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1.
J Fungi (Basel) ; 7(11)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34829192

RESUMO

Chromatin remodeling is mediated in part by post-translational acetylation/deacetylation modifications of histones. Histone acetyltransferases (HATs), e.g., members of the GNAT/MYST superfamily, activate gene transcription via promotion of euchromatin formation. Here, we characterized a GNAT family HAT, Spt10 (BbSpt10), in the environmentally and economically important fungal insect pathogen, Beauveria bassiana. Targeted gene knockout of BbSpt10 resulted in impaired asexual development and morphogenesis; reduced abilities to utilize various carbon/nitrogen sources; reduced tolerance to heat, fungicides, and DNA damage stress; and attenuated virulence. The ΔBbSpt10 mutant showed disrupted cell cycle development and abnormal hyphal septation patterns. Transcriptome analyses of wild type and ΔBbSpt10 cells revealed the differential expression of 373 genes, including 153 downregulated and 220 upregulated genes. Bioinformatic analyses revealed downregulated genes to be enriched in pathways involved in amino acid metabolism, cellular transportation, cell type differentiation, and virulence, while upregulated genes were enriched in carbon/nitrogen metabolism, lipid metabolism, DNA process, and cell rescue, defense, and virulence. Downregulated virulence genes included hydrophobins, cellular transporters (ABC and MFS multidrug transporters) and cytochrome P450 detoxification genes. These data indicated broad effects of BbSpt10 on fungal development, multi-stress response, and virulence.

2.
Biomater Sci ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787604

RESUMO

Nucleic acid drugs have emerged as important therapeutics but their clinical application has been greatly limited by their large molecular weight, high polarity, negative charge and short half-life. Cationic liposomes (CLs) have gained wide attention as non-viral vectors for nucleic acid delivery. However, the absolute transfection efficiency of CLs can still be enhanced while their cytotoxicity should be decreased simultaneously. Ginsenosides, obtained from natural plants, possess a similar steroid structure to cholesterol and might be an alternative to cholesterol for acting as a membrane stabilizer of CLs. Herein, seven kinds of ginsenoside-based compounds were utilized to prepare CLs (GCLs) and their efficacy in siRNA delivery was investigated. The particle sizes of the GCLs were 90-300 nm and the siRNA delivery efficiencies were in the range of 23.6%-78.4%. Rg5-based CLs (Rg5-CLs) exhibited the highest transfection efficiency of 81% and the lowest toxicity, with 82% cell viability obtained even at high concentrations. Ginsenosides are shown as promising biomaterials as membrane stabilizers of CLs. Rg5-CLs have been demonstrated as efficient non-viral vectors with high transfection efficiency and good biocompatibility for gene delivery, possessing great potential for gene therapy.

3.
Biol Reprod ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34791059

RESUMO

Newly discovered lncRNA neurensin-2 antisense RNA 1 (NRSN2-AS1) has not been well explored in cancers. Ovarian cancer (OV) is a primary gynecologic cancer worldwide and has the highest mortality rate among gynecologic cancers. Hence, the role and underlying mechanisms of NRSN2-AS1 in OV were worth investigating. According to the results of qRT-PCR, NRSN2-AS1 displayed the remarkably high expression in OV cells, in contrast to human ovarian epithelial cells. Based on online database, the expression level of NRSN2-AS1 was significantly higher in OV tissues than that in normal ovarian tissues. The data from functional experiments indicated that NRSN2-AS1 knockdown inhibited OV cell malignant behaviors in vitro and OV tumor growth in vivo. Moreover, mechanism analysis unveiled that NRSN2-AS1 functioned as a miR-744-5p sponge to regulate PRKX expression in OV cells. The results of TOP/FOP flash and western blot assays suggested that NRSN2-AS1/miR-744-5p/PRKX axis modulated the activity of Wnt/ß-catenin signaling pathway. In summary, we validated NRSN2-AS1 functioned as a novel oncogenic lncRNA in OV and elucidated its specific molecular mechanism. This work might advance our understanding of OV and provide evidence for supporting NRSN2-AS1 as a potential biomarker for OV treatment.

4.
Small ; 17(45): e2102643, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34605165

RESUMO

Development of CAR-T therapy led to immediate success in the treatment of B cell leukemia. Manufacturing of therapy-competent functional CAR-T cells needs robust protocols for ex vivo/in vitro expansion of modified T-cells. This step is challenging, especially if non-viral low-efficiency delivery protocols are used to generate CAR-T cells. Modern protocols for CAR-T cell expansion are imperfect since non-specific stimulation results in rapid outgrowth of CAR-negative T cells, and removal of feeder cells from mixed cultures necessitates additional purification steps. To develop a specific and improved protocol for CAR-T cell expansion, cell-derived membrane vesicles are taken advantage of, and the simple structural demands of the CAR-antigen interaction. This novel approach is to make antigenic microcytospheres from common cell lines stably expressing surface-bound CAR antigens, and then use them for stimulation and expansion of CAR-T cells. The data presented in this article clearly demonstrate that this protocol produced antigen-specific vesicles with the capacity to induce stronger stimulation, proliferation, and functional activity of CAR-T cells than is possible with existing protocols. It is predicted that this new methodology will significantly advance the ability to obtain improved populations of functional CAR-T cells for therapy.

5.
Respiration ; 100(12): 1218-1229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34515207

RESUMO

BACKGROUND: Although international bronchiectasis guidelines recommended screening of nontuberculous mycobacteria (NTM) both at initial evaluation and prior to administration of macrolide treatment, data regarding NTM in bronchiectasis remain elusive. OBJECTIVE: To establish the prevalence, species, and clinical features of NTM in adults with bronchiectasis. METHODS: We searched PubMed, Embase, and Web of Science for studies published before April 2020 reporting the prevalence of NTM in adults with bronchiectasis. We only included studies with bronchiectasis confirmed by computed tomography and NTM identified by mycobacteria culture or molecular methods. Random-effects meta-analysis was employed. RESULTS: Of the 2,229 citations identified, 21 studies, including 12,454 bronchiectasis patients were included in the final meta-analysis. The overall pooled prevalence of NTM isolation and pulmonary NTM disease were 7.7% (5.0%-11.7%) (n/N = 2,677/12,454) and 4.1% (1.4%-11.4%) (n/N = 30/559), respectively, with significant heterogeneity (I2 = 97.7%, p < 0.001 and I2 = 79.9%, p = 0.007; respectively). The prevalence of NTM isolation varied significantly among different geographical regions with the highest isolation at 50.0% (47.3%-52.7%) reported in the United States. Mycobacterium avium complex and Mycobacterium abscessus complex accounted for 66 and 16.6% of all species, respectively. Some clinical and radiological differences were noted between patients with and without the presence of NTM isolation although the results are inconsistent. CONCLUSIONS: Heterogeneity in prevalence estimates of NTM isolation indicated that both local surveys to inform development of clinical services tailored to patients with bronchiectasis and population-based studies are needed. The clinical features associated with NTM in bronchiectasis and their incremental utility in studying the association is unknown and merits further investigation.

6.
Bioengineered ; 12(1): 5883-5891, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34477478

RESUMO

The incidence of peripheral hip diseases is increasing every year, and its treatment is always tricky due to the complexity of hip joint anatomy and a variety of surgical methods. This paper summarizes the application research and progress of three-dimensional (3D) printing technology in different peripheral hip diseases in recent years published by PubMed from January 2017 to July 2021 with the search terms including "3D or three-dimensional, print*, and hip*. In general, the application of 3D printing technology is mainly to print bone models of patients, make surgical plans, and simulate pre-operation, customized surgical navigation templates for precise positioning or targeted resection of tissue or bone, and customized patient-specific instruments (PSI) fully conforms to the patient's anatomical morphology. It mainly reduces operative time, intraoperative blood loss, and improves joint function. Consequently, 3D printing technology can be customized according to the patient's disease condition, which provides a new option for treating complex hip diseases and has excellent application and development potential.

7.
Data Brief ; 38: 107400, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34589567

RESUMO

This data set contains the data used in Twarog et al. (2021) to examine the robustness and utility of response surface models in drug combination analysis. It includes simulated experimental data for the evaluation of traditional index methods, as well as a processed library of interaction metrics evaluated on the Merck OncoPolyPharmacology Screen (O'Neil et al., 2016), the scripts used to implement those metrics on all tested combinations in that screen, and scripts to evaluate the performance of those metrics in comparison with real-world mechanistic classifications. Finally, the data set includes data from several published and unpublished drug combination experiments, and scripts which allow the analyses of those experiments to be replicated and applied to new data.

8.
Chem Commun (Camb) ; 57(76): 9688-9691, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34555132

RESUMO

An organoselenide compound, phenyl diselenide (PDSe), is employed as a soluble electrolyte additive to enhance the kinetics of a sulfurized polyacrylonitrile cathode, in which radical exchange in the solid-liquid interface forms dynamic S-Se bonds. Consequently, the PDSe assisted cathode exhibits enhanced battery performance in both ether and carbonate electrolytes.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34574828

RESUMO

This paper examines how economic growth and renewable energy consumption are associated with air pollution using a dynamic panel approach. Focusing on several major air pollutants, namely, particulate matter, sulfur dioxide, nitrogen oxide, and carbon monoxide, this paper tests the environmental Kuznets hypothesis and determines whether the use of renewable energy sources contributes to a reduction in air pollution. Data from a balanced panel of 145 countries for the period between 2000 and 2014 was used for the estimation of the dynamic panel model. The results of the dynamic panel model showed inverted U-shaped curves for the relationship between economic development and particulate matter and sulfur dioxide emissions. The results also revealed that increasing renewable energy consumption contributes to an improvement in air quality. Moreover, it was found that urbanization tends to decrease sulfur dioxide and nitrogen oxide emissions, while trade openness reduces particulate matter and carbon monoxide emissions but increases sulfur dioxide emissions.


Assuntos
Poluição do Ar , Desenvolvimento Econômico , Dióxido de Carbono/análise , Energia Renovável , Urbanização
10.
ACS Appl Mater Interfaces ; 13(35): 41555-41562, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34428011

RESUMO

Over-lithiated organosulfides, such as sulfurized polyacrylonitrile (SPAN), are promising candidates of lithium metal anode (LMA) protection since they could form robust solid electrolyte interphases (SEIs), which is the key toward stable lithium metal batteries. So far, the mechanism of over-lithiation and evolution of the electrode surface is poorly understood. Herein, several in situ techniques were employed to study the over-lithiation process in SPAN, including in situ Raman spectroscopy to reveal the chemical transformation and in situ electrochemical atomic force microscopy (EC-AFM) to visualize interfacial evolution. The results undoubtedly prove the breaking of the C-S bond and formation of the C-Li bond during the over-lithiation process. The nucleophilic C-Li could further trigger the decomposition of the electrolyte to form an inorganic-organic hybrid SEI on the surface of SPAN, which allows uniform Li deposition and significantly improves the cycle stability of LMAs, as supported by the in situ EC-AFM characterization as well as a series of full cell tests. New insights into the over-lithiation mechanism of SPAN should facilitate the design of organosulfides to construct stable lithium metal anodes.

11.
Ann Palliat Med ; 10(7): 7872-7883, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353075

RESUMO

BACKGROUND: meta-analysis was performed to study the therapeutic effect of hematopoietic stem cell transplantation combined with killer cells (important immune cells of the body) on leukemia, hoping to enhance the postoperative therapeutic efficiency. METHODS: literatures were searched with "Hematopoietic stem cell transplantation", "killer cell", "leukemia", "Cytokine induction", etc. as search terms using Boolean logic search. Review Manager was utilized for meta-analysis after literature screening. RESULTS: eleven literatures were included, most of which were of low-risk bias (medium-high quality). Through meta-analysis, statistical heterogeneity was found in non-recurring mortality (NRM) between control group and experimental group (Chi2 =15.69, I2=62%, P=0.02). The leukemia-free survival rate between two groups was not heterogeneous (Chi2 =13.16, I2=32%, P=0.16), without considerable difference between groups (Z=1.52, P=0.13). The incidence of graft-versus-host disease (GvHD) between the two groups was statistically heterogeneous (Chi2 =21.38, I2=67%, P=0.003). The incidence of graft-versus-host disease in experimental group was greatly inferior to controls (Z=3.87, P=0.0001). DISCUSSION: hematopoietic stem cell transplantation combined with killer cells can effectively reduce the incidence of GvHD after stem cell transplantation in patients. The prognosis of transplantation was good, and it had no obvious effect on the overall survival rate and recurrence rate.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia , Células-Tronco Hematopoéticas , Humanos , Incidência , Leucemia/terapia
12.
Am J Perinatol ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34450674

RESUMO

OBJECTIVE: This prospective randomized controlled study aimed to compare the ultrasound-guided (USG) technique with the standard single-wall puncture technique for epicutaneo-caval catheter (ECC) placement in neonates. STUDY DESIGN: A total of 100 neonates were included in this study. All enrolled neonates were randomly divided into two groups (n = 50): the USG group and the control group. The control group underwent standard single-wall puncture for ECC placement procedures, and the USG group underwent USG ECC placement procedures. RESULTS: The first attempt success rates (62 vs. 38%; p = 0.016) and the total success rates (92 vs. 74%; p = 0.017) were higher in the USG group than in the control group. The procedure time was shorter in the USG group than in the control group: 351.43 (112.95) versus 739.78 seconds (369.13), p < 0.001. The incidence of adverse events was not significantly different between the two groups. CONCLUSION: Compared with the standard single-wall puncture method, USG cannulation is superior for neonatal ECC placement, with a higher success rate, and decreases the total procedural time. KEY POINTS: · Establishing ECCs in neonates is challenging and lead to multiple attempts and adverse events.. · Information on the efficiency of USG dynamic needle tip positioning for ECCs in neonates is lacking.. · Compared with the standard puncture method, USG cannulation is superior for neonatal ECC placement..

13.
ACS Appl Mater Interfaces ; 13(32): 38425-38431, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34346230

RESUMO

Three-dimensional (3D) current collectors can effectively mitigate the volumetric expansion of working lithium metal anodes (LMAs). However, the practical utilization of 3D current collectors for lithium metal batteries remains unsatisfactory because of inhomogeneous deposition of lithium ions and an unstable solid electrolyte interphase (SEI). Herein, a facile method based on the exchange reaction between Li and AgNO3 is exploited to embed Ag nanoparticles (NPs) and LiNO3 in a carbon paper (ALCP@Li). The Ag NPs act as a seed for even lithium deposition inside the carbon matrix by virtue of their excellent lithiophilicity. Simultaneously, LiNO3 plays an effective role in stabilizing LMAs by evolving a robust N-rich SEI. As a result, such 3D LMAs show a high Coulombic efficiency in half-cells (200 cycles, 99% at 1 mA cm-2, 1 mAh cm-2) and a low overpotential (60 mV). When paired with commercial thick NCM622 and LiFePO4 cathodes, the 3D LMA-based full cells exhibit stable cycling in carbonate electrolytes.

14.
Ecotoxicol Environ Saf ; 224: 112626, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34411822

RESUMO

Cadmium (Cd) is a carcinogen that stimulates breast cancer (BC) progression. Rapamycin is a macrolide antibiotic produced by Streptomyces hygroscopicus that possesses a wide array of pharmacological activities, including anti-BC activity. However, the effects of rapamycin on Cd-increased BC progression and the underlying mechanism have not been fully elucidated. Here, we hypothesize that rapamycin antagonizes Cd-induced BC cell proliferation and metastasis by directly modulating ACSS2. In this study, we found that rapamycin efficiently inhibited Cd-induced proliferation, invasion and migration in MCF-7 and T47-D cells. Moreover, a surface plasmon resonance (SPR) assay confirmed that rapamycin directly binds to the ACSS2 protein with a calculated equilibrium dissociation constant (KD) of 18.3 µM. Molecular docking showed that there are three binding sites in the ACSS2 protein and that rapamycin binds at the coenzyme A (COA) binding site with a docking score of - 12.26 and a binding free energy of - 26.34 kcal/mol. More importantly, rapamycin suppresses Cd-induced BC progression by activating ACSS2. After cells were cotreated with an ACSS2 inhibitor, the effects of rapamycin were abolished. In conclusion, our findings suggest that rapamycin suppresses Cd-augmented BC progression by upregulating ACSS2, and ACSS2 may serve as a direct target of rapamycin for inhibiting xenobiotic (e.g., Cd)-mediated BC progression.

15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1080-1084, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362485

RESUMO

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with acute myeloid leukemia(AML) combined with paroxysmal nocturnal hemoglobinuria(PNH). METHODS: The clinical data of 13 AML combined with PNH patients treated in our hospital from January 2017 to May 2019 were collected and retrospective analyzed. The complete remission(CR) rate for induction chemotherapy was analyzed. The level of PNH+ cell before and after chemotherapy were tested by Paired t test. Kaplan-Meier method and multi-factorial Cox regression model were used to analyze the influencing factors of prognosis. RESULTS: Among the 13 patients, 11 (84.6%) cases were CR after first induction chemotherapy. The median overall survival(OS) time was 17 months(0-30 months), the median progression-free survival(PFS) time was 16 months(2-26 months). There were no significant difference in the number of PNH+ cell before and after chemotherapy (P>0.05). Multivariate Cox regression analysis showed that age,sex,the level of hemoglobin, platelet were not related to the OS of the patients(P>0.05), the level of WBC, LDH and risk stratification at first diagnosed were related to the OS of the patients(P<0.05). Kaplan-Meier survival analysis showed that the OS rate of AML combined with PNH patients with leukocyte lower than 10×109/L at first diagnosed was better than that of the patients with leukocyte higher than 10×109/L (P=0.0261). The OS rate of patients with low or standard risk was better than the patients with high risk group(P=0.0010). CONCLUSION: The patients of AML combined with PNH have higher CR rate after the first induction chemotherapy. The level of WBC and LDH at first diagnosed are the factors that affecting the OS of the patients. The OS of patients with WBC lower than 10×109/L, at first diagnosed low and medium risk are better than the other patients.


Assuntos
Hemoglobinúria Paroxística , Leucemia Mieloide Aguda , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Prognóstico , Indução de Remissão , Estudos Retrospectivos
16.
Mol Cancer Ther ; 20(11): 2151-2165, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34413129

RESUMO

Pediatric sarcomas represent a heterogeneous group of malignancies that exhibit variable response to DNA-damaging chemotherapy. Schlafen family member 11 protein (SLFN11) increases sensitivity to replicative stress and has been implicated as a potential biomarker to predict sensitivity to DNA-damaging agents (DDA). SLFN11 expression was quantified in 220 children with solid tumors using IHC. Sensitivity to the PARP inhibitor talazoparib (TAL) and the topoisomerase I inhibitor irinotecan (IRN) was assessed in sarcoma cell lines, including SLFN11 knock-out (KO) and overexpression models, and a patient-derived orthotopic xenograft model (PDOX). SLFN11 was expressed in 69% of pediatric sarcoma sampled, including 90% and 100% of Ewing sarcoma and desmoplastic small round-cell tumors, respectively, although the magnitude of expression varied widely. In sarcoma cell lines, protein expression strongly correlated with response to TAL and IRN, with SLFN11 KO resulting in significant loss of sensitivity in vitro and in vivo Surprisingly, retrospective analysis of children with sarcoma found no association between SLFN11 levels and favorable outcome. Subsequently, high SLFN11 expression was confirmed in a PDOX model derived from a patient with recurrent Ewing sarcoma who failed to respond to treatment with TAL + IRN. Selective inhibition of BCL-xL increased sensitivity to TAL + IRN in SLFN11-positive resistant tumor cells. Although SLFN11 appears to drive sensitivity to replicative stress in pediatric sarcomas, its potential to act as a biomarker may be limited to certain tumor backgrounds or contexts. Impaired apoptotic response may be one mechanism of resistance to DDA-induced replicative stress.

17.
Pest Manag Sci ; 77(12): 5407-5417, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34314099

RESUMO

BACKGROUND: Botanical pesticides play an important role in organic agricultural practices and are widely used in integrated pest management (IPM). Uvaria grandiflora was mainly reported as traditional medicines and possessed antibacterial, antioxidant, and antiprotozoal activities. Therefore, important biological activities of U. grandiflora may suggest that they have the potential to be used as botanical pesticides. RESULTS: The extract of U. grandiflora exhibited broad-spectrum inhibitory activity toward phytopathogenic fungi and oomycetes, particularly against Colletotrichum musae and Phytophthora capsici, and its secondary metabolite zeylenone also displayed strong antifungal and anti-oomycete activities against phytopathogens. Particularly, half maximal effective concentration (EC50 ) values of zeylenone against Phytophthora capsici and C. musae were 6.98 and 3.37 µg mL-1 , showing better inhibitory effects than those of commercial fungicides (azoxystrobin and osthole). Additionally, the pot experiments showed that the extract of U. grandiflora could effectively control Pseudoperonospora cubensis, Phytophthora infestans, Phytophthora capsici and Podosphaera xanthii. In the field experiment, 5% microemulsion of U. grandiflora extract exhibited 79.72% efficacy against cucumber powdery mildew at 87.5 g ha-1 on the 14th day after two sprayings, which was better than that of 21.5% trifloxystrobin and 21.5% fluopyram SC at 200.9 g ha-1 . Surprisingly, 5% microemulsion of U. grandiflora extract could promote cucumber growth significantly. Furthermore, the action mechanism analysis indicated that zeylenone may damage the cytoderm and affect energy metabolism of Phytophthora capsici. CONCLUSION: It is the first time that the extract of U. grandiflora and zeylenone have been discovered leading to broad application prospects in the development as botanical fungicides. © 2021 Society of Chemical Industry.


Assuntos
Fungicidas Industriais , Phytophthora infestans , Uvaria , Ascomicetos , Colletotrichum , Cicloexanos , Dioxanos , Fungicidas Industriais/farmacologia , Doenças das Plantas
18.
Angew Chem Int Ed Engl ; 60(36): 19730-19734, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196074

RESUMO

Herein we report a catalytic asymmetric dearomatization reaction of electron-deficient heteroarenes with α-substituted isocyanoacetates through an interrupted Barton-Zard reaction. A range of optically active pyrrolo[3,4-b]indole derivatives was obtained in good yields (up to 97 %) with high stereoselectivities (up to >20:1 dr and 97 % ee), using a catalytic system consisting of a cinchona-derived amino-phosphine and silver oxide. This reaction features wide substrate scope and mild conditions, and provides a new strategy for developing asymmetric dearomatization reactions.

19.
Zhongguo Gu Shang ; 34(7): 654-8, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34318643

RESUMO

OBJECTIVE: To analyze the correction loss after posterior segmental fixation for lumbar spine fractures and explore the related image factors. METHODS: Posterior short-segment fixation was received in 48 patients with L2-L4 fractures. There were 32 males and 16 females, with ages of 23 to 60 (45.98±8.20) yeaes. The anterior vertebrae height (AVH), vertebral wedge angle (VWA) of the injured vertebra and local kyphosis angle (LKA) were measured before operation, 1 week after operation and the final follow-up. The loss of segmental discal angle (LoSDA), LKA(LoLKA), AVH(LoAVH) were calculated between 1 week postoperative and the last follow up. Preoperative load-sharing scores(LSS), TLICS scores, and adjacent intervertebral disc injuries (IDIs) were assessed. Then the correlation between the age, follow up time, LSS, TLICS, IDIs and the correction loss was analyzed. RESULTS: The average follow-up was 12 to 18 (16.13±5.39) months. LKA, AVH and VWA at 1 week postoperative and those at the final follow up, were significantly improved compared with those preoperative (P<0.05). In the final follow up, the average LKA(5.70±3.17)° and AVH(4.31±5.95)% correction loss were observed compared with those 1 week postoperative(P<0.05). Otherwise the lose of VWA was not obvious(P>0.05). Univariate analysis showed that the SDA (r=0.706, 0.579, 0.449) and LKA(r=0.715, 0.566, 0.502) correction loss were aggravated with the increase of LSS, TLICS and IDIs, and AVH (r=-0.325, -0.219) correction loss was aggravated with the increase of LSS and TLICS(P<0.05). Multivariate analysis showed that increased LSS scores were all risk factors for segmental disc angle (SDA) loss, LKA correction loss, and AVH correction loss (P<0.05). CONCLUSION: The angle of adjacent intervertebral discs and anterior height of injured vertebrae were lost statistically after posterior short-segment pedicle screw treatment for lumbar fractures, and multivariate analysis showed that all of them were correlated with load-sharing score.


Assuntos
Parafusos Pediculares , Fraturas da Coluna Vertebral , Feminino , Fixação Interna de Fraturas , Humanos , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Masculino , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Resultado do Tratamento
20.
Nat Commun ; 12(1): 4089, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215733

RESUMO

Pediatric high-grade glioma (pHGG) is a major contributor to cancer-related death in children. In vitro and in vivo disease models reflecting the intimate connection between developmental context and pathogenesis of pHGG are essential to advance understanding and identify therapeutic vulnerabilities. Here we report establishment of 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. These models recapitulate histopathology, DNA methylation signatures, mutations and gene expression patterns of the patient tumors from which they were derived, and include rare subgroups not well-represented by existing models. We deploy 16 new and existing cell lines for high-throughput screening (HTS). In vitro HTS results predict variable in vivo response to PI3K/mTOR and MEK pathway inhibitors. These unique new models and an online interactive data portal for exploration of associated detailed molecular characterization and HTS chemical sensitivity data provide a rich resource for pediatric brain tumor research.


Assuntos
Heterogeneidade Genética/efeitos dos fármacos , Glioma/tratamento farmacológico , Glioma/genética , Animais , Neoplasias Encefálicas , Linhagem Celular Tumoral , Proliferação de Células , Criança , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Ensaios de Triagem em Larga Escala , Humanos , Camundongos , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Serina-Treonina Quinases TOR , Ensaios Antitumorais Modelo de Xenoenxerto
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