kaplan-Meier analysis showed that the non-CR probability was significantly higher in the highest tertile of GBM thickness (pË0.001). Univariate Cox proportional hazard analysis indicated that GBM thickness was associated with CR (HR per SD 0.617, 95% CI [0.471-0.809], pË0.001). After adjusting for age, duration of PMN, estimated glomerular filtration rate (eGFR), urinary protein excretion, grade of C3 deposition, and titer of serum anti-phospholipase A2 receptor (PLA2R) antibody, GBM thickness remained an independent predictor of CR (HR per SD 0.580, 95% CI [0.436-0.772], pË0.001). Further multivariable-adjusted restricted cubic spline analysis confirmed a significant reverse linear association between GBM thickness and CR (p for nonlinear = 0.1261).Conclusions: GBM thickness is an independent risk factor of CR. PMN patients with an increased level of GBM thickening at diagnosis have a lower probability of achieving CR.
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Glomerulonefritis Membranosa , Síndrome Nefrótico , Humanos , Membrana Basal Glomerular , Glomerulonefritis Membranosa/tratamiento farmacológico , Estimación de Kaplan-Meier , Receptores de Fosfolipasa A2RESUMEN
Aim: To explore the incidence, risk factors and overall outcome of the first episode of immune checkpoint inhibitor-related acute kidney injury (ICI-AKI) in Chinese patients receiving PD-1 inhibitors. Methods: Data for patients receiving PD-1 inhibitors at Jiangsu Province Hospital between December 2017 and January 2020 were retrospectively reviewed. Results: A total of 5.6% of 551 patients receiving PD-1 inhibitors developed ICI-AKI. Concomitant use of NSAIDs, ICI cycles and extrarenal immune-related adverse events may be independently associated with ICI-AKI. ICI-AKI may not be a risk factor for increased mortality or worse progression-free survival. Conclusions: ICI-AKI is relatively rare and its occurrence may not affect the overall 6-month outcome of patients receiving PD-1 inhibitors. Further studies are needed to verify these findings.
Immune checkpoint inhibitors (ICIs) have been more and more commonly used in patients with cancer. Therefore, it is important to understand the immune-related adverse events (irAEs), including immune-related renal adverse events, caused by ICIs. In this article, the authors explore the incidence, clinical features, risk factors and overall outcome of immune checkpoint inhibitor related-acute kidney injury (ICI-AKI) in Chinese patients treated with PD-1 inhibitors for the first time. Among 551 patients treated with PD-1 inhibitors, 65 patients experienced AKI and 31 patients experienced ICI-AKI. Patients with ICI-AKI may be more likely to receive nonsteroidal anti-inflammatory drugs, to receive PD-1 inhibitors for longer cycles or to experience extrarenal immune-related adverse events prior to or concomitant with ICI-AKI. The occurrence of ICI-AKI may not affect the survival time or disease progression of patients with cancer.
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Lesión Renal Aguda , Inhibidores de Puntos de Control Inmunológico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , China/epidemiología , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Incidencia , Masculino , Estudios RetrospectivosRESUMEN
PURPOSE: This study sought to explore and summarize the global state of acupuncture clinical trials enrolling cancer patients included in international registries to date. METHODS: All relevant trials evaluating acupuncture-related interventions for the treatment of cancer that were registered in 16 trial registries from January 1, 2001, through December 31, 2020, were identified. Subsequent publications related to these trials were additionally retrieved from the PubMed, Cochrane Library, Embase, CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), and Wanfang databases. We compared information included in these registries regarding completed trials with any associated publications, with a focus on study design, sample size, and selective reporting, based on the registered protocol. RESULTS: In total, 222 eligible trials across 19 countries were identified. These trials included 17 specific cancer types and 32 symptoms. The five most common cancer types were breast cancer, head and neck cancer, colorectal cancer, lung cancer, and gastric cancer, accounting for almost half of all registered trials (48.2%). The top five symptoms included in these trials were chemotherapy-induced peripheral neuropathy (CIPN), cancer-related pain, cancer-related fatigue, chemotherapy-induced nausea and vomiting (CINV), and gastrointestinal dysfunction. The overall rate of article publication was low, with publications being associated with just 33.3% of these registered trials. CONCLUSIONS: This review is the first snapshot of the landscape of acupuncture clinical trials registered in international trial registries, providing a methodological basis for the management of common treatment- and disease-related side effects among cancer patients undergoing acupuncture and offering useful information that will guide future acupuncture-focused research.
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Terapia por Acupuntura , Acupuntura , Antineoplásicos , Neoplasias de la Mama , Femenino , Humanos , Terapia por Acupuntura/métodos , Náusea/terapia , Ensayos Clínicos como AsuntoRESUMEN
OBJECTIVE: The objective of this study is to investigate the association between the serum sclerostin, the coronary artery calcification (CAC), and patient outcomes in maintenance dialysis patients. METHODS: We performed a prospective cohort study of 65 maintenance dialysis patients in 2014, including 39 patients on peritoneal dialysis and 26 on hemodialysis, and followed up for 5 years. Parameters of mineral metabolism including bone-specific alkaline phosphatase, fibroblast growth factor 23, sclerostin, and other biochemical factors were determined at the baseline. Meanwhile, the CAC score was analyzed by cardiac computed tomography. RESULTS: Serum sclerostin in hemodialysis patients was significantly higher than that in peritoneal dialysis patients (632.35 ± 369.18 vs. 228.85 ± 188.92, p < 0.001). The patients with CAC were older, receiving hemodialysis, lower Kt/V, and had longer dialysis vintage, as well as higher levels of serum 25-(OH)-vit D and sclerostin. In multivariate logistic regression analysis, older age and lower Kt/V were risk factors for CAC. The area under the receiver operating characteristic curves for prediction of CAC by sclerostin was 0.74 (95% confidence interval 0.605-0.878, p = 0.03), and the cutoff value of sclerostin is 217.55 pg/mL with the sensitivity 0.829 and specificity 0.619. After 5 years of follow-up, 51 patients survived. The patients in the survival group had significantly lower age, sclerostin levels, and low CAC scores than the nonsurvival group. Old age (≥60 years, p < 0.001) and high CAC score (≥50 Agatston unit, p = 0.031) were significant risk factors for the patient survival. CONCLUSIONS: Sclerostin is significantly elevated in dialysis patients with CAC. But sclerostin is not a risk factor for CAC. After 5 years of follow-up, patients in the survival group are younger and have lower sclerostin levels and CAC scores. But sclerostin levels are not independent risk factors for high mortality in dialysis patients.
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Enfermedad de la Arteria Coronaria , Diálisis Peritoneal , Calcificación Vascular , Humanos , Persona de Mediana Edad , Diálisis Peritoneal/efectos adversos , Estudios Prospectivos , Diálisis Renal/efectos adversosRESUMEN
OBJECTIVES: The aim of this study is to analyze the association between the ratio of overhydration and extracellular water (OH/ECW) and the ratio of extracellular water and body cell mass (ECW/BCM) measured by bioelectrical impedance and outcomes of patients with acute kidney injury (AKI) requiring kidney replacement therapy (KRT). METHODS: Patients with severe AKI treated with KRT in our hospital between September 2016 and August 2018 were enrolled. These patients were assessed using a body composition monitor before KRT, and on the 3rd day and the 7th day after initiation of KRT. The predictors mainly included OH/ECW and ECW/BCM. The association between all-cause mortality and predictors were analyzed using Cox regression. RESULTS: A total of 152 patients were included in this study with a median follow-up of 39 (interquartile range 8-742) days. The 28-day mortality, 90-day mortality, and 1-year mortality were 46.7%, 54.6%, and 60.5%, respectively. A high ratio of OH/ECW (adjusted hazard ratio per standard deviation, 1.45; 95% confidence interval = 1.15-1.82, P = .002) and a high ratio of ECW/BCM (adjusted hazard ratio per standard deviation, 1.33, 95% confidence interval = 1.07-1.64, P = .009) before KRT were associated with all-cause mortality during follow-up. Higher ECW/BCM rather than OH/ECW at 7th day was associated with poorer outcomes. Furthermore, a reduction of OH/ECW with an increase of ECW/BCM had higher 1-year mortality as compared to others (85.7% vs. 51.2%, P = .004) in patients who survived 7 days after KRT initiation. CONCLUSIONS: ECW/BCM performed better than OH/ECW in assessment of fluid status in AKI patients requiring KRT. This study suggested that a simple reduction of OH/ECW without decreasing ECW/BCM may not improve outcomes.
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Lesión Renal Aguda , Insuficiencia Cardíaca , Desequilibrio Hidroelectrolítico , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/terapia , Composición Corporal , Agua Corporal , Estudios de Cohortes , Impedancia Eléctrica , Femenino , Humanos , Masculino , Terapia de Reemplazo Renal , AguaRESUMEN
PURPOSE: The mean perfusion pressure (MPP) was recently proposed to personalized management tissue perfusion pressure in critically ill patients. Increased MPP variability (MPPV) may be associated with organ injuries. Our objective was to determine if increased MPPV was associated with subsequent deterioration of renal function in critically ill patients. METHODS: We analyzed data stored in the eICU-CRD and MIMIC-IV databases. The exposure was MPPV, measured as the coefficient of variation (CV) using the MPP data of the first 24 h after first ICU admission. The primary endpoint was deterioration of renal function, defined as new-onset or progress of acute kidney injury between 24 and 72 h after ICU admission. RESULTS: The study population consisted of 8,590 patients from eICU-CRD and 6,723 patients from MIMIC-IV database. A total of 28.4% and 30.2% of the study population experienced deteriorated renal function, respectively. Patients with deteriorated renal function had significantly higher median MPP-CV compared with those without (12.2% vs 11.5% and 12.8% vs 12.5%, p < .001). In fully adjusted multivariate logistic models, higher MPP-CV (adjusted OR per 1-SD, 1.08; 95% CI, 1.02-1.13 and adjusted OR per 1-SD, 1.06; 95% CI, 1.00-1.12, respectively) was significantly associated with greater risk of primary endpoint. The pooled analyses showed heterogeneity in patients with cardiac surgery, medical sepsis and others. CONCLUSION: Increased MPPV was associated with an increased risk of subsequent deterioration of renal function in critically ill patients with central venous pressure monitoring. Maintaining stable MPP may reduce the risk of renal function deterioration.
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Lesión Renal Aguda , Enfermedad Crítica , Humanos , Presión Venosa Central , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Estudios Retrospectivos , Perfusión , Riñón/fisiología , Unidades de Cuidados IntensivosRESUMEN
OBJECTIVE: To explore the clinicopathological features of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (anti-GBM-GN) and the prognostic values of clinical and laboratory indicators at diagnosis on renal and patient survival. METHODS: A total of 76 patients (34 males and 42 females) with anti-GBM-GN who were hospitalized in the First Affiliated Hospital of Nanjing Medical University between January 2010 and June 2021 were included in this study. The baseline clinical features, histopathological data from renal biopsies, and predictors of renal and patient survival were retrospectively analyzed. RESULTS: Among the 76 patients, the median serum creatinine at diagnosis was 618.0 (350.98, 888.25) µmol/L and the median estimated glomerular filtration rate (eGFR) was 6.62 (4.39, 14.41) mL/min. Of these 76 patients, 55 (72.4%) received initial kidney replacement therapy (KRT) and 39 (51.3%) received plasma exchange or double-filtered plasmapheresis (DFPP). During a median follow-up duration of 28.5 (6.0, 71.8) months, 53 (69.7%) patients progressed to kidney failure with replacement therapy (KFRT) and received maintenance dialysis. Initial KRT (HR = 3.48, 95% CI = 1.22-9.97, p = 0.020) was a significant risk factor for renal survival. During the follow-up, 49 (64.5%) of 76 patients survived. Age (≥60 years, HR = 4.13, 95% CI = 1.65-10.38, p = 0.003) and initial KRT (HR = 2.87, 95% CI = 1.01-8.14, p = 0.047) were predictive of patient survival. CONCLUSIONS: Among patients with anti-GBM-GN, initial KRT at presentation was predictive of KFRT while older age and initial KRT were associated with higher all-cause mortality.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular , Glomerulonefritis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/patología , Estudios Retrospectivos , Glomerulonefritis/terapia , Glomerulonefritis/complicaciones , Membrana Basal Glomerular/patología , Riñón/patologíaRESUMEN
BACKGROUND: Epidermal wax is an important factor affecting the storage quality of fruits and vegetables. Previous studies have shown that the epidermal wax of fruits undergoes significant changes during storage, but there are few studies on the effects of different storage methods on the changes in waxes and the relationship with storage quality. To investigate the effect of cuticular wax on the postharvest physiology in fragrant pear, equal numbers of fragrant pear fruits were stored in room temperature storage (control), cold storage and controlled atmosphere (CA) storage environs, respectively. RESULTS: Gas chromatography-mass spectrometry analysis revealed that the prevailing compositions of cuticular wax of fragrant pear were alkanes, alkenes, alcohols, aldehydes, esters and fatty acids. Compared with the control, cold storage and CA storage significantly inhibited changes in postharvest physiology, total wax contents and wax compositions of fragrant pear, and the effects of CA storage were more pronounced than cold storage. Under different storage methods, total wax contents and wax compositions show different correlations with various physiological indicators. CONCLUSION: The results obtained in the present study indicate that cold storage and CA storage altered the fragrant pear cuticular wax contents and constituents, thus changing the postharvest physiology quality. The changes in the metabolism of wax components caused by the changes in storage environment mainly affect the changes in the hardness of fragrant pears. The present study provides a theoretical basis for the preservation and storage of fruits. © 2022 Society of Chemical Industry.
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Pyrus , Frutas/química , Cromatografía de Gases y Espectrometría de Masas , Odorantes , Pyrus/química , Ceras/químicaRESUMEN
OBJECTIVE: The aim of this study was to investigate the effect of 10.6-µm laser moxibustion and electroacupuncture in 5-fluorouracil (5-Fu)-induced diarrhea model rats. METHODS: Forty-eight Sprague Dawley rats were randomly divided into 4 groups: a normal group, model group, 10.6-µm laser moxibustion (LM) group, and electroacupuncture (EA) group. Diarrhea was induced by 5-Fu (50 mg/kg) injection in 36 rats; the LM and EA groups received treatment at acupoint ST36 (Zusanli) on hind limbs once a day for 6 days. RESULTS: 5-Fu injection caused body weight decline and diarrhea. From the 5th to 7th day, the LM group showed higher body weights than the model group (P < 0.05). On the 6th day, diarrhea score of the LM group was better than that of the EA group (P < 0.05). Both scores of the LM group and EA group were better than that of model group (P < 0.05). The LM group and EA group both had better intestine pathological scores and lower endotoxin (ET) and diamine oxide (DAO) activity than the model group (P < 0.01). The LM group got better pathological scores than the EA group (P < 0.01). Ultramicroscopic structures of the model group showed severe damage while the LM group and EA group remained good in their small intestines. The model group had obviously decreased occludin protein in intestine tissues than the control group (P < 0.01), while occludin expressions in the LM group and EA group were both obviously increased compared with the model group (P < 0.01). CONCLUSION: LM and EA treatment on ST36 could alleviate damage to intestinal barrier function and alleviate diarrhea caused by 5-Fu.
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Diarrea/inducido químicamente , Electroacupuntura/métodos , Fluorouracilo/efectos adversos , Moxibustión/métodos , Puntos de Acupuntura , Animales , Humanos , Rayos Láser , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Continuous renal replacement therapy (CRRT) has become an important multiple organ support therapy and it is widely used in the intensive care unit (ICU). The aim of this study was to clarify the association between CRRT and 28-day mortality in critically ill coronavirus disease 2019 (-COVID-19) patients receiving mechanical ventilation. MATERIALS AND METHODS: 112 respiratory decompensated critically ill adult patients with COVID-19 admitted to a COVID-19-designated ICU were included in this retrospective cohort study. Data on demographic information, comorbidities, laboratory findings upon ICU admission, and clinical outcomes were collected. The Kaplan-Meier method and Cox proportional hazard model were applied to determine the potential risk factors associated with 28-day mortality. RESULTS: The median age was 65.7 years, 67.8% were males, and 58.9% patients had at least one comorbidity. The median scores of the Charlson Comorbidity Index and Sequential Organ Failure Assessment (SOFA) were 3 and 7, respectively. Acute kidney injury (AKI) occurred in 57 critically ill patients upon ICU admission; 43 patients were classified as stage 2 - 3 AKI, and 36 patients were treated with CRRT. Age > 65 years, high SOFA score, damaged cardiac function, poor nutrition, and severe infection were significantly associated with increased 28-day mortality. AKI patients receiving CRRT had lower 28-day mortality compared with those not receiving CRRT (HR = 0.35, 95% CI: 0.21 - 0.58, p < 0.001). Initiating CRRT within 72 hours after mechanical ventilation did not improve survival after CRRT initiation. CONCLUSION: AKI prevalence and 28-day mortality are high in critically ill patients with COVID-19 receiving mechanical ventilation. CRRT plays a part in decreasing the mortality of critically ill COVID-19 patients with AKI receiving mechanical ventilation.