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1.
Front Endocrinol (Lausanne) ; 12: 735824, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721294

RESUMO

Purpose: Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus (T2DM) patients. Methods: Embase, Medline, ClinicalTrials.gov, and Cochrane CENTRAL were searched for relevant trials. All data analyses were performed with STATA (12.0) and R language (3.6.0). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining data for the fracture effects of anti-diabetic drugs, including sodium-glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, meglitinides, α-glucosidase inhibitors, thiazolidinediones, biguanides, insulin, and sulfonylureas. Results: One hundred seventeen eligible randomized controlled trials (RCTs) with 221,364 participants were included in this study. Compared with placebo, trelagliptin (RR 3.51; 1.58-13.70) increased the risk of fracture, whereas albiglutide (RR 0.29; 0.04-0.93) and voglibose (RR 0.03; 0-0.11) decreased the risk of fracture. Other medications were comparable in terms of their effects on fracture risk, and no statistical significance was observed. In terms of fractures, voglibose (0.01%) may be the safest option, and trelagliptin (13.64%) may be the worst. Sensitivity analysis results were consistent with those of the main analysis. No statistically significant differences were observed in the regression coefficients of age (1.03; 0.32-2.1), follow-up duration (0.79; 0.27-1.64), and sex distribution (0.63; 0.15-1.56). Conclusions: We found varied results on the association between the use of anti-diabetic drugs and fracture risk. Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference. Other drugs were comparable in terms of their effects on fracture risk. Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, while others (such as dulaglutide, exenatide, liraglutide, semaglutide, lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show benefits. The risk of fracture was independent of age, sex distribution, and the duration of exposure to anti-diabetic drugs. When developing individualized treatment strategies, the clinical efficacy of anti-diabetic drugs must be weighed against their benefits and risks brought about by individual differences of patients. Systematic Review Registration: This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464).

2.
Ecotoxicol Environ Saf ; 228: 112993, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34808507

RESUMO

Acute exposure to cadmium (Cd) causes vacuolar degeneration in buffalo rat liver 3 A (BRL 3 A) cells. The present study aimed to determine the relationship between Cd-induced microtubule damage and intracellular vacuolar degeneration. Western blotting results showed that Cd damaged the microtubule network and downregulated the expression of microtubule-associated proteins-kinesin-1 heavy chain (KIF5B), γ-tubulin, and acetylated α-tubulin in BRL 3 A cells. Immunofluorescence staining revealed that Cd inhibited interactions between α-tubulin and microtubule-associated protein 4 (MAP4) as well as KIF5B. Increasing Cd concentrations decreased the levels of the lipid kinase, PIKfyve, which regulates the activity of endosome-lysosome fission. Immunofluorescence and transmission electron microscopy revealed vacuole-like organelles that were late endosomes and lysosomes. The PIKfyve inhibitor, YM201636, and the microtubule depolymerizer, nocodazole, aggravated Cd-induced endosome-lysosome enlargement. Knocking down the kif5b gene that encodes KIF5B intensified the enlargement of endosome-lysosomes and expression of early endosome antigen 1 (EEA1), Ras-related protein Rab-7a (RAB7), and lysosome-associated membrane glycoprotein 2 (LAMP2). Nocodazole, YM201636, and the knockdown of kif5b blocked autophagic flux. We concluded that Cd-induced damage to the microtubule network is the main reason for endosome-lysosome enlargement and autophagic flux blockage in BRL 3 A cells, and kinesin-1 plays a critical role in this process.

3.
Cancer Med ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34816622

RESUMO

BACKGROUND: Anal squamous cell carcinoma (ASCC) is a rare malignant tumor with increasing incidence. The goal of our study was to analyze the treatment outcome and prognostic factors of ASCC in South China in the past half-century. METHODS: This study retrospectively included 59 patients with ASCC admitted from 1975 to 2018 in Sun Yat-sen University cancer center. The clinical records and follow-up information of all patients were collected. Survival analysis and univariate and multivariate regression analyses were performed using the "survival" and "survminer" packages of R software. RESULTS: In 59 patients, 5 patients had distant metastasis at diagnosis. Among 54 M0 stage patients, 33 patients received chemoradiotherapy (CRT), 19 patients received local surgery, and 2 patients refused curative treatment and received the best supportive treatment (BST). The most common grade 3-4 acute toxicities during treatment were myelosuppression and radiation dermatitis. The median follow-up time was 32 months. For the whole group, the 3-year and 5-year overall survival (OS) rates and disease-free survival (DFS) were 71.1% and 63.6%, and 73.4% and 69.0%, respectively. Multivariate regression analysis showed that the T3-4 stage was an independent prognostic risk factor for OS, progression-free survival (PFS), and DFS. And M1 was an independent prognostic risk factor for PFS and DFS. Patients in stage M0 mainly treated with CRT had better local control than those mainly treated with surgery (p = 0.027). For M0 patients, induction chemotherapy combined with CRT tends to prolong OS compared with CRT alone (p = 0.26). The 3-year colostomy-free survival for the whole group was 81.1%. CONCLUSIONS: CRT is recommended as the first choice for the treatment of M0 stage ASCC. Induction chemotherapy may bring better survival benefits for some patients. Patients with ASCC in China seem to have a better local control rate, which suggested different treatment strategies may be needed in China.

4.
Int J Colorectal Dis ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34786597

RESUMO

PURPOSE: Rectal bleeding is a common symptom of colorectal cancer. In this paper, we describe and evaluate the operation of a central access and triage system for patients with rectal bleeding, which uses a "high-risk"/ "low-risk" designation based on the referring doctor's subjective designation and a 10-item symptom checklist. METHODS: A total of 1846 patients, referred between February 1, 2016, and December 31, 2018, were included. Exclusion criteria were the following: incorrect patient identification number, duplicate records, and pre-diagnosed gastrointestinal cancer. Data was obtained by chart review. Sensitivity, specificity, and positive and negative predictive values were calculated for each item on the symptom checklist. RESULTS: Eight hundred seventy-nine (48%) patients received endoscopy, and 37 (2%) were found to have cancer. Five hundred eighty-two (32%) patients were deemed high-risk. Twenty-nine (78%) of the patients with cancer were in the high-risk group. Patients in the high-risk group had a higher incidence of cancer (5.0% vs 0.6%, p < 0.001) and shorter waits to endoscopy (201 vs 292 days). Patients designated as high-risk by the referring physician had a relative risk of 22.3 compared to those designated as low-risk. Patients deemed high-risk by the symptom checklist had a relative risk of 3.5 compared to low-risk patients. CONCLUSION: Our system stratified 29/37 (78%) of the patients found to have cancer as high-risk. A total of 8/37 (22%) patients with cancer were deemed low-risk. Our research has identified two variables (weight loss and anemia) which have been added to our referral symptom checklist. This study helped us identify areas for refinement of our triage system. These findings are of interest to physicians who treat colorectal cancer.

5.
Environ Toxicol ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34773443

RESUMO

Colorectal cancer (CRC) is one of the prevalent types of human malignancies and ranks as the second leading cause of cancer-associated death worldwide. Dysregulated miRNAs have been promulgated as oncogenes or tumor-suppressive genes participating in the initiation and progression of CRC. A recent study reported that miR-346 was highly expressed in CRC patients. However, the biological role and underlying mechanism of miR-346 in CRC remain elusive. qRT-PCR and western blot assays were employed to detect miR-346 and LIM homeobox domain 6 (LHX6) expression in CRC cells. Cell proliferation was evaluated by CCK-8 and BrdU assays. Apoptosis was evaluated by TUNEL assay. The interaction between miR-346 and LHX6 was assessed by luciferase reporter assay. Results showed that miR-346 expression was increased and LHX6 expression was reduced in CRC cells. miR-346 knockdown and LHX6 overexpression inhibited proliferation and promoted apoptosis of CRC cells. Additionally, we found that miR-346 negatively regulated LHX6 expression in CRC cells by directly targeting LHX6. LHX6 knockdown partially attenuated anti-miR-346-induced proliferation reduction and apoptosis promotion in CRC cells. Furthermore, miR-346 knockdown inhibited the protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway in CRC cells by targeting LHX6. The present study indicated that miR-346 knockdown repressed cell growth in CRC cells by upregulating LHX6, and this was associated with inactivation of the Akt/mTOR pathway.

7.
J Appl Lab Med ; 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599588

RESUMO

BACKGROUND: Laboratory stewardship programs aim to improve the use of laboratory resources, including reducing inappropriate testing. These programs should engage all healthcare stakeholder groups, including all levels of laboratory staff. Medical laboratory technologists (MLTs) are highly skilled professionals and are well positioned to play a supportive role in stewardship but may be overlooked. The aim of this study is to identify the barriers to MLT participation in stewardship activities. METHODS: We developed and disseminated a self-administered survey to MLTs in Canada to assess their knowledge and attitudes toward inappropriate laboratory utilizatioz and explore perceived barriers to taking on an active role in stewardship initiatives. Themes were identified in open-ended responses and mapped to the Theoretical Domains Framework (TDF). RESULTS: MLTs feel accountable for helping ensure appropriate resource use and recognize that it is an important issue to address. However, they experience significant barriers and have low intention to act. The self-reported barrier most frequently described was lack of time arising from excessive workloads, but other constraints exist. Themes mapped to the TDF most strongly in the domain of environmental context and resources, supporting evidence that workplace structure and culture play key roles in impacting this group. CONCLUSIONS: To meaningfully engage MLTs in stewardship activities, these barriers should be addressed. Highlighting MLT expertise and creating communication structures and opportunities for their unique contributions may be fruitful.

8.
Vet Sci ; 8(10)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34679063

RESUMO

Bones play an important role in maintaining the level of calcium in blood. They provide support for soft tissues and hematopoiesis and undergo continuous renewal throughout life. In addition, vitamin D is involved in regulating bone and calcium homeostasis. Galectin-3 (Gal-3) is a ß-galactoside-binding protein that can regulate bone cell differentiation and function. Here, we aimed to study the regulatory effects of Gal-3 on vitamin-D-regulated osteoclastogenesis and bone resorption in chicken. Gal-3 expression in bone marrow stromal cells (BMSCs) from 18-day-old chicken embryos was inhibited or overexpressed. BMSCs were then co-cultured with bone marrow monocytes/macrophages (BMMs) with or without addition of 1α,25(OH)2D3. The results showed that 1α,25(OH)2D3 upregulated the expression of Gal-3 mRNA and receptor activator of nuclear-factor κB ligand (RANKL) expression in BMSCs and promoted osteoclastogenesis, as shown by the upregulated expression of osteoclast (OC) markers (CtsK, CAII, MMP-9, and TRAP) and increased bone resorption, a method for measuring the bone resorption area in vitro. Knockdown of Gal-3 by small-interfering RNA (siRNA) in BMSCs downregulated the expression of RANKL mRNA and attenuated the effects of 1α,25(OH)2D3 on osteoclastogenesis and bone resorption. Conversely, overexpression of Gal-3 in BMSCs enhanced the effects of osteoclastogenesis and bone resorption by increasing the expression of RANKL mRNA. These results demonstrated that Gal-3 mediates the differentiation and bone resorption of osteoclasts regulated by 1α,25(OH)2D3.

9.
Diabetol Metab Syndr ; 13(1): 119, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702362

RESUMO

BACKGROUND: Time in range (TIR) is advocated as key metric of glycemic control and is reported to be associated with microvascular complications of diabetes. Sudomotor dysfunction is among the earliest detectable diabetic peripheral neuropathy (DPN). We set about to research the relationship between TIR including overnight TIR and sudomotor function detected by SUDOSCAN with the intention of exploring the correlation of TIR including overnight TIR and early DPN in type 1 diabetes (T1D). METHODS: 95 patients with T1D were enrolled. TIR including nocturnal TIR of 3.9-10.0 mmol/L was evaluated with CGM. SUDOSCAN measured feet electrochemical skin conductance (FESC) and sudomotor dysfunction was defined as average FESC < 60µS. Logistic regressions were applied to examine the independent association of TIR and overnight TIR with sudomotor function. RESULTS: The overall prevalence of sudomotor dysfunction was 28.42%. Patients with sudomotor dysfunction had significantly lower TIR for the whole recorded phase and for nighttime. The sudomotor dysfunction prevalence progressively declined with the ascending tertiles of TIR and nocturnal TIR (P for trend < 0.05). Correlation analysis showed that the relationship between nocturnal TIR and FESC was stronger than that between TIR and FESC with correlation coefficients were respectively 0.362 and 0.356 (P < 0.001). Finally, logistic regression analysis indicated the independently negative relation between TIR and nocturnal TIR and sudomotor dysfunction (P < 0.05), and the correlation between nocturnal TIR and sudomotor dysfunction was more statistically significant. CONCLUSIONS: TIR is negatively correlated with sudomotor dysfunction in T1D independent of HbA1c. Furthermore, decreased nocturnal TIR is more closely related to the impaired function of sudomotor nerves in sweat glands.

10.
PeerJ ; 9: e12147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616615

RESUMO

Purpose: Breast cancer (BC) is characterized by concealed onset, delayed diagnosis, and high fatality rates making it particularly dangerous to patients' health. The purpose of this study was to use comprehensive bioinformatics analysis and experimental verification to find a new biomarker for BC diagnosis. Methods: We comprehensively analyzed microRNA (miRNA) and mRNA expression profiles from the Gene Expression Omnibus (GEO) and screened out differentially-expressed (DE) miRNAs and mRNAs. We used the miRNet website to predict potential DE-miRNA target genes. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID), we performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on overlapping potential target genes and DE-mRNAs. The protein-protein interaction (PPI) network was then established. The miRNA-mRNA regulatory network was constructed using Cytoscape and the analysis results were visualized. We verified the expression of the most up-regulated DE-miRNA using reverse transcription and a quantitative polymerase chain reaction in BC tissue. The diagnostic value of the most up-regulated DE-miRNA was further explored across three levels: plasma-derived exosomes, cells, and cell exosomes. Results: Our comprehensive bioinformatics analysis and experimental results showed that hsa-miR-21-5p was significantly up-regulated in BC tissue, cells, and exosomes. Our results also revealed that tumor-derived hsa-miR-21-5p could be packaged in exosomes and released into peripheral blood. Additionally, when evaluating the diagnostic value of plasma exosomal hsa-miR-21-5p, we found that it was significantly up-regulated in BC patients. Receiver operating characteristic (ROC) analysis also confirmed that hsa-miR-21-5p could effectively distinguish healthy people from BC patients. The sensitivity and specificity were 86.7% and 93.3%, respectively. Conclusion: This study's results showed that plasma exosomal hsa-miR-21-5p could be used as a biomarker for BC diagnosis.

11.
Appl Opt ; 60(25): 7834-7843, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613259

RESUMO

Spectral resolution is a key parameter of a spectrometer. Typically, the Rayleigh criterion is used to evaluate spectral resolution; however, it is not applicable to a single-lens-based spectrometer, as its principle is different from that using a prism or grating. Therefore, this work proposes that a method resolution is a key parameter to evaluate spectral resolution by exploiting the concept of focus depth. Accordingly, the spectral resolution is determined using three factors, namely, aperture factor F of the lens, pixel size p of the charge-coupled device, and the derivative of the rate of change of focal length with respect to wavelength f'(λ). The proposed method is verified by simulations with the following lens parameters: a diameter of 50.8 mm, focal length of 200 mm at 587.6 nm, and F=3.94. The calculated and simulated spectral resolution values are, respectively, 1.7 nm and 1.2 nm at 480 nm. Based on an analysis of the influences of F, p, and f'(λ) on the spectral resolution, increasing f'(λ) or decreasing both F and p might improve the spectral resolution. Finally, the proposed method is validated via experiments for lenses with different F values as well as materials, and we determine their spectral resolutions; these results are observed to be similar to the calculated values.

12.
Mol Med Rep ; 24(6)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34651663

RESUMO

Diffuse large B­cell lymphoma (DLBCL) is the most common type of non­Hodgkin lymphoma worldwide. Several studies have indicated that Homo sapiens (hsa)­microRNA (miR)­429 exerts a tumor­suppressive effect on a variety of malignant tumors. To the best of our knowledge, the molecular function and mechanism of action of hsa­miR­429 in DLBCL have not been evaluated to date. The present study demonstrated that the expression of hsa­miR­429 in DLBCL cells was significantly reduced. hsa­miR­429 inhibited the proliferation of the DLBCL cell lines, SUDHL­4 and DB, and promoted apoptosis. A dual luciferase reporter assay was used to demonstrate that chromobox 8 (CBX8) was the target gene of hsa­miR­429. Overexpression of CBX8 promoted the proliferation of SUDHL­4 and DB cells and inhibited apoptosis, thereby playing a cancer­promoting role. Transfection of hsa­miR­429 mimic into DB cells overexpressing CBX8 antagonized the effect of CBX8 on the proliferation of DB cells. Moreover, the apoptotic rate was increased in DB cells overexpressing CBX8 and transfected with hsa­miR­429 mimic, while the proportion of cells in the G2/M phase was significantly reduced. These results demonstrated the antagonistic effect of hsa­miR­429 on the oncogenic function of CBX8. Therefore, in DLBCL, the tumor suppressor effect of hsa­miR­429 may be achieved by targeted downregulation of CBX8, suggesting that hsa­miR­429 may be used as a diagnostic marker and a potential nucleic acid drug for DLBCL. CBX8 may also represent an effective therapeutic target for DLBCL.

13.
Ecotoxicol Environ Saf ; 227: 112895, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34673407

RESUMO

Cadmium is an environmental pollutant that threatens the health of both humans and animals. Current studies have shown that while hepatotoxic damage induced by cadmium is closely related to autophagy, its intrinsic mechanism has not been elucidated. MicroRNA plays a regulatory role on different stages of autophagy. In this study, we investigated the mechanisms by which microRNA-155 (miR-155) regulate cadmium-induced hepatotoxicity in rat hepatocytes (BRL 3A cells) and in vivo. We found that cadmium exposure could cause liver injury in rats, resulting in a decreased liver index, increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activity, hepatocyte steatosis, and ultrastructure damage. Cadmium exposure also induced autophagy in hepatocytes, resulting in increased expression of ATG5, Belin1, LC3II, and an increased number of autophagosomes. In addition, cadmium exposure upregulated miR-155 expression, downregulated Rheb mRNA expression, and downregulated the level of protein expression in the Rheb/mTOR signaling pathway in rat hepatocytes. The overexpression of miR-155 followed by cadmium exposure upregulated the level of autophagy in BRL3A cells, whereas miR-155 inhibition had the opposite effect. In addition, miR-155 negatively regulated Rheb. A dual-luciferase reporter assay verified the negative regulatory effect of miR-155 on Rheb targeting. Knockdown of Rheb downregulated cadmium-induced autophagy. Therefore, the Rheb/mTOR signaling can negatively regulate autophagy. The present study demonstrates that miR-155 promotes cadmium-induced autophagy in rat hepatocytes by suppressing Rheb expression.


Assuntos
Cádmio , MicroRNAs , Animais , Autofagia , Cádmio/toxicidade , Hepatócitos/metabolismo , MicroRNAs/genética , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Ratos , Transdução de Sinais
14.
Artigo em Inglês | MEDLINE | ID: mdl-34526300

RESUMO

BACKGROUND: Lung cancer, the most common cause of cancer-related death in adults, has not been well studied as a subsequent malignant neoplasm (SMN) in childhood cancer survivors. We assessed prevalence, risk factors, and outcomes for lung SMN in the Childhood Cancer Survivor Study (CCSS) cohort. METHODS: Among 25,654 5-year survivors diagnosed with childhood cancer (<21 years), lung cancer was self-reported and confirmed by pathology record review. Standardized incidence ratios (SIR) and cumulative incidences were calculated, comparing survivors to the general population, and hazard ratios (HR) were estimated using Cox regression for diagnosis and treatment exposures. RESULTS: Forty-two survivors developed a lung SMN [SIR, 4.0; 95% confidence interval (CI), 2.9-5.4] with a cumulative incidence of 0.16% at 30 years from diagnosis (95% CI, 0.09%-0.23%). In a treatment model, chest radiation doses of 10-30 Gy (HR, 3.4; 95% CI, 1.05-11.0), >30-40 Gy (HR, 4.6; 95% CI, 1.5-14.3), and >40 Gy (HR, 9.1; 95% CI, 3.1-27.0) were associated with lung SMN, with a monotone dose trend (P trend < 0.001). Survivors of Hodgkin lymphoma (SIR, 9.3; 95% CI, 6.2-13.4) and bone cancer (SIR, 4.4; 95% CI, 1.8-9.1) were at greatest risk for lung SMN. CONCLUSIONS: Survivors of childhood cancer are at increased risk for lung cancer compared with the general population. Greatest risk was observed among survivors who received chest radiotherapy or with primary diagnoses of Hodgkin lymphoma or bone cancer. IMPACT: This study describes the largest number of observed lung cancers in childhood cancer survivors and elucidates need for further study in this aging and growing population.

15.
Neurochirurgie ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34534565

RESUMO

BACKGROUND: The prognosis for patients with recurrent glioblastoma (GBM) is dismal, and the question of repeat surgery at time of recurrence is common. Re-operation in the management of these patients remains controversial, as there is no randomized evidence of benefit. An all-inclusive pragmatic care trial is needed to evaluate the role of repeat resection. METHODS: 3rGBM is a multicenter, pragmatic, prospective, parallel-group randomized care trial, with 1:1 allocation to repeat resection or standard care with no repeat resection. To test the hypothesis that repeat resection can improve overall survival by at least 3 months (from 6 to 9 months), 250 adult patients with prior resection of pathology-proven glioblastoma for whom the attending surgeon believes repeat resection may improve quality survival will be enrolled. A surrogate measure of quality of life, the number of days outside of hospital/nursing/palliative care facility, will also be compared. Centers are invited to participate without financial compensation and without contracts. Clinicians may apply to local authorities to approve an investigator-led in-house trial, using a common protocol, web-based randomization platform, and simple standardized case report forms. DISCUSSION: The 3rGBM trial is a modern transparent care research framework with no additional risks, tests, or visits other than what patients would encounter in normal care. The burden of proof remains on repeat surgical management of recurrent GBM, because this management has yet to be shown beneficial. The trial is designed to help patients and surgeons manage the uncertainty regarding optimal care. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT04838782.

16.
J Environ Manage ; 300: 113711, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34509812

RESUMO

The pilot-scale partial nitrification-anaerobic ammonia oxidation (PN-Anammox) process for landfill leachate treatment has been running stably for 2 years. The degradation characteristics of nitrogen removal performance of PN-Anammox in this system were discussed during shutdown, and different recovery strategies were analyzed from the perspective of economy and easy implementation. The results showed that during the 166 d dormancy period, the decrease in Anammox bacteria activity occurred earlier than that of Anammox bacteria, and both tended to slow down after 128 d. The recovery strategy of simulated wastewater was the fastest, followed by the pretreated landfill leachate recovery strategy with inoculation of some corresponding functional sludges, while the worst strategy was the direct pretreated landfill leachate recovery strategy. The recovery start-up of the pilot-scale PN-Anammox process further showed that microbial activities were difficult to recover simultaneously during operation using raw wastewater directly due to the presence of high NH4+-N levels and the coupling process, which easily led to the accumulation of NH4+-N or NO2-N, thereby inhibiting microbial activity. The addition of some functional bacteria was more conducive to the rapid recovery of microbial activity. This study provides a new strategy for the rapid recovery of microbial activity for the engineering application of the PN-Anammox process.


Assuntos
Nitrificação , Poluentes Químicos da Água , Reatores Biológicos , Desnitrificação , Nitrogênio , Oxirredução , Esgotos
17.
Front Neurol ; 12: 670567, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484095

RESUMO

Background: Motor progression varies even among those with a single diagnosis such as Parkinson's disease (PD) and little is known about the trajectory of motor signs prior to death. Understanding deterioration patterns may help clinicians counsel patients and proactively plan interdisciplinary care, including palliative care. The objective of this study was to examine and describe Unified Parkinson's Disease Rating Scale motor score (UPDRS-III) trajectories at the end of life in PD. Methods: A retrospective chart review was performed for deceased PD patients who attended the Parkinson and Movement Disorders Program at the University of Alberta for at least 5 years between 1999 and 2018. UPDRS-III scores were recorded for all visits. Trajectory patterns were visualized with Loess curves stratified by sex and age at diagnosis. Piecewise linear models were used to individually model the UPDRS-III scores, and the trajectories obtained were clustered based on their features. Results: Among the 202 charts reviewed, 84 meeting inclusion criteria were analyzed. The UPDRS-III increased over time regardless of sex and age. Distinct trajectory variations present in PD (e.g., Consistent Deterioration, Stability-Deterioration, Improvement-Deterioration, Deterioration-Improvement-Deterioration) were identified. Twenty-five percent of the patients were classified as Undetermined/Irregular trajectories. In addition, regardless of trajectory type, many patients experienced a steep increase in UPDRS-III approaching death. Those with disease diagnosis after age 65 years had a shorter survival time, compared to PD patients with a younger age of onset. Conclusion: Our study identified dominant types of motor trajectory in PD that can help clinicians understand their patients' course of illness. This information can help counsel patients regarding the variability in motor deterioration and should alert physicians to recognize a terminal decline. Age of disease onset was correlated with survival time.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34491667

RESUMO

BACKGROUND: The subtypes of chronic urticaria share a common clinical expression, but may show differences phenotypically. Meanwhile, two or more different subtypes of chronic urticaria can coexist in any given patient which may involve different phenotypes. AIMS: The study aims to compare the two phenotypes in terms of demographics, clinical profile and treatment response. METHODS: In this retrospective study, 2678 chronic urticaria patients were divided into the single subtype chronic urticaria group and mixed subtype chronic urticaria group as was appropriate.The differences in the clinical features, possible causes, urticaria activity score of seven days, dermatology life quality index score, laboratory investigations and response to treatments were evaluated among the two groups. RESULTS: An obvious female predominance was detected in chronic urticaria, especially in mixed subtype chronic urticaria patients. Of the 2678 chronic urticaria patients, there were 837(31.25%) mixed subtype chronic urticaria. Chronic spontaneous urticaria combined with symptomatic dermographism was the most common group in the mixed subtype chronic urticaria. Patients with mixed subtype chronic urticaria were more likely to have associated chest tightness/shortness of breath and showed greater urticaria activity. In patients with single subtype chronic urticaria, the positive rate of family history with allergic rhinitis, asthma or urticaria was lower. Based on evaluation of the treatment, control with second-generation antihistamines at licensed doses was achieved in only 38.83% of mixed subtype chronic urticaria patients, compared with 56.32% of patients with single subtype. LIMITATIONS: First, this study was a single-center design retrospective study. Second, omalizumab treatment was not included. Third, the differences between different subtypes of mixed subtype chronic urticaria were not discussed in detail. CONCLUSION: This study showed that mixed subtype chronic urticaria had some distinct features. Comprehensive knowledge about it may help us define effective therapeutic strategies and improve symptom control and the quality of life for chronic urticaria patients.

19.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3165-3170, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467709

RESUMO

Nucleic acid aptamers, broad-spectrum target-specific single-stranded oligonucleotides, serve as molecules in targeted therapy, targeted delivery and disease diagnosis for the treatment of tumor or microbial infection and clinical detection. Due to the existence of components in the use of traditional Chinese medicine(TCM), the target is difficult to concentrate and the specificity of treatment is poor. The effective components of TCM are toxic components, so a highly sensitive detection method is urgently needed to reduce the toxicity problem at the same time. The combined application of TCM and modern medical treatment strategy are difficult and cannot improve the therapeutic effect. Aptamers, advantageous in biosensors, aptamer-nanoparticles for targeted drug delivery, and aptamer-siRNA chimeras, are expected to connect Chinese medicinals with nanotechnology, diagnostic technology and combined therapies. We summarized the preparation, screening, and modification techniques of nucleic acid aptamers and the biomedical applications and advantages in therapy, targeting, and diagnosis, aiming at providing a reference for the in-depth research and development in TCM.


Assuntos
Aptâmeros de Nucleotídeos , Ácidos Nucleicos , Sistemas de Liberação de Medicamentos , Medicina Tradicional Chinesa , RNA Interferente Pequeno
20.
PLoS Pathog ; 17(9): e1009847, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34492084

RESUMO

Increasing evidence suggests that Kaposi's sarcoma (KS) arises from Kaposi's sarcoma-associated herpesvirus (KSHV)-infected mesenchymal stem cells (MSCs) through mesenchymal-to-endothelial transition (MEndT). KSHV infection promotes MSC differentiation of endothelial lineage and acquisition of tumorigeneic phenotypes. To understand how KSHV induces MEndT and transforms MSCs to KS cells, we investigated the mechanism underlying KSHV-mediated MSC endothelial lineage differentiation. Like embryonic stem cells, MSC differentiation and fate determination are under epigenetic control. Prospero homeobox 1 (PROX1) is a master regulator that controls lymphatic vessel development and endothelial differentiation. We found that the PROX1 gene in MSCs harbors a distinctive bivalent epigenetic signature consisting of both active marker H3K4me3 and repressive marker H3K27me3, which poises expression of the genes, allowing timely activation upon differentiation signals or environmental stimuli. KSHV infection effectively resolves the bivalent chromatin by decreasing H3K27me3 and increasing H3K4me3 to activate the PROX1 gene. vIL-6 signaling leads to the recruitment of MLL2 and SET1 complexes to the PROX1 promoter to increase H3K4me3, and the vGPCR-VEGF-A axis is responsible for removing PRC2 from the promoter to reduce H3K27me3. Therefore, through a dual signaling process, KSHV activates PROX1 gene expression and initiates MEndT, which renders MSC tumorigenic features including angiogenesis, invasion and migration.

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