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1.
Nat Commun ; 12(1): 907, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568645

RESUMO

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are two distinct autoimmune diseases that manifest with chronic synovial inflammation. Here, we show that CD4+ T cells from patients with RA and PsA have increased expression of the pore-forming calcium channel component ORAI3, thereby increasing the activity of the arachidonic acid-regulated calcium-selective (ARC) channel and making T cells sensitive to arachidonic acid. A similar increase does not occur in T cells from patients with systemic lupus erythematosus. Increased ORAI3 transcription in RA and PsA T cells is caused by reduced IKAROS expression, a transcriptional repressor of the ORAI3 promoter. Stimulation of the ARC channel with arachidonic acid induces not only a calcium influx, but also the phosphorylation of components of the T cell receptor signaling cascade. In a human synovium chimeric mouse model, silencing ORAI3 expression in adoptively transferred T cells from patients with RA attenuates tissue inflammation, while adoptive transfer of T cells from healthy individuals with reduced expression of IKAROS induces synovitis. We propose that increased ARC activity due to reduced IKAROS expression makes T cells more responsive and contributes to chronic inflammation in RA and PsA.

2.
Ann Palliat Med ; 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33548999

RESUMO

BACKGROUND: Nowadays, controlling nutritional status (CONUT) has been used as a prognostic factor in variety of cancers. However, no consensus has been reached on the prognostic value of CONUT in lung cancer. In this study, we aim to investigate the role of CONUT in survival of patients with lung cancer. METHODS: EMBASE, web of science, and Medline were used to search articles in English-language journals. The association between CONUT score and survival of patients with lung cancer was evaluated by using pooled HRs and their 95% CIs. Chi-square test and I-Square was used to test heterogeneity among studies. Analyses were all performed using Stata 13.0 (Stata Corporation, College Station, TX). RESULTS: Eight studies with 1,836 patients were eventually included in this meta-analysis. The pooled results showed that high CONUT score had an unfavorable impact on OS (HR =1.63, 95% CI: 1.30-2.04), DFS (HR =1.75, 95% CI: 1.35-2.26), CSS (HR =1.45, 95% CI: 1.01-2.07) and PFS (HR =1.67, 95% CI: 0.99-2.35), compared with those with low-CONUT. CONCLUSIONS: CONUT can be used as a predictor of prognosis in patients with lung cancer. HighCONUT score was significantly associated with poor OS, DFS, CSS and PFS.

3.
Nat Commun ; 12(1): 902, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568671

RESUMO

We previously found that B and AGL6 proteins form L (OAP3-2/OAGL6-2/OPI) and SP (OAP3-1/OAGL6-1/OPI) complexes to determine lip/sepal/petal identities in orchids. Here, we show that the functional L' (OAP3-1/OAGL6-2/OPI) and SP' (OAP3-2/OAGL6-1/OPI) complexes likely exist and AP3/PI/AGL6 genes have acquired additional functions during evolution. We demonstrate that the presumed L' complex changes the structure of the lower lateral sepals and helps the lips fit properly in the center of the flower. In addition, we find that OAP3-1/OAGL6-1/OPI in SP along with presumed SP' complexes regulate anthocyanin accumulation and pigmentation, whereas presumed L' along with OAP3-2/OAGL6-2/OPI in L complexes promotes red spot formation in the perianth. Furthermore, the B functional proteins OAP3-1/OPI and OAGL6-1 in the SP complex could function separately to suppress sepal/petal senescence and promote pedicel abscission, respectively. These findings expand the current knowledge behind the multifunctional evolution of the B and AGL6 genes in plants.

4.
Innate Immun ; 27(2): 201-209, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33576722

RESUMO

Increasing evidence indicates that signal transducer and activator of transcription 3 (STAT3), a vital transcription factor, plays crucial roles in the regulation of inflammation. STAT3 has become a novel therapeutic target for intervention in inflammation-related disorders. However, it remains unclear whether STAT3 plays a part in acute hepatic damage. To investigate the effects of STAT3 here, LPS/d-GalN-induced hepatic damage was induced in mice, the STAT3 inhibitor Stattic was administered, and the degree of liver injury, inflammation, and hepatocyte apoptosis were investigated. The results showed that Stattic mitigated the hepatic morphologic abnormalities and decreased the level of aminotransferase in LPS/D-GalN-insulted mice. The results also indicated that Stattic decreased the levels of TNF-α and IL-6, prevented the activation of the caspase cascade, suppressed cleavage of PARP, and decreased the quantity of TUNEL-positive cells. These results suggest that Stattic provided protective benefits in LPS/d-GalN-induced hepatic damage, and the protective effects might be associated with its anti-inflammatory and anti-apoptotic effects. Therefore, STAT3 might become a novel target for intervening in inflammation-based and apoptosis-based hepatic disorders.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33540113

RESUMO

OBJECTIVES: To investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia. METHODS: This retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed. RESULTS: In total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37-0.92; model 2: aOR 0.37, 95% CI 0.21-0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2. CONCLUSIONS: Adjunctive nebulized colistin was associated with lower day 14 clinical failure rate, but not lower 14-day mortality rate, in critically ill patients with nosocomial pneumonia caused by colistin-susceptible CR-GNB.

6.
J Med Internet Res ; 23(2): e19651, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591282

RESUMO

BACKGROUND: Violence against doctors in China is a serious problem that has attracted attention from both domestic and international media. OBJECTIVE: This study investigates readers' responses to media reports on violence against doctors to identify attitudes toward perpetrators and physicians and examine if such trends are influenced by national policies. METHODS: We searched 17 Chinese violence against doctors reports in international media sources from 2011 to 2020. We then tracked back the original reports and web crawled the 19,220 comments in China. To ascertain the possible turning point of public opinion, we searched violence against doctors-related policies from Tsinghua University ipolicy database from 2011 to 2020, and found 19 policies enacted by the Chinese central government aimed at alleviating the intense patient-physician relationship. We then conducted a series of interrupted time series analyses to examine the influence of these policies on public sentiment toward violence against doctors over time. RESULTS: The interrupted time series analysis (ITSA) showed that the change in public sentiment toward violence against doctors reports was temporally associated with government interventions. The declarations of 10 of the public policies were followed by increases in the proportion of online public opinion in support of doctors (average slope changes of 0.010, P<.05). A decline in the proportion of online public opinion that blamed doctors (average level change of -0.784, P<.05) followed the declaration of 3 policies. CONCLUSIONS: The government's administrative interventions effectively shaped public opinion but only temporarily. Continued public policy interventions are needed to sustain the reduction of hostility toward medical doctors.

7.
Cells ; 10(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572403

RESUMO

Septins are GTP-binding proteins that form heteromeric filaments for proper cell growth and migration. Among the septins, septin7 (SEPT7) is an important component of all septin filaments. Here we show that protein kinase A (PKA) phosphorylates SEPT7 at Thr197, thus disrupting septin filament dynamics and ciliogenesis. The Thr197 residue of SEPT7, a PKA phosphorylating site, was conserved among different species. Treatment with cAMP or overexpression of PKA catalytic subunit (PKACA2) induced SEPT7 phosphorylation, followed by disruption of septin filament formation. Constitutive phosphorylation of SEPT7 at Thr197 reduced SEPT7‒SEPT7 interaction, but did not affect SEPT7‒SEPT6‒SEPT2 or SEPT4 interaction. Moreover, we noted that SEPT7 interacted with PKACA2 via its GTP-binding domain. Furthermore, PKA-mediated SEPT7 phosphorylation disrupted primary cilia formation. Thus, our data uncover the novel biological function of SEPT7 phosphorylation in septin filament polymerization and primary cilia formation.

8.
Nat Chem Biol ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558715

RESUMO

Intensiometric genetically encoded biosensors, based on allosteric modulation of the fluorescence of a single fluorescent protein, are powerful tools for enabling imaging of neural activities and other cellular biochemical events. The archetypical example of such biosensors is the GCaMP series of Ca2+ biosensors, which have been steadily improved over the past two decades and are now indispensable tools for neuroscience. However, no other biosensors have reached levels of performance, or had revolutionary impacts within specific disciplines, comparable to that of the Ca2+ biosensors. Of the many reasons why this has been the case, a critical one has been a general black-box view of biosensor structure and mechanism. With this Perspective, we aim to summarize what is known about biosensor structure and mechanisms and, based on this foundation, provide guidelines to accelerate the development of a broader range of biosensors with performance comparable to that of the GCaMP series.

9.
Neurochem Res ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33550530

RESUMO

Paclitaxel is a common chemotherapeutic agent in cancer treatment, while it often causes chemotherapy-induced peripheral neuropathy (CIPN), which manifested as hyperalgesia and allodynia, and its mechanism remains largely unknown. The previous study has shown that matrix metalloproteinase-2 (MMP-2) plays a pivotal role in spinal nerve ligation (SNL) induced neuropathic pain, but its function in CIPN and exact molecular mechanisms underlying upregulation is not explored. Our present study revealed that MMP-2 is also upregulated in paclitaxel induced neuropathic pain (NP), and knockdown it by siRNA can ameliorate mechanical allodynia. Since DNA methylation is closely related to gene transcription, we explored the methylation status of the MMP-2 gene and demonstrated that MMP-2 upregulation is related to the reduced methylation level of its promoter. DNA methylation is mediated by DNA methyltransferases (DNMTs), and previous studies suggested that three main types of DNMTs can undergo SUMOylation. Our next study revealed that SUMO1 modification of DNMT3b is significantly enhanced. Intrathecal administration of SUMOylation inhibitor, ginkgolic acid (GA), could reverse enhanced SUMO1 modification of DNMT3b and upregulation of MMP-2 in the model rats. Further investigation suggested that DNMT3b binding activity to the promoter region of the MMP-2 gene is significantly decreased in paclitaxel treated rats, and the administration of GA can reverse these effects, which is also accompanied by changes in the promoter methylation status of the MMP-2 gene. Our study demonstrates that MMP-2 up-regulation mediated by DNMT3b SUMOylation is essential for paclitaxel induced NP development, which brings us new therapeutic options for CIPN.

11.
J Mol Neurosci ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33403595

RESUMO

The association of apolipoprotein AIV (APOA4) with depression or plasma levels of lipids and glucose has been inconsistently reported. However, interplays between APOA4 and depression on the levels have not been explored yet. The present study aimed to investigate plasma levels of APOA4, lipids, and glucose in adolescents with different genotypes of APOA4 rs5104 and with or without depression. Depressive symptoms were assessed in 631 adolescents by Beck Depression Inventory (BDI). A total score of 14 was defined as the cutoff point for depression. Plasma levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glucose, and insulin were measured by routine methods, and APOA4 by enzyme-linked immunosorbent assays. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analyses and verified by DNA sequencing. Female adolescents had higher prevalence of depression than male subjects only in G allele carriers (p = 0.015), but not in AA homozygotes. Risk factors of depression and predictors of depression severity were different between G allele carriers and AA homozygotes. Lower levels of glucose (p = 0.003) were observed in male G allele carriers than those in male AA homozygotes and increased TG levels (p = 0.008) in female G allele carriers when compared with those in female AA homozygotes. When both APOA4 rs5104 and depression were taken into account, subjects with depression had higher levels of plasma APOA4 than adolescents without depression only in female G allele carriers (p = 0.043), but no significant changes of plasma lipids and glucose. Depression augments plasma APOA4 levels without changes of plasma lipids and glucose in female adolescents carrying G allele of APOA4 rs5104. These results may provide a novel explanation for the inconsistent relationship between depression, APOA4, and plasma levels of lipids and glucose in the literature.

12.
Sci Rep ; 11(1): 1078, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441798

RESUMO

Sleep quality is important to health and life quality. Lack of sleep can lead to a variety of health issues and reduce in daytime function. Recent study by Fultz et al. also indicated that sleep is crucial to brain metabolism. Delta power in sleep EEG often indicates good sleep quality while alpha power usually indicates sleep interruptions and poor sleep quality. Essential oil has been speculated to improve sleep quality. Previous studies also suggest essential oil aroma may affect human brain activity when applied awake. However, those studies were often not blinded, which makes the effectiveness and mechanism of aroma a heavily debated topic. In this study, we aim to explore the effect of essential oil aroma on human sleep quality and sleep EEG in a single-blinded setup. The aroma was released when the participants are asleep, which kept the influence of psychological expectation to the minimum. We recruited nine young, healthy participants with regular lifestyle and no sleep problem. All participants reported better sleep quality and more daytime vigorous after exposing to lavender aroma in sleep. We also observed that upon lavender aroma releases, alpha wave in wake stage was reduced while delta wave in slow-wave sleep (SWS) was increased. Lastly, we found that lavender oil promote occurrence of SWS. Overall, our study results show that essential oil aroma can be used to promote both subjective and objective sleep quality in healthy human subjects. This makes aroma intervention a potential solution for poor sleep quality and insomnia.

13.
Acta Radiol ; : 284185120980001, 2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33455413

RESUMO

BACKGROUND: Fibular flaps have been widely used for mandibular and maxillary reconstructions. On occasion, anatomical variants of fibular arteries (FA) will be encountered. PURPOSE: Although anatomical variants of FA during fibular harvest have been reported, controversy exists regarding whether simple color Doppler ultrasonography (CDU) and physical examinations (PE) are sufficient for early preoperative detection. MATERIAL AND METHODS: A 10-year retrospective analysis in our department was performed to find the patients with various FA anomalies confirmed by computed tomography angiography (CTA) or intraoperative findings. RESULTS: A total number of 19 FA anomalies were found either pre- or intraoperatively in 16 patients, in whom three cases were with bilateral FA variants. Type IIIC variants, also called arteria peronea magna (great peroneal artery), were confirmed in two legs, while the majority (13 legs) had type IIIA hypoplastic/aplastic posterior tibialis arteries (PTA). Four legs had new type IIID (low FA and PTA bifurcations). Preoperative CDU and PE only suspected anomalies in two legs. Six cases proceeded with using the affected fibulas, within whom vascular grafts were used in half of them for lengthening the FA pedicle. Local ischemia, partial soleus muscle necrosis, and claudication were reported in one. CONCLUSIONS: Routine CTA before every fibular harvest, rather than simple PE and CDU, should be added for screening contraindications and ensuring safety for fibular flap harvest.

14.
Pharmacology ; : 1-12, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33486482

RESUMO

INTRODUCTION: Although oxidative stress has been demonstrated to mediate acute ethanol-induced changes in autophagy in the heart, the precise mechanism behind redox regulation in acute ethanol heart disease remains largely unknown. METHODS: Wild-type C57BL/6 mice were intraperitoneally injected with ethanol (3 g/kg/day) for 3 consecutive days. The effects of ethanol on cultured primary cardiomyocytes and H9c2 myoblasts were also studied in vitro. Levels of autophagic flux, cardiac apoptosis and function, reactive oxygen species (ROS) accumulation, NOX4, and NOX2 were examined. The NOX4 gene was knocked down with NOX4 siRNA. RESULTS: In this study, we demonstrated that schisandrin B inhibited acute ethanol-induced autophagy and sequent apoptosis. In addition, schisandrin B treatment improved cardiac function in ethanol-treated mice. Furthermore, NOX4 protein expression was increased during acute ethanol exposure, and the upregulation of NOX4 was significantly inhibited by schisandrin B treatment. The knockdown of NOX4 prevented ROS accumulation, cell autophagy, and apoptosis. CONCLUSION: These results highlight that NOX4 is a critical mediator of ROS and elaborate the role of the NOX4/ROS axis in the effect of schisandrin B on autophagy and autophagy-mediated apoptosis in acute ethanol exposure, which suggests a therapeutic strategy for acute alcoholic cardiomyopathy.

15.
Can J Gastroenterol Hepatol ; 2021: 6692511, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33489994

RESUMO

Background: Some autoimmune hepatitis (AIH) patients have elevated serum IgG4 levels, and the clinical characteristics of such patients are currently incompletely characterized. Aim: To analyze the clinical features and possible pathogenesis of AIH with elevated serum IgG4 levels. Methods: According to their serum IgG4 value, patients were divided into elevated IgG4 (IgG4 > 1.35 g/l) and normal IgG4 (IgG4 ≤ 1.35 g/l) groups. Results: Among the 152 patients included in this study, those in the elevated IgG4 group had the following characteristics: older onset age (56 ± 11.43 years vs. 49.49 ± 13.04 years, P=0.005), higher proportion of males (34.15% vs. 12.61%, P=0.002), higher prevalence of cirrhosis (56.10% vs. 36.04%, P=0.026), lower prevalence of extrahepatic autoimmune diseases (9.76% vs. 27.3%, P=0.023), and higher levels of IL-17 and IL-22 (P < 0.05). Logistic regression analysis results showed that elevated serum IgG4 levels and male sex were risk factors for AIH cirrhosis (male: odds ratio (OR) = 4.293, 95% confidence interval (CI): 1.592-11.575, P=0.004; and elevated serum IgG4: OR = 2.566, 95% CI: 1.065-6.187, P=0.036). No significant differences were found for the remission rate within 6 months between the two groups (69.70% vs. 76.14%, P=0.470). Conclusion: The male proportion and cirrhosis prevalence were higher in AIH with elevated serum IgG4 levels at the time of diagnosis. Male sex and elevated serum IgG4 levels are independent risk factors for AIH cirrhosis, and TH17 cells are more likely involved in the pathogenesis of this type of AIH.

16.
Eur J Hosp Pharm ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414258

RESUMO

BACKGROUND: There is a significant correlation between augmented renal clearance (ARC) and lower serum trough concentrations of vancomycin (VCM) during therapy. There is a need to evaluate the predictive performance of the population pharmacokinetic (PPK) model used for individual calculation of dosage regimens in ARC patients. OBJECTIVE: Our study aimed to estimate the predictive performance differences of the reported VCM PPK software JPKD-vancomycin and SmartDose in patients with varying renal function status, especially those with ARC. METHODS: Patients receiving VCM treatment from May 2014 to December 2019 were enrolled, and divided into the ARC group, the normal renal function (NRF) group, and the impaired renal function (IRF) group. VCM dosage, trough concentration, area under the curve (AUC) and pharmacokinetic parameters were compared among the three groups. The predictive performance of PPK software was expressed using absolute prediction error (APE), sensitivity, specificity, and regression coefficient (r2) of linear regression analysis between the measured VCM trough concentration and the predicted trough concentration. RESULTS: A total of 388 patients were included: 86 patients in the ARC group, 241 patients in the NRF group, and 61 patients in the IRF group. The daily dose of the adjusted regimen in the ARC group was higher than in the NRF group, but the trough concentration was significantly lower than in the NRF group (2.8±0.6 g vs 1.9±0.6 g, p<0.001; 10.5±5.1 mg/L vs 12.9±6.8 mg/L, p=0.030). The percentage of trough concentrations lower than 10 mg/L was 84.9% in the ARC group. Compared with the APE of the initial dosage regimen, the APE of the adjusted regimen calculated by JPKD was lower in the ARC group (p=0.041) and the NRF group (p<0.001). Specificity of JPKD and SmartDose in the ARC group was higher than in the NRF group (p<0.001; p<0.001). According to the linear regression analysis, the coefficients of determination (r2) were all >0.6 for the initial regimen and adjusted regimen of VCM in the ARC and NRF groups, and the r2 of the adjusted regimen of JPKD was >0.8 in the ARC and NRF groups. In the IRF group, 31.1% of patients had a change in serum creatinine (Scr) level of >50%. The r2 increased from 0.527 to 0.7347 in SmartDose and from 0.55 to 0.7802 in JPKD when using Scr at the sampling time. The ARC group showed a significant decrease in AUC (p<0.001) and an increase in clearance rate (p<0.001) when compared to the NRF group. CONCLUSION: ARC was significantly associated with subtherapeutic serum VCM concentration. The pharmacokinetic parameters of VCM were diverse in patients with different renal function status. The PPK model JPKD and SmartDose had a good predictive performance for predicting VCM trough concentrations of the ARC and NRF patients, especially using JPKD for prediction of the adjusted regimen. The change of Scr is a main factor affecting the accuracy of software prediction.

17.
New Phytol ; 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33421144

RESUMO

The bipolar spindle structure in meiosis is essential for faithful chromosome segregation. PUTATIVE RECOMBINATION INITIATION DEFECT 1 (PRD1) previously has been shown to participate in the formation of DNA double strand breaks (DSBs). However, the role of PRD1 in meiotic spindle assembly has not been elucidated. Here, we reveal by both genetic analysis and immunostaining technology that PRD1 is involved in spindle assembly in rice (Oryza sativa) meiosis. We show that DSB formation and bipolar spindle assembly are disturbed in prd1 meiocytes. PRD1 signals display a dynamic pattern of localization from covering entire chromosomes at leptotene to congregating at the centromere region after leptotene. Centromeric localization of PRD1 signals depends on the organization of leptotene chromosomes, but not on DSB formation and axis establishment. PRD1 exhibits interaction and co-localization with several kinetochore components. We also find that bi-orientation of sister kinetochores within a univalent induced by mutation of REC8 can restore bipolarity in prd1. Furthermore, PRD1 directly interacts with REC8 and SGO1, suggesting that PRD1 may play a role in regulating the orientation of sister kinetochores. Taken together, we speculate that PRD1 promotes bipolar spindle assembly, presumably by modulating the orientation of sister kinetochores in rice meiosis.

18.
Medicine (Baltimore) ; 100(2): e23881, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466131

RESUMO

BACKGROUND: In recent years, intra articular injection of platelet rich plasma has attracted increasing attention. The major aim of our current randomized controlled double-blind study was to compare long-term outcomes of intra-articular injection of hyaluronic acid or platelet rich plasma in the treatment of the patients with knee osteoarthritis. METHODS: This is a kind of double-blind, randomized, prospective, and comparative clinical investigation with the allocation ratio of 1:1 and was approved by our institutional review Committee. Between 2020 and 2021, altogether 2 hundred patients will be selected to participate in our present study. We will report the randomized experiments in accordance with the guidelines of Consolidated Standards of Reporting Trials and then offer the Consolidated Standards of Reporting Trials flow chart. The inclusion criteria were: patients aged from 40 to 70 years old, patients with chief complaint history of at least 1 month and knee joint pain for nearly 6 months, need the analgesic drug treatment, and radiology confirmed knee osteoarthritis. The eligible patients would be randomly divided into 2 groups through applying the random numbers generated by computer before surgery. Outcomes after treatment were assessed using the Western Ontario and McMaster University and the scoring systems of visual analogue scale which were recorded through questionnaires accomplished via the patients prior to the first injection and then at three and six months, 1 and 2 years follow-up. Any adverse events occurred within 1 year after surgery were recorded during follow-up. RESULTS: This should suggest whether biological methods can offer more lasting outcomes than the viscosification. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry6265).


Assuntos
Ácido Hialurônico/uso terapêutico , Osteoartrite do Joelho/terapia , Plasma Rico em Plaquetas , Viscossuplementos/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Amplitude de Movimento Articular , Viscossuplementos/administração & dosagem
19.
J Hematol Oncol ; 14(1): 18, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461583

RESUMO

Accurate interpretation of BRCA1/2 variants is critical for risk assessment and precise treatment of breast cancer (BC). Hence, the establishment of an ethnicity-based BRCA1/2 variant database of the Chinese population is of paramount importance. In this study, panel-based sequencing served to detect BRCA1/2 variants in a Chinese multicenter cohort of 21,216 BC patients and 6434 healthy controls. Overall, the percentage of subjects carrying pathogenic variants was 5.5% (1174/21,216) in BC patients and 1.1% (71/6434) in healthy controls. We identified 13 pathogenic variants as high-frequency variants that had a frequency of > 0.45‰ in BC patients (≥ 10 in 21,216 patients), none of which has been reported in Caucasians. Pathogenic BRCA1/2 variants correlated with younger onset age, higher frequencies of bilateral and triple-negative BC (TNBC), invasive carcinomas, high histological grades, and family history of BC and other cancers. Furthermore, the percentage of the subjects carrying VUS was 9.8% (2071/21,216) in BC patients and 6.9% (446/6434) in healthy controls. Based on our cohort study, we unambiguously reclassified 7 out of the 858 VUS resulting in lower VUS ratio in patients (from 9.8 to 7.9%) as well as in healthy control (from 6.9 to 5.3%). We also re-analyzed the 100 variants in 13 exons (2-5 and 15-23) of the BRCA1 genes using a functional assay (saturation genome editing; SGE). 55 of the 59 VUS had distinct status in the SGE study: 24 (43.6%) were pathogenic, and 31 (56.4%) were benign. Strong ethnicity-specific occurrences of pathogenic BRCA1/2 variants were identified in the Chinese population. Hence, the findings provide rationale and sequencing information for the implementation of BRCA1/2 variants tailored to the Chinese population into clinical risk assessment.

20.
PLoS One ; 16(1): e0245968, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33493204

RESUMO

BACKGROUND: Tympanic membrane (TM) perforation is quite common in the clinical setting. Chronic TM perforations require surgical treatments such as myringoplasty. Currently, platelet-rich plasma (PRP) is a novel, effective substance that is increasingly utilized for TM perforation repair. This study aims to evaluate the effectiveness of PRP in the application of TM perforation repair. METHODS: A systematic search was conducted to screen the Medline, Embase, Cochrane, Scopus and Web of Science databases up to July 2020. Studies were identified in accordance with the selection criteria by two coauthors independently. Data regarding the healing and hearing outcomes were pooled and analyzed via Review Manager version 5.3 and STATA version 12.0 software. Odds ratio (OR) was utilized to compare the closure rate. Furthermore, the results of hearing improvements and incidence of complications were also compared to evaluate the effectiveness of PRP. RESULTS: A total of eight studies with 455 participants were eligible according to the selection criteria. Compared to conventional surgery, the OR of closure was 2.70 (95% CI: 1.27 to 5.76, P = 0.01, I2 = 0%) in randomized controlled trial (RCT) subgroup and 6.18 (95% CI: 2.22 to 17.25, P = 0.0005, I2 = 0) in non-RCT subgroup. The overall OR of closure was 3.69 (95% CI: 2.02 to 6.74, P<0.0001, I2 = 0%), suggesting a significant effect on the healing of TM perforation. Between preoperative and postoperative hearing results, there is no statistical difference between the PRP and the control groups. Additionally, the use of PRP resulted in a lower incidence of complication than the use of conventional approaches. CONCLUSION: The application of PRP during the TM surgeries can enhance the closure rate, provide similar hearing improvements and decrease the incidence of postoperative complications. Given these advantages, PRP can be considered an effective treatment for TM regeneration.

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