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Polymer membranes are widely used in separation processes including desalination1, organic solvent nanofiltration2,3 and crude oil fractionation4,5. Nevertheless, direct evidence of subnanometre pores and a feasible method of manipulating their size is still challenging because of the molecular fluctuations of poorly defined voids in polymers6. Macrocycles with intrinsic cavities could potentially tackle this challenge. However, unfunctionalized macrocycles with indistinguishable reactivities tend towards disordered packing in films hundreds of nanometres thick7-9, hindering cavity interconnection and formation of through-pores. Here, we synthesized selectively functionalized macrocycles with differentiated reactivities that preferentially aligned to create well-defined pores across an ultrathin nanofilm. The ordered structure was enhanced by reducing the nanofilm thickness down to several nanometres. This orientated architecture enabled direct visualization of subnanometre macrocycle pores in the nanofilm surfaces, with the size tailored to ångström precision by varying the macrocycle identity. Aligned macrocycle membranes provided twice the methanol permeance and higher selectivity compared to disordered counterparts. Used in high-value separations, exemplified here by enriching cannabidiol oil, they achieved one order of magnitude faster ethanol transport and threefold higher enrichment than commercial state-of-the-art membranes. This approach offers a feasible strategy for creating subnanometre channels in polymer membranes, and demonstrates their potential for accurate molecular separations.
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BACKGROUND: The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-µg doses (30 days apart) of ZF2001 or placebo. The primary end point was the occurrence of symptomatic coronavirus disease 2019 (Covid-19), as confirmed on polymerase-chain-reaction assay, at least 7 days after receipt of the third dose. A key secondary efficacy end point was the occurrence of severe-to-critical Covid-19 (including Covid-19-related death) at least 7 days after receipt of the third dose. RESULTS: Between December 12, 2020, and December 15, 2021, a total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data, were included in the updated primary efficacy analysis that was conducted at the second data cutoff date of December 15, 2021. In the updated analysis, primary end-point cases were reported in 158 of 12,625 participants in the ZF2001 group and in 580 of 12,568 participants in the placebo group, for a vaccine efficacy of 75.7% (95% confidence interval [CI], 71.0 to 79.8). Severe-to-critical Covid-19 occurred in 6 participants in the ZF2001 group and in 43 in the placebo group, for a vaccine efficacy of 87.6% (95% CI, 70.6 to 95.7); Covid-19-related death occurred in 2 and 12 participants, respectively, for a vaccine efficacy of 86.5% (95% CI, 38.9 to 98.5). The incidence of adverse events and serious adverse events was balanced in the two groups, and there were no vaccine-related deaths. Most adverse reactions (98.5%) were of grade 1 or 2. CONCLUSIONS: In a large cohort of adults, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least 6 months after full vaccination. (Funded by the National Science and Technology Major Project and others; ClinicalTrials.gov number, NCT04646590.).
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Vacinas contra COVID-19 , COVID-19 , Vacinas de Subunidades Antigênicas , Adolescente , Adulto , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/uso terapêutico , Método Duplo-Cego , Humanos , SARS-CoV-2 , Vacinação , Vacinas , Vacinas de Subunidades Antigênicas/efeitos adversos , Vacinas de Subunidades Antigênicas/uso terapêutico , Adulto JovemRESUMO
Base-catalyzed diastereodivergent and regioselective domino processes of triketone enones with arylacetaldehydes for the synthesis of tetrahydrofuro[2,3-b]furans with four consecutive stereocenters are reported. Good yields and diastereoselectivities are obtained when DBU is employed as a catalyst; in contrast, Et3N delivers a different diastereomer in excellent diastereoselectivity. This work offers many advantages, including switchable diastereoselectivity, cheap base catalysts, and a simple operation.
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BACKGROUND: Patients treated with drug-coated balloons (DCB) have the theoretical advantage of adopting a low-intensity antiplatelet regimen due to the absence of struts and polymers. Nevertheless, the optimal antiplatelet strategy for patients undergoing DCB-only treatment remains a topic of debate and has not been investigated in randomized trials. METHODS: The REC-CAGEFREE II is an investigator-initiated, prospective, open-label, multi-center, randomized, non-inferiority trial aimed to enroll 1908 patients from ≥ 40 interventional cardiology centers in China to evaluate the non-inferiority of an antiplatelet regimen consisting of Aspirin plus Ticagrelor for one month, followed by five months Ticagrelor monotherapy, and then Aspirin monotherapy for six months (Experimental group) compared to the conventional treatment of Aspirin plus Ticagrelor for 12 months (Reference group) in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) using paclitaxel-coated balloons (DCB) exclusively. Participants will be randomly assigned to the Experimental or Reference group in a 1:1 ratio. The randomization will be stratified based on the center and the type of lesion being treated (De novo or in-stent restenosis). The primary endpoint is net adverse clinical events (NACE) within 12 months of PCI, which includes the composite of all-cause death, any stroke, any myocardial infarction, any revascularization and Bleeding Academic Research Consortium (BARC) defined type 3 or 5 bleeding. The secondary endpoint, any ischemic and bleeding event, which includes all-cause death, any stroke, MI, BARC-defined type 3 bleeding, any revascularization, and BARC-defined type 2 bleeding events, will be treated as having hierarchical clinical importance in the above order and analyzed using the win ratio method. DISCUSSION: The ongoing REC-CAGEFREE II trial aims to assess the efficacy and safety of a low-intensity antiplatelet approach among ACS patients with DCB. If non-inferiority is shown, the novel antiplatelet approach could provide an alternative treatment for ACS patients with DCB. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04971356.
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Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Humanos , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/tratamento farmacológico , Aspirina , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Acidente Vascular Cerebral/etiologia , Ticagrelor/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Estudos de Equivalência como AsuntoRESUMO
BACKGROUND: Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. STUDY DESIGN: The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. DISCUSSION: The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. TRIAL REGISTRATION: Registered on clinicaltrial.gov (NCT04561739).
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Angioplastia Coronária com Balão , Cateteres Cardíacos , Fármacos Cardiovasculares , Materiais Revestidos Biocompatíveis , Doença da Artéria Coronariana , Paclitaxel , Humanos , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/mortalidade , Resultado do Tratamento , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , China , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Fatores de Tempo , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Stents , Idoso , Stents Farmacológicos , Estudos de Equivalência como Asunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: The palatal mucosa exhibits a notable ability to regenerate without causing scarring during the process of wound healing, rendering it a highly valuable reservoir of mesenchymal stem cells (MSCs). The aim of this review is to summarize the different sources of MSCs derived from hard palatal (PMSCs), thereby presenting a promising avenue for the utilization of regenerative medicine. MATERIALS AND METHODS: Pertinent literatures focused on the sources, identification methods, and advantageous characteristics of PMSCs are obtained from PubMed and Web of Science. RESULTS: PMSCs, originating from the hard palate periosteum, subepithelial adipose tissue, and lamina propria, have been successfully isolated and characterized, with positive markers for MSCs and negative markers for hematopoietic stem cells. Moreover, PMSCs demonstrate resistance to inflammatory stimuli, enabling uninterrupted osteogenesis in the presence of inflammation. Additionally, PMSCs possess a notable migratory capacity, facilitating prompt arrival at the site of injury. Furthermore, PMSCs exhibit various advantageous inherent in stem cells, including clonogenicity, self-renewal capability, and pluripotent differentiation potential. CONCLUSIONS: PMSCs have stem cell-related properties and can be used for regenerative medicine of cells and tissues in the future.
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Conditional power (CP) serves as a widely utilized approach for futility monitoring in group sequential designs. However, adopting the CP methods may lead to inadequate control of the type II error rate at the desired level. In this study, we introduce a flexible beta spending function tailored to regulate the type II error rate while employing CP based on a predetermined standardized effect size for futility monitoring (a so-called CP-beta spending function). This function delineates the expenditure of type II error rate across the entirety of the trial. Unlike other existing beta spending functions, the CP-beta spending function seamlessly incorporates beta spending concept into the CP framework, facilitating precise stagewise control of the type II error rate during futility monitoring. In addition, the stopping boundaries derived from the CP-beta spending function can be calculated via integration akin to other traditional beta spending function methods. Furthermore, the proposed CP-beta spending function accommodates various thresholds on the CP-scale at different stages of the trial, ensuring its adaptability across different information time scenarios. These attributes render the CP-beta spending function competitive among other forms of beta spending functions, making it applicable to any trials in group sequential designs with straightforward implementation. Both simulation study and example from an acute ischemic stroke trial demonstrate that the proposed method accurately captures expected power, even when the initially determined sample size does not consider futility stopping, and exhibits a good performance in maintaining overall type I error rates for evident futility.
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AVC Isquêmico , Projetos de Pesquisa , Humanos , Tamanho da Amostra , Simulação por Computador , Futilidade MédicaRESUMO
Gastric cancer is one of the deadliest malignant tumors, and half of the patients develop recurrences or metastasis within 5 years after eradication therapy. Cancer stem cells (CSCs) are considered to be important in this progress. The sonic hedgehog (SHH) pathway plays an important role in the maintenance of gastric CSCs characteristics. The p63 proteins are vital transcription factors belonging to the p53 family, while their functions in regulating CSCs remain unclear. The preventive effects of dietary diallyl trisulfide (DATS) against human gastric cancer have been verified. However, whether DATS can target gastric CSCs are poorly understood. Here, we investigated the role of ΔNp63/SHH pathway in gastric CSCs and the inhibitory effect of DATS on gastric CSCs via ΔNp63/SHH pathway. We found that ΔNp63 was upregulated in serum-free medium cultured gastric tumorspheres compared with the parental cells. Overexpression of ΔNp63 elevated the self-renewal capacity and CSC markers' levels in gastric sphere-forming cells. Furthermore, we found that ΔNp63 directly bound to the promoter region of Gli1, the key transcriptional factor of SHH pathway, to enhance its expression and to activate SHH pathway. In addition, it was revealed that DATS effectively inhibited gastric CSC properties both in vitro and in vivo settings. Activation of SHH pathway attenuated the suppressive effects of DATS on the stemness of gastric cancer. Moreover, DATS suppression of gastric CSC properties was also diminished by ΔNp63 upregulation through SHH pathway activation. These findings illustrated the role of ΔNp63/SHH pathway in DATS inhibition of gastric cancer stemness. Taken together, the present study suggested for the first time that DATS inhibited gastric CSCs properties by ΔNp63/SHH pathway.
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Proteínas Hedgehog , Neoplasias Gástricas , Humanos , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/farmacologia , Neoplasias Gástricas/patologia , Transdução de Sinais , Fatores de Transcrição/metabolismo , Células-Tronco Neoplásicas/patologia , Linhagem Celular TumoralRESUMO
Membranes with high selectivity offer an attractive route to molecular separations, where technologies such as distillation and chromatography are energy intensive. However, it remains challenging to fine tune the structure and porosity in membranes, particularly to separate molecules of similar size. Here, we report a process for producing composite membranes that comprise crystalline porous organic cage films fabricated by interfacial synthesis on a polyacrylonitrile support. These membranes exhibit ultrafast solvent permeance and high rejection of organic dyes with molecular weights over 600 g mol-1. The crystalline cage film is dynamic, and its pore aperture can be switched in methanol to generate larger pores that provide increased methanol permeance and higher molecular weight cut-offs (1,400 g mol-1). By varying the water/methanol ratio, the film can be switched between two phases that have different selectivities, such that a single, 'smart' crystalline membrane can perform graded molecular sieving. We exemplify this by separating three organic dyes in a single-stage, single-membrane process.
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Membranas Artificiais , Água , Porosidade , SolventesRESUMO
Vitamin D deficiency is a worldwide health problem. However, the prevalence of vitamin D deficiency in Asian populations is unclear. The aims of our study were to investigate the prevalence of vitamin D deficiency and its association with different health outcomes in Asia. Searches for studies published from January 2009 to January 2021 were performed in the MEDLINE (via PubMed), EMBASE, and Web of Science databases. This study was registered in the PROSPERO database (CRD42021229841). In total, 472 studies with 746,564 subjects were included in the meta-analysis. The mean serum 25-hydroxyvitamin D (25[OH]D) concentration was 49.39 nmol/L; 20.93% of the participants had 25(OH)D levels <25 nmol/L, 22.82% had levels <30 nmol/L, 57.69% had levels <50 nmol/L, and 76.85% had levels <75 nmol/L. This review found that the prevalence of vitamin D deficiency in Asia is high. The factors significantly related to vitamin D deficiency were gender, age, altitude, region, and specific diseases (diabetes, cancer, fracture, systemic lupus erythematosus [SLE], fatty liver disease, osteopenia, thyroiditis, anemia, hepatitis, metabolic diseases, and dermatitis). These findings may serve as the foundation for more detailed public health strategies and policies on this issue.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1990850.
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Lúpus Eritematoso Sistêmico , Deficiência de Vitamina D , Humanos , Prevalência , Vitamina D , Ásia/epidemiologia , Saúde GlobalRESUMO
Circular RNAs (circRNAs) play an important role in biological activities, especially in regulating osteogenic differentiation of stem cells. However, no studies have reported the role of circRNAs in early osseointegration. Here we identified a new circRNA, circRNA422, from rat bone marrow mesenchymal stem cells (BMSCs) cultured on sandblasted, large-grit, acid-etched titanium surfaces. The results showed that circRNA422 significantly enhanced osteogenic differentiation of BMSCs with increased expression levels of alkaline phosphatase, the SP7 transcription factor (SP7/osterix), and lipoprotein receptor-related protein 5 (LRP5). Silencing of circRNA422 had opposite effects. There were two SP7 binding sites on the LRP5 promoter, indicating a direct regulatory relationship between SP7 and LRP5. circRNA422 could regulate early osseointegration in in vivo experiments. These findings revealed an important function of circRNA422 during early osseointegration. Therefore, circRNA422 may be a potential therapeutic target for enhancing implant osseointegration.
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Células-Tronco Mesenquimais , Osteogênese , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/farmacologia , Animais , Células da Medula Óssea/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osseointegração/genética , Osteogênese/genética , RNA Circular/genética , Ratos , Fator de Transcrição Sp7/metabolismo , Titânio/química , Titânio/metabolismo , Titânio/farmacologiaRESUMO
OBJECTIVES: This retrospective study aimed to evaluate early and late implant loss rates after transcrestal sinus floor elevation (TSFE) and to identify the risk factors related to these failures. MATERIAL AND METHODS: All patients treated with TSFE and simultaneous implant placement during October 2015 to March 2019 were evaluated for inclusion. A total of 802 patients with 976 implants met the inclusion criteria. Clinical and radiographic information was collected from medical records and image software. Univariate and multivariate Cox proportional hazards frailty regression models were performed to identify potential risk factors associated with early and late implant loss after TSFE. RESULTS: The 3-year cumulative implant survival rate was 96.9% (95% CI 95.8%-98.0%). Twelve implants in 12 patients were lost before or at the abutment connection, while 24 implants in 24 patients were lost after functional loading. The Cox frailty regression analyses indicated that two factors were correlated with early implant loss: TSFE with grafting materials, and operators with less clinical experience. As for late implant loss, RBH ≤6 mm, male sex, and certain implant brands were associated with a significantly increased failure rate. CONCLUSIONS: Transcrestal sinus floor elevation with simultaneous implant placement is a predictable treatment option in the atrophic maxilla. The presence of grafting materials and the lack of clinical experience of the surgeon were possibly associated with early implant loss, while low RBH, male sex, and certain implant brands tended to increase late implant loss.
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Implantes Dentários , Fragilidade , Levantamento do Assoalho do Seio Maxilar , Humanos , Masculino , Implantação Dentária Endóssea/métodos , Levantamento do Assoalho do Seio Maxilar/métodos , Estudos Retrospectivos , Fragilidade/cirurgia , Seio Maxilar/cirurgia , Resultado do Tratamento , Maxila/cirurgiaRESUMO
The electrophysiological function of the tongue involves complicated activities in taste sense, producing the perceptions of salty, sweet, bitter, and sour. However, therapies and prevention of taste loss arising from dysfunction in electrophysiological activity require further fundamental research. Optogenetics has revolutionized neuroscience and brought the study of sensory system to a higher level in taste. The year 2022 marks a decade of developments of optogenetics in taste since this technology was adopted from neuroscience and applied to the taste research. This review summarizes a decade of advances that define near-term translation with optogenetic tools, and newly-discovered mechanisms with the applications of these tools. The main limitations and opportunities for optogenetics in taste research are also discussed.
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BACKGROUND: This study aimed to compare the clinical outcomes of patients who underwent three-port laparoscopic radical cystectomy (LRC) with orthotopic neobladder (ONB) and traditional five-port method. METHODS: From January 2017 to November 2020, 100 patients underwent LRC + ONB at a third-level grade A hospital. RESULTS: Our study included 55 patients who underwent three-port LRC and 45 patients who underwent the five-port method. There were no significant differences in perioperative data such as operation time (253.00 ± 43.89 vs. 259.07 ± 52.31 min, P = 0.530), estimated blood loss (EBL)(97.64 ± 59.44 vs. 106.67 ± 55.35 min, P = 0.438), day to flatus (2.25 ± 1.49 vs. 2.76 ± 1.77 days, P = 0.128), day to regular diet (7.07 ± 2.99 vs. 7.96 ± 3.32 days, P = 0.165), day to pelvic drain removal (9.58 ± 3.25 vs. 10.53 ± 3.80 days, P = 0.180), and hospital stay after operation (11.62 ± 3.72 vs. 11.84 ± 4.37 days, P = 0.780) between the two groups. The only significant difference was in the treatment cost (P = 0.035). Similarly, postoperative complications, quality of life, and tumor outcomes were not significantly different between the two groups (P > 0.05). CONCLUSIONS: The three-port method is safe and feasible for patients suitable for traditional five-port LRC with an orthotopic neobladder.
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Laparoscopia , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/métodos , Estudos Retrospectivos , Qualidade de Vida , Resultado do Tratamento , Laparoscopia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologiaRESUMO
Objective: To examine the effect of perioperative precision nursing care of enhanced recovery after surgery (ERAS) on the postoperative recovery, stress response, and psychological state of colorectal cancer patients. Methods: A total of 100 patients undergoing elective laparoscopic colorectal cancer surgery were randomly assigned to an experimental group and a control group, with 50 patients in each group. The experimental group received systematic, standardized, and specialized precision nursing care in three stages, the preoperative, intraoperative, and postoperative stages, while the control group received routine nursing care. The main outcome indicators compared between the two groups included the time of the first postoperative passage of flatus and stool, ambulation, liquid-diet meal, postoperative length-of-stay, and C-reactive protein (CRP), interleukin-6 (IL-6), and homeostatic model assessment of insulin resistance (HOMR-IR) measured 1 day before surgery and 1, 3, and 5 days after surgery. Secondary outcome indicators included the anxiety and depression levels of patients measured upon admission to the hospital and 48 h after surgery by Self-rating Anxiety Scale (SAS) and Self-rating Sepression Scale (SDS), respectively. Results: In the experimental group, the time of the first postoperative passage of flatus and stool, ambulation, and liquid-diet meal and the postoperative length-of-stay were all lower than those in the control group. The postoperative CRP and IL-6 levels of the two groups were significantly higher than the preoperative levels, and the control group had higher CRP and IL-6 levels than the experimental group did, all showing significant difference ( P<0.05). The two groups presented different stress states at different points of time after surgery, with the CRP and IL-6 levels reaching the highest 3 days after surgery and then dropping to some degree afterwards. The HOMR-IR of the patients in the experimental group was significantly lower than that of the control group and the difference was significant at both 1 d and 3 d after surgery ( P<0.05). Comparison of the difference in the anxiety and the depression scores in the two groups showed significant difference ( P<0.05). Before discharge, patient satisfaction of the experimental group was significantly higher than that of the control group ( P<0.05). Conclusion: The implementation of ERAS precision nursing care can effectively promote the postoperative recovery of colorectal cancer patients, reduce the perioperative stress response, alleviate anxiety and depression, improve patient satisfaction, and hence should be extensively applied in clinical practice.
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Neoplasias Colorretais , Cuidados de Enfermagem , Humanos , Assistência Perioperatória , Interleucina-6 , Flatulência , Período Pós-Operatório , Neoplasias Colorretais/cirurgia , Tempo de Internação , Complicações Pós-OperatóriasRESUMO
It is an appealing approach to CO2 utilization through CO2 electroreduction (CO2 ER) to ethanol at high current density; however, the commonly used Cu-based catalysts cannot sustain large current during CO2 ER despite their capability for ethanol production. Herein, we report that Ag+ -doped InSe nanosheets with Se vacancies can address this grand challenge in a membrane electrode assembly (MEA) electrolyzer. As revealed by our experimental characterization and theoretical calculation, the Ag+ doping, which can tailor the electronic structure of InSe while diversifying catalytically active sites, enables the formation of key reaction intermediates and their sequential evolution into ethanol. More importantly, such a material can well work for large-current conditions in MEA electrolyzers with In2+ species stabilized via electron transfer from Ag to Se. Remarkably, in an MEA electrolyzer by coupling cathodic CO2 ER with anodic oxygen evolution reaction (OER), the optimal catalyst exhibits an ethanol Faradaic efficiency of 68.7 % and a partial current density of 186.6â mA cm-2 on the cathode with a full-cell ethanol energy efficiency of 26.1 % at 3.0â V. This work opens an avenue for large-current production of ethanol from CO2 with high selectivity and energy efficiency by rationally designing electrocatalysts.
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Objective: The interplay between chemokine C-X-C motif ligand 12 (CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently, targeting this signaling axis has emerged as a potential strategy in cancer therapy. However, the precise role of CXCL12 in clinical therapy, especially in immunotherapy for bladder cancer (BCa), remains poorly elucidated. Methods: We gathered multiple omics data from public databases to unveil the clinical relevance and tumor immune landscape associated with CXCL12 in BCa patients. Univariate and multivariate Cox regression analyses were employed to assess the independent prognostic significance of CXCL12 expression and formulate a nomogram. The expression of CXCL12 in BCa cell lines and clinical tissue samples was validated using enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry (IHC). Results: While transcriptional expression of CXCL12 exhibited a decrease in nearly all tumor tissues, CXCL12 methylation expression was notably increased in BCa tissues. Single-cell RNA analysis highlighted tissue stem cells and endothelial cells as the primary sources expressing CXCL12. Abnormal CXCL12 expression, based on transcriptional and methylation levels, correlated with various clinical characteristics in BCa patients. Functional analysis indicated enrichment of CXCL12 and its co-expression genes in immune regulation and cell adhesion. The immune landscape analysis unveiled a significant association between CXCL12 expression and M2 macrophages (CD163+ cells) in BCa tissues. Notably, CXCL12 expression emerged as a potential predictor of immunotherapy response and chemotherapy drug sensitivity in BCa patients. Conclusions: Taken together, these findings suggest aberrant production of CXCL12 in BCa tissues, potentially influencing the treatment responses of affected individuals.
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BACKGROUND: Due to a combination of high morbidity and lack of effective treatments, gastric cancer (GC) remains a major cause of cancer-related death all over the world. H19, as a paternally imprinted long noncoding RNA (lncRNA), has been found dysregulated in GC. AIM: The aim of this study is to elucidate the specific mechanism of H19 in GC. METHODS: Bioinformatic analysis and quantitative real-time PCR analysis were utilized to test the expression pattern of H19 in GC tissues and cell lines. Wound healing, transwell, immunofluorescence assay, and Western blot assays were conducted to test cell malignant phenotypes. Meanwhile, TOP/FOP flash assay was to analyze the relationship of H19 and Wnt/ß-catenin signaling. Also, mice xenograft models were to evaluate the influence of H19 on tumor growth. RESULTS: H19 was overexpressed in GC tissues and cell lines and related to poor prognosis for GC patients. In vitro and in vivo assays verified the promotion of H19 on GC cell epithelial to mesenchymal transition (EMT) and metastasis. Mechanistically, H19 could induce ß-catenin to transfer into nucleus and activate Wnt/ß-catenin signaling, thus promoting EMT and metastasis of GC cells. CONCLUSION: Our findings proved the mechanism of H19-mediated metastasis via activating Wnt/ß-catenin signaling, which provides a promising target for developing new therapeutic strategies in GC.
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RNA Longo não Codificante , Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Metástase Neoplásica , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/patologia , Via de Sinalização Wnt/genética , beta Catenina/genética , beta Catenina/metabolismoRESUMO
OBJECTIVES: To retrospectively compare multilevel volumetric changes in both hard and soft tissues between antral pseudocyst (AP) removal and retainment before maxillary sinus floor augmentation (MSFA) and immediate implant placement. MATERIAL AND METHODS: Twenty-six patients with 38 implants placed from 2016 to 2021 were included and divided according to a cohort design as follows: 13 removing the cyst (RC group) and 13 "leaving alone" the cyst (LC group). 3D radiographic parameters (primary outcome), 2D parameters and clinical records (secondary outcome) involving both hard and soft tissues were evaluated for four periods (T1: immediate postoperative, T2: 6-month, T3: 12-month, and T4: 2- to 5- year follow-up). Possible confounding factors, including sinus anatomical features and implant distribution, were also analyzed to eliminate their disturbance. RESULTS: The 3D volumetric change rate of bone grafts in the RC group (-9.32% ± 10.01%) from T2 to T3 was significantly lower than that in the LC group (-19.8% ± 10.59%) (p < .05). The change rate of apical bone height (ABH), endo-sinus bone gain (ESBG) and other 2D parameters were not significantly different between the two groups. 5.3% implants in RC group and 9.1% implants in LC group failed during follow-ups. 0% postoperative complications were observed in RC group. The Schneiderian membrane of RC group was significantly thinner than that of LC group at two measuring points in sinus. CONCLUSION: The present study demonstrated that compared to AP retainment, AP removal before MSFA and immediate implant placement can obtain higher bone graft volumetric stability and favorable prognosis.
Assuntos
Cistos , Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Humanos , Estudos Retrospectivos , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia , Transplante Ósseo , Cistos/diagnóstico por imagem , Cistos/cirurgia , Implantação Dentária EndósseaRESUMO
BACKGROUND: Heart rate variability (HRV), a sensitive marker of stress and autonomic nervous disorders, was significantly decreased in cardiovascular disease, inflammation, and surgical injury. However, the effect of radical gastrectomy on HRV parameters needs to be further investigated. METHODS: A prospective, observational study including 45 consecutive enrolled patients undergoing radical gastrectomy in our enhanced recovery after surgery (ERAS) programs was conducted. Frequency- and time-domain parameters of HRV from 1 day prior to operation to 4 days postoperatively were continuously measured. Meanwhile, plasma cortisol and inflammatory markers were recorded and correlated to HRV parameters. RESULTS: Heart rate variability showed a solidly circadian rhythm. Anesthesia severely disturbed HRV parameters, resulting in a reduction of most of the HRV parameters. Frequency-domain parameter (including VLF) and time-domain parameters (including the SDNN, SDANN, and triangular index) of HRV demonstrated a significant reduction compared to preoperative values on the postoperative day 1 (Pod1), and these HRV parameters could return to baseline on Pod2 or Pod3, indicating surgical stress and autonomic nerve dysfunction existed in the early postoperative period. Inflammatory biomarkers were significantly elevated on Pod1 and Pod3. Plasma cortisol decreased significantly on Pod1 and Pod3. Both inflammatory biomarkers and plasma cortisol had no significant correlation with HRV parameters. CONCLUSIONS: Compared with plasma cortisol and inflammation biomarkers, HRV is more sensitive to detect surgical stress and autonomic nervous dysfunction induced by radical gastrectomy in patients with gastric cancer.