RESUMO
Calcineurin inhibitors, such as cyclosporine and tacrolimus (FK506), are commonly used immunosuppressants for preserving transplanted organs and tissues. However, these drugs can cause severe and persistent pain. GluA2-lacking, calcium-permeable AMPA receptors (CP-AMPARs) are implicated in various neurological disorders, including neuropathic pain. It is unclear whether and how constitutive calcineurin, a Ca2+/calmodulin protein phosphatase, controls synaptic CP-AMPARs. In this study, we found that blocking CP-AMPARs with IEM-1460 markedly reduced the amplitude of AMPAR-EPSCs in excitatory neurons expressing vesicular glutamate transporter-2 (VGluT2), but not in inhibitory neurons expressing vesicular GABA transporter, in the spinal cord of FK506-treated male and female mice. FK506 treatment also caused an inward rectification in the current-voltage relationship of AMPAR-EPSCs specifically in VGluT2 neurons. Intrathecal injection of IEM-1460 rapidly alleviated pain hypersensitivity in FK506-treated mice. Furthermore, FK506 treatment substantially increased physical interaction of α2δ-1 with GluA1 and GluA2 in the spinal cord and reduced GluA1/GluA2 heteromers in endoplasmic reticulum-enriched fractions of spinal cords. Correspondingly, inhibiting α2δ-1 with pregabalin, Cacna2d1 genetic knock-out, or disrupting α2δ-1-AMPAR interactions with an α2δ-1 C terminus peptide reversed inward rectification of AMPAR-EPSCs in spinal VGluT2 neurons caused by FK506 treatment. In addition, CK2 inhibition reversed FK506 treatment-induced pain hypersensitivity, α2δ-1 interactions with GluA1 and GluA2, and inward rectification of AMPAR-EPSCs in spinal VGluT2 neurons. Thus, the increased prevalence of synaptic CP-AMPARs in spinal excitatory neurons plays a major role in calcineurin inhibitor-induced pain hypersensitivity. Calcineurin and CK2 antagonistically regulate postsynaptic CP-AMPARs through α2δ-1-mediated GluA1/GluA2 heteromeric assembly in the spinal dorsal horn.
Assuntos
Calcineurina , Caseína Quinase II , Receptores de AMPA , Medula Espinal , Tacrolimo , Animais , Receptores de AMPA/metabolismo , Camundongos , Calcineurina/metabolismo , Masculino , Feminino , Tacrolimo/farmacologia , Medula Espinal/metabolismo , Medula Espinal/efeitos dos fármacos , Caseína Quinase II/metabolismo , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Sinapses/fisiologia , Inibidores de Calcineurina/farmacologia , Fenótipo , Canais de CálcioRESUMO
To optimise soldier protection within body armour systems, knowledge of the boundaries of essential thoraco-abdominal organs is necessary to inform coverage requirements. However, existing methods of organ boundary identification are costly and time consuming, limiting widespread adoption for use on soldier populations. The aim of this study was to evaluate a novel method of using 3D organ models to identify essential organ boundaries from low dose planar X-rays and 3D external surface scans of the human torso. The results revealed that, while possible to reconstruct 3D organs using template 3D organ models placed over X-ray images, the boundary data (relating to the size and position of each organ) obtained from the reconstructed organs differed significantly from MRI organ data. The magnitude of difference varied between organs. The most accurate anatomical boundaries were the left, right, and inferior boundaries of the heart, and lateral boundaries for the liver and spleen. Visual inspection of the data demonstrated that 11 of 18 organ models were successfully integrated within the 3D space of the participant's surface scan. These results suggest that, if this method is further refined and evaluated, it has potential to be used as a tool for estimating body armour coverage requirements.
Assuntos
Abdome , Antropometria , Imageamento Tridimensional , Fígado , Imageamento por Ressonância Magnética , Humanos , Antropometria/métodos , Masculino , Fígado/diagnóstico por imagem , Fígado/anatomia & histologia , Adulto , Abdome/diagnóstico por imagem , Abdome/anatomia & histologia , Tórax/diagnóstico por imagem , Tórax/anatomia & histologia , Baço/diagnóstico por imagem , Baço/anatomia & histologia , Roupa de Proteção , Tronco/diagnóstico por imagem , Militares , Coração/diagnóstico por imagem , Coração/anatomia & histologia , Adulto Jovem , FemininoRESUMO
Associative learning involves complex interactions of multiple cognitive factors. While adult subjects can articulate these factors verbally, for model animals such as macaques, we rely on behavioral outputs. In our study, we used pupillary responses as an alternative measure to capture these underlying cognitive changes. We recorded the dynamic changes in the pupils of three male macaques when they learned the associations between visual stimuli and reward sizes under the classical Pavlovian experimental paradigm. We found that during the long-term learning process, the gradual changes in the pupillary response reflect the changes in the cognitive state of the animals. The pupillary response can be explained by a linear combination of components corresponding to multiple cognitive factors. These components reflect the impact of visual stimuli on the pupils, the prediction of reward values associated with the visual stimuli, and the macaques' understanding of the current experimental reward rules. The changing patterns of these factors during interday and intraday learning clearly demonstrate the enhancement of current reward-stimulus association and the weakening of previous reward-stimulus association. Our study shows that the dynamic response of pupils can serve as an objective indicator to characterize the psychological changes of animals, understand their learning process, and provide important tools for exploring animal behavior during the learning process.
Assuntos
Aprendizagem por Associação , Cognição , Condicionamento Clássico , Pupila , Recompensa , Animais , Masculino , Aprendizagem por Associação/fisiologia , Pupila/fisiologia , Condicionamento Clássico/fisiologia , Cognição/fisiologia , Estimulação Luminosa/métodos , Macaca mulatta , Reflexo Pupilar/fisiologiaRESUMO
BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.
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Anticorpos Monoclonais Humanizados , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Sunitinibe/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Previous studies have shown that the left hemisphere dominates motor function, often observed through homotopic activation measurements. Using a functional connectivity approach, this study investigated the lateralization of the sensorimotor cortex during handwriting and drawing, two complex visuomotor tasks with varying contextual demands. We found that both left- and right-lateralized connectivity in the primary motor cortex (M1), dorsal premotor cortex (PMd), somatosensory cortex, and visual regions were evident in adults (males and females), primarily in an interhemispheric integrative fashion. Critically, these lateralization tendencies remained highly invariant across task contexts, representing a task-invariant neural architecture for encoding fundamental motor programs consistently implemented in different task contexts. Additionally, the PMd exhibited a slight variation in lateralization degree between task contexts, reflecting the ability of the high-order motor system to adapt to varying task demands. However, connectivity-based lateralization of the sensorimotor cortex was not detected in 10-year-old children (males and females), suggesting that the maturation of connectivity-based lateralization requires prolonged development. In summary, this study demonstrates both task-invariant and task-sensitive connectivity lateralization in sensorimotor cortices that support the resilience and adaptability of skilled visuomotor performance. These findings align with the hierarchical organization of the motor system and underscore the significance of the functional connectivity-based approach in studying functional lateralization.
Assuntos
Córtex Motor , Córtex Sensório-Motor , Adulto , Masculino , Feminino , Criança , Humanos , Imageamento por Ressonância Magnética , Córtex Motor/fisiologia , Córtex Somatossensorial , Mapeamento EncefálicoRESUMO
K+-Cl- cotransporter-2 (KCC2) critically controls neuronal chloride homeostasis and maintains normal synaptic inhibition by GABA and glycine. Nerve injury diminishes synaptic inhibition in the spinal cord via KCC2 impairment. However, how KCC2 regulates nociceptive input to spinal excitatory and inhibitory neurons remains elusive. Here, we show that basal GABA reversal potentials were significantly more depolarized in vesicular GABA transporter (VGAT)-expressing inhibitory neurons than those in vesicular glutamate transporter-2 (VGluT2)-expressing excitatory neurons in spinal cords of male and female mice. Strikingly, inhibiting KCC2 with VU0463271 increased currents elicited by puff NMDA and the NMDAR-mediated frequency of mEPSCs in VGluT2, but not in VGAT, dorsal horn neurons. Notably, VU0463271 had no effect on EPSCs monosynaptically evoked from the dorsal root in VGluT2 neurons. Furthermore, VU0463271 augmented α2δ-1-NMDAR interactions and their protein levels in spinal cord synaptosomes. In Cacna2d1 KO mice, VU0463271 had no effect on puff NMDA currents or the mEPSC frequency in dorsal horn neurons. Disrupting α2δ-1-NMDAR interactions with α2δ-1 C-terminus mimicking peptide diminished VU0463271-induced potentiation in the mEPSC frequency and puff NMDA currents in VGluT2 neurons. Additionally, intrathecal injection of VU0463271 reduced mechanical and thermal thresholds in wild-type mice, but not in Cacna2d1 KO mice. VU0463271-induced pain hypersensitivity in mice was abrogated by co-treatment with the NMDAR antagonist, pregabalin (an α2δ-1 inhibitory ligand), or α2δ-1 C-terminus mimicking peptide. Our findings suggest that KCC2 controls presynaptic and postsynaptic NMDAR activity specifically in excitatory dorsal horn neurons. KCC2 impairment preferentially potentiates nociceptive transmission between spinal excitatory interneurons via α2δ-1-bound NMDARs.Significance statementImpaired function of potassium-chloride cotransporter-2 (KCC2), a key regulator of neuronal inhibition, in the spinal cord plays a major role in neuropathic pain. This study unveils that KCC2 controls spinal nociceptive synaptic strength via NMDA receptors in a cell type- and synapse type-specific manner. KCC2 inhibition preferentially augments presynaptic and postsynaptic NMDA receptor activity in spinal excitatory interneurons via α2δ-1 (previously known as a calcium channel subunit). Importantly, spinal KCC2 impairment triggers pain hypersensitivity through α2δ-1-coupled NMDA receptors. These findings pinpoint the cell and molecular substrates for the reciprocal relationship between spinal synaptic inhibition and excitation in chronic neuropathic pain. Targeting both KCC2 and α2δ-1NMDA receptor complexes could be an effective strategy in managing neuropathic pain conditions.
Assuntos
Receptores de N-Metil-D-Aspartato , Simportadores , Animais , Feminino , Masculino , Camundongos , Ácido gama-Aminobutírico/metabolismo , N-Metilaspartato/farmacologia , Peptídeos/farmacologia , Células do Corno Posterior/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Medula Espinal/metabolismo , Simportadores/genética , Simportadores/metabolismo , Sinapses/metabolismoRESUMO
This article explores how race, sex, and gender are better thought of as a continuum rather than binary categories. Starting with a discussion of intersectionality, we examine the importance of ethnic-racial identity and explore unique cultural considerations for working with Black, Latinx, and AAPI transgender and nonbinary youth. We then examine intersex youth and variations of sex development, as well as specific challenges they face. Finally, we explore nonbinary gender identities and the importance of individually tailoring affirming interventions. For all sections, we highlight the strengths and resilience of the youth and offer clinical recommendations for child and adolescent providers.
Assuntos
Identidade de Gênero , Pessoas Transgênero , Criança , Adolescente , Humanos , Saúde MentalRESUMO
OBJECTIVE: To evaluate the feasibility and safety of one- stage bilateral video-assisted thoracic surgery (VATS) for resection of bilateral multiple pulmonary nodules (BMPNs). METHODS: We analyzed the clinical characteristics, pathological features, perioperative outcomes and follow-up data of 41 patients with BMPNs undergoing one-stage bilateral VATS from July, 2011 to August, 2021. RESULTS: One-stage bilateral VATS was performed uneventfully in 40 of the patients, and conversion to open surgery occurred in 1 case. The surgical approaches included bilateral lobectomy (4.9%), lobar-sublobar resection (36.6%) and sublobar-sublobar resection (58.5%) with a mean operative time of 196.3±54.5 min, a mean blood loss of 224.6±139.5 mL, a mean thoracic drainage duration of 4.7±1.1 days and a mean hospital stay of 14±3.8 days. Pathological examination revealed bilateral primary lung cancer in 15 cases, unilateral primary lung cancer in 21 cases and bilateral benign lesions in 5 cases. A total of 112 pulmonary nodules were resected, including 67 malignant and 45 benign lesions. Postoperative complications included pulmonary infection (5 cases), respiratory failure (2 cases), asthma attack (2 cases), atrial fibrillation (2 cases), and drug-induced liver injury (1 case). No perioperative death occurred in these patients, who had a 1-year survival rate of 97.6%. CONCLUSION: With appropriate preoperative screening and perioperative management, one-stage bilateral VATS is feasible and safe for resection of BMPNs.
Assuntos
Nódulos Pulmonares Múltiplos , Humanos , Cirurgia Torácica Vídeoassistida , Estudos de Viabilidade , Complicações Pós-Operatórias , DrenagemRESUMO
Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase â prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase â ¡ clinical trial should be 6.4 mg/m(2).
Assuntos
Antineoplásicos , Neoplasias , Neutropenia , Humanos , Antineoplásicos/efeitos adversos , Dose Máxima Tolerável , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Estudos ProspectivosRESUMO
Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage â ¢ and 4 of stage â £. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
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Quimiorradioterapia , Neoplasias da Bexiga Urinária , Humanos , Idoso , Resultado do Tratamento , Estudos Retrospectivos , Terapia Combinada , Quimiorradioterapia/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Thyroid cancer is one of the malignancy cancers. CircRNA, a non-coding RNA, plays an important role in the development of cancer. The relationship and roles of circ_0124055, miR-486-3p and MTA1 in thyroid cancer have not been reported. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to analyze the RNA levels of circ_0124055, miR-486-3p and MTA1. Western blot was conducted to analyze the protein levels of MTA1, Epithelial cadherin (E-cadherin) and Neuro cadherin (N-cadherin). Subcellular localization assay was used to analyze circ_0124055 location in thyroid cancer cells. Colony formation assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay were carried out to analyze cell proliferation. Cell migration and invasion were analyzed by wound-healing assay and transwell assay. Flow cytometry assay was performed to investigate cell apoptosis. Dual-luciferase reporter assay and RIP assay were employed to analyze the interactions among circ_0124055, miR-486-3p and MTA1. Immunohistochemical (IHC) assay was performed to assess the expression of Ki67, MTA1 and E-cadherin in tumor tissues. Thyroid cancer tumor growth in vivo was evaluated by tumor xenograft mouse model assay. RESULTS: The expression of circ_0124055 was up-regulated in tumor tissues and cells. Knockdown of circ_0124055 could inhibit thyroid cancer cell proliferation, migration and invasion and promote cell apoptosis, accompanied by the dysregulation of E-cadherin and N-cadherin expression. Circ_0124055 could target miR-486-3p, and miR-486-3p could target MTA1. MiR-486-3p inhibitor could restore the effect of circ_0124055 knockdown in the progression of thyroid cancer. Moreover, MTA1 overexpression weakened the inhibitory effects of miR-486-3p mimics on the progression of thyroid cancer. Further, circ_0124055 could influence tumor growth in vivo. CONCLUSION: Circ_0124055 promoted the progression of thyroid cancer cells through the miR-486-3p /MTA1 axis.
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MicroRNAs , Neoplasias da Glândula Tireoide , Humanos , Animais , Camundongos , Neoplasias da Glândula Tireoide/genética , Apoptose , Caderinas/genética , Proliferação de Células , MicroRNAs/genética , Linhagem Celular TumoralRESUMO
To optimise fit and protection of body armour systems, knowledge of the location of thoracoabdominal organ boundaries is required. The aims of this study were (i) determine the effect of sex on essential and desirable thoracoabdominal organ boundaries, and (ii) compare essential thoracoabdominal organ boundaries with small and large hard ballistic plate sizes from the National Institute of Justice (NIJ) and determine if coverage requirements differ between sexes. 33 males and 33 females underwent supine magnetic resonance imaging of their thoracoabdominal organs. Male participants on average displayed more laterally and inferiorly positioned essential and desirable organ boundaries than females. Based on NIJ plate sizes, insufficient coverage of essential organs was identified for male and female participants. A greater range of body armour sizes and designs that better cater to the diverse anatomy of soldier populations is warranted, but must be considered in the context of ergonomic and performance implications.
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Militares , Roupa de Proteção , Feminino , Humanos , Masculino , Tamanho Corporal , Fatores SexuaisRESUMO
The early period of Sino-American communication in Chinese materia medica referred to the historical period from the 17th century, European trade overseas and the frequent communication of missionaries, to 1848 when gold prospectors from China travelled to America. This paper reviewed and examined the three historical events in this period : the spread, trade, and introduction of tea; the first edition of the United States Pharmacopoeia and its collection of Chinese medicines and preparations; and the discovery and trade of American ginseng hoping to explore the basic historical facts of the spread and exchange of Chinese medicine between China and America in the early period. The paper explored these historical factors, provided effective references for developing cooperation in public health between China and America and the start of the constructing of a Global Community of Health for All.
Assuntos
Materia Medica , Medicina Tradicional Chinesa , China , História do Século XIX , História do Século XVIII , Estados Unidos , Materia Medica/história , História do Século XVII , Medicina Tradicional Chinesa/históriaRESUMO
Recent studies show that the human adult visual system exhibits neural plasticity. For instance, short-term monocular deprivation shifts the eye dominance in favor of the deprived eye. This phenomenon is believed to occur in the primary visual cortex by reinstating neural plasticity. However, it is unknown whether the changes in eye dominance after monocularly depriving the visual input can also be induced by alternately depriving both eyes. In this study, we found no changes in binocular balance and interocular correlation sensitivity after a rapid (7 Hz), alternate and monocular deprivation for one hour in adults. Therefore, the effect of short-term monocular deprivation cannot seem to be emulated by alternately and rapidly depriving both eyes.Significance statementPrevious work has shown that short-term binocular function disruption, which its most extreme form is monocular deprivation, could induce neural plasticity in adult visual system. In this study, we found a balanced deprivation of binocular function could not induce a neuroplastic change in human adults. It appears that ocular dominance plasticity in human adults is unique in so far as it is only driven by an input imbalance not balanced deprivation of binocular function.
RESUMO
Expansive clays are found in many countries worldwide, and they exhibit inherent volume change during the seasonal moisture variation causing cracks, heaves, and damages to the overlying pavements. Chemical stabilisation is one of the most used approaches to treat the expansive clay subgrades. Cement, Lime and Fly ash are the most commonly used stabilisers, in which fly is cheaper and a by-product obtained from the coal power plant. This paper reviews fly ash stabilisation on various clay types, including low plasticity clays, high plasticity clays, silty clays, organic clays, and peats. The review begins with the properties of fly ash, followed by the characteristics of fly ash stabilised subgrades. The micro-level mechanism, physical, mechanical, and hydraulic characteristics of stabilised pavements are presented graphically for the Class C, and F fly ashes. The micro-level studies reveal that the pozzolanic reaction is stronger than the cation exchange during the fly ash stabilisation. The unconfined compressive strength (UCS), California bearing ratio (CBR) and resilient modulus (Mr) increased with the fly ash addition and curing time for most soft soils except peat clays. Based on the mechanical and hydraulic characteristics, using 15% class C fly ash with 7 days of curing is recommended for optimum performance. Although few research studies confirm that the leachate limit of stabilised soil is within the acceptable limit, further studies are required to investigate the uptake of heavy metals and other certain carcinogenic contaminants. This study will provide key information for researchers and Engineers on the selection of fly ash stabilisation measures for expansive subgrades.
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Cinza de Carvão , Metais Pesados , Argila , Carvão Mineral , SoloRESUMO
Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase â ¡ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.
Assuntos
Neoplasias Colorretais , Radiocirurgia , Humanos , Fígado/patologia , Pulmão/patologia , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodosRESUMO
Plant-derived volatile organic compounds (VOCs) play pivotal roles in interactions with insect herbivores. Individual VOCs can be directly toxic or deterrent, serve as signal molecules to attract natural enemies, and/or be perceived by distal plant tissues as a priming signal to prepare for expected herbivory. Environmental conditions, as well as the specific plant-insect interaction being investigated, strongly influence the observed functions of VOC blends. The complexity of plant-insect chemical communication via VOCs is further enriched by the sophisticated molecular perception mechanisms of insects, which can respond to one or more VOCs and thereby influence insect behavior in a manner that has yet to be fully elucidated. Despite numerous gaps in the current understanding of VOC-mediated plant-insect interactions, successful pest management strategies such as push-pull systems, synthetic odorant traps, and crop cultivars with modified VOC profiles have been developed to supplement chemical pesticide applications and enable more sustainable agricultural practices. Future studies in this field would benefit from examining the responses of both plants and insects in the same experiment to gain a more complete view of these interactive systems. Furthermore, a molecular evolutionary study of key genetic elements of the ecological interaction phenotypes could provide new insights into VOC-mediated plant communication with insect herbivores.
Assuntos
Herbivoria , Compostos Orgânicos Voláteis , Animais , Insetos , PlantasRESUMO
OBJECTIVE: To compare different types of diabetic macular edema (DME) classified based on optical coherence tomography (OCT) for their responses to Conbercept injection and analyze the factors that affect the treatment responses. METHODS: We retrospectively analyzed the clinical data of 65 patients (76 eyes) with DME diagnosed and treated with intravitreal injection of Conbercept (1+PRN) in our hospital from February, 2019 to February, 2021. According to OCT findings, DME in these patients was classified into cystic macular edema (CME; 28 eyes), serous retinal detachment (SRD; 33 eyes), and diffuse retinal thickening (DRT; 15 eyes). The best corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before and at 3 months after the first treatment. The baseline OCT characteristics of different types of DME were compared, and the correlation of these OCT characteristics with the treatment response to Conbercept was analyzed. RESULTS: All the patients showed significant improvement of the BCVA 3 months after the treatment (P < 0.05). For all the 3 types of DME, the CRT at 3 months after the first treatment was significantly reduced as compared to the baseline (P < 0.05). The number of hyperreflective foci (HF) in the outer retina and the proportion of ellipsoid zone (EZ) interruption were the greatest in SRD group (P < 0.05). The baseline outer retinal HF was significantly correlated with the baseline CRT, CRT changes and CRT after treatment (all P < 0.05). The patients with baseline outer limiting membrane (ELM)/ EZ disruption had poorer baseline BCVA, greater baseline CRT, greater variation of CRT and poorer BCVA at 3 months after treatment (all P < 0.05). CONCLUSION: For all the 3 types of DME, treatment with intravitreal injection of Conbercept can significantly improve the BCVA and CRT of the patients. DME of the SRD type has the best morphological response to Conbercept, while the DRT type has a relatively poor response. A greater number of HF at baseline may indicate a better morphological response to Conbercept treatment, and baseline ELM/EZ disruption may suggest a poor visual prognosis at 3 months after treatment.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Inibidores da Angiogênese , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/tratamento farmacológico , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico por imagem , Edema Macular/tratamento farmacológico , Proteínas Recombinantes de Fusão , Retina/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular , Acuidade VisualRESUMO
OBJECTIVE: Because of the limited treatment options available, oral lopinavir/ritonavir (LPR) was used for treating coronavirus disease (COVID-19) in pediatric patients. This study aimed to assess the efficacy and safety of LPR in COVID-19 pediatric patients with mild symptoms. PATIENTS AND METHODS: This retrospective multicenter analysis included hospitalized children with mild COVID-19 who received LPR at one of 13 hospitals in China from January 1, 2020, to June 1, 2020. Patients treated with LPR were matched with patients not treated with LPR (1:4) according to age, sex, and length of symptom onset and hospitalization. Descriptive statistics and non-parametric tests were applied to compare differences between groups. Kaplan-Meier probability curves and Cox regression models were used to analyze nasal swab turning negative time (recovery time) and hospital discharge days. RESULTS: In total, 23 patients treated with LPR were matched with 92 untreated controls. The median age of patients was 6 years, and 56.52% of them were male. All patients were discharged from the hospital after being cured. The treatment group had a longer nasal swab turning negative time (hazard ratio [HR] 5.33; 95% CI: 1.94-14.67; p = 0.001) than the control group. LPR treatment was also associated with a longer hospitalization time (HR 2.01; 95% CI: 1.24-3.29; p = 0.005). After adjusting for the influence of LPR treatment, adverse drug reaction events were associated with a longer nasopharyngeal swab negative time (HR 4.67; 95% CI 1.35-16.11; p = 0.015). CONCLUSIONS: For children with mild COVID-19, LPR is inferior to conventional treatment in reducing virus shedding time and hospitalization duration and is associated with increased adverse reactions.
Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , SARS-CoV-2 , Administração Oral , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Criança , China , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Masculino , Estudos Retrospectivos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversosRESUMO
Objective: To analyze the features of degenerating cystic thyroid nodules (DCTN) on conventional ultrasound and contrast-enhanced ultrasound (CEUS), and to explore the differentiation between DCTN and papillary thyroid carcinomas (PTC). Methods: A total of 46 DCTN (39 cases, including 12 males and 27 females, with an age range of 25 to 76 years) and 36 PTC (32 cases, including 8 males and 24 females, with an age range of 23 to 68 years) diagnosed via fine- needle aspiration (FNA) or surgery from February 2019 to January 2020 in the First Affiliated Hospital of Nanchang University were enrolled. The size, shape, margin, echogenicity, presence of shadowing, calcification and vascularity of DCTN and PTC were retrospectively evaluated, and 28 DCTN and 30 PTC underwent CEUS were separately analyzed and compared.The t test, χ² test or Fisher's exact test were implemented to compare the features of ultrasound among the two groups. The binary Logistic regression test was performed to determine whether the feature whose difference was statistically significant was an independent predictive risk factor. Results: A univariate analysis indicated that DCTN more frequently showed wider-than-tall shapes, marked hypoechogenicity, well-defined margin and no or dot-lined enhancement (wider-than-tall shapes: 36 vs. 17, χ2=8.511; well-defined margin: 30 vs. 15, χ2=4.523; marked hypoechogenicity: 27 vs. 9, χ2=9.310; no or dot-lined enhancement: 24 vs. 3, χ2=33.369; all Pï¼0.05). A multivariate analysis demonstrated that wider-than-tall shapes, well-defined margin and marked hypoechogenicity were independent predictors for DCTN (OR values were 5.204, 3.134 and 5.042, P values were 0.003, 0.031, and 0.003, respectively). Among 28 DCTN, 15 showed a decrease in mean maximum diameter (24.3±11.4 mm) with a mean time span of (18.6±10.5) months between the presence and absence of suspicious ultrasound features. Conclusions: Compared with PTC, DCTN shows the ultrasound characteristics of wider-than-tall shapes, well-defined margin, marked hypoechogenicity and no or dot-lined enhancement pattern. Ultrasound follow-up can help to identify spontaneous DCTN.