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2.
Transplant Rev (Orlando) ; 38(3): 100842, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38537484

RESUMO

AIMS: Tacrolimus (Tac) is commonly prescribed in solid organ transplantation to prevent immune-mediated damage to the graft. However, its pharmacokinetics show substantial variability between and within patients. Intra-patient variability of tacrolimus (Tac-IPV) has emerged as a novel marker to predict transplant outcomes. Numerous studies report varying associations between Tac-IPV and clinical outcomes, with Tac-IPV measures showing wide discrepancies among these studies. This inconsistency could be a significant factor that influences the various outcomes reported in different studies. Our review comprehensively assesses the relationship between various Tac-IPV measures and their associations with clinical outcomes in transplant patients. METHODS: A comprehensive literature search was conducted using the PubMed and Embase databases, covering the period from 2004 to March 31, 2023. The search focused on studies that examined the relationship between Tac-IPV and clinical outcomes in kidney transplantation (KT). The inclusion criteria were specific to studies addressing Tac-IPV, including measures such as standard deviation (SD), coefficient of variation (CV), time-weighted coefficient of variability (CV), mean absolute deviation (MAD), and Tac variability score (TVS). Clinical outcomes included the development of de novo donor-specific antibodies (dnDSA), rejection episodes, graft loss, and graft failure. RESULTS: Among the 33 studies that met the inclusion criteria, a notable proportion presented conflicting findings in their assessment of various Tac-IPV measures regarding dnDSA, rejection episodes, graft loss, and graft failure. CONCLUSIONS: Most studies have identified a correlation between high Tac-IPV and poor clinical outcomes; however, this relationship is multifactorial. Influencing factors include the metabolic status of KT patients, the timing of Tac-IPV calculations, and the criteria for defining high and low Tac-IPV thresholds, including the size and selection method. CV, MAD, and TWCV are the metrics that are most frequently used to determine Tac-IPV. Additionally, most of the methods for establishing Tac-IPV thresholds typically employ receiver operating characteristic (ROC) curves and median values. It is also notable that studies examining the clinical significance of Tac-IPV often include tacrolimus levels measured six months after kidney transplantation.

3.
Clin Chem ; 70(2): 434-443, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38069911

RESUMO

BACKGROUND: Tracing patient-specific tumor mutations in cell-free DNA (cfDNA) for minimal residual disease (MRD) detection is promising but challenging. Assaying more mutations and cfDNA stands to improve MRD detection but requires highly accurate, efficient sequencing methods and proper calibration to prevent false detection with bespoke tests. METHODS: MAESTRO (Minor Allele Enriched Sequencing Through Recognition Oligonucleotides) uses mutation-specific oligonucleotide probes to enrich cfDNA libraries for tumor mutations and enable their accurate detection with minimal sequencing. A new approach, MAESTRO-Pool, which entails pooling MAESTRO probes for all patients and applying these to all samples from all patients, was used to screen for 22 333 tumor mutations from 9 melanoma patients in 98 plasma samples. This enabled quantification of MRD detection in patient-matched samples and false detection in unmatched samples from other patients. To detect MRD, a new dynamic MRD caller was used that computes a probability for MRD detection based on the number of mutations and cfDNA molecules sequenced, thereby calibrating for variations in each bespoke test. RESULTS: MAESTRO-Pool enabled sensitive detection of MRD down to 0.78 parts per million (ppm), reflecting a 10- to 100-fold improvement over existing tests. Of the 8 MRD positive samples with ultra-low tumor fractions <10 ppm, 7 were either in upward-trend preceding recurrence or downward-trend aligning with response. Of 784 patient-unmatched tests, only one was found as MRD positive (tumor fraction = 2.7 ppm), suggesting high specificity. CONCLUSIONS: MAESTRO-Pool enables massively parallel, tumor-informed MRD testing with concurrent benchmarking of bespoke MRD tests. Meanwhile, our new MRD caller enables more mutations and cfDNA molecules to be tested without compromising specificity. These improve the ability for detecting traces of MRD from blood.


Assuntos
Ácidos Nucleicos Livres , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasia Residual/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Estudos de Coortes , Mutação
4.
Medicine (Baltimore) ; 102(50): e36387, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38115313

RESUMO

BACKGROUND: The cost-effectiveness of sotorasib and its reasonable price in the United States (US) and China remain unknown. Our objective was to estimate the price at which sotorasib could be economical as second-line treatment for advanced non-small-cell lung cancer patients with Kirsten rat sarcoma viral oncogene homolog p.G12C-mutation in 2 countries. METHODS: We conducted an economic evaluation from the perspective of US and Chinese payers. To analyze US patients, we built a partitioned survival model. However, since we lacked Asian-specific overall survival data, we created a state transition model for the Chinese patients. We obtained patients' baseline characteristics and clinical data from CodeBreaK200, while utilities and costs were gathered from public databases and published literature. We calculated costs (US dollar), life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. We conducted price simulation to guide pricing strategies. Additionally, we assessed the reliability of our results through sensitivity analyses, scenario analyses, and subgroup analyses. RESULTS: The incremental cost-effectiveness ratios of sotorasib compared to docetaxel were $1501,852 per quality-adjusted life-years (QALY) in the US and $469,106/QALY in China, respectively, which meant sotorasib was unlikely to be economical at the currently available price of $20,878 (240 × 120 mg) in both countries. Price simulation results revealed that sotorasib would be preferred at a price lower than $1400 at the willingness-to-pay threshold of $37,376 in China and a price lower than $2220 at the willingness-to-pay threshold of $150,000 in the US. Sensitivity, scenario, and subgroup analyses showed that these conclusions were generally robust, the model was most sensitive to the utilities of progression-free survival and post-progression survival. CONCLUSIONS: Sotorasib could potentially be a cost-effective therapy in the US and China following price reductions. Our evidence-based pricing strategy can assist decision-makers and clinicians in making optimal decisions. However, further analysis of budget impact and affordability is needed.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Estados Unidos , Docetaxel/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Análise de Custo-Efetividade , Custos de Medicamentos , Reprodutibilidade dos Testes , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Análise Custo-Benefício , Anos de Vida Ajustados por Qualidade de Vida
5.
Nanomaterials (Basel) ; 13(16)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37630895

RESUMO

The growing demands for material longevity in marine environments necessitate the development of highly efficient, low-cost, and durable corrosion-protective coatings. Although magnesium alloys are widely used in the automotive and aerospace industries, severe corrosion issues still hinder their long-term service in naval architecture. In the present work, an epoxy composite coating containing sericite nanosheets is prepared on the AZ31B Mg alloy using a one-step electrophoretic deposition method to improve corrosion resistance. Due to the polyetherimide (PEI) modification, positively charged sericite nanosheets can be highly orientated in an epoxy coating under the influence of an electric field. The sericite-incorporated epoxy coating prepared in the emulsion with 4 wt.% sericite exhibits the highest corrosion resistance, with its corrosion current density being 6 orders of magnitude lower than that of the substrate. Electrochemical measurements and immersion tests showed that the highly orientated sericite nanosheets in the epoxy coating have an excellent barrier effect against corrosive media, thus significantly improving the long-term anti-corrosion performance of the epoxy coating. This work provides new insight into the design of lamellar filler/epoxy coatings with superior anticorrosion performance and shows promise in the corrosion protection of magnesium alloys.

6.
Nat Genet ; 55(5): 871-879, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37106072

RESUMO

Detecting mutations from single DNA molecules is crucial in many fields but challenging. Next-generation sequencing (NGS) affords tremendous throughput but cannot directly sequence double-stranded DNA molecules ('single duplexes') to discern the true mutations on both strands. Here we present Concatenating Original Duplex for Error Correction (CODEC), which confers single duplex resolution to NGS. CODEC affords 1,000-fold higher accuracy than NGS, using up to 100-fold fewer reads than duplex sequencing. CODEC revealed mutation frequencies of 2.72 × 10-8 in sperm of a 39-year-old individual, and somatic mutations acquired with age in blood cells. CODEC detected genome-wide, clonal hematopoiesis mutations from single DNA molecules, single mutated duplexes from tumor genomes and liquid biopsies, microsatellite instability with 10-fold greater sensitivity and mutational signatures, and specific tumor mutations with up to 100-fold fewer reads. CODEC enables more precise genetic testing and reveals biologically significant mutations, which are commonly obscured by NGS errors.


Assuntos
Neoplasias , Sêmen , Masculino , Humanos , Adulto , Mutação/genética , Neoplasias/genética , Neoplasias/diagnóstico , Análise de Sequência de DNA , DNA , Sequenciamento de Nucleotídeos em Larga Escala
7.
medRxiv ; 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36945501

RESUMO

Purpose: To examine circulating tumor DNA (ctDNA) and its association with residual cancer burden (RCB) using an ultrasensitive assay in patients with triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy (NAT). Patients and Methods: We identified responders (RCB-0/1) and matched non-responders (RCB-2/3) from the phase II TBCRC 030 prospective study of neoadjuvant paclitaxel vs. cisplatin in TNBC. We collected plasma samples at baseline, three weeks, and twelve weeks (end of therapy). We created personalized ctDNA assays utilizing MAESTRO mutation enrichment sequencing. We explored associations between ctDNA and RCB status and disease recurrence. Results: Of 139 patients, 68 had complete samples and no additional NAT. Twenty-two were responders and 19 of those had sufficient tissue for whole-genome sequencing. We identified an additional 19 non-responders for a matched case-control analysis of 38 patients using a MAESTRO ctDNA assay tracking 319-1000 variants (median 1000) to 114 plasma samples from 3 timepoints. Overall, ctDNA positivity was 100% at baseline, 79% at week 3, and 55% at week 12. Median tumor fraction (TFx) was 3.7 × 10 -4 (range: 7.9 × 10 -7 to 4.9 × 10 -1 ). TFx decreased 285-fold from baseline to week 3 in responders and 24-fold in non-responders. Week 12 ctDNA clearance correlated with RCB: clearance was observed in 10/11 patients with RCB-0, 3/8 with RCB-1, 4/15 with RCB-2, and 0/4 with RCB-3. Among 6 patients with known recurrence five had persistent ctDNA at week 12. Conclusion: NAT for TNBC reduced ctDNA TFx by 285-fold in responders and 24-fold in non-responders. In 58% (22/38) of patients, ctDNA TFx dropped below the detection level of a commercially available test, emphasizing the need for sensitive tests. Additional studies will determine if ctDNA-guided approaches can improve outcomes.

8.
Genes Genomics ; 45(1): 49-57, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36399309

RESUMO

BACKGROUND: Adriamycin (ADR) is an effective treatment for breast cancer; nevertheless, it is often linked with acquired resistance in breast cancer cells, reducing ADR's therapeutic efficacy and increasing the risk of recurrence and poor prognosis. It has been revealed that the zinc-finger transcription factor pleomorphic adenoma gene like-2 (PLAGL2) is required for epithelial to mesenchymal transition (EMT) in cancer cells. Recent data indicates that PLAGL2 is also involved in regulating chemotherapeutic drug resistance, albeit the exact mechanism by which this happens remains unknown. OBJECTIVE: This study examines the effect of PLAGL2 on adriamycin resistance and EMT in breast cancer cells. METHODS: The small interfering RNA (siRNA) targeting PLAGL2 was transfected to breast cancer cells to alter PLAGL2 expression. Cell counting kit-8 (CCK-8) and colony formation assay detected cell growth and proliferation rate. Moreover, wound-healing and transwell assays were conducted to evaluate migration and invasion. Western blot (WB) checked the apoptosis and EMT-associated proteins. RESULTS: PLAGL2 expression is associated with breast cancer cells' acquired resistance to ADR in this investigation. Additionally, deletion of PLAGL2 was associated with enhanced sensitivity to ADR, reduced proliferation, migration, and invasion capabilities, increased E-cadherin levels, and reduced Wnt6, ß-catenin, and DVL1 levels in ADR-resistant breast cancer cells (MCF-7/ADR and MDA-MB-231/ADR cells). PLAGL2 could bind to the promoter region of Wnt6 and promote its expression. Additionally, the results of this research established that Wnt signaling is implicated in breast cancer cells' resistance to ADR since BML-284, a Wnt signaling activator partly restored the sensitivity of MCF-7/ADR and MDA-MB-231/ADR cells to ADR. CONCLUSION: PLAGL2 promotes adriamycin resistance and cell aggressiveness in breast cancer cells via activating the Wnt signaling pathway.


Assuntos
Neoplasias da Mama , Doxorrubicina , Humanos , Feminino , Doxorrubicina/farmacologia , Via de Sinalização Wnt , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Transição Epitelial-Mesenquimal/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , RNA Interferente Pequeno , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a RNA/genética
9.
ACS Nano ; 16(8): 12620-12634, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35856940

RESUMO

Wearable sensors have recently attracted extensive interest not only in the field of healthcare monitoring but also for convenient and intelligent human-machine interactions. However, challenges such as wearable comfort, multiple applicable conditions, and differentiation of mechanical stimuli are yet to be fully addressed. Herein, we developed a breathable and waterproof electronic skin (E-skin) that can perceive pressure/strain with nonoverlapping signals. The synergistic effect from magnetic attraction and nanoscaled aggregation renders the E-skin with microscaled pores for breathability and three-dimensional microcilia for superhydrophobicity. Upon applied pressure, the bending of conductive microcilia enables sufficient contacts for resistance decrease, while the stretching causes increased resistance due to the separation of conductive materials. The optimized E-skin exhibits a high gauge factor of 7.747 for small strain (0-80%) and a detection limit down to 0.04%. The three-dimensional microcilia also exhibit a sensitivity of -0.0198 kPa-1 (0-3 kPa) and a broad detection range up to 200 kPa with robustness. The E-skin can reliably and precisely distinguish kinds of the human joint motions, covering a broad spectrum including bending, stretching, and pressure. With the nonoverlapping readouts, ternary inputs "1", "0", and "-1" could be produced with different stimuli, which expands the command capacity for logic outputs such as effective Morse code and intuitive robotic control. Owing to the rapid response, long-term stability (10 000 cycles), breathability, and superhydrophobicity, we believe that the E-skin can be widely applied as wearable devices from body motion monitoring to human-machine interactions toward a more convenient and intelligent future.


Assuntos
Dispositivos Eletrônicos Vestíveis , Humanos , Condutividade Elétrica , Movimento (Física)
10.
Chin Med J (Engl) ; 135(7): 828-836, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35288506

RESUMO

BACKGROUND: Keloids are benign fibrous growths that are caused by excessive tissue build-up. Severe keloids exert more significant effects on patients' quality of life than do mild keloids. We aimed to identify factors associated with the progression from mild keloids to severe keloids, as distinct from those associated with the formation of keloids. METHODS: In this retrospective case-control study, 251 patients diagnosed with keloids at West China Hospital between November 2018 and April 2021 were grouped according to the severity of lesions (mild [n = 162] or severe [n = 89]). We collected their basic characteristics, living habits, incomes, comorbidities, and keloid characteristics from Electronic Medical Records in the hospital and the patients' interviews. Conditional multivariable regression was performed to identify the independent risk factors for the progression of keloids. RESULTS: Eighty-nine patients (35.5%) were classified as having severe keloids. We found the distribution of severe keloids varied with sex, age, excessive scrubbing of keloids, family income, the comorbidity of rheumatism, disease duration, characteristics of the location, location in sites of high-stretch tension, the severity and frequency of pain, the severity of pruritus, and infection. Multivariable analysis revealed significant associations between severe keloids and infection (odds ratio [OR], 3.55; P = 0.005), excessive scrubbing of keloids (OR, 8.65; P = 0.001), low or middle family income (OR, 13.44; P = 0.021), comorbidity of rheumatism (OR, 18.97; P = 0.021), multiple keloids located at multiple sites (OR, 3.18; P = 0.033), and disease duration > 15 years (OR, 2.98; P = 0.046). CONCLUSION: Doctors should implement more active and thorough measures to minimize the progression of mild keloids in patients who have any of the following risk factors: infection, excessive scrubbing of keloids, low or middle family income, comorbidity of rheumatism, multiple keloids located at multiple sites, and disease duration > 15 years.


Assuntos
Queloide , Doenças Reumáticas , Estudos de Casos e Controles , Humanos , Queloide/epidemiologia , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco
11.
Nat Biomed Eng ; 6(3): 257-266, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35301450

RESUMO

Assaying for large numbers of low-frequency mutations requires sequencing at extremely high depth and accuracy. Increasing sequencing depth aids the detection of low-frequency mutations yet limits the number of loci that can be simultaneously probed. Here we report a method for the accurate tracking of thousands of distinct mutations that requires substantially fewer reads per locus than conventional hybrid-capture duplex sequencing. The method, which we named MAESTRO (for minor-allele-enriched sequencing through recognition oligonucleotides), combines massively parallel mutation enrichment with duplex sequencing to track up to 10,000 low-frequency mutations, with up to 100-fold fewer reads per locus. We show that MAESTRO can be used to test for chimaerism by tracking donor-exclusive single-nucleotide polymorphisms in sheared genomic DNA from human cell lines, to validate whole-exome sequencing and whole-genome sequencing for the detection of mutations in breast-tumour samples from 16 patients, and to monitor the patients for minimal residual disease via the analysis of cell-free DNA from liquid biopsies. MAESTRO improves the breadth, depth, accuracy and efficiency of mutation testing by sequencing.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise de Sequência de DNA/métodos
12.
Cancer Med ; 11(16): 3093-3105, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35297216

RESUMO

INTRODUCTION: The main emphasis of the research about adjuvant imatinib for high-risk gastrointestinal stromal tumors (GISTs) is prolonging the treatment duration and ignores the heterogeneous that 10-year recurrence rates ranged from about 20%-100%. Thus, this study evaluated the effect of different durations of adjuvant imatinib on outcomes in high-risk GISTs to explore the feasibility of individual treatment. METHODS: We analyzed 855 high-risk GIST patients from three centers who underwent macroscopically complete resection between December 2007 and September 2020. The patients were divided into training (n =564) and two validation cohorts (n = 238 and53) based on their source. Recurrence-free survival (RFS) was the primary point. Cox multivariate analysis was used to develop the nomogram. C-index, time-dependent area under the curves, and calibration plots were used to assess the performance of the nomogram. RESULTS: Univariate analysis showed that longer adjuvant imatinib was significantly associated with better 5-year RFS (p < 0.0001). Further investigation identified that the same high-risk patients with lower tumor-associated recurrence risk benefitted little from prolonged treatment and that the recommended adjuvant imatinib duration was insufficient for those with higher recurrence risk. A nomogram for predicting 2-, 3-, and 5-year RFS based on different treatment durations and four major risk factors, namely, tumor site, size, mitotic count, and rupture status, was built and validated, with a C-index of 0.82, 0.74, and 0.70 in training and two external validation cohorts, respectively. An online dynamic nomogram was further developed for clinical applications (https://ruolinliu666.shinyapps.io/GIST/), offering predictive recurrence rates based on different treatment durations and tumor features. CONCLUSIONS: We developed a nomogram to predict the recurrence risk for high-risk patients according to tumor features and treatment durations of imatinib to help physicians on decision-making for individualized treatment duration.


Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia/patologia , Nomogramas , Estudos Retrospectivos , Fatores de Risco
13.
J Craniofac Surg ; 33(1): 203-205, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34267134

RESUMO

ABSTRACT: High-voltage (≥1000 V) electrical injury is always related to high mortality and poor prognosis. The incidence rates of the high-voltage electrical injuries of the neck are lower than those of the other parts of the body. This article reports a case of the reconstruction of severe neck scar contracture after electrical injury. Compared with cases of scar contractures caused by nonelectrical injuries, this case had the following remarkable characteristics: extremely severe difficult airway, contracture scars involving whole layers of tissue, muscle and nerve damage, mandibular retraction, and poor occlusal relationship. The chief complaints of the patient upon admission, including forced position and continuous salivation, were greatly relieved through several operations by using different kinds of flaps and offering support to the flap from the palmar tendon and relocated mandible. However, the problem of salivation was incompletely solved. This problem might be caused by damage to related nerves and masticatory muscle function caused by high-voltage electrical injury. The patient was satisfied with the recovery of his appearance and movement function.


Assuntos
Queimaduras , Contratura , Procedimentos de Cirurgia Plástica , Queimaduras/cirurgia , Cicatriz/cirurgia , Contratura/etiologia , Contratura/cirurgia , Humanos , Pescoço/cirurgia , Transplante de Pele , Retalhos Cirúrgicos , Resultado do Tratamento
14.
Nucleic Acids Res ; 50(1): e1, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-34591958

RESUMO

Accurate DNA sequencing is crucial in biomedicine. Underlying the most accurate methods is the assumption that a mutation is true if altered bases are present on both strands of the DNA duplex. We now show that this assumption can be wrong. We establish that current methods to prepare DNA for sequencing, via 'End Repair/dA-Tailing,' may substantially resynthesize strands, leading amplifiable lesions or alterations on one strand to become indiscernible from true mutations on both strands. Indeed, we discovered that 7-17% and 32-57% of interior 'duplex base pairs' from cell-free DNA and formalin-fixed tumor biopsies, respectively, could be resynthesized in vitro and potentially introduce false mutations. To address this, we present Duplex-Repair, and show that it limits interior duplex base pair resynthesis by 8- to 464-fold, rescues the impact of induced DNA damage, and affords up to 8.9-fold more accurate duplex sequencing. Our study uncovers a major Achilles' heel in sequencing and offers a solution to restore high accuracy.


Assuntos
Neoplasias da Mama/genética , DNA/análise , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Feminino , Humanos , Estrutura Molecular
15.
Cancer Cell Int ; 21(1): 614, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809619

RESUMO

BACKGROUND: Most previous studies compared the risk for non-melanoma skin cancer (NMSC) in biologic-treated common inflammatory diseases with the general population. Whether the increased NMSC risk is caused by the disease itself, the biologics, or both remains unknown. METHODS: We systematically searched PubMed, Embase, Medline, Web of Science, and Cochrane Library from inception to May 2021. Studies were included if they assessed the risk of NMSC for rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis patients treated with biologics compared with patients not receiving biologics. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model. RESULTS: The current meta-analysis included 12 studies. Compared with patients with the inflammatory disease without biologics, patients receiving biological therapy were associated with an increased risk for NMSC (RR 1.25, 95% CI 1.14 to 1.37), especially in patients with RA (RR 1.24, 95% CI 1.13 to 1.36) and psoriasis (RR 1.28, 95% CI 1.07 to 1.52), but not in patients with IBD (RR 1.49, 95% CI 0.46 to 4.91). The risks for squamous cell skin cancer and basal cell skin cancer were both increased for patients receiving biologics. However, the risk of NMSC did not increase in patients treated with biologics less than 2 years. CONCLUSIONS: Current evidence suggests that increased risk of NMSC was identified in RA and psoriasis treated with biologics compared with patients not receiving biologics, but not in patients with IBD. The inner cause for the increased risk of NMSC in IBD patients should be further discussed.

16.
Free Radic Biol Med ; 156: 83-98, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32305646

RESUMO

Resveratrol (RSV) is a natural polyphenol with anti-obesity effects. However, the mechanisms of anti-obesity remain unclear due to its low bioavailability. Recent evidence demonstrates that gut microbiota plays a key role in obesity. This spurred us to investigate whether the anti-obesity effects of RSV are related to modulations in the gut microbiota and metabolic functions. Here, RSV significantly improved metabolic phenotype and intestinal oxidative stress in the high-fat diet (HFD)-fed mice. A multi-omics approach was used to systematically profile the microbial signatures at both the phylogenetic and functional levels using 16S rRNA gene sequencing and metagenome. At the phylogenetic level, RSV treatment significantly modulated the gut microbiota composition in HFD-fed mice, characterized with increased Blautia abundance and decreased Desulfovibrio and Lachnospiraceae_NK4A136_group abundance. At the functional level, RSV significantly decreased the enrichment of pathways linked to host metabolic disease and increased the enrichment of pathways involved in the generation of small metabolites. Besides, the fecal microbiota transplantation experiment showed anti-obesity and microbiota-modulating effects similar to those observed in the oral RSV-feeding experiment. Furthermore, metabolomic analysis and antibiotic treatment verified that 4-hydroxyphenylacetic acid (4-HPA) and 3-hydroxyphenylpropionic acid (3-HPP) were the two gut metabolites of RSV, which contribute to improving lipid metabolism in vitro. Moreover, the content of 4-HPA and 3-HPP exhibited strong correlation with the intestinal oxidative state. We concluded that the RSV-mediated alteration of gut microbiota, related gut metabolites and redox state of the intestinal environment contributed to prevention of metabolic syndrome in HFD-fed mice.


Assuntos
Dieta Hiperlipídica , Microbioma Gastrointestinal , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/etiologia , Filogenia , RNA Ribossômico 16S/genética , Resveratrol
17.
Nat Commun ; 10(1): 1041, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833567

RESUMO

Accurate detection of somatic mutations is still a challenge in cancer analysis. Here we present NeuSomatic, the first convolutional neural network approach for somatic mutation detection, which significantly outperforms previous methods on different sequencing platforms, sequencing strategies, and tumor purities. NeuSomatic summarizes sequence alignments into small matrices and incorporates more than a hundred features to capture mutation signals effectively. It can be used universally as a stand-alone somatic mutation detection method or with an ensemble of existing methods to achieve the highest accuracy.


Assuntos
Biologia Computacional/métodos , Análise Mutacional de DNA/métodos , Aprendizado de Máquina , Mutação , Redes Neurais de Computação , Biologia Computacional/instrumentação , Análise Mutacional de DNA/instrumentação , Bases de Dados Genéticas , Diploide , Exoma , Genes Neoplásicos , Humanos , Neoplasias/genética , Alinhamento de Sequência , Análise de Sequência de DNA/instrumentação , Análise de Sequência de DNA/métodos
18.
Int J Legal Med ; 133(3): 733-743, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30820645

RESUMO

Prior to implementing a new kit into application, developmental validation should be conducted to demonstrate the robustness and applicability of the kit. In this study, 24 Y-STR loci from the AGCU Y SUPP STR kit were tested including 11 loci overlapping with other commercial kits (DYS385a/b, DYS635, DYS533, DYS481, DYS549, DYS460, DYS527a/b, DYS522, and DYS444) and 13 new loci (DYS531, DYS630, DYS622, DYS552, DYS510, DYS459a/b, DYS446, DYS443, DYS587, Y-GATA-A10, DYS520, and DYS557). Developmental validation including PCR-related studies, sensitivity, stability, and species specificity studies were conducted. The performance of the kit in genotyping case-type samples was also estimated. The results indicated that the kit is robust, accurate and sensitive and is able to detect male samples without being affected by female samples or other species. Population data were obtained with this kit in Chinese Xibe group as well. Totally 139 different haplotypes were obtained from 167 male samples and demonstrated that this typing system is relatively discriminative.


Assuntos
Cromossomos Humanos Y , Técnicas de Genotipagem/instrumentação , Repetições de Microssatélites , Animais , China , Impressões Digitais de DNA , Etnicidade/genética , Feminino , Técnicas de Genotipagem/métodos , Humanos , Masculino , Reação em Cadeia da Polimerase , Especificidade da Espécie
19.
Plast Reconstr Surg ; 143(3): 711-721, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30601325

RESUMO

BACKGROUND: Choosing implant shape (round or anatomical) is one of the most essential yet controversial decisions in cosmetic breast augmentation. Many surgeons choose implant shape based on personal experience or expert opinion. This is the first systematic review and meta-analysis comparing the aesthetic effect between anatomical and round implants in primary cosmetic breast augmentation. METHODS: The authors searched the PubMed, MEDLINE, Embase, ScienceDirect, Web of Knowledge, Scopus, and Cochrane Central Register of Controlled Trials databases for studies that compared anatomical and round implants in primary cosmetic breast augmentation. Primary outcomes were postoperative aesthetic effect and correct identification rate of implant shape. Random effects models were used to obtain pooled standardized mean difference and 95 percent confidence intervals. RESULTS: One randomized comparative and four observational comparative studies met the inclusion criteria. No aesthetic superiority was found in the anatomical implant group with regard to overall appearance (standardized mean difference, 0.06; 95 percent CI, -0.40 to 0.53), naturalness (standardized mean difference, 0.18; 95 percent CI, -1.51 to 1.15), projection, upper pole contour, and lower pole contour. Pooled correct identification rate of implant shape by plastic surgeons was 52 percent (95 percent CI, 0.46 to 0.58). CONCLUSIONS: Generally, anatomical implants do not seem to have an aesthetic superiority compared to round implants. Plastic surgeons seemed to be unable to accurately differentiate the two implant shapes in vivo. Further studies should focus on identifying the specific indications for the use of anatomical implants.


Assuntos
Implante Mamário/instrumentação , Implantes de Mama , Mama/anatomia & histologia , Estética , Mama/cirurgia , Implante Mamário/métodos , Feminino , Humanos , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Int Wound J ; 16(2): 479-485, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30588742

RESUMO

We aimed to report the clinical features of squamous cell carcinoma (SCC) occurring on scalp scar tissue among a Chinese population, demonstrate its pathological progress, analyse the prognosis-related factors, and share our clinical experience of managing this rare disease in practice. A retrospective study was conducted at West China Hospital from January 2013 to January 2018 aiming to identify patients with a diagnosis of SCC or squamous atypical hyperplasia arising from scalp scars. Their medical records were reviewed, and related data were retrieved. Follow up was conducted, and informed consent was obtained by phone calls in June 2018. Of the 31 scalp Marjolin's ulcer (MU) patients, the average latency period and post-ulceration period were 42.9 years and 37.5 months, respectively. Among them, 30 patients (97%) were diagnosed with cancer more than 5 years after initial injury, and 25 patients (80.7%) experienced a pre-ulceration period longer than 20 years. A negative correlation between scalp MU's post-ulceration period and its pre-ulceration period was identified. Only burn scars caused post-ulceration periods of more than 24 months (7/19). Incomplete healing wounds experienced a significantly shorter latency period (P = 0.004) and longer post-ulceration period than others (P < 0.0001). However, the depth of tumour infiltration and complete tumour resection were the only two independent factors that significantly dictated patients' survival in this study. In conclusion, the scalp scaring tissue experienced a long-term stable period but would transform to malignancy rapidly and progressively once ulceration formed. The underlying malignant transformation mechanism remains unclear. Thus, we recommend scalp scarring tissue to be radically removed.


Assuntos
Carcinoma de Células Escamosas/fisiopatologia , Carcinoma de Células Escamosas/cirurgia , Cicatriz/fisiopatologia , Couro Cabeludo/fisiopatologia , Neoplasias Cutâneas/fisiopatologia , Neoplasias Cutâneas/cirurgia , Adulto , Carcinoma de Células Escamosas/diagnóstico , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico
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