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1.
BMJ Open ; 14(10): e084991, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39419623

RESUMO

OBJECTIVE: Zanubrutinib is a second-generation Bruton's tyrosine kinase inhibitor that has been approved for the treatment of several B cell malignancies. The aim of this study was to evaluate adverse events (AEs) associated with zanubrutinib based on the real-world data. DESIGN: A disproportionality analysis was performed to identify the potential zanubrutinib-related AEs. SETTING: The Food and Drug Administration AE Reporting System database from the fourth quarter of 2019 to the third quarter of 2023. MAIN OUTCOME MEASURES: The results of the disproportionality analyses were presented as reported ORs (RORs). When the lower limit of the 95% CI for the ROR is greater than 1 and the number of AE reports is≥3, it indicates that the preferred term (PT) may be a positive AE signal. RESULTS: A total of 846 AE reports with zanubrutinib as the primary suspect drug were obtained, with 2826 AEs. A total of 74 positive PT signals were detected across 18 system organ classes (SOCs). The most significant signal for SOC was 'blood and lymphatic system disorders' (ROR=2.8, 95% CI 2.3 to 3.3), while the most significant signal for PT was 'haemorrhage subcutaneous' (ROR=190.8, 95% CI 128.0 to 284.5). 13 unexpected off-label AEs were also observed, such as abnormal hair texture, skin discolouration, hypernatraemia, pericardial effusion and hypersomnia. The median time to onset of AEs associated with zanubrutinib was 51 days (IQR 13-192 days) and was consistent with the early failure model. In comparison with zanubrutinib monotherapy, the combination of zanubrutinib and rituximab therapy was linked to a higher risk of specific AEs, including myelosuppression, pneumonia, leucopenia, thrombocytopenia, abdominal pain, anaemia, pancytopenia and respiratory failure. Furthermore, the combination of zanubrutinib and chemotherapy increased the risk of several severe AEs, such as cardiac arrest, elevated blood lactate dehydrogenase levels and pancytopenia. CONCLUSIONS: The results of the analysis provided valuable insights into the safety profile of zanubrutinib-treated patients, which was helpful for clinical monitoring and identifying potential AEs related to zanubrutinib.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Inibidores de Proteínas Quinases , Pirazóis , Pirimidinas , Humanos , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Inibidores de Proteínas Quinases/efeitos adversos , Masculino , Feminino , Estados Unidos , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Pessoa de Meia-Idade , Bases de Dados Factuais , Antineoplásicos/efeitos adversos , United States Food and Drug Administration , Idoso , Adulto
2.
Sci Rep ; 14(1): 21768, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39300099

RESUMO

In fringe projection profilometry based on temporal phase unwrapping, determining a fringe order map commonly requires a large number of fringes. To reduce the fringe number, this paper proposes a concise absolute phase retrieval algorithm just by projecting four fringes. The first two orthogonal fringes with relatively large frequency can collect reliable height information. The second two fringes are designed the same as the first two, but the only difference is that each 2π-phase of them is shifted by a unique amount, which can robustly label a large number of fringe orders. For decoding the fringes, we develop an average intensity one-time extraction algorithm, which allows for the rapid acquisition of the two pairs of alternating current components. From this, the wrapped phase containing height information and the stair-coded phase providing fringe orders can be directly extracted by arctangent operation in a point-to-point manner. Furthermore, we also develop a universal fringe order correction algorithm that can simultaneously correct the common errors and the misalignment between the wrapped phase and fringe orders. Experiment results demonstrate that this method achieves comparable accuracy and adaptability to the phase-coding method, while utilizing two fewer fringes.

3.
Signal Transduct Target Ther ; 9(1): 229, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39227388

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare and frequently fatal lymphoma subtype. The programmed death-1 (PD-1) pathway has emerged as a potential therapeutic target, but the effectiveness of PD-1 antibody sintilimab in combination with immunochemotherapy as a frontline treatment for PCNSL remains to be determined. In this phase 2 trial (ChiCTR1900027433) with a safety run-in, we included patients aged 18-70 with newly diagnosed PCNSL. Participants underwent six 21-day cycles of a SMTR regimen, which includes sintilimab (200 mg, Day 0), rituximab (375 mg/m2, Day 0), methotrexate (3.0 g/m2, Day 1 or 1.0 g/m2 for patients aged ≥65 years), and temozolomide (150 mg/m2/d, Days 1-5). Among 27 evaluable patients, the overall response rate (ORR) was 96.3% (95% confidence interval: 81-99.9%), with 25 complete responses. At a median follow-up of 24.4 months, the medians for duration of response, progression-free survival (PFS), and overall survival were not reached. The most common grade 3-4 treatment-related toxicities were increased levels of alanine aminotransferase (17.9%) and aspartate aminotransferase (14.3%). Additionally, baseline levels of interferon-α and the IL10/IL6 ratio in cerebrospinal fluid emerged as potential predictors of PFS, achieving areas under the curve of 0.88 and 0.84, respectively, at 2 years. Whole-exome sequencing revealed a higher prevalence of RTK-RAS and PI3K pathway mutations in the durable clinical benefit group, while a greater frequency of Notch and Hippo pathway mutations in the no durable benefit group. These findings suggest the SMTR regimen is highly efficacious and tolerable for newly diagnosed PCNSL, warranting further investigation.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Nervoso Central , Metotrexato , Rituximab , Temozolomida , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Rituximab/administração & dosagem , Temozolomida/administração & dosagem , Temozolomida/farmacologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/imunologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Adulto , Linfoma/tratamento farmacológico , Linfoma/genética , Linfoma/imunologia
4.
Aesthetic Plast Surg ; 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39331082

RESUMO

BACKGROUND: Full-incision double-eyelid blepharoplasty can result in upper eyelid skin numbness postoperatively. However, few studies have examined sensory loss after eyelid surgery. We propose a novel surgical approach with selective sensory nerve preservation to prevent postoperative upper eyelid numbness. METHODS: We enrolled 90 patients who underwent full-incision double-eyelid blepharoplasty with selective sensory nerve preservation from March 2021 to February 2022. Major longitudinal nerves that spread vertically to the palpebral margin under the orbicularis oculi muscle in the medial portion of the upper eyelid were dissected and carefully preserved. Eyelid sensation was measured using a Cochet-Bonnet filament-type esthesiometer at four predetermined anatomical locations in the upper eyelid. The mean esthesiometry reading was calculated at the preoperative and 2-week and final postoperative visits. RESULTS: The follow-up duration was 2-4 months (mean, 3 months). The mean esthesiometry readings at the inferonasal location were 5.22 cm (n=170, SD=0.28) preoperatively, 5.21 cm (n=170, SD=0.31) at 2 weeks postoperatively, and 5.22 cm (n=170, SD=0.29) at the final postoperative visits. Sensation was not significantly different between the second visit and the baseline (P=0.014) or between the final visit and the baseline (P=0.158). None of the patients reported a reduction in their subjective eyelid sensation. CONCLUSIONS: Full-incision double-eyelid blepharoplasty with selective sensory nerve preservation can prevent postoperative upper eyelid numbness while producing reliable and dynamic palpebral creases. The vital nerve branches of the upper eyelid can be preserved, thereby retaining skin sensation near the margin of the eyelid. We propose a novel full-incision double-eyelid blepharoplasty technique that incorporates selective sensory nerve preservation to prevent postoperative upper eyelid numbness. Full-incision double-eyelid blepharoplasty with selective sensory nerve preservation can prevent postoperative upper eyelid numbness while producing reliable and dynamic palpebral creases. The vital nerve branches of the upper eyelid can be preserved, thereby retaining skin sensation near the margin of the eyelid. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

5.
Int J Biol Macromol ; 279(Pt 4): 135621, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39276896

RESUMO

Skin wound healing is a multifaceted biological process that encompasses a variety of cell types and intricate signaling pathways. Recent research has uncovered that exosomes derived from adipose stem cells, commonly referred to as ADSC exosomes, play a crucial role in facilitating the healing process. Moreover, it has been demonstrated that an anoxic, or low-oxygen, environment significantly enhances the effectiveness of these exosomes in promoting skin repair. The primary objective of this study was to investigate the underlying mechanisms through which ADSC exosomes contribute to Skin wound healing, particularly by regulating the long non-coding RNA known as NORAD under hypoxic conditions. A significant focus of our research was to examine the interplay between the microRNA miR-524-5p and the Pumilio protein, as we aimed to understand how these molecular interactions might influence the overall healing process. In this study, ADSC exosomes were extracted by simulating hypoxia in vitro and their effects on the proliferation and migration of skin fibroblasts (FB) were evaluated. The expression levels of NORAD, miR-524-5p and Pumilio were analyzed by fluorescence quantitative PCR. Pumilio protein was silenced by siRNA technique to evaluate its role in ADSC exosome-mediated wound healing. The experimental results showed that under hypoxia conditions, NORAD levels in ADSC exosomes increased significantly and could effectively regulate the expression of miR-524-5p. After Pumilio protein silencing, the proliferation and migration ability of fibroblasts were significantly reduced, indicating that Pumilio protein played a role in the process of wound healing. By inhibiting miR-524-5p, the expression of Pumilio protein was restored, further confirming its regulatory mechanism.


Assuntos
Tecido Adiposo , Exossomos , MicroRNAs , RNA Longo não Codificante , Proteínas de Ligação a RNA , Pele , Cicatrização , MicroRNAs/genética , MicroRNAs/metabolismo , Cicatrização/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Exossomos/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Pele/metabolismo , Proliferação de Células/genética , Células-Tronco/metabolismo , Células-Tronco/citologia , Movimento Celular/genética , Hipóxia Celular/genética , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Fibroblastos/metabolismo , Transdução de Sinais
6.
Clin Epidemiol ; 16: 617-630, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39280118

RESUMO

Purpose: Drug-induced gynecomastia significantly affects patient health and quality of life. This study aimed to perform an exploratory analysis of gynecomastia reports and the most commonly associated medications within the FAERS database. Patients and Methods: A comprehensive analysis of the FAERS from January 2004 to December 2023 was conducted. Disproportionality analysis and subsequent sensitivity analysis were performed to identify drugs potentially associated with gynecomastia, utilizing the reported odds ratio (ROR). Logistic regression analysis was employed to assess potential risk factors. The Weibull shape parameter (WSP) test was used to assess the time-to-onset characteristics of the top drugs associated with gynecomastia. Results: The study identified 30,265 cases of gynecomastia, primarily associated with nervous system drugs, accounting for 85.50% of cases. Notably, risperidone accounted for 80.81% of the total cases. Among the 165 agents with ≥ 5 cases of gynecomastia, the strongest signals were exhibited by risperidone (ROR 602.38, 95% CI 585.07-620.20), dutasteride (ROR 17.18, 95% CI 15.55-18.89), spironolactone (ROR 15.8, 95% CI 13.99-17.83), and paliperidone (ROR 7.16, 95% CI 6.55-7.84). In the sensitivity analysis of disproportionality, unexpected associations were observed, such as montelukast (n = 21, ROR 1.94, 95% CI 1.26-2.98). The logistic regression analysis indicated that the risk of risperidone-induced gynecomastia was significantly lower in adults compared to pediatric patients (OR 0.12, 95% CI 0.09-0.15) and in patients with higher body weight than in those with lower body weight (OR 5.24, 95% CI 3.62-7.76). The WSP test showed that gynecomastia induced by most of the top 10 common agents tends to occur in an early failure mode. Conclusion: The rankings and signal strengths of drugs associated with gynecomastia were extracted from the FAERS. The age distribution and time-to-onset distribution of the top 10 drugs linked to gynecomastia were investigated, which can facilitate accurate clinical recognition of drug-induced gynecomastia.

8.
Clin Spine Surg ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39053002

RESUMO

STUDY DESIGN: An experimental study in a cervical intervertebral fusion goat model. OBJECTIVE: To investigate the effect of bioactive xenogeneic porcine cancellous bone applied to the intervertebral fusion of goat cervical vertebrae. SUMMARY OF BACKGROUND DATA: Although autogenous bone achieves satisfied outcome in cervical intervertebral fusion, it is limited and cause several complications. The application of xenogeneic bone has potential to solve these problems. METHODS: Thirty local goats were randomly divided into 3 groups: group A (12 goats): autogenous tricortical iliac bone group; group B (6 goats): polyetheretherketone (PEEK) cage with autologous bone; and group C (12 goats): PEEK cage with bioactive xenogeneic porcine cancellous bone. C3-C4 discectomy was performed in each group and the above bone graft and bone graft substitutes were implanted. Lateral cervical spine x-rays were taken at preoperative; immediately postoperative; and 4, 8, 12, and 24 weeks postoperatively every goat. Disc space heights (DSHs) were measured on lateral x-rays. CT examination was performed at 12 and 24 weeks after surgery for the fusion score. After 4 and 8 weeks after surgery, 3 goats were euthanized in both groups A and C to evaluate the immune rejection response through histology. At 12 and 24 weeks after surgery, 3 goats were euthanized in each group. The cervical implants fusion outcome was evaluated through specimen histology observation. RESULT: As time extended, the immune rejection of bioactive xenogeneic porcine cancellous bone gradually subsided. Radiology, specimen observation, and histology manifested that the C3-4 vertebral bodies of goats in each group gradually fused. All the goats in each group achieved bony fusion at 24 weeks after surgery. In terms of preventing intervertebral space collapse, the PEEK cage could achieve better results. There was no significant difference in the remaining experimental data (P>0.05). CONCLUSIONS: Bioactive xenogeneic porcine cancellous bone can obtain satisfied fusion outcomes in cervical intervertebral fusion and is an ideal intervertebral fusion material in goats.

9.
Appl Opt ; 63(16): 4284-4292, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856604

RESUMO

The development of modern large-scale spectroscopic survey telescopes responds to the urgent demand for spectral information in astronomical research. Tsinghua University has previously proposed a 6.5 m MUltiplexed Survey Telescope consisting of a Ritchey-Chretien configuration and a 1.8 m multi-element wide-field corrector, achieving excellent performance and world-leading survey efficiency. However, an optimized 1.65 m multi-element corrector with five lenses is proposed to overcome the constraints on glass uniformity and verification in fabrication of the previous corrector design. It maintains outstanding image quality, with the 80% enclosed energy diameter not more than 0.559 arcsec within 3° FoV over up to a 55° zenith angle. The optimized optical system does not revise the working mode of the ADC or the curvature of the primary mirror while ensuring the reasonability and accuracy of manufacturing of large corrector elements. It provides a more feasible reference optical design for the MUltiplexed Survey Telescope in subsequent iterations and communications with manufacturers.

10.
J Plast Reconstr Aesthet Surg ; 94: 119-127, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38776626

RESUMO

BACKGROUND: The efficient resurfacing of multiple adjacent defects (MADs) requires precise reconstructive strategy. Various approaches (e.g., several flap transferring or prelamination of the recipient site) have been reported, but recipient-site impairments, pain, long hospitalization, and low cost-benefit results fatefully considered them as compromise approaches. This study aims to evaluate the feasibility of MADs reconstruction with free multipaddle superficial circumflex iliac artery perforator (SCIAP) flaps. METHODS: From Dec 2015 to Dec 2020, we enrolled patients with upper and lower extremity defects treated with various multipaddle SCIAP flaps (2-paddle, 3-paddle, and 4-paddle). Patient demographics and outcomes of each group were collected. RESULTS: Thirty-two, 21, and 6 patients underwent 2-paddle, 3-paddle, and 4-paddle SCIAP flaps transfers, respectively. All multipaddle SCIAP flaps survived without vascular problems, and the donor sites were closed directly. Except for 3 cases of 2-paddle SCIAP flaps drained by superficial circumflex iliac vein venous return, most cases (n = 56) were drained by venae comitans. Minor complications, including partial flap necrosis (4 cases) and lateral femoral cutaneous nerve palsies (11 cases), were treated conservatively. All patients were satisfied with the reconstructive outcome. CONCLUSION: Multiple adjacent defects reconstruction is still a Gordian knot and lacks a golden standard. The free multipaddle SCIAP flap was demonstrated as a promising alternative, not only enriching its versatility but also initially highlighting the "replace need with need" reconstructive demand.


Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Retalho Perfurante/irrigação sanguínea , Procedimentos de Cirurgia Plástica/métodos , Idoso , Artéria Ilíaca/cirurgia , Estudos de Viabilidade , Estudos Retrospectivos , Retalhos de Tecido Biológico , Adulto Jovem , Adolescente , Extremidade Inferior/cirurgia , Extremidade Superior/cirurgia , Sobrevivência de Enxerto
11.
J Affect Disord ; 360: 97-107, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38821367

RESUMO

BACKGROUND: Higher suicide rates were observed in patients diagnosed with lymphoma. In this study, we accurately identified patients with high-risk lymphoma for suicide by constructing a nomogram with a view to effective interventions and reducing the risk of suicide. METHODS: 235,806 patients diagnosed with lymphoma between 2000 and 2020 were picked from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training (N = 165,064) and validation set (N = 70,742). A combination of the Least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression identified the predictors that constructed the nomogram. To assess the discrimination, calibration, clinical applicability, and generalization of this nomogram, we implemented receiver operating characteristic curves (ROC), calibration curves, decision curve analysis (DCA), and internal validation. The robustness of the results was assessed by the competing risks regression model. RESULTS: Age at diagnosis, gender, ethnicity, marital status, stage, surgery, radiotherapy, and annual household income were key predictors of suicide in lymphoma patients. A nomogram was created to visualize the risk of suicide after a lymphoma diagnosis. The c-index for the training set was 0.773, and the validation set was 0.777. The calibration curve for the nomogram fitted well with the diagonal and the clinical decision curve indicated its clinical benefit. LIMITATION: The effects of unmeasured and unnoticed biases and confounders were difficult to eliminate due to retrospective studies. CONCLUSION: A convenient and reliable model has been constructed that will help to individualize and accurately quantify the risk of suicide in patients diagnosed with lymphoma.


Assuntos
Linfoma , Nomogramas , Programa de SEER , Suicídio , Humanos , Feminino , Masculino , Linfoma/epidemiologia , Linfoma/psicologia , Pessoa de Meia-Idade , Suicídio/estatística & dados numéricos , Adulto , Idoso , Fatores de Risco , Modelos de Riscos Proporcionais , Curva ROC
12.
Sci Rep ; 14(1): 12315, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811602

RESUMO

Land-use change is a direct driver of biodiversity loss, projection and future land use change often consider a topical issue in response to climate change. Yet few studies have projected land-use changes over Africa, owing to large uncertainties. We project changes in land-use and land-use transfer under future climate for three specified time periods: 2021-2040, 2041-2060, and 2081-2100, and compares the performance of various scenarios using observational land-use data for the year 2020 and projected land-use under seven Shared Socioeconomic Pathways Scenarios (SSP): SSP1-1.9, SSP1-2.6, SSP2-4.5, SSP3-7.0, SSP4-3.4, SSP4-6.0 and SSP5-8.5 from 2015 to 2100 in Africa. The observational land-use types for the year 2020 depict a change and show linear relationship between observational and simulated land-use with a strong correlation of 0.89 (P < 0.01) over Africa. Relative to the reference period (1995-2014), for (2021-2040), (2041-2060), (2081-2100), barren land and forest land are projected to decrease by an average of (6%, 11%, 16%), (9%, 19%, 38%) respectively, while, crop land, grassland and urban land area are projected to increase by (36%, 58%, and 105%), (4%, 7% and 11%), and (139%, 275% and 450%) respectively. Results show a substantial variations of land use transfer between scenarios with major from barren land to crop land, for the whole future period (2015-2100). Although SSP4-3.4 project the least transfer. Population and GDP show a relationship with cropland and barren land. The greatest conversion of barren land to crop land could endanger biodiversity and have negative effects on how well the African continent's ecosystem's function.

13.
BMC Cancer ; 24(1): 654, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811891

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system. METHODS: A network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Five clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%. CONCLUSIONS AND RELEVANCE: Among the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China.


Assuntos
Análise Custo-Benefício , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Inibidores de Checkpoint Imunológico , Metanálise em Rede , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/economia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/economia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Cadeias de Markov , Nivolumabe/uso terapêutico , Nivolumabe/economia , Análise de Custo-Efetividade
14.
Artigo em Inglês | MEDLINE | ID: mdl-38631127

RESUMO

As an invasive alien animal, Pomacea canaliculata poses a great danger to the ecology and human beings. Recently, there has been a gradual shift towards bio-friendly control. Based on the development of RNA interference and CRISPR technology as molecular regulatory techniques for pest control, it was determined if the knockout of genes related to sex differentiation in P. canaliculata could induce sterility, thereby helping in population control. However, the knowledge of sex differentiation- and development-related genes in P. canaliculata is currently lacking. Here, transcriptomic approaches were used to study the genes expressed in the two genders of P. canaliculata at various developmental stages. Gonad transcriptomes of immature or mature males and females were compared, revealing 12,063 genes with sex-specific expression, of which 6066 were male- and 5997 were female-specific. Among the latter, 581 and 235 genes were up-regulated in immature and mature females, respectively. The sex-specific expressed genes identified included GnRHR2 and TSSK3 in males and ZAR1 and WNT4 in females. Of the genes, six were involved in reproduction: CCNBLIP1, MND1, DMC1, DLC1, MRE11, and E(sev)2B. Compared to immature snail gonads, the expression of HSP90 and CDK1 was markedly reduced in gonadal. It was hypothesized that the two were associated with the development of females. These findings provided new insights into crucial genetic information on sex differentiation and development in P. canaliculata. Additionally, some candidate genes were explored, which can contribute to future studies on controlling P. canaliculata using molecular regulatory techniques.


Assuntos
Perfilação da Expressão Gênica , Diferenciação Sexual , Transcriptoma , Animais , Diferenciação Sexual/genética , Masculino , Feminino , Gônadas/metabolismo , Gônadas/crescimento & desenvolvimento , Gastrópodes/genética , Gastrópodes/crescimento & desenvolvimento , Desenvolvimento Sexual/genética , Regulação da Expressão Gênica no Desenvolvimento
15.
Mayo Clin Proc ; 99(6): 940-952, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38530689

RESUMO

OBJECTIVE: To investigate whether hypotensive patients diagnosed with heart failure and reduced ejection fraction (HFrEF) might benefit from angiotensin receptor-neprilysin inhibitors (ARNis) in real-world practice because patients with baseline systolic blood pressure (SBP) of less than 100 mm Hg have been excluded from landmark trials. PATIENTS AND METHODS: In this multicenter study conducted between January 1, 2013, and December 31, 2021, a total of 7562 symptomatic patients with HFrEF were enrolled and grouped by SBP (hypotension was defined as an SBP of less than 100 mm Hg) and ARNi use as follows: group 1, hypotensive/non-ARNi users (n=484); group 2, hypotensive/ARNi users (n=308); group 3, nonhypotensive/non-ARNi users (n=4560); and group 4, nonhypotensive/ARNi users (n=2210). Inverse probability of treatment weighting was used to balance baseline characteristics for survival analysis. RESULTS: Diverse baseline characteristics and lower rates of medication use were found among non-ARNi users compared with ARNi users. Hypotensive/ARNi users had lower ARNi initiation doses than nonhypotensive/ARNi users. We observed significantly lower mortality, composite heart failure hospitalization, and CV death for hypotensive/ARNi and the other 2 nonhypotensive groups (groups 3 and 4) during a median follow-up of 3.43 years (all P<.05), with a similar effect on reverse remodeling for the hypotensive/ARNi group compared with the hypotensive/non-ARNi group. The event-free survival benefits of ARNi vs renin-angiotensin system inhibitors were consistent with the lower boundary of SBP for clinical benefits found until 88 mm Hg (spline curves) after inverse probability of treatment weighting. CONCLUSION: Patients with HFrEF and hypotension may still benefit from ARNi treatment. Patients with hypotensive HFrEF should not be routinely excluded from ARNi use in a real-world setting.


Assuntos
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca , Hipotensão , Volume Sistólico , Valsartana , Remodelação Ventricular , Humanos , Valsartana/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Masculino , Aminobutiratos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Feminino , Volume Sistólico/efeitos dos fármacos , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Remodelação Ventricular/efeitos dos fármacos , Hipotensão/tratamento farmacológico , Hipotensão/mortalidade , Pessoa de Meia-Idade , Tetrazóis/uso terapêutico , Neprilisina/antagonistas & inibidores , Resultado do Tratamento
16.
Small Methods ; : e2400078, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38537103

RESUMO

As one of the most promising renewable energies, wind energy is abundant in the natural environment. However, it is still challenging to effectively collect wind energy because of its variable wind speed and unpredictable direction. Here, a triboelectric nanogenerator, which is inspired by ancient Chinese wind bells, has been developed to collect energy from variable-speed and multi-directional wind. The wind-bell-inspired triboelectric nanogenerator (W-TENG) has the capability to generate electricity even at a very low wind speed of 0.5 m s-1. Furthermore, it is able to harvest wind energy effectively from all directions (0-360 degrees). The parameter-optimized W-TENG achieves a maximum output voltage of 9.3 V and a maximum current of 0.63 µA. Electronic devices including a digital watch and 40 light-emitting diodes (LEDs) are successfully powered by the designed W-TENG, demonstrating its applicability. In this study, it is believed that a novel and effective strategy is provided to harvest energy from variable-speed and multi-directional wind.

17.
World Neurosurg ; 181: e411-e421, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37858864

RESUMO

OBJECTIVE: Evaluate the efficacy, safety, and patient satisfaction of transradial access (TRA) compared with conventional transfemoral access (TFA) for diagnostic cerebral angiography in elderly patients (≥65 years of age). METHODS: We performed a retrospective review of patients receiving cerebral angiography via TRA or TFA between October 2020 and December 2021 at 3 institutions. Basic patient characteristics, angiographic data, postoperative complications, and patient satisfaction were collected for analysis. RESULTS: Of the 357 enrolled elderly patients, 175 were performed through TRA and 182 were performed through TFA. There was no significant difference in mean fluoroscopy time (8.6 ± 3.8 minutes vs. 9.1 ± 3.1 minutes; P = 0.103) and radiation exposure (47.7 ± 10.8 Gy-cm2 vs. 49.8 ± 11.3 Gy-cm2; P = 0.068) between the TRA and TFA groups. However, the TRA group had a shorter procedural time (54.7 ± 6.2 minutes vs. 61.1 ± 5.6 minutes; P < 0.001) and less contrast agent (83.2 ± 28.1 mL vs. 100.1 ± 26.2 mL; P < 0.001) than the TFA group. In terms of safety, the incidence of minor vascular access complications in the TRA group was lower than that in the TFA group (1.7% vs. 8.8%; P = 0.003). The incidence of serious complications and neurologic complications in the TRA group was also lower, although the difference was not statistically significant. Overall patient satisfaction was higher in the TRA group than that in the TFA group. CONCLUSIONS: TRA was an efficient and safe alternative to conventional TFA in elderly patients who underwent diagnostic cerebral angiography and who underwent TRA were more satisfied. Findings supported the radial-first strategy for cerebral angiography in elderly populations.


Assuntos
Cateterismo Periférico , Exposição à Radiação , Humanos , Idoso , Angiografia Cerebral , Artéria Radial , Meios de Contraste , Satisfação do Paciente , Estudos Retrospectivos , Resultado do Tratamento
18.
Parasitol Int ; 98: 102817, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37852573

RESUMO

Based on morphology and ITS sequence data, we identify and supplementally describe Gyrodactylus pseudorasborae Ondracková, Seifertová & Tkachenko, 2023 on the fins of topmouth gudgeon (Pseudoraspora parva) from freshwaters of southern China. The highest similarity (99.57% and 99.47%) to G. pseudorasborae suggested they were the same species. Prevalence and mean intensity were 45% and 2.3, respectively. The gyrodactylid species morphologically resembled G. pseudorasborae recorded from the same host species P. parva in Czech Republic, Ukraine, and Central China. But there were slight morphological differences in the shape and size of the marginal hook. Comparisons of marginal hook sickles of various Gyrodactylus species suggested that G. pseudorasborae and G. parvae were members of the G. wageneri-group. A molecular phylogeny of G. pseudorasborae with related species is presented and discussed within the context of the mechanism of local evolution of these sister species.


Assuntos
Cyprinidae , Doenças dos Peixes , Trematódeos , Animais , Cyprinidae/parasitologia , Filogenia , República Tcheca/epidemiologia , Ucrânia , Doenças dos Peixes/epidemiologia , Doenças dos Peixes/parasitologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-37971465

RESUMO

Background: Facial skin relaxation has become an important part in solving the problem of facial rejuvenation. Minimally invasive or noninvasive skin-tightening procedures have become a trend for facial rejuvenation. Bipolar radiofrequency (RF) is a new option for treating skin relaxation and is more effective than noninvasive surgery without surgical incision. Objective: To explore the effect of different bipolar RF powers on the area of the original box, changes of skin and subcutaneous tissue thickness and numbers of fibroblasts in rabbits. Design: The research team performed an animal study. Setting: This study took place in Affiliated Hospital of Nanjing University of Chinese Medicine. Participants: Eighteen common-grade adult New Zealand rabbits (female, 2.5-3.0 kg). Methods: Bipolar radiofrequency therapy was given to a girl rabbit on the left side of the treatment area. Standard HE and Masson staining were performed to assess the pathological changes, area of the original box and the number of fibroblasts in skin and subcutaneous tissues. Outcome Measures: (1) The area of the original box, changes of skin and subcutaneous tissue thickness, and numbers of fibroblasts under different bipolar RF temperatures or under different bipolar RF powers immediately after surgery, 1 month after surgery and 3 months after surgery were observed. (2) Standard HE and Masson staining results. Results: Under the condition of certain instrument power, at 36de 38d and 40nd the area of the original box shrank to different degrees immediately after surgery (16.54±0.37, 17.78±0.03, 17.19±0.01), 1 month after surgery (16.59±0.31, 17.82±0.01, 18.34±0.30) and 3 months after surgery (16.89±0.12, 18.16±0.14, 19.23±0.32) compared with that before surgery (P < .05). Under specific temperature conditions, at 16 W, 18 W, 20 W, and 22 W, the area of the original box shrank to different degrees immediately after surgery (16.40±0.49, 15.55±0.57, 17.54±0.12, 16.19±0.27), 1 month after surgery (16.88±0.12, 17.46±0.02, 18.05±0.35, 19.41±0.08) and 3 months after surgery (19.09±1.01, 18.30±0.69, 20.00±0.29, 21.20±0.90) compared with that before surgery (P < .05). When the power was fixed, the thickness of skin and subcutaneous tissue decreased immediately after surgery (6.7, 6.8, 7), 1 month after surgery (6, 6.1, 6.3) and 3 months after surgery (6.4, 6.5, 6.2) at different temperatures (P < .05). When the temperature was fixed, the thickness of skin and subcutaneous tissue decreased immediately after surgery (6.1, 6.08, 6.03), 1 month after surgery (6.2, 6.15, 6.13), and 3 months after surgery (6.2, 6.23, 6.03) under different powers (P < .05). Under the condition of certain instrument power, at 36de 38d and 40n, the number of fibroblasts increased to different degrees immediately after surgery (26.54±2.37, 30.78±3.03, 37.19±4.01), 1 month after surgery (28.59±2.31, 34.82±3.01, 40.34±4.30), and 3 months after surgery (30.89±0.12, 38.16±0.14, 42.23±0.32) compared with that before surgery, and all were statistically significant (P < .05). Under specific temperature conditions, at 16 W, 18 W, 20 W, and 22 W, the number of fibroblasts increased to different degrees immediately after surgery (28.29±2.49, 30.97±3.57, 38.74±3.12, 45.68±4.27), 1 month after surgery (30.88±3.12, 32.46±4.02, 41.05±0.35, 50.41±0.08), and 3 months after surgery (29.99±2.01, 33.30±2.69, 39.00±3.29, 23.20±2.90) compared with that before surgery, and all were statistically significant (P < .05). Conclusions: Our study clarifies that bipolar RF can decrease the skin and subcutaneous tissue thickness and increase the numbers of fibroblasts at the temperature of 36°C, 38°C, and 40°C and frequency of 16-22 W, which has a therapeutical effect on skin contraction. Our study might effectively improve the skin slack of patients, and the postoperative maintenance rate is high, and will not cause obvious complications. This study may provide a theoretical direction for clinicians to tighten the skin of patients using bipolar RF.

20.
Commun Biol ; 6(1): 1181, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37985711

RESUMO

Primary liver cancer (PLC) poses a leading threat to human health, and its treatment options are limited. Meanwhile, the investigation of homogeneity and heterogeneity among PLCs remains challenging. Here, using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). Taking a high-resolution perspective, our observations revealed that CHC cells exhibit internally discordant phenotypes, whereas ICC and HCC exhibit distinct tumor-specific features. Specifically, ICC was found to be the primary source of cancer-associated fibroblasts, while HCC exhibited disrupted metabolism and greater individual heterogeneity of T cells. We further revealed a diversity of intermediate-state cells residing in the tumor-peritumor junctional zone, including a congregation of CPE+ intermediate-state endothelial cells (ECs), which harbored the molecular characteristics of tumor-associated ECs and normal ECs. This architecture offers insights into molecular characteristics of PLC microenvironment, and hints that the tumor-peritumor junctional zone could serve as a targeted region for precise therapeutical strategies.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Células Endoteliais/metabolismo , Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/genética , Ductos Biliares Intra-Hepáticos , Microambiente Tumoral/genética
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