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1.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1870(1): 159566, 2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39349136

RESUMEN

The translocator protein, TSPO, has been implicated in a wide range of cellular processes exerted from its position in the outer mitochondrial membrane from where it influences lipid metabolism and mitochondrial oxidative activity. Understanding how this protein regulates a profusion of processes requires further elucidation and to that end we have examined lipid metabolism and used an RNAseq strategy to compare transcript abundance in wildtype and Tspo knockout (KO) mouse liver. The levels of cholesterol, triglyceride and phospholipid were significantly elevated in the KO mouse liver. The expression of cholesterol homeostasis genes was markedly downregulated. Determination of the differential expression revealed that many genes were either up- or downregulated in the KO animals. However, a striking observation within the results was a decrease of transcripts for protein degradation proteins in KO animals while protease inhibitors were enriched. When the entire abundance data-set was analysed with CEMiTool, and revealed a module of proteins that were under-represented in the KO animals. These could subsequently be formed into a network comprising three interlinked clusters at the centre of which were proteins of cytoplasmic ribosomes with gene ontology terms suggesting impairment to translation. The largest cluster was dominated by proteins of lipid metabolism but also contained disparate systems of iron metabolism and behaviour. The third cluster was dominated by proteins of the electron transport chain and oxidative phosphorylation. These findings suggest that TSPO contributes to lipid metabolism, detoxification of active oxygen species and oxidative phosphorylation, and regulates mitochondrial retrograde signalling.

3.
Int Immunopharmacol ; 142(Pt A): 113043, 2024 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-39216120

RESUMEN

OBJECTIVE: Limited research has focused on the role of dihydrouridine synthases (DUS) family members in human tumors. Our previous findings indicated an impact of dihydrouridine synthase 4 like (DUS4L) on cell proliferation and apoptosis in lung adenocarcinoma (LUAD) A549 cell, yet its broader functions and regulatory mechanisms in LUAD remain elusive. METHODS: Using a LUAD tissue microarray and immunohistochemical (IHC) staining, we validated variations in DUS4L protein expression levels among LUAD patients and assessed its clinical significance. Additional experiments using short hairpin RNA (shRNA) against DUS4L (sh-DUS4L-2), LUAD cell lines, cell function assays (including wound healing, transwell migration and invasion, colony formation, and apoptosis assays), and mouse tumor xenografts were performed to examine the biological roles of DUS4L in LUAD progression. RNA sequencing, proteomic analyses, mass spectrometry, and co-immunoprecipitation experiments were conducted to identify and validate DUS4L-regulated downstream target genes and signaling pathways. RESULTS: We identified a consistent upregulation of DUS4L in LUAD tissues. In vitro and in vivo experiments underscored the inhibitory effect of DUS4L downregulation on LUAD progression, including migration, invasion, and proliferation. Mechanistically, DUS4L was found to interact with the signaling molecule GRB2, promoting LUAD progression and metastasis by inducing epithelial-mesenchymal transition (EMT) via the PI3K/AKT and ERK/MAPK pathways. CONCLUSION: Our results establish the functional role of DUS4L in driving the progression and metastasis of LUAD, implicating its potential as a candidate therapeutic target for LUAD.


Asunto(s)
Proteína Adaptadora GRB2 , Neoplasias Pulmonares , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Humanos , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Proteína Adaptadora GRB2/metabolismo , Proteína Adaptadora GRB2/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones , Invasividad Neoplásica , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Ratones Desnudos , Movimiento Celular , Células A549 , Femenino , Masculino , Sistema de Señalización de MAP Quinasas , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Línea Celular Tumoral , Ratones Endogámicos BALB C , Metástasis de la Neoplasia , Transducción de Señal , Apoptosis
5.
Commun Biol ; 7(1): 916, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39080467

RESUMEN

Cytokines have attracted sustained attention due to their multi-functional cellular response in immunotherapy. However, their application was limited to their short half-time, narrow therapeutic window, and undesired side effects. To address this issue, we developed a portable smart blue-light controlled (PSLC) device based on optogenetic technology. By combining this PSLC device with blue-light controlled gene modules, we successfully achieved the targeted regulation of cytokine expression within the tumor microenvironment. To alter the tumor microenvironment of solid tumors, pro-inflammatory cytokines were selected as blue-light controlled molecules. The results show that blue-light effectively regulates the expression of pro-inflammatory cytokines both in vitro and in vivo. This strategy leads to enhanced and activated tumor-infiltrating immune cells, which facilitated to overcome the immunosuppressive microenvironment, resulting in significant tumor shrinkage in tumor-bearing mice. Hence, our study offers a unique strategy for cytokine therapy and a convenient device for animal studies in optogenetic immunotherapy.


Asunto(s)
Citocinas , Luz , Optogenética , Microambiente Tumoral , Animales , Citocinas/metabolismo , Ratones , Optogenética/métodos , Optogenética/instrumentación , Humanos , Línea Celular Tumoral , Inmunoterapia/métodos , Femenino , Regulación Neoplásica de la Expresión Génica , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/metabolismo
6.
Artículo en Inglés | MEDLINE | ID: mdl-39073408

RESUMEN

Two Gram-stain-negative, aerobic, rod-shaped, non-endospore-forming and motile bacterial strains, designated IT1137T and S025T, were isolated from an intertidal sediment sample collected from the Fildes Peninsula (King George Island, Maritime Antarctica) and a soil sample under red snow in the Ny-Ålesund region (Svalbard, High Arctic), respectively. The 16S rRNA gene sequence similarity values grouped them in the genus Pseudomonas. The two strains were characterized phenotypically using API 20E, API 20NE, API ZYM and Biolog GENIII tests and chemotaxonomically by their fatty acid contents, polar lipids and respiratory quinones. Multilocus sequence analysis (concatenated 16S rRNA, gyrB, rpoB and rpoD sequences), together with genome comparisons by average nucleotide identity and digital DNA-DNA hybridization, were performed. The results showed that the similarity values of the two isolates with the type strains of related Pseudomonas species were below the recognized thresholds for species definition. Based on polyphasic taxonomy analysis, it can be concluded that strains IT1137T and S025T represent two novel species of the genus Pseudomonas, for which the names Pseudomonas paeninsulae sp. nov. (type strain IT1137T=PMCC 100533T=CCTCC AB 2023226T=JCM 36637T) and Pseudomonas svalbardensis sp. nov. (type strain S025T=PMCC 200367T= CCTCC AB 2023225T=JCM 36638T) are proposed.


Asunto(s)
Técnicas de Tipificación Bacteriana , ADN Bacteriano , Ácidos Grasos , Sedimentos Geológicos , Tipificación de Secuencias Multilocus , Hibridación de Ácido Nucleico , Filogenia , Pseudomonas , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Microbiología del Suelo , ARN Ribosómico 16S/genética , Pseudomonas/genética , Pseudomonas/clasificación , Pseudomonas/aislamiento & purificación , Sedimentos Geológicos/microbiología , ADN Bacteriano/genética , Regiones Árticas , Regiones Antárticas , Ácidos Grasos/análisis , Svalbard , Composición de Base , Quinonas/análisis
7.
Chin J Integr Med ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990478

RESUMEN

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.

9.
BMC Anesthesiol ; 24(1): 174, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745175

RESUMEN

BACKGROUND: Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded. RESULTS: A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients. CONCLUSIONS: A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope. TRIAL REGISTRATION: The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Relación Dosis-Respuesta a Droga , Duodenoscopios , Hipnóticos y Sedantes , Humanos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Masculino , Femenino , Hipnóticos y Sedantes/administración & dosificación , Anciano , Alfentanilo/administración & dosificación , Persona de Mediana Edad , Benzodiazepinas/administración & dosificación
10.
J Pain Res ; 17: 1583-1594, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38707266

RESUMEN

Objective: Moderate-to-severe pain is the most common clinical symptom in patients with hepatocellular carcinoma (HCC).This trial aimed to analyze the clinical efficacy of Transcutaneous electrical acupoint stimulation (TEAS) in patients of HCC with severe pain and provide a reliable reference for optimizing the clinical diagnostic and therapeutic strategies of HCC. Methods: A total of 104 eligible patients were randomly allocated to experimental and control groups in a ratio of 1:1.The treatment was administered for 1 week continuously. Patients in both groups were followed up 1 week after the end of the treatment.The primary outcome measure was the Numerical Rating Scale (NRS) score, whereas the secondary outcome measures included Brief Pain Inventory BPI-Q3, Q4, Q5 scores, analgesic dose, frequency of opioid-induced gastrointestinal side effects, Karnofsky Performance Status (KPS), Quality of Life Scale - Liver Cancer (QOL-LC), and Brief Fatigue Inventory (BFI) scores. Results: The NRS scores of experimental group was significantly lower after treatment and at the follow-up than baseline (average P<0.01), there were also statistical differences between the groups at the above time points (average P<0.01). BPI-Q3, -Q4, and -Q5 scores in the experimental group were decreased after treatment when compared with those before treatment (average P<0.01). Furthermore, there were significant improvements of gastrointestinal side effects, KPS, QOL-LC and BPI in the experimental group after treatment, and the above results were statistically significant compared to the control group. Conclusion: 7-day TEAS treatment can significantly enhance the analgesic effect and maintain for the following week, also reduce the incidence of gastrointestinal side effects caused by opioids, and improve the quality of life of patients with moderate-to-severe HCC-related pain, which has reliable safety and certain clinical promotion value.

11.
J Thorac Dis ; 16(3): 2070-2081, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38617762

RESUMEN

Background: Electrical impedance tomography (EIT) is a relatively recent functional imaging technique that is both noninvasive and radiation free. EIT measures the associated voltage when a weak current is applied to the surface of the human body to determine the distribution of electrical resistance within tissues. We performed a bibliometrics-based review to explore the geographic hotspots of current research and future trends developing in the field of EIT for mechanical ventilation. Methods: The Web of Science database was searched from its inception to June 25, 2023. CiteSpace software was used to visualize and analyze the relevant literature and identify the most impactful literature, trends, and hotspots. Results: 363 articles describing EIT use in mechanical ventilation were identified. A fluctuating growth in the number of publications was observed from 1998 to 2023. Germany had the highest number of articles (n=154), followed by Italy (n=53) and China (n=52). A cluster analysis of keyword co-occurrence revealed that "titration", "ventilator-related lung injury", and "oxygenation" were the most actively researched terms associated with the use of EIT in mechanically ventilated patients. Conclusions: Significant progress has been made in EIT research for mechanical ventilation. EIT research is limited to a small number of countries with a present research focus on the prevention and treatment of ventilator-related lung injury, oxygenation status, and prone ventilation. These topics are expected to remain research hotspots in the future.

12.
J Asian Nat Prod Res ; 26(8): 930-944, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38598409

RESUMEN

A sensitive UPLC-HRMS method was developed and validated for simultaneous quantification of four active flavonoids from Chimonanthus nitens Leaf Granules (CNLG) in biological matrix. The method was utilized in pharmacokinetic study of the four flavonoids in rats as well as other evaluation assays in vitro. It was revealed that rutin, nicotiflorin, and astragalin had poor oral bioavailability in rats possibly due to low intestinal permeability and metabolism in intestinal flora. Kaempferol underwent rapid glucuronidation and sulphation in rat plasma with medium permeability coefficient. The results provided valuable data for future research and development of CNLG flavonoids.


Asunto(s)
Flavonoides , Quempferoles , Hojas de la Planta , Animales , Flavonoides/farmacocinética , Flavonoides/química , Hojas de la Planta/química , Ratas , Quempferoles/farmacocinética , Quempferoles/química , Estructura Molecular , Masculino , Rutina/farmacocinética , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Ratas Sprague-Dawley , Calycanthaceae/química , Cromatografía Liquida/métodos , Disponibilidad Biológica , Espectrometría de Masas/métodos , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Líquida con Espectrometría de Masas
13.
World J Gastrointest Surg ; 16(2): 345-356, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38463348

RESUMEN

BACKGROUND: Although accurately evaluating the overall survival (OS) of gastric cancer patients remains difficult, radiomics is considered an important option for studying prognosis. AIM: To develop a robust and unbiased biomarker for predicting OS using machine learning and computed tomography (CT) image radiomics. METHODS: This study included 181 stage II/III gastric cancer patients, 141 from Lichuan People's Hospital, and 40 from the Cancer Imaging Archive (TCIA). Primary tumors in the preoperative unenhanced CT images were outlined as regions of interest (ROI), and approximately 1700 radiomics features were extracted from each ROI. The skeletal muscle index (SMI) and skeletal muscle density (SMD) were measured using CT images from the lower margin of the third lumbar vertebra. Using the least absolute shrinkage and selection operator regression with 5-fold cross-validation, 36 radiomics features were identified as important predictors, and the OS-associated CT image radiomics score (OACRS) was calculated for each patient using these important predictors. RESULTS: Patients with a high OACRS had a poorer prognosis than those with a low OACRS score (P < 0.05) and those in the TCIA cohort. Univariate and multivariate analyses revealed that OACRS was a risk factor [RR = 3.023 (1.896-4.365), P < 0.001] independent of SMI, SMD, and pathological features. Moreover, OACRS outperformed SMI and SMD and could improve OS prediction (P < 0.05). CONCLUSION: A novel biomarker based on machine learning and radiomics was developed that exhibited exceptional OS discrimination potential.

14.
Altern Ther Health Med ; 30(10): 448-453, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38401082

RESUMEN

Objective: This study aimed to assess the impact of combined moxibustion therapy and Gua sha on enhancing functional independence, reducing fall risk, and alleviating pain in patients undergoing post-rehabilitation for multiple cerebral infarctions. Methods: In a prospective clinical trial, 67 patients diagnosed with multiple cerebral infarctions (age range: 40 to 93 years) were enrolled. Baseline health characteristics included a median hospital stay of 10 days, prevalent medical conditions such as hypertension (64.18%), and various comorbidities like spondylosis (17.91%) and heart disease (14.93%). Patients received moxibustion treatment daily for 20-30 minutes on specific acupoints of the upper and lower extremities. Additionally, Gua sha therapy targeting the the head, back, chest, abdomen, and selected acupoints was administered twice a week with an interval of 3 to 4 days. Assessments included Barthel Index (BI) for functional independence, Morse Fall Scale (MFS) for fall risk, and Visual Analogue Scale (VAS) for pain intensity before and after the intervention. Results: After one week of rehabilitation, significant improvements were observed in the patient's functional independence, as indicated by a median BI score of 100 (IQR: 95-100), compared to the pre-rehabilitation median score of 95 (IQR: 90-100). The MFS score also showed a significant decrease after rehabilitation, with a median score of 35 (IQR: 35-45) compared to the pre-rehabilitation median score of 45 (IQR: 35-45). Additionally, pain intensity significantly decreased, with a median VAS score of 0 (range: 0-2) after rehabilitation, compared to the pre-rehabilitation median score of 0 (range: 0-3). Conclusion: Combined moxibustion therapy and Gua sha demonstrated positive effects on functional independence, fall risk reduction, and pain alleviation in post-rehabilitation for multiple cerebral infarctions. These findings suggest the potential of moxibustion and Gua sha as complementary interventions in stroke rehabilitation. The observed improvements in functional independence, fall risk, and pain underscore the potential benefits of these therapies for patients with multiple cerebral infarctions. Further exploration could delve into long-term effects, larger-scale trials, and mechanistic studies to elucidate the underlying pathways of efficacy.


Asunto(s)
Infarto Cerebral , Moxibustión , Humanos , Moxibustión/métodos , Persona de Mediana Edad , Masculino , Femenino , Anciano , Adulto , Infarto Cerebral/rehabilitación , Infarto Cerebral/terapia , Estudios Prospectivos , Anciano de 80 o más Años
15.
Zhongguo Zhong Yao Za Zhi ; 49(2): 509-517, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38403326

RESUMEN

This study investigated the absorption profile of Wuwei Qingzhuo San in different intestinal segments and the absorption characteristics of its alkaloids(piperine, piperanine, piperlonguminine, and dihydropiperlonguminine). The everted gut sac model was established, and the chemical components of Wuwei Qingzhuo San in different intestinal segments were detected by UPLC-Q-TOF-MS. The content of piperine, piperanine, piperlonguminine, and dihydropiperlonguminine in intestinal absorption fluid was determined by UPLC-Q-TRAP-MS and the absorption parameters were calculated. The absorption characteristics in different intestinal segments at different time were analyzed. As a result, 27, 27, 8, and 6 absorbent components from Wuwei Qingzhuo San were detected in the intestinal cyst fluid of jejunum, ileum, duodenum, and colon by UPLC-Q-TOF-MS technology, respectively. It was also found that piperine, piperanine, piperlonguminine, and dihydropiperlonguminine from Wuwei Qingzhuo San showed linear absorption in various intestinal segments, with r values exceeding 0.9. In terms of absorption content, the components were ranked as piperine>piperanine>dihydropiperlonguminine>piperlonguminine in various intestinal segments, but the absorption rate and mechanism of each component varied. The results demonstrate that the absorption of the components of Wuwei Qingzhuo San in different intestinal segments is selective and is not a simple semi-permeable membrane permeation process.


Asunto(s)
Alcaloides , Piperidinas , Alcamidas Poliinsaturadas , Benzodioxoles , Absorción Intestinal
16.
J Integr Med ; 22(1): 22-31, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38199885

RESUMEN

BACKGROUND: Irritable bowel syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with altered bowel habits. Several clinical studies have demonstrated the effectiveness of acupuncture and moxibustion for IBS. Many systematic reviews of acupuncture and moxibustion for IBS have been published in recent years, but their results are not entirely consistent. OBJECTIVE: To evaluate the methodological, reporting, and evidence quality of systematic reviews of acupuncture and moxibustion for IBS. SEARCH STRATEGY: Systematic reviews of acupuncture and moxibustion for IBS published before February 20, 2023 were searched in eight databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP Database for Chinese Technical Periodicals, and China Biology Medicine. The keywords used for literature search were acupuncture, moxibustion, systematic review, meta-analysis, and irritable bowel syndrome. INCLUSION CRITERIA: Systematic reviews and meta-analyses of randomized controlled trials of acupuncture and moxibustion for IBS were included. DATA EXTRACTION AND ANALYSIS: Relevant information was independently extracted by two investigators. The A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020), and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used to evaluate the methodological quality, reporting quality and evidence quality, respectively. RESULTS: A total of 342 studies were retrieved and 15 systematic reviews were included. The results of AMSTAR 2 showed low methodological quality in 2 studies and very low methodological quality in the remaining 13 studies, with main issues being failure to register a protocol, incomplete search strategy, not providing a list of excluded studies, incomplete consideration of the risk of bias in the included studies, and a failure to assess the publication bias. The results of PRISMA 2020 showed seriously deficient reporting quality of 2 studies, somewhat deficient reporting quality of 12 studies, and relatively complete reporting quality of 1 study, with the main problems being lack of a complete search strategy, non-availability of a list of excluded studies with justification for their exclusion, not conducting heterogeneity and sensitivity analyses, not evaluating the credibility of the evidence, and not registering the protocol. The results of GRADE showed that the quality of the evidence is low or very low. CONCLUSION: Most included systematic reviews interpreted findings to suggest that acupuncture and moxibustion have benefits for IBS. However, there is a need to improve the methodological, reporting and evidence quality of the systematic reviews. Larger, multicenter, rigorously designed randomized controlled trials and high-quality systematic reviews are required to obtain more robust evidence. PLEASE CITE THIS ARTICLE AS: Ma YY, Hao Z, Chen ZY, Shen YX, Liu HR, Wu HG, Bao CH. Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review. J Integr Med. 2024; 22(1): 22-31.


Asunto(s)
Terapia por Acupuntura , Síndrome del Colon Irritable , Moxibustión , Síndrome del Colon Irritable/terapia , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Artículo en Inglés | MEDLINE | ID: mdl-37863170

RESUMEN

A growing body of evidences reveal that abnormal gray matter morphology is constrained by normal brain network architecture in neurodegenerative and psychiatric disorders. However, whether this finding holds true in obsessive-compulsive disorder (OCD) remains unknown. In the current study, we aimed to investigate the association between gray matter morphological abnormities and normal structural covariance network architecture in OCD. First, gray matter morphological abnormities were obtained between 98 medicine-naive and first-episode patients with OCD and 130 healthy controls (HCs). Then, putative disease epicenters whose structural connectome profiles in HCs most resembled the morphological differences pattern were identified using a backfoward stepwise regression analysis. A set of brain regions were identified as putative disease epicenters whose structural connectome architecture significantly explained 59.94% variance of morphological abnormalities. These disease epicenters comprised brain regions implicated in high-order cognitive functions and sensory/motor processing. Other brain regions with stronger structural connections to disease epicenters exhibited greater vulnerability to disease. Together, these results suggest that gray matter abnormities are constrained by structural connectome and provide new insights into the possible pathological progression in OCD.


Asunto(s)
Sustancia Gris , Trastorno Obsesivo Compulsivo , Humanos , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Imagen por Resonancia Magnética/métodos , Corteza Cerebral/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/psicología
18.
Blood Cancer J ; 13(1): 178, 2023 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-38052803

RESUMEN

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.


Asunto(s)
Arsénico , Leucemia Promielocítica Aguda , Niño , Humanos , Arsénico/efectos adversos , Trióxido de Arsénico/efectos adversos , Arsenicales/efectos adversos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Resultado del Tratamiento , Tretinoina/uso terapéutico
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(12): 1282-1286, 2023 Dec 15.
Artículo en Chino | MEDLINE | ID: mdl-38112148

RESUMEN

This article reports two cases of children with B-cell acute lymphoblastic leukemia (B-ALL) complicated by invasive fungal disease (IFD) who received bridging treatment using blinatumomab. Case 1 was a 4-month-old female infant who experienced recurrent high fever and limb weakness during chemotherapy. Blood culture was negative, and next-generation sequencing (NGS) of peripheral blood, bronchoalveolar lavage fluid, and cerebrospinal fluid were all negative. Chest CT and cranial MRI revealed obvious infection foci. Case 2 was a 2-year-old male patient who experienced recurrent high fever with multiple inflammatory masses during chemotherapy. Candida tropicalis was detected in peripheral blood and abscess fluid using NGS, while blood culture and imaging examinations showed no obvious abnormalities. After antifungal and blinatumomab therapy, both cases showed significant improvement in symptoms, signs, and imaging, and B-ALL remained in continuous remission. The report indicates that bridging treatment with blinatumomab in children with B-ALL complicated by IFD can rebuild the immune system and control the underlying disease in the presence of immunosuppression and severe fungal infection.


Asunto(s)
Anticuerpos Biespecíficos , Infecciones Fúngicas Invasoras , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Preescolar , Femenino , Humanos , Lactante , Masculino , Anticuerpos Biespecíficos/uso terapéutico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Inducción de Remisión
20.
Ophthalmol Ther ; 12(6): 3361-3372, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37853298

RESUMEN

INTRODUCTION: This study evaluated novel automatic dual rotational Risley prisms (ADRRPs) as a vergence exercise tool for patients with myopia to improve accommodative lag and accommodative facility. METHODS: Participants with myopia aged 20-24 years were recruited. After vergence exercises with prisms (treatment group) or plano lenses (control group) using ADRRPs for 10 min, measurements were taken using an open-field autorefractor (Grand Seiko WAM-5500) at viewing distances of 0.4 m and 6.0 m. We measured accommodative facility using a ± 2.00 D accommodative flipper. RESULTS: A total of 56 participants (treatment group, 39; control group, 17) performed vergence exercises using ADRRPs. Participants in the treatment group showed improvements in accommodative lag at a 0.4 m viewing distance, with measurements of 0.57 D (right eye; OD) and 0.53 D (left eye; OS) and 0.21 D (OD) and 0.27 D (OS) before and after the exercises, respectively (p < 0.001). Over-refractions using an open-field autorefractor with spherical equivalent contact lenses at a 6.0 m viewing distance were - 0.01 ± 0.30 D (OD) and 0.03 ± 0.34 D (OS) and 0.15 ± 0.32 D (OD) and 0.19 ± 0.28 D (OS) before and after the exercises, respectively (difference + 0.16 D; p < 0.001). Accommodative facility values before and after exercises were 14.88 ± 3.36 and 15.59 ± 3.60 cpm, respectively (p < 0.01). No significant differences in accommodative lag, relaxation, and accommodative facility before and after exercise were observed in the control group. CONCLUSIONS: Using ADRRPs in vergence exercises can improve accommodative lag, accommodative facility, and accommodative relaxation in adults with myopia. Further research to evaluate persistent and long-term effects is needed.

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