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1.
Int J Stroke ; : 17474930221125993, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36082948

RESUMO

BACKGROUND: In China, disparities in the quality of stroke care still exist and implementing quality improvement is still a challenge. AIMS: To determine whether the intervention by Shanghai Stroke Service System (4S) has helped to improve adherence to stroke-care guidelines and patient outcome. METHODS: 4S is a regional stroke network with real-time data extraction among its 61 stroke centers in Shanghai. A total of 11 key performance indicators (KPIs) were evaluated. The primary outcomes were a composite measure and an all-or-none measure of adherence to 11 KPIs. The secondary outcomes were length of hospital stay and in-hospital mortality. RESULTS: The study enrolled 92,395 patients (mean age 69.0±12.5 years, 65.2% men) with acute ischemic stroke hospitalized within 7 days of onset in Shanghai from January 2015 to December 2020. More patients received guideline recommended care between 2018-2020 than those between 2015-2017 (composite measure 87.1% vs 83.6%; absolute difference 2.9%, 95%CI [2.7% to 3.2%], P<0.001; all-or-none measure 49.2% vs 44.8% patients; absolute difference 3.5%, 95%CI [2.7% to 4.2%], P<0.001). Further analysis of individual KPIs showed an absolute increase in 6 KPIs ranging from 3.4% to 8.9% (P<0.001 for all comparisons). Compared to 2015-2017, hospital length of stay was shorter (10.95 vs 11.90 days; absolute difference -1.08, 95%CI [-1.18 to -0.99], P<0.001) and in-hospital mortality was significantly reduced (RR 0.88, 95% CI [0.79-0.98]; P=0.01) in 2018-2020. CONCLUSIONS: The 4S intervention was associated with increased adherence to the stroke-care guidelines, which further translated to improved clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02735226.

2.
Adv Healthc Mater ; : e2200971, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36056927

RESUMO

Regulatory T cells overexpressing SPARC (secreted protein acidic and cysteine rich) (Sparchigh Tregs) can help repair infarct tissues after acute myocardial infarction (AMI). This research demonstrates that Sparchigh Treg-derived extracellular vesicles (EVs) effectively improved cardiac function through proinflammatory factors IL-1ß, IL-6, and TNF-α inhibition and collagen synthesis related gene Col3a1 promotion in AMI; moreover, a composite hydrogel-EVs system (DHPM(4APPC)_EVs) is designed based on Sparchigh Treg-derived EVs with CXCR2 overexpressing and pH/H2 O2 /MMP9 temporally responsive gel microspheres. In AMI, due to the levels of chemokine, pH, H2 O2 , and MMP9 enzymes in the infarct area, DHPM(4APPC)_EVs can effectively target the infarct area, release the loaded EVs, form the gel to capture the released EVs, and slowly release the captured EVs, contribute to promote EVs to stay in the infarct area for a long time to play the repair function, so as to reduce myocardial injury and promote the improvement of cardiac function. The proposed system in this research provides a potential approach for the treatment of AMI in the future.

3.
Vet Res ; 53(1): 69, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064470

RESUMO

Chicken cathelicidin-2 (CATH-2) as a host defense peptide has been identified to have potent antimicrobial and immunomodulatory activities. Here, we reported the mechanism by which CATH-2 modulates NLRP3 inflammasome activation. Our results show that CATH-2 and ATP as a positive control induced secretion of IL-1ß and IL-1α in LPS-primed macrophages but did not affect secretion of IL-6, IL-12 and TNF-α. Furthermore, CATH-2 induced caspase-1 activation and oligomerization of apoptosis-associated speck-like protein containing a carboxy- terminal caspase recruitment domain (ASC), which is essential for NLRP3 inflammasome activation. However, CATH-2 failed to induce IL-1ß secretion in Nlrp3-/-, Asc-/- and Casp1-/- macrophages. Notably, IL-1ß and NLRP3 mRNA expression were not affected by CATH-2. In addition, CATH-2-induced NLRP3 inflammasome activation was mediated by K+ efflux but independent of the P2X7 receptor that is required for ATP-mediated K+ efflux. Gene interference of NEK7 kinase which has been identified to directly interact with NLRP3, significantly reduced IL-1ß secretion and caspase-1 activation induced by CATH-2. Furthermore, confocal microscopy shows that CATH-2 significantly induced lysosomal leakage with the diffusion of dextran fluorescent signal. Cathepsin B inhibitors completely abrogated IL-1ß secretion and caspase-1 activation as well as attenuating the formation of ASC specks induced by CATH-2. These results all indicate that CATH-2-induced activation of NLRP3 inflammasome is mediated by K+ efflux, and involves the NEK7 protein and cathepsin B. In conclusion, our study shows that CATH-2 acts as a second signal to activate NLRP3 inflammasome. Our study provides new insight into CATH-2 modulating immune response.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Trifosfato de Adenosina , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas de Transporte/genética , Caspase 1 , Catepsina B/metabolismo , Galinhas/metabolismo , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
4.
Nat Commun ; 13(1): 5046, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068193

RESUMO

Green hydrogen produced by water splitting using renewable energy is the most promising energy carrier of the low-carbon economy. However, the geographic mismatch between renewables distribution and freshwater availability poses a significant challenge to its production. Here, we demonstrate a method of direct hydrogen production from the air, namely, in situ capture of freshwater from the atmosphere using hygroscopic electrolyte and electrolysis powered by solar or wind with a current density up to 574 mA cm-2. A prototype of such has been established and operated for 12 consecutive days with a stable performance at a Faradaic efficiency around 95%. This so-called direct air electrolysis (DAE) module can work under a bone-dry environment with a relative humidity of 4%, overcoming water supply issues and producing green hydrogen sustainably with minimal impact to the environment. The DAE modules can be easily scaled to provide hydrogen to remote, (semi-) arid, and scattered areas.

6.
Biomed Res Int ; 2022: 7514898, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046451

RESUMO

Helical CT plain scan has high spatial and area resolution, which is beneficial to the extraction of CT features of pulmonary nodules, and is of great significance for the diagnosis and differential diagnosis of pulmonary diseases. In order to deeply study the role of visual sensor image algorithm in CT image, this paper adopts clinical simulation method, data fusion method, and image acquisition method to collect images, analyze CT image features, and simplify the algorithm and create a CT model that can better diagnose secondary tuberculosis and lung cancer. We selected 45 patients with lung disease in this group, with an average age of 38 years. At the same time, the consistency analysis results of the diameter and plain CT value data of the five groups of cases measured by two observers are between 0.82 and 0.88, which has a good consistency. We could find that the nodule diameters of the five groups of cases were different (F =16.99, P < 0.01), and the difference was statistically significant (P < 0.06), indicating that our data are not only accurate but also very reliable. ROC was used to analyze the precise value of CT values in the pulmonary tuberculosis group and lung cancer group, intrapulmonary lymph node group, and pulmonary hamartoma group to determine the cutoff value. The results showed that the AUC values of the pulmonary tuberculosis group and the lung cancer group were 0.788, and the middle was the largest, indicating that the values were guaranteed. The basic realization starts with visual sensor technology and designs a clinical model that can more accurately identify CT images and differential diagnosis.


Assuntos
Pneumopatias , Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Tuberculose Pulmonar , Adulto , Diagnóstico Diferencial , Humanos , Pulmão/patologia , Pneumopatias/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Nódulo Pulmonar Solitário/diagnóstico , Tomografia Computadorizada Espiral/métodos , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/patologia
7.
Pest Manag Sci ; 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36056789

RESUMO

BACKGROUND: Phytoseiid mites are important natural enemies of spider mites. Sex-determination mechanism are important basic scientific issues in the reproduction and evolution of predatory mites. Clarifying sex-determination mechanism may provide reference for exploring genetic approach to have the phytoseiid mites produce more female offspring, which could improve their effectiveness as a biological control agent. RESULTS: We used transcriptome sequencing to identify and characterize 20 putative sex-determination genes in the phytoseiid mite Neoseiulus californicus, a species with uncommon pseudo-arrhenotoky, including doublesex-like (dsx1-like), transformer-2 (tra-2), intersex (ix), and fruitless-like (BTB2). A significant negative correlation was found between prey stress and offspring sex ratio. But the most genes identified showed no difference in expression between the groups with lowest and highest female offspring ratios. The hatching rate and sex ratio of female offspring were reduced when the ix gene was silenced, and the oviposition days and fecundity were reduced when the BTB2 gene was silenced. The fecundity was reduced when the tra2 gene was silenced and the snf gene is essential for oviposition in female. There was no effect on reproduction and female sex determination when silencing the dsx1-like and dsx2-like gene. CONCLUSION: The genes BTB2, tra2 and snf are involved in oviposition, and ix may be involved in female sex determination and egg formation in Neoseiulus californicus. The results are conductive to further understanding molecular regulatory mechanism of sex determination in predatory mites and may provide a reference for better use of this predatory by producing more females. © 2022 Society of Chemical Industry.

8.
Nanoscale ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047440

RESUMO

Two-dimensional (2D) elementary tellurium (Te) has attracted intensive attention due to its potential applications in short-wave infrared photodetector devices. Here, we report hydrothermally synthesized 2D Te nanoflakes for short-wave infrared photodetectors with high performance. A Te-based photodetector exhibits a peak responsivity of 51.85 A W-1 at a 1550 nm wavelength, attributed to the efficient absorption of the phonons of 2D Te nanoflakes. Besides, the rising and decay time of the Te photodetector is calculated to be ∼19 µs and ∼21 µs, respectively, due to the rapid diffusion of charge carriers. In addition, Te-photodetectors exhibit a high specific detectivity (D*) of 1.88 × 1010 Jones and a superior external quantum efficiency (EQE) of 4148%. Our findings have demonstrated the development of high-performance short-wave infrared photodetectors with fast responses based on 2D Te nanoflakes.

9.
Toxicol Appl Pharmacol ; : 116232, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36089000

RESUMO

The overexpression of centromere protein K (CENPK) is a major contributor to the malignant progression of numerous cancers. To date, the detailed functions and mechanisms of CENPK in breast carcinoma are not fully elucidated. The goals of this project were to comprehensively address the relevance of CENPK in breast carcinoma. The initial investigation by TCGA analysis revealed a high expression level of CENPK in breast carcinoma. Subsequently, an immunoblotting assay confirmed that CENPK is highly expressed in the clinical samples of breast carcinoma. In vitro experiments elucidated that the inhibition of CENPK produced substantial anticancer effects, including a reduction of proliferation, the inhibition of epithelial-mesenchymal transition, the induction of cell cycle arrest and chemosensitivity. Mechanism research unveiled a role for CENPK in mediating the focal adhesion kinase (FAK1)/PI3K/AKT/mTOR pathway. Inhibiting the FAK/PI3K/AKT/mTOR pathway was able to reverse CENPK-elicited cancer-promoting effects. Additionally, CENPK-silenced breast carcinoma cells exhibited low tumorigenicity in vivo. In summary, our data demonstrated that CENPK inhibition provided an excellent anticancer effect for breast carcinoma by regulating FAK/PI3K/AKT/mTOR pathway. This work illustrates a novel molecular mechanism for CENPK in breast carcinoma and suggests CENPK inhibition as a promising targeted therapy for breast carcinoma.

10.
Oncogene ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085418

RESUMO

Exosomes can selectively secrete harmful metabolic substances from cells to maintain cellular homeostasis, and complex crosstalk occurs between exosomes and tumor-associated macrophages (TAMs) in the glioma immune microenvironment. However, the precise mechanisms by which these exosome-encapsulated cargos create an immunosuppressive microenvironment remain unclear. Herein, we investigated the effect of glioma-derived exosomes (GDEs) on macrophage polarization and glioma progression. We performed sequencing analysis of cerebrospinal fluid (CSF) and tumor tissues from glioma patients to identify functional microRNAs (miRNAs). High levels of miR-3591-3p were found in CSF and GDEs but not in normal brain tissue or glial cells. Functionally, GDEs and miR-3591-3p significantly induced M2 macrophage polarization and increased the secretion of IL10 and TGFß1, which in turn promoted glioma invasion and migration. Moreover, miR-3591-3p overexpression in glioma cell lines resulted in G2/M arrest and markedly increased apoptosis. Mechanistically, miR-3591-3p can directly target CBLB and MAPK1 in macrophages and glioma cells, respectively, and further activate the JAK2/PI3K/AKT/mTOR, JAK2/STAT3, and MAPK signaling pathways. In vivo experiments confirmed that macrophages lentivirally transduced with miR-3591-3p can significantly promote glioma progression. Thus, our study demonstrates that tumor-suppressive miR-3591-3p in glioma cells can be secreted via exosomes and target TAMs to induce the formation of an immunosuppressive microenvironment. Collectively, these findings provide new insights into the role of glioma exosomal miRNAs in mediating the establishment of an immunosuppressive tumor microenvironment and show that miR-3591-3p may be a valuable biomarker and that blocking the encapsulation of miR-3591-3p into exosomes may become a novel immunotherapeutic strategy for glioma.

11.
J Synchrotron Radiat ; 29(Pt 5): 1241-1250, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36073883

RESUMO

In synchrotron radiation X-ray imaging, the imaging field of view and spatial resolution are mutually restricted, which makes it impossible to have both a large field of view and high resolution when carrying out experiments. Constructing an oversampled image through the micro-scanning method and using the deconvolution algorithm to eliminate the point spread function introduced by pixel overlap can increase the resolution under a fixed imaging field of view, thereby improving the ratio of the field of view to the spatial resolution. In this paper, numerical simulation and synchrotron radiation experiments are carried out with a different number of micro-scanning steps. In numerical simulation experiments only affected by the image pixel size, as the number of micro-scanning steps increases, the ability of the oversampled image with deconvolution to improve the resolution is stronger. The achievable resolution of the oversampled image with deconvolution is basically the same as that of the sample image. In the synchrotron radiation experiments, the resolution of the oversampled image with deconvolution in the 2 × 2 mode is significantly improved. However, as the number of micro-scanning steps increases, the resolution improvement is limited, or even no longer improved. Finally, by analyzing the results of numerical simulation and synchrotron radiation experiments, three factors (four other factors affecting the resolution besides the camera resolution, translational accuracy of micro-scanning, and the signal-to-noise ratio of projections) affecting the micro-scanning method are proposed and verified by experiments.

12.
Front Pharmacol ; 13: 953871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120306

RESUMO

Inflammation is an innate immune response to infection, and it is the main factor causing bodily injury and other complications in the pathological process. Ginsenoside Rh4 (G-Rh4), a minor ginsenoside of Panax ginseng C. A. Meyer and Panax notoginseng, has excellent pharmacological properties. However, many of its major pharmacological mechanisms, including anti-inflammatory actions, remain unrevealed. In this study, network pharmacology and an experimental approach were employed to elucidate the drug target and pathways of G-Rh4 in treating inflammation. The potential targets of G-Rh4 were selected from the multi-source databases, and 58 overlapping gene symbols related to G-Rh4 and inflammation were obtained for generating a protein-protein interaction (PPI) network. Molecular docking revealed the high affinities between key proteins and G-Rh4. Gene ontology (GO) and pathway enrichment analyses were used to analyze the screened core targets and explore the target-pathway networks. It was found that the JAK-STAT signaling pathway, TNF signaling pathway, NF-κB signaling pathway, and PI3K-Akt signaling pathway may be the key and main pathways of G-Rh4 to treat inflammation. Additionally, the potential molecular mechanisms of G-Rh4 predicted from network pharmacology analysis were validated in RAW264.7 cells. RT-PCR, Western blot, and ELISA analysis indicated that G-Rh4 significantly inhibited the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß, as well as inflammation-related enzymes in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Moreover, in vitro experiments evaluated that Ginsenoside Rh4 exerts anti-inflammatory effects via the NF-κB and STAT3 signaling pathways. It is believed that our study will provide the basic scientific evidence that G-Rh4 has potential anti-inflammatory effects for further clinical studies.

14.
Environ Toxicol ; 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36114797

RESUMO

Dysregulated follicular development may lead to follicular atresia, and this is associated with oxidative stress in granulosa cells. Kurarinone is a natural compound possessing multiple activities, including antioxidative ability. However, the role of kurarinone in granulosa cell damage during follicular atresia remains unknown. Human ovarian granulosa KGN cells were treated with hydrogen peroxide (H2 O2 ) to induce cellular damage. Cytotoxicity was investigated by lactate dehydrogenase (LDH) release assay. Oxidative stress was evaluated by detection of reactive oxygen species (ROS) generation and oxidative biomarker levels. Cell apoptosis was evaluated by flow cytometry, a Cell Death Detection ELISA Kit, and a Caspase-3 Assay Kit. The downstream target and related signaling pathway were analyzed by western blotting. Kurarinone attenuated H2 O2 -induced LDH release in KGN cells. Kurarinone relieved H2 O2 -induced increase in ROS generation and malondialdehyde level as well as decrease in superoxide dismutase-1 activity and heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1 mRNA levels. Kurarinone inhibited H2 O2 -induced apoptosis in KGN cells. Kurarinone targeted insulin-like growth factor 1 (IGF1) and upregulated IGF1 expression to activate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling. IGF1 silencing attenuated the suppressive effects of kurarinone on H2 O2 -induced oxidative stress and apoptosis in KGN cells. In conclusion, kurarinone attenuates H2 O2 -induced oxidative stress and apoptosis in KGN cells through activating the PI3K/Akt signaling by upregulating IGF1 expression, indicating the therapeutic potential of kurarinone in follicular atresia.

15.
Front Oncol ; 12: 934978, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059692

RESUMO

Objectives: This study aimed to examine the incidence of bifid pancreatic duct (BPD) in pancreaticoduodenectomy (PD) and clarify its impact on clinically relevant postoperative pancreatic fistula (CR-POPF). Background: Until now, all the literature about BPD during PD are published as case reports, and the incidence of BPD in PD and its impact on CR-POPF remain unknown. Results: A total of 438 consecutive PDs were divided into two groups: the former year group and the latter year group. The former year group included 215 consecutive PDs, while the latter year group included 223. In the latter year group, we found 16 BPDs during PD (O-BPD); the incidence of O-BPD is 7.17%. Of them, there were eight patients who had BPD in the preoperative imaging (I-BPD). All the I-BPDs are O-BPDs; which means that 50% of O-BPDs were a single pancreatic duct in the preoperative imaging (I-SPD). There were 17 I-BPDs in the 438 consecutive PDs; the incidence of I-BPD is 3.88%. In the former year group, the rate of severe complications of I-BPD and I-SPD is 77.78% and 27.18%, respectively (p = 0.003); the rate of CR-POPF of I-BPD is higher than I-SPD, 55.56% vs. 27.18%, but there were no statistically significant differences. In the latter year group, the rate of severe complications of O-BPD and O-SPD is 50% and 18.36%, and the rate of CR-POPF of O-BPD and O-SPD is 37.5% and 22.22%, respectively; both of them have statistically significant differences, and the p-value is 0.003 and 0.006, respectively. In the subgroup analysis, both the rate of severe complications and the rate of CR-POPF of I-BPD were higher than O-BPD, 77.78% vs. 50%, and 55.56% vs. 37.5%, but there were no statistically significant differences in both of them; the p-value is 0.174 and 0.434, respectively. Univariate and multivariate analyses showed that BPD was an independent risk factor of CR-POPF. Conclusions: The incidence of O-BPD in PD is 7.17%, 50% of O-BPDs were I-SPD, and the incidence of I-BPD is 3.88%. BPD is an independent risk factor of CR-POPF. The suture closure method may be a simple, safe, and effective method in dealing with BPD in PD.

16.
J Clin Lipidol ; 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-36064883

RESUMO

BACKGROUND: GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, is a crucial partner for lipoprotein lipase (LPL) in plasma triglyceride metabolism. GPIHBP1 autoantibodies block LPL binding to GPIHBP1 and lead to severe hypertriglyceridemia (HTG) and HTG-induced acute pancreatitis (HTG-AP). We sought to define the incidence of GPIHBP1 autoantibodies in patients with HTG-AP. OBJECTIVE: We determined the incidence of GPIHBP1 autoantibody in HTG-AP patients, and compared the clinical features and long-term outcomes between GPIHBP1 autoantibody-positive and negative groups. METHODS: An enzyme-linked immunosorbent assay was used to screen for GPIHBP1 autoantibody in 116 HTG-AP patients hospitalized from Jan 1, 2015 to Aug 31, 2019. All patients were followed up for 24 months. The primary outcome was the recurrence rate of HTG-AP during the two-year follow-up period. The incidence of recurrent episodes was analyzed by the Kaplan-Meier method and multivariable Cox regression was used to identify risk factors. RESULTS: GPIHBP1 autoantibodies were present in 17 of 116 study patients (14.66%). The 2-year recurrence rate of HTG-AP was much higher in the GPIHBP1 autoantibody-positive group (35%, 6 in 17) than in the negative group (4%, 4 in 99). The multivariable Cox regression analysis showed that GPIHBP1 autoantibody was an independent risk factor for HTG-AP recurrence in two years. CONCLUSIONS: The presence of GPIHBP1 autoantibody is common in patients with HTG-AP, and is an independent risk factor for two-year recurrence of HTG-AP.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36067098

RESUMO

Depression is a common mental illness which has brought great harm to the individuals. With recent evidence that many objective physiological signals are associated with depression, automated detection of depression is urgent and important for the growing concern of mental illness. We investigate the problem of classifying depression by facial expressions, which may aid in online diagnosis and rehabilitation engineering of depression. In this work, We propose a weakly supervised learning approach employing multiple instance learning (MIL) on 150 videos data from 75 depressed and 75 healthy subjects. In addition, we present a novel MIL dual-stream aggregator that considers both the instance-level and the bag-level in order to emphasize the information with symptoms. Specifically, our method named ADDMIL uses max-pooling at the instance level to capture symptom information and further integrates the contribution of each instance at the bag level using attention weights. Our method achieves 74.7% accuracy and 74.5% recall on the collected dataset, which not only improves 10.1% accuracy and 9.8% recall over the baseline but also exceeds the best accuracy result of MIL-based method by 2.1%. Our work achieves results that are comparable to the state-of-the-art methods and demonstrates that multiple instance learning has great potential for depression classification. We present for the first time a weakly supervised learning approach in the detection of depression through raw facial expressions, which may provide a new framework for other psychiatric disorders detection methods.

18.
Front Immunol ; 13: 989966, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090976

RESUMO

Immune checkpoint inhibitors (ICIs) have had a revolutionary effect on the treatment of patients with advanced non-small cell lung cancer (NSCLC), especially squamous cell lung cancer. However, ICIs may cause associated immune-related adverse events (ir-AEs). No case of sintilimab-induced toxic epidermal necrolysis (TEN) has been reported. In this report, we discussed a patient with advanced NSCLC and comorbid pulmonary tuberculosis who underwent immunotherapy and chemotherapy as neoadjuvant therapy and anti-tuberculosis therapy concurrently. Partial response (PR) of the tumor was achieved after three cycles of neoadjuvant therapy without cutaneous toxicities. Video-assisted thoracoscopic surgery (VATS) left lower lobectomy was performed successfully. Sintilimab and chemotherapy were administered as adjuvant therapy, after which the patient suffered severe TEN that rapidly progressed to cover >50% of the skin. TEN was associated with extensive rashes of the trunk and pruritus. With history of sintilimab use, clinical symptoms, and physical examination, TEN was diagnosed. Intravenous methylprednisolone and oral prednisone were administered until the patient totally recovered from the cutaneous toxicities caused by sintilimab. Monitoring of such rare but severe cutaneous toxicities is essential in patients who are treated with sintilimab.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Dermatopatias , Síndrome de Stevens-Johnson , Tuberculose Pulmonar , Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Dermatopatias/induzido quimicamente , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico
19.
Phytomedicine ; 106: 154429, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36099652

RESUMO

BACKGROUND: High prevalence and reoccurrence rate of nephrolithiasis bring about serious socioeconomic and healthcare burden, necessitating the need of effective therapeutic agents. Previous study revealed that gallic acid (GAL) alters the nucleation pathway of calcium oxalate (CaOx). On the other hand, it appears protective role against oxidative injury. Whether GAL could protect against crystal-induced lesion in vivo, and its underlying mechanism is yet unsolved. PURPOSE: This study aims to investigate the protective effects of GAL on the crystal-induced renal injury and its underlying mechanism in the mouse model of stone formation induced by glyoxylic acid. STUDY DESIGN AND METHODS: The mouse model of stone formation was established via successive intraperitoneal injection of glyoxylate. Proximal tubular epithelial cell line HK-2 treated with calcium oxalate monohydrate (COM) was used as in vitro model. The protective role of GAL on nephrolithiasis was tested by determination of tubular injury, crystal deposition and adhesion, levels of inflammatory cytokines, macrophage infiltration and the redox status of kidney. In vitro, effect of GAL on the ROS level and oxidative tubular injury induced by COM were detected, as well as major antioxidant pathway Nrf2/HO-1. RESULTS: Administration of GAL alleviates the renal deposition and adhesion of CaOx stone. Meanwhile, GAL ameliorates the inflammation and renal tubular injury. Level of intracellular ROS, osteopontin and CD44 are reduced, either in the mouse model of stone formation or in the COM-treated HK-2 cells after treatment of GAL. Mechanistically, GAL activates Nrf2/HO-1 pathway in HK-2 cells. Silencing Nrf2 abrogates the protective effect of GAL on the oxidative injury and adhesion of COM in HK-2 cells. CONCLUSION: Taken together, our study demonstrates the protective effect of GAL on the deposition of kidney stone and consequent tubular injury. Induction of the antioxidant pathway Nrf2/HO-1 was found to decrease the level of ROS and oxidative injury, thus implying that GAL could be a potential therapeutic agent for the treatment of nephrolithiasis.

20.
Environ Sci Technol ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129490

RESUMO

Nitroaromatic compounds (NACs) not only are strongly absorbing chromophores but also adversely affect human health. NACs can be emitted from incomplete combustions and can derive secondarily through photochemical reactions. Here, emission experiments were conducted for 31 fuel-stove combinations to elucidate variations in, and influencing factors of, NAC emission factors (EF∑NACs) and to explore potential tracers for different combustion sources. EF∑NACs varied by 2 orders of magnitude among different combinations. Differences in fuel type contributed more than the stove difference to the observed variation. EF∑NACs for biomass pellets was approximately 66% lower than that for raw biomass, although the bulk organic and brown carbon EFs were 95% lower. 2-Nitro-1-naphthol was the most abundant individual compound, followed by 4-nitrocatechol, while acid compounds (salicylic acid and benzoic acid) were low in abundance (<1%). Substantially different profiles were observed between coal and biomass burning emissions. Biomass burning had more single-ring-based phenolic compounds with more 4-nitrocatechol, while in coal combustion, more two-ring products were produced. This study demonstrated much lower ratios of 2-nitro-1-naphthol/4-nitrocatechol for biomass in both traditional (2.0 ± 3.5) and improved stoves (3.0 ± 2.1) than for coals (15 ± 6). Coal and biomass burning differed in not only EF∑NACs but also compound profile, consequently leading to distinct health and climate impacts; moreover, the ratio of 2-nitro-1-naphthol/4-nitrocatechol may be used in source apportionment of NACs.

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