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1.
Haematologica ; 108(9): 2467-2475, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36951150

RESUMO

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered "cured" of the disease. We aimed to evaluate the statistical "cure" of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients' perspective.


Assuntos
Linfoma Extranodal de Células T-NK , Humanos , Idoso , Prognóstico , Estudos Retrospectivos , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/terapia , Fatores de Risco , Células Matadoras Naturais/patologia
2.
Ann Hematol ; 102(9): 2459-2469, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37306711

RESUMO

Recently, progression-free survival at 24 months (PFS24) was defined as clinically relevant for patients with extranodal NK/T cell lymphoma. Herein, the clinical data from two independent random cohorts (696 patients each in the primary and validation datasets) were used to develop and validate a risk index for PFS24 (PFS24-RI), and evaluate its ability to predict early progression. Patients achieving PFS24 had a 5-year overall survival (OS) of 95.8%, whereas OS was only 21.2% in those failing PFS24 (P<0.001). PFS24 was an important predictor of subsequent OS, independent of risk stratification. The proportion of patients achieving PFS24 and 5-year OS rates correlated linearly among risk-stratified groups. Based on multivariate analysis of the primary dataset, the PFS24-RI included five risk factors: stage II or III/IV, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group score ≥2, primary tumor invasion, and extra-upper aerodigestive tract. PFS24-RI stratified the patients into low-risk (0), intermediate-risk (1-2), high-risk (≥3) groups with different prognoses. Harrell's C-index of PFS24-RI for PFS24 prediction was 0.667 in the validation dataset, indicating a good discriminative ability. PFS24-RI calibration indicated that the actual observed and predicted probability of failing PFS24 agreed well. PFS24-RI provided the probability of achieving PFS24 at an individual patient level.


Assuntos
Linfoma Extranodal de Células T-NK , Humanos , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão , Células Matadoras Naturais/patologia , Estudos Retrospectivos
3.
Anal Chem ; 93(36): 12447-12455, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34449219

RESUMO

Alzheimer's disease (AD), known as a progressive neurodegenerative disorder, has had a terrible impact on the health of aged people. Due to its severity, early diagnosis of AD is significant to retard the progress and provide timely treatment. Here, we report a fluorescence ratio detection of AD biomarker amyloid ß oligomers (AßOs) by combining highly doped upconversion nanoparticles-SiO2@metal-organic framework/black hole quencher (H-USM/BHQ-1) microspheres with optical tweezer (OT) microscopic imaging. Optical trapping a single microsphere not only avoids the interference of fluid viscosity but also provides a high power density laser source to efficiently stimulate upconversion luminescence (UCL) of highly doped upconversion nanoparticles (H-UCNPs). Under this condition, H-UCNPs show stronger UCL and greater power-dependent properties compared to low-doped ones. Moreover, the closely packed quenching molecules BHQ-1 on a metal-organic framework (ZIF-8) exhibit excellent quenching efficiency for upconversion 525 and 540 nm emission. Also, the luminescent resonance energy transfer efficiency reaches 89.58%. When different concentrations of AßOs are present, the UCL540 recovers due to the decomposition of ZIF-8 and the release of BHQ-1. Using 540 and 654 nm emission ratio of highly doped UCNPs as reporters, the limit of detection reaches 28.4 pM for the quantitative determination of AßOs. Besides, this strategy is able to selectively quantify the AßO concentration. Therefore, we demonstrated the combination of optical trapping and highly doped UCNPs which is applied for the detection of AßOs with high sensitivity and specificity.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Idoso , Peptídeos beta-Amiloides , Humanos , Microesferas , Dióxido de Silício
4.
Chem Biodivers ; 18(10): e2100578, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34499797

RESUMO

Chemical investigation of the marine sponge Dysidea avara, collected from the South China Sea, yielded 13 steroids, including nine new (1-9) and four known (10-13) ones. The new structures were elucidated as (3S,14R)-3,14-dihydroxycholesta-5,8-dien-7-one (1), (22E,24R)-7α-ethoxy-5α,6α-epoxyergosta-8(14),22-dien-3ß-ol (2), 3ß-hydroxy-7α-ethoxy-5α,6α-epoxy-8(14)-cholestene (3), 3ß,5α-dihydroxy-6α-ethoxychofesta-7,9(11)-diene (4), 3ß,5α-dihydroxy-6ß-ethoxycholest-7-ene (5), (22E,24R)-24-ethoxy-3ß,5α-dihydroxy-6ß-ethoxyergosta-7,22-diene (6), (22E)-3ß,5α-dihydroxy-6ß-ethoxycholesta-7,22-diene (7), 24-ethoxy-3ß,5α-dihydroxy-6ß-ethoxycholest-7-ene (8 and 9), by extensive spectroscopic analyses, such as HR-ESI-MS, 1D and 2D NMR data. The absolute configuration of 1 was assigned by comparison the experimental ECD spectra with the calculated ones. Among the 13 metabolites, compounds 1, 4, 11, 12, and 13 showed NF-κB inhibitory activities in human HER-293 cells with IC50 values of 6.4, 18.7, 8.1, 9.6, and 7.5 µM, respectively. Preliminary structure-activity relationship analysis unveiled that the conjugated ketones or unsaturated double bonds might be the functional groups for the five active steroids.


Assuntos
Dysidea/química , NF-kappa B/antagonistas & inibidores , Esteroides/farmacologia , Animais , China , Células HEK293 , Humanos , Conformação Molecular , NF-kappa B/metabolismo , Estereoisomerismo , Esteroides/química , Esteroides/isolamento & purificação
5.
Am J Hematol ; 95(9): 1047-1056, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32449800

RESUMO

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new-regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram-revised risk index (NRI). A comparative study was performed using propensity score-matched (PSM) analysis. Adding new-regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression-free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate-risk/high-risk patients, but not for low-risk patients. For intermediate-risk/high-risk patients, RT + CT and CT + RT resulted in non-significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk-based, response-adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate-risk/high-risk early-stage patients with ENKTCL in the modern treatment era.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia , Linfoma Extranodal de Células T-NK , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/terapia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Taxa de Sobrevida
6.
Ecotoxicol Environ Saf ; 189: 109979, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31835044

RESUMO

The sediments of water bodies are not only pollutants sink but also sources of pollution. The assessment for the whole-sediment toxicity is still challenging research. Although the application of immobilized algal bead could overcome the practical difficulties in sediment toxicity assay, the weak growth and reduced sensitivity of algae inside the bead restricted its application. In this study, a sediment toxicity test was developed using immobilized sediment and Chlorella vulgaris. The immobilized sediment was prepared by mixing 2 g freeze-dried sediment and 15-mL 3% (w/v) alginate and hardened in a 4% (w/v) CaCl2 solution. Based on a C. vulgaris growth inhibition test and using the immobilized sediment, the median effective concentration value (EC50) of the spiked Cu and diuron was 506.23 and 2.37 mg/kg respectively, lower than that of using immobilized algae (719.62 and 3.12 mg/kg respectively). The Cu and diuron concentrations in the corresponding overlying water from the spiked immobilized and free sediment showed that sediment pollutants' diffusion capacity was not decreased after immobilization. By using the immobilized sediment in algae toxicity bioassay, the changes in the sediment toxicity of a polluted river before and after dredging was evaluated. The C. vulgaris growth inhibition in sediment A decreased from 81.94% to 8.43%; sediment B remained unchanged; sediment C stimulated the growth of C. vulgaris before dredging (-15.56%), but inhibited the algae growth after dredging (26.88%), and sediment D decreased growth inhibition from 32.66% to -12.60%.


Assuntos
Chlorella vulgaris/efeitos dos fármacos , Sedimentos Geológicos/química , Testes de Toxicidade/métodos , Poluentes Químicos da Água/toxicidade , Alginatos/química , Cloreto de Cálcio/química , Chlorella vulgaris/crescimento & desenvolvimento , Cobre/análise , Cobre/toxicidade , Diurona/análise , Diurona/toxicidade , Rios/química , Poluentes Químicos da Água/análise
7.
Bull Environ Contam Toxicol ; 105(6): 874-881, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33231746

RESUMO

Most of the pollutants discharged into the water will deposit at the bottom of the river and may cause biological toxicity. Daphnia magna-elutriate toxicity bioassay was usually applied to evaluate sediment toxicity. However, the loss of hydrophobic pollutants during the elutriating will lead to the underestimation of sediment toxicity. The purpose of this study is to apply the optimized immobilized sediments to D. magna test, so it can be directly exposed to the sediments and get accurate sediment toxicity results. The optimized immobilized sediment was prepared by mixing 1 g sediment with 7.5 mL 3% (w/v) alginate and hardened in a 4% (w/v) CaCl2 solution. Based on D. magna acute toxicity test, the median lethal concentration values (LC50) of the spiked Cu and diuron measured by using immobilized sediment were both lower than that of using the elutriate, in which the difference of Cu-LC50 reached a significant level. The toxicity changes of sediment in the polluted rivers before and after dredging were then be evaluated by using the immobilized sediment. The toxicity of the sediments at four sites decreased from acute-toxic (pro-dredging) to slight-acute-toxic and nontoxic (post-dredging).


Assuntos
Sedimentos Geológicos/química , Poluentes Químicos da Água/toxicidade , Animais , Bioensaio , Daphnia , Diurona , Poluentes Ambientais , Poluição Ambiental , Dose Letal Mediana , Rios/química , Testes de Toxicidade Aguda , Água , Poluentes Químicos da Água/análise
8.
Int J Cancer ; 144(9): 2227-2238, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30374974

RESUMO

Vasculogenic mimicry (VM) is a special vascular pattern in malignant tumors, which is composed of highly aggressive tumor cells. This tumor cell-mediated blood supply pattern is closely associated with a poor prognosis in cancer patients. The interaction of axon guidance factor Sema4D and its high affinity receptor plexinB1 could activate small GTPase RhoA and its downstream ROCKs; this process has an active role in the migration of endothelial cells and tumor angiogenesis. Here, we have begun to uncover the role of this pathway in VM formation in non-small cell lung cancer (NSCLC). First, we confirmed this special form of vasculature in NSCLC tissues and found the existence of VM channels in tumor tissues was correlated with Sema4D expression. Further, we found that inhibition of Sema4D in the human NSCLC cells H1299 and HCC827 reduces VM formation both in vitro and in vivo. Moreover, we demonstrated that downregulating the expression of plexinB1 by siRNA expressing vectors and inhibiting the RhoA/ROCK signaling pathway using fasudil can reduce VM formation of H1299 and HCC827 cells. Finally, we found that suppression of Sema4D leads to less stress fibers and depleted the motility of H1299 and HCC827 cells. Collectively, our study implicates Sema4D plays an important role in the process of VM formation in NSCLC through activating the RhoA/ROCK pathway and regulating tumor cell plasticity and migration. Modulation of the Sema4D/plexinB1 and downstream RhoA/ROCK pathway may prevent the tumor blood supply through the VM pattern, which may eventually halt growth and metastasis of NSCLC.


Assuntos
Antígenos CD/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Neovascularização Patológica/patologia , Proteínas do Tecido Nervoso/metabolismo , Receptores de Superfície Celular/metabolismo , Semaforinas/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Células A549 , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Células Endoteliais/fisiologia , Ativação Enzimática , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas do Tecido Nervoso/genética , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , RNA Interferente Pequeno/genética , Receptores de Superfície Celular/genética , Semaforinas/antagonistas & inibidores , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
9.
Brain Behav Immun ; 81: 111-121, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31176001

RESUMO

PURPOSE: Elevated catecholamines in the tumor microenvironment often correlate with tumor development. However, the mechanisms by which catecholamines modulate lung cancer growth are still poorly understood. This study is aimed at examining the functions and mechanisms of catecholamine-induced macrophage polarization in angiogenesis and tumor development. EXPERIMENTAL DESIGN: We established in vitro and in vivo models to investigate the relationship between catecholamines and macrophages in lung cancer. Flow cytometry, cytokine detection, tube formation assay, immunofluorescence, and western blot analysis were performed, and animal models were also used to explore the underlying mechanism of catecholamine-induced macrophage polarization and host immunological response. RESULTS: Catecholamines were shown to be secreted into tumor under the control of the sympathetic nerve system to maintain the pro-tumoral microenvironment. In vivo, the chemical depletion of the natural catecholamine stock with 6OHDA could reduce the release of catecholamines within tumor tissues, restrain the function of alternatively activated M2 macrophage, attenuate tumor neovascularization, and inhibit tumor growth. In vitro, catecholamine treatment triggered the M2 polarization of macrophages, enhanced the expression of VEGF, promoted tumor angiogenesis, and these catecholamine-stimulated effects could be reversed by the adrenergic receptor antagonist propranolol. In addition to regulating tumor-associated macrophages (TAM) recruitment, decreasing catecholamine levels could also shift the immunosuppressive microenvironment by decreasing myeloid-derived suppressor cells' (MDSCs) recruitment and facilitating dendritic cells' (DCs) activation, potentially resulting in a positive antitumor immune response. CONCLUSION: Our study demonstrates the potential of adrenergic stress and catecholamine-driven adrenergic signaling of TAMs to regulate the immune status of a tumor microenvironment and provides promising targets for anticancer therapies.


Assuntos
Catecolaminas/metabolismo , Neoplasias Pulmonares/metabolismo , Neovascularização Patológica/fisiopatologia , Animais , Catecolaminas/fisiologia , Linhagem Celular Tumoral , Movimento Celular/imunologia , Citocinas/metabolismo , Humanos , Ativação de Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais , Microambiente Tumoral
10.
Diabetol Metab Syndr ; 16(1): 136, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907296

RESUMO

BACKGROUND: The interplay between diabetes mellitus (DM), glycemic traits, and vascular and valvular calcifications is intricate and multifactorial. Exploring potential mediators may illuminate underlying pathways and identify novel therapeutic targets. METHODS: We utilized univariable and multivariable Mendelian randomization (MR) analyses to investigate associations and mediation effects. Additionally, the multivariable MR analyses incorporated cardiometabolic risk factors, allowing us to account for potential confounders. RESULTS: Type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) were positively associated with both coronary artery calcification (CAC) and calcific aortic valvular stenosis (CAVS). However, fasting glucose (FG) was only linked to CAVS and showed no association with CAC. Additionally, CAVS demonstrated a causal effect on FG. Calcium levels partially mediated the impact of T2DM on both types of calcifications. Specifically, serum calcium was positively associated with both CAC and CAVS. The mediation effects of calcium levels on the impact of T2DM on CAC and CAVS were 6.063% and 3.939%, respectively. The associations between T2DM and HbA1c with calcifications were influenced by body mass index (BMI) and smoking status. However, these associations were generally reduced after adjusting for hypertension. CONCLUSION: Our findings suggest a genetically supported causal relationship between DM, glycemic traits, and vascular and valvular calcifications, with serum calcium playing a critical mediating role.

11.
Cancer Rep (Hoboken) ; 6(5): e1800, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36919649

RESUMO

BACKGROUND: The gastrointestinal (GI) tract is the second most frequent extranasal involvement site for ENKTL. This study aimed to explore the clinicopathological features, treatment models, survival outcomes, and prognosis of gastrointestinal ENKTL (GI-ENKTL). METHODS: The clinical data of GI-ENKTL patients were extracted from the China Lymphoma Collaborative Group (CLCG) database and were analyzed retrospectively. RESULTS: A total of 30 patients were enrolled, with a male/female ratio of 4:1 and a median age of 42 years. Twenty-nine patients received chemotherapy, of whom 15 patients received asparaginase-based (ASP-based) regimens. Moreover, seven received surgery and three received radiotherapy. The overall response an d complete remission rates were 50.0% and 30.0% for the whole cohort, 50.0% and 37.5% for patients treated with ASP-based regimens, and 50.0% and 25.0% for those treated with non-ASP-based regimens, respectively. The median follow-up was 12.9 months and the 1-year overall survival rate was 40.0% for the whole cohort. For those patients in an early stage, ASP-based regimens resulted in a superior 1-year progression-free survival rate compared to non-ASP-based regimens (100.0% vs. 36.0%, p = .07). However, ASP-based regimens did not improve survival in patients at an advanced stage. CONCLUSION: GI-ENKTL still has a poor prognosis, even in the era of modern asparaginase-based treatment strategies.


Assuntos
Neoplasias Gastrointestinais , Linfoma Extranodal de Células T-NK , Humanos , Masculino , Feminino , Adulto , Asparaginase , Estudos Retrospectivos , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/patologia , Prognóstico , Neoplasias Gastrointestinais/tratamento farmacológico , Células Matadoras Naturais/patologia
12.
EJHaem ; 4(1): 78-89, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36819187

RESUMO

This study aimed to investigate the characteristics and prognosis of distant metastasis (DM) after primary treatment for early-stage extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTCL). A total of 1619 patients from the China Lymphoma Collaborative Group database were retrospectively reviewed. The cumulative incidence of DM was assessed using Fine and Gray's competing risk analysis. The correlation between DM sites was evaluated using phi coefficients, while DM sites were classified using hierarchical clustering. Regression analysis was used to assess the linear correlation between DM-free survival (DMFS) and overall survival (OS). The 5-year cumulative DM rate was 26.2%, with the highest annual hazard rate being in the first year (14.9%). The most frequent DM sites were the skin and soft tissues (SSTs, 32.4%) and distant lymph nodes (LNs, 31.3%). DM sites were categorized into four subgroups of distinct prognosis - distant LN, SST, extracutaneous site, and lymphoma-associated hemophagocytic lymphohistiocytosis. SST or distant LN, solitary metastasis, and late-onset DM demonstrated a relatively favorable prognosis. Contemporary chemotherapy significantly decreased DM rates and improved DMFS. Decreased DM rates were further associated with increased OS probabilities. Our findings improve the understanding of the variable clinical behaviors of early-stage ENKTCL based on four distinct DM sites and thus provide guidance for future therapeutic decisions, metastatic surveillance, and translational trial design.

13.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 6): o1621-2, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22719425

RESUMO

In the title mol-ecule, C(30)H(42)N(6)O(2), the amide-substituted N atoms of the tetra-zine ring deviate from the approximate plane of the four other atoms in the ring by 0.457 (3) and 0.463 (3) Å, forming a boat conformation. The two benzene rings form a dihedral angle of 47.69 (9)°. Intra-molecular N-H⋯N and weak C-H⋯O hydrogen bonds are observed.

14.
ACS Sens ; 7(5): 1572-1580, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35482449

RESUMO

Although great headway has been made in DNAzyme-based detection of Pb2+, its adaptability, sensitivity, and accessibility in complex media still need to be improved. For this, we introduce new ways to surmount these hurdles. First, a spherical nucleic acid (SNA) fluorescence probe (Au nanoparticles-DNAzyme probe) is utilized to specifically identify Pb2+ and its suitability for precise detection of Pb2+ in complex samples due to its excellent nuclease resistance. Second, the sensitivity of Pb2+ detection is greatly enhanced via the use of a clustered regularly interspaced short palindromic repeats-Cas12a with target recognition accuracy to amplify the fluorescent signal upon the trans cleavage of the SNA (signal probe), and the limit of detection reaches as low as 86 fM. Third, we boost the fluorescence on photonic crystal chips with a bionic periodic arrangement by employing a straightforward detection device (smartphone and portable UV lamp) to achieve on-site detection of Pb2+ with the limit of detection as low as 24 pM. Based on the abovementioned efforts, the modified Pb2+ fluorescence sensor has the advantages of higher sensitivity, better specificity, accessibility, less sample consumption, and so forth. Moreover, it can be applied to accurately detect Pb2+ in complex biological or environmental samples, which is of great promise for widespread applications.


Assuntos
DNA Catalítico , Nanopartículas Metálicas , Sistemas CRISPR-Cas , Ouro , Chumbo
15.
Front Public Health ; 10: 1023797, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36582384

RESUMO

Objective: This study aimed to provide a basis for epidemic prevention and control measures as well as the management of re-positive personnel by analyzing and summarizing the characteristics of re-positive patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infections discharged from a hospital in the Ningxia Hui Autonomous Region in 2021. Methods: This case-control study included a total of 45 patients with Delta variant infections diagnosed in the Fourth People's Hospital of the Ningxia Hui Autonomous Region between October 17 and November 28, 2021. Based on the nucleic acid test results post-discharge, the patients were dichotomized into re-positive and non-re-positive groups. Based on the time of the first re-positive test, the re-positive group was further divided into <7 and ≥7 days groups to compare their clinical characteristics and explore the possible influencing factors of this re-positivity. Results: Of the 45 total patients, 16 were re-positive (re-positivity rate: 35.6%), including four patients who were re-positive after 2 weeks (re-positivity rate: 8.8%). The median time of the first re-positive after discharge was 7 days (IQR: 14-3). The re-positive group was younger than the non-re-positive group (35 vs. 53, P < 0.05), had a higher proportion of patients who were not receiving antiviral therapy (56.2 vs. 17.2%, P < 0.05). The median CT value of nucleic acid in the re-positive group was considerably greater than that at admission (36.7 vs. 22.6 P < 0.05). The findings demonstrated that neutralizing antibody treatment significantly raised the average IgG antibody level in patients, particularly in those who had not received COVID-19 vaccine (P < 0.05). The median lowest nucleic acid CT value of the ≥7 days group during the re-positive period and the immunoglobulin G (IgG) antibody level at discharge were lower than those in the <7 days group (P < 0.05). When compared to the non-positive group, patients in the ≥7 days group had a higher median virus nucleic acid CT value (27.1 vs. 19.2, P < 0.05) and absolute number of lymphocytes at admission (1,360 vs. 952, P < 0.05), and a lower IgG antibody level at discharge (P < 0.05). Conclusions: In conclusion, this study found that: (1) The re-positivity rate of SARS-CoV-2 Delta variant infection in this group was 35.6%, while the re-positivity rate was the same as that of the original strain 2 weeks after discharge (8.0%). (2) Young people, patients who did not use antiviral therapy or had low IgG antibody levels at discharge were more likely to have re-positive. And the CT value of nucleic acid at the time of initial infection was higher in re-positive group. We speculated that the higher the CT value of nucleic acid at the time of initial infection, the longer the intermittent shedding time of the virus. (3) Re-positive patients were asymptomatic. The median CT value of nucleic acid was > 35 at the re-positive time, and the close contacts were not detected as positive. The overall transmission risk of re-positive patients is low.


Assuntos
COVID-19 , Ácidos Nucleicos , Humanos , Adolescente , SARS-CoV-2/genética , Estudos de Casos e Controles , Assistência ao Convalescente , Vacinas contra COVID-19 , Alta do Paciente , Antivirais , Imunoglobulina G
16.
World J Clin Cases ; 9(33): 10249-10256, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34904096

RESUMO

BACKGROUND: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a progressive chronic disease that is inherited in an autosomal dominant fashion. Symptoms include hyperuricemia, gout, interstitial nephritis, renal cysts, and progressive renal damage that can lead to end-stage renal disease. Mutations in the uromodulin gene (UMOD) characterize the ADTKD-UMOD clinical subtype of this disease. To date, > 100 UMOD mutations have been identified. Early diagnosis of ADTKD-UMOD is important to treat the disease, slow down disease progression, and facilitate the identification of potentially affected family members. CASE SUMMARY: We report a 40-year-old man harboring a novel heterozygous missense mutation in UMOD (c.554G>T; p. Arg185Leu). The patient had hyperuricemia, gout, and chronic kidney disease. The same mutation was detected in his daughter, aunt and cousin. CONCLUSION: A single nucleotide substitution in exon 3 of UMOD was responsible for the heterozygous missense mutation (c.554G>T, p.Arg185Leu).

17.
World J Clin Cases ; 9(22): 6510-6514, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34435019

RESUMO

BACKGROUND: Abdominal hemorrhage is a complication of peritoneal dialysis catheter (PDC) insertion that cannot be neglected, and its causes are mainly related to surgical injury. This article reports a case of massive abdominal hemorrhage that was caused by a rare rupture of corpus luteum shortly after PDC during the initiation of peritoneal dialysis (PD) insertion. CASE SUMMARY: A 37-year-old woman was surgically placed a Tenckhoff catheter because of end-stage renal disease. On the third postoperative day, the color of the abdominal drainage fluid was pink, and deepened gradually. It turned pale after initiating conservative treatment. On the tenth postoperative day, the color of the abdominal drainage fluid suddenly turned dark red, and the color progressively deepened. The patient's hemoglobin dropped from 88 g/L to 57 g/L. Abdominal computed tomography (CT) indicated abdominal effusion and a high-density shadow in the abdominal cavity. The surgeon performed a laparotomy and found that the corpus luteum had ruptured on the right side and a left ovarian blood body had formed. The gynecologist repaired the ovary and performed a bilateral oophoroplasty. After the operation, the patient stopped bleeding and hemodialysis was temporarily stopped. PD was resumed after half a month. The patient's condition improved, and she was discharged 14 d after the laparotomy. CONCLUSION: If abdominal hemorrhage occurs in women of childbearing age after PDC insertion, luteal rupture should be considered as the cause.

18.
PLoS One ; 16(9): e0255504, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473729

RESUMO

Benzophenone (BPs) and 4-Methylbenzylidene Camphor are used as ultraviolet (UV) filters to protect the skin and hair in personal care products. The discharging of the three chemicals may endanger the receiving water ecosystem. In the present study, the mutagenicity of BP-6, BP-8, and 4-Methylbenzylidene Camphor was tested using the Salmonella typhimurium reverse mutation test (Ames test) in the system with and without rat liver microsomal preparations (S9). Four S.typhimurium strains, TA97, TA98, TA100, and TA102 were employed in the Ames tests. The mutagenicity was detected from all three chemicals. The addition of S9 increased the mutation ratios of three chemicals to four strains, except BP-6 to TA100 strain and 4-MBC to TA97 and TA98 strain. In the mixed experiment, all positive effects were detected in the absence of S9. However, the results all became negative in the presence of S9. For the mixture of BP-6 and 4-MBC, positive results were detected on four tester strains except for the TA100 strain. For the mixture of BP-6, BP-8, and 4-MBC, positive results were detected on four strains. The mixture test results showed antagonism in mutagenicity for the mixture of BP-6 and 4-MBC to TA98 and TA100 strains and the mixture of BP-6, BP-8, and 4-MBC to TA100 and TA102 strains.


Assuntos
Benzofenonas/toxicidade , Cânfora/análogos & derivados , Mutagênese/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Salmonella typhimurium/efeitos dos fármacos , Protetores Solares/toxicidade , Raios Ultravioleta/efeitos adversos , Animais , Bioensaio , Cânfora/toxicidade , Monitoramento Ambiental/métodos , Humanos , Microssomos Hepáticos/efeitos dos fármacos , Ratos , Salmonella typhimurium/genética
19.
Leukemia ; 35(6): 1671-1682, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32943751

RESUMO

Limited evidence supports the use of early endpoints to evaluate the success of initial treatment of extranodal NK/T-cell lymphoma (ENKTCL) in the modern era. We aim to analyze progression-free survival at 24 months (PFS24) and subsequent overall survival (OS) in a large-scale multicenter cohort of patients. 1790 patients were included from the China Lymphoma Collaborative Group (CLCG) database. Subsequent OS was defined from the time of PFS24 or progression within 24 months to death. OS was compared with age- and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Patients who did not achieve PFS24 had a median OS of 5.3 months after progression, with 5-year OS rate of 19.2% and the SMR of 71.4 (95% CI, 62.9-81.1). In contrast, 74% patients achieved PFS24, and the SMR after achieving PFS24 was 1.77 (95% CI, 1.34-2.34). The observed OS rate after PFS24 versus expected OS rate at 5 years was 92.2% versus 94.3%. Similarly, superior outcomes following PFS24 were observed in early-stage patients (5-year OS rate, 92.9%). Patients achieving PFS24 had excellent outcome, whereas patients exhibiting earlier progression had a poor survival. These marked differences suggest that PFS24 may be used for study design and risk stratification in ENKTCL.


Assuntos
Linfoma Extranodal de Células T-NK/mortalidade , Adulto , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfoma Extranodal de Células T-NK/patologia , Linfoma Extranodal de Células T-NK/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
Leukemia ; 35(1): 130-142, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32152465

RESUMO

Derived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell's C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.


Assuntos
Tomada de Decisão Clínica , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/mortalidade , Nomogramas , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Área Sob a Curva , Gerenciamento Clínico , Feminino , Humanos , Linfoma Extranodal de Células T-NK/diagnóstico , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos Testes , Análise de Sobrevida
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