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1.
Arch Gerontol Geriatr ; 127: 105548, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38964053

RESUMEN

PURPOSE: Despite the ongoing rise in hip fractures and the adverse effects of hearing impairment (HI) on increased mortality and morbidity, research addressing the influence of HI on mortality risk or complications in patients with hip fractures remains absent. This study aimed to analyze the effects of HI on mortality and treatment outcomes among patients with hip fracture. METHODS: We retrospectively collected data from consecutive patients diagnosed with hip fractures between January 2007 and March 2022 who had auditory examination records. From the initially enrolled 265 patients, data for 58 with HI and 58 without HI (control group) were extracted using a 1:1 propensity score matching. The primary outcome included comparison of mortality rates, and the secondary outcome encompassed the comparison of postoperative medical and surgical complications. RESULTS: The 1-year cumulative mortality rate was not significantly different between the HI and control groups, but the overall cumulative mortality rate was significantly higher in the HI than in the control group (63.0 % and 48.6, respectively; P = 0.046) in a follow-up period of up to 16 years. The HI group had a significantly higher incidence of "second hip fractures due to falls" than the control group (P = 0.016), although no differences in other medical and surgical complications were revealed. CONCLUSIONS: Awareness of the long-term risk of higher mortality when managing patients with hip fracture and HI is important. To reduce the risk of second hip fractures, paying more attention to fall prevention education and taking a more proactive approach, especially for those with HI.

2.
Hinyokika Kiyo ; 70(5): 129-131, 2024 May.
Artículo en Japonés | MEDLINE | ID: mdl-38966923

RESUMEN

The patient was a 71-year-old male whose chief complaint was a scrotum mass. The mass had gradually increased in size without any associated symptoms. The physical examination revealed a pedunculated, radish brown, and elastic soft tumor (4. 5×3. 5×3. 0 cm) in the right scrotum. Blood chemical analysis of HbA1c and squamous carcinoma antigen were 8. 3% and 38. 4 ng/ml (≦1. 5), respectively. This tumor was successfully treated with surgical resection. Histopathological examination showed condyloma acuminatum without malignant findings. Giant condyloma acuminatum commonly affects the genital and perianal areas. An immunocompromised state generally exists in the background of the patients.


Asunto(s)
Escroto , Humanos , Masculino , Anciano , Escroto/patología , Escroto/cirugía , Condiloma Acuminado/cirugía , Condiloma Acuminado/patología , Neoplasias de los Genitales Masculinos/patología , Neoplasias de los Genitales Masculinos/cirugía , Tumor de Buschke-Lowenstein/patología , Tumor de Buschke-Lowenstein/cirugía
3.
Artículo en Inglés | MEDLINE | ID: mdl-38985549

RESUMEN

Intracellular electrophysiology, a vital and versatile technique in cellular neuroscience, is typically conducted using the patch-clamp method. Despite its effectiveness, this method poses challenges due to its complexity and low throughput. The pursuit of multi-channel parallel neural intracellular recording has been a long-standing goal, yet achieving reliable and consistent scaling has been elusive because of several technological barriers. In this work, we introduce a micropower integrated circuit, optimized for scalable, high-throughput in vitro intrinsically intracellular electrophysiology. This system is capable of simultaneous recording and stimulation, implementing all essential functions such as signal amplification, acquisition, and control, with a direct interface to electrodes integrated on the chip. The electrophysiology system-on-chip (eSoC), fabricated in 180nm CMOS, measures 2.236 mm × 2.236 mm. It contains four 8 × 8 arrays of nanowire electrodes, each with a 50 µm pitch, placed over the top-metal layer on the chip surface, totaling 256 channels. Each channel has a power consumption of 0.47 µW, suitable for current stimulation and voltage recording, and covers 80 dB adjustable range at a sampling rate of 25 kHz. Experimental recordings with the eSoC from cultured neurons in vitro validate its functionality in accurately resolving chemically induced multi-unit intracellular electrical activity.

4.
FASEB J ; 38(13): e23759, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38949635

RESUMEN

The epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti-EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR-targeting immunotoxin consisting of a clinically proven anti-EGFR IgG (cetuximab; CTX) and a toxin fragment (LR-LO10) derived from Pseudomonas exotoxin A (PE) using a novel site-specific conjugation technology (peptide-directed photo-crosslinking reaction), as an alternative option. The immunotoxin (CTX-LR-LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor-2. Treatment of EGFR-positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX-LR-LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR-LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX-LR-LO10 may serve as a new therapeutic agent targeting EGFR-positive cancers.


Asunto(s)
ADP Ribosa Transferasas , Receptores ErbB , Exotoxinas , Neoplasias de Cabeza y Cuello , Inmunoglobulina G , Inmunotoxinas , Exotoxina A de Pseudomonas aeruginosa , Factores de Virulencia , Humanos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Receptores ErbB/inmunología , Animales , Inmunotoxinas/farmacología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/metabolismo , Ratones , Inmunoglobulina G/farmacología , Línea Celular Tumoral , Exotoxinas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Cetuximab/farmacología , Ratones Desnudos , Toxinas Bacterianas , Apoptosis/efectos de los fármacos , Ratones Endogámicos BALB C , Femenino , Movimiento Celular/efectos de los fármacos , Antineoplásicos/farmacología
5.
Food Sci Anim Resour ; 44(4): 899-911, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38974732

RESUMEN

This research investigated the synergic outcome of high intensity ultrasound (HIU) treatment and wet-dry combined aging (WDCA) on physiochemical characteristics and lipid oxidation during refrigerated storage to ameliorate pork meat's quality and shelf life. The CIE b* values, cooking loss (CL %), and pH of the HIU treated samples were higher than those of the control over the aging period. They were significantly (p<0.05) modified by the aging period and ultrasound (US) treatment. However, the released water (RW %) and moisture were not significantly influenced by US treatment (p>0.05). The Warner-Bratzler shear force of HIU-treated samples was lower over control values except in 7-14 d, and it showed a significant difference between control and US treatment according to the significance of HIU (p<0.05). The thiobarbituric acid reactive substance of HIU-treated samples was significantly higher (p<0.05) than control values over the aging period. These results suggested that HIU treatment and WDCA showed a synergistic effect of maximizing the tenderness, but lipid oxidation was higher than before ultrasonic treatment. In agreement with this, the most favorable approach would involve implementing wet aging for a period of two weeks followed by dry aging for a period not exceeding one week after the application of HIU.

6.
J Tissue Viability ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38937250

RESUMEN

PURPOSE: This study aimed to analyze if a multi-foam core mattress with a laminated cover can reduce the incidence of pressure injuries, compared to an alternating air mattress overlay among critically ill patients in acute settings. DESIGN: Prospective observational study. PARTICIPANTS: and setting: Patients with a Braden scale score ≤16 on intensive care unit admission at five general hospitals in Korea were included in this study between February 2022 and March 2022. METHODS: One hundred and twenty patients in acute settings were enrolled and categorized into two groups: a multi-form core mattress with a laminated cover group (n = 60) and an alternating air mattress overlay group (n = 60). Data were collected for 7 days by wound care nurses. RESULTS: Pressure injury developed at a significantly lower rate in the multi-form core mattress with a laminated cover group (n = 4/60, 6.7 %) than in the alternating air mattress overlay group (n = 25/60, 25.0 %) (P = 0.011). Using a multi-foam core mattress with a laminated cover demonstrated a protective effect against pressure injuries (odds ratio 0.123, 95 % confidence interval 0.024-0.620, P = 0.011). CONCLUSIONS: A multi-foam core mattress with a laminated cover was significantly more effective than an alternating air mattress overlay in preventing pressure injury in critically ill patients.

8.
Clin Orthop Surg ; 16(3): 363-373, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38827761

RESUMEN

Background: Operative management with intramedullary nail fixation remains the definitive treatment of choice for osteoporotic subtrochanteric (ST) fractures; however, there remains no consensus regarding the proper nail length. We aimed to use 3-dimensional finite element (FE) analysis to determine the optimal nail length for the safe fixation of osteoporotic ST fractures. Methods: Nine modes of FE models were constructed using 9 different lengths of cephalomedullary nails (short nails: 170, 180, and 200 mm; long nails: 280, 300, 320, 340, 360, and 380 mm) from the same company. The interfragmentary motion was analyzed. Additionally, the peak von Mises stress (PVMS) in the cortical bone, cancellous bone of the femoral head, and the nail were measured, and the yielding risk for each subject was investigated. Results: Long nails were associated with less interfragmentary motion. In the cortical bone, the PVMS of short nails was observed at the distal locking screw holes of the femoral medial cortex; however, in long nails, the PVMS was observed at the lag screw holes on the lateral cortex. The mean yielding risk of long nails was 40.1% lower than that of short nails. For the cancellous bone of the femoral head, the PVMS in all 9 FE models was in the same area: at the apex of the femoral head. There was no difference in the yielding risk between short and long nails. For implants, the PVMS was at the distal locking screw hole of the nail body in the short nails and the nail body at the fracture level in the long nails. The mean yielding risk was 74.9% lower for long nails than that for short nails. Conclusions: Compared to short nails, long nails with a length of 320 mm or more showed less interfragmentary motion and lower yielding risk in low-level osteoporotic ST fractures. The FE analysis supports long nails as a safer option than short nails, especially for treating transverse-type low-level osteoporotic ST fractures.


Asunto(s)
Clavos Ortopédicos , Análisis de Elementos Finitos , Fijación Intramedular de Fracturas , Fracturas de Cadera , Fracturas Osteoporóticas , Humanos , Fracturas Osteoporóticas/cirugía , Fijación Intramedular de Fracturas/métodos , Fijación Intramedular de Fracturas/instrumentación , Fracturas de Cadera/cirugía , Femenino , Anciano
9.
Clin Orthop Surg ; 16(3): 430-440, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38827763

RESUMEN

Background: Computer-assisted navigation surgery (CAS) during primary total knee arthroplasty (TKA) may help improve outcomes for patients with extra-articular deformity (EAD); however, this has not been extensively studied. Therefore, we aimed to investigate the clinical and radiological outcomes following primary TKA using CAS in patients with EAD. Methods: We searched Medline, Embase, and the Cochrane Library up to March 3, 2023 for studies investigating surgical outcomes of using the navigation system for TKA to treat patients with EAD. From 14 studies, 539 knees with EAD that underwent navigation TKA were enrolled. We investigated the knee range of motion (ROM), outcome scores at final follow-up (Knee Society Score [KSS] and Knee Functional Score [KFS]), and pre- and postoperative mechanical hip-knee-ankle (mHKA) angle using lower extremity scanogram. The meta-analysis was based on the single-arm method, and all data were pooled using a random-effects model. Results: Following our meta-analyses, the mean knee ROM changed from 87.0° (95% confidence interval [CI], 75.9°-98.1°) preoperatively to 109.4° (95% CI, 97.9°-120.8°) postoperatively. The adjusted KSS was 93.45 points (95% CI, 88.36-98.54 points), and the adjusted KFS was 91.57 points (95% CI, 86.80-96.33 points) in knees with EAD that underwent CAS-TKA. As a radiological outcome, the mHKA angle changed from 169.53° (95% CI, 166.90°-172.16°) preoperatively to 178.81° (95% CI, 178.31°-179.30°) postoperatively. Conclusions: CAS-TKA yielded positive clinical results and demonstrated a satisfactory alignment of the lower limb's mechanical axis. CAS-TKA showed promise for primary TKA procedures, demonstrating favorable clinical and radiological outcomes even in complex cases involving EAD.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Rango del Movimiento Articular , Cirugía Asistida por Computador , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Cirugía Asistida por Computador/métodos , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/diagnóstico por imagen
10.
Inorg Chem ; 63(25): 11506-11522, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38856726

RESUMEN

The catalytic efficacy of the monobipyridyl (η6-para-Cymene)Ru(II) half-metallocene, [(p-Cym)Ru(bpy)Cl]+ was evaluated in both mixed homogeneous (dye + catalyst) and heterogeneous hybrid systems (dye/TiO2/Catalyst) for photochemical CO2 reduction. A series of homogeneous photolysis experiments revealed that the (p-Cym)Ru(II) catalyst engages in two competitive routes for CO2 reduction (CO2 to formate conversion via RuII-hydride vs CO2 to CO conversion through a RuII-COOH intermediate). The conversion activity and product selectivity were notably impacted by the pKa value and the concentration of the proton source added. When a more acidic TEOA additive was introduced, the half-metallocene Ru(II) catalyst leaned toward producing formate through the RuII-H mechanism, with a formate selectivity of 86%. On the other hand, in homogeneous catalysis with TFE additive, the CO2-to-formate conversion through RuII-H was less effective, yielding a more efficient CO2-to-CO conversion with a selectivity of >80% (TONformate of 140 and TONCO of 626 over 48 h). The preference between the two pathways was elucidated through an electrochemical mechanistic study, monitoring the fate of the metal-hydride intermediate. Compared to the homogeneous system, the TiO2-heterogenized (p-Cym)Ru(II) catalyst demonstrated enhanced and enduring performance, attaining TONs of 1000 for CO2-to-CO and 665 for CO2-to-formate.

11.
ACS Appl Mater Interfaces ; 16(24): 31085-31097, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38837183

RESUMEN

Carbon dioxide (CO2) conversion into value-added chemicals/fuels by utilizing solar energy is a sustainable way to mitigate our dependence on fossil fuels and stimulate a carbon-neutral economy. However, the efficient and affordable conversion of CO2 is still an ongoing challenge. Here, we report an interfacially synthesized visible-light-active Ni(II)-integrated covalent organic frameworks (TaTpBpy-Ni COFs) film as a photocatalyst for efficient CO2 conversion into carboxylic acid under ambient conditions. Notably, the TaTpBpy-Ni COFs film showed excellent photocatalytic activity for the carboxylation of various arylamines with CO2 to the corresponding arylcarboxylic acid via C-N bond activation under solar-light irradiation. Moreover, this carboxylation protocol exhibits mild reaction conditions and good functional group tolerance without the necessity of using stoichiometric metallic reductants. This work shows a benchmark example of not only the interfacially synthesized COFs film used as a photocatalyst for solar-light energy utilization but also the selective solar chemical production system of arylcarboxylic acid directly from CO2.

12.
Proc Natl Acad Sci U S A ; 121(21): e2321388121, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38748583

RESUMEN

Protocadherin19 (PCDH19)-related epilepsy syndrome is a rare disorder characterized by early-onset epilepsy, intellectual disability, and autistic behaviors. PCDH19 is located on the X chromosome and encodes a calcium-dependent single-pass transmembrane protein, which regulates cell-to-cell adhesion through homophilic binding. In human, 90% of heterozygous females, containing PCDH19 wild-type and mutant cells due to random X inactivation, are affected, whereas mutant males, containing only mutant cells, are typically not. The current view, the cellular interference, is that the altered interactions between wild-type and mutant cells during development, rather than loss of function itself, are responsible. However, studies using Pcdh19 knockout mice showed that the complete loss of function also causes autism-like behaviors both in males and females, suggesting that other functions of PCDH19 may also contribute to pathogenesis. To address whether mosaicism is required for PCDH19-related epilepsy, we generated Xenopus tropicalis tadpoles with complete or mosaic loss of function by injecting antisense morpholino oligonucleotides into the blastomeres of neural lineage at different stages of development. We found that either mosaic or complete knockdown results in seizure-like behaviors, which could be rescued by antiseizure medication, and repetitive behaviors. Our results suggest that the loss of PCDH19 function itself, in addition to cellular interference, may also contribute to PCDH19-related epilepsy.


Asunto(s)
Cadherinas , Epilepsia , Mosaicismo , Protocadherinas , Xenopus , Animales , Cadherinas/genética , Cadherinas/metabolismo , Femenino , Epilepsia/genética , Epilepsia/metabolismo , Masculino , Conducta Animal , Humanos
13.
BMJ Open ; 14(5): e079417, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38777592

RESUMEN

OBJECTIVES: We aimed to develop an automated method for measuring the volume of the psoas muscle using CT to aid sarcopenia research efficiently. METHODS: We used a data set comprising the CT scans of 520 participants who underwent health check-ups at a health promotion centre. We developed a psoas muscle segmentation model using deep learning in a three-step process based on the nnU-Net method. The automated segmentation method was evaluated for accuracy, reliability, and time required for the measurement. RESULTS: The Dice similarity coefficient was used to compare the manual segmentation with automated segmentation; an average Dice score of 0.927 ± 0.019 was obtained, with no critical outliers. Our automated segmentation system had an average measurement time of 2 min 20 s ± 20 s, which was 48 times shorter than that of the manual measurement method (111 min 6 s ± 25 min 25 s). CONCLUSION: We have successfully developed an automated segmentation method to measure the psoas muscle volume that ensures consistent and unbiased estimates across a wide range of CT images.


Asunto(s)
Aprendizaje Profundo , Músculos Psoas , Sarcopenia , Tomografía Computarizada por Rayos X , Humanos , Músculos Psoas/diagnóstico por imagen , Músculos Psoas/anatomía & histología , Tomografía Computarizada por Rayos X/métodos , Estudios Transversales , Femenino , Masculino , Sarcopenia/diagnóstico por imagen , Reproducibilidad de los Resultados , Persona de Mediana Edad , Anciano , Adulto , Tamaño de los Órganos
14.
PLoS One ; 19(5): e0303871, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38768233

RESUMEN

This study aimed to investigate the impact of the cumulative burden of metabolic syndrome (MetS) on the incidence of retinal vein occlusion (RVO) in young adults. We included 1,408,093 subjects aged ≥20 and <40 years without a history of RVO who underwent four consecutive annual health examinations during 2009-2012 from the database of the Korean National Health Insurance Service. The metabolic burden was evaluated based on the cumulative number of MetS diagnoses at each health examination (0-4 times) and the cumulative number of each MetS component diagnosed at each health examination (0-4 times per MetS component). Cox proportional hazards models were used to estimate the risk of RVO according to metabolic burden. The risk of RVO was positively correlated with the cumulative number of MetS diagnoses over the four health examinations. All five MetS components were independently associated with an increased risk of RVO. Subgroup analysis for the impact of MetS on RVO occurrence revealed that MetS had a greater impact on female subjects (P <0.001). Prompt detection of metabolic derangements and their treatment might be important to decrease the risk of RVO in young adults, especially women.


Asunto(s)
Síndrome Metabólico , Oclusión de la Vena Retiniana , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/complicaciones , Oclusión de la Vena Retiniana/epidemiología , Oclusión de la Vena Retiniana/etiología , Femenino , Masculino , Adulto , República de Corea/epidemiología , Factores de Riesgo , Adulto Joven , Modelos de Riesgos Proporcionales , Incidencia
15.
Artículo en Inglés | MEDLINE | ID: mdl-38714474

RESUMEN

BACKGROUND: Despite a higher risk of classical Hodgkin lymphoma (cHL) in people with HIV and the demonstrated safety and efficacy of PD-1 blockade in cHL, there are limited data on the use of these agents in HIV-associated cHL (HIV-cHL). PATIENTS/METHODS: We retrospectively identified patients with HIV-cHL from the "Cancer Therapy using Checkpoint inhibitors in People with HIV-International (CATCH-IT)" database who received nivolumab or pembrolizumab, alone or in combination with other agents, and reviewed records for demographics, disease characteristics, immune-mediated adverse events (imAEs), and treatment outcomes. Changes in CD4+ T-cell counts with treatment were measured via Wilcoxon signed-rank tests. Overall response rate (ORR) was defined as the proportion of patients with partial or complete response (PR/CR) per 2014 Lugano classification. RESULTS: We identified 23 patients with HIV-cHL who received a median of 6 cycles of PD-1 blockade: 1 as 1st-line, 6 as 2nd-line, and 16 as ≥3rd-line therapy. Seventeen (74%) patients received monotherapy, 5 (22%) received nivolumab plus brentuximab vedotin, and 1 received nivolumab plus ifosfamide, carboplatin, and etoposide. The median baseline CD4+ T-cell count was 155 cells/µL, which increased to 310 cells/µL at end-of-treatment (P = .009). Three patients had grade 3 imAEs; none required treatment discontinuation. The ORR was 83% with median duration of response of 19.7 months. The median progression-free survival was 21.2 months and did not differ between patients with <200 versus ≥200 CD4+ cells/µL (P = .95). CONCLUSION: Our findings support the use of PD-1 blockade in HIV-cHL for the same indications as the general population with cHL.

16.
Sci Rep ; 14(1): 8015, 2024 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580719

RESUMEN

Plant-specific transcription factors (TFs) are responsible for regulating the genes involved in the development of plant-specific organs and response systems for adaptation to terrestrial environments. This includes the development of efficient water transport systems, efficient reproductive organs, and the ability to withstand the effects of terrestrial factors, such as UV radiation, temperature fluctuations, and soil-related stress factors, and evolutionary advantages over land predators. In rice and Arabidopsis, INDETERMINATE DOMAIN (IDD) TFs are plant-specific TFs with crucial functions, such as development, reproduction, and stress response. However, in tomatoes, IDD TFs remain uncharacterized. Here, we examined the presence, distribution, structure, characteristics, and expression patterns of SlIDDs. Database searches, multiple alignments, and motif alignments suggested that 24 TFs were related to Arabidopsis IDDs. 18 IDDs had two characteristic C2H2 domains and two C2HC domains in their coding regions. Expression analyses suggest that some IDDs exhibit multi-stress responsive properties and can respond to specific stress conditions, while others can respond to multiple stress conditions in shoots and roots, either in a tissue-specific or universal manner. Moreover, co-expression database analyses suggested potential interaction partners within IDD family and other proteins. This study functionally characterized SlIDDs, which can be studied using molecular and bioinformatics methods for crop improvement.


Asunto(s)
Arabidopsis , Solanum lycopersicum , Solanum lycopersicum/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Filogenia
17.
Transl Lung Cancer Res ; 13(3): 475-490, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38601456

RESUMEN

Background: Immunotherapies using anti-programmed cell death ligand-1 (PD-L1) agents have recently shown remarkable outcomes in patients with non-small cell lung cancer (NSCLC). However, there was a poor correlation between PD-L1 expression and treatment response. Many researchers have focused on the clinicopathological factors associated with prognosis, but the results are conflicting. In the present study, we investigated the clinicopathological significance of PD-L1 overexpression in NSCLC cells. Methods: In total, 344 NSCLC cases with PD-L1 assays were retrospectively analyzed. PD-L1 expression was evaluated via immunohistochemical staining using antibodies against SP263 and SP142. The correlation between clinicopathological factors and PD-L1 expression was analyzed for various clinicopathological features. Results: PD-L1 expression significantly correlated with several poor clinicopathological factors, including the solid component of adenocarcinoma, lymphatic invasion, and recurrence. Squamous cell carcinoma, older age, and male sex were also associated with PD-L1 expression. However, we could not observe correlation between PD-L1 expression and disease-free survival (DFS). A novel finding was that lower metastasis was associated with high PD-L1 expression of SP142 in tumor-infiltrating immune cells (ICs). Conclusions: PD-L1 expression in NSCLC is associated with adverse clinicopathological features and recurrence; therefore, it could be utilized to predict poor prognosis. Furthermore, the high PD-L1 expression of SP142 in tumor-infiltrating ICs could be a potential marker for low metastasis.

18.
Life (Basel) ; 14(4)2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38672740

RESUMEN

BACKGROUND: This study aimed to investigate the efficacy and safety of digital therapeutics (DTx), EASYBREATH, for pulmonary rehabilitation (PR) in patients with chronic respiratory diseases (CRDs). MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at multiple centers. Participants were randomly allocated 1:1 to the DTx group (DTxG), provided with DTx using EASYBREATH. The DTxG underwent an 8-week PR program with evaluations conducted at baseline, four weeks, and eight weeks. The control group (CG) underwent one PR session and was advised to exercise and undergo the same evaluation. The primary outcome was the change in six-minute walking distance (6MWD) over eight weeks, and secondary outcomes included changes in scores of Modified Medical Research Council (mMRC), chronic obstructive pulmonary disease assessment test (CAT), and St. George's respiratory questionnaire (SGRQ). RESULTS: The change in 6MWD after eight weeks demonstrated a significant difference between the DTxG and CG (57.68 m vs. 21.71 m, p = 0.0008). The change in mMRC scores (p = 0.0008), CAT scores (p < 0.0001), and total SGRQ scores (p = 0.0003) also showed a significant difference between the groups after eight weeks. CONCLUSIONS: EASYBREATH significantly improved exercise capacity, alleviated dyspnea, and enhanced the overall quality of life at eight weeks. EASYBREATH is a highly accessible, time-efficient, and effective treatment option for CRD with high compliance.

19.
Pharmaceutics ; 16(4)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38675118

RESUMEN

Enzalutamide (ENZ), marketed under the brand name Xtandi® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.

20.
Pharmaceuticals (Basel) ; 17(4)2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38675422

RESUMEN

Lycii Radicis Cortex (LRC) is a traditional medicine in East Asia with various beneficial effects, including antioxidant, anti-inflammatory, anti-tumor, anti-diabetic, and anti-depressant properties. However, its potential effects on skeletal muscle atrophy have not been studied. In this study, the protective effects of LRC extract (LRCE) on dexamethasone (DEX)-induced muscle atrophy were investigated in C2C12 myotubes and mice. We evaluated the effect of LRCE on improving muscle atrophy using a variety of methods, including immunofluorescence staining, quantitative polymerase chain reaction (qPCR), Western blot, measurements of oxidative stress, apoptosis, ATP levels, and muscle tissue analysis. The results showed that LRCE improved myotube diameter, fusion index, superoxide dismutase (SOD) activity, mitochondrial content, ATP levels, expression of myogenin and myosin heavy chain (MHC), and reduced reactive oxygen species (ROS) production in dexamethasone-induced C2C12 myotubes. LRCE also enhanced protein synthesis and reduced protein degradation in the myotubes. In mice treated with DEX, LRCE restored calf thickness, decreased mRNA levels of muscle-specific RING finger protein 1 (MuRF1) and atrogin-1, and increased insulin-like growth factor 1 (IGF-1) mRNA level. Moreover, LRCE also repaired gastrocnemius muscle atrophy caused by DEX. Although human studies are not available, various preclinical studies have identified potential protective effects of LRCE against muscle atrophy, suggesting that it could be utilized in the prevention and treatment of muscle atrophy.

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