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1.
Am J Sports Med ; : 3635465211068854, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35044262

RESUMO

BACKGROUND: Fatty infiltration of the rotator cuff muscles is highly related to poor outcomes after rotator cuff tears. Fat fraction (FF) based on traditional 2-dimensional measurements (2D-FF) from a single sagittal Y-view slice cannot determine intramuscular FF in the rotator cuff muscles; the newly developed 3-dimensional method (3D-FF) is supposed to precede 2D measurements for intramuscular FF evaluation in accuracy and reliability. PURPOSE: (1) To measure 3D-FF and (2) to compare 3D-FF and 2D-FF in terms of quantitative values and intra- and interobserver agreement. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Six-point Dixon magnetic resonance imaging was performed in patients with full-thickness supraspinatus tears. 2D-FF was calculated on a single sagittal Y-view. Semiautomatic segmentation software (ITK-SNAP) was used to reconstruct 3D volumes of the supraspinatus muscle and fat. 3D-FF was obtained by dividing the fat volume by the total volume of the supraspinatus muscle. A paired t test was used to compare the individual differences between 2D-FF and 3D-FF results. Linear regression and Bland-Altman analyses were performed to determine the agreement between 2D-FF and 3D-FF. Intraclass correlation coefficients (ICCs) were calculated to determine intra- and interobserver agreement. RESULTS: The 3D muscular and fatty models presented an inhomogeneous distribution of intramuscular fat in the supraspinatus, indicating the superiority of 3D-FF over 2D-FF in capturing all muscle morphologic information. 2D-FF was significantly higher than 3D-FF in the supraspinatus with large (19.5% ± 5.9% vs 16.2% ± 3.7%; P = .002) and massive (34.8% ± 13.3% vs 26.2% ± 9.4%; P < .001) rotator cuff tears. 2D-FF overestimated the FF compared with 3D-FF by >50% in 14.7% of all patients and by >15% in 67.6% of patients with large or massive RCTs. The discrepancy between 2D-FF and 3D-FF increased with increasing mean FF. The intra- and interobserver agreement of 3D-FF (ICCs, 0.89-0.99 and 0.89-0.95) was superior to that of 2D-FF (ICCs, 0.71-0.95 and 0.64-0.79). CONCLUSION: 3D-FF indicated an inhomogeneous distribution of intramuscular fat by capturing all muscle and fat morphologic information. In patients with large and massive rotator cuff tears, 2D-FF of the supraspinatus was significantly higher than 3D-FF. 3D-FF was more reliable than 2D-FF for estimating fatty infiltration in the supraspinatus, with better intra- and interobserver agreement.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35047049

RESUMO

The prevalence and risk factors of intracranial atherosclerotic stenosis (ICAS) located in the anterior circulation (AC) and posterior circulation (PC) has been scarcely noted in the general population. We aimed to determine ICAS prevalence and risk factor profile of AC and PC in a representative population. Data were from the China Hypertension Survey of Beijing. In total, 4800 people aged 35 years or older were enrolled in this subsurvey for ICAS, and 3954 participants were eligible for analysis. ICAS was assessed by transcranial Doppler. The prevalence of ICAS in AC was much greater than that in PC (11.9% vs. 4.2%), and subjects with ICAS in PC were 3.9 years older than those with ICAS in AC. Multivariable logistics regression showed that the odds of hypertension and diabetes increased by 79% (OR: 1.79, 95% CI: 1.40-2.27) and 35% (OR: 1.35, 95% CI: 1.04-1.75) in those with AC vascular lesions and by 3.35 times (OR: 3.35, 95% CI: 2.49-4.50) and 71% (OR: 1.71, 95% CI: 1.19-2.46) in those with PC vascular lesions compared with those without vascular lesions. Most modifiable vascular risk factors for ICAS appeared to exert similar magnitudes of risk for PC to AC lesions.

3.
J Hazard Mater ; 424(Pt B): 127463, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34687998

RESUMO

Traffic-related air pollution (TRAP) has shown enormous environmental toxicity, but its cardiorespiratory health impact on chronic obstructive pulmonary disease (COPD) has been less studied. We followed a panel of 45 COPD patients with 4 repeated clinical visits across 14 months in a traffic-predominated urban area of Beijing, China, with concurrent measurements of TRAP metrics (fine particulate matter, black carbon, oxides of nitrogen and carbon monoxide). Linear mixed-effect models were performed to evaluate the associations and potential pathways linking traffic pollution to indicators of spirometry, cardiac injury, inflammation and oxidative stress. We observed that interquartile range increases in moving averages of TRAP exposures at prior up to 7 days were associated with significant reductions in large and small airway functions, namely decreases in forced vital capacity of 3.1-9.3% and forced expiratory flow 25-75% of 5.9-16.4%. Higher TRAP levels were also associated with worsening of biomarkers relevant to lung injury (hepatocyte growth factor and surfactant protein D) and cardiac injury (high-sensitivity cardiac troponin I, B-type natriuretic peptide and soluble ST2), as well as enhanced airway/systemic inflammation and oxidative stress. Mediation analyses showed that TRAP exposures may prompt cardiac injury, possibly via worsening pulmonary pathophysiology. These findings highlight the importance of traffic pollution control priority in urban areas.

4.
J Mol Biol ; 434(2): 167369, 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34852272

RESUMO

The highly conserved multifunctional polymerase-associated factor 1 (Paf1) complex (PAF1C), which consists of five core subunits: Ctr9, Paf1, Leo1, Cdc73, and Rtf1, acts as a diverse hub that regulates all stages of RNA polymerase II-mediated transcription and various other cellular functions. However, the underlying mechanisms remain unclear. Here, we report the crystal structure of the core module derived from a quaternary Ctr9/Paf1/Cdc73/Rtf1 complex of S. cerevisiae PAF1C, which reveals interfaces between the tetratricopeptide repeat module in Ctr9 and Cdc73 or Rtf1, and find that the Ctr9/Paf1 subcomplex is the key scaffold for PAF1C assembly. Our study demonstrates that Cdc73 binds Ctr9/Paf1 subcomplex with a very similar conformation within thermophilic fungi or human PAF1C, and that the binding of Cdc73 to PAF1C is important for yeast growth. Importantly, our structure reveals for the first time that the extreme C-terminus of Rtf1 adopts an "L"-shaped structure, which interacts with Ctr9 specifically. In addition, disruption of the binding of either Cdc73 or Rtf1 to PAF1C greatly affects the normal level of histone H2B K123 monoubiquitination in vivo. Collectively, our results provide a structural insight into the architecture of the quaternary Ctr9/Paf1/Cdc73/Rtf1 complex and PAF1C functional regulation.

5.
Respir Res ; 22(1): 310, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893078

RESUMO

BACKGROUND: Aetiology detection is crucial in the diagnosis and treatment of ventilator-associated pneumonia (VAP). However, the detection method needs improvement. In this study, we used Nanopore sequencing to build a quick detection protocol and compared the efficiency of different methods for detecting 7 VAP pathogens. METHODS: The endotracheal aspirate (ETA) of 83 patients with suspected VAP from Peking University Third Hospital (PUTH) was collected, saponins were used to deplete host genomes, and PCR- or non-PCR-amplified library construction methods were used and compared. Sequence was performed with MinION equipment and local data analysis methods were used for sequencing and data analysis. RESULTS: Saponin depletion effectively removed 11 of 12 human genomes, while most pathogenic bacterial genome results showed no significant difference except for S. pneumoniae. Moreover, the average sequence time decreased from 19.6 h to 3.62 h. The non-PCR amplification method and PCR amplification method for library build has a similar average sensitivity (85.8% vs. 86.35%), but the non-PCR amplification method has a better average specificity (100% VS 91.15%), and required less time. The whole method takes 5-6 h from ETA extraction to pathogen classification. After analysing the 7 pathogens enrolled in our study, the average sensitivity of metagenomic sequencing was approximately 2.4 times higher than that of clinical culture (89.15% vs. 37.77%), and the average specificity was 98.8%. CONCLUSIONS: Using saponins to remove the human genome and a non-PCR amplification method to build libraries can be used for the identification of pathogens in the ETA of VAP patients within 6 h by MinION, which provides a new approach for the rapid identification of pathogens in clinical departments.

6.
J Am Med Dir Assoc ; 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34932988

RESUMO

OBJECTIVE: To establish and validate a nomogram that predicts the risk of sarcopenia for community-dwelling older residents. DESIGN: Retrospective study. SETTING AND PARTICIPANTS: A total of 1050 community-dwelling older adults. METHODS: Data from a survey of community-dwelling older residents (≥60 years old) in Hunan, China, from June to September 2019 were retrospectively analyzed. The survey included general demographic information, diet, and exercise habits. Sarcopenia diagnosis was according to 2019 Asian Working Group for Sarcopenia criteria. Participants were randomly divided into the development group and validation groups. Independent risk factors were screened by multivariate logistic regression analysis. Based on the independent risk factors, a nomogram model was developed to predict the risk of sarcopenia for community-dwelling older adults. Both in the development and validation sets, the discrimination, calibration, and clinical practicability of the nomogram were verified using receiver operating characteristic curve analysis, Hosmer-Lemeshow test, and decision curve analysis, respectively. RESULTS: Sarcopenia was identified in 263 (25.0%) participants. Age, body mass index, marital status, regular physical activity habit, uninterrupted sedentary time, and dietary diversity score were significant contributors to sarcopenia risk. A nomogram for predicting sarcopenia in community-dwelling older adults was developed using these factors. Receiver operating characteristic curve analysis showed that the area under the curve was 0.827 (95% CI 0.792-0.860) and 0.755 (95% CI 0.680-0.837) in the development and validation sets, respectively. The Hosmer-Lemeshow test yielded P values of .609 and .565, respectively, for the 2 sets. The nomogram demonstrated a high net benefit in the clinical decision curve in both sets. CONCLUSIONS AND IMPLICATIONS: This study developed and validated a risk prediction nomogram for sarcopenia among community-dwelling older adults. Sarcopenia risk was classified as low (<11%), moderate (11%-70%), and high (>70%). This nomogram provides an accurate visual tool to medical staff, caregivers, and older adults for prediction, early intervention, and graded management of sarcopenia.

7.
Comput Math Methods Med ; 2021: 1732176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966440

RESUMO

Circular RNA (circRNA) is closely related to tumorigenesis and cancer progression. Yet, the roles of cancer-specific circRNAs in the circRNA-related ceRNA network of breast cancer (BRCA) remain unclear. The aim of this study was to construct a ceRNA network associated with circRNA and to explore new therapeutic and prognostic targets and biomarkers for breast cancer. We downloaded the circRNA expression profile of BRCA from Gene Expression Omnibus (GEO) microarray datasets and downloaded the miRNA and mRNA expression profiles of BRCA from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were identified, and a competitive endogenous RNA (ceRNA) regulatory network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Gene ontology and pathway enrichment analyses were performed on mRNAs regulated by circRNAs in ceRNA networks. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network were performed. A total of 72 DEcircRNAs, 158 DEmiRNAs, and 2762 DE mRNAs were identified. The constructed ceRNA network contains 60 circRNA-miRNA pairs and 140 miRNA-mRNA pairs, including 40 circRNAs, 30 miRNAs, and 100 mRNAs. Functional enrichment indicated that DEmRNAs regulated by DEcircRNAs in ceRNA networks were significantly enriched in the PI3K-Akt signaling pathway, microRNAs in cancer, and proteoglycans in cancer. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network showed that 13 mRNAs and 6 miRNAs were significantly associated with overall survival, and 48 miRNA-mRNA interaction pairs had a significant negative correlation. A PPI network was established, and 21 hub genes were determined from the network. This study provides an effective bioinformatics basis for further understanding of the molecular mechanisms and predictions of breast cancer. A better understanding of the circRNA-related ceRNA network in BRCA will help identify potential biomarkers for diagnosis and prognosis.

8.
J Int Med Res ; 49(10): 3000605211053769, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34719988

RESUMO

Congenital granular cell epulis (CGCE) is a rare benign soft tissue lesion that usually originates from the neonatal gingiva and can lead to difficulty in breathing and feeding upon birth. This current case report describes a female newborn with a gingival mass that was identified by prenatal fetal ultrasonography. At birth, the oral mass was observed to protrude from the mouth, which adversely affected feeding. The lips could not be closed. The breathing was unaffected. Through a multidisciplinary team approach involving several healthcare professionals, the mass was successfully removed under general anaesthesia during an uncomplicated surgical procedure. Postoperative histopathological examination confirmed that the mass was a CGCE of the newborn. The infant recovered well after the operation.


Assuntos
Neoplasias Gengivais , Tumor de Células Granulares , Feminino , Neoplasias Gengivais/diagnóstico por imagem , Neoplasias Gengivais/cirurgia , Tumor de Células Granulares/diagnóstico por imagem , Tumor de Células Granulares/cirurgia , Humanos , Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal
9.
Trials ; 22(1): 834, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819117

RESUMO

BACKGROUND: The benefits of mother's own milk (MOM) for preterm infants have been widely recognized. Many studies have shown that the rate of breastfeeding of premature infants remains very low. Although many studies use measures to promote breastfeeding, few high-quality cluster randomized controlled studies have evaluated the effectiveness of these measures. WeChat is an instant messaging software for smart terminals, and WeChat mini-programs have been widely used to promote health and self-management in China. Based on this background, we designed a randomized controlled study based on WeChat mini-programs to promote MOM feeding of premature infants in the neonatal intensive care unit (NICU). METHODS/DESIGN: This study will evaluate the effectiveness of WeChat mini-programs to increase the consumption of MOM feeding in twelve NICUs in Jiangsu Province, namely, six "intervention" NICUs and six "control" NICUs. The study process is as follows: (1) design and preparation, (2) NICU recruitment and training, (3) interpretation and analysis of baseline data, (4) quality control implementation process, and (5) data analysis feedback and publication of study reports. The primary outcome is the proportion of MOM feeding of premature infants during NICU hospitalization. The secondary outcomes are as follows: (1) time to initiation of MOM feeding (hours) and proportion of first-time MOM feeding (%), (2) duration of parenteral nutrition (days), (3) time to total gastrointestinal feeding (days), (4) hospitalization time and hospitalization cost, and (5) incidence of complications (necrotizing enterocolitis, bronchopulmonary dysplasia, feeding intolerance, late-onset sepsis, retinopathy of prematurity). DISCUSSION: This study is the first cluster randomized controlled trial on the intervention of using a WeChat mini-program-based lactation consultant for premature infants in the NICU in China. We hope this study can improve the consumption of MOM by NICU premature infants during hospitalization through the intervention of WeChat mini-programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04383379. Registered on May 5, 2020.


Assuntos
Consultores , Unidades de Terapia Intensiva Neonatal , Aleitamento Materno , Feminino , Promoção da Saúde , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Lactação , Leite Humano , Mães , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Ecotoxicol Environ Saf ; 227: 112936, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34755631

RESUMO

This study investigated the presence of 18 dioxin-like and non-dioxin-like polychlorinated biphenyls (dl- and ndl-PCBs), heavy metals (Cd, Hg, Pb, and As) in Chinese mitten crabs (Eriocheir sinensis) and their distribution in Jiangsu, China. Risk assessment and source apportionment were employed for evaluating the eco-toxicological impact and human exposure. It was found that the compositions of PCBs varied spatially, suggesting different sources of pollutants, whilst PCB 28, 105, 114, and 126 were consistently found in all sample types, suggesting a common pollution source remained, and the bio-accumulation process was in effect. The total PCBs in sediment were found much higher than in water, and brown meat had the highest and most diverse PCB congeners among all tissues. The presence of heavy metals was found in all samples in descending order of As>Cd>Pb>Hg and in the order of shell>brown meat>white meat>gill for crabs. The results of risk assessment indicated that the potential carcinogenic and non-carcinogenic risks were within the acceptable range for long-term consumption of the crabs overall. However, the highest toxic equivalent (TEQ), carcinogenic, and non-carcinogenic risks were all recorded in Location C, where dl-PCB 126, 169, and As contributed to the majority of the risks. The ecological risk posed by all HMs was low, but cases of serious point source pollution have been found in the investigated regions, and risks caused by Cd individually should raise concerns. Source apportionment study revealed that the contaminants mostly originated from anthropogenic activities. Natural deposition and transportation played an important role as well.


Assuntos
Braquiúros/química , Exposição Dietética , Metais Pesados , Bifenilos Policlorados , Agricultura , Animais , China , Ecossistema , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Bifenilos Policlorados/análise , Medição de Risco
11.
Front Cardiovasc Med ; 8: 751519, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765657

RESUMO

Background: Obstructive sleep apnea is an atherogenesis factor of which chronic intermittent hypoxia is a prominent feature. Chronic intermittent hypoxia (CIH) exposure can sufficiently activate the sympathetic system, which acts on the ß3 adrenergic receptors of brown adipose tissue (BAT). However, the activity of BAT and its function in CIH-induced atherosclerosis have not been fully elucidated. Methods: This study involved ApoE-/- mice which were fed with a high-fat diet for 12 weeks and grouped into control and CIH group. During the last 8 weeks, mice in the CIH group were housed in cages to deliver CIH (12 h per day, cyclic inspiratory oxygen fraction 5-20.9%, 180 s cycle). Atherosclerotic plaques were evaluated by Oil Red O, hematoxylin and eosin, Masson staining, and immunohistochemistry. Afterward, we conducted immunohistochemistry, western blotting, and qRT-PCR of uncoupling protein 1 (UCP1) to investigate the activation of BAT. The level of serum total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and free fatty acid (FFA) were measured. Finally, RNA-Sequencing was deployed to explore the differentially expressed genes (DEGs) and their enriched pathways between control and CIH groups. Results: Chronic intermittent hypoxia exposure promoted atherosclerotic plaque area with increasing CD68, α-SMA, and collagen in plaques. BAT activation was presented during CIH exposure with UCP1 up-regulated. Serum TC, triglyceride, LDL-c, and FFA were increased accompanied by BAT activation. HDL-c was decreased. Mechanistically, 43 lipolysis and lipid metabolism-associated mRNA showed different expression profiling between the groups. Calcium, MAPK, and adrenergic signaling pathway included the most gene number among the significantly enriched pathways. Conclusion: This study first demonstrated that BAT activation is involved in the progression of CIH-induced atherosclerosis, possibly by stimulating lipolysis.

12.
J Immunol Methods ; 500: 113196, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34838793

RESUMO

Inactivated Mycoplasma hyopneumoniae vaccine is used extensively to control M. hyopneumoniae infection worldwide. Quantification techniques are essential in the process of standardizing and validating vaccines. In this study, we developed and optimized an indirect competitive enzyme linked immunosorbent assay (ic-ELISA) for the rapid quantification of M. hyopneumoniae antigen during vaccine production. Briefly, whole M. hyopneumoniae antigen was coated onto microtiter plates, and a polyclonal antibody against M. hyopneumoniae recombinant elongation factor thermo unstable (EF-Tu) protein was prepared and added with the samples to be tested. The methods were optimized and showed significant reproducibility, with coefficients of variation of 4.01% and 6.14% for the intra-and inter-assays, respectively. Quantification of M. hyopneumoniae cultures at different growth stages using the ic-ELISA test showed a similar curve to that of the traditional color changing units (CCU) assay, with a delay in the time when the amount reached the peak and started to fall. In the inactivated vaccine production process, the cultures could be harvested later than that for the live vaccine, at about 12 h after the end of the logarithmic growth phase. Different batches of cultures were measured for their relative potency value compared with the in-house reference vaccine, which was used to determine whether the cultures met the antigen amount requirements for vaccine preparation. The curves of the CCU titer and ic-ELISA titer in the logarithmic phase correlated strongly and a linear regression equation was established to calculate the CCU values rapidly using the ic-ELISA results. In conclusion, an ic-ELISA method was established to rapidly assess the amount of antigen in an M. hyopneumoniae culture during the vaccine production process.

13.
Adv Sci (Weinh) ; 8(23): e2102593, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34687159

RESUMO

Fast and accurate identification of microbial pathogens is critical for the proper treatment of infections. Traditional culture-based diagnosis in clinics is increasingly supplemented by metagenomic next-generation-sequencing (mNGS). Here, RNA/cDNA-targeted sequencing (meta-transcriptomics using NGS (mtNGS)) is established to reduce the host nucleotide percentage in clinic samples and by combining with Oxford Nanopore Technology (ONT) platforms (meta-transcriptomics using third-generation sequencing, mtTGS) to improve the sequencing time. It shows that mtNGS improves the ratio of microbial reads, facilitates bacterial identification using multiple-strategies, and discovers fungi, viruses, and antibiotic resistance genes, and displaying agreement with clinical findings. Furthermore, longer reads in mtTGS lead to additional improvement in pathogen identification and also accelerate the clinical diagnosis. Additionally, primary tests utilizing direct-RNA sequencing and targeted sequencing of ONT show that ONT displays important potential but must be further developed. This study presents the potential of RNA-targeted pathogen identification in clinical samples, especially when combined with the newest developments in ONT.

14.
J Phys Chem B ; 125(41): 11548-11556, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34615358

RESUMO

Aggregation-induced emission (AIE) fluorescent molecules with unique photoelectric properties have received extensive attention due to the wide range of applications. In this work, two novel phenothiazine-based luminophores DPE-PTZ-Cl and DPE-PTZ-CF3 were designed based on the frontier molecular orbital (FMO) theory and construction strategy of AIEgens. As expected, both of the luminophores displayed typical AIE behavior and realized the spatial separation of FMOs, which was confirmed by the positive solvatochromism behavior. Their AIE properties could be attributed to the twisted three-dimensional (3D) conformation. Such a conformation resulted from "butterfly-like" phenothiazine and a multirotor structure of diphenylethylene. The spatial separation of FMOs originated from the push-pull electronic synergistic effect of the donor-acceptor (D-A) architecture. Interestingly, DPE-PTZ-Cl also showed a rare blue-shifted mechanochromic (MC) luminescence property. Single-crystal X-ray diffraction (SCXRD) and powder X-ray diffraction (PXRD) experiments were carried out to reveal that the phase transformation between crystalline and amorphous states was responsible for the peculiar solid-state luminescence phenomenon.

15.
BMC Cancer ; 21(1): 1078, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615494

RESUMO

BACKGROUND: Cervical cancer is a common malignancy of the female genital tract. Treatment options for cervical cancer patients diagnosed at FIGO (2009) stage IB2 and IIA2 remains controversial. METHODS: We perform a Bayesian network meta-analysis to directly or indirectly compare various interventions for FIGO (2009) IB2 and IIA2 disease, in order to improve our understand of the optimal treatment strategy for these women. Three databases were searched for articles published between 1971 and 2020. Data on included study characteristics, outcomes, and risk of bias were abstracted by two reviewers. RESULTS: Seven thousand four hundred eighty-six articles were identified. Thirteen randomized controlled trials of FIGO (2009) IB2 and IIA2 cervical cancer patients were included in the final analysis. These trials used six different interventions: concomitant chemoradiotherapy (CCRT), radical surgery (RS), radical surgery following chemoradiotherapy (CCRT+RS), neoadjuvant chemotherapy followed by radical surgery (NACT+RS), adjuvant radiotherapy followed by Radical surgery (RT + RS), radiotherapy alone (RT).SUCRA ranking of OS and Relapse identified CCRT+RS and CCRT as the best interventions, respectively. Systematic clustering analysis identified the CCRT group as a unique cluster. CONCLUSION: These data suggest that CCRT may be the best approach for improving the clinical outcome of cervical cancer patients diagnosed at FIGO (2009) stage IB2/IIA2. Phase III randomized trials should be performed in order to robustly assess the relative efficacy of available treatment strategies in this disease context.


Assuntos
Quimiorradioterapia , Metanálise em Rede , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Teorema de Bayes , Viés , Feminino , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/cirurgia
16.
Artigo em Inglês | MEDLINE | ID: mdl-34658118

RESUMO

Protein stability and evolvability influence each other. Although protein dynamics play essential roles in various catalytically important properties, their high flexibility and diversity makes it difficult to incorporate such properties into rational engineering. Therefore, how to unlock the potential evolvability in a user-friendly rational design process remains a challenge. In this endeavor, we describe a method for engineering an enantioselective alcohol dehydrogenase. It enables synthetically important substrate acceptance for 4-chlorophenyl pyridine-2-yl ketone, and perfect stereocontrol of both (S)- and (R)-configured products. Thermodynamic analysis unveiled the subtle interaction between enzyme stability and evolvability, while computational studies provided insights into the origin of selectivity and substrate recognition. Preparative-scale synthesis of the (S)-product (73 % yield; >99 % ee) was performed on a gram-scale. This proof-of-principle study demonstrates that interfaced proline residues can be rationally engineered to unlock evolvability and thus provide access to new biocatalysts with highly improved catalytic performance.

17.
Mol Pain ; 17: 17448069211042117, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34505815

RESUMO

BACKGROUND: Pain is an unpleasant sensory experience that usually plays a protective role. Inflammatory pain is often severe and stubborn, which has a great impact on the quality of life of patients. However, there has been no breakthrough in the treatment strategy and mechanism of inflammatory pain. METHODS: This study investigated the analgesic effect of tetrahydropalmatine (THP) in rats injected with complete Freund's adjuvant (CFA)-induced inflammatory pain. Allodynia and gait analysis of rats were used to evaluate the analgesic effect at different time points before and after operation. THP (2.5, 5, and 10 mg/kg) was administered intraperitoneally once daily for 7 days post Day 3. The expression levels of TNF-α and IL-1ß in the spinal cord were measured by enzyme-linked immunosorbent assay. The activation of astrocytes and microglial cells in the spinal cord was tested by western blot before and after THP treatment. The apoptosis of glial cells was tested by flow cytometry after treatment with THP in the primary cultured glial cell model. RESULTS: CFA treatment induced significant allodynia and caused abnormal gait in rats. Administration of THP at 10 mg/kg significantly alleviated CFA-induced inflammatory pain behaviors. Moreover, CFA-induced activation of glial cells and the increased levels of TNF-α and IL-1ß were inhibited by THP administration. In addition, THP promotes apoptosis in primary cultured glial cells. This study suggests the possible clinical utility of THP in the treatment of inflammatory pain. CONCLUSION: THP plays an analgesic role by inhibiting the activation of glial cells and promoting apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Alcaloides de Berberina/farmacologia , Inflamação/tratamento farmacológico , Neuroglia/efeitos dos fármacos , Dor/tratamento farmacológico , Animais , Astrócitos/metabolismo , Modelos Animais de Doenças , Adjuvante de Freund/efeitos adversos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Masculino , Microglia/efeitos dos fármacos , Neuroglia/metabolismo , Dor/metabolismo , Ratos Sprague-Dawley , Medula Espinal/metabolismo
18.
J Environ Manage ; 299: 113624, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467867

RESUMO

Phytoremediation is one of the effective, economic and green approaches to cope with the increasing worldwide heavy metal (HM) pollution. Here, we evaluate the effects of functional carbon nanodots (FCNs) against the hyperaccumulation capacity as well as the physiological and genetic responses of water hyacinth under Pb2+ or/and Cd2+ stress. The bioaccumulation efficiency, HM content and transfer factor, biomass, root development, chlorophyll content, antioxidant system and genes expression are investigated at various concentration of HMs. Based on the excellent adsorption capacity and plant growth regulation ability, FCNs and nitrogen doped FCNs (N-FCNs) cooperate with water hyacinth to improve their HMs removal efficiencies. FCNs and N-FCNs immobilize excess HMs ions in plant, smartly regulate enzymatic levels to mitigate oxidative damage, as well as regulate the microelement uptake and related gene expression, thus improve plant tolerance against HMs stress. Although Pb and Cd have antagonistic effects on bioaccumulation of water hyacinth to the single metal, FCNs and N-FCNs can cooperate with water hyacinth to raise the removal efficiency of HMs in water, and enhance plant tolerance under Pb-Cd combined stress. The promotion effects of FCNs and N-FCNs on phytoremediation are more effective than conventional carbon nanomaterials, including carbon nanotubes and graphene oxides. These findings demonstrate that the application of FCNs or N-FCNs can improve the phytoremediation efficiency in the restoration of HMs contaminated water area. This study provides important insights into the possibility of using FCNs-based nanomaterials and water hyacinth as synergistic system for remediation of Cd-Pb contaminated water area.


Assuntos
Eichhornia , Metais Pesados , Nanotubos de Carbono , Poluentes do Solo , Biodegradação Ambiental , Cádmio/toxicidade , Chumbo , Metais Pesados/análise , Solo , Poluentes do Solo/análise
19.
Proc Natl Acad Sci U S A ; 118(33)2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34385316

RESUMO

The highly conserved multifunctional polymerase-associated factor 1 (Paf1) complex (PAF1C), composed of five core subunits Paf1, Leo1, Ctr9, Cdc73, and Rtf1, participates in all stages of transcription and is required for the Rad6/Bre1-mediated monoubiquitination of histone H2B (H2Bub). However, the molecular mechanisms underlying the contributions of the PAF1C subunits to H2Bub are not fully understood. Here, we report that Ctr9, acting as a hub, interacts with the carboxyl-terminal acidic tail of Rad6, which is required for PAF1C-induced stimulation of H2Bub. Importantly, we found that the Ras-like domain of Cdc73 has the potential to accelerate ubiquitin discharge from Rad6 and thus facilitates H2Bub, a process that might be conserved from yeast to humans. Moreover, we found that Rtf1 HMD stimulates H2Bub, probably through accelerating ubiquitin discharge from Rad6 alone or in cooperation with Cdc73 and Bre1, and that the Paf1/Leo1 heterodimer in PAF1C specifically recognizes the histone H3 tail of nucleosomal substrates, stimulating H2Bub. Collectively, our biochemical results indicate that intact PAF1C is required to efficiently stimulate Rad6/Bre1-mediated H2Bub.

20.
Int J Gen Med ; 14: 3989-3997, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349548

RESUMO

Objective: To explore whether current smoking could influence plaque characteristics and determine its correlation to the irregular surface and calcification of carotid plaque. Methods: Three hundred and seventeen patients with severe carotid atherosclerosis stenosis (SCAS) detected by color duplex flow imaging (CDFI) and confirmed by CT angiography (CTA) were recruited. The results of laboratory parameters were collected by using electronic database of the hospital. Computerized tomography (CT) scanning and high-resolution ultrasonography were performed for assessment of plaque morphology, respectively. Results: All enrolled smokers and non-smokers had no significant difference among all characteristics not related to smoking. CT scanning could efficiently identify the difference among enrolled smokers and non-smokers not only for the characteristics related to smoking but also the onsets of carotid plaque. Surface morphology was also efficiently detected by ultrasonography. Further ridge trace analysis showed that ultrasonography is efficient for diagnosis of calcified plaque compared with gold standard for plaque diagnosis. Further correlation analysis showed that ultrasonography parameters could offer reliable evidence for plaque scores, which was associated with age index. Ultrasonography parameters could efficiently differentiate plaque morphologies among enrolled smokers and never-smokers. Conclusion: Current smoking was positively associated with plaque calcification onsets, and smoking cessation could efficiently attenuate such injury. High-frequency ultrasound can clearly distinguish the details of calcification with promising clinical significance for current smoking patients.

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