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1.
Mol Med ; 30(1): 119, 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39129004

RESUMEN

BACKGROUND: AGTPBP1 is a cytosolic carboxypeptidase that cleaves poly-glutamic acids from the C terminus or side chains of α/ß tubulins. Although its dysregulated expression has been linked to the development of non-small cell lung cancer, the specific roles and mechanisms of AGTPBP1 in pancreatic cancer (PC) have yet to be fully understood. In this study, we examined the role of AGTPBP1 on PC in vitro and in vivo. METHODS: Immunohistochemistry was used to examine the expression of AGTPBP1 in PC and non-cancerous tissues. Additionally, we assessed the malignant behaviors of PC cells following siRNA-mediated AGTPBP1 knockdown both in vitro and in vivo. RNA sequencing and bioinformatics analysis were performed to identify the differentially expressed genes regulated by AGTPBP1. RESULTS: We determined that AGTPBP1 was overexpressed in PC tissues and the higher expression of AGTPBP1 was closely related to the location of tumors. AGTPBP1 inhibition can significantly decrease cell progression in vivo and in vitro. Moreover, the knockdown of AGTPBP1 inhibited the expression of ERK1/2, P-ERK1/2, MYLK, and TUBB4B proteins via the ERK signaling pathway. CONCLUSION: Our research indicates that AGTPBP1 may be a putative therapeutic target for PC.


Asunto(s)
Carboxipeptidasas , Regulación Neoplásica de la Expresión Génica , Sistema de Señalización de MAP Quinasas , Microtúbulos , Neoplasias Pancreáticas , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Carboxipeptidasas/metabolismo , Carboxipeptidasas/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Progresión de la Enfermedad , Microtúbulos/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/genética , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/metabolismo , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/metabolismo
2.
J Antimicrob Chemother ; 79(9): 2251-2258, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-38980760

RESUMEN

BACKGROUND: Acanthamoeba spp. is the causative agent of Acanthamoeba keratitis and granulomatous amoebic encephalitis. Strathclyde minor groove binders (S-MGBs) are a promising new class of anti-infective agent that have been shown to be effective against many infectious organisms. OBJECTIVES: To synthesize and evaluate the anti-Acanthamoeba activity of a panel of S-MGBs, and therefore determine the potential of this class for further development. METHODS: A panel of 12 S-MGBs was synthesized and anti-Acanthamoeba activity was determined using an alamarBlue™-based trophocidal assay against Acanthamoeba castellanii. Cross-screening against Trypanosoma brucei brucei, Staphylococcus aureus and Escherichia coli was used to investigate selective potency. Cytotoxicity against HEK293 cells allowed for selective toxicity to be measured. DNA binding studies were carried out using native mass spectrometry and DNA thermal shift assays. RESULTS AND DISCUSSION: S-MGB-241 has an IC50 of 6.6 µM against A. castellanii, comparable to the clinically used miltefosine (5.6 µM) and negligible activity against the other organisms. It was also found to have an IC50 > 100 µM against HEK293 cells, demonstrating low cytotoxicity. S-MGB-241 binds to DNA as a dimer, albeit weakly compared to other S-MGBs previously studied. This was confirmed by DNA thermal shift assay with a ΔTm = 1 ±â€Š0.1°C. CONCLUSIONS: Together, these data provide confidence that S-MGBs can be further optimized to generate new, potent treatments for Acanthameoba spp. infections. In particular, S-MGB-241, has been identified as a 'hit' compound that is selectively active against A. castellanii, providing a starting point from which to begin optimization of DNA binding and potency.


Asunto(s)
Acanthamoeba castellanii , Acanthamoeba castellanii/efectos de los fármacos , Humanos , Células HEK293 , Escherichia coli/efectos de los fármacos , Antiprotozoarios/farmacología , Trypanosoma brucei brucei/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Pruebas de Sensibilidad Parasitaria , Supervivencia Celular/efectos de los fármacos
3.
Gastrointest Endosc ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39048038

RESUMEN

BACKGROUND AND AIMS: The risk and pathologic factors of recurrence after endoscopic resection (ER) for superficial esophageal squamous cell carcinoma (ESCC) are inconsistent across studies. We evaluated this in a systematic review and meta-analysis. METHODS: The data of recurrence in such patients were extracted from all studies. Risk ratios (RRs) were combined using random-effects meta-analysis to assess pooled recurrence rate and pathologic risk factors. Relapse-free survival was combined using the Kaplan-Meier method to estimate the relationship between various pathologic factors and recurrence time. RESULTS: We identified 26 studies, with a total of 5100 patients and 321 with recurrences (pooled rate, 6.2%). The risk of recurrence was significantly higher in positive vertical margin (RR, 4.51; 95% confidence interval [CI], 2.16-9.44), positive horizontal margin (RR, 2.54; 95% CI, 1.57-4.13), lymphovascular invasion (LVI) (RR, 2.33; 95% CI, 1.75-3.11; P < .001), lymphatic invasion (LI) (RR, 2.24; 95% CI, 1.24-4.06), and tumor invading submucosa of ≤200 µm (SM1) (RR, 1.71; 95% CI, 1.32-2.21, compared to muscularis mucosa). Patients with LI (hazard ratio, 2.47; 95% CI, 1.24-4.90; P = .02) and LVI (HR, 2.36; 95% CI, 2.22-4.59; P = .0006) tended to have earlier recurrence after ER. CONCLUSIONS: The recurrence rate of superficial esophageal squamous cell carcinoma after ER is acceptable. Patients with positive margins, LVI, LI, and SM1 need to pay significant attention to the risk of recurrence. LI and VI should be evaluated separately. (PROSPERO CRD42023406309.).

4.
Cell Biol Toxicol ; 40(1): 84, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39382613

RESUMEN

Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients' TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3). Hsa_circ_0001165 acts as a miRNA sponge for miR-381-3p, increasing the expression of tensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches.


Asunto(s)
Proliferación Celular , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Factor 4A Eucariótico de Iniciación , Regulación Neoplásica de la Expresión Génica , MicroARNs , ARN Circular , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Línea Celular Tumoral , Factor 4A Eucariótico de Iniciación/genética , Factor 4A Eucariótico de Iniciación/metabolismo , Proliferación Celular/genética , Animales , Regulación Neoplásica de la Expresión Génica/genética , Masculino , Movimiento Celular/genética , Progresión de la Enfermedad , Ratones Desnudos , Femenino , Ratones , Persona de Mediana Edad , Ratones Endogámicos BALB C , Transducción de Señal/genética , ARN Helicasas DEAD-box
5.
Acta Pharmacol Sin ; 45(10): 2186-2198, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38858494

RESUMEN

T cell engaging bispecific antibodies (TCBs) have recently become significant in cancer treatment. In this study we developed MSLN490, a novel TCB designed to target mesothelin (MSLN), a glycosylphosphatidylinositol (GPI)-linked glycoprotein highly expressed in various cancers, and evaluated its efficacy against solid tumors. CDR walking and phage display techniques were used to improve affinity of the parental antibody M912, resulting in a pool of antibodies with different affinities to MSLN. From this pool, various bispecific antibodies (BsAbs) were assembled. Notably, MSLN490 with its IgG-[L]-scFv structure displayed remarkable anti-tumor activity against MSLN-expressing tumors (EC50: 0.16 pM in HT-29-hMSLN cells). Furthermore, MSLN490 remained effective even in the presence of non-membrane-anchored MSLN (soluble MSLN). Moreover, the anti-tumor activity of MSLN490 was enhanced when combined with either Atezolizumab or TAA × CD28 BsAbs. Notably, a synergistic effect was observed between MSLN490 and paclitaxel, as paclitaxel disrupted the immunosuppressive microenvironment within solid tumors, enhancing immune cells infiltration and improved anti-tumor efficacy. Overall, MSLN490 exhibits robust anti-tumor activity, resilience to soluble MSLN interference, and enhanced anti-tumor effects when combined with other therapies, offering a promising future for the treatment of a variety of solid tumors. This study provides a strong foundation for further exploration of MSLN490's clinical potential.


Asunto(s)
Proteínas Ligadas a GPI , Mesotelina , Humanos , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/antagonistas & inhibidores , Animales , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/farmacología , Paclitaxel/uso terapéutico , Paclitaxel/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/terapia , Ratones , Femenino , Células HT29 , Ratones Endogámicos BALB C , Ratones Desnudos , Línea Celular Tumoral , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología
6.
Pak J Med Sci ; 40(6): 1054-1062, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38952510

RESUMEN

Objectives: To investigate risk factors for severe maternal morbidity (SMM) in pregnant women with hypertensive disorders of pregnancy (HDP) and to develop a risk prediction model. Methods: A prospective observational cohort study was conducted among pregnant women who were hospitalized for hypertensive disorders of pregnancy (HDP) between January 2016 and December 2020 in Fujian College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Province, China (a training set), and a risk predictive model was constructed. Pregnant women with HDP who were hospitalized between January 2021 and December 2021 were selected as a validation set. Concordance index (C-index) and calibration curves were used to test predictive model discrimination and calibration. Results: We included 970 pregnant women (790 in the training set and 180 in the validation set). Least absolute shrinkage and selection operator regression was used to screen for nine related variables such as intra-uterine growth retardation (IUGR), diastolic blood pressure (DBP) and systolic blood pressure (SBP) at suspected diagnosis, total bilirubin, albumin (ALB), uric acid, total cholesterol, serum magnesium, and suspected gestational age. SBP at suspected diagnosis (OR =1.22, 95%CI:1.08-1.42) and total cholesterol (OR = 1.78, 95%CI:1.17-2.80) were independent risk factors of severe maternal morbidity in pregnant women with HDP. A nomogram was constructed, and internal validation of the nomogram model was done using the bootstrap self-sampling method. C-index in the training and the validation set was 0.798 and 0.909, respectively. Conclusion: Our prediction model can be used to determine gestational hypertension severity in pregnant women.

7.
Acta Pharmacol Sin ; 44(7): 1455-1463, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36707721

RESUMEN

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2.


Asunto(s)
Anticuerpos Biespecíficos , COVID-19 , Humanos , SARS-CoV-2 , Terapéutica Combinada de Anticuerpos , Pruebas de Neutralización , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Neutralizantes
8.
Chin Med Sci J ; 38(2): 109-116, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37006198

RESUMEN

Objective To investigate the clinical symptoms experienced by patients with thoracic spinal tumors and verify the associated symptoms that are predictive of a decline in muscle strength in the lower limbs. Methods A single-center, retrospective cross-sectional study was conducted on in-patients diagnosed with epidural thoracic spinal tumors between January 2011 and May 2021. The study involved a review of electronic medical records and radiographs and the collection of clinical data. The differences in clinical manifestations between patients with constipation and those without constipation were analyzed. Binary logistic regression analyses were performed to identify risk factors associated with a decline in muscle strength in the lower limbs.Results A total of 227 patients were enrolled, including 131 patients with constipation and 96 without constipation. The constipation group had a significantly higher proportion of patients who experienced difficulty walking or paralysis compared to those without constipation prior to surgery (83.2% vs. 17.7%, χ2 = 99.035,P < 0.001). Constipation (OR = 9.522, 95%CI: 4.150-21.849, P < 0.001) and urinary retention (OR = 14.490, 95%CI: 4.543-46.213, P < 0.001) were independent risk factors for muscle strength decline in the lower limbs. Conclusions The study observed that patients with thoracic spinal tumors who experienced constipation symptoms had a higher incidence of lower limb weakness. Moreover, the analysis revealed that constipation and urinary retention were independent risk factors associated with a preoperative decline in muscle strength of lower limbs.


Asunto(s)
Neoplasias de la Columna Vertebral , Retención Urinaria , Humanos , Estreñimiento/etiología , Estudios Transversales , Extremidad Inferior , Fuerza Muscular , Estudios Retrospectivos
9.
Biol Pharm Bull ; 45(11): 1616-1626, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36328497

RESUMEN

The dysregulation of certain long non-coding RNAs (lncRNAs) has been considered to be involved in neuropsychiatric disorders such as depression, implying the vital role of these transcripts. We have previously identified many differentially expressed lncRNAs in chronic unpredictable mild stress (CUMS) induced mice. Among them, lncRNA Gm16638-201 was highly expressed in the hippocampus (HIP) of CUMS, but the specific role and the underlying mechanisms remain unclear. Here, we reported that lncRNA Gm16638-201 was highly expressed in the prefrontal cortex (PFC) of CUMS induced depressive mice. Bioinformatic analysis shows that Gm16638-201 is mainly located in the cytoplasm. Nine neurological-related genes (Elmo2, Satb1, Hnrnpul1, Sipa1l3, Mapt, Tada3, Sgip1, IL-16, and StarD5) were predicted to be regulated in cis or trans by Gm16638-201 and involved into the 14-3-3Ɛ neurotrophic signaling pathway. We further confirmed the down-regulation of 14-3-3Ɛ and the nine predicted target genes in the PFC of CUMS mice except for Sgip1 and IL-16. In addition, they were also down-regulated in the primary cortical cell cultures with overexpression of Gm16638-201 constructed using an adenoviral-medicated gene expression system. In conclusion, we found that overexpression of Gm16638-201 negatively regulated several target genes and inhibited the 14-3-3Ɛ pathway in the PFC of CUMS induced depressive mice. This promising result suggests that Gm16638-201 may be a potential novel therapeutic target for depression.


Asunto(s)
Antidepresivos , ARN Largo no Codificante , Ratones , Animales , Antidepresivos/uso terapéutico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Depresión/tratamiento farmacológico , Estrés Psicológico/metabolismo , Interleucina-16/metabolismo , Modelos Animales de Enfermedad , Corteza Prefrontal/metabolismo , Hipocampo/metabolismo , Proteínas del Citoesqueleto/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Factores de Transcripción/metabolismo
10.
Mediators Inflamm ; 2022: 4917550, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35153622

RESUMEN

To date, Kawasaki disease (KD) has only been able to be diagnosed and evaluated using clinical characteristics. Additionally, the therapeutic effect and cardiovascular complications could not be verified until its occurrence. The present retrospective study analyzed the dynamic alterations of inflammatory cytokines, platelet (PLT) count, and subgroups of lymphocytes, such as cluster of differentiation (CD) 8+ T cells and CD19+ B cells, under different conditions in 64 children with KD. The percentage distribution of lymphocyte subgroups and the altered neutrophil lymphocyte ratio demonstrated that the inflammatory response was dominated by the B cell-mediated humoral immune response before intravenous immunoglobulin (IVIG) treatment, but mainly by T cells via cellular cytotoxic effects after IVIG treatment. Among the different types of inflammatory cytokines, the results of the present study revealed that the altered levels of interleukin-2 receptor (IL-2R) and interleukin-10 (IL-10) were closely associated with the percentage of CD8+ T cells and CD19+ B cells. Additionally, the two cytokines exhibited more sensitive fluctuations based on the status of the children with KD in various circumstances compared with other indexes, such as the percentages of CD8+ T cells and CD19+ B cells or the PLT count. These results suggested that children with KD who are ≥4 years old may benefit from IVIG but will not benefit from decreased platelet activation or suffer less cardiovascular complications. Additionally, starting clopidogrel usage earlier as an antiplatelet strategy should be considered based on the observed continuous rise in the PLT count in children with KD receiving IVIG. In conclusion, dynamically monitoring the levels of IL-2R and IL-10 has the potential to provide indications of the intensity and development of the inflammatory response in children with KD and may contribute to the early prediction and adjustment of pathological and pharmacological effects of therapy.


Asunto(s)
Síndrome Mucocutáneo Linfonodular , Antiinflamatorios/uso terapéutico , Linfocitos T CD8-positivos , Niño , Preescolar , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Interleucina-10/uso terapéutico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Receptores de Interleucina-2 , Estudios Retrospectivos
11.
Adv Physiol Educ ; 46(2): 319-324, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35357953

RESUMEN

Due to the COVID-19 pandemic during spring semester 2020, teachers and students were forced to engage in online instruction. However, there is little evidence on the feasibility of online physiology teaching. This study demonstrated a 3-wk preliminary online physiology course based on Rain Classroom assisted by the mobile application WeChat. Eighty-seven nursing undergraduate students attended an online physiology course during the spring semester of the 2019-2020 academic year from March 9 to March 29. We determined the effects of the online physiology learning based on in-class tests, preclass preparation, and review rates for the course materials. We also measured the students' perceptions and attitudes about online learning with a questionnaire survey. Posttest scores from the first week to the third week in online physiology course (7.22 ± 1.83, 7.68 ± 2.09, and 6.21 ± 2.92, respectively) exceeded the pretest scores (5.32 ± 2.14, 6.26 ± 2.49, and 3.72 ± 2.22, respectively), and this finding was statistically significant (all P < 0.001). Moreover, the pretest scores were significant positive predictors of final grade (all P < 0.01). In addition, the percentage of preclass preparation increased in 3 wk, from 43.68% to 57.47% to 68.97%. From the first week to the third week, the review rate increased from 86.21% to 91.95%; however, the second week was the lowest of all (72.41%). Finally, students' perceptions about their online physiology learning experiences were favorable. In conclusion, online physiology instruction based on Rain Classroom assisted by WeChat was an effective strategy during the COVID-19 pandemic.


Asunto(s)
COVID-19 , Educación a Distancia , Humanos , Pandemias , Estudiantes
12.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(3): 425-433, 2021 Jun 25.
Artículo en Zh | MEDLINE | ID: mdl-34180187

RESUMEN

Motor imaging therapy is of great significance to the rehabilitation of patients with stroke or motor dysfunction, but there are few studies on lower limb motor imagination. When electrical stimulation is applied to the posterior tibial nerve of the ankle, the steady-state somatosensory evoked potentials (SSSEP) can be induced at the electrical stimulation frequency. In order to better realize the classification of lower extremity motor imagination, improve the classification effect, and enrich the instruction set of lower extremity motor imagination, this paper designs two experimental paradigms: Motor imaging (MI) paradigm and Hybrid paradigm. The Hybrid paradigm contains electrical stimulation assistance. Ten healthy college students were recruited to complete the unilateral movement imagination task of left and right foot in two paradigms. Through time-frequency analysis and classification accuracy analysis, it is found that compared with MI paradigm, Hybrid paradigm could get obvious SSSEP and ERD features. The average classification accuracy of subjects in the Hybrid paradigm was 78.61%, which was obviously higher than the MI paradigm. It proves that electrical stimulation has a positive role in promoting the classification training of lower limb motor imagination.


Asunto(s)
Interfaces Cerebro-Computador , Estimulación Eléctrica , Electroencefalografía , Humanos , Imaginación , Extremidad Inferior , Movimiento
13.
BMC Anesthesiol ; 20(1): 2, 2020 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-31901229

RESUMEN

BACKGROUND: As an essential component of multimodal analgesia approaches after total knee arthroplasty (TKA), local infiltration analgesia (LIA) can be classified into peri-articular injection (PAI) and intra-articular injection (IAI) according to administration techniques. Currently, there is no definite answer to the optimal choice between the two techniques. Our study aims to investigate analgesic efficacy and safety of PAI versus IAI in patients receiving simultaneous bilateral TKA. METHODS: This randomized controlled trial was conducted from February 2017 and finished in July 2018. Sixty patients eligible for simultaneous bilateral total knee arthroplasty were randomly assigned to receive PAI on one side and IAI on another. Primary outcomes included numerical rating scale (NRS) pain score at rest or during activity at 3 h, 6 h, 12 h, 24 h, 48 h, and 72 h following surgery. Secondary outcomes contained active or passive range of motion (ROM) at 1, 2, and 3 days after surgery, time to perform straight leg raise, wound drainage, operation time, and wound complications. RESULTS: Patients experienced lower NRS pain scores of the knee receiving PAI compared with that with PAI during the first 48 h after surgery. The largest difference of NRS pain score at rest occurred at 48 h (PAI: 0.68, 95%CI[0.37, 0.98]; IAI: 2.63, 95%CI [2.16, 3.09]; P < 0.001); and the largest difference of NRS pain score during activity also took place at 48 h (PAI: 2.46, 95%CI [2.07, 2.85]; IAI: 3.90, 95%CI [3.27, 4.52]; P = 0.001). PAI group had better results of range of motion and time to perform straight leg raise when compared with IAI group. There were no differences in operation time, wound drainage, and wound complication. CONCLUSION: PAI had the superior performance of pain relief and improvement of range of motion to IAI. Therefore, the administration technique of peri-articular injection is recommended when performing local infiltration analgesia after total knee arthroplasty. TRIAL REGISTRATION: The trial was retrospectively registered in the Chinese Clinical Trial Registry as ChiCTR1800020420 on 29th December, 2018. LEVEL OF EVIDENCE: Therapeutic Level I.


Asunto(s)
Anestesia Local/métodos , Anestésicos Locales/administración & dosificación , Artroplastia de Reemplazo de Rodilla/métodos , Cartílago Articular , Inyecciones Intraarticulares , Anciano , Femenino , Humanos , Inyecciones , Complicaciones Intraoperatorias/epidemiología , Masculino , Persona de Mediana Edad , Tempo Operativo , Dolor/epidemiología , Dolor/prevención & control , Manejo del Dolor/métodos , Dimensión del Dolor , Dolor Postoperatorio/epidemiología , Rango del Movimiento Articular , Resultado del Tratamiento
14.
Int J Mol Sci ; 21(2)2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31968672

RESUMEN

Cancer is one of the most serious diseases endangering human health. In view of the side effects caused by chemotherapy and radiotherapy, it is necessary to develop low-toxic anti-cancer compounds. Polyphenols are natural compounds with anti-cancer properties and their application is a considerable choice. Pro-senescence therapy is a recently proposed anti-cancer strategy and has been shown to effectively inhibit cancer. It is of great significance to clarify the mechanisms of polyphenols on tumor suppression by inducing senescence. In this review, we delineated the characteristics of senescent cells, and summarized the mechanisms of polyphenols targeting tumor microenvironment and inducing cancer cell senescence for cancer prevention and therapy. Although many studies have shown that polyphenols effectively inhibit cancer by targeting senescence, it warrants further investigation in preclinical and clinical studies.


Asunto(s)
Neoplasias/tratamiento farmacológico , Polifenoles/farmacología , Línea Celular Tumoral , Senescencia Celular/efectos de los fármacos , Humanos , Microambiente Tumoral/efectos de los fármacos
15.
Zhonghua Nan Ke Xue ; 26(4): 357-363, 2020 Apr.
Artículo en Zh | MEDLINE | ID: mdl-33351305

RESUMEN

The pathogenesis of male infertility is rather complicated. The establishment of animal models, especially mouse models, of male infertility, provides a model basis for the studies of the roles and molecular mechanisms of infertility-related genes. Currently there are mainly three types of mouse models for biomedical researches, namely, the mouse model made by the knockout, knock-in or gene capture method, transgenic mouse model, and chemically induced point mutant mouse model. This review summarizes male infertility - related gene knockout mouse models, aiming to find a suitable animal model for studying the pathogenesis of male infertility.


Asunto(s)
Modelos Animales de Enfermedad , Infertilidad Masculina , Animales , Técnicas de Inactivación de Genes , Humanos , Infertilidad Masculina/genética , Masculino , Ratones , Ratones Noqueados
16.
Toxicol Appl Pharmacol ; 364: 45-54, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30529164

RESUMEN

Defective autophagy in vascular smooth muscle cells (VSMCs) is the principal cause of atherosclerosis. This study aimed to investigate the effect of astragaloside IV (AS-IV) on VSMCs autophagy. In vivo, ApoE-/- mice were fed with high-fat diet ad libitum for eight weeks, with or without AS-IV (25 mg/kg, daily). In vitro, human VSMCs were cultured and treated with ß-Glycerophosphate (10 mmol/L) and AS-IV (50 µg/ml). VSMCs autophagy, mineralization, expression of p-ERK1/2, p-mTOR, and autophagy-related proteins (LC3 II/I, p62, and Beclin 1) were detected. Increased autophagy and mineralization was observed in VSMCs in thoracic aorta of mice and in in vitro VSMCs model of atherosclerosis. AS-IV administration attenuated the autophagy and mineralization in VSMCs. Reverse expression profiles of H19 and DUSP5 were observed. AS-IV inhibited DUSP5 and autophagy-related proteins and increased expression of H19, level of p-ERK1/2 and p-mTOR. Further, autophagy and mineralization level in VSMCs were in line with DUSP5 expression level, but in contrast to H19, p-ERK1/2, and p-mTOR profiles. We demonstrated that AS-IV could attenuate autophagy and mineralization of VSMCs in atherosclerosis, which may be associated with H19 overexpression and DUSP5 inhibition.


Asunto(s)
Aterosclerosis/prevención & control , Autofagia/efectos de los fármacos , Fosfatasas de Especificidad Dual/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , ARN Largo no Codificante/metabolismo , Saponinas/farmacología , Triterpenos/farmacología , Calcificación Vascular/prevención & control , Animales , Aterosclerosis/enzimología , Aterosclerosis/genética , Aterosclerosis/patología , Proteínas Relacionadas con la Autofagia/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Fosfatasas de Especificidad Dual/genética , Humanos , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Músculo Liso Vascular/enzimología , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/enzimología , Miocitos del Músculo Liso/patología , Fosforilación , Placa Aterosclerótica , ARN Largo no Codificante/genética , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Calcificación Vascular/enzimología , Calcificación Vascular/genética , Calcificación Vascular/patología
17.
Int J Syst Evol Microbiol ; 69(3): 752-760, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30648942

RESUMEN

Assessment of the bacterial diversity associated with a decaying fern, Athyrium wallichianum Ching, revealed the presence of a novel bacterial strain named M46T. It was Gram-stain-negative, rod-shaped, non-motile and aerobic with cellulose and xylan degradation abilities. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain M46T was affiliated to the genus Sphingobacterium, exhibiting the highest sequence similarity of 97.9 % to Sphingobacterium ginsenosidimutans THG 07T, Sphingobacterium canadense CR11T and Sphingobacterium detergens6.2 ST. Multilocus sequence analysis (MLSA) based on concatenated sequences of the rpoB, cpn60 and 16S rRNA genes showed that strain M46T clustered together with S. canadense CR11T. The genome of strain M46T had a G+C content of 40.6 mol% and chromosome of 6 853 865 bp. Average nucleotide identity (ANI) between strain M46T and S. detergens 6.2 ST and S. siyangense SY1T was 85.1 and 78.1 %, respectively. DNA-DNA relatedness values among strain M46T and other closely related Sphingobacterium species were <70 %. ANI and DNA-DNA relatedness findings strongly supported M46T as a putative novel strain of Sphingobacterium. The predominant fatty acids of strain M46T were iso-C15 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and iso-C17 : 0 3-OH, and MK-7 was the dominant isoprenoid quinone. The polar lipid profile of strain M46T contained phosphatidylethanolamine as the dominant component, while minor amounts of phosphoglycolipid, one unidentified aminophospholipid, two unidentified phospholipids and four unidentified lipids were also detected. Based on 16S rRNA gene sequence similarities, MLSA results, genomic characteristics, and phenotypic and biochemotaxonomic analyses, strain M46T is considered to represent a novel species in the genus Sphingobacterium, for which the name Sphingobacterium athyrii sp. nov. is proposed. The type strain is M46T (=CGMCC 1.13466T=JCM 32543T).


Asunto(s)
Helechos/microbiología , Filogenia , Sphingobacterium/clasificación , Técnicas de Tipificación Bacteriana , Composición de Base , Celulosa/metabolismo , ADN Bacteriano/genética , Ácidos Grasos/química , Genes Bacterianos , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Sphingobacterium/aislamiento & purificación , Tibet , Vitamina K 2/análogos & derivados , Vitamina K 2/química , Xilanos/metabolismo
18.
Sensors (Basel) ; 19(10)2019 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-31130689

RESUMEN

Crop-type identification is very important in agricultural regions. Most researchers in this area have focused on exploring the ability of synthetic-aperture radar (SAR) sensors to identify crops. This paper uses multi-source (Sentinel-1, Sentinel-2, and Landsat-8) and multi-temporal data to identify crop types. The change detection method was used to analyze spectral and indices information in time series. Significant differences in crop growth status during the growing season were found. Then, three obviously differentiated time features were extracted. Three advanced machine learning algorithms (Support Vector Machine, Artificial Neural Network, and Random Forest, RF) were used to identify the crop types. The results showed that the detection of (Vertical-vertical) VV, (Vertical-horizontal) VH, and Cross Ratio (CR) changes was effective for identifying land cover. Moreover, the red-edge changes were obviously different according to crop growth periods. Sentinel-2 and Landsat-8 showed different normalized difference vegetation index (NDVI) changes also. By using single remote sensing data to classify crops, Sentinel-2 produced the highest overall accuracy (0.91) and Kappa coefficient (0.89). The combination of Sentinel-1, Sentinel-2, and Landsat-8 data provided the best overall accuracy (0.93) and Kappa coefficient (0.91). The RF method had the best performance in terms of identity classification. In addition, the indices feature dominated the classification results. The combination of phenological period information with multi-source remote sensing data can be used to explore a crop area and its status in the growing season. The results of crop classification can be used to analyze the density and distribution of crops. This study can also allow to determine crop growth status, improve crop yield estimation accuracy, and provide a basis for crop management.


Asunto(s)
Algoritmos , Productos Agrícolas/clasificación , Tecnología de Sensores Remotos/métodos , Sistemas de Información Geográfica , Imágenes Satelitales , Triticum/crecimiento & desarrollo , Clima Tropical , Zea mays/crecimiento & desarrollo
19.
Adv Physiol Educ ; 42(3): 449-453, 2018 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-29972058

RESUMEN

Peer instruction has been used extensively in lecture courses; however, there is little evidence of its use in laboratory courses. The purpose of the present study was to describe the implementation of the peer instruction method in a physiology laboratory course in China. Second-year medical students attended a 6-wk physiology laboratory course in the fall semester of the 2016-2017 school year. In the six new physiology laboratory classes, peer instruction strategies were used to substitute for the traditional short, didactic lectures. The effects of peer instruction were measured by in-class quizzes and confidence levels. The students' evaluations of peer instruction were measured by a Likert scale questionnaire. Peer instruction significantly improved the mean score on quizzes (0.53 ± 0.50 vs. 0.68 ± 0.47, P < 0.001) and confidence levels (2.36 ± 0.66 vs. 2.80 ± 0.45, P < 0.001). Furthermore, for individual incorrect answers, 39.07% changed to correct answers after peer instruction, whereas, for correct answers, 6.61% were changed to an incorrect response. Overall, significantly more students changed their answers from incorrect to correct than from correct to incorrect [χ2: 333.11; degrees of freedom (df): 1; P < 0.001]. Therefore, the positive effects of peer instruction were higher than the negative effects (χ2: 244.55; df: 1; P < 0.001). Moreover, student evaluations of peer instruction were highly positive. In conclusion, the implementation of peer instruction to the physiology laboratory course is an effective strategy to enhance students' performance on in-class quizzes and confidence levels. In addition, the attitude of students toward peer instruction was favorable.


Asunto(s)
Curriculum , Evaluación Educacional/métodos , Grupo Paritario , Fisiología/educación , Estudiantes de Medicina , China , Curriculum/normas , Evaluación Educacional/normas , Humanos
20.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 35(3): 343-349, 2018 06 25.
Artículo en Zh | MEDLINE | ID: mdl-29938940

RESUMEN

Event-related desynchronization (ERD) is the basic feature of electroencephalogram (EEG), and the brain-computer interface based on motor imagery (MI-BCI) with the foundation of the analysis of ERD is of great significance in motor function recovery. The valid ERD characteristics extracted from EEG are the key to the performance of the BCI, so the study of which kind of stimulation mode can prompt subjects to generate more obvious characteristics of ERD is crucial. Four different stimulation modes are designed in this paper, and the effects of motion imagery tasks under static text stimulation, grip video stimulation, serial motion video stimulation of fingers as well as serial motion video stimulation of fingers with sound on the characteristics of ERD are analyzed. Combining the analysis of time-frequency spectrum, the power spectral density curve, ERD value and brain topographic map, it is shown that the ERD under serial motion video stimulation of fingers and serial motion video stimulation of fingers with sound modes is much stronger and has wider range of activation, and the BCI based on the analysis of ERD will have a better effect on practical application. As a result, the recognition and acceptance of the users of BCI system are improved in some extent.


Asunto(s)
Interfaces Cerebro-Computador , Electroencefalografía , Dedos , Fuerza de la Mano , Humanos , Recuperación de la Función
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