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The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.
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BACKGROUND: Liver cancer (LC) screening, such as AFP test and abdominal ultrasound, is an effective way to prevent LC, one of the most common cancers worldwide. Despite the proven screening benefits, screening participation among high-risk populations for LC remains low. This suggests that targeted, systematic, and effective interventions should be provided to improve knowledge and awareness related to LC screening, enhance screening intentions, and thereby promote screening behaviors. Telephone is people's main medium of daily communication and mHealth-based programs offer a potential and effective solution for promoting health behaviors. The purpose of this study is to develop and implement a mHealth (WeChat app) based intervention guided by Fogg's Behavior Model (FBM) to augment the knowledge of LC prevention among people at risk of LC and enhance their motivation for screening, and to validate its effectiveness in improving LC screening. METHODS: We propose a two-arm, single-blind randomized controlled trial with 82 at-risk individuals of LC, delivering a 6-month mHealth-based intervention program with optional health counseling. Recruitment will be through tertiary hospitals and community organizations in 4 districts in Heng Yang. In total, 82 individuals at high risk for HCC will be randomized 1:1 to intervention or control (usual care) groups. The intervention group will receive intervention, whose contents are based on the FBM model, via multiple forms of media including PowerPoint presentation, multimedia video, health information booklet and screening message, which is delivered in the WeChat Applet. Control dyads will be provided with usual health education. Outcomes will be assessed at baseline and post-intervention. DISCUSSION: The findings of this study will provide evidence of the benefits of utilizing mHealth-based approaches in intervention development to enhance the effectiveness of screening adherence for high-risk people of LC. Further, the findings would provide reference to the potential incorporation of the targeted intervention in local community organizations. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2400080530) Date registered: 31/1/2024.
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Detección Precoz del Cáncer , Neoplasias Hepáticas , Telemedicina , Humanos , Detección Precoz del Cáncer/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/prevención & control , Método Simple Ciego , Masculino , Femenino , China , Persona de Mediana Edad , Adulto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: BBV152 (Covaxin™) is a whole-virion inactivated SARS-CoV-2 vaccine mixed with an immune adjuvant. We aimed to compare immune responses after booster vaccination with heterologous BBV152 versus homologous mRNA vaccine. METHODS: We conducted a randomized, participant-blinded, controlled trial. Fifty mRNA-vaccinated participants were enrolled and randomized to receive an mRNA booster (n = 26) or BBV152 (n = 24). Blood samples were collected pre-vaccination, and at Day 7, 28, 180 and 360 post-booster for analysis of humoral and cellular immune responses. Primary end point was the SARS-CoV-2 anti-spike antibody titer at day 28. RESULTS: Recruitment began in January 2022 and was terminated early due to the BBV152 group meeting pre-specified criteria for futility. At Day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBV152 (2004 IU/mL; 95 % confidence interval [CI], 1132-3548) vs mRNA (26,669 IU/mL; 95 % CI, 21,330-33,266; p < 0.0001), but comparable levels of spike-specific CD4 and cytotoxic T-cells were observed. Anti-spike antibody titers remained significantly different at Day 180: BBV152 4467 IU/mL (95 % CI, 1959-10,186) vs mRNA 20,749 IU/mL (95 % CI, 12,303-35,075; p = 0.0017). Levels of surrogate virus neutralizing antibodies against ancestral and Omicron subvariants BA.1 and BA.2 were significantly higher among mRNA recipients at Day 180, including after adjusting for intercurrent infection. By Day 360, anti-spike antibody titers and neutralizing antibody levels against Omicron subvariants became similar between vaccine groups. By the end of the study, 16 in each arm (mRNA 64 % and BBV152 69.6 %) had breakthrough infections and time to COVID-19 infection between vaccine groups were similar (p = 0.63). CONCLUSIONS: Wild-type SARS-CoV-2 anti-spike antibody titer and surrogate virus neutralizing test levels against wild-type SARS-CoV-2 and Omicron subvariants BA.1/BA.2/BA.5 were significantly higher at Day 28 and 180 in individuals who received booster vaccination with an mRNA vaccine compared with BBV152. CLINICAL TRIAL REGISTRATION NUMBER: NCT05142319.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Inmunogenicidad Vacunal , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Femenino , Masculino , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Adulto , Inmunización Secundaria/métodos , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de ARNm/inmunología , Adulto Joven , Inmunidad Humoral , Inmunidad Celular , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificaciónRESUMEN
Since the advent of formamidinium (FA)-based perovskite photovoltaics (PVs), significant performance enhancements have been achieved. However, a critical challenge persists: the propensity for void formation in the perovskite film at the buried perovskite-interlayer interface has a deleterious effect on device performance. With most emerging perovskite PVs adopting the p-i-n architecture, the specific challenge lies at the perovskite-hole transport layer (HTL) interface, with previous strategies to overcome this limitation being limited to specific perovskite-HTL combinations; thus, the lack of universal approaches represents a bottleneck. Here, we present a novel strategy that overcomes the formation of such voids (microstructural defects) through a film treatment with methylammonium chloride (MACl). Specifically, our work introduces MACl via a sequential deposition method, having a profound impact on the microstructural defect density at the critical buried interface. Our technique is independent of both the HTL and the perovskite film thickness, highlighting the universal nature of this approach. By employing device photoluminescence measurements and conductive atomic force microscopy, we reveal that when present, such voids impede charge extraction, thereby diminishing device short-circuit current. Through comprehensive steady-state and transient photoluminescence spectroscopy analysis, we demonstrate that by implementing our MACl treatment to remedy these voids, devices with reduced defect states, suppressed nonradiative recombination, and extended carrier lifetimes of up to 2.3 µs can be prepared. Furthermore, our novel treatment reduces the stringent constraints around antisolvent choice and dripping time, significantly extending the processing window for the perovskite absorber layer and offering significantly greater flexibility for device fabrication.
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BACKGROUND: Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy. METHODS: We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) versus heterologous (mRNA-1273) booster vaccination in 100 BNT162b2-vaccinated infection-naïve individuals enrolled from October 2021. Post hoc analysis was performed to assess the impact of SARS-CoV-2 infection on humoral and cellular immune responses against wild-type SARS-CoV-2 and/or Omicron subvariants. FINDINGS: 93 participants completed the study at day 360. 71% (66/93) of participants reported first SARS-CoV-2 Omicron infection by the end of the study with similar proportions of infections between homologous and heterologous booster groups (72.3% [34/47] vs 69.6% [32/46]; p = 0.82). Mean wildtype SARS-CoV-2 anti-S-RBD antibody level was significantly higher in heterologous booster group compared with homologous group at day 180 (14,588 IU/mL; 95% CI, 10,186-20,893 vs 7447 IU/mL; 4646-11,912; p = 0.025). Participants who experienced breakthrough infections during the Omicron BA.1/2 wave had significantly higher anti-S-RBD antibody levels against wildtype SARS-CoV-2 and antibody neutralisation against BA.1 and pre-emergent BA.5 compared with infection-naïve participants. Regardless of hybrid immunity status, wildtype SARS-CoV-2 anti-S-RBD antibody level declined significantly after six months post-booster or post-SARS-CoV-2 infection. INTERPRETATION: Booster vaccination with mRNA-1273 was associated with significantly higher antibody levels compared with BNT162b2. Antibody responses are narrower and decline faster among uninfected, vaccinated individuals. Boosters may be more effective if administered shortly before infection outbreaks and at least six months after last infection or booster. FUNDING: Singapore NMRC, USFDA, MRC.
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Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Humanos , SARS-CoV-2/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Femenino , Adulto , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Persona de Mediana Edad , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacuna nCoV-2019 mRNA-1273/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Inmunogenicidad Vacunal , Inmunidad Humoral , Vacunación/métodos , Anciano , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto Joven , Infección IrruptivaRESUMEN
BACKGROUND: Macitentan, either as monotherapy or part of combination therapy, improved clinical outcomes in patients with pulmonary artery hypertension (PAH) in clinical trials. Evidence on the effectiveness and safety of macitentan administered in real-world clinical practice in China is limited. METHODS: This real-world, retrospective, multicenter chart review study was conducted at seven hospitals in China. Adult patients with a diagnosis of PAH who initiated macitentan and had medical assessments at 3-7 months after macitentan initiation were included. The primary outcomes were changes in the World Health Organization functional class (WHO-FC), 6-min walk distance (6MWD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)/B-type natriuretic peptide from baseline to first follow-up visit (months 3-7). Serious adverse events (SAEs) and adverse drug reactions (ADRs) of macitentan were collected. RESULTS: From 30 August 2021 to 31 March 2022, 214 eligible patients were included in the safety analysis set and 105 patients were included in the analysis of effectiveness. At the first follow-up visit compared with baseline, significant changes in WHO-FC were observed (p = .04), 93.5% patients had their WHO-FC improved (25.8%) or maintained (67.7%). 6MWD changed by a mean (standard deviation [SD]) of 45.0 (81.4) meters (p < .001), with 94.7% having their 6MWD improved (34.7%) or maintained (60.0%). The mean (SD) of NT-proBNP decreased from 1667.4 (3233.0) ng/L to 1090.0 (2230.1) ng/L (p < .001). In the safety analysis set, 24 (11.2%) patients experienced at least one ADR and/or SAE. ADRs and SAEs were reported in 11 (5.1%) and 18 (8.4%), respectively. No deaths or unexpected safety events were observed. CONCLUSION: This study provided real-world evidence on the clinical benefits and good tolerance of macitentan in Chinese patients with PAH treated in routine clinical practice.
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Hipertensión Arterial Pulmonar , Pirimidinas , Sulfonamidas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , China , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/administración & dosificación , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Adulto , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Resultado del Tratamiento , AncianoRESUMEN
OBJECTIVES: The emergence of new SARS-CoV-2 variants has led to the development of Omicron-targeting bivalent mRNA vaccines. It is crucial to understand how bivalent vaccines may improve antibody responses against new variants. METHODS: A total of 107 participants, who had three COVID-19 WT mRNA vaccine doses, were recruited, and given either a monovalent (WT) or a bivalent mRNA vaccination (Pfizer/BioNTech Bivalent (WT and BA.4/BA.5) or Moderna Bivalent (WT and BA.1). Blood samples were taken before booster and at 28 days post-booster. RESULTS: We found significantly lower fold change in serum binding IgA responses against BA.1, BA.5 and EG.5.1 spike in the bivalent booster group, compared with the monovalent (WT) booster group, following vaccination. However, this was only observed in individuals with prior infection. The relative fold change in serum binding IgA response was more skewed towards WT over variant (BA.1, BA.5 or EG.5.1) spike in previously infected bivalent-booster-vaccinees, as compared with previously infected monovalent-(WT)-booster-vaccinees. CONCLUSION: The findings suggest imprinting of antibody responses that is shaped by the first vaccination (WT spike). Previous infection also affects the boosting effect of follow-up vaccination. Studies are needed to understand how to induce a robust and long-lasting IgA immunity for protection against COVID-19 infection.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunoglobulina A , SARS-CoV-2 , Humanos , Inmunoglobulina A/sangre , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/virología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Masculino , Femenino , Adulto , Anticuerpos Antivirales/sangre , Persona de Mediana Edad , Vacunas de ARNm , Inmunización Secundaria , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Vacunación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Anciano , Adulto JovenRESUMEN
In layered Li-rich materials, over stoichiometric Li forms an ordered occupation of LiTM6 in transition metal (TM) layer, showing a honeycomb superstructure along [001] direction. At the atomic scale, the instability of the superstructure at high voltage is the root cause of problems such as capacity/voltage decay of Li-rich materials. Here a Li-rich material with a high Li/Ni disorder is reported, these interlayer Ni atoms locate above the honeycomb superstructure and share adjacent O coordination with honeycomb TM. These NiâO bonds act as cable-stayed bridge to the honeycomb plane, and improve the high-voltage stability. The cable-stayed honeycomb superstructure is confirmed by in situ X-ray diffraction to have a unique cell evolution mechanism that it can alleviate interlaminar lattice strain by promoting in-plane expansion along a-axis and inhibiting c-axis stretching. Electrochemical tests also demonstrate significantly improved long cycle performance after 500 cycles (86% for Li-rich/Li half cell and 82% for Li-rich/Si-C full cell) and reduced irreversible oxygen release. This work proves the feasibility of achieving outstanding stability of lithium-rich materials through superstructure regulation and provides new insights for the development of the next-generation high-energy-density cathodes.
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Dynapenia and multimorbidity are common health problems affecting older adults. However, few studies have systematically reviewed the association between dynapenia and multimorbidity. Therefore, this systematic review aimed to provide a comprehensive overview of studies on the association between these conditions. We searched four electronic databases for relevant articles published in July 2023. The main inclusion criteria were the following: (1) a description of dynapenia, which indicates loss of muscle strength and (2) a description of multimorbidity with two or more chronic diseases. Five studies met these inclusion criteria. In all five of these studies, the participants were community-dwelling older adults. All the studies showed an association between dynapenia and multimorbidity. The prevalence of dynapenia and multimorbidity ranged from 16% to 25.9%. The results of our systematic review demonstrated that dynapenia in older adults increases the risk of multimorbidity. We propose that interventions and reversible changes in dynapenia can prevent multimorbidity.
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At the end of 2022, the adjustment of the coronavirus disease 2019 (COVID-19) pandemic control policy in China resulted in a large-scale increase in public infection. To compare the fertility parameters of male patients before and after the adjustments of the COVID-19 pandemic control policy in China, we collected data on patients' medical histories and laboratory examinations on their first visits between June 2022 and March 2023 in five different hospitals. Data were divided into five groups according to the timeline of the policy adjustment. The data we collected from male patients included semen quality and serum reproductive hormone levels, and intergroup comparisons were made using the Mann-Whitney U and Chi-square tests. In total, 16 784 cases underwent regular semen analysis, 11 180 had sperm morphology assessments, and 7200 had reproductive hormone analyses. The data showed declining trends in semen volume, sperm motility, and the progressive sperm motility rate after the policy adjustment. Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate. Sperm morphology analysis showed increased neck and tail abnormalities after the policy adjustment. No significant change in hormone levels was observed. Following the adjustment of the COVID-19 prevention policy in China, a decline in sperm motility and morphology was observed. This trend may gradually recover over 2 months. After the policy adjustment, reproductive hormone levels were relatively stable throughout, except for an increase in luteinizing hormone (LH). These changes in semen parameters suggest that the policy adjustment had a short- to medium-term impact on male reproductive function.
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COVID-19 , Análisis de Semen , Motilidad Espermática , Humanos , Masculino , COVID-19/prevención & control , COVID-19/epidemiología , China/epidemiología , Adulto , SARS-CoV-2 , Persona de Mediana Edad , Hormona Luteinizante/sangre , Testosterona/sangre , Espermatozoides , Infertilidad Masculina/prevención & control , Hormona Folículo Estimulante/sangreRESUMEN
Deep gluteal syndrome (DGS) is caused by sciatic nerve entrapment. Because fascial entrapment neuropathies may occur in multiple locations, ultrasound-guided nerve hydrodissection is a key component of DGS treatment. In this study, we examined the clinical outcomes of patients with DGS undergoing ultrasound-guided sciatic nerve hydrodissection. A 10 mL mixture consisting of 5% dextrose, 0.2% lidocaine (Xylocaine), and 4 mg betamethasone (Rinderon) was used for nerve hydrodissection. Clinical outcomes were evaluated using Numeric Rating Scale (NRS) scores of pain, the proportion of patients with favorable outcomes (reduction of ≥50% in pain), the duration for which patients exhibited favorable outcomes (percentage of follow-up duration), and the occurrence of major complications and minor side effects. A total of 53 patients were consecutively included and followed up for 3 to 19 months. After the initial injection, the NRS scores significantly improved at 1 week, 1 month, 3 months, and the final follow-up. Specifically, 73.6%, 71.7%, 64.2%, and 62.3% of the patients exhibited favorable outcomes at 1 week, 1 month, 3 months, and the final follow-up, respectively. The median duration for which the patients exhibited favorable outcomes was 84.7% of the follow-up period. Three patients (5.7%) experienced transient dizziness and vomiting, which resolved without further treatment. No vessel or nerve puncture was observed. Overall, ultrasound-guided sciatic nerve hydrodissection is a safe procedure that mitigates the pain associated with DGS. To achieve favorable outcomes, three consecutive injections 3 weeks apart are required.
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Three CPs [Zn2(PDA)2(BMIOPE)2·3H2O]n (1), [Co(Br-BDC)(BMIOPE)]n (2) and [Co(MIP)(BMIOPE)]n (3) were synthesized by solvothermal method based on dual-ligand strategy (H2PDA, Br-H2BDC, BMIOPE and H2MIP are 1,3-phenylenediacetic acid, 5-bromo-isophthalic acid, 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether and 5-methylisophthalic acid, respectively). Complexes 1 and 3 exhibit twofold parallel interwoven sql nets. Complex 2 is 2D layer structure. The luminescence property investigations showed that complexes 1-3 could act as multi-responsive fluorescent sensors to detect UO22+, Cr2O72- and CrO42- and nitrofurantoin (NFT) through fluorescence turn-off process, presenting excellent sensitivity and selectivity. Finally, the possible fluorescent quenching mechanisms of complexes 1-3 toward the above pollutants are also further investigated by employing spectroscopic methods and quantum chemical calculations. The fluorescence lifetime measurements manifest the mechanism of fluorescence quenching is static quenching process.
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A novel ZnII coordination polymer, namely, poly[{µ2-bis[4-(2-methyl-1H-imidazol-1-yl)phenyl]methanone-κ2N3:N3'}(µ2-5-bromobenzene-1,3-dicarboxylato-κ2O1:O3)zinc(II)], [Zn(C8H3BrO4)(C21H18N4O)]n or [Zn(Br-BDC)(MIPMO)]n, (I), has been synthesized by the solvothermal method using 5-bromoisophthalic acid (Br-H2BDC), bis[4-(2-methyl-1H-imidazol-1-yl)phenyl]methanone (MIPMO) and Zn(NO3)2·6H2O. Structure analysis showed that compound (I) displays twofold parallel interwoven sql nets. Fluorescence experiments confirmed that the compound can sensitively and selectively detect nitrofurantoin (NFT) in aqueous medium. In addition, the possible fluorescence quenching mechanisms of compound (I) toward NFT are investigated.
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DEC1 is a helix-loop-helix (bHLH) transcription factor, whose deregulation has been observed in several tumors. However, the effects of the dysregulation of this gene on epithelial-mesenchymal transition (EMT) are controversial, with its roles in gastric cancer (GC) remaining unclear. In the present study, we focused on the impact of DEC1 on EMT and cell mobility in gastric cancer. We found that DEC1 expression positively correlated with TGF-ß1 and EMT markers in tumor issues, and that DEC1 facilitated TGF-ß1-induced EMT in gastric cancer. In addition, gastric cancer cell migration potential was reduced after DEC1 knockdown. Using murine metastasis models, we confirmed that DEC1 promoted GC metastasis and further explored the correlation of DEC1 with TGF-ß1 and E-cadherin in vivo. Chromatin immunoprecipitation (ChIP) assays revealed that DEC1 could directly interact with the promoter region of TGF-ß1. These results suggest that DEC1 functions as a tumor enhancer that partially participates in TGF-ß1-mediated EMT processes in GC, thus contributing to tumor metastasis.
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STATEMENT OF PROBLEM: A trial restoration is an important diagnostic tool that can be fabricated through analog or digital pathways. Digital workflows may have improved accuracy, but this is yet to be demonstrated conclusively. PURPOSE: The purpose of this in vitro study was to compare the dimensional accuracy of trial restorations produced by different analog (molded) and digital (milled and 3D printed) methods. Parameters studied included fabrication methods, Shore-A hardness of silicone putty indices, length of span, and labial tooth levels. MATERIAL AND METHODS: Digital additive trial restorations were designed on a single virtual cast from maxillary right to left lateral incisor teeth (4 teeth) and from maxillary right to left first premolar teeth (8 teeth). Both designs were identical on the 4 anterior teeth. Each digital trial restoration was 3-dimensionally (3D) printed to produce reference casts. The original cast was 3D printed to produce 44 replica casts. There were 8 experimental groups (4 analog and 4 digital) with 10 specimens each. For the analog groups, 20 silicone indices per reference cast were made: 10 from standard silicone putty (63 to 70 Shore-A hardness) and 10 from hard silicone putty (90 Shore-A hardness). The analog trial restorations were molded on replica casts with silicone indices and bis-acryl resin. The digital trial restorations were either milled or 3D printed and adapted onto replica casts. Each trial restoration was scanned and digitally superimposed onto respective scanned reference casts. Measurements were recorded at 3 levels: cervical, middle, and incisal. The independent samples Kruskal-Wallis, 2-sample Mann-Whitney, and Bonferroni tests were used to compare the distribution of accuracy among all groups (α=.05). RESULTS: The dimensional accuracy of the different trial restoration fabrication methods was comparable in terms of median values of trueness (how close the readings were to the reference), and no statistically significant difference was found among them (P>.05). When the dimensional accuracy in terms of precision (how close the readings were to each other) were analyzed, the hard putty groups demonstrated a statistically significant better outcome, whereas standard putty consistently showed the poorest result. The incisal level displayed the most significant deviation (P=.005) when all groups were compared. The incisal discrepancy values of the short-span standard putty trial restoration varied by as much as 0.84 mm in some specimens. CONCLUSIONS: Milled and 3D printed trial restoration fabrication techniques showed dimensional accuracy comparable with that of the analog groups. However, the choice of silicone putty was shown to affect the dimensional accuracy of an analog molded trial restoration. A high Shore-A hardness silicone putty produced the best precision and should be used when fabricating an analog molded trial restoration.
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BACKGROUND: Hepatocellular carcinoma (HCC) is widely recognized as a globally prevalent malignancy. Immunotherapy is a promising therapy for HCC patients. Increasing evidence suggests that lncRNAs are involved in HCC progression and immunotherapy. AIM: The study reveals the mechanistic role of long non-coding RNA (lncRNA) FOXD1-AS1 in regulating migration, invasion, circulating tumor cells (CTCs), epithelial-mesenchymal transition (EMT), and immune escape in HCC in vitro. METHODS: This study employed real-time PCR (RT-qPCR) to measure FOXD1-AS1, miR-615-3p, and programmed death-ligand 1 (PD-L1). The interactions of FOXD1-AS1, miR-615-3p, and PD-L1 were validated via dual-luciferase reporter gene and ribonucleoprotein immunoprecipitation (RIP) assay. In vivo experimentation involves BALB/c mice and BALB/c nude mice to investigate the impact of HCC metastasis. RESULTS: The upregulation of lncRNA FOXD1-AS1 in malignant tissues significantly correlates with poor prognosis. The investigation was implemented on the impact of lncRNA FOXD1-AS1 on the migratory, invasive, and EMT of HCC cells. It has been observed that the lncRNA FOXD1-AS1 significantly influences the generation and metastasis of MCTC in vivo analysis. In mechanistic analysis, lncRNA FOXD1-AS1 enhanced immune escape in HCC via upregulation of PD-L1, which acted as a ceRNA by sequestering miR-615-3p. Additionally, lncRNA FOXD1-AS1 was found to modulate the EMT of CTCs through the activation of the PI3K/AKT pathway. CONCLUSION: This study presents compelling evidence supporting the role of lncRNA FOXD1-AS1 as a miRNA sponge that sequesters miR-655-3p and protects PD-L1 from suppression.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Animales , Ratones , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Antígeno B7-H1/genética , Fosfatidilinositol 3-Quinasas/genética , ARN Largo no Codificante/genética , Ratones Desnudos , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Transición Epitelial-Mesenquimal/genética , Factores de Transcripción Forkhead/genéticaRESUMEN
The COVID-19 pandemic exposed older adults to high risk of sarcopenia. This study aimed to investigate the prevalence of sarcopenia and its risk factors among Japanese community-dwelling older adults during the COVID-19 pandemic. We collected data through questionnaires and physical measurements among 242 older adults. Sarcopenia was assessed using the Asian Working Group for Sarcopenia 2019 criteria. The results revealed that 14.5% had sarcopenia, which was significantly associated with age, nutritional status, number of prescription medications, body mass index, and self-rated health. On multivariate analysis, the risk of malnutrition was independently significantly associated with sarcopenia. Approximately 70% of participants reported decreased social interaction and going outside, but with no significant association with sarcopenia. In addition, approximately 65% of the participants had an exercise habit and went outside at least once a week, thus maintaining a good level of activity. These findings suggest that prevention of sarcopenia during the pandemic required provision of opportunities for older adults to remain active and positive assessment of nutritional status and well-being.
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COVID-19 , Sarcopenia , Humanos , Anciano , Sarcopenia/epidemiología , Vida Independiente , Estudios Transversales , Pandemias , Japón/epidemiología , COVID-19/epidemiología , Factores de Riesgo , Evaluación Geriátrica/métodosRESUMEN
Objective: To study the application value of Ilizarov bone handling technology in the treatment of tibial bone defect caused by osteomyelitis segmental resection. Methods: 78 patients with tibial bone defects after osteomyelitis segmental resection admitted to our hospital from January 2018 to August 2019 were retrospectively analyzed and assigned to the Ilizarov bone handling group (38 cases) and the fibular segmental transplantation group (40 cases). The perioperative indexes between the groups were compared (external fixation time, complete weight-bearing time, and intraoperative bleeding volume). The ankle function and knee function of patients were assessed before and 6 months after treatment and the occurrence of postoperative complications were counted. Results: The external fixation time and full weight-bearing time in the Ilizarov bone handling group were significantly shorter than those in the fibular segment transplantation group, and the intraoperative bleeding was less, with statistically significant differences (P < .05). Compared to the pre-treatment period, Baird's scores and HHS scores of the patients in both groups increased significantly after 6 months of treatment, and both scores in the Ilizarov bone handling group were significantly higher than those in the fibular segment transplantation group, and the differences were statistically significant (P < .05). The postoperative complication statistics showed that the complication rate of the Ilizarov bone handling group was significantly lower than that of the fibular segment transplantation group (P < .05). Conclusion: The Ilizarov bone transfer technique is less invasive than the fibular bone grafting technique used in the treatment of patients with osteomyelitis segmental resection-induced tibial bone defects, with the former having the advantages of less traumatization, faster recovery of the patients, better recovery of knee and ankle functions, and fewer complications, which is of high value for clinical application.
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BACKGROUND/AIM: One-third of newly diagnosed colorectal cancer cases are rectal cancers. Multimodal treatment regimens including surgery, radiotherapy, and chemotherapy improve local control and survival outcome and decrease tumor relapse for patients with rectal adenocarcinoma (READ). However, stratification of patients to predict their responses is urgently needed to improve therapeutic responses. PATIENTS AND METHODS: Immunostainings of CD3+, CD8+, and CD45RO+ immune cell subsets within the tumor microenvironment were evaluated using immunohistochemistry in two hundred seventy-nine READ patients. RESULTS: In this study, we found that examination of the adaptive immune response by quantifying CD3+, CD8+, and CD45RO+ immune cell subsets, provides improved and independent prognostic value for patients with READ. Regardless of conventional clinical and pathologic parameters, the densities of T cell subsets were strongly related to a better prognosis in patients with READ. High density of intratumoral immune cells is associated with absence of nodal metastasis, lymphovascular invasion, and perineural invasion. Moreover, high tumor-infiltrating lymphocyte (TIL) subsets were associated with favorable survival outcome in patients with READ, especially high-risk patients with advanced READ. CONCLUSION: Immune cell subsets including CD3, CD8, and CD45RO within the tumor microenvironment were independent prognostic factors for patients with READ.
Asunto(s)
Adenocarcinoma , Neoplasias del Recto , Humanos , Pronóstico , Microambiente Tumoral , Recurrencia Local de Neoplasia/patología , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Antígenos Comunes de Leucocito , Adenocarcinoma/terapia , Adenocarcinoma/patología , Linfocitos Infiltrantes de Tumor , Linfocitos T CD8-positivosRESUMEN
Obstructive sleep apnea (OSA) is a prevalent complication that affects up to 60% of children and adolescents with obesity. It is associated with poorer cardiometabolic outcomes and neurocognitive deficits. Appropriate screening and intervention for OSA are crucial in the management of children with obesity. We performed a scoping review of international and national pediatric obesity (n = 30) and pediatric OSA (n = 10) management guidelines to evaluate the recommendations on OSA screening in pediatric obesity. Sixteen (53%) of the pediatric obesity guidelines had incorporated OSA screening to varying extents, with no consistent recommendations on when and how to screen for OSA, and subsequent management of OSA in children with obesity. We provide our recommendations that are based on the strength and certainty of evidence presented. These include a clinical-based screening for OSA in all children with body mass index (BMI) ≥ 85th percentile or those with rapid BMI gain (upward crossing of 2 BMI percentiles) and the use of overnight polysomnography to confirm the diagnosis of OSA in those with high clinical suspicion. We discuss further management of OSA unique to children with obesity. An appropriate screening strategy for OSA would facilitate timely intervention that has been shown to improve cardiometabolic and neurocognitive outcomes.