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Objective: To identify the risk factors contributing to cerebral microbleeds (CMBs), analyze the correlation between the quantity and distribution of CMBs and overall cognitive performance, including specific cognitive domains in patients, and investigate the underlying mechanisms by which CMBs impact cognitive function. Methods: Patients diagnosed with cerebral small vessel disease were recruited between September 2022 and September 2023. Clinical baseline data were systematically gathered. The Montreal Cognitive Assessment (MoCA) was employed to evaluate patients' cognitive status. CMBs were identified via susceptibility-weighted imaging (SWI), noting their locations and quantities. Patients were categorized into two cohorts: those without CMBs and those with CMBs. This division facilitated the comparison of basic clinical data and laboratory indicators, aiming to elucidate the risk factors associated with CMBs. Within the CMBs cohort, patients were further classified based on the number of CMBs into mild, moderate, and severe groups, and according to CMBs' locations into deep, cortical-subcortical, and mixed groups. Spearman correlation analysis and ANOVA were utilized to compare the total MoCA scores, as well as scores in specific cognitive domains, across these groups. This approach enabled the analysis of the relationship between the quantity and location of CMBs and cognitive impairment. Results: Statistically significant differences were noted between patients with and without cerebral microbleeds (CMBs) regarding gender, age, hypertension, diabetes, history of cerebral infarction, history of alcohol consumption, glycosylated hemoglobin levels, low-density lipoprotein cholesterol, and homocysteine levels (p < .05). Multifactorial logistic regression analysis identified age, hypertension, diabetes, history of alcohol consumption, and elevated homocysteine as independent risk factors for the development of CMBs. Spearman correlation analysis revealed a linear correlation between the presence of CMBs and the total score of the MoCA (r = -.837, p < .001). The group with CMBs demonstrated a significant decline in visuospatial execution function and delayed recall abilities compared to the group without CMBs (p < .05). Specifically, deep CMBs were linked to impairments in visuospatial execution function, naming, attention, computational ability, language, delayed recall, and orientation (p < .05). Cortical-subcortical CMBs affected visuospatial execution function, attention, computational ability, and delayed recall ability(p < .05). Mixed CMBs impacted visuospatial execution function and naming (p < .05). Conclusion: Age, hypertension, diabetes, history of alcohol consumption, and elevated homocysteine levels are key independent risk factors for CMBs. There exists a linear relationship between the severity of CMBs and the extent of cognitive impairment. Patients with CMBs show notable deterioration in visuospatial execution function and delayed recall abilities. Furthermore, the location of CMBs influences various specific cognitive domains.

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Calcium oxalate (CaOx) kidney stones are common and recurrent, lacking pharmacological prevention. Randall's plaques (RPs), calcium deposits in renal papillae, serve as niduses for some CaOx stones. This study explores the role of osteogenic-like cells in RP formation resembling ossification. CaP crystals deposit around renal tubules, interstitium, and blood vessels in RP tissues. Human renal interstitial fibroblasts (hRIFs) exhibit the highest osteogenic-like differentiation potential compared to chloride voltage-gated channel Ka positive tubular epithelial cells, aquaporin 2 positive collecting duct cells, and vascular endothelial cells, echoing the upregulated osteogenic markers primarily in hRIFs within RP tissues. Utilizing RNA-seq, osteomodulin (OMD) is found to be upregulated in hRIFs within RP tissues and hRIFs following osteogenic induction. Furthermore, OMD colocalizes with CaP crystals and calcium vesicles within RP tissues. OMD can enhance osteogenic-like differentiation of hRIFs in vitro and in vivo. Additionally, crystal deposits are attenuated in mice with Omd deletion in renal interstitial fibroblasts following CaOx nephrocalcinosis induction. Mechanically, a positive feedback loop of OMD/BMP2/BMPR1A/RUNX2/OMD drives hRIFs to adopt osteogenic-like fates, by which OMD induces osteogenic-like microenvironment of renal interstitium to participate in RP formation. We identify OMD upregulation as a pathological feature of RP, paving the way for preventing CaOx stones.

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BACKGROUND: We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to investigate whether the priority of clopidogrel plus aspirin to aspirin alone was consistent between patients with and without stroke pathogenesis of large-artery atherosclerosis (LAA). METHODS AND RESULTS: Patients with stroke classification randomized to a clopidogrel-plus-aspirin group and aspirin-alone group in a modified intention-to-treat analysis set of ATAMIS were classified into LAA and non-LAA subtypes. The primary outcome was early neurologic deterioration at 7 days, defined as a >2-point increase in National Institutes of Health Stroke Scale score compared with baseline, and safety outcomes were bleeding events and intracranial hemorrhage. We compared treatment effects in each stroke subtype and investigated the interaction. Among 2910 patients, 225 were assigned into the LAA subtype (119 in the clopidogrel-plus-aspirin group and 106 in the aspirin-alone group) and 2685 into the non-LAA subtype (1380 in the clopidogrel-plus-aspirin group and 1305 in the aspirin-alone group). Median age was 66 years, and 35% were women. A lower proportion of early neurologic deterioration was found to be associated with dual antiplatelet therapy in the LAA subtype (adjusted risk difference, -10.4% [95% CI, -16.2% to -4.7%]; P=0.001) but not in the non-LAA subtype (adjusted risk difference, -1.4% [95% CI, -2.6% to 0.1%]; P=0.06). No significant interaction was found (P=0.11). CONCLUSIONS: Compared with the non-LAA subtype, patients with stroke of the LAA subtype may get more benefit from dual antiplatelet therapy with clopidogrel plus aspirin with respect to early neurologic deterioration at 7 days. REGISTRATION: URL: clinicaltrials.gov; UnIque identifier: NCT02869009.

Asunto(s)

Aspirina , Clopidogrel , Terapia Antiplaquetaria Doble , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Femenino , Masculino , Anciano , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Aspirina/efectos adversos , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Terapia Antiplaquetaria Doble/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/diagnóstico , Aterosclerosis/complicaciones , Índice de Severidad de la Enfermedad , Quimioterapia Combinada

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INTRODUCTION: Acupuncture is widely used for metabolic-associated fatty liver disease (MAFLD) treatment; however, the clinical efficacy has not been confirmed due to the lack of high-level evidence-based clinical practice. The purpose of this study is to design a research protocol that will be used to determine the efficacy of acupuncture versus sham acupuncture (SHA) for MAFLD treatment. METHODS AND ANALYSIS: This will be a multicentre, randomised and sham-controlled trial. Ninety-eight participants with MAFLD will be enrolled in this trial. Participants will be randomly assigned in a 1:1 ratio to receive acupuncture or SHA for 12 weeks. The primary outcome is the rate of patients with a 30% relative decline in liver fat after 12 weeks of treatment in MRI-proton density fat fraction (MRI-PDFF), which will be obtained by quantitative chemical shift imaging such as the multipoint Dixon method at 0, 12 and 24 weeks. Secondary outcomes include the changes in the relative liver fat content measured by MRI-PDFF, magnetic resonance elastography, liver function, lipid metabolism, homeostatic model assessment for insulin resistance (HOMA-IR) and serum high sensitivity C reactive protein, which will be obtained at 0, 6, 12 and 24 weeks. Body measurement indicators (body mass index, waist circumference, hip circumference and waist-to-hip ratio) will be obtained at 0, 3, 6, 9, 12 and 24 weeks. The alteration in the gut microbiota composition and its metabolism will be assessed by 16S ribosomal RNA sequencing and liquid chromatography-mass spectrometry at 0 and 12 weeks. ETHICS AND DISSEMINATION: This study protocol has been approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (2023-1347-114-01). The results of this study will be published in a peer-reviewed journal and presented at academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300075701.

Asunto(s)

Terapia por Acupuntura , Enfermedad del Hígado Graso no Alcohólico , Humanos , Terapia por Acupuntura/métodos , Enfermedad del Hígado Graso no Alcohólico/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Imagen por Resonancia Magnética , Resultado del Tratamiento , Adulto , Estudios Multicéntricos como Asunto , Persona de Mediana Edad , Masculino , Femenino , Resistencia a la Insulina , Hígado/metabolismo , Hígado/diagnóstico por imagen

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BACKGROUND: To systematically evaluate the safety and efficacy of Deucravacitinib for moderate to severe plaque psoriasis. MATERIALS AND METHODS: Randomized controlled trials (RCTs) of Deucravacitinib for moderate to severe plaque psoriasis in PubMed, Cochrane Library, Embase, and Web of Science were searched from database establishment to April 2023. Literature quality was independently evaluated by two investigators using the Cochrane risk-of-bias assessment tool, and the systematic analysis was made using StateSE15 and RevMan 5.3 software. RESULTS: Four RCTs were included, including 1751 patients with moderate to severe plaque psoriasis. Meta-analysis showed that the differences in efficacy and adverse events (AEs) between the Deucravacitinib group and placebo group were significant (p < 0.05). The patients in the Deucravacitinib group took orally 3-12 mg daily for 12 sequential weeks or 6 mg daily for 52 sequential weeks. Psoriasis Area and Severity Index (PASI) reduced by 75% (PASI 75), (PASI 90), and (PASI 100), static Physician Global Assessment (sPGA) of 0 or 1 (sPGA 0/1), Dermatology Life Quality Index of 0 or 1 (DLQI 0/1), and Psoriasis Symptoms and Signs Diary (PSSD) were significantly higher in the Deucravacitinib group compared to the placebo group, with significant differences (p < 0.05). The most frequently encountered AEs after treatment in the Deucravacitinib group was nasopharyngitis. CONCLUSION: Oral administration of Deucravacitinib is effective for moderate to severe plaque psoriasis. Attention should be paid to the occurrence of AEs, and more RCTs are required to evaluate the relationship between the dose and safety and efficacy.

Asunto(s)

Psoriasis , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento

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Cholangiocarcinoma (CCA) is a hepatobiliary carcinoma with uncontrolled cell proliferation, poor prognosis, and high mortality. The ovarian tumor structural domain (OTU) containing protein 6B (OTUD6B) belongs to the OTU deubiquitin family and is vital in tumor development. However, its expression and biological function in CCA remain unknown. The expression of OTUD6B in CCA was analyzed using TIMER2.0, UALCAN, and GEO databases. MTT, clonal formation assay, immunofluorescence staining, immunohistochemistry staining, and flow cytometry examined the regulation of OTUD6B on cell proliferation, cycle, and apoptosis. The effects of OTUD6B on tumor volume and weight were assessed using the xenograft tumor model. The activities of PTK2 and STAT3 were detected by western blot and CO-IP. The biological database identified that OTUD6B was upregulated in CCA. In CCA cells, OTUD6B knockdown reduced CCA cell proliferation and promoted apoptosis. Cell cycle analysis indicated that the cycle stopped at the G0/G1 phase after OTU6B downregulation. Furthermore, OTUD6B knockdown resulted in a decrease in tumor volume and weight in xenograft tumor models. Mechanistically, OTUD6B is involved in the deubiquitination of PTK2. PTK2 further affected the phosphorylation of STAT3 thereby regulating the CCA process. Our study demonstrates that OTUD6B knockdown participates in the ubiquitination of PTK2 and phosphorylation of STAT3 to alleviate the process of CCA. These results suggest that OTUD6B may be a potential new strategy for CCA treatment.

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Objectives: Newborns and small infants are unable to cooperate actively during diagnostic procedures; therefore, sedation is often employee to maintain immobilization and obtain high-quality images. However, these procedures are often indicated in sick, vulnerable, or hemodynamically unstable neonates and young infants, which raises the associated risks of sedation. This study summarizes our 4-year of experience with safe and effective procedural sedation in this vulnerable population. Study design: This retrospective study analyzed data on neonates and young infants who underwent non-painful diagnostic procedures from December 2019 to November 2023. Patients were categorized into the neonate (aged≦ 28 days) and the young infant (29 days ≦ aged ≦ 90 days) groups. Results: Non-pharmacological strategies, including sleeping naturally, swaddling/facilitated tucking, non-nutritive sucking, and skin-to-skin care, can achieve a success rate for sedation about 98.4%. In terms of pharmacological methods, our institution primarily utilizes chloral hydrate for procedural sedation in neonates and young infants undergoing non-painful diagnostic procedures. Midazolam serves as an alternative sedative. Chloral hydrate alone demonstrated a 92.5% success rate on the first attempt, compared to midazolam alone, with an 85.11% success rate. Neonates experienced a higher incidence of adverse events during sedation compared to young infants. Conclusion: This study reviews our 4-year experience with procedural sedation in neonates and young infants. Chloral hydrate demonstrated a high degree of safety and efficacy in this population. However, supervision by skilled medical personnel and extended observation is required. In our institution, the experience with midazolam is limited in this population, and further research is warranted to establish its safety and efficacy. Non-pharmacological strategies can achieve an acceptable rate of sedation success, which can be used based on patient's tolerance.

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Background: We conducted a post-hoc analysis of the RICAMIS trial to investigate the effect of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) on the efficacy of remote ischemic conditioning treatment. Methods: In this post-hoc analysis, NLR, PLR, and SII were measured before randomization. Patients were divided into two groups based on their cut-off values: high vs low NLR, high vs low PLR, and high vs low SII groups. Each group was further subdivided into RIC and control groups. The primary endpoint was a poor outcome (mRS 2-6 at 90 days). Differences in the primary endpoint between the RIC and control subgroups were compared, and the interactions of treatment assignment with NLR, PLR, and SII were evaluated. Results: A total of 1679 patients were included in the final analysis. Compared with the control group, RIC significantly improved functional outcomes regardless of the inflammation status. The improved probability of poor outcome in the RIC vs control group was numerically greater in the high vs low inflammation group (NLR, 7.8% vs 5.1%; PLR, 7% vs 6.5%; SII, 9% vs 5.3%). However, we did not find an interaction effect of an intervention (RIC or control) with different NLR, PLR, or SII on clinical outcomes (P > 0.05). In addition, the NLR and SII were independently associated with functional outcomes in all patients, regardless of whether they received RIC. Conclusion: Inflammation may not affect the efficacy of RIC in patients with acute moderate ischemic stroke, although a lower probability of poor outcome at 90 days was identified in patients with a high vs low inflammatory status.

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BACKGROUND: Preventive treatment of tuberculosis infection (TBI) is considered a crucial strategy to prevent and control tuberculosis (TB). However, the acceptance and completion rates of preventive therapy for TBI are still far from optimistic. Evidence is mounting that TB knowledge and stigma may have a substantial effect on acceptance of TBI treatment. This study aimed to explore the effect of stigma on the relationship between the level of TB knowledge and acceptance of TBI treatment. METHODS: 7017 general population were included in the study. We adjusted for the covariates at the individual. Stepwise logistic regression was used to examine the moderating role of TB stigma and also explore the association between TB knowledge and acceptance of TBI treatment. RESULTS: The acceptance rate of TBI treatment among the respondents was 84.38% (n = 5921). Among respondents, a significant positive correlation between acceptance of TBI treatment and TB knowledge (OR = 1.096,95%CI = 1.073,1.118). Additionally, the association between TB knowledge and acceptance of TBI treatment was found to be moderated by TB stigma. In other words, TB stigma was found to weaken the impact of TB knowledge on acceptance of TBI treatment (OR = 0.994,95%CI = 0.991,0.996). CONCLUSION: The findings of the study indicated that having a high level of awareness about TB can enhance the general population's acceptability of TBI treatment. TB stigma moderated this association; it weakened the relationship between TB knowledge and individuals' willingness to accept TBI treatment. To mitigate TB stigma and enhance the intention of individuals with TBI to accept preventive therapy, it is imperative to enhance TB-related health education.

Asunto(s)

Conocimientos, Actitudes y Práctica en Salud , Aceptación de la Atención de Salud , Estigma Social , Tuberculosis , Humanos , China , Femenino , Masculino , Estudios Transversales , Adulto , Persona de Mediana Edad , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Tuberculosis/psicología , Tuberculosis/prevención & control , Adulto Joven , Adolescente , Anciano , Encuestas y Cuestionarios

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The assembly and patterning engineering in two-dimensional (2D) materials hold importance for chip-level designs incorporating multifunctional detectors. At present, the patterning and stacking methods of 2D materials inevitably introduce impurity instability and functional limitations. Here, the space-confined chemical vapor deposition method is employed to achieve state-of-the-art kirigami structures of self-assembled WS2, featuring various layer combinations and stacking configurations. With this technique as a foundation, the WS2 nano-kirigami is integrated with metasurface design, achieving a photodetector with bidirectional polarization-sensitive detection capability in the infrared spectrum. Nano-kirigami can eliminate some of the uncontrollable factors in the processing of 2D material devices, providing a freely designed platform for chip-level multifunctional detection across multiple modules.

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PURPOSE: This study aimed to measure and analyze the transverse indicators of normodivergent patients with different sagittal skeletal malocclusions, to explore the transverse characteristics of different sagittal skeletal malocclusions. METHODS: Lateral cephalograms and CBCT of 90 normodivergent patients with skeletal Class Ⅰ, Ⅱ and Ⅲ in their permanent dentition were collected. Dolphin software was applied to measure the widths of the basal bone, alveolar bone, dental arch and buccolingual inclination angle of the corresponding teeth in the maxillary and mandibular canine, premolar and molar areas. SPSS 22.0 software package was applied for statistical analysis of the data. RESULTS: The widths of the mandibular basal bone in canine, premolar and molar areas of skeletal Class Ⅲ were (27.15±2.74), (39.30±2.82) and (59.97±2.93) mm, respectively. The widths of the mandibular alveolar bone of skeletal Class Ⅲ were (25.38±1.78), (34.51±2.28) and (47.72±2.73) mm, respectively. The dental arch widths of the maxillary premolar and mandibular canine areas of skeletal Class Ⅲ were (48.70±2.35) and (30.69±2.31)mm, respectively. The above data of skeletal Class Ⅲ were significantly larger than those of skeletal Class Ⅰ and Ⅱ(P＜0.01). The dental arch widths of the maxillary canine, maxillary molar and mandibular molar areas of skeletal Class Ⅲ were (38.88±1.90), (59.51±3.40) and (56.01±2.86)mm, respectively, which were significantly larger than those of skeletal Class Ⅱ(P＜0.05). The maxillomandibular width difference of basal bone in the canine, premolar and molar areas of skeletal Class Ⅲ were (4.69±2.84), (2.31±2.39) and (3.27±2.05) mm, respectively, which were significantly less than that of skeletal Class Ⅰ and Ⅱ(P＜0.01). Compared with skeletal Class Ⅰ, the maxillary canines and first molars of skeletal Class Ⅱ had larger lingual inclination level, while the maxillary first premolars and first molars of skeletal Class Ⅲ had larger buccal inclination level, the mandibular canines and the mandibular first premolars of skeletal Class Ⅲ had larger lingual inclination level(P＜0.01). CONCLUSIONS: For normodivergent patients, the width of the mandibular base bone, alveolar bone, and maxillary and mandibular dental arch in skeletal Class Ⅲ is the widest, which is more likely to have width discrepancy in basal bone. In skeletal Class Ⅲ, the maxillary teeth are buccally inclined, and the mandibular teeth are ingually inclined. In skeletal Class Ⅱ, the maxillary teeth are lingually inclined, and the mandibular teeth are compensatory upright.

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Cefalometría , Arco Dental , Mandíbula , Maxilar , Humanos , Mandíbula/anatomía & histología , Mandíbula/diagnóstico por imagen , Cefalometría/métodos , Maxilar/anatomía & histología , Maxilar/diagnóstico por imagen , Arco Dental/anatomía & histología , Maloclusión/patología , Tomografía Computarizada de Haz Cónico/métodos , Diente Molar/anatomía & histología , Diente Molar/diagnóstico por imagen , Diente Canino/anatomía & histología , Diente Canino/diagnóstico por imagen , Diente Premolar/anatomía & histología , Diente Premolar/diagnóstico por imagen , Maloclusión de Angle Clase III , Proceso Alveolar/anatomía & histología , Proceso Alveolar/diagnóstico por imagen , Dentición Permanente

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Background: The Centre for Disease Control and Prevention in Yangquan, China, has taken a series of preventive and control measures in response to the increasing trend of Kala-Azar. In response, we propose a new model to more scientifically evaluate the effectiveness of these interventions. Methods: We obtained the incidence data of Kala-Azar from 2017 to 2021 from the Centre for Disease Control and Prevention (CDC) in Yangquan. We constructed Poisson segmented regression model, harmonic Poisson segmental regression model, and improved harmonic Poisson segmented regression model, and used the three models to explain the intervention effect, respectively. Finally, we selected the optimal model by comparing the fitting effects of the three models. Results: The primary analysis showed an underlying upward trend of Kala-Azar before intervention [incidence rate ratio (IRR): 1.045, 95% confidence interval (CI): 1.027-1.063, p < 0.001]. In terms of long-term effects, the rise of Kala-Azar slowed down significantly after the intervention (IRR:0.960, 95%CI:0.927-0.995, p = 0.026), and the risk of Kala-Azar increased by 0.3% for each additional month after intervention (ß1 + ß3 = 0.003, IRR = 1.003). The results of the model fitting effect showed that the improved harmonic Poisson segmental regression model had the best fitting effect, and the values of MSE, MAE, and RMSE were the lowest, which were 0.017, 0.101, and 0.130, respectively. Conclusion: In the long term, the intervention measures taken by the Yangquan CDC can well curb the upward trend of Kala-Azar. The improved harmonic Poisson segmented regression model has higher fitting performance, which can provide a certain scientific reference for the evaluation of the intervention effect of seasonal infectious diseases.

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Leishmaniasis Visceral , Humanos , China/epidemiología , Leishmaniasis Visceral/prevención & control , Leishmaniasis Visceral/epidemiología , Distribución de Poisson , Incidencia , Análisis de Regresión , Masculino , Femenino , Modelos Estadísticos

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Background and Purpose: Sex differences in acute ischemic stroke have been widely investigated, but the difference in acute ischemic stroke patients who received intravenous thrombolysis is not well understood. The current study was to investigate the issue based on a prospective cohort. Methods: From the Intravenous Thrombolysis Registry for Chinese Ischemic Stroke within 4.5h onset (INTRECIS) cohort, a total of 953 eligible patients with acute ischemic stroke were enrolled in final analysis. Based on 3-month modified Rankin scale score (mRS), patients were classified into good outcome group (mRS 0-1) and poor outcome group (mRS 2-6). Univariate and multivariate logistic regression analyses were used to identify predictive factors for clinical outcome in male or female patients. Results: Of the 953 patients treated with intravenous thrombolysis, 314 (32.9 %) were women. At day 90, we found no significant gender differences in good outcome (72.5 % vs 65.6 %, adjusted p = 0.414). We got the same results after propensity score matching (69.5 % vs 63.4 %, adjusted p = 0.637). Furthermore, we found that initial National Institute of Health Stroke Scale (NIHSS) score (odd ratio [OR] 0.877; 95 % CI 0.847-0.909, p < 0.001) and serum creatinine (OR 0.993; 95 % CI 0.986-1.000, p = 0 0.043) were found to be independent risk factors for poor outcome in male patients, while initial NIHSS score (OR 0.879; 95 % CI 0.839-0.920, p < 0.001), age (OR 0.970; 95 % CI 0.946-0.995, p = 0.017), systolic blood pressure (OR 0.984; 95 % CI 0.972-0.996, p = 0.007) and small artery occlusion (OR 2.718; 95 % CI 1.065-6.936, p = 0.036) in female patients. Conclusions: In this study, we found no gender difference in clinical outcome of thrombolysed stroke patients, but a difference in risk factors predicting outcome in male vs female patients was identified for the first time.

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AIMS: A myokine secreted by skeletal muscles during exercise called irisin mitigates ischemia-reperfusion (I/R) injury in epithelial cells of various organs by limiting damage to mitochondria. We test whether irisin may preserve the mitochondrial integrity and function in renal tubular epithelial cells and protect against ischemia-reperfusion-induced acute kidney injury (AKI). METHODS: We correlated serum irisin levels with serum creatinine and BUN levels from both AKI patients and healthy individuals. In mice with irisin administration, various renal injury markers such as serum creatinine, BUN, kidney injury molecule-1 (Kim-1), and neutrophil gelatinase-associated lipocalin (NGAL), and renal histopathology were assessed after I/R. To identify the potential mechanisms of the protective of irisin's protective effect, we perfused proximal tubules under confocal microscopy and analyzed kidney tissues by qPCR, western blot, and immunohistochemistry. RESULTS: Serum irisin correlated inversely with serum creatinine and BUN levels were significantly lower in AKI patients than in healthy subjects. Administering irisin to mice after I/R decreased biomarker levels for AKI including serum creatinine, BUN, Kim-1, NAGL and lessened histological changes. In kidney tissues of mice, irisin upregulated the mitochondrial autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3), the mitochondrial autophagy pathway-related proteins PTEN-induced putative kinase 1 (PINK1) and Parkinson's disease 2 parkin (PARK2) and downregulated the reactive substrate protein sequestosome 1 (P62) and mitochondrial membrane proteins translocase of outer mitochondrial membrane 20 (TOM20) and translocase of inner mitochondrial membrane 23 (TIM23). CONCLUSION: Irisin protects against renal I/R injury, which may involve the preservation of mitochondrial integrity and function.

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Lesión Renal Aguda , Fibronectinas , Ratones Endogámicos C57BL , Mitocondrias , Daño por Reperfusión , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Animales , Mitocondrias/metabolismo , Fibronectinas/metabolismo , Humanos , Ratones , Masculino , Células Epiteliales/metabolismo , Túbulos Renales/patología , Túbulos Renales/metabolismo , Femenino

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The development of novel drugs from basic science to clinical practice requires several years, much effort, and cost. Drug repurposing can promote the utilization of clinical drugs in cancer therapy. Recent studies have shown the potential effects of lomitapide on treating malignancies, which is currently used for the treatment of familial hypercholesterolemia. We systematically review possible functions and mechanisms of lomitapide as an anti-tumor compound, regarding the aspects of apoptosis, autophagy, and metabolism of tumor cells, to support repurposing lomitapide for the clinical treatment of tumors.

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The visceral adiposity index (VAI) and handgrip strength (HGS) are identified as important objectives for the prevention of illness. Nevertheless, there is limited understanding regarding the impact of the VAI and HGS on cardiometabolic multimorbidity (CMM). We aimed to ascertain the impact of the VAI and HGS on CMM among middle-aged and older people. Data spanning from 2011 to 2020 were derived from the China Health and Retirement Longitudinal Study (CHARLS). In total, 7909 individuals aged 45 years and older were included. Cox proportional hazard regression was utilized to examine the correlation among the VAI, HGS, and CMM. Throughout the 10-year follow-up, we determined that both the VAI (HR = 1.330; 95%CI = 1.179-1.500) and HGS (HR = 0.745, 95%CI = 0.645-0.861) exhibited significant associations with CMM risk. Individuals exposed to both a high VAI and low HGS were found to have higher hazards of CMM (HR = 1.377, 95%CI = 1.120-1.694) in contrast to participants exposed to one or none of these conditions. The older (HR = 1.414; 95%CI = 1.053-1.899) and male (HR = 1.586; 95%CI = 1.114-2.256) groups are more likely to experience CMM risk. Our findings suggest that both the VAI and HGS have significant effects on CMM risk. Appropriate interventions focused on vulnerable groups are recommended to prevent the incidence of CMM.

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Fuerza de la Mano , Multimorbilidad , Humanos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Estudios Longitudinales , China/epidemiología , Obesidad Abdominal/epidemiología , Grasa Intraabdominal , Enfermedades Cardiovasculares/epidemiología , Modelos de Riesgos Proporcionales

RESUMEN

Background: Retrograde intrarenal surgery (RIRS) is the main treatments for upper urinary tract stones. The Ureteral Access Sheath (UAS) serves as a supplementary tool, facilitating direct kidney access during RIRS. High quality of evidence comparing tip bendable suction ureteral access sheath (S-UAS) with traditional UAS in RIRS for the treatment of renal and ureteral stones is lacking. The purpose of the study is to compare the efficacy and safety of S-UAS with traditional UAS in RIRS for the treatment of renal or ureteral stones ≤30 mm. Methods: An international, multicenter, and superiority randomized controlled trial included 320 intention-to-treat patients across 8 medical centers in China, the Philippines, Malaysia and Turkey from August 2023 to February 2024. The inclusion criteria were patients ≥18 years old with renal or ureteral stones ≤30 mm. RIRS was performed using either S-UAS or traditional UAS. The primary outcome was the immediately stone-free rate (SFR). Secondary outcomes included SFR 3 months after operation, operating time, hospital stay, auxiliary procedures, complications (using the Clavien-Dindo grading system), and improvement in the Quality of Life (QoL) score. Differences between proportions [risk difference (RD)]/means [mean difference (MD)] and 95% confidence intervals (CI) were presented. This study is registered at ClinicalTrials.gov: NCT05952635. Findings: The S-UAS group demonstrated a significantly higher immediately SFR (81.3% versus 49.4%; RD 31.9%; 95% CI 22.5%-41.7%; p = 0.004) compared to the traditional UAS group, as determined by the one-side superiority test. Additionally, the S-UAS group exhibited a higher SFR at 3 months post-operation (87.5% versus 70.0%; RD 17.5%; 95% CI 8.7%-26.3%; p < 0.001), lower postoperative fever rate (RD -11.9%; 95% CI -18.7% to -4.9%; p < 0.001), reduced use of stone baskets (RD -70.6%; 95% CI -77.8% to -63.5%; p < 0.001), and better QoL improvement (MD 7.25; 95% CI 2.21-12.29; p = 0.005). No statistically significant differences were observed in operation time, hospital stay, or the need for second-stage RIRS. Interpretation: In RIRS for upper urinary tract stones ≤30 mm, S-UAS exhibited superior performance compared to traditional UAS, demonstrating higher SFR, reduced postoperative fever rate, and improved QoL outcomes. S-UAS emerges as a prudent and advantageous alternative to traditional UAS for RIRS. Funding: National Natural Science Foundation of China and Guangdong Province, and Zhejiang Medicine and Health Program.

RESUMEN

Systolic blood pressure variability (SBPV) is associated with outcome in acute ischemic stroke. Remote ischemic conditioning (RIC) has been demonstrated to be effective in stroke and may affect blood pressure. Relationship between SBPV and RIC treatment after stroke warrants investigation. A total of 1707 patients from per-protocol analysis set of RICAMIS study were included. The SBPV was calculated based on blood pressure measured at admission, Day 7, and Day 12. (I) To investigate the effect of SBPV on efficacy of RIC in stroke, patients were divided into High and Low categories in each SBPV parameter. Primary outcome was excellent functional outcome at 90 days. Compared with Control, efficacy of RIC in each category and interaction between categories were investigated. (II) To investigate the effect of RIC treatment on SBPV, SBPV parameters were compared between RIC and Control groups. Compared with Control, a higher likelihood of primary outcome in RIC was found in high category (max-min: adjusted risk difference [RD] = 7.2, 95% CI 1.2-13.1, P = 0.02; standard deviation: adjusted RD = 11.5, 95% CI 1.6-21.4, P = 0.02; coefficient of variation: adjusted RD = 11.2, 95% CI 1.4-21.0, P = 0.03). Significant interaction of RIC on outcomes were found between High and Low standard deviations (adjusted P < 0.05). No significant difference in SBPV parameters were found between treatment groups. This is the first report that Chinese patients with acute moderate ischemic stroke and presenting with higher SBPV, who were non-cardioemoblic stroke and not candidates for intravenous thrombolysis or endovascular therapy, would benefit more from RIC with respect to functional outcomes at 90 days, but 2-week RIC treatment has no effect on SBPV during hospital.

Asunto(s)

Presión Sanguínea , Precondicionamiento Isquémico , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Presión Sanguínea/fisiología , Anciano , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/fisiopatología , Persona de Mediana Edad , Precondicionamiento Isquémico/métodos , Resultado del Tratamiento , Sístole/fisiología

RESUMEN

BACKGROUND: Systolic blood pressure (SBP) was a predictor of early neurological deterioration (END) in stroke. We performed a secondary analysis of ARAMIS trial to investigate whether baseline SBP affects the effect of dual antiplatelet versus intravenous alteplase on END. METHODS: This post hoc analysis included patients in the as-treated analysis set. According to SBP at admission, patients were divided into SBP ≥140 mmHg and SBP <140 mmHg subgroups. In each subgroup, patients were further classified into dual antiplatelet and intravenous alteplase treatment groups based on study drug actually received. Primary outcome was END, defined as an increase of ≥2 in the NIHSS score from baseline within 24 h. We investigated effect of dual antiplatelet vs intravenous alteplase on END in SBP subgroups and their interaction effect with subgroups. RESULTS: A total of 723 patients from as-treated analysis set were included: 344 were assigned into dual antiplatelet group and 379 into intravenous alteplase group. For primary outcome, there was more treatment effect of dual antiplatelet in SBP ≥140 mmHg subgroup (adjusted RD, -5.2%; 95% CI, -8.2% to -2.3%; p < 0.001) and no effect in SBP <140 mmHg subgroup (adjusted RD, -0.1%; 95% CI, -8.0% to 7.7%; p = 0.97), but no significant interaction between subgroups was found (adjusted p = 0.20). CONCLUSIONS: Among patients with minor nondisabling acute ischemic stroke, dual antiplatelet may be better than alteplase with respect to preventing END within 24 h when baseline SBP ≥140 mmHg.

Asunto(s)

Presión Sanguínea , Fibrinolíticos , Inhibidores de Agregación Plaquetaria , Accidente Cerebrovascular , Activador de Tejido Plasminógeno , Humanos , Masculino , Femenino , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Anciano , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Tejido Plasminógeno/administración & dosificación , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/complicaciones , Anciano de 80 o más Años , Método Doble Ciego , Accidente Cerebrovascular Isquémico/tratamiento farmacológico