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1.
Front Med (Lausanne) ; 8: 739251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760899

RESUMO

Sarcopenia, characterized by the excessive loss of skeletal muscle mass, strength, and function, is associated with the overall poor muscle performance status of the elderly, and occurs more frequently in those with chronic diseases. The causes of sarcopenia are multifactorial due to the inherent relationship between muscles and molecular mechanisms, such as mitochondrial function, inflammatory pathways, and circulating hormones. Age-related changes in sex steroid hormone concentrations, including testosterone, estrogen, progesterone, and their precursors and derivatives, are an important aspect of the pathogenesis of sarcopenia. In this review, we provide an understanding of the treatment of sarcopenia through the regulation of sex steroid hormones. The potential benefits and future research emphasis of each sex steroid hormone therapeutic intervention (testosterone, SARMs, estrogen, SERMs, DHEA, and progesterone) for sarcopenia are discussed. Enhanced understanding of the role of sex steroid hormones in the treatment for sarcopenia could lead to the development of hormone therapeutic approaches in combination with specific exercise and nutrition regimens.

2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(11): 1087-1090, 2021 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-34729749

RESUMO

OBJECTIVE: To explore the correlation between the genotypes and metabolic markers and microstructure of bones in children with Gitelman syndrome (GS). METHODS: For 15 children with GS and 10 healthy individuals, baseline data and bone metabolic markers including parathyroid hormone, alkaline phosphatase, osteocalcin, N-terminal propeptide of type I procollagen, beta isomer of the C-terminal telopeptide of type I collagen and 25-hydroxyvitamin D, high-resolution peripheral quantitative computed tomography indicators (volumetric bone mineral density, bone microstructure indicators) were collected. Genetic testing was carried out to determine their genotypes. RESULTS: The volumetric bone mineral density, bone geometry and bone microstructure parameters of the GS group were better than those of the healthy controls (P<0.05). Variants of the SLC12A3 gene were identified in 9 of the 15 patients but none of the 10 healthy controls. CONCLUSION: The phenotype of GS children is influenced by the interaction of genetic variants, though the phenotype associated with high frequency mutations showed no specificity. There is also a correlation between their genotype and the bone microstructure.


Assuntos
Síndrome de Gitelman , Biomarcadores , Osso e Ossos , Criança , Colágeno Tipo I/genética , Genótipo , Humanos , Osteocalcina/genética , Fragmentos de Peptídeos , Membro 3 da Família 12 de Carreador de Soluto
3.
Mol Cancer Ther ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725191

RESUMO

Hepatocellular carcinoma (HCC) is a world leading cause of cancer-related mortality, and currently no curative treatment for advanced HCC is available. Glypican-3 (GPC3) is an attractive target for HCC immunotherapy. The present study explored the efficacy of six GPC3-targeted bispecific antibodies, alone or in combination with chemotherapeutic drug Irinotecan, for the treatment of HCC. The bispecific antibodies were constructed using three different structures, knob-into-hole (KH), scFv-scFv-hFc, and scFv-hFc-scFv, where CD3-targeting monoclonal antibody OKT3 (scFv) was paired with two representative GPC3 monoclonal antibodies hYP7 (scFv) and HN3 (VH only) that target different epitopes. The In vitro cell killing assay revealed that all bispecific antibodies efficiently killed GPC3 positive cancer cells, with hYP7-KH, hYP7-OKT3-hFc, and HN3-KH being most potent. In vivo xenograft mouse studies demonstrated that all bispecific antibodies suppressed tumor growth similarly, with hYP7-OKT3-hFc performing slightly better. Combination of hYP7-OKT3-hFc with Irinotecan dramatically improved the efficacy and arrested tumor growth of HepG2, Hep3B, and G1 in xenograft mice. Our results demonstrated that the cell surface proximal bispecific antibody hYP7-OKT3 was superior in terms of potency and the GPC3-targeted bispecific antibody combined with Irinotecan was much potent to control HCC growth.

4.
Small ; 17(46): e2103125, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34612010

RESUMO

Stimuli-responsive crystals capable of energy conversion have emerged as promising materials for smart sensors, actuators, wearable devices, and robotics. Here, a novel ferrocene-based organic molecule crystal (Fc-Cz) that possesses anisotropic piezoelectric, optical, and mechanical properties is reported. It is demonstrated that the new crystal Fc-Cz can be used as an ultrasensitive piezoelectric material in fabricating strain sensors. The flexible sensor made of crystal Fc-Cz can detect small strains/deformations and motions with a fast response speed. Analysis based on density functional theory (DFT) indicates that an external pressure can affect the dipole moment by changing the molecular configuration of the asymmetric single crystal Fc-Cz in the crystalline state, leading to a change of polarity, and thereby an enhanced dielectric constant. This work demonstrates a new artificial organic small molecule for high-performance tactile sensors, indicating its great potential for developing low-cost flexible wearable sensors.

5.
J Diabetes Investig ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510805

RESUMO

AIMS/INTRODUCTION: We aimed to explore whether the association between obesity and congenital heart defects (CHDs) can be mediated by maternal pregestational diabetes (PGDM). MATERIALS AND METHODS: We included 53,708 mother-infant pairs with deliveries between 2017 and 2019 from the Birth Cohort in Shenzhen. Mothers were categorized into four groups: the underweight group (body mass index [BMI] <18.5), normal weight group (18.5 ≤ BMI < 24), overweight group (24 ≤ BMI < 28) and obesity group (BMI ≥28). Multivariable logistic regression models were used to evaluate the association between BMI and CHDs. Mediation analysis was used to confirm the effect of PGDM on the association between maternal obesity and CHDs. RESULTS: The proportion of obese individuals in the Birth Cohort in Shenzhen was 2.11%. Overall, 372 (0.69%) infants were diagnosed with CHDs. Maternal obesity was associated with an increased risk of CHDs (odds ratio 1.97, 95% confidence interval 1.14-3.41). The mediation effect of PGDM on the association between maternal obesity and CHDs was significant (odds ratio 1.18, 95% confidence interval 1.06-1.32). The estimated mediation proportion was 24.83%. CONCLUSIONS: Maternal obesity was associated with increased risk for CHDs, and PGDM partially mediated the association between maternal obesity and CHDs.

6.
Phys Chem Chem Phys ; 23(37): 20901-20908, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34528642

RESUMO

Similar to most semiconductors, low-dimensional GaN materials also have the problem of asymmetric doping, that is, it is quite difficult to form p-type conductivity compared to n-type conductivity. Here, we have discussed the geometry, structure, and electronic defect properties of a two-dimensional graphene-like gallium nitride (g-GaN) monolayer belonging to the group III-V compounds, doped with different elements (In, Mg, Zn) at the Ga site. Based on first principles calculations, we found that substituting Ga (low concentration impurities) with Mg would be a better choice for fabricating a p-type doping semiconductor under N-rich conditions, which is essential for understanding the properties of impurity defects and intrinsic defects in the g-GaN monolayer (using the "transfer to real state" model). Moreover, the g-GaN monolayer is dynamically stable and can remain stable even in high-temperature conditions. This research provides insight for increasing the hole concentration and preparing potential high-performance optoelectronic devices using low-dimensional GaN materials.

8.
J Anat ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34411284

RESUMO

Repaired unilateral cleft lip and palate (UCLP) is often accompanied by the deformity and asymmetry of the nasal region. Three-dimensional analysis was performed to investigate the relationship between nasal soft- and hard-tissue asymmetries, as well as the changes in nasal asymmetry with age, among children with repaired UCLP (age: 6-12 years). Forty-seven patients were included in this study. Their computed tomography records were retrieved for analysis of the 3D asymmetry of 10 landmarks of the nasal soft and hard tissues. We observed that asymmetry was more severe in nasal hard tissues than in soft tissues, particularly in the sagittal dimension. Compared with patients aged 6-9 years old, patients aged 10 to 12 years old had significantly increased vertical asymmetry at the base of the alar groove (Gbase, p = 0.027) and the lateral point of the piriform aperture (LPA), (p < 0.001). The correlation between the LPA and the alar region was weak to moderate (r = 0.290 to 0.488). In conclusion, we found no evidence of growth and development in nasal hard-tissue asymmetry among 6- to 12-year-old children with repaired UCLP, except for the vertical dimension. Nasal soft tissue exhibited a more preferable symmetry than hard tissue, and this could be attributed to the compensatory growth of nasal soft tissue, particularly in the vertical and sagittal dimensions. The weak to moderate correlations between nasal soft-tissue asymmetry and hard-tissue asymmetry were observed in the three dimensions. Surgeons should consider these factors when repositioning the nasal alar and controlling the size of the nostrils.

9.
J Hum Genet ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34376796

RESUMO

Despite the dramatic underrepresentation of non-European populations in human genetics studies, researchers continue to exclude participants of non-European ancestry, as well as variants rare in European populations, even when these data are available. This practice perpetuates existing research disparities and can lead to important and large effect size associations being missed. Here, we conducted genome-wide association studies (GWAS) of 31 serum and urine biomarker quantitative traits in African (n = 9354), East Asian (n = 2559), and South Asian (n = 9823) ancestry UK Biobank (UKBB) participants. We adjusted for all known GWAS catalog variants for each trait, as well as novel signals identified in a recent European ancestry-focused analysis of UKBB participants. We identify 7 novel signals in African ancestry and 2 novel signals in South Asian ancestry participants (p < 1.61E-10). Many of these signals are highly plausible, including a cis pQTL for the gene encoding gamma-glutamyl transferase and PIEZO1 and G6PD variants with impacts on HbA1c through likely erythrocytic mechanisms. This work illustrates the importance of using the genetic data we already have in diverse populations, with novel discoveries possible in even modest sample sizes.

10.
J Clin Pharm Ther ; 46(5): 1441-1458, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34254696

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The benefits of local infiltration analgesia (LIA) in knee arthroplasty (KA) have been well-documented. However, it is unknown whether adding a corticosteroid to the composition of the LIA is beneficial. This study aimed to investigate the efficacy and safety of administering periarticular steroids intraoperatively in patients who underwent KA through a systematic review and meta-analysis. METHODS: A systematic search was conducted to identify relevant randomized controlled trials in the PubMed, Embase, Web of Science and Cochrane databases up to January 19th, 2021 to perform a meta-analysis. Outcome variables included pain scores, total opioid consumption, knee range of motion (ROM) and postoperative complications. RESULTS: Corticosteroid injections did not reduce pain scores at 6, 12, 24 or 72 h postoperatively, although a minimal degree of transient pain relief was achieved at 48 h postoperatively compared with those in the placebo group, nor was there a significant difference in total opioid consumption. However, patients receiving corticosteroids did exhibit a transient ROM increase on postoperative days 1, 2 and 3. Since the minimal clinically important difference (MCID) for ROM is unclear, it is unknown if the improvement in ROM is clinically significant. WHAT IS NEW AND CONCLUSION: Our specific end-point analysis demonstrated that corticosteroid administration did not provide pain relief or reduce opioid consumption compared with placebo. However, corticosteroids might provide a statistically significant, though transient and minimal improvement in knee ROM after KA, although no firm conclusions about the benefits of administering corticosteroids in KA can be made based on the available evidence.

11.
Nat Commun ; 12(1): 4030, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188060

RESUMO

Van der Waals integration with abundant two-dimensional materials provides a broad basis for assembling functional devices. In a specific van der Waals heterojunction, the band alignment engineering is crucial and feasible to realize high performance and multifunctionality. Here, we design a ferroelectric-tuned van der Waals heterojunction device structure by integrating a GeSe/MoS2 VHJ and poly (vinylidene fluoride-trifluoroethylene)-based ferroelectric polymer. An ultrahigh electric field derived from the ferroelectric polarization can effectively modulate the band alignment of the GeSe/MoS2 heterojunction. Band alignment transition of the heterojunction from type II to type I is demonstrated. The combination of anisotropic GeSe with MoS2 realizes a high-performance polarization-sensitive photodetector exhibiting low dark current of approximately 1.5 pA, quick response of 14 µs, and high detectivity of 4.7 × 1012 Jones. Dichroism ratios are also enhanced by ferroelectric polarization in a broad spectrum from visible to near-infrared. The ferroelectric-tuned GeSe/MoS2 van der Waals heterojunction has great potential for multifunctional detection applications in sophisticated light information sensing. More profoundly, the ferroelectric-tuned van der Waals heterojunction structure provides a valid band-engineering approach to creating versatile devices.

12.
ACS Omega ; 6(22): 14230-14241, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34124446

RESUMO

Highly conductive and elastic three-dimensional (3D) porous carbon materials are ideal platforms to fabricate electrodes for high-performance compressible supercapacitors. Herein, a robust, highly conductive, and elastic carbon foam (CF) hybrid material is reported, which is fabricated by integrating cellulose nanofiber/multiwalled carbon nanotube (CNF/MWCNT) aerogel sheets with a melamine sponge (MS), followed by carbonization. The carbonized CNF/MWCNT aerogel sheets contribute to the high conductivity and specific surface area of the CF, and the 3D network-like skeleton derived from the carbonization of the MS enhances the elasticity and stability of the CF. More importantly, the CF possesses good scalability, allowing the introduction of electroactive materials such as polypyrrole (PPy) and Fe3O4 to fabricate high-performance compressible PPy-CF and Fe3O4-CF electrodes. Moreover, an assembled PPy-CF//Fe3O4-CF device shows reversible charging-discharging at a voltage of 1.6 V and demonstrates a high specific capacitance (172.5 F/g) and an outstanding energy density (59.9 W h/kg). The device exhibits capacitance retention rates reaching 98.3% and stable energy storage characteristics even under different degrees of compressive deformation. This study offers a scalable strategy for fabricating high-performance compressible supercapacitors, thereby providing a new means of satisfying the energy storage needs of portable electronic devices that are prone to deformation.

13.
Biomaterials ; 275: 120984, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34186235

RESUMO

Critical size bone defects are frequently caused by accidental trauma, oncologic surgery, and infection. Distraction osteogenesis (DO) is a useful technique to promote the repair of critical size bone defects. However, DO is usually a lengthy treatment, therefore accompanied with increased risks of complications such as infections and delayed union. Here, we demonstrated that magnesium (Mg) nail implantation into the marrow cavity degraded gradually accompanied with about 4-fold increase of new bone formation and over 5-fold of new vessel formation as compared with DO alone group in the 5 mm femoral segmental defect rat model at 2 weeks after distraction. Mg nail upregulated the expression of calcitonin gene-related peptide (CGRP) in the new bone as compared with the DO alone group. We further revealed that blockade of the sensory nerve by overdose capsaicin blunted Mg nail enhanced critical size bone defect repair during the DO process. CGRP concentration-dependently promoted endothelial cell migration and tube formation. Meanwhile, CGRP promoted the phosphorylation of focal adhesion kinase (FAK) at Y397 site and elevated the expression of vascular endothelial growth factor A (VEGFA). Moreover, inhibitor/antagonist of CGRP receptor, FAK, and VEGF receptor blocked the Mg nail stimulated vessel and bone formation. We revealed, for the first time, a CGRP-FAK-VEGF signaling axis linking sensory nerve and endothelial cells, which may be the main mechanism underlying Mg-enhanced critical size bone defect repair when combined with DO, suggesting a great potential of Mg implants in reducing DO treatment time for clinical applications.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Osteogênese por Distração , Animais , Regeneração Óssea , Calcitonina , Células Endoteliais , Proteína-Tirosina Quinases de Adesão Focal , Magnésio , Osteogênese , Ratos , Fator A de Crescimento do Endotélio Vascular
14.
Oncol Lett ; 22(1): 542, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34079595

RESUMO

Targeting inhibitory immune checkpoint molecules has significantly altered cancer treatment regimens. T cell immunoglobulin and mucin domain 3 (TIM3) is one of the major inhibitory immune checkpoints expressed on T cells. Blocking the engagement of TIM3 and its inhibitory ligand galectin-9 may potentiate the effects of immunotherapy or overcome the adaptive resistance to the therapeutic blockade of programmed cell death protein 1, cytotoxic T-lymphocyte-associated protein 4, B- and T-lymphocyte attenuator and lymphocyte-activation gene 3, amongst others, as each of these immune checkpoints harbors unique properties that set it apart from the rest. Heavy chain variable fragment (VH)-derived single-domain antibodies (sdAbs) represent a class of expanding drug candidates. These sdAbs have unique advantages, including their minimal size in the antibody class, ease of expression, broad scope for modular structure design and re-engineering, and excellent tumor penetration. In the present study, two sdAbs, TIM3-R23 and TIM3-R53, were generated by immunizing rabbits with the recombinant extracellular domain of TIM3 and applying phage display technology. These sdAbs were easily expressed in mammalian cells. The purified sdAbs were able to bind to both recombinant and cell surface TIM3, and blocked it from binding to the ligand galectin-9. In vivo studies demonstrated that TIM3-R53 was able to potentiate the antitumor activity of chimeric antigen receptor T cells that targeted mesothelin. In conclusion, the results of the present study suggested that TIM3-R53 may be a novel and attractive immune checkpoint inhibitor against TIM3, which is worthy of further investigation.

15.
Nanoscale ; 13(23): 10579-10586, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34100510

RESUMO

As a new two-dimensional elemental layered semiconductor, black phosphorus (b-P) has received tremendous attention due to its excellent physical and chemical properties and has potential applications in the fields of catalysis, energy, and micro/nano-optoelectronic devices. However, studies have found that b-P is very unstable and will decompose within a few minutes under humid air conditions. Element doping is an effective method for adjusting the physical and chemical properties of crystals. Theoretical and experimental studies have confirmed that the stability of b-P crystals is significantly improved after arsenic doping, and the crystals also exhibit excellent photoresponse and electrical transport performances. In this work, we investigate the physical properties of a component of black arsenic phosphorus crystals (b-As0.084P0.916) and the potential applications in field effect transistors (FETs) and broadband photodetectors. An obvious ambipolar behavior is observed in the transfer characteristics of b-As0.084P0.916 based FETs, with drain current modulation on the order of 105 and the highest charge-carrier mobility of up to 147 cm2 V-1 s-1. The physisorption of atmospheric species on the surface of the FETs is the main factor for the formation of Schottky contacts between the Au electrodes and the b-As0.084P0.916 crystal. Temperature-dependent electrical characteristics show that the Fermi level shifts from the valence band to the middle level between the conduction band and valence band as the temperature decreases. In addition, the FETs also exhibit excellent photoresponse properties from the visible to near-infrared region (450-2200 nm), with a responsivity of 37 A W-1, a specific detectivity of 7.18 × 1010 Jones, and a fast response speed (τrise ≈ 0.04 s and τdecay ≈ 0.14 s). These results suggest that b-As0.084P0.916 crystals are a promising candidate for future electronic and optoelectronic devices.

16.
Bioact Mater ; 6(11): 4176-4185, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33997501

RESUMO

Displaced fractures of patella often require open reduction surgery and internal fixation to restore the extensor continuity and articular congruity. Fracture fixation with biodegradable magnesium (Mg) pins enhanced fracture healing. We hypothesized that fixation with Mg pins and their degradation over time would enhance healing of patellar fracture radiologically, mechanically, and histologically. Transverse patellar fracture surgery was performed on thirty-two 18-weeks old female New Zealand White Rabbits. The fracture was fixed with a pin made of stainless steel or pure Mg, and a figure-of-eight stainless steel band wire. Samples were harvested at week 8 or 12, and assessed with microCT, tensile testing, microindentation, and histology. Microarchitectural analysis showed that Mg group showed 12% higher in the ratio of bone volume to tissue volume at week 8, and 38.4% higher of bone volume at week 12. Tensile testing showed that the failure load and stiffness of Mg group were 66.9% and 104% higher than the control group at week 8, respectively. At week 12, Mg group was 60.8% higher in ultimate strength than the control group. Microindentation showed that, compared to the Control group, Mg group showed 49.9% higher Vickers hardness and 31% higher elastic modulus at week 8 and 12, respectively. At week 12, the new bone of Mg group remodelled to laminar bone, but those of the control group remained woven bone-like. Fixation of transverse patellar fracture with Mg pins and its degradation enhanced new bone formation and mechanical properties of the repaired patella compared to the Control group.

17.
Opt Lett ; 46(10): 2376-2379, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33988587

RESUMO

With the recently developed single-shot time-stretch dispersive Fourier transform technique, we investigate the buildup process of an all-polarization-maintaining soliton mode-locked fiber laser. Considering the multi-pulse competitions and the evolution of the survived pulse, we find an optimal range of intra-cavity energy for self-starting related to the saturation energy of the employed saturable absorber. Under the conditions, one dominant pulse can build up quickly against the others, and it finally drives to single-pulse operation. The conclusions drawn here hold for other soliton mode-locked lasers.

18.
Eur J Nutr ; 60(8): 4379-4392, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34052917

RESUMO

PURPOSE: Corticosteroid (CS) therapy for infectious and rheumatological diseases showed to decrease serum magnesium (Mg++) level and induce muscle atrophy in patients. The present study investigated the effects of Mg++ supplementation on preventing CS-induced muscle atrophy in an animal model, which provided experimental data for potential clinical translation. METHODS: Twelve 24-week-old male Sprague-Dawley rats were treated with lipopolysaccharide (LPS) and CS methylprednisolone (MPS) to induce muscle atrophy, with half of the rats also given daily 50 mg/kg Mg++ oral supplementation. Additional six rats without LPS + CS treatments were used as normal controls. After treatment for 6 weeks, serum was collected for Mg++ quantification, animal dual-energy X-ray absorptiometry (DXA) was performed for tissue composition, and the extensor digitorum longus (EDL) was collected for muscle functional test and histology including muscle fiber size, intramuscular fat infiltration and fiber typing. In vitro myotube atrophy model was used to study the in vitro effect associated with in vivo muscle atrophy. RESULTS: LPS + CS treatments induced hypomagnesemia while the serum Mg++ level was in normal range after Mg++ supplementation. DXA showed 53.0% lower fat percent and 29.7% higher lean mass in LPS + CS + Mg group when compared to LPS + CS group. Muscle functional test showed 22.2% higher specific twitch force and 40.3% higher specific tetanic force in LPS + CS + Mg group when compared to LPS + CS group. Histological analysis showed 4.1% higher proportion of muscle fibers area to total area and 63.6% lower intramuscular fat infiltration in EDL sections in LPS + CS + Mg group when compared to LPS + CS group. LPS + CS + Mg group had 33.0% higher area proportion and 29.4% higher cross-sectional area (CSA) of type IIb muscle fiber. Myoblast culture results showed that Mg++ supplementation group had larger myotube diameter. The mRNA expressions of the muscle atrophy marker genes MuRF1 and MAFbx were lower in Mg++ supplementation group both in vitro and in vivo. CONCLUSION: The current study demonstrated that Mg++ supplementation successfully alleviated CS-associated muscle atrophy in rats at both functional and morphology levels, indicating a translational potential for patients undergoing CS therapy. This study provided the evidence for the first time that Mg++ supplementation could prevent muscle atrophy-an adverse effect of CS therapy, currently also adopted for treating coronavirus disease 2019 (COVID-19).


Assuntos
COVID-19 , Magnésio , Corticosteroides , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Humanos , Masculino , Fibras Musculares Esqueléticas , Músculo Esquelético , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , SARS-CoV-2
19.
BMC Cancer ; 21(1): 426, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865364

RESUMO

BACKGROUND: In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy. METHODS: All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP ± B) and paclitaxel-carboplatin with bevacizumab (PC + B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem + B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events. RESULTS: Data of 3139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP ± B and PC + B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP ± B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC + B (all P < 0.05). PP ± B resulted in higher rates of grade 3/4 anemia and thrombocytopenia, but lower rates of neutropenia, febrile neutropenia, and sensory neuropathy than PC + B (all P < 0.001). The other three RCTs were included in an analysis that compared Pem + B and B as a maintenance treatment. Compared with B, Pem + B maintenance treatment resulted in significant improvements in OS (HR, 0.88), PFS (HR, 0.64), and PFSR1y (RR, 0.70), but higher rates of anemia, thrombocytopenia, and neutropenia (all P < 0.001). CONCLUSION: Although the first-line PP + B regimen had longer PFS and PFSR1y than the PC + B regimen, no OS difference was observed. Addition of pemetrexed to bevacizumab as maintenance therapy significantly improved OS compared with bevacizumab maintenance alone, but led to more toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Quimioterapia de Indução , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Quimioterapia de Manutenção , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Pemetrexede/administração & dosagem , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
Bioinformatics ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33904580

RESUMO

 : Biclustering is a generalization of clustering used to identify simultaneous grouping patterns in observations (rows) and features (columns) of a data matrix. Recently, the biclustering task has been formulated as a convex optimization problem. While this convex recasting of the problem has attractive properties, existing algorithms do not scale well. To address this problem and make convex biclustering a practical tool for analyzing larger data, we propose an implementation of fast convex biclustering called COBRAC to reduce the computing time by iteratively compressing problem size along the solution path. We apply COBRAC to several gene expression datasets to demonstrate its effectiveness and efficiency. Besides the standalone version for COBRAC, we also developed a related online web server for online calculation and visualization of the downloadable interactive results. AVAILABILITY: The source code and test data are available at https://github.com/haidyi/cvxbiclustr or https://zenodo.org/record/4620218. The web server is available at https://cvxbiclustr.ericchi.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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