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Aptamers are single-stranded DNA or RNA oligos that can bind to a variety of targets with high specificity and selectivity and thus are widely used in the field of biosensing and disease therapies. Aptamers are generated by SELEX, which is a time-consuming procedure. In this study, using in silico and computational tools, we attempt to predict whether an aptamer can interact with a specific protein target. We present multiple data representations of protein and aptamer pairs and multiple machine-learning-based models to predict aptamer-protein interactions with a fair degree of selectivity. One of our models showed 96.5% accuracy and 97% precision, which are significantly better than those of the previously reported models. Additionally, we used molecular docking and SPR binding assays for two aptamers and the predicted targets as examples to exhibit the robustness of the APIPred algorithm. This reported model can be used for the high throughput screening of aptamer-protein pairs for targeting cancer and rapidly evolving viral epidemics.
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Aptâmeros de Nucleotídeos , Simulação de Acoplamento Molecular , Aptâmeros de Nucleotídeos/química , Técnica de Seleção de Aptâmeros/métodosRESUMO
OBJECTIVE: This research aims to compare the clinical outcomes of VBE-TLIF and MIS-TLIF for the treatment of patients with single-level degenerative lumbar diseases. METHODS: Ninety patients were enrolled in this study. The estimated blood loss, operation time, postoperative hospitalization days, time to functional exercise, amount of surgical drain and inflammatory index were recorded. The visual analog scale, Oswestry dysfunction index and modified MacNab criteria were used to assessed the patient's back and leg pain, functional status and clinical satisfaction rates. RESULTS: The average operation time of the VBE-TLIF group was longer than that of the MIS-TLIF group. The time for functional exercise, length of hospital stay, estimated blood loss and amount of surgical drain in the VBE-TLIF group were relative shorter than those in the MIS-TLIF group. Additionally, the levels of CRP, neutrophil, IL-6 and CPK in the VBE-TLIF group were significantly lower than those in the MIS-TLIF group at postoperative days 1 and 3, respectively (P < 0.001). Patients undergoing VBE-TLIF had significantly lower back VAS scores than those in the MIS-TLIF group on postoperative days 1 and 3 (P < 0.001). No significant differences were found in the clinical satisfaction rates (95.83 vs. 95.24%, P = 0.458) or interbody fusion rate (97.92 vs. 95.24%, P = 0.730) between these two surgical procedures. CONCLUSIONS: Both VBE-TLIF and MIS-TLIF are safe and effective surgical procedures for patients with lumbar diseases, but VBE-TLIF technique is a preferred surgical procedure with merits of reduced surgical trauma and quicker recovery.
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Vértebras Lombares , Fusão Vertebral , Humanos , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Fusão Vertebral/métodos , Região Lombossacral/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: The aim was to determine preoperative gut microbiota metabolites that may be associated with postoperative delirium (POD) development in patients and further study in rodents. SUMMARY BACKGROUND DATA: POD occurs in 9% to 50% of older patients undergoing anesthesia/surgery but lacks effective treatments or prevention. High-throughput metabolomics using liquid chromatography with tandem mass spectrometry has accelerated disease-related biomarkers discovery. We performed metabolomic studies in humans to identify potential metabolite biomarkers linked to POD and examined potential mechanisms in rodents. METHODS: We performed a prospective observational cohort study to examine the metabolomic changes that were associated with the development of POD. Then the gut microbiota-related metabolomic changes were recapitulated by gut microbiota perturbation in rodents. POD was assessed in mice using a battery of behavioral tests including novel objective test, Y-maze test, open-field test, and buried food test. The mechanisms through which gut microbiota-related metabolomic changes influenced POD were examined using chemogenetics. RESULTS: Indole-3-propionic acid (IPA) is a gut microbiota metabolite that belongs to the indole family. Baseline plasma levels of IPA were significantly inversely correlated with the onset of POD in 103 (17 cases) human individuals. This relationship was validated in preclinical mouse models for POD: reducing IPA levels through gut microbiota perturbation promoted POD-like behavior. More importantly, IPA administration deterred POD-like behavior. Colonization of germ-free mice with mutant Clostridium sporogenes that did not produce IPA-promoted POD-like behavior. Chemogenetic studies revealed that the protective effect of IPA in mice was mediated, in part, by peroxisome proliferator-activated receptor gamma coactivator 1-alpha in hippocampal interneurons. CONCLUSIONS: Gut microbiota-derived IPA is an important molecule implicated in the pathogenesis of POD, which could potentially be harnessed for POD prevention.
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Delírio do Despertar , Microbioma Gastrointestinal , Humanos , Camundongos , Animais , Estudos Prospectivos , Indóis/metabolismo , Indóis/farmacologia , BiomarcadoresRESUMO
This study aimed to improve the removal of nitrogen treating rural domestic sewage by developing a novel strategy for achieving partial nitrification-anammox (PNA) in an integrated vertical subsurface flow constructed wetland (VSFCW). The influent ammonia was oxidized to nitrite in the partial nitrification VSFCW (VSFCWPN), and 5 mg/L of hydroxylamine was added under the appropriate dissolved oxygen concentration level (1.2 ± 0.2 mg/L) to stabilize the average nitrite accumulation rate at 88.24% and maintain the effluent NO2--N/NH4+-N ratio at 1.26 ± 0.15. The effluent from VSFCWPN was introduced to the following chamber (VSFCWAN), where ammonia and nitrite were removed by the autotrophic anammox process. This implementation achieved high removal efficiencies for chemical oxygen demand, total nitrogen, and PO43--P, reaching 86.26%, 90.22%, and 78.94%, respectively, with influent concentrations of 120.75 mg/L, 60.02 mg/L, and 5.05 mg/L. Substrate samples were collected from 10 cm height (PN1, AN1) and 25 cm height (PN2, AN2). Microbial community analysis showed that Nitrosomonas dominated the community composition in VSFCWPN, with an increase from 1.61% in the inoculated sludgePN to 16.31% (PN1) and 12.09% (PN2). Meanwhile, Ca. Brocadia accounted for 44.81% (AN1) and 36.50% (AN2) in VSFCWAN. These results confirm the feasibility of the proposed strategy for establishing PNA and efficiently treating rural domestic sewage in an integrated VSFCW.
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Nitrificação , Esgotos , Desnitrificação , Oxidação Anaeróbia da Amônia , Nitrogênio , Áreas Alagadas , Amônia/química , Nitritos , Oxirredução , Reatores BiológicosRESUMO
BACKGROUND: Gut microbiota, a consortium of diverse microorganisms residing in the gastrointestinal tract, has emerged as a key player in neuroinflammatory responses, supporting the functional relevance of the "gut-brain axis." Chronic-constriction injury of the sciatic nerve (CCI) is a commonly used animal model of neuropathic pain with a major input from T cell-mediated immune responses. In this article, we sought to examine whether gut microbiota influences CCI neuropathic pain, and, if so, whether T-cell immune responses are implicated. METHODS: We used a mixture of wide-spectrum oral antibiotics to perturbate gut microbiota in mice and then performed CCI in these animals. Nociceptive behaviors, including mechanical allodynia and thermal hyperalgesia, were examined before and after CCI. Additionally, we characterized the spinal cord infiltrating T cells by examining interferon (IFN)-γ, interleukin (IL)-17, and Foxp3. Using a Foxp3-GFP-DTR "knock-in" mouse model that allows punctual depletion of regulatory T cells, we interrogated the role of these cells in mediating the effects of gut microbiota in the context of CCI neuropathic pain. RESULTS: We found that oral antibiotics induced gut microbiota changes and attenuated the development of CCI neuropathic pain, as demonstrated by dampened mechanical allodynia and thermal hyperalgesia. Percentages of IFN-γ-producing Th1 cells and Foxp3+ regulatory T cells were significantly different between animals that received oral antibiotics (Th1 mean = 1.0, 95% confidence interval [CI], 0.9-1.2; Foxp3 mean = 8.1, 95% CI, 6.8-9.3) and those that received regular water (Th1 mean = 8.4, 95% CI, 7.8-9.0, P < .01 oral antibiotics versus water, Cohen's d = 18.8; Foxp 3 mean = 2.8, 95% CI, 2.2-3.3, P < .01 oral antibiotics versus water, Cohen's d = 6.2). These T cells characterized a skewing from a proinflammatory to an anti-inflammatory immune profile induced by gut microbiota changes. Moreover, we depleted Foxp3+ regulatory T cells and found that their depletion reversed the protection of neuropathic pain mediated by gut microbiota changes, along with a dramatic increase of IFN-γ-producing Th1 cell infiltration in the spinal cord (before depletion mean = 2.8%, 95% CI, 2.2-3.5; after depletion mean = 9.1%, 95% CI, 7.2-11.0, p < .01 before versus after, Cohen's d = 5.0). CONCLUSIONS: Gut microbiota plays a critical role in CCI neuropathic pain. This role is mediated, in part, through modulating proinflammatory and anti-inflammatory T cells.
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Bactérias/imunologia , Citocinas/metabolismo , Microbioma Gastrointestinal , Mediadores da Inflamação/metabolismo , Intestinos/microbiologia , Ciática/imunologia , Medula Espinal/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Comportamento Animal , Modelos Animais de Doenças , Disbiose , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Intestinos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Limiar da Dor , Ciática/metabolismo , Ciática/microbiologia , Ciática/fisiopatologia , Medula Espinal/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th1/metabolismoRESUMO
Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. The long-term survival rate of OS patients is stubbornly low mainly due to the chemotherapy resistance. We therefore aimed to investigate the antitumoral effects and underlying mechanisms of proanthocyanidin B2 (PB2) on OS cells in the current study. The effect of PB2 on the proliferation and apoptosis of OS cell lines was assessed by CCK-8, colony formation, and flow cytometry assays. The target gene and protein expression levels were measured by qRT-PCR and Western blotting. A xenograft mouse model was established to assess the effects of PB2 on OS proliferation and apoptosis in vivo. Results from in vitro experiments showed that PB2 inhibited the proliferation and induced apoptosis of OS cells, and also increased the expression levels of apoptosis-related proteins. Moreover, PB2 induced OS cell apoptosis through suppressing the PI3K/AKT signalling pathway. The in vivo experiments further confirmed that PB2 could inhibit OS tumour growth and induce its apoptosis. Taken together, these results suggested that PB2 inhibited the proliferation and induced apoptosis of OS cells through the suppression of the PI3K/AKT signalling pathway.
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Apoptose/efeitos dos fármacos , Osteossarcoma/enzimologia , Osteossarcoma/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proantocianidinas/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , Permeabilidade , Fosfotirosina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Fault size estimation is of great importance to bearing performance degradation assessment and life prediction. Until now, fault size estimation has generally been based on acoustic emission signals or vibration signals; an approach based on current signals has not yet been mentioned. In the present research, an approximate estimation approach based on current is introduced. The proposed approach is easy to implement for existing inverter-driven induction motors without complicated calculations and additional sensors, immune to external disturbances, and suitable for harsh conditions. Firstly, a feature transmission route from spall, to Hertzian forces, and then to friction torque is simulated based on a spall model and dynamic model of the bearing. Based on simulated results, the relation between spall size and the multiple characteristic vibration frequencies in friction torque is revealed. Secondly, the multiple characteristic vibration frequencies modulated in the current is investigated. Analysis results show that those frequencies modulated in the current are independent of each other, without spectrum overlap. Thirdly, to address the issue of which fault features modulated in the current are very weak, a fault-feature-highlighting approach based on reduced voltage frequency ratio is proposed. Finally, experimental tests were conducted. The obtained results validate that the proposed approach is feasible and effective for spall size estimation.
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This cross-sectional study aimed to identify gender differences in the cervical postures when young adults were using mobile phones, as well as the correlations between the postures and the digital devices use (computer and mobile phone). Questionnaires regarding the habits of computer and mobile phone use were administrated to 429 subjects aged from 17 to 33 years old (19.75 ± 2.58 years old). Subjects were instructed to stand habitually and use a mobile phone as in daily life; the sagittal head and cervical postures were measured by head flexion, neck flexion angle and gaze angle. Male participants had a significantly larger head flexion angle (96.41° ± 12.23° vs. 93.57° ± 12.62°, p = 0.018) and neck flexion angle (51.92° ± 9.55° vs. 47.09° ± 9.45°, p < 0.001) than females. There were significant differences in head (F = 3.62, p = 0.014) and neck flexion (F = 3.99, p = 0.009) between different amounts of computer use. Practitioner Summary: We investigated possible gender differences in head and neck postures of young adults using mobile phones, as well as the potential correlations between these postures and digital device use. We found that males displayed larger head and neck flexion angles than females, which were associated with the amount of computer use.
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Computadores/estatística & dados numéricos , Pescoço , Postura , Smartphone/estatística & dados numéricos , Adolescente , Adulto , Telefone Celular/estatística & dados numéricos , Computadores de Mão/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Masculino , Amplitude de Movimento Articular , Fatores Sexuais , Coluna Vertebral , Adulto JovemRESUMO
PURPOSE: With the dramatic growth of mobile phone usage, concerns have been raised with regard to the adverse health effects of mobile phone on spinal posture. The aim of this study was to determine the head and cervical postures by photogrammetry when viewing the mobile phone screen, compared with those in neutral standing posture. METHODS: A total of 186 subjects (81 females and 105 males) aged from 17 to 31 years old participated in this study. Subjects were instructed to stand neutrally and using mobile phone as in daily life. Using a photographic method, the sagittal head and cervical postures were assessed by head tilt angle, neck tilt angle, forward head shift and gaze angle. RESULTS: The photographic method showed a high intra-rater and inter-rater reliability in measuring the sagittal posture of cervical spine and gaze angle (ICCs ranged from 0.80 to 0.99). When looking at mobile phone, the head tilt angle significantly increased (from 74.55° to 95.22°, p = 0.000) and the neck angle decreased (from 54.68° to 38.77°, p = 0.000). The forward head posture was also confirmed by the significantly increased head shift (from 10.90 to 13.85 cm, p = 0.000). The posture assumed in mobile phone use was significantly correlated with neutral posture (p < 0.05). Males displayed a more forward head posture than females (p < 0.05). The head tilt angle was positively correlated with the gaze angle (r = 0.616, p = 0.000), while the neck tilt angle was negatively correlated with the gaze angle (r = -0.628, p = 0.000). CONCLUSIONS: Photogrammetry is a reliable, quantitative method to evaluate the head and cervical posture during mobile phone use. Compared to neutral standing, subjects display a more forward head posture when viewing the mobile phone screen, which is correlated with neutral posture, gaze angle and gender. Future studies will be needed to investigate a dose-response relationship between mobile phone use and assumed posture.
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Telefone Celular , Vértebras Cervicais/fisiologia , Cabeça/fisiologia , Pescoço/fisiologia , Fotografação , Postura/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Fotogrametria , Projetos Piloto , Reprodutibilidade dos Testes , Adulto JovemRESUMO
STUDY DESIGN: A magnetic resonance neurography (MRN)-based morphometric analysis of the working zone for posterolateral endoscopic lumbar discectomy (PELD) procedures on 32 health volunteers. OBJECTIVE: The purpose is to utilize MRN as a noninvasive evaluation of the Kambin's working zone, and further to analyze operative safety of the PELD procedures. SUMMARY OF BACKGROUND DATA: Intraoperative nerve root injuries of PELD procedures occur relative to the Kambin's triangular working zone, which has been described previously based on formalin-fixed cadaver studies. However, the investigation in living individuals is not known. Thus, it is necessary to evaluate the dimensions of the working zone on both coronal and sagittal plane by radiologic assessments. MATERIALS AND METHODS: MRN images of 32 health volunteers (average age 26.8 y; 18 men, 14 women) were analyzed from L1-L2 to L5-S1. On the coronal plane, we measured the distance from the superior endplate to the nerve root exiting from the dura (distance a), the distance from lateral aspect of the dura to the medial aspect of the nerve root along the superior endplate (distance b), and the angle between the nerve root and plane of the corresponding disk (angle α). On the transversal plane, the vertical distance from the upper facet surface to the exiting nerve root at the lower/upper disk margin level (distance c/d) was also measured. RESULTS: On the coronal plane, distance a was 16.69±5.07 mm (range, 6.60-26.10 mm), distance b was 13.64±2.52 mm (range, 9.30-21.20 mm), angle α was 55.45±7.14 degrees (range, 40.00-73.00 degrees). Distance c on the transversal plane was 5.01±2.66 mm (range, 1.30-13.10 mm) and distance d was 1.99±1.26 mm (range, 0.70-7.80 mm). All these measurements increased as the spine level went down. CONCLUSIONS: The study indicated that MRN was a feasible noninvasive tool to evaluate the anatomic dimensions in the Kambin's working zone. Before PELD, radiologic measurements of this working zone were recommended to perform a safer procedure.
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Discotomia/métodos , Endoscopia/métodos , Vértebras Lombares/patologia , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Ortopédicos/métodos , Adulto , Cadáver , Dura-Máter/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Raízes Nervosas Espinhais/patologia , Raízes Nervosas Espinhais/cirurgia , Adulto JovemRESUMO
Background: As a crucial juncture in students' educational journey, junior high school presents challenges that profoundly influence well-being and academic performance. Physical activity emerges as a pivotal factor shaping the holistic development of junior high school students. Beyond its recognized impact on physical and mental health, engaging in regular physical activity proves effective in augmenting students' adaptability to school life. Despite its importance, the mechanisms through which physical activity influences school adaptation in junior high school students remain understudied in academic research. Objective: In exploring the potential mechanisms, this study aims to validate the mediating roles of resilience and coping styles by examining the association between physical activity and school adaptation among junior high school students. Methods: This study employed cross-sectional survey approach among junior high school students in China. Through the convenience sampling, 1,488 participants aged from 12 to 16 years old (Average age = 13.59, SD = 1.017) from two Junior high schools in Changsha City, Hunan Province were recruited to complete the Physical Activity Scale, School Adaptation Questionnaire for Junior High School Students, Resilience Scale for Adolescents, and Simple Coping Styles Questionnaire. For data analysis, the SPSS 26.0 and Amos 26.0 were used for statistical processing. Results: The results showed that physical activity exhibited a significant correlation with school adaptation (r = 0.656, p < 0.001). Resilience, positive coping style and negative coping style played partial mediating roles between physical activity and school adaptation, with the effect size were 0.229, 0.170, 0.171. The chain mediation effect size of resilience and positive coping style was 0.042, while the chain mediation effect size of resilience and negative coping style was 0.050. Conclusion: Physical activity positively predicts Chinese junior high school students' school adaptation through resilience and coping styles, suggesting that junior high school students should engage in regular physical activity, so as to improve their resilience and positive coping styles, mitigating negative coping styles, thus promoting their school adaptation.
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Objective: To explore the effective targets of Celecoxib in the treatment of heterotopic ossification using network pharmacology methods. Methods: Potential molecules related to heterotopic ossification were obtained by retrieving the GEO and CTD databases and intersecting them. Potential binding targets of Celecoxib were acquired from the STITCH database. A protein-protein interaction network was constructed between potential binding targets of Celecoxib and potential related molecules of heterotopic ossification using the STRING database. Molecules in the protein-protein interaction network were further analyzed using GO and KEGG enrichment analysis in R software, followed by enrichment analysis of active molecules in the Celecoxib-heterotopic ossification target dataset. Hub genes were selected based on the "degree" value and enrichment within the protein-protein interaction network. The binding affinity of hub genes to Celecoxib was observed using molecular docking techniques. Finally, in vitro experiments were conducted to validate the effectiveness of hub genes and explore their regulatory role in the progression of heterotopic ossification. Additionally, the therapeutic effect of Celecoxib, which modulates the expression of the hub genes, was investigated in the treatment of heterotopic ossification. Results: 568 potential molecules related to heterotopic ossification and 76 potential binding targets of Celecoxib were identified. After intersection, 13 potential functional molecules in Celecoxib's treatment of heterotopic ossification were obtained. KEGG analysis suggested pathways such as Rheumatoid arthritis, NF-kappa B signaling pathway, Pathways in cancer, Antifolate resistance, MicroRNAs in cancer play a role in the treatment of heterotopic ossification by Celecoxib. Further enrichment analysis of the 13 potential functional molecules identified 5 hub genes: IL6, CCND1, PTGS2, IGFBP3, CDH1. Molecular docking results indicated that Celecoxib displayed excellent binding affinity with CCND1 among the 5 hub genes. Experimental validation found that CCND1 is highly expressed in the progression of heterotopic ossification, promoting heterotopic ossification in the early stages and inhibiting it in the later stages, with Celecoxib's treatment of heterotopic ossification depending on CCND1. Conclusion: In the process of treating heterotopic ossification with Celecoxib, immune and inflammatory signaling pathways play a significant role. The therapeutic effect of Celecoxib on heterotopic ossification depends on the hub gene CCND1, which plays different roles at different stages of the progression of heterotopic ossification, ultimately inhibiting the occurrence of heterotopic ossification.
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Aging is generally associated with declining somatosensory function, which seems at odds with the high prevalence of chronic pain in older people. This discrepancy is partly related to the high prevalence of degenerative diseases such as osteoarthritis in older people. However, whether aging alters pain processing in the primary somatosensory cortex (S1), and if so, whether it promotes pain chronification is largely unknown. Herein, we report that older mice displayed prolonged nociceptive behavior following nerve injury when compared with mature adult mice. The expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) in S1 was decreased in older mice, whereas PGC-1α haploinsufficiency promoted prolonged nociceptive behavior after nerve injury. Both aging and PGC-1α haploinsufficiency led to abnormal S1 neural dynamics, revealed by intravital two-photon calcium imaging. Manipulating S1 neural dynamics affected nociceptive behavior after nerve injury: chemogenetic inhibition of S1 interneurons aggravated nociceptive behavior in naive mice; chemogenetic activation of S1 interneurons alleviated nociceptive behavior in older mice. More interestingly, adeno-associated virus-mediated expression of PGC-1α in S1 interneurons ameliorated aging-associated chronification of nociceptive behavior as well as aging-related S1 neural dynamic changes. Taken together, our results showed that aging-associated decrease of PGC-1α promotes pain chronification, which might be harnessed to alleviate the burden of chronic pain in older individuals.
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Envelhecimento , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Animais , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Envelhecimento/metabolismo , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Córtex Somatossensorial/metabolismo , Dor Crônica/metabolismoRESUMO
Cortical neural dynamics mediate information processing for the cerebral cortex, which is implicated in fundamental biological processes such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes the cortical network into an aberrant state and, if so, whether it can be brought back to a "normal" operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with spontaneous pain-like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized neural dynamics revealed by intravital two-photon calcium imaging. This synchronization was underpinned by local GABAergic interneuron hypoactivity. Pain-induced cortical synchronization could be attenuated by manipulating local S1 networks or clinically effective pain therapies. Specifically, both chemogenetic inhibition of pain-related c-Fos-expressing neurons and selective activation of GABAergic interneurons significantly attenuated S1 synchronization. Clinically effective pain therapies including carbamazepine and nerve root decompression could also dampen S1 synchronization. More important, restoring a "normal" range of neural dynamics through attenuation of pain-induced S1 synchronization alleviated pain-like behavior. These results suggest that spontaneous pain pushed the S1 regional network into a synchronized state, whereas reversal of this synchronization alleviated pain.
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Córtex Cerebral , Neuralgia , Animais , Camundongos , Interneurônios/fisiologia , Neuralgia/genética , Neuralgia/terapia , Neurônios , Córtex SomatossensorialRESUMO
Serine-rich splicing factor3 (SRSF3) plays an essential role in cell proliferation and inducing and maintaining of cancers as a proto-oncogene. However, the mechanisms of SRSF3 in pan-cancers are still unknown. In our study, a visualized prognostic landscape of SRSF3 in pan-cancer was investigated and the relationship between SRSF3 expression and immune infiltration was also investigated. The expression pattern and prognostic worth of SRSF3 among pan-cancers were explored through different databases, namely, the TCGA and Kaplan-Meier Plotter. Moreover, the survival analysis including Kaplan-Meier method for evaluating between groups was conducted. Further analyses including the correlation between expression SRSF expression and immune infiltration including tumor mutation burden (TMB), microsatellite instability (MSI) was investigated using Spearman test. In ACC, KIRP and UCEC cancer, upregulated expression of SRSF3 was associated with worse disease-free interval (DFI), representing a mechanism in promoting progression of tumor. Our results showed that SRSF3 expression was positively correlated immune cell infiltration, TMB, MSI in certain cancer types, indicating SRSF3 expression to potential value of therapy response. Additionally, we explored the functional characteristics of SRSF in vitro through western blot detecting the expression level of the apoptosis-related proteins in SW480 and 786-O cells. SRSF3 expression was upregulated in pan-cancer tissue compared with normal tissue, which confirmed by immunohistochemistry and its expression indicated poor overall survival and death-specific survival. Therefore, SRSF3 was found to be a possible biomarker for prognostic and therapeutic assessment through bioinformatic analysis. SRSF3 is expressed in various cancers and its high expression correlated to poor survival and disease progression. In summary, SRSF3 expression can be considered as a prognostic biomarker in pan-cancer and therapeutic evaluation.
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Chronic venous insufficiency (CVI) is a common disorder worldwide. Related pathophysiological mechanisms reportedly involve venous pooling and reduced venous return, leading to heaviness, aching, itchiness, tiredness, varicosities, pigmentation, and even lower limb ulceration. Approaches adopted to manage CVI at various stages of clinical-etiology-anatomy-pathophysiology include compression therapy, pharmacological treatment, ultrasound treatment, surgery, electrical or wireless microcurrent stimulation, and pulsed electromagnetic treatment. Among these, polymer-based therapeutic compression materials and wound dressings play increasingly key roles in treating all stages of CVI because of their unique physical, mechanical, chemical, and biological functions. However, the characteristics, working mechanisms, and effectiveness of these CVI treatment materials are not comprehensively understood. The present systematic review examines the structures, properties, types, and applications of various polymer-based compression materials and wound dressings used in prophylaxis and treatment of CVI. Existing problems, limitations, and future trends of CVI treatment materials are also discussed. This review could contribute to the design and application of new functional polymer materials and dressings to enhance the efficiency of CVI treatments, thereby facilitating patients' self-care ability and long-term health improvement.
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Bandagens , Bandagens Compressivas , Insuficiência Venosa/terapia , Alginatos/química , Anti-Infecciosos/química , Doença Crônica , Coloides/química , Exsudatos e Transudatos , Humanos , Teste de Materiais , Polímeros/química , Poliuretanos/química , Pressão , TêxteisRESUMO
BACKGROUND: Extensile lateral approach had been recognized as the gold standard technique for displaced intra-articular calcaneus fractures (DIACFs) while sinus tarsi approach had been increasingly valued by surgeons and comparative clinical outcome was shown in both techniques. Appropriate decisions could be made by the clinicians with the help of cost-utility analysis (CUA) about optimal healthcare for type II/III calcaneus fracture. METHOD: A single-center, retrospective study was conducted in which basic characteristics, clinical outcomes, and health care costs of 109 patients had been obtained and analyzed. Changes in health-related quality of life (HRQoL) scores, validated by EuroQol five-dimensional-three levels (EQ-5D-3L), were used to enumerate quality-adjusted life years (QALYs). Cost-effectiveness was determined by the incremental cost per QALY. RESULTS: One hundred nine patients were enrolled in our study including 62 in the ELA group and 47 in the STA group. There were no significant differences between these two groups in mean total cost, laboratory, and radiographic evaluation expense, surgery, anesthesia, and antibiotic expense. The expense of internal fixation materials ($3289.0 ± 543.9) versus ($2630.6 ± 763.7) and analgesia ($145.8 ± 85.6) versus ($102.9 ± 62.7) in ELA group were significantly higher than in the STA group (P < .001, P = .008, respectively). Visual Analogue Scale (VAS) scores showed significant difference at postoperative 3 and 5 days (P < .001). American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and the Bohlers' and Gissane angle showed no significant differences between the two groups before and after the operation. The cost-effectiveness ratios of ELA and STA were $8766.8 ± 2835.2/QALY and $7914.9 ± 1822.0/QALY respectively, and incremental cost-effectiveness ratio (ICERs) of ELA over STA was $32110.00/QALY, but both showed no significant difference. CONCLUSION: Both ELA and STA techniques are effective operative procedures for the patients with calcaneus fracture. Moreover, STA seems to be more reasonable for its merits including less postoperative pain, and less expense of analgesia as well as internal fixation materials. LEVEL OF EVIDENCE: 5.
Assuntos
Calcâneo/cirurgia , Análise Custo-Benefício , Fixação Interna de Fraturas/economia , Fixação Interna de Fraturas/métodos , Custos de Cuidados de Saúde , Fraturas Intra-Articulares/economia , Fraturas Intra-Articulares/cirurgia , Adulto , Analgesia/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/prevenção & controle , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The technique of percutaneous endoscopic lumbar discectomy (PELD) as a transforaminal approach has been used to treat highly migrated lower lumbar disc herniations. However, due to the different anatomic characteristics of the upper lumbar spine, conventional transforaminal PELD may fail to remove the highly migrated upper lumbar disc nucleus pulposus. Therefore, the purpose of this study was to describe a novel surgical technique, two-level PELD, for the treatment of highly migrated upper lumbar disc herniations and to report its related clinical outcomes. CASE SUMMARY: A 60-year-old male presented with a complaint of pain at his lower back and right lower limb. The patient received 3 mo of conservative treatments but the symptoms were not alleviated. Physical examination revealed a positive femoral nerve stretch test and a negative straight leg raise test for the right leg, and preoperative visual analog scale (VAS) score for the lower back was 6 points and for the right leg was 8 points. Magnetic resonance imaging (MRI) demonstrated L2-L3 disc herniation on the right side and the herniated nucleus pulposus migrated to the upper margin of L2 vertebral body. According to physical examination and imaging findings, surgery was the primary consideration. Therefore, the patient underwent surgical treatment with two-level PELD. The pain symptom was relieved and the VAS score for back and thigh pain was one point postoperatively. The patient was asymptomatic and follow-up MRI scan 1 year after operation revealed no residual nucleus pulposus. CONCLUSION: Two-level PELD as a transforaminal approach can be a safe and effective procedure for highly migrated upper lumbar disc herniation.
RESUMO
Wenyang Lishui decoction (WYD) has been frequently used to treat patients with membranous nephropathy (MN) in China. Our previous study in vitro showed that WYD aqueous extract could alleviate F-actin reorganization of podocytes induced by serum from idiopathic membranous nephropathy (IMN) patients. This study aims to investigate the effects and molecular mechanisms of WYD on MN. MN rat models were induced by cationic bovine serum albumin. Experimental rats were divided into four groups: normal, model, WYD, and benazepril. The normal group consisted of normal rats receiving distilled water for four weeks, while the model, WYD, and benazepril groups consisted of MN rats receiving distilled water, 16.5 g/kg/day WYD aqueous extract, and 10 mg/kg/day benazepril, respectively. Alanine aminotransferase, kidney function, albumin, and 24 h urine total protein (UTP) were measured. Hematoxylin-eosin and electron microscopy analyses were performed. Mouse podocytes were induced to develop cell models by serum from IMN patients with antibody to the M-type phospholipase A2 receptor and spleen and kidney Yang deficiency syndrome. They were divided into five groups: control, model, 2 mg/ml WYD, 4 mg/ml WYD, and 8 mg/ml WYD. CCK-8 assays, flow cytometry, qRT-PCR, and Western blot analyses were performed. In the animal experiment, side effects of WYD were not found. Also, there was no significant difference in kidney function among the groups. In addition, UTP level was significantly reduced, and kidney histological damage was restored in both WYD and benazepril groups but difference in UTP level between them was not found. In the cell experiment, apoptosis rate was increased in the model group while it was decreased by coincubation with WYD. Besides, mRNA and protein levels of p53 were decreased, and those of Bcl-2 were increased by treatment using WYD. In conclusion, WYD could reduce proteinuria and ameliorate podocyte injury by regulating the expression of p53 and Bcl-2. The study is registered in the Chinese Clinical Trial Registry (ChiCTR-OCH-14005137).
RESUMO
OBJECTIVE: To summarize the research progress of surgical procedures in osteochondral lesions of the talus (OLT). METHODS: By consulting the related literature of OLT in recent years, the advantages and disadvantages of various surgical treatment schemes were analyzed and summarized. RESULTS: There are many surgical treatments for OLT, including bone marrow stimulation, osteochondral transplantation, autologous chondrocyte transplantation, and biologically assisted therapy. Various schemes have different indications and limitations. With the continuous development of various technologies, the effectiveness of OLT treatment will gradually improve. CONCLUSION: There are still many difficulties and controversies in the treatment of OLT, and there is no unified treatment plan. It is suggested that individualized operation plan should be formulated according to the specific conditions of patients.