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RNA processing is increasingly recognized as a critical control point in the regulation of different hematopoietic lineages including megakaryocytes responsible for the production of platelets. Platelets are anucleate cytoplasts that contain a rich repertoire of RNAs encoding proteins with essential platelet functions derived from the parent megakaryocyte. It is largely unknown how RNA binding proteins contribute to the development and functions of megakaryocytes and platelets. We show that serine-arginine-rich splicing factor 3 (SRSF3) is essential for megakaryocyte maturation and generation of functional platelets. Megakaryocyte-specific deletion of Srsf3 in mice led to macrothrombocytopenia characterized by megakaryocyte maturation arrest, dramatically reduced platelet counts, and abnormally large functionally compromised platelets. SRSF3 deficient megakaryocytes failed to reprogram their transcriptome during maturation and to load platelets with RNAs required for normal platelet function. SRSF3 depletion led to nuclear accumulation of megakaryocyte mRNAs, demonstrating that SRSF3 deploys similar RNA regulatory mechanisms in megakaryocytes as in other cell types. Our study further suggests that SRSF3 plays a role in sorting cytoplasmic megakaryocyte RNAs into platelets and demonstrates how SRSF3-mediated RNA processing forms a central part of megakaryocyte gene regulation. Understanding SRSF3 functions in megakaryocytes and platelets provides key insights into normal thrombopoiesis and platelet pathologies as SRSF3 RNA targets in megakaryocytes are associated with platelet diseases.
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Plaquetas/metabolismo , Megacariócitos/metabolismo , RNA Mensageiro , Fatores de Processamento de Serina-Arginina , Trombocitopenia , Trombopoese/genética , Animais , Camundongos , Camundongos Knockout , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo , Trombocitopenia/genética , Trombocitopenia/metabolismoRESUMO
AIM: This study aimed to reveal the unique microenvironment of peri-implantitis through single-cell analysis. MATERIALS AND METHODS: Herein, we performed single-cell RNA sequencing (scRNA-seq) of biopsies from patients with peri-implantitis (PI) and compared the results with healthy individuals (H) and patients with periodontitis (PD). RESULTS: Decreased numbers of stromal cells and increased immune cells were found in the PI group, which implies a severe inflammatory infiltration. The fibroblasts were found to be heterogeneous and the specific pro-inflammatory CXCL13+ sub-cluster was more represented in the PI group, in contrast to the PD and H groups. Furthermore, more neutrophil infiltration was detected in the PI group than in the PD group, and cell-cell communication and ligand-receptor pairs revealed most neutrophils were recruited by CXCL13+ fibroblasts through CXCL8/CXCL6-CXCR2/CXCR1. Notably, our study demonstrated that the unique microenvironment of the PI group promoted the differentiation of monocyte/macrophage lineage cells into osteoclasts, which might explain the faster and more severe bone resorption in the progression of PI than PD. CONCLUSIONS: Collectively, this study suggests a unique immune microenvironment of PI, which may explain the differences between PI and PD in the clinic. These outcomes will aid in finding new specific and effective treatments for PI.
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AIM: To undertake a meta-analysis of the prognostic value of cardiac magnetic resonance imaging feature tracking (CMR-FT) in patients with light-chain cardiac amyloidosis (LCA). MATERIALS AND METHODS: A systematic search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. All analyses were conducted using RevMan 5.3 software. RESULTS: Eight studies were included with 663 patients. For the left ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired global circumferential (GCS), radial (GRS) and longitudinal (GLS) strain in survivors of LCA (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.09-1.25; 0.95, 0.93-0.96; 1.12, 1.05-1.20, all p<0.001). For ejection fraction (EF) and mass index, surviving patients had higher EFs and mass index (OR 0.96, 95% CI 0.96-0.97; 1.01, 1.01-1.02). For the right ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired GLS and GRS in survivors of LCA (OR 1.11, 95% CI 1.08-1.15; 0.93, 0.90-0.96, all p<0.001). Surviving patients had higher EFs (OR 0.97, 95% CI 0.96-0.98, p<0.001). Upon removing the studies one by one, there was no significant change in the results of the study. Both analyses showed no apparent publication deviation on funnel plots. CONCLUSION: Parameters derived from CMR-FT technology are promising new predictors for LCA, and are easily available and reliable. Patients with poor myocardial deformability are at highest risk of death.
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Amiloidose , Função Ventricular Esquerda , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Prognóstico , Imageamento por Ressonância Magnética , Amiloidose/diagnóstico por imagem , Valor Preditivo dos Testes , Volume SistólicoRESUMO
AIM: Natural bioactive products have been tested as alternative antimicrobial agents. This study evaluated the effect of Punica granatum extract (PGE) on oral multispecies biofilms. METHODOLOGY: Lyophilized extracts from pomegranate peel were prepared, and the punicalagin content was assessed by ultra-performance liquid chromatography (UPLC). Oral multispecies biofilms from 2 donors were grown on four collagen-coated hydroxyapatite discs. After incubation for 7 days or 3 weeks, the biofilms were exposed to water (control), 2% CHX, 10% PGE, 20% PGE or 30% PGE for 3 min. The proportions of dead bacteria were assessed by the live/dead staining and confocal microscopy. After the analysis, the best PGE concentration (30%) was combined with CHX. The experimental phases were repeated using water, 2% CHX, 30% PGE and 30% PGE + 2% CHX. Five random areas of the biofilm on each disc were scanned, resulting in 20 scanned areas for each group. RESULTS: Regarding the biofilm volume, no differences were found amongst solutions (p = .111). The PGE solution killed bacteria effectively in 1-week, 2-week and 3-week-old-plaque biofilms, ranging from 37 to 55.3%, depending on the PGE concentration. The 30% PGE (a) (p = .0009) had greater antibiofilm effectiveness than 2% CHX (b), which killed bacteria in the 25.2 to 48.7% range. The 10% and 20% PGE had intermediate values (ab), without significant differences from 30% PGE (p = 1.002). Water (c) had the lowest proportion of dead bacteria (p < .00001) in a range of 5 to 6.7% and lower effectiveness in killing bacteria (p < .05). The PGE alone or mixed with 2% CHX had greater anti-biofilm effectiveness than CHX (p < .05). The old plaque biofilms were more resistant than the 7-day-old plaque (p < .05). CONCLUSIONS: The 30% PGE (alone or combined with CHX) exhibited a greater antibiofilm effect on oral multispecies biofilms grown on hydroxyapatite discs than 2% CHX.
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Objective: To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023. Methods: An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University's HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis. Results: A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance (χ2=30.435, P<0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4+T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P<0.05).Multivariate logistic analysis showed that the baseline CD4+T cell count was <200/µl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P<0.05). Conclusion: The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4+T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.
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Síndrome da Imunodeficiência Adquirida , Farmacorresistência Viral , Genótipo , HIV-1 , Humanos , Farmacorresistência Viral/genética , HIV-1/genética , HIV-1/efeitos dos fármacos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia , Mutação , China/epidemiologiaRESUMO
Objective: To explore the distribution of allergen-specific IgE (sIgE) for children with atopic dermatitis in Tianjin City and provide the evidences of clinical diagnosis and treatment. Methods: A retrospective cross-sectional study was conducted to analyze the children who were suspected of atopic dermatitis and tested for serum sIgE in the Tianjin Children's Hospital from March 2021 to February 2023. Using first detection results only, a total of 1 841 serum samples were tested for twenty common allergens. The method was the enzyme-linked immune capture assay. The allergen epidemiological characteristics were statistically analyzed by Chi square test based on the children's characteristics and factors such as different sexes, ages and seasons by the mass data. Results: Among the 1 841 cases, the results showed that 1 247 (67.73%) were sensitized to at least 1 allergen-sIgE, comprising to 49.86% (918/1 841) to food allergen-sIgE and 47.96% (883/1 841) to aeroallergen-sIgE. The top three food allergens-sIgE were egg 32.10% (591/1 841), milk 25.91% (477/1 841) and wheat flour 14.61% (269/1 841); the top three positive rates of aeroallergens-sIgE were house dust 24.33% (448/1 841), alternaria 20.59% (379/1 841) and dermatophagoides farinae 14.83% (273/1 841). The positive rates of food allergens-sIgE were the highest in the 1-3 years old group (64.11%, 434/677) (χ2=122.854, P<0.001), while the positive rates of aeroallergens-sIgE were higher in the 11-14 years old group (71.26%, 62/87) (χ2=134.968, P<0.001). No seasonal difference was revealed in the overall positive rate of food allergen-sIgE and aeroallergen-sIgE (χ2=4.047, P=0.256; χ2=7.549, P=0.056). The positive rates of soybean-sIgE and milk-sIgE were the highest in summer (χ2=11.329, P=0.010; χ2=28.720, P<0.001), whereas alternaria-sIgE and mugwort-sIgE were the highest in summer and autumn, respectively (χ2=8.462, P=0.037; χ2=10.641, P=0.014). Among the 1 841 cases, 32.21% were sensitized to three or more allergens-sIgE. The sIgE concentration levels of egg, milk and house dust were mainly level 1 to 2, and the proportions of level 3 and above were all under 15%; although the positive rates of crab, shrimp, and peanut were low, the proportions of grade 3 and above were all beyond 30%. Children sensitized to alternaria, dermatophagoides farinae, mugwort, and cat dander had higher sIgE concentration levels, which were 68.07%, 49.45%, 56.57% and 47.83% respectively. Conclusions: This study can reflect the epidemic characteristics of allergen-sIgE in children with atopic dermatitis in Tianjin region to a certain extent. Allergen-sIgE positivity in patients differed by age, and there were seasonal differences and grade distribution differences in the positive rates of some allergens-sIgE. It is necessary to reasonably avoid the high-risk allergens according to the epidemiological characteristics and clinical symptoms, which provide valuable information for the prevention, diagnosis and treatment of atopic dermatitis.
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Alérgenos , Dermatite Atópica , Imunoglobulina E , Humanos , Dermatite Atópica/imunologia , Estudos Transversais , Alérgenos/imunologia , Criança , Estudos Retrospectivos , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Pré-Escolar , Masculino , Feminino , China , Adolescente , Lactente , Hipersensibilidade Alimentar/imunologiaRESUMO
Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyps, asthma and the development of significant airway symptoms following the ingestion of aspirin and other nonsteroid anti-inflammatory drugs (NSAIDs). At present, aspirin challenge is the gold standard for diagnosis. Aspirin desensitization and aspirin therapy after desensitization (ATAD) is one of the classical therapies. This paper described the application of aspirin desensitization and ATAD in AERD and provided the reference for the comprehensive treatment of AERD.
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Aspirina , Asma , Humanos , Aspirina/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , SíndromeRESUMO
Objective: To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children. Methods: Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis. Results: Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211Gâ >â A accounted for 37.5% (6/16), c.1456Tâ >â G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin (tâ =â 5.539, Pâ <â 0.05), and indirect bilirubin (tâ =â 5.312, Pâ <â 0.05). However, there was no significant difference in direct bilirubin levels (tâ =â 1.223, Pâ >â 0.05) and age of onset (tâ =â 0.3611, Pâ >â 0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456Tâ >â G homozygous mutations had the highest serum bilirubin levels. Conclusion: The common pathogenic variants of the UGT1A1 gene sequence are c.1456Tâ >â G, c.211Gâ >â A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.
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Síndrome de Crigler-Najjar , Doença de Gilbert , Hiperbilirrubinemia , Criança , Humanos , Bilirrubina , Doença de Gilbert/genética , Glucuronosiltransferase/genética , Hiperbilirrubinemia/genética , Mutação , Estudos RetrospectivosRESUMO
Objective: To establish biological exposure index (BEI) of occupational exposure to arsenic and its inorganic compounds through occupational epidemiology and the regression analysis of internal and external exposure of workers. Methods: In November 2021, 125 workers with occupational exposure to arsenic and its inorganic compounds and 49 office administrators in a non-ferrous metal smelter in Yunnan Province were selected as the exposure group and control group, respectively. Air samples from the workplace of the study subjects on weekdays were collected and arsenic concentrations were determined. Urine samples were collected in end-of-work weekend and high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was used to detect the levels of trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , monomethyl arsenic (MMA) and dimethyl arsenic (DMA) in urine. The correlations between arsenic concentration in the workplace air and arsenic species in urine of workers were analyzed. Arsenic exposure concentration and the level of urinary arsenic (ΣiAs+MMA+DMA) of workers was analyzed by linear regression and the BEI of arsenic and its inorganic compounds in the workplace was proposed based on the results of micronucleus test. Results: The median of time-weighted average concentration (C(TWA)) of arsenic in the workplace air of the exposure group was 0.0116 mg/m(3), and the over-standard rate was 71.2% (89/125) . The concentrations of iAs(3+), iAs(5+), inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) ãMMAãDMA and urinary arsenic in the exposure group were higher than those in the control group at the end of shift, and the differences were statistically significant (P<0.05) . The concentration of arsenic in the workplace air had the strongest correlation with the concentration of urinary arsenic at the end of the shift (r(s)=0.909, P<0.001) . The regression equation was lg (y) =7.662+2.968lg (x) (r=0.821, P<0.05) . According to the occupational exposure limit (OEL) of arsenic in China, the concentration of urinary arsenic in the end-of-work weekend was calculated to be 53.2 µg/L. Combined with the results of micronucleus test, the BEI of occupational exposure to arsenic and its inorganic compounds in the workplace was proposed to be 50 µg/L. Conclusion: The urinary arsenic in the end-of-work weekend can be used as a biomarker of occupational exposure to arsenic, and its BEI is recommended to be 50 µg/L.
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Arsênio , Arsenicais , Exposição Ocupacional , Humanos , Arsênio/urina , China , Exposição Ocupacional/análiseRESUMO
Objective: To explore the correlation between urinary arsenic and health effects through the determination and analysis of urinary arsenic levels in occupational arsenic exposed workers. Methods: In November 2021, 95 workers exposed to arsenic and its inorganic compounds and 31 administrative personnel from a non-ferrous metal smelter in Yunnan Province were selected as the contact group and control group, respectively. Urine forms of arsenic, blood tumor markers, liver function were detected, and micronucleus test was used to analyze the chromosome damage. The correlation between urine forms of arsenic and health effects were analyzed. Results: Compared with the control group, the concentrations of urinary trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) , monomethyl arsenic (MMA) , dimethyl arsenic (DMA) and urinary arsenic (ΣiAs+MMA+DMA) at the end of class in contact group were higher (P<0.05) . There was no statistically significant difference in blood tumor markers and liver function indicators between the two groups (P>0.05) . Compared with the control group, the peripheral blood micronucleus rate and cell micronucleus rate in the contact group were significantly increased (P<0.05) . The urinary arsenic, iAs(5+), inorganic arsenic and DMA were positively correlated with peripheral blood micronucleus rate in contact group (r(s)=0.48, 0.34, 0.37, 0.23, P<0.05) , and the urinary arsenic, iAs(5+), DMA were positively correlated with peripheral blood micronucleus rate (r(s)=0.48, 0.34, 0.26, P<0.05) . Conclusion: There is a significant correlation between different valence states of arsenic in the urine and abnormal health effects of occupational arsenic exposed workers. It is necessary to strengthen the detection of arsenic species in the urine of occupational arsenic exposed workers to better protect their health.
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Arsênio , Arsenicais , Exposição Ocupacional , Humanos , Arsênio/urina , China , Arsenicais/efeitos adversos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Biomarcadores TumoraisRESUMO
OBJECTIVE: To assess pain severity and interference with life in women after different types of breast cancer surgery and the demographic, treatment-related, and psychosocial variables associated with these pain outcomes. SUMMARY OF BACKGROUND DATA: Data are conflicting regarding pain outcomes and quality of life (QOL) among women who undergo different types of breast surgery. METHODS: Women with nonhereditary breast cancer completed the brief pain inventory before surgery and at 1, 6, 12, and 18 months postsurgery. We assessed associations between pain outcomes and CPM status and mastectomy status using multivariable repeated measures models. We assessed associations between pain outcome and QOL and decision satisfaction. RESULTS: Of 288 women (mean age 56 years, 58% non-Hispanic White), 50 had CPM, 75 had unilateral mastectomy, and 163 had BCS. Mean pain severity scores were higher at one (2.78 vs 1.9, P = 0.016) and 6 months (2.79 vs 1.96, P = 0.031) postsurgery in women who had CPM versus those who did not, but there was no difference at 12 and 18 months. Comparing mastectomy versus BCS, pain severity was higher at 1 and 12 months. There was a significant interaction between pain severity and time point for CPM ( P = 0.006), but not mastectomy status ( P = 0.069). Regardless of surgery type, Black women had higher pain severity ( P = 0.004) than White women. Higher pain interference was associated with lower QOL ( P < 0.001) and lower decision satisfaction ( P = 0.034). CONCLUSIONS: Providers should counsel women considering mastectomy about the potential for greater acute pain and its impact on overall well-being. Racial/ethnic disparities in pain exist and influence pain management in breast surgical patients.
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Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Mastectomia , DorRESUMO
BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Terapia Neoadjuvante/métodos , Neoplasias Esofágicas/tratamento farmacológico , Esofagectomia , Estudos Prospectivos , Quimiorradioterapia/métodos , Estudos RetrospectivosRESUMO
The ^{18}O(α,γ)^{22}Ne reaction is critical for AGB star nucleosynthesis due to its connection to the abundances of several key isotopes, such as ^{21}Ne and ^{22}Ne. However, the ambiguous resonance energy and spin-parity of the dominant 470 keV resonance leads to substantial uncertainty in the ^{18}O(α,γ)^{22}Ne reaction rate for the temperature of interest. We have measured the resonance energies and strengths of the low-energy resonances in ^{18}O(α,γ)^{22}Ne at the Jinping Underground Nuclear Astrophysics experimental facility (JUNA) with improved precision. The key 470 keV resonance energy has been measured to be E_{α}=474.0±1.1 keV, with such high precision achieved for the first time. The spin-parity of this resonance state is determined to be 1^{-}, removing discrepancies in the resonance strengths in earlier studies. The results significantly improve the precision of the ^{18}O(α,γ)^{22}Ne reaction rates by up to about 10 times compared with the previous data at typical AGB temperatures of 0.1-0.3 GK. We demonstrate that such improvement leads to precise ^{21}Ne abundance predictions, with an impact on probing the origin of meteoritic stardust SiC grains from AGB stars.
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AIM: To analyse the correlation between apparent diffusion coefficients (ADC) derived from intratumoural and peritumoural regions with prognostic factors and immune-inflammatory markers in breast cancer (BC). MATERIALS AND METHODS: In this retrospective study, 89 patients (age range, 28-66 years; median, 45 years) with a diagnosis of invasive BC who underwent routine blood tests and multiparametric magnetic resonance imaging (MRI) were enrolled. The study cohort was stratified according to tumour maximum cross-section ≥20 mm, lymph node metastasis (LNM), time-signal intensity curve (TIC) type, and receptor status. Minimum, maximum, mean, and heterogeneity values of tumour ADC (ADCtmin, ADCtmax, ADCtmean, and ADCheter), maximum values of peritumoural ADC (ADCpmax), and the ratio of peritumoural-tumour ADC (ADCratio) were obtained on the ADC maps. Linear regression analyses were performed to investigate the correlation between immune-inflammatory markers, prognostic factors and ADC values. RESULTS: HER-2 was positively associated with ADCtmax, ADCtmean, and ADCpmax values (ß = 0.306, p=0.004; ß = 0.283, p=0.007; ß = 0.262, p=0.007, respectively), while platelet-to-lymphocyte ratio (PLR) was positively associated with ADCpmax and ADCratio values (ß = 0.227, p=0.020; ß = 0.231, p=0.020, respectively). Among ADC parameters, ADCpmax showed the highest predictive values for evaluating the presence of LNM (AUC, 0.751; sensitivity, 70.4%; specificity, 77.1%). CONCLUSION: The ADCpmax value could provide additional assistance in predicting prognostic factors of BC.
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Neoplasias da Mama , Imagem de Difusão por Ressonância Magnética , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Biomarcadores/análise , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Correlação de Dados , Metástase Linfática/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Modelos LinearesRESUMO
PURPOSE: Our aim was to perform a propensity score-matched study to compare the long-term functional outcomes and quality of life following intersphincteric resection vs. low anterior resection (LAR) with very low anastomosis. METHODS: Patients who underwent intersphincteric resection or low anterior resection with low anastomosis (≤ 4 cm from the anal verge) for rectal cancer between January 2017 and June 2020 were retrospectively included. A propensity score-matching process was performed. Functional outcomes and quality of life were assessed using the European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L), EORC-QLQ C30, EORC-QLQ CR29, Low Anterior Resection Syndrome (LARS), Wexner, and International Prostate Symptom Score (IPSS) questionnaires. The primary outcome was the presence of LARS at least 12 months after surgery. The second outcome was the postoperative quality of life of included patients. RESULTS: After propensity matching, 128 patients were included, including 58 males and 70 females with a median age of 59.5. Patients in the intersphincteric resection group showed a higher incidence of incontinence to flatus (32.8% versus 14.0%, p = 0.043) and stools (42.2% versus 21.9%, p = 0.046), pain/discomfort (25.0% versus 7.8%, p = 0.001), and bowel dysfunction, while the LARS scores (15.0 versus 13.2, p = 0.461) and major LARS rates (26.6% versus 14.1%, p = 0.078) were comparable in both groups. CONCLUSION: ISR leads to increased bowel incontinence rate and increased anal pain, without affecting the grade of low anterior resection syndrome, fecal urgency, and clustering. LAR might be the preferred sphincteric-preserving approach when negative resection margins and a safe anastomosis are guaranteed. Patients should be fully informed about potential functional impairment after sphincter-preservation procedures.
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Incontinência Fecal , Neoplasias Retais , Masculino , Feminino , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/complicações , Síndrome de Ressecção Anterior Baixa , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Qualidade de Vida , Pontuação de Propensão , Canal Anal/cirurgia , DorRESUMO
Objective: To investigate the quality of life and associated factors in patients with coronary heart disease (CHD) in China. Methods: A cross-sectional study of 25 provinces and cities in China was performed from June to September 2020. A questionnaire was used to collect the socio-demographic and clinical information of patients with CHD, while the European Five-dimensional Quality of Life Scale (EQ-5D) was used to assess the quality of life. Multiple linear regression model was performed to analyze the associated factors. Results: The median age of the 1 075 responders was 60 (52, 67) years, and 797 (74.1%) were men. The EQ-5D and EQ-VAS indices were 0.7 (0.5, 0.8) and 60.0 (40.0, 80.0). Among the five dimensions in the quality of life scale, the frequency of anxiety/depression was the highest (59.8%), while problems in self-care was the lowest (35.8%). In the multiple linear regression model, female, increasing age, obesity, comorbidity(ies), anxiety/depression, social media channels, and receiving the CABG therapy were associated with the lower EQ-5D index (all P<0.05). In addition, increasing age, obesity, comorbidity (ies), depression, anxiety and depression, social media channels, and receiving the CABG therapy were associated with lower EQ-VAS index (all P<0.05). Conclusion: Over half of the patients with CHD in China have a low quality of life, which is related to gender, age, obesity, treatment pathway, the presence or absence of comorbidity (ies), and psychological state. In addition to managing the adverse effects of traditional socio-demographic factors on the quality of life, clinical practices should pay attention to the psychological state of patients. Moreover, establishing a WeChat group for doctor-patient communication could improve the quality of life of CHD patients.
Assuntos
Doença das Coronárias , Qualidade de Vida , Masculino , Humanos , Feminino , Qualidade de Vida/psicologia , Autorrelato , Estudos Transversais , Inquéritos e Questionários , ObesidadeRESUMO
Objective: To investigate the correlation of spinopelvic alignment according to Roussouly classification on the occurrence of adjacent segment disease (ASD) in the patients undergoing fusion surgery for lumbar degenerative diseases. Methods: A cross-sectional study. Clinical data of 166 consecutive patients who had undergone lumbar fusion between January 2009 and January 2019 in the Affiliated Changzhou Second People's Hospital of Nanjing Medical University and Affiliated Drum Tower Hospital of Medical School of Nanjing University were retrospectively reviewed. There were 59 males and 107 females, with an average age of (58.6±9.5) years (ranged 41-78 years). Fusion length averagely spanned (1.7±0.7) levels (ranged 1-3 levels). The patients were classified by both "theoretical" (based on pelvic incidence (PI)) and "current"(based on sacral slope (SS)) Roussouly types. The patients were classified as "matched" if their "current" shape matched the "theoretical" type and otherwise as "unmatched". Multivariate logistic regression analysis of the variables recruited from univariate analyses was performed to identify the factors independently associated with the development of ASD after lumbar fusion. Results: The average follow-up duration after initial surgery was (49.2±20.7) months (ranged 25 to 134 months). Thirty (18.1%, 30/166) patients were diagnosed as ASD. Postoperatively, two thirds of the patients who suffered ASD after surgery were unmatched, while 36.8% (50/136) of the patients without ASD had unmatched type. Univariate analyses showed that older age, more fusion levels, float fusion, pre-and postoperative worse spinopelvic alignment, and postoperative unmatched Roussouly type were identified as risk factors of ASD. Multivariate logistic regression analysis identified postoperative Roussouly type mismatch (OR=3.310, 95%CI: 1.282-8.545, P=0.013), old age (OR=1.074, 95%CI: 1.019-1.131, P=0.008) and postoperative SS (OR=0.928, 95%CI: 0.865-0.995, P=0.036) as the independent risk factors of development of ASD after lumbar fusion. Conclusion: A significant association between postoperative sagittal malalignment and occurrence of ASD is detected, the evaluation of sagittal alignment by Roussouly classification could help predict the occurrence of ASD.
Assuntos
Hospitais , Região Lombossacral , Feminino , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Estudos Retrospectivos , PelveRESUMO
Objective: To investigate the role of neutrophil extracellular traps (NETs) in immune checkpoint inhibitor-associated myocarditis (ICIAM) with programmed death protein-1 (PD-1) inhibitors involvement, and to explore the therapeutic potential of targeting NETs in the treatment of ICIAM. Methods: Thirty 6-week-old male BALB/c mice were randomly divided into control group (n=10), myocarditis group (n=10), and treatment group (n=10). Apart from the control group, each mouse was subcutaneously injected with 100 µl of complete Freund's adjuvant containing 250 µg of mouse cardiac troponin I peptide on the 1st and 7th day. Starting on the 8th day, PD-1 inhibitor (15 µg/per mouse) was intraperitoneally injected every other day for a total of 5 times. Since 1 day before the beginning of PD-1+TnI injection, the treatment group was injected with PF-1355 (50 mg·kg-1·d-1) for 16 consecutive days. The mice's general state was observed during the whole process. Real-time fluorescence quantitative PCR (RTFQ-PCR) was carried out to evaluate the transcriptional regulation of neutrophil related chemokines, NETs, pyronecrosis related factors and proinflammatory cytokines. Immunohistochemistry, immunofluorescence and western blot were applied to determine the changes of pyrosis related molecules. Echocardiography showed the differences of main cardiac indexes while cardiac pathology compared the degree of inflammatory infiltration in 3 gruops. Results: The immunofluorescence intensity of myocardial NETs in the myocarditis group was significantly increased compared to the control group mice (2.49±0.08 and 0.99±0.26, P<0.001). The protein expression levels of pyroptosis-related NLRP3, cleaved-Caspase 1, Caspase 1, cleaved-GSDMD, GSDMD, IL-1ß and IL-18 in myocardial tissue of the model group were higher than those of the control group (all P<0.05). After treatment with PF-1355, compared to the myocarditis group, the left ventricular ejection fraction (LVEF) (73.58%±5.31% and 58.12%±3.19%, P<0.001) and left ventricular fraction shortening (LVFS) (39.78%±4.31% and 33.89%±2.19%, P<0.001) increased. H-E staining showed a reduction in inflammatory infiltration area in the treatment group compared to the myocarditis group (30.12%±3.57% and 14.92%±2.46%, P<0.001). The immunofluorescence intensity of NETs decreased in the treatment group compared to the myocarditis group (2.52±0.04 and 1.03±0.05, P<0.001). The levels of NLRP3 and other pyroptosis-related molecules were downregulated in the treatment group compared to the myocarditis group (all P<0.05). Conclusions: NETs lead to myocardial cell pyroptosis by activating the NLRP3 inflammasome in PD-1 inhibitor-associated myocarditis. The specific MPO inhibitor PF-1355 shows a therapeutic potential by regulating the formation of NETs, decreasing NLRP3 level and relieving myocardial pyroptosis, thus reducing myocardial damage.
Assuntos
Armadilhas Extracelulares , Miocardite , Camundongos , Masculino , Animais , Miocardite/metabolismo , Miocardite/patologia , Inibidores de Checkpoint Imunológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Armadilhas Extracelulares/metabolismo , Volume Sistólico , Caspase 1/metabolismo , Receptor de Morte Celular Programada 1 , Função Ventricular Esquerda , Inflamassomos/metabolismoRESUMO
This study analyzed the clinical and imaging data of 81 glioma patients who underwent brain synthetic MRI and diffusion weighted imaging (DWI) examination in the General Hospital of Ningxia Medical University from August 2020 to September 2021 to explore the value of synthetic MRI relaxation quantitative value in predicting the genotype of isocitrate dehydrogenase 1 (IDH1) in gliomas. There were 44 males and 37 females, those patients with an aged 50.0 (36.5, 59.0) years. The tumor pre-T1, pre-T2, pre-PD, post-T1 and ADC values were obtained by outlining the region of interest (ROI). Univariate analysis was used to compare the differences of parameter values between groups, and the receiver operating characteristic was used to evaluate the diagnostic efficacy of each parameter value in predicting glioma IDH1 genotype. The results showed that the pre-T1 and pre-PD values [M (Q1, Q3)] of IDH1m glioma were lower than those of IDH1w glioma [1 462.75 (1 306.41, 1 567.75) ms vs 1 532.83 (1 434.67, 1 617.67) ms, 84.18 (82.28, 86.41) pu vs 85.85 (84.65, 86.90) pu] (all P<0.05). The post-T1 and ADC values of IDH1m glioma were higher than those of IDH1w glioma [1 054.50 (631.92, 1 262.63) ms vs 669.67 (535.17, 823.33) ms, 1.20 (0.86, 1.35) ×10-3 mm2/s vs 0.80 (0.76, 0.93) ×10-3 mm2/s] (all P<0.05). The AUC of the combined model (pre-T1+pre-PD+post-T1+ADC+Age) is 0.828 (95%CI:0.729-0.903). Synthetic MRI relaxation quantitative values are helpful to distinguish IDH1 genotypes in glioma. The diagnostic efficacy of the multi-parameter combined model based on pre-T1, pre-PD, post-T1, ADC, and age is better than that of the single parameter, and it can be used as an effective strategy to improve the differential diagnosis ability of gliomas molecular markers.
Assuntos
Glioma , Isocitrato Desidrogenase , Feminino , Humanos , Masculino , Imagem de Difusão por Ressonância Magnética , Genótipo , Glioma/genética , Isocitrato Desidrogenase/genética , Imageamento por Ressonância Magnética , Adulto , Pessoa de Meia-IdadeRESUMO
Objective: To analyze the effect and prognosis of infant kidney transplantation. Methods: Clinical data of 37 cases of infant kidney transplantation under 3 years old in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from June 1, 2017 to July 31, 2022 were retrospectively collected. These 37 cases included 31 primary kidney transplantation and 6 secondary kidney transplantation. Kaplan-Meier method was used to draw the survival curve of the transplanted kidney and the recipient, and the prognosis and complications were analyzed. Median follow-up was 18 months (range: 6-66 months). Results: The recipients were 20 males and 17 females, with a median age of 16 months (range: 2 months, 26 days to 36 months) and a median weight of 8 kg (range: 3.2 to 14.0 kg). The youngest child was only 2 months, 26 days old, and weighed only 3.2 kg. The most common primary disease of recipients was congenital nephrotic syndrome (13 cases, 41.9%). Intra-abdominal transplantation occurred in 19 cases (51.3%) and intra-iliac fossa transplantation occurred in the remaining 18 cases (48.6%). Postoperative renal function recovery was delayed in 7 cases (18.9%), and thrombosis caused renal function loss in 5 cases (13.5%), of which 4 cases received second renal transplantation and were successful. During the follow-up period, there were 11 cases of acute rejection (29.7%) and 6 cases of CMV pneumonia (16.2%). The estimated glomerular filtration rate 1 year after transplantation was higher than that 1 month after surgery [(101.9±22.1) vs (71.1±25.6) ml/(min·1.73m2), P<0.001], and remained constant 2 years after transplantation. Both the 1-year and 2-year survival rates of the transplanted kidney were 85.3%, and both the 1-year and 2-year survival rates of the recipients were 96.8%. Conclusion: Although the implementation of infant kidney transplantation is difficult, it can still achieve relatively satisfactory efficacy and prognosis.