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1. This study calculated descriptive statistics for the production traits of two broiler populations: 1) the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF white broilers), including fat and lean lines; and 2) the Guangxi yellow broilers. Their genetic parameters were estimated, including (co)variance components, heritability (h2) and genetic correlations (rg), using the REML method.2. Heritability estimates (h2) for NEAUHLF white broilers ranged from 0.07 to 0.61. Traits with high heritability (h2 >0.3) included body weight at 3, 5 and 7 weeks of age (BW3, BW5, BW7), carcass weight (CW), metatarsal circumference (MeC), liver weight (LW), gizzard weight (GW), spleen weight (SW) and testis weight (TeW), while in Guangxi yellow broilers, heritability estimates ranged from 0.18 to 0.76, with every trait exhibiting high heritability, except for SW (0.18).3. Positive genetic correlations for NEAUHLF were found (rg >0.3, ranging from 0.31 to 0.84) between BW7 and metatarsal length (MeL), MeC, body oblique length (BoL), chest angle (ChA), LW, GW, heart weight (HW) and SW. Genetic correlations between abdominal fat weight (AFW) and BW1, BW3, BW5, CW, MeL, keel length (KeL), BoL and LW were positive (rg >0.3, ranging from 0.31 to 0.58).4. Among the Guangxi population, BW (125 d of age) showed strong positive genetic correlations with all other traits (rg >0.3, ranging from 0.30 to 0.99), while AFW displayed strong positive genetic correlations with leg muscle weight (LeW), CW, BW and thigh diameter (TD) (rg >0.3, ranging from 0.44 to 0.51).5. It was concluded that the characteristics of the two populations were different, which means there is a need to use different strategies when performing the breeding work to improve productivity and efficiency in both broiler populations.

RESUMEN

The formation of a plasma sheath on the surface of spacecraft or satellites during high-speed atmospheric entry is a significant factor that affects communication and radar detection. Experimental research apparatus for electromagnetic science can simulate this plasma sheath and study the interaction mechanisms between electromagnetic waves and plasma sheaths. Electron density is a crucial parameter for this research. Therefore, in this paper, a HCN heterodyne interferometer has been designed to measure the electron densities of the device, which range from 1 × 109 to 3 × 1013 cm-3 and the pressure ranges from 50 to 1500 Pa. The light source is a HCN laser with a wavelength of 337 µm, which exhibits higher spatial resolution compared to microwave interferometers. The interferometer is configured as a Mach-Zehnder interferometer, which generates an intermediate frequency through the Doppler shift achieved by a rotating grating. The spatial and temporal resolution of the HCN interferometry reach ∼14 mm and 100 µs, respectively. Antenna-coupled ALGaN/GaN-HEMT detectors have been utilized, as they possess higher sensitivity-with a typical reduction factor responsivity of around 900 V/W-than VDI planar-diode Integrated Conical Horn Fundamental Mixers in HCN interferometry. Recently, the initial results of the HCN interferometer designed for ERAES have been obtained during an experimental campaign, demonstrating a phase resolution of up to 0.04π.

RESUMEN

Objective: To investigate the efficacy of Da Vinci robotic transanal minimally invasive surgery (R-TAMIS) for rectal neoplasms. Methods: The patients of rectal neoplasms who underwent R-TAMIS and were regularly followed up at the First Medical Center of Chinese PLA General Hospital from January 2021 to January 2024 were retropectively selected. Follow-up visits were conducted at 1, 2, and 4 weeks postoperatively, and then every 3 months until January 20, 2024. The perioperative situation, postoperative histopathological results, and follow-up status of the patients were observed. Results: A total of 17 patients were included, including 10 males and 7 females, aged 35-80 (59±13) years. Eleven patients underwent surgery using the da Vinci® Si robot, while 6 patients underwent surgery using the da Vinci® Xi robot. The height of the resected tumor from the anal verge [M (Q1, Q3)] was 3.5 (3.0, 3.8) cm. The total operative time was 55.0 (50.0, 55.0) minutes, the platform installation time was 32.5 (30.0, 35.0) minutes. The actual surgical operation time was 22.5 (20.0, 27.5) minutes. Intraoperative blood loss was 9.2 (5.0, 10.0) ml. The postoperative hospital stay was 3.2 (3.0, 3.8) days. The total treatment cost was (29 447±4 765) yuan. Two patients who achieved clinical complete remission after neoadjuvant chemoradiotherapy experienced incision dehiscence one week postoperatively, which was resolved after four weeks of rectal irrigation therapy. All surgical specimens were intact, and all resection margins were negative. A total of 44(31,73) weeks were followed up, without local recurrence or distant metastasis. Conclusion: Da Vinci robotic transanal minimally invasive local resection may be a safe and feasible treatment option for rectal neoplasms.

Asunto(s)

Procedimientos Quirúrgicos Mínimamente Invasivos , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Neoplasias del Recto/cirugía , Masculino , Persona de Mediana Edad , Femenino , Procedimientos Quirúrgicos Robotizados/métodos , Anciano , Adulto , Anciano de 80 o más Años , Canal Anal/cirugía , Tempo Operativo , Cirugía Endoscópica Transanal/métodos , Resultado del Tratamiento , Tiempo de Internación

Asunto(s)

Neoplasias Pulmonares , Proteína EWS de Unión a ARN , Humanos , Proteína EWS de Unión a ARN/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Mixosarcoma/genética , Mixosarcoma/patología , Mixosarcoma/cirugía , Masculino , Femenino , Proteínas de Fusión Oncogénica/genética , Persona de Mediana Edad

Asunto(s)

Inhibidor p16 de la Quinasa Dependiente de Ciclina , Tumor de Células de la Granulosa , Neoplasias Ováricas , Proteína p53 Supresora de Tumor , Humanos , Femenino , Tumor de Células de la Granulosa/genética , Tumor de Células de la Granulosa/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Adolescente , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Mutación , Recurrencia Local de Neoplasia

RESUMEN

Objective: To explore the clinical warning value of ischemic modified albumin (IMA) and IMA to human serum albumin (HSA) ratio (IMAR) in the development of pre-eclampsia (PE) and its severity. Methods: A total of 156 pregnant women with PE admitted to the Haidian District Maternal and Child Health Hospital of Beijing from April 2022 to March 2023 were collected as the PE group, and 156 healthy pregnant women with the same age and gestational age were matched as the control group. PE pregnant women were further divided into severe PE group (78 cases) and non-severe PE group (78 cases). Severe PE pregnant women were divided into emergency group (42 cases) and non-emergency group (36 cases) according to the disease progression time.All pregnant women were stratified according to their HSA levels (<30 g/L, 30-32 g/L, ≥32 g/L), and the peripheral blood IMA, HSA, and IMAR of pregnant women in different periods and subgroups were compared, and also the difference of IMA levels in umbilical artery blood. Bivariate correlation analysis was used to explore the correlation between severe PE and IMA or IMAR, and receiver operating characteristic (ROC) curves was used to analyze the diagnostic value of IMA, HSA, and IMAR for PE and severe PE. Results: (1) The IMA level and IMAR in peripheral serum of pregnant women in the PE group at diagnosis, and the IMA level in umbilical artery blood at delivery, and peripheral serum at 2 days after delivery were higher than those in the control group. The HSA level in peripheral serum was lower than that in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (2) The IMA level and IMAR in the peripheral serum of pregnant women with severe PE were higher than those in the non-severe PE group at diagnosis, while the HSA level were lower than those in the non-severe PE group. The differences were statistically significant (all P<0.05). At diagnosis, the IMA level and IMAR in peripheral serum of pregnant women in the emergency group were higher than those in the non-emergency group, while the HSA level was lower than that in the non-emergency group. The differences were statistically significant (all P<0.05). When diagnosed, the peripheral serum IMA levels of pregnant women in the PE group were compared between subgroups with HSA<30 g/L, 30-32 g/L, ≥32 g/L, and there was no statistically significant difference (F=0.366, P=0.694). However, the IMAR was compared between the three subgroups, and the difference was statistically significant (F=28.544, P<0.001), which increased with the decrease of HSA levels. In the subgroup with HSA≥32 g/L, the peripheral serum IMA level and IMAR of pregnant women in the PE group were higher than those in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (3) The severe PE manifestations positively correlated with peripheral serum IMAR at diagnosis include systolic blood pressure (r=0.279), mean arterial pressure (r=0.212), and urinary protein quantification (r=0.277), while the severe PE manifestations negatively correlated include HSA levels (r=-0.644) and newborn birth weight (r=-0.305), all of which were significantly correlated (P<0.05). (4) The area under curve (AUC) for IMAR diagnosis of PE was 0.875 (95%CI: 0.833-0.916), with the highest diagnostic efficiency at a cutoff value of 2.06, sensitivity of 72.5%, and specificity of 85.1%. The AUC for diagnosing severe PE was 0.871 (95%CI: 0.822-0.919), with the highest diagnostic efficacy at a cutoff value of 2.18, sensitivity of 72.3%, and specificity of 88.3%. The diagnostic efficacy of IMAR for PE and severe PE were higher than those of IMA and HSA levels. Conclusions: The level of IMA and IMAR in pregnant women with PE are higher than those in normal pregnant women. IMA and IMAR are correlated with the severity of PE, with IMAR changes occurring earlier and more significantly. IMAR could be considered as one of the evaluation indicators for the development of PE, or as a more sensitive PE severity warning indicator than HSA.

Asunto(s)

Biomarcadores , Preeclampsia , Albúmina Sérica Humana , Albúmina Sérica , Humanos , Femenino , Preeclampsia/sangre , Preeclampsia/diagnóstico , Embarazo , Biomarcadores/sangre , Adulto , Estudios de Casos y Controles , Índice de Severidad de la Enfermedad , Curva ROC

RESUMEN

We show that multi-GeV laser wakefield electron accelerators in meter-scale, low density hydrodynamic plasma waveguides operate in a new nonlinear propagation regime dominated by sustained beating of lowest order modes of the ponderomotively modified channel; this occurs whether or not the injected pulse is linearly matched to the guide. For a continuously doped gas jet, this emergent mode beating effect leads to axially modulated enhancement of ionization injection and a multi-GeV energy spectrum of multiple quasimonoenergetic peaks; the same process in a locally doped jet produces single multi-GeV peaks with <10% energy spread. A three-stage model of drive laser pulse evolution and ionization injection characterizes the beating effect and explains our experimental results.

RESUMEN

Tooth development is a complex process orchestrated by intricate gene regulatory networks, involving both odontogenic epithelium and ectomesenchyme. Six1, a pivotal transcription factor (TF), is involved in the development of the lower incisor. However, its precise role during incisor development and the molecular mechanisms underpinning its regulatory functions remain poorly understood. This study employs Six1 deletion mouse models to elucidate the critical regulatory role of Six1 in governing dental mesenchyme development. By performing single-cell RNA sequencing, we constructed a comprehensive transcriptome atlas of tooth germ development from the bud to bell stage. Our analyses suggest that the dental follicle and the dental papilla (DP) are differentiated from dental ectomesenchyme (DEM) and identify the key TFs underlying these distinct states. Notably, we show that Dlx1, Dlx2, and Dlx5 (Dlx1/2/5) may function as the key TFs that promote the formation of DP. We further show that the deletion of Six1 perturbs dental mesenchyme development by impeding the transitions from DEM to DP states. Importantly, SIX1 directly binds to the promoters of Dlx1/2/5 to promote their co-expression, which subsequently leads to widespread epigenetic and transcriptional remodeling. In summary, our findings unveil Six1's indispensable role in incisor development, offering key insights into TF-driven regulatory networks that govern dental mesenchyme cell fate transitions during tooth development.

Asunto(s)

Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio , Incisivo , Odontogénesis , Factores de Transcripción , Animales , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Ratones , Incisivo/embriología , Incisivo/crecimiento & desarrollo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Odontogénesis/genética , Odontogénesis/fisiología , Germen Dentario/embriología , Germen Dentario/metabolismo , Mesodermo/embriología

RESUMEN

Objective: To analyze the correlation between drug-induced sleep endoscopy (DISE), results, polysomnography (PSG) indicators, and clinical parameters in patients with obstructive sleep apnea (OSA), and to establish and validate a predictive model for tongue base plane obstruction. Methods: This retrospective study analyzed 117 OSA patients diagnosed via PSG and treated at the Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, between October 2014 and March 2022. The cohort comprised of 114 males and 3 females, with an age range of 20 to 54 years (mean age 38.1±8.4 years). Data on DISE results, PSG results, and clinical indicators were collected for all 117 patients. Logistic regression analysis was performed to identify relevant indicators, and a predictive model for tongue base plane obstruction was constructed and internally validated using the R programming language. Results: Univariate logistic regression analysis identified four independent risk factors for predicting tongue root plane obstruction: tonsil grading, N2, N3, and rapid eye movement sleep(REM) stage [OR:0.412(0.260~0.652),1.045(1.012~1.079),0.943(0.903~0.984),0.961(0.925~0.998),P <0.05]. Multivariate logistic regression analysis confirmed tonsil grading and N3 sleep stage (12.48±12.22%) as significant predictors. A nomogram model incorporating these factors demonstrated good predictive performance, with an area under curve(AUC) of 0.82 (95%CI: 0.548-1.000), an optimal cutoff of 0.519, a specificity of 80.0%, and a sensitivity of 86.7%. Internal validation of the model in the validation cohort yielded an AUC of 0.751 (95%CI: 0.625-0.876). Conclusions: Tongue base plane obstruction observed during DISE in OSA patients is associated with tonsil grading and N3 sleep stage duration. The predictive model developed for tongue base plane obstruction based on DISE demonstrates good efficacy, as evidenced by its internal validation.

Asunto(s)

Endoscopía , Polisomnografía , Apnea Obstructiva del Sueño , Lengua , Humanos , Apnea Obstructiva del Sueño/diagnóstico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Endoscopía/métodos , Factores de Riesgo , Adulto Joven , Modelos Logísticos , Sueño REM

RESUMEN

PURPOSE: This study aimed to design an autodelineation model based on convolutional neural networks for generating high-risk clinical target volumes and organs at risk in image-guided adaptive brachytherapy for cervical cancer. MATERIALS AND METHODS: A novel SERes-u-net was trained and tested using CT scans from 98 patients with locally advanced cervical cancer who underwent image-guided adaptive brachytherapy. The Dice similarity coefficient, 95th percentile Hausdorff distance, and clinical assessment were used for evaluation. RESULTS: The mean Dice similarity coefficients of our model were 80.8%, 91.9%, 85.2%, 60.4%, and 82.8% for the high-risk clinical target volumes, bladder, rectum, sigmoid, and bowel loops, respectively. The corresponding 95th percentile Hausdorff distances were 5.23mm, 4.75mm, 4.06mm, 30.0mm, and 20.5mm. The evaluation results revealed that 99.3% of the convolutional neural networks-generated high-risk clinical target volumes slices were acceptable for oncologist A and 100% for oncologist B. Most segmentations of the organs at risk were clinically acceptable, except for the 25% sigmoid, which required significant revision in the opinion of oncologist A. There was a significant difference in the clinical evaluation of convolutional neural networks-generated high-risk clinical target volumes between the two oncologists (P<0.001), whereas the score differences of the organs at risk were not significant between the two oncologists. In the consistency evaluation, a large discrepancy was observed between senior and junior clinicians. About 40% of SERes-u-net-generated contours were thought to be better by junior clinicians. CONCLUSION: The high-risk clinical target volumes and organs at risk of cervical cancer generated by the proposed convolutional neural networks model can be used clinically, potentially improving segmentation consistency and efficiency of contouring in image-guided adaptive brachytherapy workflow.

Asunto(s)

Braquiterapia , Redes Neurales de la Computación , Órganos en Riesgo , Radioterapia Guiada por Imagen , Recto , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Braquiterapia/métodos , Órganos en Riesgo/diagnóstico por imagen , Órganos en Riesgo/efectos de la radiación , Femenino , Radioterapia Guiada por Imagen/métodos , Recto/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Vejiga Urinaria/diagnóstico por imagen , Vejiga Urinaria/efectos de la radiación , Colon Sigmoide/diagnóstico por imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Persona de Mediana Edad , Adulto

RESUMEN

Since the effects of once-daily antihypertensive (HT) medications are more pronounced within the first few hours of ingestion, evening administration of anti-HT medications can be a feasible treatment for nocturnal HT. However, no relevant meta-analysis has been conducted in patients with nocturnal HT. This meta-analysis included randomized controlled trials involving patients with elevated mean nocturnal blood pressure (BP) and compared evening anti-HT administration with morning administration. Multiple databases, including grey literature (e.g. clincialtrial.gov), were searched. Study selection and data extraction were conducted by two independent authors. Risk of bias assessment and overall quality of evidence were conducted using Cochrane risk-of-bias tool and GRADE by two independent authors. A total of 107 studies were included, 76 of which were investigated in China and had not been identified in previous reviews. Only one trial was ranked low risk-of-bias. Evening administration of anti-HT medications was effective in reducing nocturnal systolic BP (4.12-9.10 mmHg; I2 = 80.5-95.2%) and diastolic BP (3.38-5.87 mmHg; I2 = 87.4-95.6%). Subgroup analyses found that the effectiveness of evening administration was contributed by data from the Hermida group and China. Evening administration did not provide additional nocturnal/daytime/24-h BP reduction in non-Hermida/non-China studies (I2 = 0) and in meta-analyses that included studies with unclear or low risk of bias. The effectiveness of nocturnal BP reduction was similar across different types, doses, and half-lives of medications. Evening administration of anti-HT medications may reduce proteinuria, left ventricular hypertrophy (LVH), nondipping and morning surge. The overall quality of evidence was ranked as very low to low. Our results highlight the scarcity of low risk-of-bias studies and emphasize the need for such trials to evaluate the efficacy of evening dosing of anti-HT medications as a standard treatment for patients with nocturnal HT across diverse populations.

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Antihipertensivos , Ritmo Circadiano , Hipertensión , Humanos , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Esquema de Medicación , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

As of 2020, penetrating injuries became the leading cause of death among children and adolescents ages 1-19 in the United States. For the patients who initially survive and receive advanced medical care, vascular injuries are a significant cause of morbidity and additionally trigger notable trauma team angst. Moreover, penetrating injuries can lead to life-threatening hemorrhage and/or limb-threatening ischemia if not addressed promptly. Vascular injury management demands timely and unique expertise, particularly for pediatric patients. As the frequency of vascular injuries requiring operative management increases, it becomes clear that an ad hoc approach is not ideal. An integrated team would provide the best approach for rapid hemorrhage control and revascularization, but the structure of vascular response teams at children's hospitals is highly variable. In part 1 of this review, we will evaluate the scope and extent of the epidemic of traumatic vascular injuries in pediatric patients, review current evidence and outcomes, discuss various challenges and advantages of different team structures, and outline potential outcome targets and pediatric vascular trauma response solutions. LEVEL OF EVIDENCE: n/a.

RESUMEN

As of 2020, penetrating injuries became the leading cause of death among children and adolescents ages 1-19 in the United States. For those patients who survive and receive advanced medical care, vascular injuries are a significant cause of morbidity and trigger notable trauma team angst. Moreover, penetrating injuries can lead to life-threatening hemorrhage and/or limb-threatening ischemia if not addressed promptly. Vascular injury management demands timely and unique expertise, particularly for pediatric patients. In part 1 of this review, we discussed the scope and extent of the epidemic of traumatic vascular injuries in pediatric patients, reviewed current evidence and outcomes, discussed various challenges and advantages of a myriad of existing team structures, and outlined potential outcome targets and solutions. However, in order to optimize care for pediatric vascular trauma, we must also understand the fundamental best practice principles, surgical options and approaches, medical management, and recommendations for ongoing, outpatient follow-up. In part 2, we will address the best evidence, combined with expert consensus, regarding strategies for diagnosing, managing, and ongoing follow-up of vascular trauma, with particular focus on the nuances that define the unique approaches to pediatric patients. LEVEL OF EVIDENCE: n/a.

RESUMEN

Objective: To study the clinicopathological features, immunohistochemical phenotypes, molecular changes, differential diagnosis and prognosis of isolated intraductal carcinoma of the prostate (iIDC-P). Methods: Three iIDC-P cases were collected retrospectively from 2016 to 2022 at Ningbo Clinical Pathology Diagnosis Center, Ningbo, China. The clinicopathologic features and immunophenotypic profiles were studied using light microscopy and immunohistochemistry. A targeted next-generation sequencing panel was used to analyze cancer-associated mutations. Follow-up and literature review were also performed. Results: The patients' ages were 61, 67 and 77 years, and their preoperative prostate specific antigen (PSA) levels were 7.99, 7.99 and 4.86 µg/L, respectively. Case 1 and 2 were diagnosed on needle biopsy and radical prostatectomy (RP) specimens, and case 3 was diagnosed on a specimen of transurethral resection of the prostate (TURP). The RP specimen was entirely submitted for histologic examination. In the case 1, iIDC-P was found in one tissue core (involving two ducts) in the biopsy specimen, and in 6 sections (diameter, 0.3-1.1 cm) from the radical prostatectomy specimen, and one section had separate foci of low-grade acinar adenocarcinoma (diameter, 0.05 cm). In the case 2, 6 tissue sections from the biopsy specimens showed iIDC-P, and 13 sections from RP specimen showed iIDC-P (diameter, 0.5-1.6 cm), and the other 3 sections had separate low grade acinar adenocarcinoma (diameter, 0.6 cm). In the case 3, 5 tissue blocks from the TURP specimen showed iIDC-P. The case 1 and 2 showed solid architecture with expansile proliferation of neoplastic cells in native ducts and acini. The case 3 showed dense or loose cribriform pattern, with marked cytological atypia, and frequent mitotic figures. Comedonecrosis was found in solid or dense cribriform glands in the case 2. Immunohistochemically, surrounding basal cells were highlighted using high-molecular-weight cytokeratin (34ßE12 and CK5/6) and p63, while P504s was positive in the tumor cells. The tumor cells were also positive for AR and prostate markers (NKX3.1, PSA and PSAP), and negative for GATA3. The iIDC-P and acinar adenocarcinoma both showed weak PTEN expression and no ERG (nuclear) expression. In case 2 and 3, targeted sequencing revealed activated oncogenic driver mutations in MAPK and PI3K pathway genes (KRAS, MTOR and PTEN). In addition, pathogenic mutation in TP53 and FOXA1 mutation were found in the case 2 and 3, respectively. No case demonstrated TMPRSS2::ERG translocation. All cases were microsatellite stable and had lower tumor mutation burdens (range, 2.1-3.1 muts/Mb). The patients showed no biochemical recurrence or metastasis after follow-up of 16-91 months. Conclusions: iIDC-P is a special type of intraductal carcinoma of the prostate and differs from intraductal carcinoma within high-grade prostate cancer. iIDC-P has unique molecular characteristics and may represent as a molecularly unique in situ tumor of prostate cancer.

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Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/cirugía , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Antígeno Prostático Específico/metabolismo , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Diagnóstico Diferencial , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/genética , Carcinoma Intraductal no Infiltrante/metabolismo , Proteínas de Homeodominio/metabolismo , Proteínas de Homeodominio/genética , Carcinoma Ductal/patología , Carcinoma Ductal/genética , Carcinoma Ductal/metabolismo , Carcinoma Ductal/cirugía , Resección Transuretral de la Próstata , Racemasas y Epimerasas/metabolismo , Racemasas y Epimerasas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Pronóstico , Queratinas , Proteínas de la Membrana

RESUMEN

Objective: To discuss the efficacy and safety of the dual immunotherapy of nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer (NSCLC) who are double negative for driver gene and programmed death-ligand 1 (PD-L1) expression. Methods: We conducted a retrospective collection of clinical data for 61 patients with advanced NSCLC who were negative for both driver genes and PD-L1 and received dual immunotherapy with nivolumab plus ipilimumab at the First Affiliated Hospital of Guangzhou Medical University from January 2019 to June 2023. Based on treatment conditions, patients were divided into first-line and non-first-line dual immunotherapy groups. Patients were followed up monthly, with the follow-up period ending on October 1, 2023. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute in the United States. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in progression-free survival (PFS) and overall survival (OS) between first-line and non-first-line dual immunotherapy patients. The influence factors of PFS were analyzed using a multivariate Cox proportional hazards regression model. Results: Among the 61 NSCLC patients, 49 were male (80.3%), with an age range of 23-88 years [(65.3±7.4) years]. There were 14 cases (23.0%) classified as stage ⅢC and 47 cases (77.0%) classified as stage Ⅳ according to TNM staging. Forty cases (65.6%) received non-first-line treatment. The objective response rate (ORR) was 24.6% (15/61), and the disease control rate (DCR) was 52.5% (32/61). All 61 patients were followed up, with a median follow-up time of 17.8 months. The median PFS was 6.0 months (95%CI: 5.5-6.4 months), and the median OS was 17.0 months (95%CI: 14.8-19.2 months). For patients receiving first-line dual immunotherapy, the median PFS was longer than for those receiving non-first-line dual immunotherapy [7.0 months (95%CI: 6.0-7.9 months) vs 4.0 months (95%CI: 3.3-4.6 months), P<0.001]; similarly, the median OS for patients receiving first-line dual immunotherapy was longer than for those receiving non-first-line dual immunotherapy [19.0 months (95%CI: 18.1-19.9 months) vs 13.0 months (95%CI: 10.8-15.1 months), P<0.001]. Multivariate Cox risk regression model analysis showed that distant tumor metastasis (HR=1.414, 95%CI: 1.253-1.725), non-first-line dual immunotherapy (HR=1.412, 95%CI: 1.184-1.652), and tumor mutation burden<10 mut/Mb (HR=1.328, 95%CI: 1.151-1.546) were risk factors for PFS, while non-squamous carcinoma (HR=0.917, 95%CI: 0.823-0.984) was a protective factor for PFS. Immune-related adverse reactions occurred in 41 cases (67.2%), including 21 cases (32.8%) of grade 3-4 adverse reactions. Eight cases (13.1%) discontinued treatment, and there were no deaths. Conclusions: Dual immunotherapy with nivolumab plus ipilimumab can be a treatment option for driver gene and PD-L1 double-negative advanced NSCLC. Distant tumor metastasis, non-first-line dual immunotherapy, and tumor mutation burden<10 mut/Mb are risk factors affecting patients' PFS, while non-squamous cell carcinoma is a protective factor affecting patients' PFS.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antígeno B7-H1/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven , Adulto , Anciano de 80 o más Años

RESUMEN

Despite the recent advances in quantum technology, the problem of controlling the light emission properties of quantum emitters used in numerous applications remains: a large spectral width, low intensity, blinking, photodegradation, biocompatibility, etc. In this work, we present the theoretical and experimental investigation of quantum light sources - mesoscopic systems consisting of fluorescent molecules in a thin polydopamine layer coupled with metallic or dielectric nanoparticles. Polydopamines possess many attractive adhesive and optical properties that promise their use as host media for dye molecules. However, numerous attempts to incorporate fluorescent molecules into polydopamines have failed, as polydopamine has been shown to be a very efficient fluorescence quencher through Förster resonance energy transfer and/or photoinduced electron transfer. Using the system as an example, we demonstrate new insights into the interactions between molecules and electromagnetic fields by carefully shaping its energy levels through strong matter-wave coupling of molecules to metallic nanoparticles. We show that the strong coupling effectively suppresses the quenching of fluorescent molecules in polydopamine, opening new possibilities for imaging.

RESUMEN

Innate inflammation promotes tumor development, although the role of innate inflammatory cytokines in established human tumors is unclear. Herein, we report clinical and translational results from a phase Ib trial testing whether IL1ß blockade in human pancreatic cancer would alleviate myeloid immunosuppression and reveal antitumor T-cell responses to PD1 blockade. Patients with treatment-naïve advanced pancreatic ductal adenocarcinoma (n = 10) were treated with canakinumab, a high-affinity monoclonal human antiinterleukin-1ß (IL1ß), the PD1 blocking antibody spartalizumab, and gemcitabine/n(ab)paclitaxel. Analysis of paired peripheral blood from patients in the trial versus patients receiving multiagent chemotherapy showed a modest increase in HLA-DR+CD38+ activated CD8+ T cells and a decrease in circulating monocytic myeloid-derived suppressor cells (MDSC) by flow cytometry for patients in the trial but not in controls. Similarly, we used patient serum to differentiate monocytic MDSCs in vitro and showed that functional inhibition of T-cell proliferation was reduced when using on-treatment serum samples from patients in the trial but not when using serum from patients treated with chemotherapy alone. Within the tumor, we observed few changes in suppressive myeloid-cell populations or activated T cells as assessed by single-cell transcriptional profiling or multiplex immunofluorescence, although increases in CD8+ T cells suggest that improvements in the tumor immune microenvironment might be revealed by a larger study. Overall, the data indicate that exposure to PD1 and IL1ß blockade induced a modest reactivation of peripheral CD8+ T cells and decreased circulating monocytic MDSCs; however, these changes did not lead to similarly uniform alterations in the tumor microenvironment.

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Protocolos de Quimioterapia Combinada Antineoplásica , Interleucina-1beta , Células Supresoras de Origen Mieloide , Neoplasias Pancreáticas , Receptor de Muerte Celular Programada 1 , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/inmunología , Interleucina-1beta/antagonistas & inhibidores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/efectos de los fármacos , Células Supresoras de Origen Mieloide/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Masculino , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Anciano , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Desoxicitidina/administración & dosificación , Persona de Mediana Edad , Gemcitabina , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Paclitaxel/uso terapéutico , Paclitaxel/administración & dosificación , Paclitaxel/farmacología , Metástasis de la Neoplasia , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología

RESUMEN

AIM: To investigate the application value of dual-layer detector computed tomography (CT) single-energy spectral images for reducing artefacts in the lower cervical spine. MATERIALS AND METHODS: Sixty-three patients who underwent neck examination using spectral CT between March 2022 and January 2023 were selected as the participants. Conventional mixed-energy images and spectral imaging data at 40-200 KeV were obtained from the spectral CT scans. The standard deviation (SD), signal-to-noise ratio (SNR), |CTdifference| (the difference in CT value between the C6-7 and C3-4 artefact regions), and contrast-to-noise ratio (CNR) of the C6-7 spinal canal were measured. The image quality of the artefact region in the conventional and single images were compared. RESULTS: The SDintervertebral disc value was highest in the single-level 40 KeV images and lowest in the 120 KeV images (P<0.05). The SNR was lowest in the 40 KeV images (2.07 ± 2.74) and highest in the 120 KeV images (6.20 ± 5.26) (P<0.05). The CTdifference was highest in the 40 KeV images and lowest in the 120 KeV images (108.38 vs. 10.63 ± 8.58). The subjective image quality scores were lowest in the 40 KeV images and highest in the 120 KeV images. CONCLUSION: Our findings suggest that single-energy 120 KeV images may offer benefits such as low SDintervertebral disc, elevated SNR, higher CNR, and improved image quality.

Asunto(s)

Artefactos , Vértebras Cervicales , Tomografía Computarizada por Rayos X , Humanos , Vértebras Cervicales/diagnóstico por imagen , Masculino , Femenino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Adulto , Anciano , Relación Señal-Ruido , Imagen Radiográfica por Emisión de Doble Fotón/métodos , Anciano de 80 o más Años

RESUMEN

Objective: To explore the effect and molecular mechanism of circ_0000263 on HeLa cell activity, apoptosis, telomerase activity, and radiosensitivity. Methods: The Hela cells were divided into si-NC, si-circ, vector, circ_0000263, anti-NC, anti-miR-338-3p, miR-NC, miR-338-3p, si-circ+anti-NC, si-circ+ anti-miR-338-3p, si-circ+vector, si-circ+TERT, sh-NC, sh-circ groups. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_0000263 and miR-338-3p. Cell clone formation array was used to detect cell survival; cell counting kit-8 (CCK-8) to detect cell proliferation; flow cytometry to detect apoptosis; western blot method to detect the expressions of proliferating cell nuclear antigen (PCNA), Cleaved-casp3, telomerase reverse transcriptase (TERT) proteins; double luciferase assay to detect the targeting relationships of circ_0000263 and miR-338-3p, miR-338-3p and TERT; telomere repeat amplification enzyme linked immunosorbent assay (TRAR-ELISA) to detect telomerase activity. Results: Circ_0000263 was highly expressed in Hela cells, miR-338-3p was low expressed, and TERT was highly expressed; circ_0000263 was also highly expressed in Hela cells treated with radiation (P＜0.05). Knockdown of circ_0000263 inhibited the clone formation and cell proliferation ability of HeLa cells, and enhanced the radiosensitivity and apoptosis of HeLa cells. In contrast, knockdown of circ_0000263 decreased PCNA protein expression level and enhanced Cleaved-casp3 protein expression level in HeLa cells (P＜0.05). The apoptosis rate in the si-circ group was (13.19±1.12)%, which was higher than (6.80±0.62)% of si-NC group (P＜0.05). The apoptosis rate in the si-circ+4 Gy group was (24.82±1.57)%, which was higher than (17.00±0.96)% of si-NC+4 Gy group (P＜0.05). Circ_0000263 targeted regulated miR-338-3p, and miR-338-3p targeted regulated TERT. MiR-338-3p was lowly expressed in HeLa cells, and knockdown of circ_0000263 elevated miR-338-3p expression level in HeLa cells. Circ_0000263 regulated TERT expression and inhibited telomerase activity through miR-338-3p. MiR-338-3p/TERT can restore the effect of circ_0000263 on the radiosensitivity of Hela cells. The apoptosis rate in the si-circ+anti-NC group was (27.37±0.89)%, which was higher than (18.22±1.18)% of the si-circ+anti-miR-338-3p group (P＜0.05). The apoptosis rate in the si-circ+vector group was (27.55±0.48)%, which was higher than (20.10±0.68)% of si-circ+TERT group (P＜0.05). After 72 hours of radiation by 4 Gy, the cell survival fraction of si-circ+anti-NC group was 0.41±0.02, which was lower than 0.66±0.03 of the si-circ+anti-miR-338-3p group (P＜0.05); the cell survival fraction of si-circ+vector group was 0.42±0.05, which was lower than 0.70±0.03 of si-circ+TERT group (P＜0.05). Conclusion: Inhibiting the expression of circ_0000263 supresses the proliferation of Hela cells by regulating miR-338-3p/TERT, promotes apoptosis, inhibits telomerase activity, increases the radiosensitivity of cancer cells, and provides a theoretical basis for improving the radiosensitivity of Hela cells.

Asunto(s)

Apoptosis , Proliferación Celular , MicroARNs , Tolerancia a Radiación , Telomerasa , Humanos , Células HeLa , MicroARNs/metabolismo , MicroARNs/genética , Telomerasa/genética , Telomerasa/metabolismo , Apoptosis/efectos de la radiación , ARN Circular/genética , ARN Circular/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Antígeno Nuclear de Célula en Proliferación/genética

RESUMEN

BACKGROUND: Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer's disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH). OBJECTIVES: 1) To assess the relationship between baseline WMH volume and baseline MCH. 2) To assess the relationship between longitudinal WMH accumulation and last MRI MCH during the double-blind phase of the A4 trial. DESIGN: A multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing solanezumab with placebo given as infusions once every 4 weeks over 4.5 years in subjects with preclinical AD, defined as having evidence of elevated brain amyloid before the stage of clinically evident cognitive impairment, with an optional open-label extension period. SETTING: Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study. PARTICIPANTS: A sample of 1157 cognitively unimpaired older adults (mean age = 71.9 years [SD = 4.8 years], 59% women, 59% APOE ε4 carriers). MEASUREMENTS: A linear regression model was used to assess the impact of baseline MCH amount (0, 1, 2+) on WMH volume. A linear mixed-effects model was used to assess the impact of last MRI MCH on longitudinal WMH. All models were corrected for age, sex, grey matter volume, cortical amyloid PET, APOE ε4 status, and treatment group. RESULTS: Baseline WMH volume was greater in individuals with more than one MCH compared to those with no MCH (t=4.8, p<0.001). The longitudinal increase in WMH amongst individuals with one (t=2.3, p=0.025) and more than one MCH (t=6.7, p<0.001) at the last MRI was greater than those with no MCH. CONCLUSION: These results indicate a strong association between WMH and MCH, a common manifestation of cerebral amyloid angiopathy and ARIA-H. These results suggest that increased WMH volume may represent an early sign of vessel amyloidosis, likely prior to the emergence of MCH.

Asunto(s)

Enfermedad de Alzheimer , Anticuerpos Monoclonales Humanizados , Imagen por Resonancia Magnética , Sustancia Blanca , Humanos , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/tratamiento farmacológico , Femenino , Masculino , Anciano , Sustancia Blanca/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/efectos de los fármacos , Método Doble Ciego , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síntomas Prodrómicos