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1.
Chronic Dis Transl Med ; 8(2): 112-123, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35774423

RESUMO

Breast cancer (BC) is the most prevalent malignancy worldwide, and a continued upward trend has been predicted in the coming decades. Screening in selected targeted populations, which is effective in reducing cancer-related mortality, has been widely implemented in many countries. This review summarizes the advances in BC screening techniques, organized or opportunistic BC screening programs across different countries, and screening modalities recommended by different academic authorities. Mammography is the most widely used and effective technique for BC screening. Other complementary techniques include ultrasound, clinical breast examination, and magnetic resonance imaging. Novel screening tests, including digital breast tomosynthesis and liquid biopsies, are still under development. Globally, the implementation status of BC screening programs is uneven, which is reflected by differences in screening modes, techniques, and population coverage. The recommended optimal screening strategies varied according to the authoritative guidelines. The effectiveness of current screening programs is influenced by several factors, including low detection rate, high false-positive rate, and unsatisfactory coverage and uptake rates. Exploration of accurate BC risk prediction models and the development of risk-stratified screening strategies are highly warranted in future research.

2.
Chaos ; 32(6): 061103, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35778146

RESUMO

In this work, we consider the nonparametric estimation problem of the drift function of stochastic differential equations driven by the α-stable Lévy process. We first optimize the Kullback-Leibler divergence between the path probabilities of two stochastic differential equations with different drift functions. We then construct the variational formula based on the stationary Fokker-Planck equation using the Lagrangian multiplier. Moreover, we apply the empirical distribution to replace the stationary density, combining it with the data information, and we present the estimator of the drift function from the perspective of the process. In the numerical experiment, we investigate the effect of the different amounts of data and different α values. The experimental results demonstrate that the estimation result of the drift function is related to both and that the exact drift function agrees well with the estimated result. The estimation result will be better when the amount of data increases, and the estimation result is also better when the α value increases.

3.
Front Plant Sci ; 13: 904178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720564

RESUMO

As an important economic and medicinal crop, Amomum tsao-ko is rich in volatile oils and widely used in food additives, essential oils, and traditional Chinese medicine. However, the lack of the genome remains a limiting factor for understanding its medicinal properties at the molecular level. Here, based on 288.72 Gb of PacBio long reads and 105.45 Gb of Illumina paired-end short reads, we assembled a draft genome for A. tsao-ko (2.70 Gb in size, contig N50 of 2.45 Mb). Approximately 90.07% of the predicted genes were annotated in public databases. Based on comparative genomic analysis, genes involved in secondary metabolite biosynthesis, flavonoid metabolism, and terpenoid biosynthesis showed significant expansion. Notably, the DXS, GGPPS, and CYP450 genes, which participate in rate-limiting steps for terpenoid backbone biosynthesis and modification, may form the genetic basis for essential oil formation in A. tsao-ko. The assembled A. tsao-ko draft genome provides a valuable genetic resource for understanding the unique features of this plant and for further evolutionary and agronomic studies of Zingiberaceae species.

4.
Infect Drug Resist ; 15: 3161-3171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35747334

RESUMO

Purpose: To compare antimicrobial resistance, virulence, clinical characteristics, and risk factors between carbapenem-resistant K. pneumoniae (CRKP) and carbapenem-susceptible K. pneumoniae (CSKP) isolates from patients with bloodstream infections (BSIs) in China. Patients and Methods: The clinical data of 103 patients with K. pneumoniae BSI from 10 hospitals were retrospectively analyzed. The minimum inhibitory concentrations of 15 antibiotics against the bacteria were determined. A Galleria mellonella infection model was used to evaluate virulence of the isolates. Kaplan-Meier curves were calculated to evaluate the 28-day and in-hospital survival rates of the isolates. The risk factors for CRKP and CSKP infection and respective mortality rate were evaluated by univariate analysis, and independent risk factors were evaluated using the multivariate logistic regression model. Results: Our results indicated that CRKP isolates were more resistant to most tested antibiotics than CSKP isolates. The G. mellonella infection model was used to demonstrate that CRKP isolates were more virulent than CSKP isolates. We found that in-hospital deaths occurred in 39.3% (22/56) of patients with CRKP BSIs and were significantly higher than those in patients with CSKP infections (19.1%, 9/47). Patients infected with CRKP isolates had poorer outcomes than those infected with the CSKP strains. For in-hospital mortality of CRKP BSIs, the independent risk factors included carbapenem-resistant Enterobacterales bacteremia and length of hospitalization after the onset of BSI. Conclusion: Our findings confirm that CRKP isolates are more drug-resistant than CSKP isolates and are associated with poorer outcomes. To prevent CRKP infection, strict infection control strategies and active surveillance should be implemented in hospitals.

5.
J Oncol ; 2022: 9390611, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693981

RESUMO

Cancer-derived exosomes participate in carcinogenesis and progression of cancers, including metastasis and drug-resistance. Of note, CTCF has been suggested to induce drug resistance in various cancers. Herein, we aim to investigate the role of cisplatin- (CDDP-) resistant osteosarcoma- (OS-) derived exosomal CTCF in OS cell resistance to CDDP and its mechanistic basis. Differentially expressed transcription factors, long noncoding RNAs (lncRNAs), miRNAs, and genes in OS were retrieved using bioinformatics approaches. Exosomes were extracted from CDDP-resistant OS cells and then cocultured with parental OS cells, followed by lentiviral transduction to manipulate the expression of CTCF, IGF2-AS, miR-579-3p, and MSH6. We assessed the in vitro and in vivo effects on malignant phenotypes, autophagy, CDDP sensitivity, and tumor formation of OS cells. It was established that CTCF and IGF2-AS were highly expressed in CDDP-resistant OS cells, and the CDDP-resistant OS cell-derived exosomal CTCF enhanced IGF2-AS transcription. CDDP-resistant OS-derived exosomes transmitted CTCF to OS cells and increased CDDP resistance in OS cells by activating an autophagy-dependent pathway. Mechanistically, CTCF activated IGF2-AS transcription and IGF2-AS competitively bound to miR-579-3p to upregulate MSH6 expression. Additionally, the promoting function of exosomal CTCF-mediated IGF2-AS/miR-579-3p/MSH6 in OS cell resistance to CDDP was confirmed in vivo. Taken together, CDDP-resistant OS-derived exosomal CTCF enhanced resistance of OS cells to CDDP via activating the autophagy-dependent pathway, providing a potential therapeutic consideration for OS treatment.

6.
China CDC Wkly ; 4(15): 322-328, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35548454

RESUMO

Colorectal cancer (CRC) ranks third among the most commonly diagnosed cancers in China. Despite proof that screening can decrease CRC incidence and mortality, there are still gaps remaining between CRC screening objectives and reality in China. In this review, we provided an overview of the status of CRC screening in China. First, we summarized the current CRC screening programs and strategies in China. Second, we reviewed the authoritative CRC screening and early detection guidelines in China to orient future evidence-based guideline development. Finally, we identified current challenges and further provided some suggestions to improve the implementation of CRC screening programs. To maximize the effectiveness of CRC screening, further research on risk prediction models including polygenic risk scores and prior screening outcomes, novel biomarkers and artificial intelligence, and personalized screening strategies are recommended. Both cohort study and microsimulation techniques are recommended for long-term evaluations of the effectiveness of CRC screening strategies.

7.
BMC Musculoskelet Disord ; 23(1): 512, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35637466

RESUMO

BACKGROUND: The autogenous iliac bone graft is the first choice of surgical treatment for long bone non-union. However, many factors limit the use of autogenous bone, such as insufficient bone harvest and complications in the donor site. This study aimed to pilot-test the effectiveness of the cortical allograft strut augmented with Platelet-rich plasma (PRP) on long bone non-union in the lower limb. METHOD: This study was a one-armed pilot trial, with thirteen men and four women patients scheduled for surgery. Revision surgery for managing long bone non-union included debridement, internal fixation of the cortical allograft strut, and adding PRP in the fracture site. After surgery, outcome measurements of healing rate, healing time, the incidence of revision, and complications, were assessed at least one-year follow-up. RESULTS: Fourteen of seventeen participants completed all follow-ups. The mean age of 14 patients was 35.9 years (range, 18-56 years), and the mean BMI was 22.44 ± 1.53 kg/m2. All nonunions united after the operation. The mean healing time was 4.6 ± 0.7 months. There was no revision or complication. CONCLUSION: Cortical allograft strut augmented with PRP led to healing long bone non-union in the lower limb. More clinical research is required before widespread use.


Assuntos
Prótese de Quadril , Plasma Rico em Plaquetas , Adolescente , Adulto , Aloenxertos , Feminino , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
8.
Front Oncol ; 12: 883401, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530306

RESUMO

Introduction: A microsimulation model provides important references for decision-making regarding colorectal cancer (CRC) prevention strategies, yet such a well-validated model is scarce in China. Methods: We comprehensively introduce the development of MIcrosimulation Model for the prevention and Intervention of Colorectal Cancer in China (MIMIC-CRC). The MIMIC-CRC was first constructed to simulate the natural history of CRC based on the adenoma-carcinoma pathway. The parameters were calibrated and validated using data from population-based cancer registry data and CRC screening programs. Furthermore, to assess the model's external validity, we compared the model-derived results to outcome patterns of a sigmoidoscopy screening trial in the UK [UK Flexible Sigmoidoscopy Screening (UKFSS) trial]. Finally, we evaluated the application potential of the MIMIC-CRC model in CRC screening by comparing the 8 different strategies. Results: We found that most of the model-predicted colorectal lesion prevalence was within the 95% CIs of observed prevalence in a large population-based CRC screening program in China. In addition, model-predicted sex- and age-specific CRC incidence and mortality were equivalent to the registry-based data. The hazard ratios of model-estimated CRC-related incidence and mortality for sigmoidoscopy screening compared to no screening were 0.60 and 0.51, respectively, which were comparable to the reported results of the UKFSS trial. Moreover, we found that all 8 strategies could reduce CRC incidence and mortality compared to no screening. Conclusions: The well-calibrated and validated MIMIC-CRC model may represent a valid tool to assess the comparative effectiveness of CRC screening strategies and will be useful for further decision-making to CRC prevention.

9.
Mol Biol Evol ; 39(5)2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35485492

RESUMO

The antibiotic resistance crisis continues to threaten human health. Better predictions of the evolution of antibiotic resistance genes could contribute to the design of more sustainable treatment strategies. However, comprehensive prediction of antibiotic resistance gene evolution via laboratory approaches remains challenging. By combining site-specific integration and high-throughput sequencing, we quantified relative growth under the respective selection of cefotaxime or ceftazidime selection in ∼23,000 Escherichia coli MG1655 strains that each carried a unique, single-copy variant of the extended-spectrum ß-lactamase gene blaCTX-M-14 at the chromosomal att HK022 site. Significant synergistic pleiotropy was observed within four subgenic regions, suggesting key regions for the evolution of resistance to both antibiotics. Moreover, we propose PEARP and PEARR, two deep-learning models with strong clinical correlations, for the prospective and retrospective prediction of blaCTX-M-14 evolution, respectively. Single to quintuple mutations of blaCTX-M-14 predicted to confer resistance by PEARP were significantly enriched among the clinical isolates harboring blaCTX-M-14 variants, and the PEARR scores matched the minimal inhibitory concentrations obtained for the 31 intermediates in all hypothetical trajectories. Altogether, we conclude that the measurement of local fitness landscape enables prediction of the evolutionary trajectories of antibiotic resistance genes, which could be useful for a broad range of clinical applications, from resistance prediction to designing novel treatment strategies.


Assuntos
Infecções por Escherichia coli , beta-Lactamases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Escherichia coli/genética , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Estudos Prospectivos , Estudos Retrospectivos , beta-Lactamases/genética
10.
BMC Ophthalmol ; 22(1): 155, 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35366826

RESUMO

PURPOSE: Glaucoma is a generic term of a highly different disease group of optic neuropathies, which the leading cause of irreversible vision in the world. There are few biomarkers available for clinical prediction and diagnosis, and the diagnosis of patients is mostly delayed. METHODS: Differential gene expression of transcriptome sequencing data (GSE9944 and GSE2378) for normal samples and glaucoma samples from the GEO database were analyzed. Furthermore, based on different algorithms (Logistic Regression (LR), Random Forest (RF), lasso regression (LASSO)) two diagnostic models are constructed and diagnostic markers are screened. GO and KEGG analyses revealed the possible mechanism of differential genes in the pathogenesis of glaucoma. ROC curve confirmed the effectiveness. RESULTS: LR-RF model included 3 key genes (NAMPT, ADH1C, ENO2), and the LASSO model outputted 5 genes (IFI16, RFTN1, NAMPT, ADH1C, and ENO2), both algorithms have excellent diagnostic efficiency. ROC curve confirmed that the three biomarkers ADH1C, ENO2, and NAMPT were effective in the diagnosis of glaucoma. Next, the expression analysis of the three diagnostic biomarkers in glaucoma and control samples confirmed that NAMPT and ADH1C were up-regulated in glaucoma samples, and ENO2 was down-regulated. Correlation analysis showed that ENO2 was significantly negatively correlated with ADH1C (cor = -0.865714202) and NAMPT (cor = -0.730541227). Finally, three compounds for the treatment of glaucoma were obtained in the TCMs database: acetylsalicylic acid, 7-o-methylisomucitol and scutellarin which were applied to molecular docking with the diagnostic biomarker ENO2. CONCLUSIONS: In conclusion, our research shows that ENO2, NAMPT, and ADH1C can be used as diagnostic markers for glaucoma, and ENO2 can be used as a therapeutic target.


Assuntos
Glaucoma , Biomarcadores , Glaucoma/diagnóstico , Glaucoma/genética , Glaucoma/patologia , Humanos , Aprendizado de Máquina , Simulação de Acoplamento Molecular , Transcriptoma
12.
Emerg Microbes Infect ; 11(1): 1236-1249, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35437117

RESUMO

The global dissemination of the mobilized colistin resistance gene, mcr-1, threatens human health. Recent studies by our group and others have shown that the withdrawal of colistin as a feed additive dramatically reduced the prevalence of mcr-1. Although it is accepted that the rapid reduction in mcr-1 prevalence may have resulted, to some extent, from the toxic effects of MCR-1, the detailed mechanism remains unclear. Here, we found that MCR-1 damaged the outer membrane (OM) permeability in Escherichia coli and Klebsiella pneumonia and that this event was associated with MCR-1-mediated cell shrinkage and death during the stationary phase. Notably, the capacity of MCR-1-expressing cells for recovery from the stationary phase under improved conditions was reduced in a time-dependent manner. We also showed that mutations in the potential lipid-A-binding pocket of MCR-1, but not in the catalytic domain, restored OM permeability and cell viability. During the stationary phase, PbgA, a sensor of periplasmic lipid-A and LpxC production that performed the first step in lipid-A synthesis, was reduced after MCR-1 expression, suggesting that MCR-1 disrupted lipid homeostasis. Consistent with this, the overexpression of LpxC completely reversed the MCR-1-induced OM permeability defect. We propose that MCR-1 causes lipid remodelling that results in an OM permeability defect, thus compromising the viability of Gram-negative bacteria. These findings extended our understanding of the effect of MCR-1 on bacterial physiology and provided a potential strategy for eliminating drug-resistant bacteria.


Assuntos
Colistina , Proteínas de Escherichia coli , Bactérias Gram-Negativas , Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Escherichia coli , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/metabolismo , Humanos , Plasmídeos
13.
Front Oncol ; 12: 693395, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35321425

RESUMO

Ferroptosis is caused by accumulation of iron-dependent lipid peroxidation, which is characterized by reduction in cell volume and increase in mitochondrial membrane density. Studies have shown that ferroptosis contributes to the development and progression of numerous major diseases, including hepatocellular carcinoma (HCC). As a unique biomedical resource, Traditional Chinese Medicine (TCM) has been widely used in the treatment of HCC. In this present study, Scutellaria barbata was used to treat HCC cells in vitro, and the results revealed that S. barbata suppressed HCC cell growth through inducing ferroptosis. Next, the exploration of the molecular mechanism on how S. barbata induced ferroptosis in HCC cells suggested that S. barbata may induce ferroptosis by promoting iron perioxidation and lipid ROS metabolism. Finally, S. barbata also inhibited HCC tumorigenicity in vivo by inducing ferroptosis of HCC cells. These results provided theoretical basis for explaining the mechanism of TCM treatment for HCC and offered therapeutic opportunities for HCC patients.

14.
Front Physiol ; 13: 824203, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250625

RESUMO

The Tachinidae are natural enemies of many lepidopteran and coleopteran pests of crops, forests, and fruits. However, host-tachinid parasitoid interactions have been largely unexplored. In this study, we investigated the effects of tachinids on host biological traits, using Exorista japonica, a generalist parasitoid, and the silkworm Bombyx mori, its lepidopteran host, as models. We observed that E. japonica parasitoidism did not affect silkworm larval body weight gain and cocooning rate, whereas they caused shortened duration of molting from the final instar to the pupal stage, abnormal molting from larval to pupal stages, and a subsequent decrease in host emergence rate. Moreover, a decrease in juvenile hormone (JH) titer and an increase in 20-hydroxyecdysone (20E) titer in the hemolymph of parasitized silkworms occurred. The transcription of JH and 20E responsive genes was downregulated in mature parasitized hosts, but upregulated in parasitized prepupae while Fushi tarazu factor 1 (Ftz-f1), a nuclear receptor essential in larval ecdysis, showed dramatically reduced expression in parasitized hosts at both the mature and prepupal stages. Moreover, the transcriptional levels of BmFtz-f1 and its downstream target genes encoding cuticle proteins were downregulated in epidermis of parasitized hosts. Meanwhile, the content of trehalose was decreased in the hemolymph, while chitin content in the epidermis was increased in parasitized silkworm prepupae. These data reveal that the host may fine-tune JH and 20E synthesis to shorten developmental duration to combat established E. japonica infestation, while E. japonica silences BmFtz-f1 transcription to inhibit host pupation. This discovery highlights the novel target mechanism of tachinid parasitoids and provides new clues to host/tachinid parasitoid relationships.

15.
Eur Radiol ; 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35258672

RESUMO

OBJECTIVES: To propose a novel functional Coronary Artery Disease-Reporting and Data System (CAD-RADS) category system integrated with coronary CT angiography (CCTA)-derived fractional flow reserve (FFRCT) and to validate its effect on therapeutic decision and prognosis in patients with coronary artery disease (CAD). METHODS: Firstly, we proposed a novel functional CAD-RADS and evaluated the performance of functional CAD-RADS for guiding treatment strategies with actual clinical treatment as a reference standard in a retrospective multicenter cohort with CCTA and invasive FFR performed in all patients (n = 466). Net reclassification improvement (NRI) of functional CAD-RADS over anatomical CAD-RADS was calculated. Secondly, the prognostic value of functional CAD-RADS in a prospective two-arm cohort (566 [FFRCT arm] vs. 567 [CCTA arm]) was calculated, after a 1-year follow-up, functional CAD-RADS in FFRCT arm (n = 513) and anatomical CAD-RADS in CCTA arm (n = 511) to determine patients at risk of adverse outcomes were compared with a Cox hazard proportional model. RESULTS: Functional CAD-RADS demonstrated superior value over anatomical CAD-RADS (AUC: 0.828 vs. 0.681, p < 0.001) and comparable performance to FFR (AUC: 0.828 vs. 0.848, p = 0.253) in guiding therapeutic decisions. Functional CAD-RADS resulted in the revision of management plan as determined by anatomical CAD-RADS in 30.0% of patients (n = 140) (NRI = 0.369, p < 0.001). Functional CAD-RADS was an independent predictor for 1-year outcomes with indexes of concordance of 0.795 and the corresponding value was 0.751 in anatomical CAD-RADS. CONCLUSION: The novel functional CAD-RADS gained incremental value in guiding therapeutic decision-making compared with anatomical CAD-RADS and comparable power in 1-year prognosis with anatomical CAD-RADS in a real-world scenario. KEY POINTS: • The novel functional CAD-RADS category system with FFRCT integrated into the anatomical CAD-RADS categories was originally proposed. • The novel functional CAD-RADS category system was validated superior value over anatomical CAD-RADS (AUC: 0.828 vs. 0.681, p < 0.001) in guiding therapeutic decisions and revised management plan in 30.0% of patients as determined by anatomical CAD-RADS (net reclassification improvement index = 0.369, p < 0.001). • Functional CAD-RADS was an independent predictor with an index of concordance of 0.795 and 0.751 in anatomical CAD-RADS for 1-year prognosis of adverse outcomes.

16.
Lancet Respir Med ; 10(4): 378-391, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35276087

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. Data on the effectiveness of one-off low-dose CT (LDCT) in reducing lung cancer mortality and all-cause mortality are needed to inform screening programmes in countries with limited medical resources. We aimed to evaluate the effectiveness of one-off LDCT screening in the early detection of lung cancer in China. METHODS: A multicentre, population-based, prospective cohort study was done in 12 cities of eight provinces across China, recruiting individuals aged 40-74 years who were asymptomatic for lung cancer with no lung cancer history. Participants were classified as at high risk or low risk of lung cancer using a sex-specific risk score that incorporated cigarette smoking, level of physical activity, occupational exposures, history of chronic respiratory diseases, family history of lung cancer, diet, and passive smoking (women only). Participants at high risk were invited for a one-off LDCT scan and were classified into screened and non-screened groups on the basis of whether or not they had the scan. Lung cancer incidence density, lung cancer mortality, and all-cause mortality were calculated for the screened and non-screened groups. The effectiveness of a one-off LDCT scan was evaluated by a comparison of the screened and non-screened groups in terms of lung cancer mortality and all-cause mortality in the period from cohort entry until administrative censoring (June 20, 2020). Inverse probability weighting was adopted to account for potential imbalanced factors between the two groups and Cox proportional hazards model was used to estimate the weighted associations between mortality and one-off LDCT scans. FINDINGS: Between Feb 19, 2013, and Oct 31, 2018, 1 032 639 individuals were assessed for eligibility. 1 016 740 participants were enrolled in the study, of whom 3581 had a lung cancer diagnosis after a median follow-up of 3·6 years (IQR 2·8-5·1). Among the 223 302 participants at high risk, 79 581 (35·6%) had an LDCT scan (screened group) and 143 721 (64·4%) did not (non-screened group). After inverse probability weighting, lung cancer incidence density was 47·0% higher (hazard ratio 1·47 [95% CI 1·27-1·70]; p<0·0001), lung cancer mortality was 31·0% lower (0·69 [95% CI 0·53-0·92]; p=0·010) and all-cause mortality was 32·0% lower (0·68 [0·57-0·82]; p<0·0001) for participants in the screened group compared with those in the non-screened group. INTERPRETATION: One-off LDCT screening was associated with significantly lower lung cancer mortality and all-cause mortality in a large population in China. Our results point to the promise of one-off LDCT screening in countries with limited medical resources. Further studies are needed to explore interactions by subgroup-including sex, age, smoking status, and economic status-to develop population-specific screening strategies. FUNDING: Ministry of Finance and National Health Commission of the People's Republic of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Adulto , Idoso , China/epidemiologia , Estudos de Coortes , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos
17.
Artigo em Inglês | MEDLINE | ID: mdl-35238173

RESUMO

AIM: This study aims at understanding mammographic density profile in China by comparing the density between women in China and Australia. METHODS: Data of 3250 women aged 45-69 were obtained from the Cancer Screening Program in Urban China and data of 1384 Australian counterparts at same age range were gathered from the Lifepool project. Demographic and reproductive details and mammograms for each cohort were collected. Mammographic density was assessed using AutoDensity, and two metrics, percentage density (PD) and dense area (DA), were applied. T-tests were used to compare the means of mammographic density between two populations of all, premenopausal, and postmenopausal women. Two-way ANOVA was conducted to examine interactions of population (Chinese/Australian) and each variable of interest upon mammographic density. RESULTS: Chinese women had 9.61%, 8.20%, and 9.28% higher PD than their Australian counterparts in all, premenopausal, and postmenopausal women, respectively (all p < 0.001). The mean differences in DA between two population were 1.81 cm2 (p < 0.001), 0.55 cm2 (p = 0.472), and 1.76 cm2 (p = 0.003) for all, premenopausal, and postmenopausal women, respectively. There were significant interactions between population and age (F[4, 4624] = 4.12, p = 0.003), BMI (F[2, 4628] = 3.92, p = 0.020), age at first birth (F[1, 4250] = 11.69, p < 0.001), breastfeeding history (F[1, 4479] = 17.79, p < 0.001), and breastfeeding duration (F[1, 3526] = 66.90, p < 0.001) upon PD. Interaction was only found for breastfeeding history (F[1, 4479] = 4.79, p = 0.029) and breastfeeding duration (F[1, 3526] = 17.72, p < 0.001) for DA. CONCLUSIONS: Both PD and DA were found to be higher in Chinese women compared to Australian women. The density difference by menopause status was shown and breastfeeding history affected breast density differently in both populations.

18.
Artigo em Inglês | MEDLINE | ID: mdl-35263809

RESUMO

BACKGROUND AND AIM: The risk-adapted screening strategy showed satisfying colorectal cancer (CRC) screening yield and efficiency. We therefore further explored the diagnostic performance variation of this strategy using different risk prediction models. METHODS: A literature search was conducted to identify studies evaluating risk models for advanced colorectal neoplasm (ACN). The included models were retrospectively validated in a subset sample (N = 3219) from a population-based CRC screening trial in China. Diagnosis-related indictors were compared between the risk-adapted screening strategy using different models and the fecal immunochemical test (FIT)-only strategy. For simulated populations with ACN prevalence of 3% to 12%, the trade-off of additional false positives for each additional true positive were calculated. RESULTS: We included 14 eligible risk models with the area under the curves ranging 0.570 to 0.652 in the validation set. The overall sensitivities of the risk-adapted screening strategy using different risk models for ACN varied from 46.0% to 69.8%, higher than FIT (21.9%), but at the expense of specificities (51.6% to 78.3% vs 97.1%). For population having ACN prevalence of 3%, risk-adapted screening strategies needed 20.5 to 31.1 additional false positives for each additional true positive compared with FIT, and respective number would substantially reduce (4.7 to 7.1) as the ACN prevalence increased to 12%. CONCLUSIONS: Risk-adapted screening strategy using the current risk models showed improved sensitivity for ACN compared with FIT, at the cost of increased colonoscopy workload. The optimal strategy for screening practice should be tailored considering the disease burden and availability of healthcare resources.

19.
Adv Sci (Weinh) ; 9(13): e2104682, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35240008

RESUMO

Direct cell reprogramming, also called transdifferentiation, is valuable for cell fate studies and regenerative medicine. Current approaches to transdifferentiation are usually achieved by directly targeting the nuclear functions, such as manipulating the lineage-specific transcriptional factors, microRNAs, and epigenetic modifications. Here, a robust method to convert fibroblasts to neurons through targeting the cytoskeleton followed by exposure to lineage-specification surroundings is reported. Treatment of human foreskin fibroblasts with a single molecule inhibitor of the actomyosin contraction, can disrupt the cytoskeleton, promote cell softening and nuclear export of YAP/TAZ, and induce a neuron-like state. These neuron-like cells can be further converted into mature neurons, while single-cell RNA-seq shows the homogeneity of these cells during the induction process. Finally, transcriptomic analysis shows that cytoskeletal disruption collapses the original lineage expression profile and evokes an intermediate state. These findings shed a light on the underestimated role of the cytoskeleton in maintaining cell identity and provide a paradigm for lineage conversion through the regulation of mechanical properties.


Assuntos
Transdiferenciação Celular , Fibroblastos , Diferenciação Celular , Reprogramação Celular , Fibroblastos/fisiologia , Humanos , Neurônios
20.
Cancer ; 128(11): 2138-2147, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35315510

RESUMO

BACKGROUND: Patients with refractory central nervous system leukemia (CNSL) have a dismal prognosis and lack effective therapy. Case reports have shown that sorafenib is effective against brain metastases, including leukemia. METHODS: To explore the efficacy of sorafenib combined with conventional therapies for refractory CNSL, a phase 2 study was conducted. The primary end point was the complete remission rate (CRR) within 8 weeks of treatment. Secondary end points included the overall response rate (ORR), event-free survival (EFS), overall survival (OS), and adverse events (AEs). RESULTS: Twenty-six patients with refractory CNSL were enrolled; they included 17 with isolated CNSL, 7 with hematological relapse, and 2 with another extramedullary relapse. After 8 weeks of treatment, 21 patients achieved complete remission, 2 achieved partial remission, and 3 achieved no remission for a CRR of 80.8% (95% CI, 62.1%-91.5%) and an ORR of 88.5% (95% CI, 71.0%-96.0%). Twenty patients survived, and 6 died. The 2-year EFS and OS rates were 75.0% (95% CI, 54.5%-88.3%) and 76.9% (95% CI, 54.2%-90.4%), respectively. Six patients experienced grade 3 or 4 treatment-related AEs, including moderate chronic graft-vs-host disease (n = 3), grade 3 or 4 acute graft-vs-host disease (n = 2), and grade 3 skin rash (n = 1). No treatment-related deaths occurred during the therapy of refractory CNSL. CONCLUSIONS: Sorafenib combined with conventional therapies is effective and safe for refractory CNSL. LAY SUMMARY: Sorafenib combined with conventional therapies is effective and safe for refractory central nervous system leukemia.


Assuntos
Neoplasias do Sistema Nervoso Central , Doença Enxerto-Hospedeiro , Leucemia , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Humanos , Recidiva , Estudos Retrospectivos , Sorafenibe
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