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A high-efficiency porous adsorbent, MOF-199/carboxylated cellulose fibers (MOF-199/CCF), was synthesized in situ at room temperature through carboxylation modification, simple sonication, and vacuum drying. The sonication method produced small MOF-199 particles (tens of nanometers), which allowed for uniform distribution of MOF-199 on CCF and improved its efficiency. The presence of CCF carriers reduces the agglomeration of MOF-199 and enhances its performance. The BET-specific surface area of MOF-199/CCF is 264.83 m2 g-1, which is much larger than that of CCF (2.31 m2 g-1), proving the successful modification of CCF by MOF-199. MOF-199/CCF exhibits better adsorption capacity than CCF, with an adsorption capacity of 659.6 mg g-1 of methylene blue within 30 minutes, and good recycling performance. This work presents a straightforward method for preparing efficient cellulose-based adsorbent materials and offers a novel approach for synthesizing MOF composites.
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Objective: At present, several important trials have been published show that perioperative immunotherapy combined with chemotherapy can improve the prognosis of patients with resectable non-small cell lung cancer, which further optimizes treatment options. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of perioperative immunotherapy combined with chemotherapy in resectable non-small cell lung cancer. Methods: The following databases were searched for relevant studies: PubMed, EMBASE, Cochrane library (updated 12 October 2023). All randomized trials comparing perioperative immunotherapy combined with chemotherapy versus chemotherapy alone in resectable non-small cell lung cancer were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), event-free survival (EFS), pathological complete response (pCR), major pathological response (MPR), R0 resection rate, rate of underwent surgery and adverse events (AEs). Results: A total of 2912 patients (1453 receiving perioperative immunotherapy plus chemotherapy and 1459 receiving chemotherapy alone) were included in this systematic review and meta-analysis. The result showed that compared with chemotherapy alone, combined therapy significantly improved OS (HR = 0.68;95% CI: 0.56-0.83), EFS (HR = 0.58;95% CI: 0.51-0.65), pCR (OR = 7.53;95% CI: 4.63-12.26), MPR (OR = 5.03;95% CI: 3.40-7.44), R0 resection (OR = 1.58;95% CI: 1.152.18) and rate of underwent surgery (OR = 1.25;95% CI: 1.04-1.49). However, combination therapy was associated with higher risk of severe adverse event (OR = 1.46;95% CI: 1.19-1.78; P=0.0002), grade 3 and higher treatment-related adverse event (TRAE) (OR = 1.25;95% CI: 1.06-1.49; P=0.010), TRAE that led to interruption (OR = 1.90;95% CI: 1.34-2.68; P=0.0003) and immune-related adverse event (OR = 2.78;95% CI: 2.18-3.55; P<0.00001). Significant benefits were observed across most subgroups of EFS and pCR. However, no statistical differences were observed for EFS of never smoked (HR = 0.73;95% CI: 0.51-1.05) and EGFR-mutation positive (HR = 0.35;95% CI: 0.04-3.03). Conclusion: This systematic review and meta-analysis found superior efficacy associated with perioperative immunotherapy plus chemotherapy compared with chemotherapy alone in both tumor regression and prolonged survival in resectable NSCLC, but increased the risk of TRAE, so monitoring for adverse events is warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42023476786).
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Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Terapia Neoadyuvante , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Quimioterapia Adyuvante , Ensayos Clínicos Fase III como Asunto , Terapia Combinada , Inmunoterapia/métodos , Inmunoterapia/efectos adversos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Terapia Neoadyuvante/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Sarcoma is a heterogeneous malignancy arising from interstitial tissue. Anthracycline-based therapy is the first-line treatment recommended by guidelines for patients with locally advanced or metastatic unresectable sarcoma. Recently, targeted therapies, in particular tyrosine kinase inhibitors (TKIs), have made significant progress in the treatment of sarcoma, and their efficacy has been investigated in randomized controlled trials. The aim of this meta-analysis is to evaluate the efficacy of TKIs in patients with advanced or metastatic sarcoma who have previously received chemotherapy. METHODS: We completed a meta-analysis after conducting literature searches in PubMed, Embase, and Cochrane. The single-drug, placebo-controlled, randomized controlled clinical trials of TKIs in patients with advanced or progressive sarcoma who have previously received chemotherapy are available for inclusion in the study. The observation results were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The subgroup analysis was performed according to histological subtypes of sarcoma. RESULTS: This study included 6 studies, including 1033 patients. The ORR (OR: 7.99, 95% CI: 3.62-19.61, Pâ <â .00001), DCR (OR: 2.54, 95% CI: 1.27-5.08, Pâ =â .009), PFS (HR: 0.46, 95% CI: 0.34-0.62, Pâ <â .00001), and OS (HR: 0.80, 95% CI: 0.67-0.96, Pâ =â .02) of patients treated with TKIs were better than those in the placebo group. CONCLUSIONS: In patients with advanced sarcoma, TKIs have been shown to have advantages in terms of ORR, DCR and PFS and OS. Multi-targeted TKIs may be considered as one of the second-line treatment options for sarcoma patients who have received prior chemotherapy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias Primarias Secundarias , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Primarias Secundarias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológicoRESUMEN
BACKGROUND: Currently, the optimal treatment for neoadjuvant therapy for locally advanced esophageal cancer is not clear, and there is no evidence that neoadjuvant chemoradiotherapy (nCRT) is superior to neoadjuvant chemotherapy (nCT). Due to the publication of new clinical trials and defects in previous meta-analyses, we conducted an updated meta-analysis to evaluate the efficacy and safety of nCRT and nCT. METHODS: The following databases were searched for studies: PubMed, EMBASE, and Cochrane library (updated to April 22, 2023). All randomized trials comparing nCRT with nCT in locally advanced esophageal cancer met the inclusion criteria. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes assessed from the trials included overall survival (OS), progression-free survival (PFS), pathological complete response (pCR), R0 resection rate, postoperative complications, postoperative mortality, and grade 3 or higher adverse events (3â +â AEs). RESULTS: This systematic review and meta-analysis included 7 randomized controlled studies involving 1372 patients (686 receiving nCRT and 686 receiving nCT). Compared with nCT, nCRT significantly improved OS (HRâ =â 0.80; 95% CI: 0.68-0.94), PFS (HRâ =â 0.78; 95% CI: 0.66-0.93), pCR (ORâ =â 13.00; 95% CI: 7.82-21.61) and R0 resection (ORâ =â 1.84; 95% CI: 1.32-2.57), but was associated with higher postoperative mortality (ORâ =â 2.31; 95% CI: 1.26-4.25) and grade 3â +â AEs (ORâ =â 2.21; 95% CI: 1.36-3.58). There was no significant difference in postoperative complications between nCRT and nCT (ORâ =â 1.15; 95% CI: 0.82-1.61). Subgroup analysis showed significant survival benefit in squamous cell carcinoma (HRâ =â 0.80; 95% CI: 0.68-0.98), but not in adenocarcinoma (HRâ =â 0.80; 95% CI: 0.63-1.08). CONCLUSIONS: Our meta-analysis found superior efficacy associated with nCRT compared with nCT in both tumor regression and prolonged survival, but increased the risk of postoperative mortality and grade 3â +â AEs. Esophageal squamous cell carcinoma was more likely to benefit from nCRT than esophageal adenocarcinoma in the term of OS.
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Adenocarcinoma , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Terapia Neoadyuvante , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Adenocarcinoma/cirugía , QuimioradioterapiaRESUMEN
Objective: Zolbetuximab is a "first-in-class" chimeric lgG1 monoclonal antibody targeting Claudin18.2 (CLDN 18.2). In recent years, several important trials have been published showing that zolbetuximab is associated with improved prognosis in patients with advanced gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. This promises great change to the current treatment landscape. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zolbetuximab for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma. Methods: The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane library (updated 10 June 2023). All randomized trials comparing zolbetuximab plus chemotherapy versus first-line chemotherapy alone for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results: This systematic review and meta-analysis included three randomized controlled studies involving 1,402 patients (699 receiving zolbetuximab plus chemotherapy and 703 receiving chemotherapy alone). Compared with chemotherapy alone, zolbetuximab plus chemotherapy significantly improved OS (HR = 0.73; 95% CI: 0.68-0.84) and PFS (HR = 0.64; 95% CI: 0.50-0.82), but did not result in a higher ORR (RR = 0.92; 95% CI: 0.82-1.03). Further analysis of CLDN 18.2 expression showed a more significant benefit for OS (HR = 0.69; 95% CI: 0.55-0.87; p = 0.002) and PFS (HR = 0.61; 95% CI: 0.44-0.84; p = 0.003) from zolbetuximab in patients with high expression, while there was significant benefit in patients with lower expression. In terms of AEs, zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but increased risk of nausea and vomiting were more common. Conclusion: This systematic review and meta-analysis revealed that the effect of zolbetuximab plus chemotherapy was superior to that of chemotherapy alone for first-line treatment of advanced CLDN 18.2-positive G/GEJ adenocarcinoma. Thus, zolbetuximab plus chemotherapy represents a new first-line treatment for these patients. Zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but was generally manageable. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42023437126).
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INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Terapia Neoadyuvante , Carcinoma de Células Escamosas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Once-weekly insulin is expected to improve treatment compliance and durability and lead to better glycemic control. Several clinical trials on once-weekly insulin have recently been published. We conducted a systematic review and meta-analysis to investigate the efficacy and safety of once-weekly insulin versus once-daily insulin in type 2 diabetes (T2D). METHODS: The following databases were searched for studies: PubMed, EMBASE, and Cochrane library (From January 1, 1946 to May 9, 2023). All randomized trials comparing weekly versus daily insulin in T2D were eligible for inclusion. Data analysis was performed using STATA 17.0 software (Stata Corporation, College Station, TX). The main outcomes and indexes included reduction in Hemoglobin A1c (HbA1c), fasting plasma glucose and bodyweight, proportion of patients achieving HbA1câ <â 7%, time-in-range 70 to 180 mg/dL and adverse events. RESULTS: This systematic review and meta-analysis included 7 randomized controlled studies involving 2391 patients (1347 receiving 1-week insulin and 1044 receiving 1-day insulin). Once-weekly insulin was not inferior to once-daily insulin in HbA1c change [estimated treatment difference (ETD)â =â -0.05; 95% confidence intervals (CI): -0.14 to 0.04), HbA1câ <â 7% (odds ratioâ =â 1.14; 95% CI: 0.87-1.50), fasting plasma glucose (ETDâ =â 0.09; 95% CI: -0.19 to 0.36) and body weight loss (ETDâ =â 0.27; 95% CI: -0.36 to 0.91). In terms of time-in-range 70 to 180 mg/dL, weekly insulin was superior to daily insulin (MTDâ =â 3.84; 95% CI: 1.55-6.08). Icodec was associated with higher incidence of all adverse events (odds ratioâ =â 1.20; 95% CI: 1.03-1.48; Pâ =â .024), but did not result in high risk of serious and severe adverse events. Moreover, icodec and Basal Insulin Fc did not result in higher incidence of hypoglycemia compared with insulin daily. CONCLUSION: Our meta-analysis found that insulin weekly was well tolerated and effective for glycemic control. Once-weekly insulin was not inferior to once-daily insulin in both efficacy and safety in T2D.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Insulina Glargina/efectos adversos , Hemoglobina Glucada , Glucemia , Insulina/efectos adversosRESUMEN
Background: The addition of endocrine therapy to salvage radiotherapy (SRT) is expected to further improve the prognosis of patients with biochemical recurrence of prostate cancer after radical prostatectomy (RP). The quantitative synthesis of clinical outcomes of SRT combined with endocrine therapy is limited. Whether salvage radiotherapy plus endocrine therapy remains inconclusive. We performed a systematic review and meta-analysis of existing randomized controlled trials to evaluate the efficacy and safety of salvage radiotherapy combined with endocrine therapy in patients with biochemical recurrence after radical prostatectomy. Methods: A systematic search of PubMed, EMBASE, and the Cochrane library was performed for articles published between January 1, 2012 and October 10, 2022. Data were analyzed using Review Manager 5.4.1 (Cochrane Collaboration Software). Main outcome and measures included biochemical progression-free survival (bPFS), metastasis free survival (MFS), overall survival (OS), and Grade 3 or higher adverse events (3+AEs), including acute and late adverse events. Results: In this systematic review and meta-analysis, 4 randomized controlled studies enrolling 2731 male (1374 of whom received SRT combined with endocrine therapy and 1357 controls) met the inclusion criteria. SRT combined with endocrine therapy were related to significantly improve bPFS (HR=0.52; 95% CI: 0.46 0.59; p<0.00001) and MFS (HR=0.75; 95% CI: 0.64 0.88; p<0.001). Compared with SRT alone, the combination therapy tended to be associated with prolong OS (HR=0.83; 95% CI: 0.69-1.01; p=0.06), but not statistically significant. At early follow-up, the risk of acute AEs was comparable in the two groups (RR=1.04; 95% CI: 0.22-4.85). However, the risk of late AEs was higher in the combination group at later follow-up (RR=1.33; 95% CI: 1.09-1.62). Conclusions: This systematic review and meta-analysis found superior efficacy associated with adding endocrine therapy to SRT compared with SRT alone in patients with biochemical recurrence after RP. Additional endocrine therapy is safe and feasible for patients with biochemical recurrence after RP. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42022365432).
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Intelligent reversible crosslinked micelles that have a good balance of structure stability in normal tissue and controlled drug release responded to the tumor microenvironment are highly promising novel drug delivery systems. However, to date, there have been very few reports about mesoscale simulations of drug-loaded polymeric reversible crosslinked micelles. Here, dissipative particle dynamics (DPD) simulation, the nearest-neighbor bonding principle, and the nearest media-bead bond breaking principle were used to investigate the influence of physiological environment along with low tumor pH and reduction microenvironment on the stability and doxorubicin (DOX) distribution of the star polymer [PCL-b-P(HEMA-Se-SeË)-b-PPEGMA]6 diselenide crosslinked micelles with different diselenide crosslinking levels (CLs). The self-assembly process results obtained by DPD simulations reveal the formation of three-layer spherical micelles with the loaded DOX mainly distributed at the interfacial regions of the inner PCL core and middle HEMA layer. The structural stability and DOX loading capacity of the micelles can be improved by appropriately increasing the CL based on the nearest-neighbor bonding principle due to the effect of the pressure exerted by the crosslink that squeezes the loaded drugs from the intermediate and interfacial layers into the micelle core. Furthermore, the effect of breaking of the diselenide bond on the drug release properties was investigated through the use of the nearest media-bead bond breaking principle. A low CL gives rise to intense drug release, increasing the toxic side effects on the system. With the increase in the CL, the micelles show the transformation from local crosslinking to compact crosslinking, leading to slower drug release. Therefore, this work can provide some guidance on the mesoscale for the structural design and controlled construction of reversible crosslinked micelles for smart drug delivery systems.
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Antibióticos Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos , Modelos Químicos , Compuestos de Selenio/química , Simulación por Computador , Composición de Medicamentos/métodos , Liberación de Fármacos , Estabilidad de Medicamentos , Metacrilatos/química , Micelas , Ácidos Polimetacrílicos/químicaRESUMEN
The macroscopic flow geometry has long been assumed to have little impact on dynamic wetting behavior of liquids on solid surfaces. This study experimentally studied both spontaneous spreading and forced wetting of several kinds of Newtonian and non-Newtonian fluids to study the effect of the macroscopic flow geometry on dynamic wetting. The relationship between the dynamic contact angle, θ(D), and the velocity of the moving contact line, U, indicates that the macroscopic flow geometry does not influence the advancing dynamic wetting behavior of Newtonian fluids, but does influence the advancing dynamic wetting behavior of non-Newtonian fluids, which had not been discovered before.
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Humectabilidad , Hidrodinámica , ViscosidadRESUMEN
Hydrodynamic models are generally applied to describe the dynamic wetting of newtonian or non-newtonian fluids on a solid surface. Conversely, the molecular-kinetic paradigm is only utilized for spreading newtonian fluids while considering the movement of a contact line as a molecular hopping process. This study extended the molecular-kinetic paradigm to the wetting behavior of non-newtonian fluids, while assuming there are n fluid components at the contact line regime interacting simultaneously with a solid surface during front movement. The limiting cases of the derived model at slow and fast moving speeds were discussed. Moreover, the derived model was validated based on dynamic contact angle data of three carboxymethylcellulose (CMC) aqueous solutions measured using the force-balance method. Best-fit parameters were used to interpret the wetting dynamics of CMC solutions.
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Spreading non-Newtonian liquids with non-power-law rheology on completely wetting surfaces are seldom investigated. This study assessed the wetting behavior of polydimethylsiloxane (PDMS), a Newtonian fluid, two carboxymethylcellulose (CMC) sodium solutions, a PDMS+2%w/w silica nanoparticle suspension and three polyethylene glycol (PEG400)+5-10%w/w silica nanoparticle suspensions (non-power-law fluids) on a mica surface. The theta(D)-U and R-t data for spreading drops of the six tested, non-power-law fluids can be described by power-law wetting models. We propose that this behavior is attributable to a uniform shear rate (a few tens to a few hundreds of s(-1)) distributed over the thin-film regime that controls spreading dynamics. Estimated film thickness was below the resolution of an optical microscope for direct observation. Approximating a general non-Newtonian fluid spreading as a power-law fluid greatly simplifies theoretical analysis and data interpretation.
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This paper aims at providing a summary of the theoretical models available for non-Newtonian fluid spreading dynamics. Experimental findings and model predictions for a Newtonian fluid spreading test are briefly reviewed. Then how the complete wetting and partial wetting power-law fluids spread over a solid substrate is examined. The possible extension of Newtonian fluid models to power-law fluids is also discussed.