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OBJECTIVE: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning. METHODS: A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed. RESULTS: Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1ß (MIP-1ß) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1ß were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal. CONCLUSION: Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.
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Lesión Renal Aguda , Terapia de Reemplazo Renal Continuo , Herbicidas , Humanos , Masculino , Femenino , Herbicidas/envenenamiento , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Lesión Renal Aguda/terapia , Lesión Renal Aguda/inducido químicamente , Citocinas/sangre , Paraquat/envenenamiento , Diquat/envenenamiento , Adulto Joven , Anciano , Hemofiltración/métodos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/terapiaRESUMEN
An ultra-high sensitivity pH sensor based on vertical organic electrochemical transistors (vOECT) with extended gate was proposed. The vOECT, which exhibited high transconductance (gm), was for the first time used in the preparation of a pH sensor. The extended gate was modified by electrochemical deposition of polyaniline (PANI) using the cyclic voltammetry (CV) technique. Open circuit potential (OCP) measurements were used to optimize the scan rate, showing a super-Nernstian sensitivity at all scan rates. The pH sensor based on vOECT with extended gate was investigated at different pH levels, and it exhibited an ultra-high sensitivity of 3363.6 µA/pH in the pH range 5-9, which was about 36 times greater than the maximum current sensitivity (91 µA/pH) of other transistor-based pH sensors, to the best of our knowledge. This pH sensor performed excellently in terms of reversibility, long-term stability, and selectivity. To confirm the reliability of the pH sensor, we conducted measurements on real samples using this pH sensor and compared the results with those obtained from a standard pH meter. The ultra-high sensitivity pH sensor based on vOECT with extended gate offers a sensitive and promising alternative in environmental monitoring, food safety, chemistry, clinical diagnostics, and bio-sensing applications.
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Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.
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OBJECTIVE: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute liver failure (ALF). METHODS: In this retrospective study, we enrolled patients with ALF (serum total bilirubin >10 mg/dL or Model for End-Stage Liver Disease [MELD] Score >18) hospitalized between August 2017 and August 2022. All patients had at least two sessions of FPSA-CVVH. The primary measure of treatment efficacy was the reduction ratios (RRs) of bilirubin after each session of FPSA-CVVH. RESULTS: Seventy-eight patients with ALF were enrolled. The MELD score at baseline was 22.9 ± 7.5. The mean total bilirubin was 22.05 ± 5.94 mg/dL, direct bilirubin was 16.33 ± 4.60 mg/dL and indirect bilirubin was 3.43 ± 1.60 mg/dL. One hundred and eighty seven sessions of FPSA-CVVH treatment lasting 8 hours each were performed. After a single session, serum total bilirubin, direct bilirubin and indirect bilirubin were significantly decreased. RRs were 52.0% ± 7.6% for total bilirubin, 59.4% ± 13.0% for direct bilirubin and 36.9% ± 15.4% for indirect bilirubin. Twenty nine patients (37.2%) survived and were discharged from the hospital, 12 of them recovered their liver function while the remaining 17 patients needed intermittent artificial liver support therapy. CONCLUSION: FPSA-CVVH therapy is an effective artificial liver support therapy in patients with ALF. It may be considered as a "bridge technique" to the recovery of liver function in critical ill patients with ALF.
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Terapia de Reemplazo Renal Continuo , Enfermedad Hepática en Estado Terminal , Fallo Hepático Agudo , Humanos , Estudios Retrospectivos , Adsorción , Índice de Severidad de la Enfermedad , Fallo Hepático Agudo/terapia , BilirrubinaRESUMEN
In order to overcome the poor solubilities of iridium-based ECL luminophores and explore self-enhanced ECL luminophores, polyethyleneimine (PEI) covalently linked with iridium complex via amide bonds (abbreviated as Ir-PEI) as a new novel intramolecular self-enhanced water-soluble ECL reagent has been unprecedently designed and successfully synthesized in this work. The chemical structure data, FT-IR spectra, photophysical, electrochemical and electrochemiluminescence of this new ECL reagent have been well characterized. In addition, in order to investigate its properties in the real applications, a corresponding new sensitive and specific ECL-based aptasensor to monitor tetracycline (TET) residues in honey and lake water has been further constructed based on this novel self-enhanced reagent of Ir-PEI in this work. This as-prepared intramolecular self-enhanced water-soluble of Ir-PEI illustrated in this work would pave a new avenue to promote the analytical applications of iridium-based ECL luminophores in the future.
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Alzheimer's disease (AD) is the most prevalent form of dementia, and it displays both clinical and molecular variability. RNA N6-methyladenosine (m6A) regulators are involved in a wide range of essential cellular processes. In this study, we aimed to identify molecular signatures associated with m6A in Alzheimer's disease and use those signatures to develop a predictive model. We examined the expression patterns of m6A regulators and immune features in Alzheimer's disease using the GSE33000 dataset. We examined the immune cell infiltration and molecular groups based on m6A-related genes in 310 Alzheimer's disease samples. The WGCNA algorithm was utilized to determine differently expressed genes within each cluster. After evaluating the strengths and weaknesses of the random forest model, the support vector machine model, the generalized linear model, and eXtreme Gradient Boosting, the best machine model was selected. Methods such as nomograms, calibration curves, judgment curve analysis, and the use of independent data sets were used to verify the accuracy of the predictions made. Alzheimer's disease and non-disease Alzheimer's groups were compared to identify dysregulated m6A-related genes and activated immune responses. In Alzheimer's disease, two molecular clusters linked to m6A were identified. Immune infiltration analysis indicated substantial variation in protection between groups. Cluster 1 included processes like the Toll-like receptor signaling cascade, positive regulation of chromatin binding, and numerous malignancies; cluster 2 included processes like the cell cycle, mRNA transport, and ubiquitin-mediated proteolysis. With a lower residual and root mean square error and a larger area under the curve (AUC = 0.951), the Random forest machine model showed the greatest discriminative performance. The resulting random forest model was based on five genes, and it performed well (AUC = 0.894) on external validation datasets. Accuracy in predicting Alzheimer's disease subgroups was also shown by analyses of nomograms, calibration curves, and decision curves. In this research, we methodically outlined the tangled web of connections between m6A and AD and created a promising prediction model for gauging the correlation between m6A subtype risk and AD pathology.
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Enfermedad de Alzheimer , ARN , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Transporte de ARN , Adenosina/genéticaRESUMEN
Heatstroke (HS) is a life-threatening injury requiring neurocritical care which could lead to central nervous system dysfunction and severe multiple organ failure syndrome. The cell-cell adhesion and cell permeability are two key factors for characterizing HS. To investigate the process of HS, a biochip-based electrical model was proposed and applied to HS. During the process, the value of TEER is associated with cell permeability and CI which represents cell-cell adhesion decreases that are consistent with the reduction in cell-cell adhesion and cell permeability characterized by proteins (occludin, VE-Cadherin and ZO-1) and RNA level. The results imply that the model can be used to monitor the biological process and other biomedical applications.
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Golpe de Calor , Humanos , Impedancia Eléctrica , Golpe de Calor/diagnóstico , Golpe de Calor/metabolismo , Adhesión Celular , Sistema Nervioso Central/metabolismo , PermeabilidadRESUMEN
OBJECTIVE: The study delves into the clinical efficacy and safety of centrifugal-membranous hybrid double filtration plasmapheresis (C/M hybrid DFPP) on severe lupus nephritis (LN) by comparing it with membranous DFPP (M DFPP). METHODS: A retrospective cohort study was conducted in 70 patients who were diagnosed with severe LN and had received DFPP treatment. RESULTS: A total of 181 DFPPs were performed, including 133 C/M hybrid DFPPs (51 patients) and 48 M DFPPs (19 patients).The ANA, A-dsDNA titer, quantitative urinary protein, and serum creatinine decreased significantly and hemoglobin increased significantly after the DFPP treatment and at third month after treatment. Two patients in the M DFPP group developed bleeding complications, and four patients in the C/M hybrid DFPP group developed perioral numbness. CONCLUSION: Although there was no significant difference in clinical efficacy between C/M hybrid DFPP and M DFPP on severe LN, the risk of bleeding complications was significantly lower in the C/M hybrid DFPP group.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Nefritis Lúpica/terapia , Nefritis Lúpica/complicaciones , Estudios Retrospectivos , Lupus Eritematoso Sistémico/complicaciones , Resultado del Tratamiento , PlasmaféresisRESUMEN
BACKGROUND: The objective response rate of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients with first-line anti-programmed cell death protein-1 (PD-1) monotherapy is only 40-45%. Single-cell RNA sequencing (scRNA-seq) enables unbiased analysis of the full variety of cells comprising the tumor microenvironment. Thus, we used scRNA-seq to assess differences among microenvironment components between therapy-resistant and therapy-sensitive groups in MSI-H/mismatch repair-deficient (dMMR) mCRC. Resistance-related cell types and genes identified by this analysis were subsequently verified in clinical samples and mouse models to further reveal the molecular mechanism of anti-PD-1 resistance in MSI-H or dMMR mCRC. METHODS: The response of primary and metastatic lesions to first-line anti-PD-1 monotherapy was evaluated by radiology. Cells from primary lesions of patients with MSI-H/dMMR mCRC were analyzed using scRNA-seq. To identify the marker genes in each cluster, distinct cell clusters were identified and subjected to subcluster analysis. Then, a proteinâprotein interaction network was constructed to identify key genes. Immunohistochemistry and immunofluorescence were applied to verify key genes and cell marker molecules in clinical samples. Immunohistochemistry, quantitative real-time PCR, and western blotting were performed to examine the expression of IL-1ß and MMP9. Moreover, quantitative analysis and sorting of myeloid-derived suppressor cells (MDSCs) and CD8+ T cells were performed using flow cytometry. RESULTS: Tumor responses in 23 patients with MSI-H/dMMR mCRC were evaluated by radiology. The objective response rate was 43.48%, and the disease control rate was 69.57%. ScRNA-seq analysis showed that, compared with the treatment-resistant group, the treatment-sensitive group accumulated more CD8+ T cells. Experiments with both clinical samples and mice indicated that infiltration of IL-1ß-driven MDSCs and inactivation of CD8+ T cells contribute to anti-PD-1 resistance in MSI-H/dMMR CRC. CONCLUSIONS: CD8+ T cells and IL-1ß were identified as the cell type and gene, respectively, with the highest correlation with anti-PD-1 resistance. Infiltration of IL-1ß-driven MDSCs was a significant factor in anti-PD-1 resistance in CRC. IL-1ß antagonists are expected to be developed as a new treatment for anti-PD-1 inhibitor resistance.
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Neoplasias Colorrectales , Inestabilidad de Microsatélites , Animales , Ratones , Linfocitos T CD8-positivos/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Inmunohistoquímica , Microambiente TumoralRESUMEN
In this work, singlet oxygen (1O2) is unprecedently recorded in the electrochemical reduction of tris(2,2'-bipyridine)ruthenium(II) [Ru(bpy)32+] in an acetonitrile solution with dissolved oxygen, which is well characterized by the specific probe of Singlet Oxygen Sensor Greens and the technique of electron-spin resonance in this work. Importantly, this new electrochemical method to produce 1O2 shows higher efficiency than the conventional photodriven method. Furthermore, taken together with the inherent advantages of electrochemical techniques compared with the photochemical/chemical-driven method, this electrochemical method would inevitably show great promise in reactive-oxygen-species-related studies in the future.
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In this work, three iridium(III) tetrazolato complexes have been designed and successfully synthesized. Beside photophysical properties, their performances in protein staining have been comprehensively investigated in this work for the first time. Notably, these iridium(III) tetrazolato complexes with high quantum efficiency exhibited much better protein staining properties than the commercial agent Coomassie Brilliant Blue (CBB) under the same experimental conditions, which may pave the way to explore new efficient iridium-based protein staining agents both for commercial markets and academic research in the future.
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Iridio , Proteínas , Coloración y EtiquetadoRESUMEN
A mononuclear iridium-based complex with a primary amine group (named Ir-NH2), a mononuclear ruthenium-based complex with a butanoic acid group (named Ru-COOH) and the corresponding heterodinuclear complex containing an iridium and ruthenium center via an amide bond bridge (named Ir-Ru) were designed and successfully synthesized in this study. The photophysical and electrochemical properties and ECL performances of these three metal complexes under various experimental conditions were well characterized. For the first time, the insights from this comprehensive comparison study indicate that the two metal-based subunits with comparable luminescent properties are significant in the design of bimetallic-based multicolor luminophores at the molecular level, which helps us to further understand the emission performances of bimetallic complexes and to rationally design more efficient corresponding organometallic luminophores with multicolor emission for wide applications in the future.
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Complejos de Coordinación , Compuestos Organometálicos , Rutenio , Amidas , Aminas , Ácido Butírico , Complejos de Coordinación/química , Iridio/química , Compuestos Organometálicos/química , Rutenio/químicaRESUMEN
OBJECTIVE: Cardiac valvular calcification (CVC) is the main cause of cardiovascular disease and all-cause death in patients with chronic kidney disease (CKD). However, the relationship between Neutrophil lymphocyte ratio (NLR) and CVC in patients with CKD is not clear. In this study, we aimed to investigate the prevalence of CVC in newly diagnosed patients with non-dialysis CKD stage 3-5 and evaluate the correlation between NLR and CVC. METHODS: A total of 483 newly diagnosed patients with non-dialysis CKD stage 3-5 were included. According to the presence of CVC, these patients were retrospectively divided into two groups: CVC group and non-CVC group. RESULTS: CVC was found in 80 patients (16.56 %), 53 (10.97 %) of whom had only aortic valve calcification (AVC), 18 (3.73 %) had mitral valve calcification (MVC), and 9 (1.86 %) had both AVC and MVC. The level of NLR in the CVC group was significantly higher than that in the non-CVC group (p=0.002). Multivariate logistic regression analysis showed that NLR was an independent risk factor for CVC (95% CI 1.017~1.225, p=0.020). ROC curve analysis showed that the area under the curve of NLR for predicting CVC was 0.610 (95% CI 0.543-0.676, p=0.002). The best cut-off point of NLR was 3.340, with a sensitivity of 49.4 % and a specificity of 70.0 %. CONCLUSION: CVC is not uncommon in newly diagnosed patients with non-dialysis CKD stage 3-5, and NLR is an independent risk factor for CVC (Tab. 4, Fig. 1, Ref. 34).
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Enfermedades de las Válvulas Cardíacas , Insuficiencia Renal Crónica , Válvula Aórtica/patología , Estenosis de la Válvula Aórtica , Calcinosis , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/epidemiología , Humanos , Linfocitos , Neutrófilos , Prevalencia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Estudios RetrospectivosRESUMEN
An iridium solvent complex (abbreviated as Ir-probe) has been synthesized and reported as a new photoluminescent "switch-on" probe to detect benzimidazole pesticides via coordination mechanism in this work. This new probe could successfully distinguish benzimidazole pesticides from other kinds of common pesticides widely used in agriculture activities. Thiabendazole (TBZ) and carbendazim (CBZ) as the representative benzimidazole pesticides, this probe exhibited good analytical performance with the linear ranges of 0.05 µM to 20 µM for TBZ and 3 µM to 40 µM for CBZ, and the corresponding limit of detection (LOD, 3σ/S) is 0.03 µM and 0.5 µM for analyzing TBZ and CBZ, respectively. In addition, the proposed method in this work also has good recoveries in analyzing TBZ and CBZ residues in the real samples.
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Plaguicidas , Bencimidazoles , Iridio , Solventes , Tiabendazol/químicaRESUMEN
Patients with locally advanced colorectal cancer (LACRC) have a high risk of recurrence and metastasis, although neoadjuvant therapy may provide some benefit. However, patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) LACRC receive little benefit from neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT). The 2015 KEYNOTE-016 trial identified MSI-H/dMMR as a biomarker indicative of immunotherapy efficacy, and pointed to the potential use of immune checkpoint inhibitors (ICIs). In 2017, the FDA approved two ICIs (pembrolizumab and nivolumab) for treatment of MSI-H/dMMR metastatic CRC (mCRC). In 2018, the CheckMate-142 trial demonstrated successful treatment of mCRC based on "double immunity" provided by nivolumab with ipilimumab, a regimen that may become a standard first-line treatment for MSI-H mCRC. In 2018, the FDA approved nivolumab alone or with ipilimumab for patients who progressed to MSI-H/dMMR mCRC after standard chemotherapy. The FDA then approved pembrolizumab alone as a first-line treatment for patients with MSI-H/dMMR CRC that was unresectable or metastatic. There is now interest in using these drugs in neoadjuvant immunotherapy (nIT) for patients with MSI-H/dMMR non-mCRC. In 2020, the NICHE trial marked the start of using nIT for CRC. This novel treatment of MSI-H/dMMR LACRC may change the approaches used for neoadjuvant therapy of other cancers. Our review of immunotherapy for CRC covers diagnosis and treatment, clinical prognostic characteristics, the mechanism of nIT, analysis of completed prospective and retrospective studies, and ongoing clinical trials, and the clinical practice of using nIT for MSI-H/dMMR LACRC. Our team also proposes a new organ-preservation strategy for patients with MSI-H/dMMR low LARC.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Colon/tratamiento farmacológico , Humanos , Inmunoterapia , Ipilimumab/uso terapéutico , Inestabilidad de Microsatélites , Terapia Neoadyuvante , Nivolumab/uso terapéutico , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had severe consequences for health and the global economy. To control the transmission, there is an urgent demand for early diagnosis and treatment in the general population. In the present study, an automatic system for SARS-CoV-2 diagnosis is designed and built to deliver high specification, high sensitivity, and high throughput with minimal workforce involvement. The system, set up with cross-priming amplification (CPA) rather than conventional reverse transcription-polymerase chain reaction (RT-PCR), was evaluated using more than 1000 real-world samples for direct comparison. This fully automated robotic system performed SARS-CoV-2 nucleic acid-based diagnosis with 192 samples in under 180 min at 100 copies per reaction in a "specimen in data out" manner. This throughput translates to a daily screening capacity of 800-1000 in an assembly-line manner with limited workforce involvement. The sensitivity of this device could be further improved using a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based assay, which opens the door to mixed samples, potentially include SARS-CoV-2 variants screening in extensively scaled testing for fighting COVID-19.
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Prueba de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2 , Algoritmos , Ingeniería Biomédica/instrumentación , Ingeniería Biomédica/métodos , Ingeniería Biomédica/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/virología , Prueba de Ácido Nucleico para COVID-19/instrumentación , Prueba de Ácido Nucleico para COVID-19/estadística & datos numéricos , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Diseño de Equipo , Ensayos Analíticos de Alto Rendimiento/instrumentación , Ensayos Analíticos de Alto Rendimiento/métodos , Ensayos Analíticos de Alto Rendimiento/estadística & datos numéricos , Humanos , Técnicas de Amplificación de Ácido Nucleico/instrumentación , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Amplificación de Ácido Nucleico/estadística & datos numéricos , Pandemias , Robótica/instrumentación , Robótica/métodos , Robótica/estadística & datos numéricos , SARS-CoV-2/genética , Sensibilidad y Especificidad , Análisis de SistemasRESUMEN
OBJECTIVE: Drug-induced acute interstitial nephritis (DAIN) is often associated with improved outcomes, whereas some patients may still progress to chronic kidney disease (CKD). The aim of this study was to evaluate the prognosis of patients with severe DAIN requiring renal replacement therapy (RRT) at baseline, and to explore the risk factors of progression to CKD. METHODS: We performed a retrospective study of patients with severe DAIN confirmed by renal biopsies in our center over a 10 years period, all the patients received RRT at presentation. The clinical and pathological characteristics at baseline were recorded, and the outcomes (renal function recovered or progressed to CKD) during follow-ups were also evaluated. Univariate and multivariate logistic regression analysis were performed to identify the independent risk factors of progression to CKD. RESULTS: Seventy-two patients who met the inclusion criteria were enrolled, 13 patients (18.0%) progressed to CKD (GFR < 60 ml/min/1.73 m2) after at least 6 months of follow-up, the remaining 59 patients achieved a favorable renal function recovery. Compared with patients who achieved renal function recovery (recovery group), the patients progressed to CKD (progression group) were older and had longer interval from symptom onset to treatment with steroids. The peak serum cystatin C concentration was higher in progression group than recovery group. Higher score of interstitial fibrosis/tubular atrophy (IFTA) and more interstitial inflammatory cells infiltration were detected in renal tissue in progression group. According to multivariable analysis, higher peak cystatin C concentration (OR = 2.443, 95% CI 1.257, 4.746, p = 0.008), longer interval to treatment with corticosteroids (OR = 1.183, 95% CI 1.035, 1.352, p = 0.014) were independent risk factors of progression to CKD. The cutoff value of cystatin C concentration was 4.34 mg/L, at which the sensitivity and specificity were 76.9% and 89.3%, respectively; the cutoff value of interval to treatment with corticosteroids was 22.5 days, at which the sensitivity and specificity were 81.8% and 79.5%, respectively. CONCLUSION: Renal function was reversible in majority of patients with severe DAIN requiring RRT when early identification and treatment. Higher peak cystatin C concentration and longer interval to treatment with corticosteroids associated with worse renal prognosis.
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Riñón/patología , Nefritis Intersticial/terapia , Recuperación de la Función , Terapia de Reemplazo Renal , Adulto , Biopsia , Creatinina/sangre , Cistatina C/sangre , Progresión de la Enfermedad , Femenino , Glucocorticoides/administración & dosificación , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/patología , Pronóstico , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PREMISE: Aquilegia is an ideal taxon for studying the evolution of adaptive radiation. Current phylogenies of Aquilegia based on different molecular markers are inconsistent, and therefore a clear and accurate phylogeny remains uncertain. Analyzing the chloroplast genome, with its simple structure and low recombination rate, may help solve this problem. METHODS: Next-generation sequencing data were generated or downloaded for Aquilegia species, enabling their chloroplast genomes to be assembled. The assemblies were used to estimate the genome characteristics and infer the phylogeny of Aquilegia. RESULTS: In this study, chloroplast genome sequences were assembled for Aquilegia species distributed across Asia, North America, and Europe. Three of the genes analyzed (petG, rpl36, and atpB) were shown to be under positive selection and may be related to adaptation. The phylogenetic tree of Aquilegia showed that its member species formed two clades with high support, North American and European species, with the Asian species being paraphyletic; A. parviflora and A. amurensis clustered with the North American species, while the remaining Asian species were found in the European clade. In addition, A. oxysepala var. kansuensis should be considered as a separate species rather than a variety. DISCUSSION: The complete chloroplast genomes of these Aquilegia species provide new insights into the reconstruction of the phylogeny of related species and contribute to the further study of this genus.
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Colorectal cancer (CRC), a common malignant tumor in the digestive tract, is a leading cause of cancer-related death. SPRY4 has been reported to act as a tumor suppressor gene in various tumors. This study aims to assess the role of SPRY4 in colorectal cancer (CRC) and uncover its underlying mechanisms. Firstly, the expression levels of SPRY4 were measured in CRC cell lines. SPRY4-overexpressing or silencing plasmids were transfected into CRC cells to regulate its expression level. CCK-8, colony formation, EdU assay, wound-healing and Transwell assays were performed to determine cell proliferation, invasion and migration abilities. Then, apoptosis was measured by flow cytometry analysis, and the expression of apoptosis-related protein was analyzed by western-blotting. Next, the in vivo tumorigenesis assay was performed in nude mice. According to the results, there was a lower expression of SPRY4 in CRC cell lines compared with normal cell line, and the overexpression of SPRY4 significantly suppressed cell proliferation, migration and invasion, and promoted apoptosis in SW480 cells. Moreover, the enhanced proliferation, invasion and migration upon SPRY4 silencing was reversed by EZH2 inhibition. In addition, we found that the overexpression of SPRY4 inhibited tumorigenesis in vivo by diminishing the size and weight of the tumors. Our study indicates that SPRY4 might be a potential tumor suppressor gene and prognostic factor for patients with CRC.
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Neoplasias Colorrectales/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Proteína Potenciadora del Homólogo Zeste 2/antagonistas & inhibidores , Proteína Potenciadora del Homólogo Zeste 2/genética , Técnicas de Silenciamiento del Gen , Humanos , Indoles/farmacología , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Ratones , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Proteínas del Tejido Nervioso/genética , Piridonas/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The floral scents of plants play a key role in plant reproduction through the communication between plants and pollinators. Aquilegia as a model species for studying evolution, however, there have been few studies on the floral scents and relationships between floral scents and pollination for Aquilegia taxa. METHODS: In this study, three types of solid-phase micro-extraction (SPME) fiber coatings (DVB/PDMS, CAR/PDMS, DVB/CAR/PDMS) were evaluated for their performance in extracting volatile organic compounds (VOCs) from flowers of Aquilegia amurensis, which can contribute to the future studies of elucidating the role of floral scents in the pollination process. RESULTS: In total, 55 VOCs were identified, and among them, 50, 47 and 45 VOCs were extracted by the DVB/CAR/PDMS fiber, CAR/PDMS fiber and DVB/PDMS fibers, respectively. Only 30 VOCs were detected in A. japonica taxa. Furthermore, the relative contents of 8 VOCs were significant different (VIP > 1 and p < 0.05) between the A. amurensis and A. japonica. CONCLUSIONS: The results can be applied in new studies of the relationships between the chemical composition of floral scents and the processes of attraction of pollinator. It may provide new ideas for rapid evolution and frequent interspecific hybridization of Aquilegia.