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Hypertrophic scar (HS) is a fibroproliferative skin disease characterized by abnormal wound healing and pathological excessive fibrosis of the skin. Currently, the molecular mechanism of the disease is still largely unknown, and there is no effective drug treatment. In this study, we explored the effect of Rynchopeterine on the formation of HS. HS fibroblasts (HSFs) were isolated from the HS tissues of patients recovering from severe burns. After treating HSFs with different concentrations of Rynchopeterine, CCK-8, EdU, and Annexin V-FITC/PI assays were used to detect the proliferation, apoptosis, and contractile ability of HSFs. RT-qPCR and Western blotting were performed to evaluate the effect of Rynchopeterine on the expression of miR-21 and hypoxia-inducible factor 1-alpha subunit suppressor (HIF1AN). The dual-luciferase reporter gene was used to verify the targeting relationship between miR-21 and HIF1AN. Rynchopeterine reduced the expression of Col1a2, Col3a1, and α-SMA, inhibited proliferation and contraction of HSFs, and increased apoptosis in a dose-dependent manner. miR-21 was highly expressed in HS tissues and HSFs, and Rynchopeterine could inhibit miR-21 expression. Overexpression of miR-21 and knockdown of HIF1AN increased proliferation, activation, contraction, and collagen synthesis of HSFs, and inhibited their apoptosis. In vivo, Rynchopeterine could reduce the collagen content of the dermis and the positive ratio of PCNA and α-SMA. Rynchopeterine is a good therapeutic agent for HS, which up-regulates the expression of HIF1AN by inhibiting miR-21, thereby inhibiting the formation of HS.
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Apoptosis , Proliferación Celular , Cicatriz Hipertrófica , Fibroblastos , MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/tratamiento farmacológico , Cicatriz Hipertrófica/patología , Cicatriz Hipertrófica/genética , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Animales , Ratones , Masculino , Células Cultivadas , Femenino , Cicatrización de Heridas/efectos de los fármacos , Oxigenasas de Función Mixta , Proteínas RepresorasRESUMEN
BACKGROUND: Lacunes are associated with cognitive impairment. We sought to identify strategic lacune locations associated with mild cognitive impairment (MCI) and subtypes of MCI among older adults, and further to examine the role of white matter hyperintensities and perivascular spaces in the association. METHODS: This population-based cross-sectional study included 1230 dementia-free participants in the brain magnetic resonance imaging substudy (2018-2020) in MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China). Lacunes were visually identified in frontal lobe, parieto-occipital lobe, temporal lobe, insula, basal ganglia, thalamus, cerebellum, and brainstem. MCI, amnestic MCI (aMCI), and nonamnestic MCI (naMCI) were defined following the Petersen's criteria. Data were analyzed using logistic regression models. RESULTS: Of the 1230 participants (age, ≥60 years; mean age, 69.40; SD, 4.30 years; 58.5% women), lacunes were detected in 357 people and MCI was defined in 286 individuals, including 243 with aMCI and 43 with naMCI. Lacunes in the supratentorial area, internal capsula, putamen/pallidum, and insula was significantly associated with increased odds ratio of MCI (multivariable-adjusted odds ratio ranged 1.40-3.21; P<0.05) and aMCI (multivariable-adjusted odds ratio ranged 1.46-3.36; P<0.05), whereas lacunes in the infratentorial area and brainstem were significantly associated with naMCI (multivariable-adjusted odds ratio ranged 2.68-3.46; P<0.01). Furthermore, the associations of lacunes in insula and internal capsula with MCI and aMCI, as well as the associations of lacunes in infratentorial area and brainstem with naMCI were present independent of white matter hyperintensities volume and perivascular spaces number. CONCLUSIONS: Lacunes in the internal capsula, putamen/pallidum, insula, and brainstem may represent the strategic lacunes that are independently associated with MCI, aMCI, or naMCI in Chinese older adults. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017758.
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In the field of chiral amine synthesis, ω-amine transaminase (ω-ATA) is one of the most established enzymes capable of asymmetric amination under optimal conditions. However, the applicability of ω-ATA toward more non-natural complex molecules remains limited due to its low transamination activity, thermostability, and narrow substrate scope. Here, by employing a combined approach of computational virtual screening strategy and combinatorial active-site saturation test/iterative saturation mutagenesis strategy, we have constructed the best variant M14C3-V5 (M14C3-V62A-V116S-E117I-L118I-V147F) with improved ω-ATA from Aspergillus terreus (AtATA) activity and thermostability toward non-natural substrate 1-acetylnaphthalene, which is the ketone precursor for producing the intermediate (R)-(+)-1-(1-naphthyl)ethylamine [(R)-NEA] of cinacalcet hydrochloride, showing activity enhancement of up to 3.4-fold compared to parent enzyme M14C3 (AtATA-F115L-M150C-H210N-M280C-V149A-L182F-L187F). The computational tools YASARA, Discovery Studio, Amber, and FoldX were applied for predicting mutation hotspots based on substrate-enzyme binding free energies and to show the possible mechanism with features related to AtATA structure, catalytic activity, and stability in silico analyses. M14C3-V5 achieved 71.8% conversion toward 50 mM 1-acetylnaphthalene in a 50 mL preparative-scale reaction for preparing (R)-NEA. Moreover, M14C3-V5 expanded the substrate scope toward aromatic ketone compounds. The generated virtual screening strategy based on the changes in binding free energies has successfully predicted the AtATA activity toward 1-acetylnaphthalene and related substrates. Together with experimental data, these approaches can serve as a gateway to explore desirable performances, expand enzyme-substrate scope, and accelerate biocatalysis.IMPORTANCEChiral amine is a crucial compound with many valuable applications. Their asymmetric synthesis employing ω-amine transaminases (ω-ATAs) is considered an attractive method. However, most ω-ATAs exhibit low activity and stability toward various non-natural substrates, which limits their industrial application. In this work, protein engineering strategy and computer-aided design are performed to evolve the activity and stability of ω-ATA from Aspergillus terreus toward non-natural substrates. After five rounds of mutations, the best variant, M14C3-V5, is obtained, showing better catalytic efficiency toward 1-acetylnaphthalene and higher thermostability than the original enzyme, M14C3. The robust combinational variant acquired displayed significant application value for pushing the asymmetric synthesis of aromatic chiral amines to a higher level.
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Aspergillus , Estabilidad de Enzimas , Transaminasas , Transaminasas/metabolismo , Transaminasas/genética , Transaminasas/química , Aspergillus/enzimología , Aspergillus/genética , Especificidad por Sustrato , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Aminas/metabolismo , Aminas/química , Dominio CatalíticoRESUMEN
BACKGROUND: Routine coagulation tests are not widely accepted diagnostic criteria of trauma-induced hypercoagulopathy (TIH) due to insensitivity. Lymphatic vessels drain approximately 10% of the interstitial fluid into the lymphatic system and form lymph. SUBJECTIVE: The purpose of this study was to identify the potential lymph biomarkers for TIH. METHODS: Eighteen male Sprague-Dawley rats were randomly assigned to the sham (non-fractured rats with sham surgery and vehicle treatment), the VEH (fractured rats with vehicle treatment) and the CLO (fractured rats with clopidogrel treatment) group. Thoracic duct lymph was obtained to perform proteomics and untargeted metabolomics. RESULTS: A total of 1207 proteins and 16,695 metabolites were identified. The top 5 GO terms of lymph proteomics indicated that oxidative stress and innate immunity were closely associated with TIH and antithrombotic therapy. The top 5 GO terms of lymph metabolomics showed that homocystine and lysophosphatidylcholine were the differential expressed metabolites (DEMs) between the sham and VEH groups, while cholic acid, docosahexaenoic acid, N1-Methyl-2-pyridone-5-carboxamide, isoleucine and testosterone are the DEMs between the VEH and CLO group. CONCLUSIONS: This study presents the first proteomic and metabolomic profiling of lymph after TIH and antithrombotic therapy, and predicts the possible lymph biomarkers for TIH.
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OBJECTIVE: To investigate the prevalence and associated factors of excessive daytime sleepiness (EDS) among rural-dwelling Chinese older adults. METHODS: We collected data on demographic, epidemiological, and clinical factors via in-person interviews and clinical examinations following a structured questionnaire. The 15-item Geriatric Depression Scale (GDS-15) was used to assess depressive symptoms, the Berlin questionnaire (BQ) to assess obstructive sleep apnea (OSA) risk; and the Epworth Sleepiness Scale (ESS) to assess sleep characteristics. EDS was defined as the total ESS score > 10. RESULTS: This population-based study engaged 4845 participants (age ≥ 65 years, 57.3% female) in the 2018 examination of the Multimodal Interventions to Delay Dementia and Disability in Rural China. The prevalence of EDS was 9.3% in the total sample, 8.3% in females, and 10.6% in males, and the prevalence decreased with advanced age. Logistic regression analysis revealed that EDS was significantly associated with age (multivariable-adjusted odds ratio [OR] = 0.97; 95% confidence interval [CI] 0.95-0.99), female sex (0.53; 0.36-0.77), hypertension (0.68; 0.54-0.85), depressive symptoms (2.68; 2.07-3.46), high OSA risk (2.11; 1.69-2.63), and poor sleep quality (2.12; 1.60-2.82). CONCLUSION: EDS affects nearly one-tenth of rural older adults in China. Older age, female sex, and hypertension were associated with a decreased likelihood of EDS, while depressive symptoms, high OSA risk, and poor sleep quality were correlated with an elevated likelihood of EDS.
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Trastornos de Somnolencia Excesiva , Población Rural , Humanos , Femenino , Masculino , Anciano , Trastornos de Somnolencia Excesiva/epidemiología , Trastornos de Somnolencia Excesiva/diagnóstico , China/epidemiología , Población Rural/estadística & datos numéricos , Prevalencia , Factores de Riesgo , Anciano de 80 o más Años , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/diagnóstico , Estudios TransversalesRESUMEN
BACKGROUND: We aimed to explore the association of sleep duration with depressive symptoms among rural-dwelling older adults in China, and to estimate the impact of substituting sleep with sedentary behavior (SB) and physical activity (PA) on the association with depressive symptoms. METHODS: This population-based cross-sectional study included 2001 rural-dwelling older adults (age ≥ 60 years, 59.2% female). Sleep duration was assessed using the Pittsburgh Sleep Quality Index. We used accelerometers to assess SB and PA, and the 15-item Geriatric Depression Scale to assess depressive symptoms. Data were analyzed using restricted cubic splines, compositional logistic regression, and isotemporal substitution models. RESULTS: Restricted cubic spline curves showed a U-shaped association between daily sleep duration and the likelihood of depressive symptoms (P-nonlinear < 0.001). Among older adults with sleep duration < 7 h/day, reallocating 60 min/day spent on SB and PA to sleep were associated with multivariable-adjusted odds ratio (OR) of 0.81 (95% confidence interval [CI] = 0.78-0.84) and 0.79 (0.76-0.82), respectively, for depressive symptoms. Among older adults with sleep duration ≥ 7 h/day, reallocating 60 min/day spent in sleep to SB and PA, and reallocating 60 min/day spent on SB to PA were associated with multivariable-adjusted OR of 0.78 (0.74-0.84), 0.73 (0.69-0.78), and 0.94 (0.92-0.96), respectively, for depressive symptoms. CONCLUSIONS: Our study reveals a U-shaped association of sleep duration with depressive symptoms in rural older adults and further shows that replacing SB and PA with sleep or vice versa is associated with reduced likelihoods of depressive symptoms depending on sleep duration.
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Depresión , Ejercicio Físico , Población Rural , Conducta Sedentaria , Sueño , Humanos , Femenino , Masculino , Anciano , Depresión/epidemiología , Estudios Transversales , Ejercicio Físico/fisiología , Persona de Mediana Edad , Sueño/fisiología , China/epidemiología , Anciano de 80 o más Años , Análisis de DatosRESUMEN
The citrus red mite, Panonychus citri, is one of the most notorious and devastating citrus pests around the world that has developed resistance to multiple chemical acaricides. In previous research, we found that spirodiclofen-resistant is related to overexpression of P450, CCE, and ABC transporter genes in P. citri. However, the regulatory mechanisms of these detoxification genes are still elusive. This study identified all hormone receptor 96 genes of P. citri. 8 PcHR96 genes contained highly conserved domains. The expression profiles showed that PcHR96h was significantly upregulated in spirodiclofen resistant strain and after exposure to spirodiclofen. RNA interference of PcHR96h decreased expression of detoxification genes and increased spirodiclofen susceptibility in P. citri. Furthermore, molecular docking, heterologous expression, and drug affinity responsive target stability demonstrated that PcHR96h can interact with spirodiclofen in vitro. Our research results indicate that PcHR96h plays an important role in regulating spirodiclofen susceptibility and provides theoretical support for the resistance management of P. citri.
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Compuestos de Espiro , Animales , Compuestos de Espiro/farmacología , Compuestos de Espiro/metabolismo , Acaricidas/farmacología , Propionatos/farmacología , Propionatos/metabolismo , Tetranychidae/efectos de los fármacos , Tetranychidae/genética , Tetranychidae/metabolismo , Simulación del Acoplamiento Molecular , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/metabolismo , Resistencia a Medicamentos/genética , 4-Butirolactona/análogos & derivadosRESUMEN
Malicious software (malware), in various forms and variants, continues to pose significant threats to user information security. Researchers have identified the effectiveness of utilizing API call sequences to identify malware. However, the evasion techniques employed by malware, such as obfuscation and complex API call sequences, challenge existing detection methods. This research addresses this issue by introducing CAFTrans, a novel transformer-based model for malware detection. We enhance the traditional transformer encoder with a one-dimensional channel attention module (1D-CAM) to improve the correlation between API call vector features, thereby enhancing feature embedding. A word frequency reinforcement module is also implemented to refine API features by preserving low-frequency API features. To capture subtle relationships between APIs and achieve more accurate identification of features for different types of malware, we leverage convolutional neural networks (CNNs) and long short-term memory (LSTM) networks. Experimental results demonstrate the effectiveness of CAFTrans, achieving state-of-the-art performance on the mal-api-2019 dataset with an F1 score of 0.65252 and an AUC of 0.8913. The findings suggest that CAFTrans improves accuracy in distinguishing between various types of malware and exhibits enhanced recognition capabilities for unknown samples and adversarial attacks.
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INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.
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Objective: Insomnia is a common symptom in subhealthy states. In patients, long-term insomnia symptoms can lead to decreased immune function, even mental depression, thus seriously affecting quality of life. Therefore, this study aims to observe the therapeutic effect of huo li su (HLS) oral solution combined with zopiclone in the treatment of insomnia to find suitable drugs for treatment. Methods: A total of 161 patients with insomnia from January 2017 to March 2022 were selected in this retrospective cohort study. The patients were divided into the observation (82 cases, receiving HLS oral solution and zopiclone) and control (79 cases, receiving zopiclone alone) groups in accordance with therapeutic drug administration. The differences in the scores of the 2 groups on the Sleep Disorder Scale (SDRS), Pittsburgh Sleep Quality Index (PSQI), Fatigue Inventory 14 (FS-14), and traditional Chinese medicine (TCM) syndromes before and after treatment were compared. Results: No significant differences in age, gender, disease duration, body mass index (BMI), and other general data were found between the 2 groups (P > .05). The TCM syndrome, PSQI, FS-14, and SDRS scores before treatment of the 2 groups were not significantly different (P < .05). After 4 weeks of treatment, the TCM syndrome, PSQI, FS-14, and SDRS scores of the observation group were significantly lower than those of the control group. Conclusion: HLS oral solution combined with zopiclone can effectively improve insomnia symptoms and is superior to zopiclone alone.
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The radon exhalation characteristics of rocks will change significantly during water saturation treatment, and radon, as an important tracer, is of great significance in predicting rock activities. In this paper, the radon exhalation characteristics of rocks after saturated with different water contents were studied by centrifugal test, radon measurement test and other indoor tests. The results show that the radon exhalation rate of rocks shows a rising and then decreasing trend with the increase of rock water saturation. The radon precipitation rate peaked at 0.7 Sw â¼ 0.8 Sw, and the high water saturation had an obvious inhibiting effect on the radon exhalation rate of rocks. The research results are of great significance in predicting the rock-water-based geological processes.
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Bilateral facial palsy with paresthesia (FDP) is a rare variant of GBS, characterized by simultaneous bilateral facial palsy and paresthesia of the distal limbs. Mounting evidence indicates that the presence of anti-GT1a IgG has a pathogenic role as an effector molecule in the development of cranial nerve palsies in certain patients with GBS, whereas anti-GT1a antibody is rarely presented positive in FDP. Here, we report the case of a 33-year-old male diagnosed with FDP presented with acute onset of bilateral facial palsy and slight paresthesias at the feet as the only neurological manifestation. An antecedent infection with no identifiable reason for the fever or skin eruptions was noted in the patient. He also exhibited cerebrospinal fluid albuminocytologic dissociation and abnormal nerve conduction studies. Notably, the testing of specific serum anti-gangliosides showed positive anti-GT1a IgG/IgM Ab. The patient responded well to intravenous immunoglobulin therapy. This case brings awareness to a rare variant of GBS, and provides the first indication that anti-GT1a antibodies play a causative role in the development of FDP. The case also suggests that prompt management with IVIG should be implemented if FDP is diagnosed.
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Autoanticuerpos , Parálisis Facial , Gangliósidos , Parestesia , Humanos , Masculino , Adulto , Parestesia/inmunología , Parestesia/diagnóstico , Parestesia/etiología , Parálisis Facial/diagnóstico , Parálisis Facial/etiología , Parálisis Facial/inmunología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Gangliósidos/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/inmunologíaRESUMEN
Accurate monitoring of tetracycline (TC) residues in the environment is crucial for avoiding contaminant risk. Herein, a novel TC biosensor was facilely designed by integrating silver nanoparticles (Ag NPs) into the porphyrin metal-organic matrix (Ag@AgPOM) as a bifunctional electrochemiluminescence (ECL) probe. Different from the step-by-step synthesis of the co-reaction accelerator and ECL emitter, the co-reaction accelerators Ag NPs were in situ-grown on the surface of 5,10,15,20-tetrakis (4-carboxyphenyl) porphyrin (TCPP) via a simple one-pot approach. Symbiotic Ag NPs on Ag@AgPOM formed an intimate interface and increased the collision efficiency of the ECL reaction, achieving the ECL enhancement of TCPP. Under the optimized conditions, the ternary ECL biosensor showed a wide linear detection range toward TC with a low detection limit of 0.14 fmol L-1. Compared with the traditional HPLC and ELISA methods, satisfied analytical adaptability made this sensing strategy feasible to monitor TC in complex environmental samples.
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This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473 and its downstream targets on FGR progression in trophoblast cells. Placental vascular distribution, placental vascular index (VIMV), CD34 expression, and histological changes were compared between control and FGR groups. FGR-related differentially expressed genes (DEGs) were analyzed and validated by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in placentae. In vitro experiments examined the regulatory relationships among LINC00473, miR-5189-5p, and StAR, followed by investigations into their impacts on cell proliferation and apoptosis. FGR placentae exhibited irregular shapes, uneven parenchymal echo, stromal dysplasia, ischemic infarction, and variable degrees of thickening in some cases. FGR samples showed less prominent mother vessel lakes, significantly lower VIMV, and decreased CD34 expression. Hematoxylin & eosin (H&E) staining revealed placental fibrosis, fibrin adhesion, infarction, and interstitial dysplasia in FGR. LINC00473, miR-5189-5p, and StAR were identified as DEG, with qPCR demonstrating a significant increase in LINC00473 and a decrease in miR-5189-5p in FGR, while both qPCR and IHC indicated a significant increase in StAR expression. LINC00473 served as an endogenous sponge against miR-5189-5p in human HTR-8/SV neo cells, and StAR expression was regulated by both LINC00473 and miR-5189-5p. Dysregulation of these genes affected cell proliferation and apoptosis. Pathological changes in the placenta are significant contributors to FGR, with placental microblood flow potentially serving as an indicator for monitoring its progression. LINC00473 and its downstream targets may modulate trophoblasts proliferation and apoptosis, thus influencing the onset of FGR, suggesting novel avenues for diagnosis and treatment.
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Apoptosis , Retardo del Crecimiento Fetal , MicroARNs , Placenta , ARN Largo no Codificante , Trofoblastos , Adulto , Femenino , Humanos , Embarazo , Apoptosis/genética , Proliferación Celular/genética , Retardo del Crecimiento Fetal/genética , Retardo del Crecimiento Fetal/patología , Retardo del Crecimiento Fetal/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Placenta/metabolismo , Placenta/irrigación sanguínea , Placenta/patología , Circulación Placentaria , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Trofoblastos/metabolismo , Trofoblastos/patologíaRESUMEN
Background: The purpose of this study was to assess the efficacy and safety of rectal modular dissection (RMD) in male patients with middle and low rectal cancer. RMD is a technique used to guide the surgical procedure for rectal mobilization, with the ultimate goal of achieving total mesorectal excision. In order to evaluate the effectiveness of RMD, a single-center, non-inferiority randomized clinical trial was carried out. Methods: Eligible patients were randomly assigned into two groups: the RMD group and the traditional rectal mobilization (TRM) group. Demographic characteristics, perioperative data and pathological results of the surgical specimens were collected for analysis. additionally, assessments of urogenital function and defecation function were conducted for all participants. Results: A total of 103 patients (RMD group 53 patients and TRM group 50 patients) were included to analyzed. There were no significant differences in age, body mass index, ASA classification, and tumor characteristics between two groups. The RMD group had significantly lower blood loss (P = 0.00), shorter operative duration (P = 0.00), and shorter hospital stay (P = 0.04) compared to the TRM group. The complete rate of mesorectal excision was higher in the RMD group (98.1%) compared to the TRM group (86.0%, P = 0.02). In terms of functional outcomes, the RMD group had better evaluation scores for urethral function (IPSS score, P = 0.01), erectile function (IIEF-5 score, P = 0.00) and defecation function (LARS score, P = 0.00) at the one-year postoperative follow-up. The 1-year disease-free survival rate was similar between the two groups (P = 0.28). Conclusions: These results suggest that RMD is an effective and safe approach for achieving total mesorectal excision while promoting better functional outcomes for patients. The trial was registered in Chinese Clinical Trial Registry (ChiCTR2100052094).
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Background: Jianpi Yangxue Qufeng Compound (JPYXQFC) is a Chinese medicine widely used in the clinical treatment of atopic dermatitis (AD) and has a significantly therapeutic effect. However, the mechanism of JPYXQFC in AD has been not understood clearly. Objective: This study aimed to explore the effect of JPYXQFC on AD model cells and rats by regulating TLR4/MyD88/NF-κB signaling pathway. Methods: The rats (n > 5) were given JPYXQFC decoction orally twice a day for three days, and their abdominal aortic blood was collected. HaCaT cell proliferation rate was tested by cell counting kit-8 (CCK-8) assays. We induced AD rat model through 2, 4-dinitrofluorobenzene (DNFB). AD rats were given oral JPYXQFC decoction and cetirizine (positive control). HaCaT cells were pretreated with JPYXQFC drug serum or cetirizine for 0.5 h and then stimulated with TNF-α/IFN-γ for 1 h. The mRNA levels of TLR4, MyD88, NF-κB, IL-4, IL-13, MCP1, TNF-α and TSLP were detected by quantitative real-time PCR (Q-RT-PCR), and TLR4/MyD88/NF-κB pathway protein expression was tested by Western blot. The total serum levels of immunoglobulin E (IgE), thymus and activation regulated chemokine/chemokine (C-C motif) ligand 17 (TARC/CCL17) were detected by enzyme-linked immunosorbent assay (ELISA). The epidermal thickness was detected by hematoxylin and eosin (HE) staining. The dermatitis area and score were measured by a ruler and a four-point scoring method, respectively. Results: JPYXQFC significantly inhibited mRNA and protein expression of the TLR4/MyD88/NF-κB pathway and Histone H3 in TNF-α/IFN-γ-induced HaCaT cells and DNFB-induced rats, decreased the mRNA of IL-4, IL-13, MCP1, CCL22, TSLP and the level of AD-related genes IgE and TAEC/CCL17 of TNF-α/IFN-γ-induced HaCaT cells. Meanwhile, JPYXQFC significantly reduced the dermatitis area and dermatitis score in DNFB-induced rats, inhibited the levels of pro-inflammatory cytokines IL-6 and TNF-α, and upregulated FLG, as well as inhibited the levels of IgE and TARC/CCL17 in the serum of AD rats. Conclusion: JPYXQFC alleviates AD by inhibiting the activation of TLR4/MyD88/NF-κB pathway.
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Objective: To compare the effectiveness of robot-assisted (RA) minimally invasive surgery versus traditional fluoroscopy-assisted (FA) open posterior fixation surgery in treating thoracolumbar fractures with ankylosing spondylitis (AS). Methods: A clinical data of 21 cases of thoracolumbar fractures with AS who met the selection criteria between December 2016 and December 2023 was retrospectively analyzed. Ten cases underwent RA minimally invasive surgery group (RA group) and 11 cases underwent FA open posterior fixation surgery (FA group). There was no significant difference in gender, age, fracture segment distribution, fracture type, time from injury to surgery, visual analogue scale (VAS) score, and American Spinal Injury Association (ASIA) grading between RA group and FA group ( P>0.05). The operation time, intraoperative blood loss, radiation exposure time, radiation dose, hospital stay, and complications of the two groups were recorded. According to Gertzbein-Robbins criteria, the accuracy of screw implantation was evaluated by CT within 1 week after surgery. During follow-up, pain and nerve function were evaluated by VAS score and ASIA grading. Results: All patients underwent surgery successfully, and there was no significant difference in operation time ( P>0.05). The intraoperative blood loss and hospital stay in the RA group were significantly less than those in the FA group ( P<0.05), and the radiation exposure time and radiation dose were significantly more than those in the FA group ( P<0.05). A total of 249 pedicle screws were implanted in the two groups, including 118 in the RA group and 131 in the FA group. According to the Gertzbein-Robbins criteria, the proportion of clinically acceptable screws (grades A and B) in the RA group was significantly higher than that in the FA group ( P<0.05). Patients in both groups were followed up 3-12 months, with an average of 6.8 months. The VAS scores of the two groups after surgery were significantly lower than those before surgery, and the differences were significant ( P<0.05). The RA group had lower scores than the fluoroscopy group at 1 week and 3 months after surgery ( P<0.05). There was no significant difference in neurological function grading between groups at 1 week and 3 months after surgery ( P>0.05). In the FA group, 1 case of deep infection and 1 case of deep vein thrombosis of lower extremity occurred, while no complication occurred in the RA group, and there was no significant difference in the incidence of complications between groups ( P>0.05). Conclusion: Both RA minimally invasive surgery and FA open posterior fixation surgery can achieve good effectiveness. Compared with the latter, the former has more advantages in terms of intraoperative blood loss, hospital stay, and accuracy of pedicle screw insertion.
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Fijación Interna de Fracturas , Vértebras Lumbares , Procedimientos Quirúrgicos Robotizados , Fracturas de la Columna Vertebral , Espondilitis Anquilosante , Vértebras Torácicas , Humanos , Estudios Retrospectivos , Espondilitis Anquilosante/cirugía , Fracturas de la Columna Vertebral/cirugía , Fluoroscopía/métodos , Vértebras Torácicas/cirugía , Vértebras Torácicas/lesiones , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Procedimientos Quirúrgicos Robotizados/métodos , Vértebras Lumbares/cirugía , Vértebras Lumbares/lesiones , Masculino , Resultado del Tratamiento , Femenino , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Tempo Operativo , Persona de Mediana Edad , Adulto , Tornillos ÓseosRESUMEN
[This retracts the article DOI: 10.3892/ol.2017.6210.].
RESUMEN
Backgrounds: The validity of heart rate variability (HRV) has been substantiated in mental workload assessments. However, cognitive tasks often coincide with physical exertion in practical mental work, but their synergic effects on HRV remains insufficiently established. The study aims were to investigate the combined effects of cognitive and physical load on autonomic nerve functions. Methods: Thirty-five healthy male subjects (aged 23.5 ± 3.3 years) were eligible and enrolled in the study. The subjects engaged in n-back cognitive tasks (1-back, 2-back, and 3-back) under three distinct physical conditions, involving isotonic contraction of the left upper limb with loads of 0 kg, 3 kg, and 5 kg. Electrocardiogram signals and cognitive task performance were recorded throughout the tasks, and post-task assessment of subjective experiences were conducted using the NASA-TLX scale. Results: The execution of n-back tasks resulted in enhanced perceptions of task-load feelings and increased reaction times among subjects, accompanied by a decline in the accuracy rate (p < 0.05). These effects were synchronously intensified by the imposition of physical load. Comparative analysis with a no-physical-load scenario revealed significant alterations in the HRV of the subjects during the cognitive task under moderate and high physical conditions. The main features were a decreased power of the high frequency component (p < 0.05) and an increased low frequency component (p < 0.05), signifying an elevation in sympathetic activity. This physiological response manifested similarly at both moderate and high physical levels. In addition, a discernible linear correlation was observed between HRV and task-load feelings, as well as task performance under the influence of physical load (p < 0.05). Conclusion: HRV can serve as a viable indicator for assessing mental workload in the context of physical activities, making it suitable for real-world mental work scenarios.