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PURPOSE: This phase I/II trial (ChiCTR2000032879) assessed the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma. METHODS AND MATERIALS: Twenty-two patients, regardless of their programmed death ligand-1 (PD-L1) status, received toripalimab combined with concurrent chemoradiotherapy (CCRT). CCRT included cisplatin (40 mg/m2, once weekly for 5 weeks), radiotherapy (45-50.4 Gy/25-28 Fx, 5 fractions weekly), followed by brachytherapy (24-30 Gy/3-5 Fx) and toripalimab (240 mg, intravenous) on days 1, 22 and 43 during CCRT. The primary endpoints were safety and 2-year progression-free survival (PFS). The secondary endpoints included 2-year local control (LC), local regional control and overall survival (OS). RESULTS: All patients successfully completed CCRT and toripalimab treatment. Grade III and higher adverse events (AEs) were observed in 11 patients (11/22, 50%), and no patient experienced grade V AEs. The objective response rate (ORR) was 100%. At the data cutoff (June 30, 2023), the median follow-up was 31.8 months (9.5 to 37.8 months). The 2-year PFS rate was 81.8%. The 2-year LC and local regional control rates were both 95.5%, and the 2-year OS rate was 90.9%. CONCLUSIONS: Toripalimab combined with CCRT achieved good tolerance and showed promising anti-tumor effects in patients with locally advanced cervical cancer.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Células Escamosas , Quimioradioterapia , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Persona de Mediana Edad , Quimioradioterapia/métodos , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Anciano , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
BACKGROUND: Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. METHODS: We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram's predictive accuracy to rigorous independent validation. RESULTS: The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28-0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64-0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65-0.74). CONCLUSIONS: In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.
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Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/patología , Quimioradioterapia/métodos , Pronóstico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Adulto , Plaquetas/patología , Anciano , Albúmina Sérica/análisis , Estadificación de Neoplasias , Adulto Joven , Modelos de Riesgos Proporcionales , Recuento de Plaquetas , Biomarcadores de Tumor/sangreRESUMEN
OBJECTIVE: Midpalatal expansion (MPE) is routinely employed to treat transverse maxillary arch deficiency. Neutrophils are indispensable for recruiting bone marrow stromal cells (BMSCs) at the initial stage of bone regeneration. This study aimed to explore whether neutrophils participate in MPE and how they function during bone formation under mechanical stretching. MATERIALS AND METHODS: The presence and phenotype of neutrophils in the midpalatal suture during expansion were detected by flow cytometry and immunofluorescence staining. The possible mechanism of neutrophil recruitment and polarization was explored in vitro by exposing vascular endothelial cells (VECs) to cyclic tensile strain. RESULTS: The number of neutrophils in the distracted suture peaked on Day 3, and N2-type neutrophils significantly increased on Day 5 after force application. The depletion of circulatory neutrophils reduced bone volume by 43.6% after 7-day expansion. The stretched VECs recruited neutrophils via a CXCR2 mechanism in vitro, which then promoted BMSC osteogenic differentiation through the VEGFA/VEGFR2 axis. Consistently, these neutrophils showed higher expression of canonical N2 phenotype genes, including CD206 and Arg1. CONCLUSIONS: These results suggested that neutrophils participated in early bone formation during MPE. Based on these findings, we propose that stretched VECs recruited and polarized neutrophils, which, in turn, induced BMSC osteogenic differentiation.
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Diferenciación Celular , Neutrófilos , Osteogénesis , Factor A de Crecimiento Endotelial Vascular , Neutrófilos/fisiología , Osteogénesis/fisiología , Animales , Factor A de Crecimiento Endotelial Vascular/metabolismo , Células Endoteliales , Células Madre Mesenquimatosas , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Técnica de Expansión Palatina , Receptores de Interleucina-8B/metabolismo , Ratones , Masculino , Células Cultivadas , Ratones Endogámicos C57BL , Infiltración Neutrófila/fisiologíaRESUMEN
BACKGROUND: Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. RESULTS: The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). CONCLUSIONS: BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.
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Bacillus subtilis , Células Asesinas Naturales , Animales , Ratones , Células Asesinas Naturales/metabolismo , Linfocitos T/metabolismo , Interferón gamma , FagocitosisRESUMEN
Exploring bidirectional CO2/HCO2- catalysis holds significant potential in constructing integrated (photo)electrochemical formate fuel cells for energy storage and applications. Herein, we report selective CO2/HCO2- electrochemical interconversion by exploiting the flexible coordination modes and rich redox properties of a versatile iron-thiolate platform, Cp*Fe(II)L (L = 1,2-Ph2PC6H4S-). Upon oxidation, this iron complex undergoes formate binding to generate a diferric formate complex, [(L-)2Fe(III)(µ-HCO2)Fe(III)]+, which exhibits remarkable electrocatalytic performance for the HCO2--to-CO2 transformation with a maximum turnover frequency (TOFmax) â¼103 s-1 and a Faraday efficiency (FE) â¼92(±4)%. Conversely, this iron system also allows for reduction at -1.85 V (vs Fc+/0) and exhibits an impressive FE â¼93 (±3)% for the CO2-to-HCO2- conversion. Mechanism studies revealed that the HCO2--to-CO2 electrocatalysis passes through dicationic [(L2)-â¢Fe(III)(µ-HCO2)Fe(III)]2+ generated by unconventional oxidation of the diferric formate species taking place at ligand L, while the CO2-to-HCO2- reduction involves a critical intermediate of [Fe(II)-H]- that was independently synthesized and structurally characterized.
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OBJECTIVE: Preeclampsia is a common disease during pregnancy that leads to fetal and maternal adverse events. Few head-to-head clinical trials are currently comparing the effectiveness of prophylactic strategies for preeclampsia. In this network meta-analysis, we aimed to compare the efficacy of prophylactic strategies for preventing preeclampsia in pregnant women at risk. DATA SOURCES: Articles published in or before September 2021 from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, references of key articles, and previous meta-analyses were manually searched. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing prophylactic strategies preventing preeclampsia with each other or with negative controls were included. METHODS: Two reviewers independently extracted data, assessed the risk of bias, and assessed evidence certainty. The efficacy of prophylactic strategies was estimated by frequentist and Bayesian network meta-analysis models. The primary composite outcome was preeclampsia/ pregnancy-induced hypertension. RESULTS: In total, 130 trials with a total of 112,916 patients were included to assess 13 prophylactic strategies. Low-molecular-weight heparin (0.60; 95% confidence interval, 0.42-0.87), vitamin D supplementation (0.65; 95% confidence interval, 0.45-0.95), and exercise (0.68; 95% confidence interval, 0.50-0.92) were as efficacious as calcium supplementation (0.71; 95% confidence interval, 0.62-0.82) and aspirin (0.79; 95% confidence interval, 0.72-0.86) in preventing preeclampsia/pregnancy-induced hypertension, with a P score ranking of 85%, 79%, 76%, 74%, and 61%, respectively. In the head-to-head comparison, no differences were found between these effective prophylactic strategies for preventing preeclampsia and pregnancy-induced hypertension, except with regard to exercise, which tended to be superior to aspirin and calcium supplementation in preventing pregnancy-induced hypertension. Furthermore, the prophylactic effects of aspirin and calcium supplementation were robust across subgroups. However, the prophylactic effects of low-molecular-weight heparin, exercise, and vitamin D supplementation on preeclampsia and pregnancy-induced hypertension varied with different risk populations, dosages, areas, etc. The certainty of the evidence was moderate to very low. CONCLUSION: Low-molecular-weight heparin, vitamin D supplementation, exercise, calcium supplementation, and aspirin reduce the risk of preeclampsia/pregnancy-induced hypertension. No significant differences between effective prophylactic strategies were found in preventing preeclampsia. These findings raise the necessity to reevaluate the prophylactic effects of low-molecular-weight heparin, vitamin D supplementation, and exercise on preeclampsia.
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Hipertensión Inducida en el Embarazo , Preeclampsia , Embarazo , Humanos , Femenino , Preeclampsia/prevención & control , Preeclampsia/tratamiento farmacológico , Hipertensión Inducida en el Embarazo/tratamiento farmacológico , Calcio , Metaanálisis en Red , Teorema de Bayes , Ensayos Clínicos Controlados Aleatorios como Asunto , Aspirina/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Vitamina D/uso terapéuticoRESUMEN
Iron tetraphenylporphyrin complex modified with four trimethylammonium groups (Fe-p-TMA) is found to be capable of catalyzing the eight-electron eight-proton reduction of CO2 to CH4 photochemically in acetonitrile. In the present work, density functional theory (DFT) calculations have been performed to investigate the reaction mechanism and to rationalize the product selectivity. Our results revealed that the initial catalyst Fe-p-TMA ([Cl-Fe(III)-LR4]4+, where L = tetraphenylporphyrin ligand with a total charge of -2, and R4 = four trimethylammonium groups with a total charge of +4) undergoes three reduction steps, accompanied by the dissociation of the chloride ion to form [Fe(II)-Lâ¢â¢2-R4]2+. [Fe(II)-Lâ¢â¢2-R4]2+, bearing a Fe(II) center ferromagnetically coupled with a tetraphenylporphyrin diradical, performs a nucleophilic attack on CO2 to produce the 1η-CO2 adduct [CO2â¢--Fe(II)-Lâ¢-R4]2+. Two intermolecular proton transfer steps then take place at the CO2 moiety of [CO2â¢--Fe(II)-Lâ¢-R4]2+, resulting in the cleavage of the C-O bond and the formation of the critical intermediate [Fe(II)-CO]4+ after releasing a water molecule. Subsequently, [Fe(II)-CO]4+ accepts three electrons and one proton to generate [CHO-Fe(II)-Lâ¢-R4]2+, which finally undergoes a successive four-electron-five-proton reduction to produce methane without forming formaldehyde, methanol, or formate. Notably, the redox non-innocent tetraphenylporphyrin ligand was found to play an important role in CO2 reduction since it could accept and transfer electron(s) during catalysis, thus keeping the ferrous ion at a relatively high oxidation state. Hydrogen evolution reaction via the formation of Fe-hydride ([Fe(II)-H]3+) turns out to endure a higher total barrier than the CO2 reduction reaction, therefore providing a reasonable explanation for the origin of the product selectivity.
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Phytate as a root exudate is rare in plants as it mainly serves as a P storage in the seeds; however, As-hyperaccumulator Pteris vittata effectively secretes phytate and utilizes phytate-P, especially under As exposure. This study investigated the effects of As on its phytate and phytase exudation and the impacts of As and/or phytate on each other's uptake in P. vittata through two hydroponic experiments. Under 10-100 µM arsenate (AsV), the exudation of phytate and phytase by P. vittata was increased by 50-72% to 20.4-23.4 µmol h-1 g-1 and by 28-104% to 18.6-29.5 nmol h-1 plant-1, but they were undetected in non-hyperaccumulator Pteris ensiformis at 10 µM AsV. Furthermore, compared to 500 µM phytate, the phytate concentration in the growth media was reduced by 69% to 155 µM, whereas the P and As contents in P. vittata fronds and roots were enhanced by 68-134% and 44-81% to 2423-2954 and 82-407 mg kg-1 under 500 µM phytate plus 50 µM AsV. The increased P/As uptake in P. vittata was probably attributed to 3.0-4.5-fold increase in expressions of P transporters PvPht1;3-1;4. Besides, under As exposure, plant P may be converted to phytate in P. vittata roots, thereby increasing phytate's contents by 84% to 840 mg kg-1. Overall, our results suggest that As-induced phytate/phytase exudation and phytate-P uptake stimulate its growth and As hyperaccumulation by P. vittata.
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6-Fitasa , Arsénico , Pteris , Contaminantes del Suelo , 6-Fitasa/metabolismo , Pteris/metabolismo , Ácido Fítico/metabolismo , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Biodegradación AmbientalRESUMEN
Cognitive behavioral therapy (CBT) is effective for pain relief in children and adolescents with functional abdominal pain disorders (FAPDs). However, few studies have focused on the FAPDs specifically and the medium-term or long-term results of CBT. In this meta-analysis, we investigated the efficacy of CBT in pediatric FAPDs and unclassified chronic or recurrent abdominal pain (CAP and RAP, respectively). We searched the PubMed, Embase, and Cochrane Library databases for related randomized controlled trials until August 2021. Eventually, 10 trials with 872 participants were included. The methodological quality of the studies was assessed, and data on two primary and four secondary outcomes of interest were extracted. We used the standardized mean difference (SMD) to measure the same outcome, and precisions of effect sizes were reported as 95% confidence intervals (CIs). We found that CBT had significantly positive effects on reducing pain intensity immediately (SMD: -0.54 [CI: -0.9, -0.19], p = 0.003), 3 months after the intervention (SMD: -0.55; [CI: -1.01, -0.1], p = 0.02) and 12 months after the intervention (SMD: -0.32; [CI: -0.56, -0.08], p = 0.008). CBT also reduced the severity of gastrointestinal symptoms, depression, and solicitousness, improved the quality of life and decreased the total social cost. Future studies should consider uniform interventions in the control group and comparing different CBT delivery methods.
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Dolor Crónico , Terapia Cognitivo-Conductual , Niño , Humanos , Adolescente , Calidad de Vida , Terapia Cognitivo-Conductual/métodos , Dolor Crónico/terapia , Dolor Crónico/psicología , Manejo del Dolor/métodos , Manejo del Dolor/psicología , Dolor Abdominal/terapiaRESUMEN
Catalytic asymmetric construction of chiral indole-fused rings has become an important issue in the chemical community because of the significance of such scaffolds. In this work, we have accomplished the first catalytic asymmetric (4+2) and (4+3) cycloadditions of 2,3-indolyldimethanols by using indoles and 2-naphthols as suitable reaction partners under the catalysis of chiral phosphoric acids, constructing enantioenriched indole-fused six-membered and seven-membered rings in high yields with excellent enantioselectivities. In addition, this approach is used to realize the first enantioselective construction of challenging tetrahydroindolocarbazole scaffolds, which are found to show promising anticancer activity. More importantly, theoretical calculations of the reaction pathways and activation mode offer an in-depth understanding of this class of indolylmethanols. This work not only settles the challenges in realizing catalytic asymmetric cycloadditions of indolyldimethanols but also provides a powerful strategy for the construction of enantioenriched indole-fused rings.
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Parent amido complexes are crucial intermediates in ammonia-based transformations. We report a well-defined ferric ammine system [Cp*Fe(1,2-Ph2PC6H4NH)(NH3)]+ ([1-NH3]+), which processes electrocatalytic ammonia oxidation to N2 and H2 at a mild potential. Through establishing elementary e-/H+ conversions with the ferric ammine, a formal Fe(IV)-amido species, [1-NH2]+, together with its conjugated Lewis acid, [1-NH3]2+, was isolated and structurally characterized for the first time. Mechanism studies indicated that further oxidation of [1-NH2]+ induces the reaction of the parent amido unit with NH3. The formation of hydrazine is realized by the non-innocent nature of the phenylamido ligand that facilitates the concerted transfer of one proton and two electrons.
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Inspired by OxdA that operates biocatalytic aldoxime dehydration, we have developed an efficient iron catalyst, Cp*Fe(1,2-Cy2PC6H4O) (1), which rapidly converts various aliphatic and aromatic aldoximes to nitriles with release of H2O at room temperature. The catalysis involves redox activation of the N-O bond by a 1e- transfer from the iron catalyst to the oxime. Such redox-mediated N-O cleavage was demonstrated by the isolation of a ferrous iminato intermediate from the reaction of the ketoxime substrate. This iron-catalyzed acceptorless dehydration approach represents a general method for the preparation of nitriles, and it also delivers salicylonitriles by catalyzing the Kemp elimination reaction.
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Hierro , Nitrilos , Catálisis , Deshidratación , Humanos , Hidroliasas/química , Hierro/química , Nitrilos/química , Oxidación-Reducción , Oximas/químicaRESUMEN
Selenate enhances arsenic (As) accumulation in As-hyperaccumulator Pteris vittata, but the associated molecular mechanisms are unclear. Here, we investigated the mechanisms of selenate-induced arsenic accumulation by exposing P. vittata to 50 µM arsenate (AsV50) and 1.25 (Se1.25) or 5 µM (Se5) selenate in hydroponics. After 2 weeks, plant biomass, plant As and Se contents, As speciation in plant and growth media, and important genes related to As detoxification in P. vittata were determined. These genes included P transporters PvPht1;3 and PvPht1;4 (AsV uptake), arsenate reductases PvHAC1 and PvHAC2 (AsV reduction), and arsenite (AsIII) antiporters PvACR3 and PvACR3;2 (AsIII translocation) in the roots, and AsIII antiporters PvACR3;1 and PvACR3;3 (AsIII sequestration) in the fronds. The results show that Se1.25 was more effective than Se5 in increasing As accumulation in both P. vittata roots and fronds, which increased by 27 and 153% to 353 and 506 mg kg-1. The As speciation analyses show that selenate increased the AsIII levels in P. vittata, with 124-282% more AsIII being translocated into the fronds. The qPCR analyses indicate that Se1.25 upregulated the gene expression of PvHAC1 by 1.2-fold, and PvACR3 and PvACR3;2 by 1.0- to 2.5-fold in the roots, and PvACR3;1 and PvACR3;3 by 0.6- to 1.1-fold in the fronds under AsV50 treatment. Though arsenate enhanced gene expression of P transporters PvPht1;3 and PvPht1;4, selenate had little effect. Our results indicate that selenate effectively increased As accumulation in P. vittata, mostly by increasing reduction of AsV to AsIII in the roots, AsIII translocation from the roots to fronds, and AsIII sequestration into the vacuoles in the fronds. The results suggest that selenate may be used to enhance phytoremediation of As-contaminated soils using P. vittata.
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Arsénico , Arsenitos , Pteris , Selenio , Contaminantes del Suelo , Antiportadores/metabolismo , Antiportadores/farmacología , Arseniato Reductasas/genética , Arseniato Reductasas/metabolismo , Arseniatos , Arsénico/metabolismo , Arsenitos/metabolismo , Biodegradación Ambiental , Raíces de Plantas/metabolismo , Pteris/genética , Pteris/metabolismo , Ácido Selénico , Selenio/metabolismo , Suelo , Contaminantes del Suelo/metabolismoRESUMEN
Multiple approaches are used to treat acne scars, but some are expensive, ineffective, and cause complications. We aimed to evaluate the efficacy and safety of ultra-pulsed CO2 fractional laser combined with 30% supramolecular salicylic acid in the treatment of acne scars in a prospective split-face control study. Twenty patients with facial symmetrical acne scars were enrolled. One side of face was randomly treated with 30% supramolecular salicylic acid, and two sides were treated with ultra-pulsed CO2 fractional laser. The Echelle d'evaluation clinique des cicatrices d'acne (ECCA) scale was used to evaluate the clinical efficacy before and 3 months after treatment, and a quartile scale was used to self-evaluate the improvement of patients. A visual analog scale was used to record pain scores after each treatment, and side effects and other adverse reactions on the face were recorded. All the patients completed treatment and follow-up. There was statistical difference in ECCA scores of bilateral facial acne scars after three treatments (p < 0.001). ECCA scores on the combined side were lower after three treatments than those on the laser side (p = 0.003). The patient satisfaction quartile scale on the combined side was higher than that on the laser side alone (p = 0.015). Ultra-pulsed CO2 fractional laser combined with 30% supramolecular salicylic acid has better efficacy in the treatment of acne scars than laser alone, and patient self-assessment of combined treatment has a greater degree of improvement in acne scars, and does not increase patient pain scores and related adverse reactions.
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Acné Vulgar , Láseres de Gas , Acné Vulgar/complicaciones , Dióxido de Carbono , Cicatriz/diagnóstico , Cicatriz/etiología , Cicatriz/terapia , Humanos , Láseres de Gas/efectos adversos , Dolor/etiología , Estudios Prospectivos , Ácido Salicílico/efectos adversos , Resultado del TratamientoRESUMEN
In this study, a series of 3-(3-pyridyl)-oxazolidone-5-methyl ester derivatives was synthesized and characterized by 1H NMR, 13C NMR, and LC-MS. The conducted screening antibacterial studies of the new 3-(3-pyridyl)-oxazolidone-5-methyl ester derivatives established that the methyl sulfonic acid esters have broad activity spectrum towards Staphylococcus aureus, Streptococcus pneumoniae, Bacillus subtilis and Staphylococcus epidermidis. Among them, compound 12e has the most potent activity, with an MIC of 16 µg/mL against B.subtilis, and could reduce the instantaneous growth rate of bacteria. Furthermore, molecular docking studies were also simulated for compound 12e to predict the specific binding mode of this compound. In addition, anthelmintic activity of these compounds was also evaluated against adult Indian earthworms (Pheretima posthuman). The results showed that compound 11b had the best effect. These results above can provide experimental reference for the development of novel antibacterial and anthelmintic drugs.
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Antihelmínticos/farmacología , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Ésteres/química , Oligoquetos/efectos de los fármacos , Oxindoles/química , Animales , Antihelmínticos/síntesis química , Antibacterianos/síntesis química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Sepsis-associated encephalopathy(SAE) caused by infections outside the central nervous system always presents extensive brain damage.It is common in clinical practice and associated with a poor prognosis.There are problems in the assessing and diagnosing of SAE.Many factors,such as sedation and mechanical ventilation,make it difficult to assess SAE,while electrophysiological examination may play a role in the assessment.We reviewed the studies of electrophysiological techniques such as electroencephalography and somatosensory evoked potentials for monitoring SAE,hoping to provide certain evidence for the clinical evaluation and diagnosis of SAE.
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Encefalopatía Asociada a la Sepsis , Sepsis , Humanos , Encefalopatía Asociada a la Sepsis/diagnóstico , Encefalopatía Asociada a la Sepsis/complicaciones , Sepsis/complicaciones , Sepsis/diagnóstico , ElectroencefalografíaRESUMEN
This study aims to investigate the compounds in the product of rice fermented with endophyte Hypoxylon sp.HD-2014 from Uncaria rhynchophylla.To be specific, normal-phase, MCI, Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC) was used to yield 12 compounds.Through spectral data analysis and comparison with previous reports, they were identified as methyl(E)-5-hydroxymethyl-6,7-dihydroxy-4,5-epoxy-octanoate-2-ene(1),(2E,6E)-nona-2,6,8-triene-4,5-diol(2), 8-O-(R)-methoxynodulisporin A(3), 3-nitropropionic acid(4), 3-nitropropionic acid methyl ester(5), 3,4-dihydroxy-phenylethanol(6), 2,4-dichlorobenzoic acid(7), cis-4-hydroxyscytalone(8), 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(9), isosclerone(10), 4H-1-benzopyran-4-one-2,3-dihydro-5-hydroxy-8-(hydroxyl-methyl)-2-methy(11), and 5-methylmellein(12), respectively.Compounds 1 and 2 were identified for the first time.In vitro cytotoxicity test indicated that compounds 1-12 had no significant inhibitory effect on A549 and HepG2 cells.Antimicrobial susceptibility testing revealed that compound 3 showed synergistic effect with the positive control chloramphenicol.
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Alcohol Feniletílico , Uncaria , Cromatografía Líquida de Alta Presión , Endófitos/metabolismo , Estructura MolecularRESUMEN
A new class of axially chiral styrene-based thiourea tertiary amine catalysts, which have unique characteristics such as an efficient synthetic route, multiple chiral elements, and multiple activating groups, has been rationally designed. These new chiral catalysts have proven to be efficient organocatalysts, enabling the chemo-, diastereo-, and enantioselective (2+4) cyclization of 2-benzothiazolimines with homophthalic anhydrides in good yields (up to 96 %) with excellent stereoselectivities (all >95:5 dr, up to 98 % ee). More importantly, theoretical calculations elucidated the important role of an axially chiral styrene moiety in controlling both the reactivity and enantioselectivity. This work not only represents the first design of styrene-based chiral thiourea tertiary amine catalysts and the first catalytic asymmetric (2+4) cyclization of 2-benzothiazolimines, but also gives an in-depth understanding of axially chiral styrene-based organocatalysts.
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PURPOSE: The aim of this study was to evaluate the impact of time to radiotherapy (TTR) after completion of chemotherapy (CT), and TTR after surgery, in breast cancer (BC) patients. PATIENTS AND METHODS: Continuous breast cancer patients treated with surgery and CT followed by radiotherapy (RT) from 2009 through 2015 were retrospectively reviewed. Patients were categorized into four groups with respect to TTR after CT, i.e. <4, 4-8, 8-12, and >12 weeks, and TTR after surgery, i.e. <147, 147-180, 180-202, and >202 days. The Cox proportional hazards model was used to identify the independent effect of TTRs. RESULTS: Overall, 989 patients were enrolled. Patients with a TTR of >12 weeks after CT showed significantly worse breast cancer-specific survival (BCSS) and overall survival (OS) compared with those who had a TTR of <4 weeks (BCSS: hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.1-0.76; OS: HR 0.33, 95% CI 0.13-0.88), 4-8 weeks (BCSS: HR 0.23, 95% CI 0.08-0.66; OS: HR 0.29, 95% CI 0.11-0.8), and 8-12 weeks (BCSS: HR 0.22, 95% CI 0.05-0.96; OS: HR 0.23, 95% CI 0.06-0.99). TTR after surgery showed no significant association with survival outcomes in the entire cohort, except in patients with hormone receptor (HR)-positive disease and those receiving mastectomy. In HR-positive tumors, a TTR after CT of >12 weeks remained an independent predictor for adverse BCSS and OS. CONCLUSION: Initiation of RT beyond 12 weeks after CT might compromise survival outcomes. Efforts should be made to avoid delaying RT, especially after completion of CT and in patients with HR-positive tumors, positive lymph nodes, and those receiving mastectomy.
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Neoplasias de la Mama , Mama , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Humanos , Mastectomía , Radioterapia Adyuvante , Estudios RetrospectivosRESUMEN
Metal-organic frameworks (MOFs) or coordination polymers (CPs)-based phosphorescence materials may provide a powerful route for photoelectric and optical recording devices. Herein, two phosphorescence ligands, iso-phthalic acid (IPA) and 2-methylimidazole (MIM), were selected to construct an nonporous CP {Zn(IPA)(MIM)2} (1) with a long-lived phosphorescence lifetime up to 552 ms. By the doping of Eosin Y (EY) dye molecules under an in situ process, the phosphorescence emission color of 1 can be expressly tuned from green to red. The light-harvesting range can also be vastly broadened from the UV to the visible region (550 nm). Photoelectron measurements reveal that the synergistic effect of bias voltage and illumination can greatly restrain electron-hole recombination for the generation of additional free charges.