Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 161
Filtrar
1.
Nat Med ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956198

RESUMO

Understanding healthcare system resilience has become paramount, particularly in the wake of the COVID-19 pandemic, which imposed unprecedented burdens on healthcare services and severely impacted public health. Resilience is defined as the system's ability to absorb, recover from and adapt to disruptions; however, despite extensive studies on this subject, we still lack empirical evidence and mathematical tools to quantify its adaptability (the ability of the system to adjust to and learn from disruptions). By analyzing millions of patients' electronic medical records across US states, we find that the COVID-19 pandemic caused two successive waves of disruptions within the healthcare systems, enabling natural experiment analysis of the adaptive capacity of each system to adapt to past disruptions. We generalized the quantification framework and found that the US healthcare systems exhibit substantial adaptability (ρ = 0.58) but only a moderate level of resilience (r = 0.70). When considering system responses across racial groups, Black and Hispanic groups were more severely impacted by pandemic disruptions than white and Asian groups. Physician abundance was the key characteristic for determining healthcare system resilience. Our results offer vital guidance in designing resilient and sustainable healthcare systems to prepare for future waves of disruptions akin to COVID-19 pandemics.

2.
Ying Yong Sheng Tai Xue Bao ; 35(4): 1083-1091, 2024 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-38884243

RESUMO

We quantified the lag time of vegetation response to drought in the Pearl River basin (PRB) based on the standardized precipitation evapotranspiration index (SPEI) and normalized difference vegetation index (NDVI), and constructed a vegetation loss probability model under drought stress based on the Bayesian theory and two-dimensional joint distribution. We further quantitatively evaluated the spatial variations of loss probability of four vegetation types (evergreen broadleaf forest, mixed forest, grassland, and cropland) under different drought intensities. The results showed that the drought risk in eastern West River, the upper reaches of North River and East River, and southern Pearl River Delta was obviously higher than that in other regions during 1982-2020. The response time of vegetation to drought in high-altitude areas in the upper reaches of PRB (mostly<3 month) was generally shorter than that in low altitude areas (>8 month). Drought exacerbated the probability of vegetation loss, with higher vulnerability of mixed forest than the other three vegetation types. The loss probability of vegetation was lower in northwestern PRB than that in central PRB.


Assuntos
Secas , Ecossistema , Florestas , Rios , Árvores , China , Árvores/crescimento & desenvolvimento , Estresse Fisiológico , Pradaria , Modelos Teóricos , Teorema de Bayes , Poaceae/crescimento & desenvolvimento
3.
J Chem Phys ; 160(6)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38349637

RESUMO

We present an approximate analytical approach to the adsorption problem of ABA triblock copolymers confined between two parallel plates in a θ solvent and give the expression of the propagator q(x, t) as a piece-wise function by solving the modified diffusion equation. In this way, the role of separation between the two plates, adsorption energy and block lengths on segment concentration profile, chain conformations, and interaction potential is then investigated, which agrees well with the numerical results. It is demonstrated that there are parallels between lengthening adsorbing A blocks and increasing surface affinity: strong adsorption and long adsorbing blocks favor the formation of loops and bridges, whereas more tails and free chains exist in the case of weak adsorption and short A blocks at large separations. For moderate and strong adsorptions, the bridging fraction begins to plummet at a separation larger than the end-to-end distance of non-adsorbing B block RB and becomes negligible at above 2RB owing to the entropy effect. The depth of the potential well in the interaction potential profile depends on the adsorption energy and A block length, while the location of the potential minimum corresponds to the onset of the sharp decrease in bridges.

4.
BMC Med Res Methodol ; 24(1): 16, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254038

RESUMO

Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Teorema de Bayes , Prognóstico , Calibragem , China/epidemiologia
5.
J Cancer ; 15(1): 126-139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164289

RESUMO

Background: KIAA1429, a member of the RNA methyltransferase complex, is involved in cancer progression; however, the clinical significance and underlying mechanism of KIAA1429 in osteosarcoma (OS) remains to be reported. Methods: We evaluated the clinical significance of KIAA1429 in OS by performing RT-qPCR, microarray, and RNA sequencing and using published data as a reference. Two KIAA1429-targeting siRNA constructs were transfected into SW1353 cells. CCK-8 assay, colony formation assays, flow cytometry and the xenograft mouse model were conducted to investigate the biological function of KIAA1429 in OS. Results: The mRNA expression of KIAA1429 was markedly upregulated in 250 OS samples as compared to that in 71 non-cancer samples (standardized mean difference = 0.67). Summary receiver operating characteristic curve analysis revealed that KIAA1429 exhibited reliable diagnostic capacity to differentiate OS samples from non-cancer samples (area under the curve = 0.83). Further, survival analysis indicated that KIAA1429 overexpression was associated with shorter overall survival time. Knocking down KIAA1429 reduced m6A methylation levels, inhibited proliferation, prevented the growth of tumors in vivo and accelerated apoptosis of OS cells. In total, 395 KIAA1429-related genes were identified among co-expressed genes and differentially expressed genes, which were enriched in the cell cycle pathway. Protein-protein interaction network analysis showed that CDK1, CCNA2, and CCNB1 were KIAA1429-related genes, serving as major network hubs in OS. Conclusions: Our findings indicate that KIAA1429 plays an oncogenic role in OS and potentially facilitates OS progression via a mechanism that involves regulating CDK1, CCNA2, and CCNB1.

6.
Small ; 20(6): e2304690, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37794605

RESUMO

MXenes are considered a promising negative electrode material for potassium ion batteries (PIBs) in view of their low potassium ion diffusion barrier and excellent electrical conductivity. However, the stacking phenomenon in practical applications severely reduces their active surface and leads to slow K+ diffusion. Herein, a facile composite template method is proposed to construct stacking-resistance 3D carbon-supported Ti3 C2 Tx (3D-C@Ti3 C2 Tx ) hollow spheres. Due to the unique structure, when used as a negative electrode material, as-prepared 3D-C@Ti3 C2 Tx hollow spheres show not only improved rate capability with 160.4 mAh g-1 at 100 mA g-1 and 133.7 mAh g-1 at 500 mA g-1 , but also stable cycling performance with 142.5 mAh g-1 specific capacity remained at 2 A g-1 after 4200 cycles. Furthermore, the full cells with 3D-C@Ti3 C2 Tx anode can operate stably for 1000 cycles at 100 mA g-1 . Moreover, the linear fit analysis demonstrates that 3D-C@Ti3 C2 Tx hollow spheres have a fast and stable capacitive potassium storage mechanism. This method is simple and easy to implement, which provide a feasible path to solve the stacking problem of 2D materials.

7.
J Am Heart Assoc ; 13(1): e029400, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38156626

RESUMO

BACKGROUND: Traditional risk evaluation models have been applied to guide public health and clinical practice in various studies. However, the application of existing methods to data sets with missing and censored data, as is often the case in electronic health records, requires additional considerations. We aimed to develop and validate a predictive model that exhibits high performance with data sets that contain missing and censored data. METHODS AND RESULTS: This is a retrospective cohort study of coronary heart disease at Weihai Municipal Hospital on unique patients aged 18 to 96 years between 2013 and 2021. A total of 169 692 participants formed our study population, of which 10 895 participants were diagnosed with coronary heart disease. Models were built for the risk of coronary heart disease based on demographic, laboratory, and medical history variables. All complete samples were assigned to the training set (n=110 325), whereas the remaining samples were assigned to the validation set (n=59 367). The area under the receiver operating characteristic curve value was 0.800 (95% CI, 0.794-0.805), and the C statistic was 0.796 (95% CI, 0.791-0.801) in the derivation cohort, and the corresponding values were 0.837 (95% CI, 0.821-0.853) and 0.838 (95% CI, 0.822-0.854) in the validation cohort. The calibration curve demonstrated its good calibration ability, and decision curve analysis showed its clinical usefulness. CONCLUSIONS: Our proposed risk prediction model has demonstrated significant effectiveness in handling the complexities of electronic health record data, which often involve extensive missing data and censoring. This approach may offer potential assistance in the use of electronic health records to enhance patient outcomes.


Assuntos
Doença das Coronárias , Registros Eletrônicos de Saúde , Humanos , Estudos Retrospectivos , Teorema de Bayes , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia
8.
ACS Nano ; 17(23): 23262-23298, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38010076

RESUMO

Cancer stem cells (CSCs) drive tumor initiation, progression, and therapeutic resistance due to their self-renewal and differentiation capabilities. Despite encouraging progress in cancer treatment, conventional approaches often fail to eliminate CSCs, necessitating the development of precise targeted strategies. Recent advances in materials science and nanotechnology have enabled promising CSC-targeted approaches, harnessing the power of tailoring nanomaterials in diverse therapeutic applications. This review provides an update on the current landscape of nanobased precision targeting approaches against CSCs. We elucidate the nuanced application of organic, inorganic, and bioinspired nanomaterials across a spectrum of therapeutic paradigms, encompassing targeted therapy, immunotherapy, and multimodal synergistic therapies. By examining the accomplishments and challenges in this potential field, we aim to inform future efforts to advance nanomaterial-based therapies toward more effective "sniping" of CSCs and tumor clearance.


Assuntos
Nanoestruturas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Diferenciação Celular , Imunoterapia , Células-Tronco Neoplásicas/patologia
9.
Int Immunopharmacol ; 124(Pt A): 110852, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37657245

RESUMO

Multiple myeloma (MM) is a bone marrow resident hematological malignancy. T helper (Th) cells play an essential role in maladjustment of immune function and promotion of myeloma cell proliferation and survival, which has not been fully elucidated. Here, we compared transcriptome profiles of CD4+ T cells in bone marrow samples of 3 healthy individuals and 10 MM patients before and after treatment using single-cell RNA sequencing. CD4+ T cells were divided into 7 clusters. Imbalanced Th17-like cell differentiation was indicated in MM based on bioinformation analyses, which involved IL2-STAT5 pathways and transcription factors NKFB1, RELA, STAT3, and GTF2A2. Pseudotime trajectory analysis of CD4+ T cell clusters further uncovered the enhanced transition of Th17-like to regulatory T (Treg) cells in MM, which was featured by expression changes of PLAC8, NKFB1, RELA, STAT3, and STAT1 along with the developmental path. Reduced cell-cell interaction between MM cells and CD4+ naïve/recently activated naïve T cells via CD74-APP might lead to imbalanced Th17-like cell differentiation. Checkpoints via TIGIT-NECTIN3 and LGALS9-CD47 in Treg and MM cells were also identified. Our study reveals imbalanced differentiation pattern of Th17-like cells and the immunosuppressive profiles in connection with MM cells, which might help to shed light on CD4+ T cell function in MM.

10.
Front Endocrinol (Lausanne) ; 14: 1176256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293505

RESUMO

Objective: We aimed to investigate the effect of Cyclocarya paliurus leaves extracts (CP) on glucose and blood lipid metabolism and its relationship with intestinal flora in type 2 diabetes mellitus (T2DM) patients. Methods: In this open-label, 84-day randomized controlled trial, a total of 38 T2DM patients were randomly assigned to the CP group or the Glipizide group (G group) in a 2:1 ratio. T2DM-associated metabolic phenotypes, gut microbiota and metabolites including short-chain fatty acids (SCFAs) and bile acids (BAs) were detected. Results: At the end of intervention, CP, like Glipizide, significantly improved HbA1c level and other glucose metabolism parameters (fasting plasma glucose (FBG), 2-hour post-meal blood glucose (2hPBG), the area under curve of oral glucose tolerance test glucose (OGTT glucose AUC)). Moreover, CP also resulted in the significant improvement in the levels of blood lipid and blood pressure. Notably, the improvement in blood lipid(triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c)) and blood pressure (diastolic blood pressure (DBP)) was significantly greater in the CP group compared with the G group. Furthermore, the liver and kidney function parameters did not significantly change in both CP group and the G group over the 84-day period. Additionally, the enrichment of potentially beneficial bacteria (Faecalibacterium and Akkermansia), SCFAs and unconjugated BAs and the depletion of potential pathogenic bacteria (Prevotella_9) and conjugated BAs were observed in the CP group, while the abundances of the gut microbial were kept stable in the G group after intervention. Conclusion: CP displays a more beneficial effect in the alleviation of T2DM-associated metabolic phenotypes than glipizide by regulating gut microbiota and metabolites in T2DM patients, with no significant effects on liver and kidney function.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Glipizida/farmacologia , População do Leste Asiático , Lipídeos , Glucose/farmacologia , Folhas de Planta/metabolismo
11.
Int J Comput Support Collab Learn ; 18(1): 101-133, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37125264

RESUMO

Learning engagement has gained increasing attention in the field of education. Previous studies have adopted conventional methods to analyze learning engagement, but these methods cannot provide timely feedback for learners. This study analyzed automated group learning engagement via deep neural network models in a computer-supported collaborative learning (CSCL) context. A quasi-experimental research design was implemented to examine the effects of the automated group learning engagement analysis and feedback approach on collaborative knowledge building, group performance, socially shared regulation, and cognitive load. In total, 120 college students participated in this study; they were assigned to 20 experimental groups and 20 control groups of three students each. The students in the experimental groups adopted the automated group learning engagement analysis and feedback approach, whereas those in the control groups used the traditional online collaborative learning approach. Both quantitative and qualitative data were collected and analyzed in depth. The results indicated significant differences in group learning engagement, group performance, collaborative knowledge building, and socially shared regulation between the experimental and control groups. The proposed approach did not increase the cognitive load for the experimental groups. The implications of the findings can potentially contribute to improving group learning engagement and group performance in CSCL.

12.
Artigo em Inglês | MEDLINE | ID: mdl-37239556

RESUMO

Volatile organic compounds (VOCs) are major indoor air pollutants that contain several toxic substances. However, there are few studies on health risk assessments of indoor VOCs in China. This study aimed to determine the concentration characteristics of VOCs on college campuses by collecting VOC samples from different locations on campus during different seasons combined with the exposure times of college students in each location obtained from a questionnaire survey to assess the possible health risks. The highest total VOC concentration (254 ± 101 µg/m3) was in the dormitory. The seasonal variation of TVOC concentrations was related to the variation of emission sources in addition to temperature. Health risk assessments of VOCs were evaluated using non-carcinogenic and carcinogenic risk values, represented by hazard quotient (HQ) and lifetime cancer risk (LCR), respectively. The non-carcinogenic risks at all sampling sites were within the safe range (HQ < 1). Dormitories had the highest carcinogenic risk, whereas the carcinogenic risk in the other three places was low (with LCR < 1.0 × 10-6). Moreover, 1,2-dichloroethane was identified as a possible carcinogenic risk substance in the dormitory due to its high LCR (1.95 × 10-6). This study provides basic data on health risks in different locations on campus and a basis for formulating measures to improve people's living environments.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Neoplasias , Compostos Orgânicos Voláteis , Humanos , Monitoramento Ambiental , Compostos Orgânicos Voláteis/análise , Universidades , Poluentes Atmosféricos/análise , Medição de Risco , Carcinógenos/análise , Carcinogênese , China/epidemiologia , Poluição do Ar em Ambientes Fechados/análise
13.
Cancer Lett ; 562: 216171, 2023 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-37054944

RESUMO

The mechanisms underlying the functional impairment and metabolic reprogramming of T lymphocytes in multiple myeloma (MM) have not been fully elucidated. In this study, single-cell RNA sequencing was used to compare gene expression profiles in T cells in bone marrow and peripheral blood of 10 newly diagnosed MM patients versus 3 healthy donors. Unbiased bioinformatics analysis revealed 9 cytotoxic T cell clusters. All 9 clusters in MM had higher expression of senescence markers (e.g., KLRG1 and CTSW) than the healthy control; some had higher expression of exhaustion-related markers (e.g., LAG3 and TNFRSF14). Pathway enrichment analyses showed downregulated amino acid metabolism and upregulated unfolded protein response (UPR) pathways, along with absent expression of glutamine transporter SLC38A2 and increased expression of UPR hallmark XBP1 in cytotoxic T cells in MM. In vitro studies revealed that XBP1 inhibited SLC38A2 by directly binding to its promoter, and silencing SLC38A2 resulted in decreased glutamine uptake and immune dysfunction of T cells. This study provided a landscape description of the immunosuppressive and metabolic features in T lymphocytes in MM, and suggested an important role of XBP1-SLC38A2 axis in T cell function.


Assuntos
Mieloma Múltiplo , Linfócitos T Citotóxicos , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Mieloma Múltiplo/genética , Glutamina , Análise de Sequência de RNA , Proteína 1 de Ligação a X-Box/genética , Sistema A de Transporte de Aminoácidos/genética
14.
Cancer Sci ; 114(7): 2750-2760, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37002866

RESUMO

Multiple myeloma (MM) is an incurable plasma cell malignancy with the hallmark of immunodeficiency, including dysfunction of T cells, NK cells, and APCs. Dysfunctional APCs have been reported to play a key role in promoting MM progression. However, the molecular mechanisms remain elusive. Here, single-cell transcriptome analysis of dendritic cells (DC) and monocytes from 10 MM patients and three healthy volunteers was performed. Both DCs and monocytes were divided into five distinct clusters, respectively. Among them, monocyte-derived DCs (mono-DC) were shown to develop from intermediate monocytes (IM) via trajectory analysis. Functional analysis showed that, compared with healthy controls, conventional DC2 (cDC2), mono-DC, and IM of MM patients exhibited impaired antigen processing and presentation capacity. Moreover, reduced regulon activity of interferon regulatory factor 1 (IRF1) was found in cDC2, mono-DC and IM of MM patients according to single-cell regulatory network inference and clustering (SCENIC) analysis, while the downstream mechanisms were distinct. Specifically in MM patients, cathepsin S (CTSS) was markedly downregulated in cDC2, major histocompatibility complex (MHC) class II transactivator (CIITA) was significantly decreased in IM, in addition both CTSS and CIITA were downregulated in mono-DC based on differentially expressed genes analysis. In vitro study validated that knockdown of Irf1 downregulated Ctss and Ciita respectively in mouse DC cell line DC2.4 and mouse monocyte/macrophage cell line RAW264.7, which ultimately inhibited proliferation of CD4+ T cells after being cocultured with DC2.4 or RAW264.7 cells. This current study unveils the distinct mechanisms of cDC2, IM, and mono-DC function impairment in MM, offering new insight into the pathogenesis of immunodeficiency.


Assuntos
Monócitos , Mieloma Múltiplo , Camundongos , Animais , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Antígenos , Apresentação de Antígeno , Células Dendríticas , Antígenos de Histocompatibilidade Classe II , Diferenciação Celular
15.
Ann Transl Med ; 11(3): 152, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36845999

RESUMO

Background: Omega-3 polyunsaturated fatty acids are known to be associated with numbers of health benefits, and which can be uptake from fish. The aim of this study was to evaluate the current evidence of associations between consumption of fish and diverse health outcomes. Here, we performed an umbrella review to summarize the breadth, strength, and validity of the evidence derived from meta-analyses and systematic reviews of fish consumption on all health outcomes. Methods: The methodological quality of the included meta-analyses and the quality of the evidence were assessed by the Assessment of Multiple Systematic Reviews (AMSTAR) and the grading of recommendations, assessment, development, and evaluation (GRADE) tools, respectively. The umbrella review identified 91 meta-analyses with 66 unique health outcomes, of which 32 outcomes were beneficial, 34 showed nonsignificant associations and only one was harmful (myeloid leukemia). Results: A total of 17 beneficial associations [all-cause mortality, prostate cancer mortality, cardiovascular disease (CVD) mortality, esophageal squamous cell carcinoma (ESCC), glioma, non-Hodgkin lymphoma (NHL), oral cancer, acute coronary syndrome (ACS), cerebrovascular disease, metabolic syndrome, age-related macular degeneration (AMD), inflammatory bowel disease (IBD), Crohn's disease (CD), triglycerides, vitamin D, high-density lipoprotein (HDL)-cholesterol, and multiple sclerosis (MS)], and eight nonsignificant associations [colorectal cancer (CRC) mortality, esophageal adenocarcinoma (EAC), prostate cancer, renal cancer, ovarian cancer, hypertension, ulcerative colitis (UC), and rheumatoid arthritis (RA)] were evaluated as moderate/high quality of evidence. According to dose-response analyses, consumption of fish, especially fatty types, seems generally safe at one-two servings per week and could exert protective effects. Conclusions: Fish consumption is often associated with a variety of health outcomes, both beneficial and harmless, but only about 34% of the associations were graded as based on a moderate/high quality of evidence, and additional multicenter high quality randomized controlled trials (RCTs) with a large sample size are needed to verify these findings in the future.

16.
Educ Inf Technol (Dordr) ; : 1-22, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36688219

RESUMO

Online collaborative learning (OCL) has been a mainstream pedagogy in the field of higher education. However, learners often produce off-topic information and engage less during online collaborative learning compared to other approaches. In addition, learners often cannot converge in knowledge, and they often do not know how to coregulate with peers. To cope with these problems, this study proposed an immediate analysis of interaction topics (IAIT) approach through deep learning technologies. The purpose of this study is to examine the effects of the IAIT approach on group performance, knowledge convergence, coregulation, and cognitive engagement in online collaborative learning. In total, 60 undergraduate students participated in this quasi-experimental study. They were assigned to either the experimental or the control groups. The students in the experimental groups conducted online collaborative learning with the IAIT approach, and the students in the control groups conducted online collaborative learning only without any particular approach. The whole study lasted for three months. Both qualitative and quantitative methods were adopted to analyze data. The results indicated that the IAIT approach significantly promoted group performance, knowledge convergence, coregulated behaviors, and cognitive engagement. The IAIT approach did not increase learners' cognitive load. The results, together with the implications for teachers, practitioners and researchers, are also discussed in depth.

17.
Cell Biosci ; 13(1): 19, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717896

RESUMO

BACKGROUND: Multiple myeloma (MM) is a hematological malignancy characterized by clonal proliferation of malignant plasma cells. Despite extensive research, molecular mechanisms in MM that drive drug sensitivity and clinic outcome remain elusive. RESULTS: Single-cell RNA sequencing was applied to study tumor heterogeneity and molecular dynamics in 10 MM individuals before and after 2 cycles of bortezomib-cyclophosphamide-dexamethasone (VCD) treatment, with 3 healthy volunteers as controls. We identified that unfolded protein response and metabolic-related program were decreased, whereas stress-associated and immune reactive programs were increased after 2 cycles of VCD treatment. Interestingly, low expression of the immune reactive program by tumor cells was associated with unfavorable drug response and poor survival in MM, which probably due to downregulation of MHC class I mediated antigen presentation and immune surveillance, and upregulation of markers related to immune escape. Furthermore, combined with immune cells profiling, we uncovered a link between tumor intrinsic immune reactive program and immunosuppressive phenotype in microenvironment, evidenced by exhausted states and expression of checkpoint molecules and suppressive genes in T cells, NK cells and monocytes. Notably, expression of YBX1 was associated with downregulation of immune activation signaling in myeloma and reduced immune cells infiltration, thereby contributed to poor prognosis. CONCLUSIONS: We dissected the tumor and immune reprogramming in MM during targeted therapy at the single-cell resolution, and identified a tumor program that integrated tumoral signaling and changes in immune microenvironment, which provided insights into understanding drug sensitivity in MM.

18.
Immunopharmacol Immunotoxicol ; 45(1): 1-9, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35950851

RESUMO

AIM: Cetuximab and panitumumab are common antibodies against epidermal growth factor receptor (EGFR) that can be used in combination with chemotherapy for the treatment of metastatic colorectal cancer (mCRC). Although these two drugs are considered to be very similar, differences in the efficacy and safety of cetuximab and panitumumab are still unclear. We conducted this meta-analysis to explore the effects and adverse reactions of cetuximab and panitumumab in the treatment of mCRC. METHODS: We searched PubMed, the Cochrane Library, Embase, Web of Science, China national knowledge infrastructure (CNKI) and WanFang databases to identify records related to the efficacy and safety of cetuximab and panitumumab in the treatment of mCRC. The search terms were "cetuximab," "panitumumab," and "colorectal cancer." The deadline of searching was April 2022. Review manager 5.4 software was used to perform the statistical analysis for this meta-analysis. Pooled hazard ratio (HR) with 95% confidence intervals (CI) were calculated to evaluate the overall survival (OS) and progression free survival (PFS) of cetuximab and panitumumab in the treatment of mCRC. RESULTS: There was no significant difference in OS, PFS, and response rate (RR) between cetuximab arm and panitumumab arm (OS: HR = 0.91, 95% CI = 0.81-1.03, p = .14; PFS: HR = 0.92, 95% CI = 0.83-1.02, p = .11; RR: OR = 1.22, 95% CI = 0.96-1.61, p = .14). We also did not observe any statistical difference between both arms in incidence of acneiform rash, severe acneiform rash, diarrhea, and severe diarrhea (acneiform rash: OR = 1.09, 95% CI = 0.84-1.42, p = .51; severe acneiform rash: OR = 1.50, 95% CI = 0.80-2.81, p = .21; diarrhea: OR = 1.08, 95% CI = 0.82-1.42, p = .58; severe diarrhea: OR = 0.90, 95% CI = 0.44-1.84, p = .77). The incidence of paronychia was decreased in the panitumumab arm, but that of hypomagnesemia and severe hypomagnesemia were decreased in the cetuximab arm. (paronychia: OR = 0.74, 95% CI = 0.55-1.00, p = .05; hypomagnesemia: OR = 1.85, 95% CI =1.41-2.41, p < .00001; severe hypomagnesemia: OR = 2.66, 95% CI = 1.52-4.67, p = .0006). CONCLUSION: There was no significant difference in OS, PFS and RR between the cetuximab arm and panitumumab arm in the treatment of mCRC. For adverse reactions, the incidence of paronychia was decreased in the panitumumab arm, and the incidence of hypomagnesemia was deceased in the cetuximab arm.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Exantema , Paroniquia , Neoplasias Retais , Humanos , Panitumumabe/efeitos adversos , Cetuximab/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Paroniquia/induzido quimicamente , Paroniquia/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Exantema/induzido quimicamente , Exantema/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica
19.
J Hazard Mater ; 443(Pt A): 130130, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36265379

RESUMO

With rapid urbanization, microplastics and natural organic matters (NOMs) are ubiquitous in aquatic environment, and microplastics could act as carriers for organic matters in the aqueous solution and may pose a potential risk. In this study, the adsorption behaviors and mechanism of typical NOM, humic acid (HA), on polyvinyl chloride (PVC) and polystyrene (PS) microplastics were investigated. Various influence factors such as solution pH, ions species and concentrations, particle size, and coexisting surfactants were studied. The results suggested that HA adsorption onto PVC and PS was low pH-dependent, and ion species and concentrations have a significant impact on the adsorption capacity. In addition, the particle size of PVC and PS microplastics exhibited a significant correlation with HA adsorption, and the adsorption process was influenced by the surfactant species and concentrations. Moreover, the adsorption behaviors of HA in different real water environments were tested, and UV aging exhibited the opposite effects on adsorption capacity of PVC and PS. Furthermore, the adsorption mechanisms of HA onto PVC and PS were explored, indicating halogen bonding, hydrogen bonding, and π-π interaction play important roles in the adsorption process.


Assuntos
Microplásticos , Poluentes Químicos da Água , Plásticos , Adsorção , Cinética , Cloreto de Polivinila , Poluentes Químicos da Água/análise , Substâncias Húmicas/análise , Água , Poliestirenos , Tensoativos , Íons
20.
Lab Med ; 54(4): 392-399, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-36355580

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of the following hemostatic markers in hypertensive disorder of pregnancy (HDP): tissue-type plasminogen activator and inhibitor-1 complex (tPAI-C), thrombomodulin, thrombin-antithrombin complex, plasmin inhibitor-plasmin complex, D-dimer, and fibrinogen degradation products. METHODS: A total of 311 individuals diagnosed with HDP and 187 healthy controls (HC) of matched gestational age were admitted, including 175 subjects with gestational hypertension, 94 with mild preeclampsia, and 42 with severe preeclampsia. RESULTS: Compared with those of the HC group, the plasma concentrations of all the hemostatic markers continuously increased with the clinical severity of the hypertensive disorder, regardless of their statistical significance. In the receiver operating characteristic analysis, tPAI-C displayed the best discrimination performance. CONCLUSION: The tPAI-C level was consistently and significantly elevated across the different HDP groups when compared with the HC group, suggesting aggravated fibrinolysis disorder increasing with the severity of the HDP.


Assuntos
Hemostáticos , Hipertensão , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Fibrinólise , Hemostáticos/farmacologia , Estudos Retrospectivos , Estudos de Casos e Controles , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA