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1.
Ann Occup Environ Med ; 36: e15, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015558

RESUMO

Background: The increasing prevalence of high body mass index (BMI) emphasizes the need for action. Understanding of BMI factors among military hospital healthcare workers remains limited. This study aims to address this gap by analyzing BMI risk factors and changes pre- and post-coronavirus 2019 pandemic among military hospital healthcare workers in central Taiwan from 2019 to 2021. Methods: Conducted at a military hospital in central Taiwan, this study analyzed anonymized health examination data from 2019 to 2021 for 483 healthcare workers. We performed generalized estimating equations to investigate trends in BMI and its association with various factors, including age, sex, job titles, military status, job tenure, work shifts, and lifestyle habits. Results: The risk of increased BMI was higher in 2021 compared to 2019 (risk ratio [RR]: 1.008, 95% confidence interval [CI]: 1.001-1.014). Individuals on rotating shifts had a higher risk of increased BMI compared to day shift workers (RR: 1.021; 95% CI: 1.008-1.035) and higher odds of obesity (odds ratio: 1.546; 95% CI: 1.099-2.175). Among obese individuals, BMI in soldiers was approximately 4.9% lower than in non-soldiers (RR: 0.951; 95% CI: 0.915-0.988). Conclusions: This study identified a significant post-pandemic increase in BMI among healthcare workers in a Taiwanese military hospital, with rotating shifts being a key risk factor for both increased BMI and obesity. Work-related factors influenced BMI changes among obese individuals, while non-work-related factors were significant for non-obese individuals. These findings highlight the broader effects of the pandemic and the specific impact of work-related factors on obese healthcare workers.

2.
J Craniofac Surg ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38838369

RESUMO

Autologous adipose tissue was recognized as a promising therapeutic option for soft tissue defects owing to its regenerative potential and ability to facilitate tissue reconstruction. However, the mechanisms by which autologous fat grafting (AFG) promotes healing remain unclear, hindering its potential applications. This study aimed to investigate the distribution and phenotypic transition of infiltrating macrophages in transplanted adipose tissue, as well as their correlation with diabetic skin defect remodeling. Streptozotocin-induced diabetic rats with full-thickness dorsal skin defects were included in this study. The transplanted adipose tissue at the skin defects was collected and analyzed using flow cytometry to determine macrophage proportion and phenotype. The healing of skin defects was evaluated, and treatment was continued until day 14 as the designated endpoint of healing, followed by histopathologic examinations. Immunostaining with CD31 and lymphatic vessel endothelial receptor-1 was performed on wound tissues to analyze angiogenesis and lymphangiogenesis, respectively. Western blot and quantitative polymerase chain reaction analyses were used to assess the expression of the representative genes involved in the healing process. The results showed early polarization of M2 macrophages in the transplanted adipose tissue, concomitant with the upregulation of growth factors and downregulation of inflammatory factors. In vivo experiments revealed that AFG significantly promoted macrophage infiltration and M2 transformation in diabetic skin defects compared to the control groups, thereby promoting tissue extracellular matrix remodeling and lymphatic and vascular regeneration. However, the beneficial effects of AFG were inhibited by macrophage depletion. This study further demonstrated the potential of AFG for treating diabetic skin defects.

3.
Nat Commun ; 15(1): 3825, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714645

RESUMO

c-di-AMP is an essential and widespread nucleotide second messenger in bacterial signaling. For most c-di-AMP synthesizing organisms, c-di-AMP homeostasis and the molecular mechanisms pertaining to its signal transduction are of great concern. Here we show that c-di-AMP binds the N-acetylglucosamine (GlcNAc)-sensing regulator DasR, indicating a direct link between c-di-AMP and GlcNAc signaling. Beyond its foundational role in cell-surface structure, GlcNAc is attractive as a major nutrient and messenger molecule regulating multiple cellular processes from bacteria to humans. We show that increased c-di-AMP levels allosterically activate DasR as a master repressor of GlcNAc utilization, causing the shutdown of the DasR-mediated GlcNAc signaling cascade and leading to a consistent enhancement in the developmental transition and antibiotic production in Saccharopolyspora erythraea. The expression of disA, encoding diadenylate cyclase, is directly repressed by the regulator DasR in response to GlcNAc signaling, thus forming a self-sustaining transcriptional feedback loop for c-di-AMP synthesis. These findings shed light on the allosteric regulation by c-di-AMP, which appears to play a prominent role in global signal integration and c-di-AMP homeostasis in bacteria and is likely widespread in streptomycetes that produce c-di-AMP.


Assuntos
Acetilglucosamina , Proteínas de Bactérias , Fosfatos de Dinucleosídeos , Regulação Bacteriana da Expressão Gênica , Saccharopolyspora , Transdução de Sinais , Acetilglucosamina/metabolismo , Regulação Alostérica , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Fosfatos de Dinucleosídeos/metabolismo , Saccharopolyspora/metabolismo , Saccharopolyspora/genética
4.
J Craniofac Surg ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38688023

RESUMO

OBJECTIVE: Suture mesenchymal stem cells (SuSCs), possessing self-renewal and multilineage differentiation abilities, play a crucial role in cranial bone growth. However, the impact of the disease-causing fibroblast growth factor receptor 2 (FGFR2) mutation on SuSCs in Crouzon syndrome has not been explored. This study aims to employ a lentivirus to overexpress Fgfr2 and investigate its role in the pathogenesis of Crouzon syndrome. METHODS: Starting with the prevalent FGFR2 mutation site in patients with Crouzon syndrome, a lentiviral vector carrying the Fgfr2.C361Y mutation was developed and transfected into SuSCs, with a determined multiplicity of infection values. The experimental group, SuSCs+Fgfr2.C361Y, was compared with the empty vector and normal SuSC groups. Cell proliferation, cycle, apoptosis, and osteogenic functionality were assessed using CCK-8 assays, flow cytometry, ALP activity assays, and real-time quantitative polymerase chain reaction. RESULTS: The lentiviral vector effectively infected SuSCs, leading to heightened Fgfr2 expression, with optimal multiplicity of infection values of 80. The experimental group demonstrated decreased proliferation activity and a higher apoptosis rate compared with controls (P < 0.05). After osteogenic induction, the experimental group showed significantly higher ALP activity than controls (P < 0.05). Real-time quantitative polymerase chain reaction indicated lower mRNA expression levels of Gli1, Axin2, Pcna, Cdk2, and Bcl-2 in the experimental group than controls, whereas Bax, Runx2, and Bmp-2 showed higher expression (P < 0.05). CONCLUSION: This study constructed a lentivirus vector to upregulate Fgfr2 expression in SuSCs, suppressing stem cell stemness by inhibiting proliferation, promoting apoptosis, and accelerating premature osteogenic differentiation, resulting in premature suture closure. These findings establish the groundwork for further understanding the pathogenesis of Crouzon syndrome.

5.
Asian J Androl ; 26(4): 409-414, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38376191

RESUMO

This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (<40 ml), TIVA emerged as a more cost-effective strategy. While Chat-LA may generally be the most cost-effective and safer anesthesia method for TP-MUF-PB, personalization of anesthesia strategies is crucial, considering specific patient demographics such as age and prostate volume.


Assuntos
Análise Custo-Benefício , Biópsia Guiada por Imagem , Próstata , Neoplasias da Próstata , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Próstata/patologia , Próstata/diagnóstico por imagem , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/economia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Imageamento por Ressonância Magnética/economia , Imageamento por Ressonância Magnética/métodos , Anestesia Local/economia , Anestesia Local/métodos , Anos de Vida Ajustados por Qualidade de Vida , Anestesia Geral/economia , Análise de Custo-Efetividade
6.
J Craniofac Surg ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315768

RESUMO

BACKGROUND: The mentalis muscle is a significant component of the lower lip; its injury could impair appearance and function. This study presents a surgical strategy for treating mentalis muscle rupture to restore muscle tension and improve function. METHODS: Medical records and photographs of 2 patients with mentalis muscle rupture were reviewed. After physical examinations, 3-dimensional computed topographies were conducted to evaluate chin appearance further. The surgical strategy was designed according to individual malformations and requests. RESULTS: Both patients injured their mentalis muscles in childhood and presented to our clinic with a concave deformity at the center of the chin and impaired mentalis muscle function. The surgical procedure involved the reconstruction of the mentalis muscle by reassembling the muscle flaps and releasing the scarred soft tissue. Both patients were satisfied with the outcome. CONCLUSIONS: Mentalis muscle rupture requires surgical correction. The study proposes an innovative approach that enables patients to achieve a more harmonious appearance and improve function.

7.
J Immunother Cancer ; 11(12)2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-38148115

RESUMO

BACKGROUND: Activating signal cointegrator 3 (ASCC3) has been identified as an oncogenic factor that impairs host immune defense. However, the underlying mechanisms of carcinogenesis and its impact on the antitumor immune response remain unclear. In this study, we aimed to investigate the molecular mechanisms of ASCC3 in the progression of non-small cell lung cancer (NSCLC). METHODS: Single-cell sequencing data from the Gene Expression Omnibus and gene expression profiles from The Cancer Genome Atlas database were analyzed. The expression, clinical relevance and biological functions of ASCC3 in NSCLC were explored. Then, RNA sequencing, immunoprecipitation, mass spectrometry, immunofluorescence, and flow cytometry analyses were conducted to explore the underlying molecular mechanisms. In addition, in vivo experiments in mouse models were conducted to explore the probability of ASCC3 knockdown to improve the efficacy of anti-Programmed Death-1 (PD-1) therapy in NSCLC. RESULTS: ASCC3 was significantly upregulated in NSCLC and correlated with poor pathological characteristics and prognosis in patients with NSCLC. Overexpression of ASCC3 promoted malignant phenotypes of NSCLC cells and induced an immunosuppressive tumor microenvironment, which was characterized by a decrease in CD8+ T cells, natural killer cells and dendritic cells but an increase in regulatory T(Treg) cells. Mechanistically, ASCC3 stabilized signal transducer and activator of transcription (STAT)3 signaling by recruiting Cullin-associated and neddylation dissociated 1 (CAND1), which inhibited ubiquitin-mediated degradation of STAT3, thereby impairing the type I interferon response of tumor cells and promoting the immunosuppression and progression of NSCLC. Furthermore, high expression of ASCC3 impaired the efficacy of anti-PD-1 therapy, and an anti-PD-1 antibody combined with ASCC3 knockdown exerted promising synergistic efficacy in a preclinical mouse model. CONCLUSION: ASCC3 could stabilize the STAT3 pathway via CAND1, reshaping the tumor microenvironment and inducing resistance to anti-PD-1 therapy, which promotes the progression of NSCLC. It is a reliable prognostic indicator and can be a target in combination therapy for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfócitos T CD8-Positivos , Proteínas Culina/genética , Terapia de Imunossupressão , Ubiquitinação , Microambiente Tumoral , Fatores de Transcrição/metabolismo , Fator de Transcrição STAT3/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo
8.
J Fungi (Basel) ; 9(12)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38132729

RESUMO

Strobilomyces, one of the most noticeable genera of Boletaceae (Boletales), is both ecologically and economically important. Although many studies have focused on Strobilomyces in China, the diversity still remains incompletely understood. In the present study, several collections of Strobilomyces from Hainan Island, tropical China were studied based on morphology and molecular phylogenetic analyses. Four species are described as new, viz. S. baozhengii, S. conicus, S. hainanensis, and S. pachycystidiatus. Detailed descriptions, color photos of fresh basidiomata, and line drawings of microstructures of the four species are presented.

9.
Int J Med Microbiol ; 313(6): 151589, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37952279

RESUMO

Candida glabrata is believed to be the underlying cause of many human ailments, including oral, gastrointestinal, and vaginal disorders. C. glabrata-caused deep-seated infections, coupled with its resistance to antifungal drugs, may contribute to a high mortality rate. Resveratrol is a polyphenol and can achieve better therapeutic effects when administered in combination with micafungin, but the underlying molecular mechanisms remain unknown. Here, we investigate the effects of varying doses of resveratrol on the proliferation, apoptosis, and activity of macrophages, which were co-cultured with micafungin-pretreated C. glabrata. Resveratrol can restore the decreased proliferative activity of macrophages caused by the phagocytosis of C. glabrata. Further investigations demonstrated that this restoration ability exhibited a dose-dependent manner, reaching the highest level at 200 µM of resveratrol. Resveratrol tended to be more effective in inhibiting macrophage apoptosis and reducing reactive oxygen species (ROS) levels with concentration increases. In addition, at medium concentrations, resveratrol may down-regulate the expression of most inflammatory cytokines, whereas at high concentrations, it started to exert pro-inflammatory functions by up-regulating their expressions. Macrophages may shift from an anti-inflammatory (M2) phenotype to an inflammatory (M1) phenotype by resveratrol at 200 µM, and from M1 to M2 at 400 µM. Our research shows that resveratrol with micafungin are effective in treating C. glabrata infections. The resveratrol-micafungin combination can reduce the production of ROS, and promote the proliferation, inhibit the apoptosis, and activate the polarization of macrophages in a dose-dependent manner. This study offers insights into how this combination works and may provide possible direction for further clinical application of the combination.


Assuntos
Candida glabrata , Equinocandinas , Feminino , Humanos , Micafungina/farmacologia , Candida glabrata/genética , Equinocandinas/farmacologia , Resveratrol/farmacologia , Espécies Reativas de Oxigênio , Antifúngicos/farmacologia , Macrófagos , Fagocitose
10.
Colorectal Dis ; 25(12): 2414-2422, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37908184

RESUMO

AIM: Sphincter-sparing surgery can be achieved in most cases of low rectal cancer with the development of intersphincteric resection. However, abdominoperineal resection is still inevitable for patients with tumours located below the dentate line. To address this, we have developed a procedure called conformal sphincteric resection (CSR) in which the corresponding part of the subcutaneous portion of the external anal sphincter and the perianal skin on the tumour side is removed to achieve a safe distal resection margin and lateral resection margin while the dentate line and the internal anal sphincter on the tumour-free side are preserved as much as possible, to achieve sphincter preservation without compromising oncological safety and functional acceptability, and to render tumour location no longer a contraindication for sphincter-sparing surgery. This is the first study to describe the concept, indication and surgical procedure of CSR and to report its preliminary surgical, oncological and functional results. METHODS: This is a retrospective, single-centre, single-arm pilot study conducted at Huashan Hospital, Fudan University. Demographic, clinicopathological, oncological and functional follow-up data were collected from 20 consecutive patients with rectal tumours located below the dentate line who underwent laparoscopic CSR by the same surgical team from June 2018 to March 2022. RESULTS: The mean distance of the tumour's lower edge from the anal verge was 13.1 ± 6.0 mm. The mean distal resection margin was 10.6 ± 4.3 mm. All circumferential resection margins were negative. There were no instances of perioperative mortality. The complication rate was 25% but all were Clavien-Dindo Grade I. Among the 20 cases, 17 were diagnosed with adenocarcinoma, one with squamous cell carcinoma and two with adenoma featuring high-grade intraepithelial neoplasia. Pathological TNM staging revealed two, seven, five, five and one case(s) in Stages 0, I, II, III and IV, respectively. The median follow-up period was 20 months (interquartile range 22 months), with no withdrawals. The overall and disease-free survival rates were both 95%. The mean Wexner incontinence score and low anterior resection syndrome score recorded 18 months following diverting ileostomy closure were 6.3 ± 3.8 and 27.3 ± 3.6, respectively. CONCLUSIONS: This study has proposed the CSR procedure for the first time, which is a technically feasible, oncologically safe and functionally acceptable procedure for carefully selected patients with rectal tumours located below the dentate line.


Assuntos
Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Canal Anal/cirurgia , Canal Anal/patologia , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Margens de Excisão , Projetos Piloto , Tratamentos com Preservação do Órgão , Síndrome , Resultado do Tratamento
11.
Front Plant Sci ; 14: 1273718, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37860253

RESUMO

The tea leafhopper, Empoasca onukii, relies on substrate-borne vibrations for sexual communication and is mainly controlled with chemical pesticides, which poses risks to the environment and food safety. Based on previous studies, we conducted a series of behavioral assays by simultaneous observation of vibration signals and movement to investigate the mating and post-copulation behavior of tea leafhoppers. During mating, the activity of E. onukii was restricted to dawn and dusk and concentrated on the sixth or seventh mature leaf below the tea bud. By comparing the time spent in locating females among different males, the timely reply of females was the key factor affecting mating success. Empoasca onukii females mated only once in their lives, while males could mate multiple times. Male rivalry behavior involved two distinct strategies. The rivals could send disruptive pulses to overlap the male calling signals, locate the courting males, and drive them away after contact. Some rivals could emit mating disruption signals (MDSs) to interrupt the ongoing identification duet and establish their own mating communication. Both identification and location duets could be interrupted by playback of MDSs, which is essential to create effective synthetic signals to disrupt mating communication of E. onukii. Our study clarified the spatial and temporal distribution of E. onukii in mating and the function of MDSs, which will be essential to develop future vibrational mating disruption techniques for E. onukii and its energy-efficient application in the field.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(8): 791-799, 2023 Aug 15.
Artigo em Chinês | MEDLINE | ID: mdl-37668025

RESUMO

OBJECTIVES: To investigate the association of single nucleotide polymorphisms (SNPs) of myeloid differentiation factor 88 (MyD88) and Toll-like receptor adaptor molecule 1 (TICAM1) and their interactions with community-acquired pneumonia (CAP) in children. METHODS: Improved multiple ligase detection reaction assay was used for detecting the polymorphisms of nine tagging SNPs of the MyD88 and TICAM1 genes in 375 children with CAP who attended the Department of Pediatrics of the Second Affiliated Hospital of Yan'an University Medical School from August 2015 to September 2017 and 306 healthy children who underwent physical examination. A logistic regression analysis was used to evaluate the association between the distribution of genotypes and their interactions with CAP in children. RESULTS: The polymorphism of the TICAM1 gene at rs11466711T/C locus was closely associated with the susceptibility to CAP in children (P<0.05). The AA genotype of rs35747610G/A locus significantly reduced risk of sepsis in children with CAP (P<0.05). The AA genotype of rs6510826G/A locus was significantly associated with the increase in C-reactive protein level in children with CAP (P<0.05). The GG genotype of the MyD88 gene at rs7744A/G locus significantly increased the risk of respiratory failure and circulatory failure (P<0.05). The multiplicative interactions between MyD88 gene rs7744A/G and TICAM1 gene rs11466711T/C, rs2292151G/A, rs35299700C/T, and rs35747610G/A loci were significantly associated with the susceptibility to CAP, the severity of CAP, and the risk of sepsis in children (P<0.05). CONCLUSIONS: The gene polymorphisms of MyD88 and TICAM1 and their interactions are closely associated with CAP in children, with a synergistic effect on the development and progression of CAP in children.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular , Infecções Comunitárias Adquiridas , Fator 88 de Diferenciação Mieloide , Pneumonia , Criança , Humanos , Proteínas Adaptadoras de Transporte Vesicular/genética , Infecções Comunitárias Adquiridas/genética , Fator 88 de Diferenciação Mieloide/genética , Pneumonia/genética , Polimorfismo de Nucleotídeo Único , Sepse
13.
BMC Complement Med Ther ; 23(1): 304, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37648989

RESUMO

INTRODUCTION: Allergic rhinitis is a global health problem that can potentially be managed through acupressure. Our clinical observations have identified Allergic Rhinitis Acupressure Therapeutic (ARAT) as a novel acupressure treatment acting on specific acupoints, which may enhance the effectiveness of acupressure. Therefore, we propose a three-arm randomized controlled trial will be conducted to investigate the efficacy and safety of ARAT for perennial allergic rhinitis (PAR). METHODS/DESIGN: In this trial, eligible 111 participants diagnosed with PAR will be randomly assigned to one of three groups: the ARAT group, the non-specific acupoints group, or the blank control group. The primary outcome will be the change in the total nasal symptom score, and the secondary outcomes will include: 1) changes in the scores of the standard version of Rhinoconjunctivitis Quality of Life Questionnaire (RQLQs); 2) acoustic rhinometry and anterior rhinomanometry; 3) changes in the scores of relief medication usage; 4) incidence of adverse events. Additionally, we will measure and compare the changes in cytokine levels (IL-5, IL-13, IFN-γ, and TSLP) in nasal secretions. The RQLQs and primary outcomes will be assessed at the beginning, middle, and end stages of the treatment period, with monthly follow-ups conducted over a total of three months. The secondary outcomes and biomarkers in nasal secretions will be measured at the beginning and end of the treatment period. Any adverse events or need for rescue medication will be carefully noted and recorded. DISCUSSION: This study may produce a new acupressure treatment prescription that is easy to learn, more targeted, and adaptable. This trial represents the first clinical investigation comparing ARAT treatment for PAR with the non-specific acupoints group and blank control group. Our data is expected to provide evidence demonstrating the safety and efficacy of ARAT for PAR patients, while also exploring the functional mechanism underlying ARAT treatment, moreover, the results offer valuable insights for healthcare professionals in managing PAR symptoms. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2300072292. Registered on June 08, 2023.


Assuntos
Acupressão , Rinite Alérgica , Humanos , Qualidade de Vida , Mucosa Nasal , Rinite Alérgica/terapia , Pontos de Acupuntura , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Cancer Treat Res Commun ; 36: 100743, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37531736

RESUMO

INTRODUCTION: We evaluated the risk factors and outcomes for patients who experienced hepatotoxicity after use of sotorasib in KRAS G12C mutated NSCLC. METHODS: Retrospective review of medical records of patients with KRAS G12C mutated NSCLC who received sotorasib between May 28th, 2021, and December 31st, 2021 across all Mayo Clinic sites, with follow up until December 31st, 2022. RESULTS: Thirty-one patients received sotorasib as standard of care treatment. Grade 3 or higher hepatoxicity was seen in 32% (10/31) patients presenting at a median of 51 days (range, 27-123) of sotorasib initiation. Baseline demographics were comparable between patients with and without ≥grade 3 hepatotoxicity, except for presence of CNS metastases and time from prior immune checkpoint inhibitor (ICI) treatment. Improvement in liver tests was observed in all patients after stopping sotorasib, and it was restarted at a lower dose in 8 patients. Despite dose reduction, hepatotoxicity requiring sotorasib discontinuation occurred in 2 patients. Twenty-eight of 31 patients had received prior ICI. Median time from prior ICI therapy was 69 days (range, 4-542). Rates of ≥grade 3 hepatoxicity were 75% (3/4), 64% (7/11) and 0% (0/13) for patients who received ICI within 30 days, 31-90 days and >90 days. None of the 3 patients without prior ICI exposure developed hepatoxicity. The median PFS and OS were 3.9 months and 9.9 months respectively. CONCLUSION: One-third of patients developed grade 3 or higher sotorasib induced hepatotoxicity. Risk of hepatotoxicity was higher in patients who received sotorasib within 90 days of ICI treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Doença Hepática Induzida por Substâncias e Drogas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Proto-Oncogênicas p21(ras) , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia
15.
Chemistry ; 29(56): e202301921, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37470684

RESUMO

Robust scaffolds were typically applied in thermally activated delayed fluorescence (TADF) molecules to suppress the non-radiative decay, trigger the fast spin-flipping, and enhance the light out-coupling efficiency. Herein, we disclosed for the first time the positive effect of flexible conformation of ancillary groups on the photophysical properties of TADF emitter. The red TADF emitter Ph-TPA with flexible conformation demonstrated small excited-state structural distortion and low reorganization energy compared to the counterpart Mc-TPA with a rigid macrocycle. Consequently, Ph-TPA showed an excellent photoluminescent quantum yield (PLQY) of 92 % and a state-of-the-art external quantum efficiency (EQE) of 30.6 % at 630 nm. This work could deepen our understanding of structure-property relationships of organic luminophores and help us to rationalize the design of efficient TADF materials.

16.
Urol J ; 20(5): 337-343, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37330690

RESUMO

PURPOSE: This study aimed to assess the importance of computed tomography (CT) imaging in the diagnostic and prognostic evaluation of renal epithelioid angiomyolipoma (EAML). MATERIALS AND METHODS: This study comprised 63 patients diagnosed with renal EAML in the First Affiliated Hospital of Soochow University during 2010-2021, who met the inclusion criteria. The clinical, pathological, and therapeutic features were analyzed to determine the optimum diagnostic and therapeutic approaches. RESULTS: Of the 63 participants, 20 were men and 43 women aged 24-74 years (average, 45.5 years). In 35 and 28 participants, the tumor was located on the left and right sides, respectively. All the patients underwent CT scanning. Most of the patients (54/63) with EAMLs demonstrated hyperattenuation, one showed isoattenuation, and eight showed hypoattenuation compared with renal parenchyma on unenhanced CT images. The diameter of each tumor was 2-25 cm (average, 5.6 cm). All the participants underwent surgical treatment. Of these, 53 were followed up for 4-128 months (median, 64 months). Among the followed-up patients, one died of the tumor, one died due to acute severe pancreatitis, and two had an ipsilateral recurrence. CONCLUSION: EAML is a relatively rare renal angiomyolipoma depleted in fat. A characteristic of hyperattenuation on unenhanced CT images in EAML can help distinguish this tumor from clear cell renal cell carcinoma. Surgical resection is the main treatment. Most EAMLs are benign, and only a few have malignant potential. However, post-surgery recurrence and metastasis may occur, especially in elderly patients, and thus close follow-up is recommended.

17.
Aging Cell ; 22(8): e13899, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37277933

RESUMO

It is reported that overweight may lead to accelerated aging. However, there is still a lack of evidence on the causal effect of overweight and aging. We collected genetic variants associated with overweight, age proxy indicators (telomere length, frailty index and facial aging), etc., from genome-wide association studies datasets. Then we performed MR analyses to explore associations between overweight and age proxy indicators. MR analyses were primarily conducted using the inverse variance weighted method, followed by various sensitivity and validation analyses. MR analyses indicated that there were significant associations of overweight on telomere length, frailty index, and facial aging (ß = -0.018, 95% CI = -0.033 to -0.003, p = 0.0162; ß = 0.055, 95% CI = 0.030-0.079, p < 0.0001; ß = 0.029, 95% CI = 0.013-0.046, p = 0.0005 respectively). Overweight also had a significant negative causality with longevity expectancy (90th survival percentile, ß = -0.220, 95% CI = -0.323 to -0.118, p < 0.0001; 99th survival percentile, ß = -0.389, 95% CI = -0.652 to -0.126, p = 0.0038). Moreover, the findings tend to favor causal links between body fat mass/body fat percentage on aging proxy indicators, but not body fat-free mass. This study provides evidence of the causality between overweight and accelerated aging (telomere length decreased, frailty index increased, facial aging increased) and lower longevity expectancy. Accordingly, the potential significance of weight control and treatment of overweight in combating accelerated aging need to be emphasized.


Assuntos
Fragilidade , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Sobrepeso/genética , Envelhecimento/genética , Polimorfismo de Nucleotídeo Único
18.
Asian J Surg ; 46(9): 3773-3776, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37308388

RESUMO

TECHNIQUE: The CHN•WU wound suture technique uses barbed sutures. The needle is inserted from the basal part of the superficial fascia at the left edge of the wound and passed through half of the reticular dermis to reach a point (1A) approximately 0.5-2 cm away from the wound edge. Occlusion is achieved at 1A at the level of the reticular dermis, and if done correctly, a shallow concavity will appear at the occlusion point on the skin. The needle is then walked along the natural curvature until it reaches the center of the wound and then moved out from the junction between the dermis and subcutaneous tissue. On the other side of the incision, the needle is inserted into the contralateral position at the junction between the dermis and subcutaneous tissue and moved along its natural curvature to achieve occlusion at the mirror site of 1A in the reticular dermis. This process is repeated until the entire wound is closed. In the end, two stitches should be applied in the opposite direction. The left barbed suture is cut and thrown. RESULTS: This technique does not break through the epidermis, has high suture efficiency and satisfactory cosmetic appearance, disperses mechanical tension, and maintains wound tensile strength. CONCLUSION: This technique was especially effective in closing high-tension wounds in the chest and extremities where the blood supply to both sides of the wound was not affected after suturing, and wound closure could be performed quickly and efficiently in one stage.


Assuntos
Procedimentos Neurocirúrgicos , Técnicas de Sutura , Humanos , Suturas , Pele , Tela Subcutânea
19.
Arch Med Sci ; 19(3): 626-632, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37313191

RESUMO

Introduction: Translocase of the inner mitochondrial membrane 50 (TIMM50) is universally considered to play a key role in several malignancies. However, its role in predicting colorectal cancer (CRC) patient prognosis remains unclear. Material and methods: A total of 192 CRC patients (123 men and 69 women) who underwent radical resection participated in this study. The patients were followed up every 3 months after surgery for 5 years. TIMM50 expression in tumour tissues was measured by quantitative real-time PCR, Western blotting and immunohistochemistry. TIMM50 expression was studied to assess correlations with clinicopathological factors and survival time. Results: TIMM50 expression increased significantly in CRC tumour tissues. Moreover, high TIMM50 expression was related to pathologic stage (p = 0.043), N stage (p = 0.048) and distant metastasis (p = 0.015), but TIMM50 expression was not related to other clinical factors. A Kaplan-Meier survival analysis indicated that patients with low TIMM50 expression had a longer overall survival than those with high TIMM50 expression (p = 0.002). Furthermore, distant metastasis and high TIMM50 expression were confirmed as independent prognostic factors for the overall survival of CRC patients in a multivariate analysis (p = 0.003). Conclusions: TIMM50 may be a key factor for monitoring CRC and a new prognosis indicator for CRC patients.

20.
J Pediatr Gastroenterol Nutr ; 77(1): 79-85, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37084335

RESUMO

OBJECTIVES: Mucosal injury in celiac disease (CD) patients can be patchy, and up to 12% of CD patients can have mucosal changes limited to the duodenal bulb. Hence, recent guidelines recommend obtaining bulb biopsies in addition to distal duodenum. This study aimed to describe a cohort of children with isolated bulb CD and assess the benefit of separating bulb biopsies. METHODS: A retrospective chart review between January 2011 and January 2022 at 2 medical centers was conducted. We included children with CD who underwent endoscopy with separated biopsies from the bulb and distal duodenum. A blinded pathologist performed Marsh-Oberhuber grading on selected cases. RESULTS: We identified 224 CD patients, of which 33 (15%) had histologically confirmed isolated bulb CD. Patients with isolated bulb CD were older at diagnosis (10 vs 8 years; P = 0.03). Median anti-tissue transglutaminase immunoglobulin A (TTG IgA) level was lower in isolate bulb CD (2.8 vs 16.7 times the upper limit of normal [ULN], P < 0.001). Almost 88% (29/33) of isolated bulb CD patients had an anti-TTG IgA value of less than 10 times the ULN. Time to anti-TTG IgA normalization (mean 14 months) was similar between the 2 groups. A pathologist review of diagnostic biopsies could not distinguish between the bulb and distal duodenum biopsies in approximately one-third of the reviewed samples. CONCLUSIONS: Separating bulb from distal duodenum biopsies can be considered during CD diagnosis, particularly in children with anti-TTG IgA levels less than 10 times the ULN. Larger prospective cohorts are needed to decide whether isolated bulb CD is a unique cohort or an early stage of the conventional CD.


Assuntos
Doença Celíaca , Criança , Humanos , Doença Celíaca/diagnóstico , Estudos Retrospectivos , Estudos Prospectivos , Duodeno/patologia , Biópsia , Autoanticorpos , Imunoglobulina A , Transglutaminases
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