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1.
Sci Rep ; 14(1): 15136, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956153

RESUMO

The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.


Assuntos
Medo , Isoflurano , Transtornos da Memória , Zona Incerta , Isoflurano/farmacologia , Isoflurano/efeitos adversos , Animais , Medo/efeitos dos fármacos , Camundongos , Transtornos da Memória/induzido quimicamente , Zona Incerta/efeitos dos fármacos , Masculino , Anestésicos Inalatórios/efeitos adversos , Anestésicos Inalatórios/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Camundongos Endogâmicos C57BL , Dexmedetomidina/farmacologia , Feminino , Proteínas Proto-Oncogênicas c-fos/metabolismo , Memória/efeitos dos fármacos
2.
Int J Hyperthermia ; 41(1): 2370969, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38945548

RESUMO

OBJECTIVE: To analyze and summarize the types, incidence rates and relevant influencing factors of adverse events (AEs) after high-intensity focused ultrasound ablation of gynecological diseases and provide reference and basis for handling such events in clinical practice. METHOD: We searched PubMed, Cochrane Library, Web of Science and Embase databases to retrieve all literature since its establishment until February 2024. We evaluated the quality of included literature and publication bias and conducted a meta-analysis of single group rates for various AEs using Stata 17.0. RESULTS: This systematic review finally included 41 articles. We summarized 34 kinds of AEs in 7 aspects and conducted a single group rate meta-analysis and sub-group analysis of 16 kinds of AEs. Among the common AEs of High-Intensity Focused Ultrasound (HIFU), the incidence of lower abdominal pain/pelvic pain is 36.1% (95% CI: 24.3%∼48.8%), vaginal bleeding is 20.6% (95% CI: 13.9%∼28.0%), vaginal discharge is 14.0% (95% CI: 9.6%∼19.1%), myoma discharge is 24% (95% CI: 14.6%∼34.8%), buttock pain is 10.8% (95% CI: 6.0%∼16.5%) and sacral pain is 10% (95% CI: 8.8%∼11.2%). Serious complications include uterine rupture, necrotic tissue obstruction requiring surgical intervention, third degree skin burns and persistent lower limb pain or movement disorders. CONCLUSION: The common AEs after HIFU surgery are mostly mild and controllable, and the incidence of serious complications is extremely low. By reasonable prevention and active intervention, these events can be further reduced, making it a safe and effective treatment method. It is a good choice for patients who crave noninvasive treatment or have other surgical contraindications.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Humanos , Feminino , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Doenças dos Genitais Femininos
3.
Angew Chem Int Ed Engl ; : e202409000, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866731

RESUMO

M-N-C single-atom catalysts (SACs) are promising electrode materials for many electro-reduction reactions. However, their stability is far from practical applications, and their deactivation mechanism has been rarely investigated. Herein, we demonstrate the structural degradation of M-N-C (M=Co, Ni, and Fe) at industrial-grade current density for long-term electro-reduction. Both M-N and N-C bonds are broken, resulting in the gradual hydrogenation and dissolution of N in the form of ammonia. The residual M is finally converted to M-containing core-shell nanoparticles after sequential dissolution, redeposition, and electro-reduction. The destruction of the M-N-C structure and the formation of nanoparticles greatly affect the electrocatalytic performance. Our work highlights the structural degradation and deactivation mechanism of M-N-C-type SACs under strong reductive conditions and provides useful information for inspiring researchers to develop new strategies to improve the electrocatalytic stability of similar types of materials.

4.
Eur Radiol ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842691
5.
J Vis Exp ; (207)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38767359

RESUMO

Chronic pelvic pain caused by the sequelae of inflammatory pelvic disease is a common clinical condition of pelvic pain in women. At present, the main challenges in its treatment are the limited effectiveness of pain relief and the frequent recurrence of symptoms, which significantly impact patients' quality of life and impose a considerable psychological burden on them. It is a clinically challenging disease. After summarizing years of treatment experience, the author's team discovered that acupoint catgut embedding demonstrated notable clinical efficacy in managing chronic pelvic pain stemming from pelvic inflammatory disease sequelae. Compared to existing Western medicine treatment methods, acupoint catgut embedding offers advantages such as a good analgesic effect, lower recurrence rate, economic benefits, and a relatively straightforward procedure. This article provides a comprehensive guide on embedding absorbable catgut into patients' acupoints for the treatment of chronic pelvic pain in females resulting from the sequelae of pelvic inflammatory disease.


Assuntos
Pontos de Acupuntura , Categute , Dor Crônica , Doença Inflamatória Pélvica , Dor Pélvica , Humanos , Dor Pélvica/terapia , Dor Pélvica/etiologia , Feminino , Dor Crônica/terapia , Dor Crônica/etiologia , Doença Inflamatória Pélvica/complicações , Doença Inflamatória Pélvica/terapia , Terapia por Acupuntura/métodos
6.
Microorganisms ; 12(5)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38792808

RESUMO

Enzyme-production microorganisms typically occupy a dominant position in composting, where cellulolytic microorganisms actively engage in the breakdown of lignocellulose. Exploring strains with high yields of cellulose-degrading enzymes holds substantial significance for the industrial production of related enzymes and the advancement of clean bioenergy. This study was inclined to screen cellulolytic bacteria, conduct genome analysis, mine cellulase-related genes, and optimize cellulase production. The potential carboxymethylcellulose-hydrolyzing bacterial strain Z2.6 was isolated from the maturation phase of pig manure-based compost with algae residuals as the feedstock and identified as Bacillus velezensis. In the draft genome of strain Z2.6, 31 related cellulolytic genes were annotated by the CAZy database, and further validation by cloning documented the existence of an endo-1,4-ß-D-glucanase (EC 3.2.1.4) belonging to the GH5 family and a ß-glucosidase (EC 3.2.1.21) belonging to the GH1 family, which are predominant types of cellulases. Through the exploration of ten factors in fermentation medium with Plackett-Burman and Box-Behnken design methodologies, maximum cellulase activity was predicted to reach 2.98 U/mL theoretically. The optimal conditions achieving this response were determined as 1.09% CMC-Na, 2.30% salinity, and 1.23% tryptone. Validation under these specified conditions yielded a cellulose activity of 3.02 U/mL, demonstrating a 3.43-fold degree of optimization. In conclusion, this comprehensive study underscored the significant capabilities of strain Z2.6 in lignocellulolytic saccharification and its potentialities for future in-depth exploration in biomass conversion.

7.
BMC Med ; 22(1): 147, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38561764

RESUMO

BACKGROUND: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. METHODS: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. RESULTS: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. CONCLUSIONS: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/genética , Estudos Prospectivos , Inteligência Artificial , Ultrassonografia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Estudos Retrospectivos
8.
Eur J Pharmacol ; 974: 176538, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38552940

RESUMO

Chemotherapy is one of the primary and indispensable intervention against cancers though it is always accompanied by severe side effects especially cachexia. Cachexia is a fatal metabolic disorder syndrome, mainly characterized by muscle loss. Oxidative stress is the key factor that trigger cachectic muscle loss by inducing imbalance in protein metabolism and apoptosis. Here, we showed an oral compound (Z526) exhibited potent alleviating effects on C2C12 myotube atrophy induced by various chemotherapeutic agents in vitro as well as mice muscle loss and impaired grip force induced by oxaliplatin in vivo. Furthermore, Z526 also could ameliorate C2C12 myotube atrophy induced by the combination of chemotherapeutic agents with conditioned medium of various tumor cells in vitro as well as mice muscle atrophy of C26 tumor-bearing mice treated with oxaliplatin. The pharmacological effects of Z526 were based on its potency in reducing oxidative stress in cachectic myocytes and muscle tissues, which inhibited the activation of NF-κB and STAT3 to decrease Atrogin-1-mediated protein degradation, activated the AKT/mTOR signaling pathway to promote protein synthesis, regulated Bcl-2/BAX ratio to reduce Caspase-3-triggered apoptosis. Our work suggested Z526 to be an optional strategy for ameliorating cachexia muscle atrophy in the multimodality treatment of cancers.


Assuntos
Antineoplásicos , Apoptose , Caquexia , Atrofia Muscular , Estresse Oxidativo , Animais , Caquexia/tratamento farmacológico , Caquexia/patologia , Caquexia/induzido quimicamente , Caquexia/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/efeitos adversos , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Masculino , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , NF-kappa B/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Linhagem Celular Tumoral , Fator de Transcrição STAT3/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Endogâmicos BALB C , Linhagem Celular , Proteínas Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia
9.
Oral Health Prev Dent ; 22: 139-144, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483398

RESUMO

PURPOSE: To examine the clinical efficacy of a chlorhexidine gargle combined with recombinant bovine basic fibroblast growth factor (rb-bFGF) gel in the treatment of recurrent oral ulcers and its effects on inflammatory factors, immune function, and recurrence rate. MATERIALS AND METHODS: Ninety-six patients with recurrent oral ulcers were randomly assigned to two groups: experimental (treatment with chlorhexidine gargle plus rb-bFGF gel) and control (treatment with chlorhexidine gargle alone) (n = 48 cases). The therapeutic efficacy, clinical improvement of symptoms, and recurrence rate within 3 months were compared between the two groups. Serum inflammatory factor and immune factor levels of patients in the two groups were measured before and after treatment. RESULTS: A statistically significantly higher total effective rate was found in patients of the experimental group (95.83%) versus the control group (81.25%) (p < 0.05). The time to onset of pain relief was shortened, the duration of pain relief was prolonged, and VAS scores for pain level were lower in the experimental than the control group (p < 0.05). Among patients in the experimental group, the number of oral ulcers and ulcer area decreased, and faster onset of pain relief and time until normal eating improved in comparison to the control group (p < 0.05). Reduced levels of IL-2, IL-6, IL-8, and TNF-α were observed in the experimental vs the control group (p < 0.05). Elevated levels of CD3+, CD4+, and NKT and reduced levels of CD8+ were found in the experimental group compared to the control group (p < 0.05). The ulcer recurrence rate of patients in the experimental group (8.33%) was notably lower in comparison to the control group (29.17%). CONCLUSION: Chlorhexidine gargle plus rb-bFGF gel can improve the clinical outcome of patients with recurrent oral ulcers. It can reduce the levels of inflammatory factors, improve immune function, and reduce the recurrence rate.


Assuntos
Clorexidina , Úlceras Orais , Humanos , Animais , Bovinos , Clorexidina/uso terapêutico , Fator 2 de Crescimento de Fibroblastos , Úlcera , Antissépticos Bucais , Resultado do Tratamento , Dor
10.
Mol Psychiatry ; 29(5): 1550-1566, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38361128

RESUMO

Major depressive disorder (MDD) is characterized by diverse debilitating symptoms that include loss of motivation and anhedonia. If multiple medications, psychotherapy, and electroconvulsive therapy fail in some patients with MDD, their condition is then termed treatment-resistant depression (TRD). MDD can be associated with abnormalities in the reward-system-dopaminergic mesolimbic pathway, in which the nucleus accumbens (NAc) and ventral tegmental area (VTA) play major roles. Deep brain stimulation (DBS) applied to the NAc alleviates the depressive symptoms of MDD. However, the mechanism underlying the effects of this DBS has remained elusive. In this study, using the chronic unpredictable mild stress (CUMS) mouse model, we investigated the behavioral and neurobiological effects of NAc-DBS on the multidimensional depression-like phenotypes induced by CUMS by integrating behavioral, in vivo microdialysis coupled with high-performance liquid chromatography-electrochemical detector (HPLC-ECD), calcium imaging, pharmacological, and genetic manipulation methods in freely moving mice. We found that long-term and repeated, but not single, NAc-DBS induced robust antidepressant responses in CUMS mice. Moreover, even a single trial NAc-DBS led to the elevation of the γ-aminobutyric acid (GABA) neurotransmitter, accompanied by the increase in dopamine (DA) neuron activity in the VTA. Both the inhibition of the GABAA receptor activity and knockdown of the GABAA-α1 gene in VTA-GABA neurons blocked the antidepressant effect of NAc-DBS in CUMS mice. Our results showed that NAc-DBS could disinhibit VTA-DA neurons by regulating the level of GABA and the activity of VTA-GABA in the VTA and could finally correct the depression-like behaviors in the CUMS mouse model.


Assuntos
Estimulação Encefálica Profunda , Depressão , Transtorno Depressivo Maior , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Núcleo Accumbens , Estresse Psicológico , Área Tegmentar Ventral , Animais , Área Tegmentar Ventral/metabolismo , Núcleo Accumbens/metabolismo , Neurônios Dopaminérgicos/metabolismo , Camundongos , Masculino , Estimulação Encefálica Profunda/métodos , Depressão/terapia , Depressão/metabolismo , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/metabolismo , Estresse Psicológico/terapia , Estresse Psicológico/metabolismo , Camundongos Endogâmicos C57BL , Dopamina/metabolismo , Comportamento Animal/fisiologia , Ácido gama-Aminobutírico/metabolismo
11.
Food Chem ; 446: 138810, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38402769

RESUMO

The effect of a high internal phase emulsion (HIPE) on three-dimensional-printed surimi gel inks was studied. Increasing the concentration of collagen peptide decreased the particle size of HIPE droplets and improved the viscoelasticity and stability. For example, when the collagen peptide concentration was 5 wt%, the viscoelasticity of the HIPE was high, as indicated by the presence of small and uniform particles, which formed a monolayer in the outer layer of the oil droplets to form stable a HIPE. A HIPE was used as the filling material to fill the surimi gel network, which reduced the porosity of the network. Surimi protein and peptides have dual emulsifying effects on the stabilization of oil. After adding the emulsion, the texture, gel properties and rheological properties of the surimi were reduced, and its printing adaptability was improved. This study provides new ideas for the production of surimi and its application in 3D printing.


Assuntos
Óleos de Peixe , Tinta , Emulsões/química , Géis/química , Peptídeos , Impressão Tridimensional , Colágeno
12.
Sleep Breath ; 28(3): 1105-1118, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38170376

RESUMO

OBJECTIVES: Heart rate variability (HRV) is becoming more prevalent as a measurable parameter in wearable sleep-monitoring devices, which are simple and effective instruments for illness evaluation. Currently, most studies on investigating OSA severity and HRV have measured heart rates during wakefulness or sleep. Therefore, the objective of this study was to investigate the circadian rhythm of HRV in male patients with OSA and its value for the estimation of OSA severity using group-based trajectory modeling. METHODS: Patients with complaints of snoring were enrolled from the Sleep Center of Shandong Qianfoshan Hospital. Patients were divided into 3 groups according to apnea hypopnea index (AHI in events/h), as follows: (<15, 15≤AHI<30, and ≥30). HRV parameters were calculated using 24 h Holter monitoring, which included time-domain and frequency-domain indices. Circadian differences in the standard deviation of normal to normal (SDNN) were evaluated for OSA severity using analysis of variance, trajectory analysis, and multinomial logistic regression. RESULTS: A total of 228 patients were enrolled, 47 with mild OSA, 48 moderate, and 133 severe. Patients with severe OSA exhibited reduced triangular index and higher very low frequency than those in the other groups. Circadian HRV showed that nocturnal SDNN was considerably higher than daytime SDNN in patients with severe OSA. The difference among the OSA groups was significant at 23, 24, 2, and 3 o'clock sharp between the severe and moderate OSA groups (all P<0.05). The heterogeneity of circadian HRV trajectories in OSA was strongly associated with OSA severity, including sleep structure and hypoxia-related parameters. Among the low-to-low, low-to-high, high-to-low, and high-to-high groups, OSA severity in the low-to-high group was the most severe, especially compared with the low-to-low and high-to-low SDNN groups, respectively. CONCLUSIONS: Circadian HRV in patients with OSA emerged as low daytime and high nocturnal in SDNN, particularly in men with severe OSA. The heterogeneity of circadian HRV revealed that trajectories with low daytime and significantly high nighttime were more strongly associated with severe OSA. Thus, circadian HRV trajectories may be useful to identify the severity of OSA.


Assuntos
Ritmo Circadiano , Frequência Cardíaca , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/diagnóstico , Masculino , Frequência Cardíaca/fisiologia , Ritmo Circadiano/fisiologia , Adulto , Pessoa de Meia-Idade , Polissonografia , Eletrocardiografia Ambulatorial
13.
AJNR Am J Neuroradiol ; 45(2): 155-162, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38238091

RESUMO

BACKGROUND AND PURPOSE: Collateral circulation plays an important role in steno-occlusive internal carotid artery disease (ICAD) to reduce the risk of stroke. We aimed to investigate the utility of planning-free random vessel-encoded arterial spin-labeling (rVE-ASL) in assessing collateral flows in patients with ICAD. MATERIALS AND METHODS: Forty patients with ICAD were prospectively recruited. The presence and extent of collateral flow were assessed and compared between rVE-ASL and DSA by using Contingency (C) and Cramer V (V) coefficients. The differences in flow territory alterations stratified by stenosis ratio and symptoms, respectively, were compared between symptomatic (n = 19) and asymptomatic (n = 21) patients by using the Fisher exact test. RESULTS: Good agreement was observed between rVE-ASL and DSA in assessing collateral flow (C = 0.762, V = 0.833, both P < .001). Patients with ICA stenosis of ≥90% were more likely to have flow alterations (P < .001). Symptomatic patients showed a higher prevalence of flow alterations in the territory of the MCA on the same side of ICAD (63.2%), compared with asymptomatic patients (23.8%, P = .012), while the flow alterations in the territory of anterior cerebral artery did not differ (P = .442). The collateral flow to MCA territory was developed primarily from the contralateral internal carotid artery (70.6%) and vertebrobasilar artery to a lesser extent (47.1%). CONCLUSIONS: rVE-ASL provides comparable information with DSA on the assessment of collateral flow. The flow alterations in the MCA territory may be attributed to symptomatic ICAD.


Assuntos
Doenças das Artérias Carótidas , Estenose das Carótidas , Humanos , Estenose das Carótidas/diagnóstico por imagem , Constrição Patológica , Marcadores de Spin , Angiografia Digital , Artéria Carótida Interna/diagnóstico por imagem , Circulação Colateral , Circulação Cerebrovascular , Angiografia por Ressonância Magnética
14.
Oncogene ; 43(9): 682-692, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38216672

RESUMO

Hepatocellular carcinoma (HCC) stands as the fifth most prevalent malignant tumor on a global scale and presents as the second leading cause of cancer-related mortality. DNA damage-based radiotherapy (RT) plays a pivotal role in the treatment of HCC. Nevertheless, radioresistance remains a primary factor contributing to the failure of radiation therapy in HCC patients. In this study, we investigated the functional role of transketolase (TKT) in the repair of DNA double-strand breaks (DSBs) in HCC. Our research unveiled that TKT is involved in DSB repair, and its depletion significantly reduces both non-homologous end joining (NHEJ) and homologous recombination (HR)-mediated DSB repair. Mechanistically, TKT interacts with PARP1 in a DNA damage-dependent manner. Furthermore, TKT undergoes PARylation by PARP1, resulting in the inhibition of its enzymatic activity, and TKT can enhance the auto-PARylation of PARP1 in response to DSBs in HCC. The depletion of TKT effectively mitigates the radioresistance of HCC, both in vitro and in mouse xenograft models. Moreover, high TKT expression confers resistance of RT in clinical HCC patients, establishing TKT as a marker for assessing the response of HCC patients who received cancer RT. In summary, our findings reveal a novel mechanism by which TKT contributes to the radioresistance of HCC. Overall, we identify the TKT-PARP1 axis as a promising potential therapeutic target for improving RT outcomes in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Quebras de DNA de Cadeia Dupla , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Transcetolase/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Reparo do DNA , DNA , Reparo do DNA por Junção de Extremidades , Reparo de DNA por Recombinação , Poli(ADP-Ribose) Polimerase-1/genética
15.
Pathol Res Pract ; 254: 155152, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38277742

RESUMO

OBJECTIVE: The aim of this study is to delineate the molecular classification features within Chinese endometrial cancer (EC) patients and to evaluate the concurrence between two widely employed methods for diagnosing EC molecular subtypes. METHODS: This retrospective observational cohort study encompassed 479 cases of EC for analysis. Utilizing next-generation sequencing (NGS) panels targeting POLE, TP53, and microsatellite instability (MSI) status, four subtypes [POLE ultramutated (POLE mut), MMR-deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP)] were classified. Immunohistochemistry (IHC) was employed to ascertain the expression of p53 and MMR proteins. RESULTS: Among the 479 patients, the distribution of EC subtypes was as follows: 28 (5.85%) POLE mut, 67 (13.99%) MMRd, 60 (12.53%) p53abn, and 324 (67.64%) NSMP. When compared to published findings on EC subtypes in the Caucasian population, our real-world data on Chinese ECs revealed a notably higher proportion of NSMP/CNL (copy number low). The evaluation of MSI/MMR status through NGS-based and IHC-based methods displayed substantial concordance (Kappa = 0.91). Slight discordance between the two techniques in identifying p53 abnormalities (Kappa = 0.83) might stem from TP53 truncating mutations, cytoplasmic p53 expression, null TP53 mutants, and well-documented challenges in interpreting p53 IHC. CONCLUSIONS: Chinese ECs exhibit distinctive molecular attributes. For accurate molecular subtyping of Chinese ECs, additional molecular markers that align with the Chinese population's characteristics should be incorporated into existing classifiers. The study's outcomes underscore a strong agreement between NGS and IHC in TP53/p53 detection and MSI assessment.


Assuntos
Neoplasias do Endométrio , Proteína Supressora de Tumor p53 , Feminino , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/genética , Estudos Retrospectivos , DNA Polimerase II/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Mutação , Instabilidade de Microssatélites , China
16.
BMC Neurol ; 24(1): 5, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166773

RESUMO

BACKGROUND: Spinal subarachnoid hematoma (SSH) is a known but rare entity that can cause cauda equina compression. The occurrence of SSH associated with aneurysmal subarachnoid hemorrhage has rarely been described in the literature. CASE PRESENTATION: A 56-year-old woman presented with subarachnoid hemorrhage secondary to a ruptured middle cerebral artery aneurysm and was managed with coiling embolization without stent assistance. There was no history of either lumbar puncture or the use of anticoagulants. The patient developed severe lumbago radiating to bilateral legs nine days after the procedure. Subsequent magnetic resonance imaging demonstrated a SSH extending from L5 to S2 and wrapping around the cauda equina. The patient was treated with intravenous methylprednisolone (250 mg/day) for four consecutive days, followed by a taper of oral prednisolone (20 mg/day) until complete recovery. Magnetic resonance imaging at one month follow-up revealed complete resolution of the SSH. CONCLUSIONS: Here, we report a case of acute cauda equina syndrome caused by a SSH after aneurysmal subarachnoid hemorrhage, which will facilitate timely intervention of patients with this disorder.


Assuntos
Síndrome da Cauda Equina , Cauda Equina , Hemorragia Subaracnóidea , Feminino , Humanos , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Síndrome da Cauda Equina/complicações , Síndrome da Cauda Equina/diagnóstico por imagem , Hematoma/etiologia , Espaço Subaracnóideo , Imageamento por Ressonância Magnética
17.
Sleep Breath ; 28(1): 173-181, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37453997

RESUMO

PURPOSE: The purpose of the study was to evaluate the quantitative relationship between Oxygen Desaturation Index (ODI) and sleep structure of obstructive sleep apnea (OSA) and cardiac remodeling. METHODS: In this study, patients were enrolled from January 2015 to October 2022, and were divided into 3 groups according to AHI: patients with AHI < 15, patients with 15 ≤ AHI < 30, and 260 patients with AHI ≥ 30. Stratified linear regression was used to analyze independent risk factors for cardiac remodeling in OSA. RESULTS: A total of 479 patients were enrolled. We found that compared with AHI < 15 group (n = 120), the group with AHI > 30 (n = 260) had increased left atrial anteroposterior diameter, left ventricular end-diastolic internal diameter, left ventricular posterior wall thickness, right ventricular anteroposterior diameter, and interventricular septal thickness (P < 0.05). The group with 15 ≤ AHI ≤ 30 (n = 99) had increased left atrial anteroposterior diameter (P < 0.05). Multivariate linear regression revealed that N2 sleep was an independent risk factor for left ventricular posterior wall thickness, with positive correlation (p < 0.05). N3 sleep was an independent risk factor for transverse right atrial diameter and right ventricular anteroposterior diameter, with negative correlation (P < 0.05). ODI was an independent risk factor for interventricular septal thickness, with positive correlation (P < 0.05). The arousal index was an independent risk factor for increased left atrial anteroposterior diameter, with positive correlation (P < 0.05). CONCLUSIONS: Increased ODI is an independent risk factor for interventricular septal thickness, while decreased slow wave sleep is an independent risk factor for right heart remodeling in OSA.


Assuntos
Oxigênio , Apneia Obstrutiva do Sono , Humanos , Remodelação Ventricular , Polissonografia , Sono
18.
J Comput Assist Tomogr ; 48(2): 298-302, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37757843

RESUMO

OBJECTIVE: This study aimed to provide an alternative approach for quantifying the volume of the ischemic core (IC) if truncation of computed tomography perfusion (CTP) occurs in clinical practice. METHODS: Baseline CTP and follow-up diffusion-weighted imaging (DWI) data from 88 patients with stroke were retrospectively collected. CTP source images (CTPSI) from the unenhanced phase to the peak arterial phase (CTPSI-A) or the peak venous phase (CTPSI-V) were collected to simulate the truncation of CTP in the arterial or venous phases, respectively. The volume of IC on CTPSI-A (V CTPSI-A ) or CTPSI-V (V CTPSI-V ) was defined as the volume of the brain tissue with >65% reduction in attenuation compared with that of the normal tissue. The volume of IC on the baseline CTP (V CTP ) was defined as a relative cerebral blood flow of <30% of that in the normal tissue. The volume of the posttreatment infarct on the follow-up DWI (V DWI ) image was manually delineated and calculated. One-way analysis of variance, Bland-Altman plots, and Spearman correlation analyses were used for the statistical analysis. RESULTS: V CTPSI-A was significantly higher than V DWI ( P < 0.001); however, no significant difference was observed between V CTP and V DWI ( P = 0.073) or between V CTPSI-V and V DWI ( P > 0.999). The mean differences between V DWI and V CTPSI-V , V DWI and V CTP , and V DWI and V CTPSI-A were 1.70 mL (limits of agreement [LoA], -56.40 to 59.70), 8.30 mL (LoA, -40.70 to 57.30), and -68.10 mL (LoA, -180.90 to 44.70), respectively. Significant correlations were observed between V DWI and V CTP ( r = 0.68, P < 0.001) and between V DWI and V CTPSI-V ( r = 0.39, P < 0.001); however, no significant correlation was observed between V DWI and V CTPSI-A ( r = 0.20, P = 0.068). CONCLUSIONS: V CTPSI-V may be a promising method for quantifying the volume of the IC if truncation of CTP occurs.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Perfusão , Isquemia Encefálica/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia
20.
Cancers (Basel) ; 15(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38067374

RESUMO

A total of 457 patients, including 241 HR+/HER2- patients, 134 HER2+ patients, and 82 TN patients, were studied. The percentage of TILs in the stroma adjacent to the tumor cells was assessed using a 10% cutoff. The low TIL percentages were 82% in the HR+ patients, 63% in the HER2+ patients, and 56% in the TN patients (p < 0.001). MRI features such as morphology as mass or non-mass enhancement (NME), shape, margin, internal enhancement, presence of peritumoral edema, and the DCE kinetic pattern were assessed. Tumor sizes were smaller in the HR+/HER2- group (p < 0.001); HER2+ was more likely to present as NME (p = 0.031); homogeneous enhancement was mostly seen in HR+ (p < 0.001); and the peritumoral edema was present in 45% HR+, 71% HER2+, and 80% TN (p < 0.001). In each subtype, the MR features between the high- vs. low-TIL groups were compared. In HR+/HER2-, peritumoral edema was more likely to be present in those with high TILs (70%) than in those with low TILs (40%, p < 0.001). In TN, those with high TILs were more likely to present a regular shape (33%) than those with low TILs (13%, p = 0.029) and more likely to present the circumscribed margin (19%) than those with low TILs (2%, p = 0.009).

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