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AIMS: Healed plaque (HP) is associated with rapid plaque growth and luminal narrowing. Thin-cap fibroatheroma (TCFA) is recognized as a precursor lesion to plaque rupture. The aim of the present study was to compare the lipid size among optical coherence tomography (OCT)-derived HP, TCFA, and thick-cap fibroatheroma (ThCFA) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). METHODS: The present study included 173 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention. Non-culprit lesions with angiographically intermediate stenosis were assessed by both OCT and NIRS-IVUS. RESULTS: The frequency of TCFA, HP, and ThCFA was 35 (20%), 53 (30%), and 85 (49%), respectively. Minimum lumen area was not significantly different between TCFA and HP, but was smaller in TCFA and HP than in ThCFA (4.6 [interquartile range {IQR}: 3.5-6.4] mm2 vs. 4.3 [3.4-5.3] mm2 vs. 6.5 [4.8-8.6] mm2, Pï¼0.001). Plaque burden was not significantly different between TCFA and HP, but was larger in TCFA and HP than in ThCFA (72 [IQR: 66-80] % vs. 75 [67-80] % vs. 62 [54-69] %, Pï¼0.001). Maximum lipid core burden index in 4mm (maxLCBI4mm) was largest in TCFA, followed by HP and ThCFA (493 [IQR: 443-606] vs. 446 [347-520] vs. 231 [161-302], Pï¼0.001). The frequency of lipid rich plaque with maxLCBI4mm ï¼400 was highest in TCFA, followed by HP and ThCFA (89% vs. 60% vs. 7%, Pï¼0.001). CONCLUSIONS: Based on NIRS-IVUS findings, non-culprit coronary HP in AMI was associated with vulnerable plaque characteristics, but not as much as TCFA.
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STUDY DESIGN: A technical note and retrospective case series. OBJECTIVE: Highly upward-migrated lumbar disc herniation (LDH) is challenging due to its problematic access and incomplete removal. The most used interlaminar approach may cause extensive bony destruction. We developed a novel translaminar approach using the unilateral portal endoscopic (UBE) technique, emphasizing effective neural decompression, and preserving the facet joint's integrity. METHODS: This retrospective study included six patients receiving UBE translaminar discectomy for highly upward-migrated LDHs from May 2019 to June 2021. The migrated disc was removed through a small keyhole on the lamina of the cranial vertebra. The treatment results were evaluated by operation time, hospital stays, complications, visual analog scale (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) score, and modified MacNab criteria. RESULTS: The mean pre-operative VAS for back pain (5.0 ± 4.9), VAS for leg pain (9.2 ± 1.0), JOA score (10.7 ± 6.6), and ODI (75.7 ± 25.3) were significantly improved to 0.3 ± 0.5, 1.2 ± 1.5, 27.3 ± 1.8, 5.0 ± 11.3 respectively at the final follow-up. Five patients had excellent, and one patient had good outcomes according to the Modified MacNab criteria. The hospital stay was 2.7 ± 0.5 days. No complication was recorded. The MRI follow-up showed complete disc removal, except for one patient with an asymptomatic residual disc. CONCLUSIONS: UBE translaminar discectomy is a safe and effective minimally invasive procedure for highly upward-migrated LDH with satisfactory treatment outcomes and nearly 100% facet joint preservation.
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Discectomía , Endoscopía , Desplazamiento del Disco Intervertebral , Vértebras Lumbares , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Vértebras Lumbares/cirugía , Vértebras Lumbares/diagnóstico por imagen , Resultado del Tratamiento , Adulto , Endoscopía/métodos , Discectomía/métodos , Anciano , Dimensión del DolorRESUMEN
Chronic pain is a universal public health problem with nearly one third of global human involved, which causes significant distressing personal burden. After painful stimulus, neurobiological changes occur not only in peripheral nervous system but also in central nervous system where somatosensory cortex is important for nociception. Being an ion channel, transient receptor potential vanilloid 1 (TRPV1) act as an inflammatory detector in the brain. Thymic stromal lymphopoietin (TSLP) is a potent neuroinflammation mediator after nerve injury. Bleomycin is applied to treat dermatologic diseases, and its administration elicits local painful sensation. However, whether bleomycin administration can cause chronic pain remains unknown. In the present study, we aimed to investigate how mice develop chronic pain after receiving repeated bleomycin administration. In addition, the relevant neurobiological brain changes after noxious stimuli were clarified. C57BL/6 mice aged five- to six-weeks were randomly classified into two group, PBS (normal) group and bleomycin group which bleomycin was intradermally administered to back five times a week over a three-week period. Calibrated forceps testing was used to measure mouse pain threshold. Western blots were used to assess neuroinflammatory response; immunofluorescence assay was used to measure the status of neuron apoptosis, glial reaction, and neuro-glial communication. Bleomycin administration induced mechanical nociception and activated both TRPV1 and TSLP/TSLPR/pSTAT5 signals in mouse somatosensory cortex. Through these pathways, bleomycin not only activates glial reaction but also causes neuronal apoptosis. TRPV1 and TSLP/TSLPR/pSTAT5 signaling had co-labeled each other by immunofluorescence assay. Taken together, our study provides a new chronic pain model by repeated intradermal bleomycin injection by activating TRPV1 and glial reaction-mediated neuroinflammation via TSLP/TSLPR/pSTAT5 signals.
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BACKGROUND: Distal forearm fractures were defined as distal radius fractures with concomitant distal ulna fractures, except ulna styloid fractures. Distal forearm fractures are common among geriatric populations, particularly those with osteoporosis. Conventionally, distal forearm fractures are reduced by a double incision approach; however, malreduction and instability of the distal radioulnar joint were not uncommon. We introduced a modified volar dual window approach to treat the distal forearm fracture and evaluate the functional outcomes and complications. METHODS: From January 2020 to June 2023, 13 patients with distal forearm fractures underwent open reduction by the modified dual window approach with locking plate fixation. After surgery, splints were applied for two weeks, and the patients underwent postoperative hand therapy for three months. The mean Quick Disabilities of the Arm, Shoulder, and Hand scores, range of motions, grip strength, postoperative radiographic parameters, and complications data were collected. RESULTS: The mean follow-up period was 12.1 months, and the mean age was 52.3 years. Average wrist flexion was 67°, extension 69°, pronation 81°, and supination 79°. Grip strength was 28.3 ± 11.5 kg, which was 88% of the uninjured opposite side. The Visual Analog Scale score during activities was recorded as 0.5 ± 0.9. The mean Quick Disabilities of the Arm, Shoulder, and Hand score was 14 ± 11.5. The postoperative radiographic parameters were as follows: radial height: 10.8 ± 1.7 mm, radial inclination: 22.6 ± 3.7°, volar tilting: 4.0 ± 3.9°, and ulnar variance: -0.4 ± 1.4 mm. All the patients achieved bone union at the final follow-up. Two patients underwent ulnar implant removal due to irritation symptoms. Neither infection, nor neurovascular injury, nor malreduction developed in these patients. CONCLUSIONS: The modified volar dual window approach can achieve good wrist function and distal forearm fracture reduction without increasing neurovascular or wound healing complications. This method is an alternative approach for distal forearm fracture, especially in comminuted distal ulna fracture or distal radioulnar joint incongruity.
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Background: Hematopoietic stem cell transplantation (HSCT) is one of the mainstream treatments for patients with hematologic malignancies. The matching status of human leukocyte antigen (HLA) between the donor and recipient is highly related to the outcomes of HSCT. Haploidentical HSCT (haplo-HSCT) has emerged as a type of HSCT for patients who cannot find a fully HLA-matched donor. In this study, we investigated whether the single nucleotide polymorphisms (SNPs) of the HLA-related genes and the genes encoding co-stimulatory molecules located on the non-HLA region are related to the outcomes of haplo-HSCT. Methods: The genomic DNAs of 24 patients and their respective donors were isolated from the peripheral blood obtained before performing haplo-HSCT. A total of 75 SNPs of the HLA-related genes (HCP5, NOTCH4, HLA-DOA, LTA, HSPA1L, BAG6, RING1, TRIM27, and HLA-DOB) and the genes located in the non-HLA genes involved in co-stimulatory signaling (CTLA4, TNFSF4, CD28, and PDCD1) were selected to explore their relationship with the outcomes after haplo-HSCT, including graft-versus-host disease, survival status, and relapse. Results: Our data revealed that specific donor or patient SNPs, including rs79327197 of the HLA-DOA gene, rs107822 and rs213210 of the RING1 gene, rs2523676 of the HCP5 gene, rs5742909 of the CTLA4 gene, rs5839828 and rs36084323 of the PDCD1 gene, and rs1234314 of the TNFSF4 gene, were significantly related to the development of adverse outcomes post-haplo-HSCT. Conclusions: These SNPs may play important roles in post-transplant immune response that can be considered during the selection of suitable donors.
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Background Alopecia areata (AA), a disorder of non-scarring hair loss with a variable relapsing and remitting course, is a common autoimmune disease in children. Although it often presents as several focal small patchy bald lesions, early onset AA can lead to a total loss of scalp hair, even body hairs, a severe subtype. Atopic diseases are common concurrent disorders in AA, especially among those with early onset severe type of hair loss. Whether atopic diseases increase the risk of AA in the paediatric population of Taiwan, remains unclear. Objective To identify if atopic diseases increase the risk of AA among pre-teens and teenagers in Taiwan. Methods From Taiwan National Health Insurance Database 2010, we used the claims data to clarify the risk of AA in pre-teens and teenagers with atopic diseases (atopic dermatitis, allergic conjunctivitis, asthma, allergic rhinitis and food allergy) as compared to the general population. Cox proportional hazards model yielded hazard ratios (HRs) to address the impact of atopic diseases, sex and age on AA risk after adjusting for covariates and subsequent stratified analyses. Results Overall, 21,070 children (10,535 patients with atopic diseases and 10,535 normal cohort) aged over nine years were recruited. During a follow-up of 15 years, 39 (0.37%) cases were identified to have AA in the atopic diseases group, while 11 (0.10%) had developed AA in the normal cohort. As compared with the normal population, the paediatric population with atopic diseases had a 9.66-fold higher risk of developing AA. The risk was greater for boys and increased with advanced age. In the atopic diseases group, pre-teens and teenagers with food allergies and Sjogren's syndrome were more likely to have AA. Limitations Only one ethnic group. Conclusion All atopic diseases enhanced the risk of developing AA in Taiwan pre-teens and teenagers. Children with atopic diseases should be monitored to look for the development of AA.
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Further improvements in perovskite solar cells require better control of ionic defects in the perovskite photoactive layer during the manufacturing stage and their usage1-5. Here we report a living passivation strategy using a hindered urea/thiocarbamate bond6-8 Lewis acid-base material (HUBLA), where dynamic covalent bonds with water and heat-activated characteristics can dynamically heal the perovskite to ensure device performance and stability. Upon exposure to moisture or heat, HUBLA generates new agents and further passivates defects in the perovskite. This passivation strategy achieved high-performance devices with a power conversion efficiency (PCE) of 25.1 per cent. HUBLA devices retained 94 per cent of their initial PCE for approximately 1,500 hours of ageing at 85 degrees Celsius in nitrogen and maintained 88 per cent of their initial PCE after 1,000 hours of ageing at 85 degrees Celsius and 30 per cent relative humidity in air.
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BACKGROUND: Acute lung injury (ALI) is a continuum of lung changes caused by multiple lung injuries, characterized by a syndrome of uncontrolled systemic inflammation that often leads to significant morbidity and death. Anti-inflammatory is one of its treatment methods, but there is no safe and available drug therapy. Syringic acid (SA) is a natural organic compound commonly found in a variety of plants, especially in certain woody plants and fruits. In modern pharmacological studies, SA has anti-inflammatory effects and therefore may be a potentially safe and available compound for the treatment of acute lung injury. PURPOSE: This study attempts to reveal the protective mechanism of SA against ALI by affecting the polarization of macrophages and the activation of NF-κB signaling pathway. Trying to find a safer and more effective drug therapy for clinical use. METHODS: We constructed the ALI model using C57BL/6 mice by intratracheal instillation of LPS (10 mg/kg). Histological analysis was performed with hematoxylin and eosin (H&E). The wet-dry ratio of the whole lung was measured to evaluate pulmonary edema. The effect of SA on macrophage M1-type was detected by flow cytometry. BCA protein quantification method was used to determine the total protein concentration in bronchoalveolar lavage fluid (BALF). The levels of Interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α in BALF were determined by the ELISA kits, and RT-qPCR was used to detect the expression levels of IL-6, IL-1ß and TNF-α mRNA of lung tissue. Western blot was used to detect the expression levels of iNOS and COX-2 and the phosphorylation of p65 and IκBα in the NF-κB pathway in lung tissue. In vitro experiments were conducted with RAW267.4 cell inflammation model induced by 100 ng/ml LPS and A549 cell inflammation model induced by 10 µg/ml LPS. The effects of SA on M1-type and M2-type macrophages of RAW267.4 macrophages induced by LPS were detected by flow cytometry. The toxicity of compound SA to A549 cells was detected by MTT method which to determine the safe dose of SA. The expressions of COX-2 and the phosphorylation of p65 and IκBα protein in NF-κB pathway were detected by Western blot. RESULTS: We found that the pre-treatment of SA significantly reduced the degree of lung injury, and the infiltration of neutrophils in the lung interstitium and alveolar space of the lung. The formation of transparent membrane in lung tissue and thickening of alveolar septum were significantly reduced compared with the model group, and the wet-dry ratio of the lung was also reduced. ELISA and RT-qPCR results showed that SA could significantly inhibit the production of IL-6, IL-1ß, TNF-α. At the same time, SA could significantly inhibit the expression of iNOS and COX-2 proteins, and could inhibit the phosphorylation of p65 and IκBα proteins. in a dose-dependent manner. In vitro experiments, we found that flow cytometry showed that SA could significantly inhibit the polarization of macrophages from M0 type macrophages to M1-type macrophages, while SA could promote the polarization of M1-type macrophages to M2-type macrophages. The results of MTT assay showed that SA had no obvious cytotoxicity to A549 cells when the concentration was not higher than 80 µM, while LPS could promote the proliferation of A549 cells. In the study of anti-inflammatory effect, SA can significantly inhibit the expression of COX-2 and the phosphorylation of p65 and IκBα proteins in LPS-induced A549 cells. CONCLUSION: SA has possessed a crucial anti-ALI role in LPS-induced mice. The mechanism was elucidated, suggesting that the inhibition of macrophage polarization to M1-type and the promotion of macrophage polarization to M2-type, as well as the inhibition of NF-κB pathway by SA may be the reasons for its anti-ALI. This finding provides important molecular evidence for the further application of SA in the clinical treatment of ALI.
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Lesión Pulmonar Aguda , Ácido Gálico , Lipopolisacáridos , Macrófagos , Ratones Endogámicos C57BL , FN-kappa B , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Ratones , Ácido Gálico/farmacología , Ácido Gálico/análogos & derivados , Macrófagos/efectos de los fármacos , FN-kappa B/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Pulmón/efectos de los fármacos , Pulmón/patología , Células RAW 264.7 , Interleucina-1beta/metabolismo , Líquido del Lavado Bronquioalveolar , Óxido Nítrico Sintasa de Tipo II/metabolismo , Interleucina-6/metabolismoRESUMEN
Evaluating the quality of herbal medicine based on the content and activity of its main components is highly beneficial. Developing an eco-friendly determination method has significant application potential. In this study, we propose a new method to simultaneously predict the total flavonoid content (TFC), xanthine oxidase inhibitory (XO) activity, and antioxidant activity (AA) of Prunus mume using near-infrared spectroscopy (NIR). Using the sodium nitrite-aluminum nitrate-sodium hydroxide colorimetric method, uric acid colorimetric method, and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) free radical scavenging activity as reference methods, we analyzed TFC, XO, and AA in 90â¯P. mume samples collected from different locations in China. The solid samples were subjected to NIR. By employing spectral preprocessing and optimizing spectral bands, we established a rapid prediction model for TFC, XO, and AA using partial least squares regression (PLS). To improve the model's performance and eliminate irrelevant variables, competitive adaptive reweighted sampling (CARS) was used to calculate the pretreated full spectrum. Evaluation model indicators included the root mean square error of cross-validation (RMSECV) and determination coefficient (R2) values. The TFC, XO, and AA model, combining optimal spectral preprocessing and spectral bands, had RMSECV values of 0.139, 0.117, and 0.121, with RCV2 values exceeding 0.92. The root mean square error of prediction (RMSEP) for the TFC, XO, and AA model on the prediction set was 0.301, 0.213, and 0.149, with determination coefficient (RP2) values of 0.915, 0.933, and 0.926. The results showed a strong correlation between NIR with TFC, XO, and AA in P. mume. Therefore, the established model was effective, suitable for the rapid quantification of TFC, XO, and AA. The prediction method is simple and rapid, and can be extended to the study of medicinal plant content and activity.
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Antioxidantes , Flavonoides , Prunus , Espectroscopía Infrarroja Corta , Xantina Oxidasa , Espectroscopía Infrarroja Corta/métodos , Flavonoides/análisis , Prunus/química , Xantina Oxidasa/antagonistas & inhibidores , Antioxidantes/análisis , Análisis de los Mínimos Cuadrados , Inhibidores Enzimáticos/análisis , Inhibidores Enzimáticos/farmacología , ChinaRESUMEN
Mantle cell lymphoma (MCL) is an incurable and aggressive subtype of non-Hodgkin B-cell lymphoma. Increased lipid uptake, storage, and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. However, no data has been explored for the roles of lipid metabolism reprogramming in MCL. Here, we identified aberrant lipid metabolism reprogramming and PRMT5 as a key regulator of cholesterol and fatty acid metabolism reprogramming in MCL patients. High PRMT5 expression predicts adverse outcome prognosis in 105 patients with MCL and GEO database (GSE93291). PRMT5 deficiency resulted in proliferation defects and cell death by CRISPR/Cas9 editing. Moreover, PRMT5 inhibitors including SH3765 and EPZ015666 worked through blocking SREBP1/2 and FASN expression in MCL. Furthermore, PRMT5 was significantly associated with MYC expression in 105 MCL samples and the GEO database (GSE93291). CRISPR MYC knockout indicated PRMT5 can promote MCL outgrowth by inducing SREBP1/2 and FASN expression through the MYC pathway.
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Proliferación Celular , Acido Graso Sintasa Tipo I , Metabolismo de los Lípidos , Linfoma de Células del Manto , Proteína-Arginina N-Metiltransferasas , Proteínas Proto-Oncogénicas c-myc , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/metabolismo , Linfoma de Células del Manto/patología , Humanos , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Acido Graso Sintasa Tipo I/metabolismo , Acido Graso Sintasa Tipo I/genética , Línea Celular Tumoral , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Regulación Neoplásica de la Expresión Génica , Animales , Ratones , Masculino , Pronóstico , Femenino , Colesterol/metabolismo , Sistemas CRISPR-Cas , Reprogramación MetabólicaAsunto(s)
Monitoreo Intraoperatorio , Tiroidectomía , Parálisis de los Pliegues Vocales , Humanos , Parálisis de los Pliegues Vocales/prevención & control , Parálisis de los Pliegues Vocales/etiología , Tiroidectomía/efectos adversos , Tiroidectomía/métodos , Monitoreo Intraoperatorio/métodos , Endoscopía/métodos , Traumatismos del Nervio Laríngeo Recurrente/prevención & control , Traumatismos del Nervio Laríngeo Recurrente/etiología , Nervio Laríngeo Recurrente , Glándula Tiroides/cirugía , Femenino , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The potential of biodegradable magnesium (Mg) skin staple has recently garnered widespread attention due to their biodegradability and biocompatibility rather than traditional stainless steel staples, the most commonly used in current clinical practice. The aim of this study is to evaluate the safety and mechanical properties of a novel biodegradable Mg skin staple. METHODS: A prototype of Mg skin staple was designed using a novel ZK60 Mg alloy. The mechanical properties of the staple were evaluated using a universal testing machine. The cytotoxicity of the staple was examined in vitro and the efficacy of the staple in wound closure was assessed in New Zealand rabbits for one and three weeks, respectively. RESULTS: The tensile strength of this Mg alloy is 258.4 MPa with 6.9% elongation. The treatment of HaCaT and L929 cells with the staple extract resulted in over 95% cell viability, indicating no cytotoxicity. In vivo, no tissue irritation was observed. No difference was found in wound healing between the Mg skin staple and the stainless steel staple after one and three weeks in the cutting wound on the back of rabbits. Some Mg skin staples spontaneously dislodged from the skin within three weeks, while others were easily removed. CONCLUSION: Our results confirm the safety, biocompatibility, and functionality of the novel Mg skin staple in wound closure. The efficacy of the staple in wound closure was demonstrated to be as effectively as conventional staples, with the added benefit of decreased long-term retention of skin staples in the wounds.