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1.
J Colloid Interface Sci ; 606(Pt 2): 913-919, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34487938

RESUMO

With the development of mobile terminals, tunable capacitors for signal processing and memristors for calculation have received a lot of attention. Combining a tunable capacitor and a memristor can improve the performance of mobile terminals and reduce space requirements. In this article, we report on Bi2NiMnO6 (BNMO) films with high dielectric tuning and nonvolatile resistive switching (RS) effects. The BNMO films are fabricated by the sol-gel method and annealed at different temperatures. It exhibits a dielectric tunability of up to 92%. This high dielectric tunability may be attributed to the modulation of the interface dipole by the electric field. When an electric field is applied, the interface dipole of the BNMO film is far away from the interface of the BNMO, and then forms a conductive channel where anions and cations are mixed. The BNMO films are found to have a double-set type effect due to its dielectric tunability properties. This work introduces an ultra-high dielectric tuning material and a new type of RS effect on BNMO thin film, which can achieve tuning and memory behavior on a device.

2.
Front Oncol ; 11: 735817, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722284

RESUMO

Purpose: To identify whether chemoradiotherapy improves survival of stage I nasopharyngeal carcinoma (NPC). Materials and Methods: NPC patients were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. Pathologically confirmed stage T1N0M0 (the 7th edition AJCC) were investigated. Overall survival (OS) and cancer-specific survival (CSS) were compared between the radiotherapy and chemoradiotherapy groups using the Kaplan-Meier method and propensity score matching (PSM) analyses. Results: This study included 91 (40.27%) patients in the chemoradiotherapy group and 135 (59.73%) patients in the radiotherapy group. Before PSM, chemoradiotherapy was associated with worse 3-year OS (74.31 vs 87.23%; P = 0.025) and 5-year OS (64.28 vs 83.12%; P = 0.001) compared to those associated with radiotherapy. Similarly, chemoradiotherapy showed worse 3-year CSS (87.01 vs 96.97%; P = 0.028) and 5-year CSS (80.39 vs. 96.97%; P = 0.002) than those of radiotherapy. After PSM, chemoradiotherapy revealed worse 5-year OS (63.10 vs. 82.49%; P = 0.031) and CSS (80.95 vs. 93.70%; P = 0.016) than radiotherapy. The multivariate regression analysis revealed that chemoradiotherapy was an independent risk prognostic factor for OS and CSS before and after PSM. Conclusion: Radiotherapy alone is recommended for stage I NPC patients.

3.
Endocrine ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34729685

RESUMO

PURPOSE: To confirm the exact break-point of a novel long-range deletion discovered in one female parathyroid carcinoma (PC) patient who has a strong family history suggesting familial hyperparathyroidism, and to investigate the expression of parafibromin in the patient's affected lesion. METHODS: Clinical information of one female patient as well as five of her relatives was collected. Their genomic DNA extracted from peripheral blood went through Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). After completing whole genome sequencing (WGS), clone sequencing was also performed, whose result was aligned with standard human genome database after Sanger sequencing. RESULTS: The medical history of recurrent hypercalcemia after parathyroidectomy and histopathological investigation confirmed that the female patient was diagnosed with PC. WGS displayed a novel 130 kb long-range deletion spanning UCHL5 to CDC73 that was later confirmed by clone sequencing. MLPA showed similar results in four of her five relatives, suggesting these people to be carriers of the same long-range deletion, and three among them had a history of primary hyperparathyroidism (PHPT) ahead of the proband's first visit. CONCLUSIONS: We discovered a novel 130 kb long-range deletion spanning CDC73 in a family of 5 persons, and the existence of the deletion was related to PHPT and PC. Our discovery validated the role of CDC73 mutation in the occurrence of PHPT and PC, which provided new information to the genetic studies of PC.

4.
Comput Intell Neurosci ; 2021: 4026132, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777492

RESUMO

Anomaly detection (AD) aims to distinguish the data points that are inconsistent with the overall pattern of the data. Recently, unsupervised anomaly detection methods have aroused huge attention. Among these methods, feature representation (FR) plays an important role, which can directly affect the performance of anomaly detection. Sparse representation (SR) can be regarded as one of matrix factorization (MF) methods, which is a powerful tool for FR. However, there are some limitations in the original SR. On the one hand, it just learns the shallow feature representations, which leads to the poor performance for anomaly detection. On the other hand, the local geometry structure information of data is ignored. To address these shortcomings, a graph regularized deep sparse representation (GRDSR) approach is proposed for unsupervised anomaly detection in this work. In GRDSR, a deep representation framework is first designed by extending the single layer MF to a multilayer MF for extracting hierarchical structure from the original data. Next, a graph regularization term is introduced to capture the intrinsic local geometric structure information of the original data during the process of FR, making the deep features preserve the neighborhood relationship well. Then, a L1-norm-based sparsity constraint is added to enhance the discriminant ability of the deep features. Finally, a reconstruction error is applied to distinguish anomalies. In order to demonstrate the effectiveness of the proposed approach, we conduct extensive experiments on ten datasets. Compared with the state-of-the-art methods, the proposed approach can achieve the best performance.


Assuntos
Aprendizado de Máquina não Supervisionado
5.
Front Cell Infect Microbiol ; 11: 757470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760723

RESUMO

Klebsiella pneumoniae can cause both hospital- and community-acquired clinical infections. Last-line antibiotics against carbapenem-resistant K. pneumoniae (CRKP), such as ceftazidime/avibactam (CZA) and tigecycline (TGC), remain limited as treatment choices. This study aimed to investigate the mechanisms by which CRKP acquires CZA and TGC resistance in vivo under ß-lactam antibiotic and TGC exposure. Three CRKP strains (XDX16, XDX31 and XDX51) were consecutively isolated from an inpatient with a urinary tract infection in two months. PFGE and MLST showed that these strains were closely related and belonged to sequence type (ST) 4496, which is a novel ST closely related to ST11. Compared to XDX16 and XDX31, XDX51 developed CZA and TGC resistance. Sequencing showed that double copies of bla KPC-2 were located on a 108 kb IncFII plasmid, increasing bla KPC-2 expression in XDX51. In addition, ramR was interrupted by Insertion sequence (IS) Kpn14 in XDX51, with this strain exhibiting upregulation of ramA, acrA and acrB expression compared with XDX16 and XDX31. Furthermore, LPS analysis suggested that the O-antigen in XDX51 was defective due to ISKpn26 insertion in the rhamnosyl transferase gene wbbL, which slightly reduced TGC susceptibility. In brief, CZA resistance was caused mainly by bla KPC-2 duplication, and TGC resistance was caused by ramR inactivation with additional LPS changes due to IS element insertion in wbbL. Notably, CRKP developed TGC and CZA resistance within one month under TGC and ß-lactam treatment without exposure to CZA. The CRKP clone ST4496 has the ability to evolve CZA and TGC resistance rapidly, posing a potential threat to inpatients during antibiotic treatment.

6.
Front Cell Infect Microbiol ; 11: 756782, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790589

RESUMO

Objectives: Recently, KPC-producing P. aeruginosa has rapidly emerged and expanded in East China. Here we described the clinical impact and characteristics of bloodstream infections (BSIs) from the dominant KPC-producing CRPA belonging to Sequence Type (ST) 463. Methods: Retrospective cohort study was performed with CRPA BSI cases from 2019 to 2020 in a hospital in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. All CRPA isolates had whole-genome sequencing, antimicrobial susceptibility testing, and serum resistance assay. Representative isolates were tested for virulence in a Galleria mellonella infection model. Results: Among the 50 CRPA BSI cases, ST463 predominated (48.0%). In multivariate analysis, we found three independent risk factors for fatal outcome: KPC carriage (OR 4.8; CI95% 1.0-23.7; P = 0.05), Pitt bacteremia score (OR 1.3; CI95% 1.0-1.6; P = 0.02), and underlying hematological disease (OR 8.5; CI95% 1.6-46.4; P = 0.01). The baseline clinical variables were not statistically different across STs, however the 28-day mortality was significantly higher in ST463 cases than that in non-ST463 cases (66.7% vs 33.3%, P = 0.03). ExoU and exoS virulence genes coexisted in all ST463 isolates, and the carbapenem resistant gene bla KPC were produced in almost all ST463 isolates, significantly higher than in the non-ST463 group(95.8% vs 7.7%, P<0.001). ST463 CRPA isolates also showed higher resistance rates to antipseudomonal cephalosporins, monobactam, and fluoroquinolones. And ST463 CRPA was confirmed hypervirulence in the larvae model. The genome of one ST463 CRPA strain showed that the bla KPC-2 gene was the sole resistance gene located on a 41,104bp plasmid pZYPA01, carried on a 7-kb composite transposon-like element flanked by two IS26 elements (IS26-Tn3-tnpA-ISKpn27-bla KPC-2-ISKpn6-IS26). Plasmid from various species presented core bla KPC-2 was franked by mobile genetic element ISKpn27 and ISKpn6. Conclusions: In the ST463 CRPA BSI cohort, the mortality rates were higher than those in the non-ST463 CRPA BSI. The ST463 CRPA clone coharboring the bla KPC and exoU/exoS genes emerged and spread in East China, which might develop to a new threat in the clinic. Our results suggest that the surveillance of the new high-risk clone, ST463 CRPA, should be strengthened in China, even worldwide in the future.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34804180

RESUMO

Background: Previous studies have shown that Ampelopsin has an inhibitory effect on human tumors. However, the effect of Ampelopsin on renal cell carcinoma (RCC) is rarely reported. Therefore, this study aims to explain the role of Ampelopsin in RCC. Methods: Different concentrations of Ampelopsin (0, 10, 25, 50, and 100 µM) were used to treat 786-O cells. Cell viability was detected by MTT assay, colony formation assay, and flow cytometry assay. Transwell assay and Wound healing assay were used to detect cell migration and invasion. Western blot analysis was applied to detect protein expression. Results: Ampelopsin inhibited cell proliferation and induced apoptosis in RCC. And Ampelopsin can inhibit cell migration and invasion in RCC. All these results changed in a dose-dependent manner. Ampelopsin (100 uM) had the strongest inhibitory effect on cell viability and metastasis. In addition, Ampelopsin negatively regulated the PI3K/AKT signaling pathway in RCC cells. Moreover, Ampelopsin was only cytotoxic to RCC cells. Conclusion: Ampelopsin inhibits cell viability and metastasis in RCC by negatively regulating the PI3K/AKT signaling pathway.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34810109

RESUMO

The study aimed to investigate whether the incidence rate of external auditory canal (EAC) fracture varies among different clinical types of condylar fracture. A retrospective cohort study was conducted in single hospital of China. Eligible patients diagnosed with mandibular condylar fractures were retrospectively reviewed. Among all patients with condylar fractures (318 cases and 437 sides), 45 cases and 59 sides (59/437 sides, 13.5%) were found with EAC fracture, including 17(17/38, 44.7%) sides of sagittal fracture of condyle (Type I), 21(21/59, 35.6%) sides of intracapsular condylar fracture (Type II), 8 (8/306, 2.6%) sides of condylar neck fracture (Type III), and 6 (6/34, 17.7%) sides of condylar base fracture (Type IV). Type III condylar fracture had a significant lower rate of EAC fracture than all other three types (all p<0.001). Type I condylar fracture had a higher rate of EAC fracture compared to Type IV (p=0.014). The incidence rates of EAC fracture in combined Type I+Type II group (38/97, 39.2%) was significantly higher than Type III (8/306,2.6%, p<0.001) and Type IV (6/34,17.7%, p=0.002). A total of 35 sides (27 patients) with combined fractures were followed up for 6 months after treatment, among whom 11 sides (7 patients) were operated for both fractures simultaneously. Neither EAC stenosis nor hearing loss was observed. Meanwhile, for 24 non-operated ears from 20 patients, all EACs showed different degrees of stenosis. In conclusion, oral and maxillofacial surgeons should pay more attention to EAC fracture combined with condylar fracture, especially for patients diagnosed with condylar head fracture. Maxillofacial fractures should be accompanied by early treatment of EAC fractures, in order to prevent EAC stenosis, hearing loss, and other complications.

9.
World J Clin Cases ; 9(29): 8694-8701, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34734047

RESUMO

BACKGROUND: Respiratory tract infections in the elderly are difficult to cure and can easily recur, thereby posing a great threat to patient prognosis and quality of life. AIM: To investigate the therapeutic effects of different antibiotics in elderly patients with respiratory tract infection. METHODS: Seventy-four elderly patients with respiratory tract infection were randomly allocated to a study (n = 37; treated with cefoperazone sodium/sulbactam sodium) or control (n = 37; treated with piperacillin sodium/tazobactam sodium on the basis of routine symptomatic support) group. Both groups were treated for 7 d. Time to symptom relief (leukocyte recovery; body temperature recovery; cough and sputum disappearance; and rale disappearance time), treatment effect, and laboratory indexes [procalcitonin (PCT), C-reactive protein (CRP), white blood cell count (WBC), and neutrophil percentage (NE)] before and 7 d after treatment and the incidence of adverse reactions were assessed. RESULTS: In the study group, the time to WBC normalization (6.79 ± 2.09 d), time to body temperature normalization (4.15 ± 1.08 d), time to disappearance of cough and sputum (6.19 ± 1.56 d), and time to disappearance of rales (6.68 ± 1.43 d) were shorter than those of the control group (8.89 ± 2.32 d, 5.81 ± 1.33 d, 8.77 ± 2.11 d, and 8.69 ± 2.12 d, respectively; P = 0.000). Total effective rate was higher in the study group (94.59% vs 75.68%, P = 0.022). Serum PCT (12.89 ± 3.96 µg/L), CRP (19.62 ± 6.44 mg/L), WBC (20.61 ± 6.38 × 109/L), and NE (86.14 ± 7.21%) levels of the study group before treatment were similar to those of the control group (14.05 ± 4.11 µg/L, 18.79 ± 5.96 mg/L, 21.21 ± 5.59 × 109/L, and 84.39 ± 6.95%, respectively) with no significant differences (P = 0.220, 0.567, 0.668, and 0.291, respectively). After 7 d of treatment, serum PCT, CRP, WBC, and NE levels in the two groups were lower than those before treatment. Serum PCT (2.01 ± 0.56 µg/L), CRP (3.11 ± 1.02 mg/L), WBC (5.10 ± 1.83 × 109/L), and NE (56.35 ± 7.17%) levels were lower in the study group than in the control group (3.29 ± 0.64 µg/L, 5.67 ± 1.23 mg/L, 8.13 ± 3.01 × 109/L, and 64.22 ± 8.08%, respectively; P = 0.000). There was no significant difference in the incidence of adverse reactions between the groups (7.50% vs 12.50%, P = 0.708). CONCLUSION: Piperacillin sodium/tazobactam sodium is superior to cefoperazone sodium/ sulbactam sodium in the treatment of elderly patients with respiratory tract infection with a similar safety profile.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34769565

RESUMO

Controlling soil erosion is beneficial to the conservation of soil resources and ecological restoration. Understanding the spatial distribution characteristics of soil erosion helps find the key areas for soil control projects and optimal scale for investing in a soil and water conservation project at the lowest cost. This study aims to answer the question of how the spatial distribution of soil erosion in Hubei Province changed between 2000 and 2020. Moreover, how do the effects of natural factors and human activities on soil erosion vary over the years? What are the differences in landscape pattern characteristics and the spatial cluster of soil erosion at multiple administrative scales? We simulated the spatial distribution of soil erosion in Hubei province from 2000 to 2020 by the Chinese Soil Loss Equation model at three administrative scales. We investigated the relationship between soil erosion and driving factors by Geodector. We explored the landscape pattern and hotspots of land at different levels of soil erosion by Fragstat and hotspot analysis. The results show that: (1) The average soil erosion rate decreased from 2000 to 2020. Soil erosion is severe in the mountainous areas of western Hubei province, while it is less severe in the central plains. (2) Land-cover type, precipitation, and normalized difference vegetation index are the most influencing factors of soil erosion in 2000-2010, 2015, and 2020, respectively. (3) The aggregation index values at the town scale are higher than those at the city and county scales, while the fractal dimension index values at the town scale are lower, which indicates that soil erosion projects are most efficient when the project unit is 'town'. (4) At the town scale, if the hotspot area (6.84% of the total area) is treated as the protection target, it can reduce 50.42% of the total soil erosion of Hubei province. Hotspots of soil erosion overlap with high erosion zones, mainly in the northwestern, northeastern, and southwestern parts of Hubei province in 2000, while the hotspots in northwestern Hubei disappear in 2020. In conclusion, land managers in Hubei should optimize the land-use structure, soil and water conservation in slope land, and eco-engineering controls at the town scale.


Assuntos
Conservação dos Recursos Naturais , Solo , China , Cidades , Monitoramento Ambiental , Humanos
11.
Calcif Tissue Int ; 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34800131

RESUMO

Paget's disease of bone (PDB) is a rare metabolic bone disorder, which is extremely rare in Asian population. This study aimed to investigate the phenotypes and the pathogenic mutations of woman with early-onset PDB. The clinical features, bone mineral density, x-ray, radionuclide bone scan, and serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and ß-carboxy-terminal cross-linked telopeptide of type 1 collagen (ß-CTX) were measured in detail. The pathogenic mutations were identified by whole-exon sequencing and confirmed by Sanger sequencing. We also evaluated the effects of intravenous infusion of zoledronic acid on the bones of the patient and summarized the phenotypic characteristics of reported patients with mutation at position 155 of the valosin-containing protein (VCP). The patient only exhibited bone pain as the initial manifestation with vertebral compression fracture and extremely elevated ALP, P1NP, and ß-CTX levels; she had no inclusion body myopathy and frontotemporal dementia. The missense mutation in exon 5 of the VCP gene (p.Arg155His) was identified by whole-exome sequencing and further confirmed by Sanger sequencing. No mutation in candidate genes of PDB, such as SQSTM1, CSF1, TM7SF4, OPTN, PFN1, and TNFRSF11A, were identified in the patient by Sanger sequencing. Rapid relief of bone pain and a marked decline in ALP, P1NP, and ß-CTX levels were observed after zoledronic acid treatment. Previously reported patients with VCP missense mutation at position 155 (R155H) always had myopathy, frontotemporal dementia, and PDB, but the patient in this study exhibited only PDB. This was the first report of R155H mutation-induced early-onset in the VCP gene in Asian population. PDB was the only manifestation having a favorable response to zoledronic acid treatment. We broadened the genetic and clinical phenotype spectra of the VCP mutation.

12.
Food Sci Nutr ; 9(11): 6162-6175, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34760247

RESUMO

The immune regulation function of ovotransferrin (OVT) explored using the RAW264.7 was induced by lipopolysaccharide (LPS) as vitro model in this study. The results showed that RAW264.7 cultured with OVT (200 µg/ml) alone not only enhanced the phagocytic activity and the production and expression of inflammatory factors, but also expression of toll-like receptor 4 (TLR4) gene was significantly promoted by OVT. OVT (50 µg/ml) significantly inhibited the secretion and expression of inflammatory factors in LPS-stimulated RAW264.7, but CD14 and TLR4 genes expressions were no obvious effects. Inflammatory cytokines and NO secreted by OVT-induced macrophages pretreated with inhibitors of TLR4 were down-regulated. We further verified the effects of OVT on inflammatory signaling pathway-related proteins through immunofluorescence and western blotting, MyD88, TLR4 and the phosphorylation of IκBα and p65 were significantly promoted by OVT, but there was no significant effects on the phosphorylation of IRF3. OVT promoted the phosphorylation of ERK and p38 in RAW264.7 and inhibited the phosphorylated expression of MAPK in LPS-mediated inflammation. These results indicated that OVT had the bidirectional immunoregulatory function through TLR4-mediated NF-κB/MAPK signaling pathway, that is, anti-inflammatory effect of low concentration and immune-enhancing activity of high concentration were showed. That provides a theoretical utilization for the development and utilization of OVT.

13.
J Bone Miner Res ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34796540

RESUMO

Tumor-induced osteomalacia TIO is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 FGF23 by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density aBMD in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral distal radius and tibia and axial lumbar spine skeleton using high-resolution peripheral quantitative computed tomography HR-pQCT and trabecular bone score TBS and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry DXA or HR-pQCT scans were enrolled. Compared with age-, sex- and BMI-matched healthy controls, TIO patients n=113 had lower vBMD, damaged microstructure and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS <1.35 was higher than that with low L1-4 aBMD Z-score Z≤-2 43.9% vs. 89.6%, p < 0.001. Higher intact fibroblast growth factor 23 iFGF23, intact parathyroid hormone iPTH, alkaline phosphatase and ß-isomerized C-terminal telopeptide of type I collagen ß-CTx levels, more severe mobility impairment and a history of fracture were associated with poorer HR-pQCT parameters but not with lower TBS. However, greater height loss and longer disease duration were correlated with worse HR-pQCT parameters and TBS. Moreover, TBS was correlated with both trabecular and cortical HR-pQCT parameters in TIO. In conclusion, we revealed impaired bone microarchitecture in the axial and peripheral skeleton in a large cohort of Chinese TIO patients. HR-pQCT parameters and TBS showed promising advantages over aBMD for assessing bone impairment in patients with TIO. A longer follow-up period is needed to observe changes in bone microarchitecture after tumor resection.

14.
J Am Chem Soc ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797070

RESUMO

The concise, collective, and asymmetric total syntheses of four schizozygane alkaloids, which feature a "Pan lid"-like hexacyclic core scaffold bearing up to six continuous stereocenters, including two quaternary ones, are described. A new method of dearomative cyclization of cyclopropanol onto the indole ring at C2 was developed to build the ABCF ring system of the schizozygane core with a ketone group. Another key skeleton-building reaction, the Heck/carbonylative lactamization cascade, ensured the rapid assembly of the hexacyclic schizozygane core and concurrent installation of an alkene group. By strategic use of these two reactions and through late-stage diversifications of the functionalized schizozygane core, the first and asymmetric total syntheses of (+)-schizozygine, (+)-3-oxo-14α,15α-epoxyschizozygine, and (+)-α-schizozygol and the total synthesis of (+)-strempeliopine have been accomplished in 11-12 steps from tryptamines.

15.
Cancers (Basel) ; 13(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34771553

RESUMO

Myelodysplastic syndromes (MDSs) are heterogeneous for their morphology, clinical characteristics, survival of patients, and evolution to acute myeloid leukemia. Different prognostic scoring systems including the International Prognostic Scoring System (IPSS), the Revised IPSS, the WHO Typed Prognostic Scoring System, and the Lower-Risk Prognostic Scoring System have been introduced for categorizing the highly variable clinical outcomes. However, not considered by current MDS prognosis classification systems, gene variants have been identified for their contribution to the clinical heterogeneity of the disease and their impact on the prognosis. Notably, TP53 mutation is independently associated with a higher risk category, resistance to conventional therapies, rapid transformation to leukemia, and a poor outcome. Herein, we discuss the features of monoallelic and biallelic TP53 mutations within MDS, their corresponding carcinogenic mechanisms, their predictive value in current standard treatments including hypomethylating agents, allogeneic hematopoietic stem cell transplantation, and lenalidomide, together with the latest progress in TP53-targeted therapy strategies, especially MDS clinical trial data.

16.
Front Plant Sci ; 12: 734775, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764966

RESUMO

Although leaf economics spectrum (LES) has been extensively tested with regional and global datasets, the correlation among functional traits of desert plants remains largely unclear. Moreover, examinations on whether and how leaf and root traits are coordinated have yielded mixed results. We investigated variations in leaf and fine-root traits across 48 species in a desert community of northern China to test the hypotheses that (1) the leaf-trait syndrome of plant species in desert shrublands follows the predictions of the global LES, and is paralleled by a similar root-trait syndrome, (2) functional traits related to nutrient contents and resource uptake are tightly coordinated between leaves and fine roots in desert ecosystems where plant growth is limited primarily by dry and nutrient-poor conditions, and (3) traits as well as their relationships vary among functional groups. Our results partially supported the LES theory. Specific leaf area (SLA) was correlated with leaf tissue density, phosphorus content, and carbon-to-nitrogen ratio, but not with leaf nitrogen content. Specific root length (SRL) was not correlated with other fine-root traits, and fine-root traits were largely independent of each other. Therefore, fine-root traits did not mirror the leaf-trait syndrome. Fine-root nitrogen and phosphorus contents, nitrogen-to-phosphorous ratio, and carbon-to-nitrogen ratio all increased with analogous leaf traits, whereas SRL was not correlated with SLA. After phylogenetic effects were considered, nutrient contents and their ratios still displayed stronger coordination between leaves and fine roots than did SRL and SLA. The overall pattern of trait variations and relationships suggested differentiation among functional groups. Our results suggest that despite the absence of a root-trait syndrome, fine-root functions in the studied desert community were probably coordinated with leaf functions with respect to nutrient allocation and use.

17.
J Infect ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34767837

RESUMO

BACKGROUND: Real-time surveillance of search behavior on the internet has achieved accessibility in measuring disease activity. In this study, we systematically assessed the associations between internet search trends of gastrointestinal (GI) symptom terms and daily newly confirmed COVID-19 cases at both global and regional levels. METHODS: Relative search volumes (RSVs) of GI symptom terms were derived from internet search engines. Time-series analyses with autoregressive integrated moving average models were conducted to fit and forecast the RSV trends of each GI symptom term before and after the COVID-19 outbreak. Generalized additive models were used to quantify the effects of RSVs of GI symptom terms on the incidence of COVID-19. In addition, dose-response analyses were applied to estimate the shape of the associations. RESULTS: The RSVs of GI symptom terms could be characterized by seasonal variation and a high correlation with symptoms of "fever" and "cough" at both global and regional levels; in particular, "diarrhea" and "loss of taste" were abnormally increased during the outbreak period of COVID-19, with elevated point changes of 1.31 and 8 times, respectively. In addition, these symptom terms could effectively predict a COVID-19 outbreak in advance, underlying the lag correlation at 12 and 5 days, respectively, and with mutual independence. The dose-response curves showed a consistent increase in daily COVID-19 risk with increasing search volumes of "diarrhea" and "loss of taste". CONCLUSION: This is the first and largest epidemiologic study that comprehensively revealed the advanced prediction of COVID-19 outbreaks at both global and regional levels via GI symptom indicators.

18.
J Clin Pharm Ther ; 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34779003

RESUMO

WHAT IS KNOWN AND OBJECTIVES: Ciclosporin (CsA), a potent immunosuppressive agent used to prevent graft-versus-host disease in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, is characterized by large inter-individual variability and a narrow therapeutic range. The aim of this study was to develop a population pharmacokinetic model for CsA in Chinese allo-HSCT recipients and to identify covariates influencing CsA pharmacokinetics. METHODS: A total of 758 retrospective drug monitoring data points were collected after intravenous infusion or oral administration of CsA from 59 patients. Population pharmacokinetic analysis was performed using nonlinear mixed effects modelling expressed by differential equations. Monte Carlo simulation was applied to optimize dosage regimens. The final model was validated using bootstrap and normalized prediction distribution errors. RESULTS AND DISCUSSION: The results showed that the daily CsA dose, haematocrit, total bile acid, C-reactive protein (CRP) and co-administration of triazole antifungal agent were identified as significant covariates for clearance (CL) of CsA. The typical value of CL was 19.8 L/h with an inter-individual variability of 13.1%. The volume of distribution was 1340 L. Bioavailability was 67.2% with an inter-individual variability of 8.5%. Dosing simulation based on the developed model indicated that patients with high CRP concentration required a higher daily dose to attain the therapeutic trough concentration. The influence of CRP ultimately on the therapy outcome of CsA is not clear, which needs further study. WHAT IS NEW AND CONCLUSION: CRP concentration was identified as a novel marker associated with CsA pharmacokinetics, which should be considered when determining the appropriate dosage of CsA in allo-HSCT recipients.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34745303

RESUMO

Background: Traditional Chinese medicine (TCM) has long been widely adopted by the Chinese people and has been covered by China's basic medical insurance schemes to treat ischemic stroke. Previous research has mainly highlighted the therapy effect of TCM on ischemic stroke patients. Some studies have demonstrated that employing TCM can reduce the medical burden on other diseases. But no research has explored whether using TCM could reduce inpatient medical cost for ischemic stroke in mainland China. The purpose of this study is to investigate the impact of the use of TCM on the total inpatient cost of ischemic stroke and to explore whether TCM has played the role of being complementary to, or an alternative for, conventional medicine to treat ischemic stroke. Methods: We conducted a national cross-sectional analysis based on a 5% random sample from claims data of China Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) schemes in 2015. Mann-Whitney test was used to compare unadjusted total inpatient cost, conventional medication cost, and nonpharmacy cost estimates. Ordinary least square regression analysis was performed to compare demographics-adjusted total inpatient cost and to examine the association between TCM cost and conventional medication cost. Results: A total of 47321 urban inpatients diagnosed with ischemic stroke were identified in our study, with 92.6% (43843) of the patients using TCM in their inpatient treatment. Total inpatient cost for TCM users was significantly higher than TCM nonusers (USD 1217 versus USD 1036, P < 0.001). Conventional medication cost was significantly lower for TCM users (USD 335 versus USD 436, P < 0.001). The average cost of TCM per patient among TCM users was USD 289. Among TCM users, conventional medication costs were found to be positively associated with TCM cost after adjusting for confounding factors (Coef. = 0.144, P < 0.001). Conclusion: Although the use of TCM reduced the cost of conventional medicine compared with TCM nonusers, TCM imposed an extra financial component on the total inpatient cost on TCM users. Our study suggests that TCM mainly played a complementary role to conventional medicine in ischemic stroke treatment in mainland China.

20.
World J Clin Cases ; 9(28): 8524-8530, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34754863

RESUMO

BACKGROUND: Endometriosis (EMs), an estrogen-dependent disease, refers to the appearance of mucosa-covered endometrial tissues (glandular and interstitial) growing in the uterine cavity outside the uterine myometrium. It is commonly seen in women aged 25 to 45, with an incidence of approximately 10%-15%. CASE SUMMARY: A 35-year-old unmarried female who denied a history of sex with an intact hymen had multiple dysmenorrhea and pain in the left lower abdomen that recurred during menstruation. Ultrasound examination revealed a dark cystic area measuring 4.9 cm × 4.6 cm on the left side with poor light transmittance, which suggested a left endometriotic cyst. The patient was treated with pain medications (four capsules t.i.d., p.o.). After one month, computed tomography of the abdomen and pelvis revealed a low-density focus measuring approximately 38 mm in diameter, a blurred mesentery fat plane in the pelvic cavity, and pelvic effusion. Ultrasound showed a complex echo density measuring 5.2 cm × 3.0 cm × 4.2 cm in the left ovarian area and a fluid sonolucent area with a depth of 2.0 cm in the pelvic cavity. Left ovarian cystectomy, electrocautery for endometriotic lesions, myomectomy, and pelvic adhesion lysis were performed under laparoscopy. The postoperative diagnosis was left ovarian chocolate cyst rupture and EMs (stage III, ovarian type, peritoneal type). CONCLUSION: Laparoscopic surgery can safely control the symptoms of EMs and effectively eradicate the disease.

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