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1.
Front Cardiovasc Med ; 9: 849027, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498031

RESUMO

Background: Varicose veins are found to be associated with increased risk of venous thromboembolism (VTE) in many observational studies, but whether varicose veins are causally associated with VTE remains unclear. Therefore, we used a series of Mendelian randomization (MR) methods to investigate that association. Methods: 23 independent single-nucleotide polymorphisms (SNPs) for varicose veins were obtained from the Pan UK Biobank analysis. The outcomes datasets for deep vein thrombosis (DVT), pulmonary embolism (PE) and venous thromboembolism (VTE) were obtained from the FinnGen study. Before analysis, body mass index (BMI) and height were included as confounders in our MR model. Basic MR [inverse-variance weighted (IVW), weight-median, penalized weighted-median and MR-Egger methods] and MR-PRESSO were performed against each outcome using the whole SNPs and SNPs after excluding those associated with confounders. If causal associations were suggested for any outcome, a basic MR validation analysis, a multivariable MR analysis with BMI and height, a Causal Analysis Using Summary Effect estimates (CAUSE), and a two-step MR analysis with BMI and height, would follow. Results: Using 21 qualified SNPs, the IVW method (OR: 1.173, 95% CI: 1.070-1.286, p < 0.001, FDR = 0.002), the weighted median method (OR: 1.255, 95% CI: 1.106-1.423, p < 0.001, FDR = 0.001), the penalized weighted median method (OR: 1.299, 95% CI: 1.128-1.495, p < 0.001, FDR = 0.001) and the MR-PRESSO (OR: 1.165, 95% CI: 1.067-1.273, p = 0.003, FDR = 0.009) suggested potential causal effect of varicose veins on DVT, but no cause effect was found for PE and VTE. Excluding SNPs associated with confounders yielded similar results. The causal association with DVT was validated using a self-reported DVT cohort (IVW, OR: 1.107, 95% CI: 1.041-1.178, p = 0.001). The causal association maintained after adjustment for height (OR = 1.105, 95% CI: 1.028-1.188, p = 0.007), BMI (OR = 1.148, 95% CI: 1.059-1.244, p < 0.001) and them both (OR = 1.104, 95% CI: 1.035-1.177, p = 0.003). The causal association also survived the strict CAUSE (p = 0.018). Finally, in two-step MR, height and BMI were found to have causal effects on both varicose veins and DVT. Conclusion: Genetically predicted varicose veins may have a causal effect on DVT and may be one of the mediators of obesity and taller height that predispose to DVT.

2.
Front Oncol ; 12: 881910, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35515126

RESUMO

This work was developed to the effects of biofilm composite nano-drug delivery system (OMVs-MSN-5-FU) on lymph node metastasis from oral squamous cell carcinoma. Mesoporous silica nanoparticles loaded with 5-FU (MSN-5-FU) were prepared first. Subsequently, the outer membrane vesicles (OMV) of Escherichia coli were collected to wrap MSN-5-FU, and then OMVs-MSN-5-FU was prepared. It was then immersed in artificial gastric juice and artificial intestinal juice to explore the drug release rate. Next, the effects of different concentrations of the nano-drug delivery systems on the proliferation activity of oral squamous carcinoma cell line KOSC-2 cl3-43 were analyzed. Tumor-bearing nude mice models were prepared by injecting human tongue squamous cell carcinoma cells Tca8113 into BALB/c-nu nude mice. They were injected with the OMVs-MSN-5-FU nano drug carrier system, and peri-carcinoma tissue and cervical lymph node tissue were harvested to observe morphological changes by Hematoxylin - eosin (HE) staining. The scanning electron microscope (SEM) results showed that all MSN, MSN-5-FU, OMV, and OMV-MSN-5-FU were spherical and uniformly distributed, with particle sizes of about 60nm, 80nm, 90nm, and 140nm, respectively. Among them, OMV had a directional core-shell structure. The cumulative drug release rates of artificial gastric juice in 48 hours were 61.2 ± 2.3% and 26.5 ± 3.1%, respectively. The 48 hours cumulative drug release rates of artificial intestinal juice were 70.5 ± 6.3% and 32.1 ± 3.8%, respectively. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. After injection of OMVS-MSN-5-FU, the number of cancer cells was significantly reduced and cervical lymph node metastasis was significantly controlled. HE staining results showed that OMVS-MSN-5-FU injection reduced the number of stained cells. Dense lymphocytes were clearly observed in the cortex of neck lymphocytes. The OMVs-MSN-5-FU drug delivery system can slow down the drug release rate, significantly inhibit the proliferation activity of oral squamous cancer cells, and control the metastasis of cancer cells to cervical lymph nodes.

3.
Front Endocrinol (Lausanne) ; 13: 854875, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574013

RESUMO

Background and Aims: Glycated hemoglobin (HbA1c) associates with the risk of arterial stiffness, and such association can be found between fasting blood glucose (FBG), postprandial blood glucose (PBG), triglyceride-glucose index (TyG index), and arterial stiffness. However, the results were inconsistent, longitudinal studies were sparse, and comparison of these glycemic parameters was less conducted. We aimed to explore the longitudinal relationship between HbA1c and arterial stiffness and compare the effect of the parameters. Methods: Data were collected from 2011 to 2019 in Beijing Health Management Cohort (BHMC) study. Cox proportional hazard models were fitted to investigate the association between the parameters and arterial stiffness. A generalized estimation equation (GEE) analysis was conducted to investigate the effect of repeated measurements of glycemic parameters. A receiver operating characteristic (ROC) analysis was performed to compare the predictive value of glycemic parameters for arterial stiffness. Results: Among 3,048 subjects, 591 were diagnosed as arterial stiffness during the follow-up. The adjusted hazard ratio (HR) [95% confidence interval (CI)] for arterial stiffness of the highest quartile group of HbA1c was 1.63 (1.22-2.18), which was higher than those of FBG, PBG, and TyG index. The nonlinear association of arterial stiffness with HbA1c and PBG was proved. The robust results of the sensitivity analysis were obtained. Conclusions: HbA1c is an important risk factor of arterial stiffness compared with PBG, FBG, and TyG index, and has a strong predictive ability for arterial stiffness among non-diabetics and the general population.

4.
Int J Mol Sci ; 23(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35563553

RESUMO

Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5'-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73+ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73+ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73+ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73+ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.

5.
Ann Palliat Med ; 11(4): 1453-1461, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35523753

RESUMO

BACKGROUND: This study was to investigate the efficacy of plastic surgery in patients with diabetic foot (DF) ulcer who had systemic treatment and local infection control. METHODS: A total of 112 patients with DF were randomly divided into surgery group and drug treatment group according to treatment methods. Firstly, the pathogenic bacteria were isolated and cultured to explore the specific factors causing glycosuria foot ulcer. Secondly, the wound recovery and average hospitalization of the patients were analyzed, and the effects of different treatment methods on the clinical cure rate and recovery rate of the patients were compared. RESULTS: The results showed that 53 patients were diagnosed with type 2 DF, accounting for 47.32%; 22 patients were diagnosed with DF disease complicated by infections, accounting for 19.64%; 25 patients were diagnosed with DF complicated by ulcers, accounting for 22.32%; and 12 patients (10.71%) were diagnosed with DF complicated by ulcer infection. Of the pathogens cultured, Enterococcus faecalis accounted for the highest proportion (19.35%). Statistical analysis was conducted on Wagner grading. It was found that with the increase of the grade, the wound recovery time of patients gradually increased, with the longest recovery time for grade V and the shortest recovery time for grade I. Additionally, with the extension of hospital stay, the area of the ulcer wound gradually decreased. In the analysis of induced factors, there were 17 cases of nail cutting, accounting for 15.18%. CONCLUSIONS: The operation of repairing DF ulcer wound under the guidance of plastic surgery principle had good efficacy, safety, and reliability, and was worthy of clinical promotion.


Assuntos
Diabetes Mellitus , Pé Diabético , Pé Diabético/diagnóstico , Pé Diabético/cirurgia , Humanos , Controle de Infecções , Reprodutibilidade dos Testes , Úlcera
6.
Epigenomics ; 14(7): 391-403, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35259923

RESUMO

Aim: To characterize the actionable biomarker for leukemic transformation (LT) of myeloproliferative neoplasms (MPNs) at the DNA damage repair promoter methylation level. Materials & methods: Bioinformatic analysis and experimental validation were performed to identify the MPNs-LT specific biomarker out of the promoter methylation of 236 DNA damage repair genes with GSE42042 dataset and an in-house cohort of 80 MPNs. Results: Hypermethylation of BRCA2 promoter was characterized as the JAK2 mutation-independent epigenetic marker for MPNs-LT and repressed mRNA and protein expression, leading to olaparib hypersensitivity in the leukemic cells from MPNs-LT. Conclusion: Expressional silence of BRCA2 by promoter methylation compels the homologous recombination deficiency and vulnerability to PARP inhibition and serves as an actionable marker for targeted therapy for MPNs-LT.


Leukemic transformation is a difficulty of myeloproliferative tumors, known as myeloproliferative neoplasms (MPNs). It is possible that DNA damage repair (DDR) dysregulation plays a very important role during the change process. To show the leukemic transformation-related change in DDR-related genes, the authors compared the promoter methylation patterns of DDR genes between leukemic transformed MPNs and long-lasting MPNs in two independent MPN associates/groups of people. The authors identified BRCA2 as the most significantly epigenetically silenced DDR gene during the leukemic transformation phase of disease. The study found that promoter hypermethylation of BRCA2 is an epigenetic marker for the leukemic transformation of MPNs, although its clinical use awaits further experimentation.


Assuntos
Transtornos Mieloproliferativos , Neoplasias , Proteína BRCA2/genética , Biomarcadores , Metilação de DNA , Humanos , Mutação , Transtornos Mieloproliferativos/genética , Neoplasias/genética , Regiões Promotoras Genéticas
7.
J Inorg Biochem ; 230: 111717, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247856

RESUMO

Traditional treatment of cancers such as chemotherapy still causes many side effects after the treatment even nowadays, therefore combination therapies by using drug delivery systems are valued by more and more scientists. However, loading multiple drugs in the nanoparticles for drug delivery system may cause insufficient drugs or functional groups, which might let the nanomaterial have fewer functions. Therefore, making the mesoporous silica nanoparticles (MSNs) have photodynamic therapy function by "doping " lanthanide ions into the material structure, can evade this problem. Moreover, with the doping of lanthanide metals, the MSNs can have not only dual imaging functions of both magnetic resonance imaging and fluorescence, but also achieve photodynamic function. To feature the material with more function, chemotherapeutic drug-doxorubicin was loaded into the pores of MSNs and then bonded hyaluronic acid which is the active target and a gatekeeper, on the surface of MSNs. Finally, an all-in-one drug delivery system" Hyaluronidase and pH-responsive mesoporous silica nanoparticles with dual-imaging activity for chemo-photodynamic therapy" is synthesized. The first part in this experiment was to confirm the physical properties of the lanthanides dopped MSN and its photodynamic treatment effect. The second part was to confirm that each organic molecule had been successfully bonded to the surface of the MSN and achieve pH and Hyaluronidase response drug release effect, The last part was to prove that the drug delivery system had a significant anticancer effect through cell experiments.


Assuntos
Elementos da Série dos Lantanídeos , Nanopartículas , Fotoquimioterapia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Hialuronoglucosaminidase , Nanopartículas/química , Nanopartículas/uso terapêutico , Fotoquimioterapia/métodos , Porosidade , Dióxido de Silício/química
8.
Front Oncol ; 12: 811347, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35296027

RESUMO

Background: Overtreatment of axillary lymph node dissection (ALND) may occur in patients with axillary positive sentinel lymph node (SLN) but negative non-SLN (NSLN). Developing a magnetic resonance imaging (MRI)-based radiomics nomogram to predict axillary NSLN metastasis in patients with SLN-positive breast cancer could effectively decrease the probability of overtreatment and optimize a personalized axillary surgical strategy. Methods: This retrospective study included 285 patients with positive SLN breast cancer. Fifty five of them had metastatic NSLNs and 230 had non-metastatic NSLNs. MRI-based radiomic features of primary tumors were extracted and MRI morphologic findings of the primary tumor and axillary lymph nodes were assessed. Four models, namely, a radiomics signature, an MRI-clinical nomogram, and two MRI-clinical-radiomics nomograms were established based on MRI morphologic findings, clinicopathologic characteristics, and MRI-based radiomic features to predict the NSLN status. The optimal predictors in each model were selected using the 5-fold cross-validation (CV) method. Their predictive performances were determined by the receiver operating characteristic (ROC) curves analysis. The area under the curves (AUCs) of different models was compared by the Delong test. Their discrimination capability, calibration curve, and clinical usefulness were also assessed. Results: The 5-fold CV analysis showed that the AUCs ranged from 0.770 to 0.847 for the radiomics signature, from 0.720 to 0.824 for the MRI-clinical nomogram, from 0.843 to 0.932 for the MRI-clinical-radiomics nomogram. The optimal predictive factors in the radiomics signature, MRI-clinical nomogram, and MRI-clinical-radiomics nomogram were one texture feature of diffusion-weighted imaging (DWI), two clinicopathologic features together with one MRI morphologic finding, and the DWI-based texture feature together with the two clinicopathologic features plus the one MRI morphologic finding, respectively. The MRI-clinical-radiomics nomogram with CA 15-3 included achieved the highest AUC compared with the radiomics signature (0.868 vs. 0.806, P <0.001) and MRI-clinical nomogram (0.868 vs. 0.761; P <0.001). In addition, the MRI-clinical-radiomics nomogram without CA 15-3 showed a higher performance than that of the radiomics signature (AUC, 0.852 vs. 0.806, P = 0.016) and the MRI-clinical nomogram (AUC, 0.852 vs. 0.761, P = 0.007). The MRI-clinical-radiomics nomograms showed good discrimination and good calibration. Decision curve analysis demonstrated that the MRI-clinical-radiomics nomograms were clinically useful. Conclusion: The MRI-clinical-radiomics nomograms developed in our study showed high predictive performance, which can be used to predict the axillary NSLN status in SLN-positive breast cancer patients before surgery.

9.
BMC Gastroenterol ; 22(1): 136, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35337294

RESUMO

BACKGROUND: Pancreatic portal hypertension (PPH) is a type of extrahepatic portal hypertension. We compared the clinical efficacy of different treatment methods for PPH caused by splenic vein stenosis in chronic pancreatitis. METHODS: This article retrospectively analyzed the PPH cases that were caused by splenic vein stenosis after chronic pancreatitis. Patients were divided into three groups according to the different treatments: splenic vein stent implantation (stent group), splenectomy, and only medications (conservative group). The treatment effects from each group were compared. RESULTS: A total of 33 patients were retrospectively analyzed in this study (9, 12, and 12 patients in each group respectively). All the procedures were successful in the stent and splenectomy groups. During the follow-up, no patient had gastrointestinal bleeding recurrence in the stent and splenectomy groups. However, in the conservative group, the incidence of portal hypertensive gastropathy and upper gastrointestinal bleeding were 50% and 25%. In the stent group, all the varicose veins at the base of the stomach had shrunk by varying degrees, and the red color signs regressed. The stent patency rate was 100%. No major complication occurred. The average platelet count at 1, 3, 6-months postoperatively were all significantly higher than the preoperative value (P < 0.05). The average postoperative hospital stay duration was significantly shorter than that of the splenectomy group (3.1 ± 1.4 days vs. 16.1 ± 8.1 days; P < 0.05). In the splenectomy group, postoperative fever occurred in 4 patients. Postoperative infection occurred in 2 patients (one with abdominal cavity infection and the other with incision infection). Delayed abdominal bleeding occurred in one patient. Portal vein thrombosis occurred in 2 patients during follow up. CONCLUSION: Percutaneous splenic vein stent implantation for PPH treatment reduces the risk of gastrointestinal bleeding with minimal invasive. It has a high safety and reliable efficacy and is worthy of further clinical promotion.


Assuntos
Hipertensão Portal , Veia Esplênica , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/cirurgia , Pâncreas , Estudos Retrospectivos , Veia Esplênica/cirurgia , Stents/efeitos adversos
10.
Angew Chem Int Ed Engl ; 61(20): e202117158, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35102683

RESUMO

In photoswitches that undergo fluorescence switching upon ultraviolet irradiation, photoluminescence and photoisomerization often occur simultaneously, leading to unstable fluorescence properties. Here, we successfully demonstrated reversible solid-state triple fluorescence switching through "Pump-Trigger" multiphoton manipulation. A novel fluorescence photoswitch, BOSA-SP, achieved green, yellow, and red fluorescence under excitation by pump light and isomerization induced by trigger light. The energy ranges of photoexcitation and photoisomerization did not overlap, enabling appropriate selection of the multiphoton light for "pump" and "trigger" photoswitching, respectively. Additionally, the large free volume of the spiropyran (SP) moiety in the solid state promoted reversible photoisomerization. Switching between "pump" and "trigger" light is useful for three-color tunable switching cell imaging, which can be exploited in programmable fluorescence switching. Furthermore, we exploited reversible dual-fluorescence switching in a single molecular system to successfully achieve two-color super-resolution imaging.


Assuntos
Raios Ultravioleta , Microscopia de Fluorescência
11.
Adv Mater ; 34(15): e2110283, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35179801

RESUMO

Deleterious effects to normal tissues and short biological half-life of sonosensitizers limit the applications of sonodynamic therapy (SDT). Herein, a new sonosensitizer (Cu(II)NS) is synthesized that consists of porphyrins, chelated Cu2+ , and poly(ethylene glycol) (PEG) to overcome the challenges of SDT. As Cu2+ contains 27 electrons, Cu(II)NS has an unpaired electron (open shell), resulting in a doublet ground state and little sonosensitivity. Overexpressed glutathione in the tumor can reduce Cu2+ to generate Cu(I)NS, leading to a singlet ground state and recuperative sonosensitivity. Additionally, PEG endows Cu(II)NS with increased blood biological half-life and enhanced tumor accumulation, further increasing the effect of SDT. Through regulating the valence state of Cu, cancer SDT with enhanced therapeutic index is achieved.


Assuntos
Neoplasias , Porfirinas , Terapia por Ultrassom , Linhagem Celular Tumoral , Glutationa , Humanos , Neoplasias/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Terapia por Ultrassom/métodos
12.
PeerJ ; 10: e12646, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35116193

RESUMO

BACKGROUND: We aimed to construct a novel epithelial-mesenchymal transition (EMT)-related gene pairs (ERGPs) signature to predict overall survival (OS) in skin cutaneous melanoma (CM) patients. METHODS: Expression data of the relevant genes, corresponding clinicopathological parameters, and follow-up data were obtained from The Cancer Genome Atlas database. Univariate Cox regression analysis was utilized to identify ERGPs significantly associated with OS, and LASSO analysis was used to identify the genes used for the construction of the ERGPs signature. The optimal cutoff value determined by the receiver operating characteristic curve was used to classify patients into high-risk and low-risk groups. Survival curves were generated using the Kaplan-Meier method, and differences between the two groups were estimated using the log-rank test. The independent external datasets GSE65904 and GSE19234 were used to verify the performance of the ERGPs signature using the area under the curve (AUC) values. In addition, we also integrated clinicopathological parameters and risk scores to develop a nomogram that can individually predict the prognosis of patients with CM. RESULTS: A total of 104 ERGPs related to OS were obtained, of which 21 ERGPs were selected for the construction of the signature. All CM patients were stratified into high-and low-risk groups based on an optimal risk score cutoff value of 0.281. According to the Kaplan-Meier analysis, the mortality rate in the low-risk group was lower than that in the high-risk group in the TCGA cohort (P < 0.001), GSE65904 cohort (P = 0.006), and GSE19234 cohort (P = 0.002). Multivariate Cox regression analysis indicated that our ERGP signature was an independent risk factor for OS in CM patients in the three cohorts (for TCGA: HR, 2.560; 95% CI [1.907-3.436]; P < 0.001; for GSE65904: HR = 2.235, 95% CI [1.492-3.347], P < 0.001; for GSE19234: HR = 2.458, 95% CI [1.065-5.669], P = 0.035). The AUC value for predicting the 5-year survival rate of patients with CM of our developed model was higher than that of two previously established prognostic signatures. Both the calibration curve and the C-index (0.752, 95% CI [0.678-0.826]) indicated that the developed nomogram was highly accurate. Most importantly, the decision curve analysis results showed that the nomogram had a higher net benefit than that of the American Joint Committee on Cancer stage system. CONCLUSION: Our study established an ERGPs signature that could be potentially used in a clinical setting as a genetic biomarker for risk stratification of CM patients. In addition, the ERGPs signature could also predict which CM patients will benefit from PD-1 and PD-L1 inhibitors.

13.
PeerJ ; 10: e12621, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35111391

RESUMO

Biodegradable household garbage contains a large amount of nitrogen, which could be used as organic fertilizer to produce organic food and significantly reduce synthetic nitrogen fertilizers. There is limited information on how large the nitrogen reservoir of biodegradable household garbage is in a certain country or region. Here we took China as a case, analyzed the amount of biodegradable household garbage resources and their nitrogen reservoirs. It was noted that the biodegradable household garbage mainly included food waste, waste paper and wood chips, with the amount being 31.56, 29.55, and 6.45 × 106 t·a-1, respectively. Accordingly, the nitrogen reservoirs were 65.31 × 104, 6.80 × 104, and 3.81 × 104 t·a-1 in China. The nitrogen reservoir of food waste accounted for 86% of the total nitrogen reservoir of biodegradable household garbage, which was equivalent to 11% of the amount of actual absorption for synthetic nitrogen fertilizers (6.20 × 106 t·a-1) by agriculture plants in China. Our findings provided a scientific basis for the classification and utilization of biodegradable household garbage.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35213715

RESUMO

OBJECTIVE: Subclinical hypothyroidism is known to increase the risk of cardiovascular diseases and mortality. However, the longitudinal association between subclinical hypothyroidism and incident metabolic syndrome remains unclear yet. METHODS: A total of 3,615 participants from Beijing Health Management Cohort (BHMC) were enrolled from 2012 to 2014, and followed through 2019. People were grouped into subclinical hypothyroidism and euthyroidism according to serum free thyroxine and thyrotropin (TSH) concentrations. We used Cox proportional hazards regression models to investigate the relationship between TSH level and incident metabolic syndrome considering the modification effect of sex and age. RESULTS: Of 3,615 participants, 1,929 were men (53.4%); mean (SD) age was 43.51 (11.73) years. Through out follow-up (median [interquartile range], 3.0 [2.8-3.2] years), 738 individuals developed metabolic syndrome. Subclinical hypothyroidism was significantly associated with metabolic syndrome development only in men, and the adjusted hazard ratio was 1.87 (95% CI: 1.21-2.90) compared with euthyroidism group. Of note, there was no increased risk of metabolic syndrome in people aged 50 years or older with subclinical hypothyroidism. CONCLUSIONS: Subclinical hypothyroidism is associated with incident metabolic syndrome in young men. Further studies are needed to evaluate the targeted threshold and benefit of thyroid hormone replacement therapy for metabolic health.

15.
Cardiovasc Diabetol ; 21(1): 32, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35209907

RESUMO

BACKGROUND: The association between visceral adiposity index (VAI) and diabetic complications has been reported in cross-sectional studies, while the effect of VAI on complication development remains unclear. This study aims to evaluate the longitudinal association of VAI and Chinese VAI (CVAI) with the incidence of diabetic nephropathy and retinopathy using a Chinese cohort. METHODS: A total of 8 948 participants with type 2 diabetes from Beijing Health Management Cohort were enrolled during 2013-2014, and followed until December 31, 2019. Nephropathy was confirmed by urine albumin/creatinine ratio and estimated glomerular filtration rate; retinopathy was diagnosed using fundus photograph. RESULTS: The mean (SD) age was 53.35 (14.66) years, and 6 154 (68.8%) were men. During a median follow-up of 4.82 years, 467 participants developed nephropathy and 90 participants developed retinopathy. One-SD increase in VAI and CVAI levels were significantly associated with an increased risk of nephropathy, and the adjusted hazard ratios (HR) were 1.127 (95% CI 1.050-1.210) and 1.165 (95% CI 1.003-1.353), respectively. On contrary, VAI and CVAI level were not associated with retinopathy after adjusting confounding factors. CONCLUSION: VAI and CVAI are independently associated with the development of nephropathy, but not retinopathy in Chinese adults with diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Doenças Retinianas , Adiposidade , Adulto , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fatores de Risco
16.
Artigo em Inglês | MEDLINE | ID: mdl-35206172

RESUMO

Soils at primary explosives sites have been contaminated by high concentrations of antimony (Sb) and co-occurring heavy metals (Cu and Zn), and are largely overlooked and neglected. In this study, we investigated Sb concentrations and species and studied the effect of combined Fe- and Fe-Al-based sorbent application on the mobility of Sb and co-occurring metals. The content of Sb in soil samples varied from 26.7 to 4255.0 mg/kg. In batch experiments, FeSO4 showed ideal Sb sorption (up to 97% sorption with 10% FeSO4·7H2O), whereas the sorptions of 10% Fe0 and 10% goethite were 72% and 41%, respectively. However, Fe-based sorbents enhanced the mobility of co-occurring Cu and Zn to varying levels, especially FeSO4·7H2O. Al(OH)3 was required to prevent Cu and Zn mobilization. In this study, 5% FeSO4·7H2O and 4% Al(OH)3 mixed with soil was the optimal combination to solve this problem, with Sb, Zn, and Cu stabilizations of 94.6%, 74.2%, and 82.2%, respectively. Column tests spiked with 5% FeSO4·7H2O, and 4% Al(OH)3 showed significant Sb (85.85%), Zn (83.9%), and Cu (94.8%) retention. The pH-regulated results indicated that acid conditioning improved Sb retention under alkaline conditions. However, no significant difference was found between the acidification sets and those without pH regulation. The experimental results showed that 5% FeSO4·7H2O + 4% Al(OH)3 without pH regulation was effective for the stabilization of Sb and co-occurring metals in primary explosive soils.


Assuntos
Substâncias Explosivas , Metais Pesados , Poluentes do Solo , Antimônio/química , Solo/química , Poluentes do Solo/análise
17.
Artigo em Inglês | MEDLINE | ID: mdl-35171781

RESUMO

Deep reinforcement learning (DRL) has recently shown its success in tackling complex combinatorial optimization problems. When these problems are extended to multiobjective ones, it becomes difficult for the existing DRL approaches to flexibly and efficiently deal with multiple subproblems determined by the weight decomposition of objectives. This article proposes a concise meta-learning-based DRL approach. It first trains a meta-model by meta-learning. The meta-model is fine-tuned with a few update steps to derive submodels for the corresponding subproblems. The Pareto front is then built accordingly. Compared with other learning-based methods, our method can greatly shorten the training time of multiple submodels. Due to the rapid and excellent adaptability of the meta-model, more submodels can be derived so as to increase the quality and diversity of the found solutions. The computational experiments on multiobjective traveling salesman problems and multiobjective vehicle routing problems with time windows demonstrate the superiority of our method over most of the learning-based and iteration-based approaches.

18.
ACS Omega ; 7(1): 160-167, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35036687

RESUMO

Formaldehyde, as a carcinogenic substance, is often intentionally used to adulterate vegetables to increase their shelf life, and the adhesive tape used to attach labels can also leave formaldehyde on the surface of vegetables. However, as the "gold" standard, gas chromatography (GC) and high-performance liquid chromatography (HPLC) are expensive for individual tests and confined to the laboratory owing to their size and a suitable detector (low-cost, portable, fast detection speed) to check formaldehyde contamination in vegetables not being available. Here, we tested formaldehyde contamination in vegetables using a low-cost and hand-held detector combined with a screen-printed electrode (SPE) amperometric sensor and an open-sourced potentiostat. The analyzer can detect a concentration of 100 µmol/L formaldehyde and achieve a good linear range between 100 and 1000 µmol/L. Furthermore, the detector successfully identified formaldehyde contamination in 53 samples of six different kinds of vegetables even after residual formaldehyde on the surface was evaporated. Most importantly, under the practicability-oriented idea, a cost-effective strategy was implemented for this detector design rather than using other pricey methods (e.g., photolithography, electron-beam evaporation, chemical deposition), which enormously reduces the cost (under ∼USD 0.5 per test) and meets all of the requirements of ASSURED device. We believe this cheap, portable detector could help law-enforcing authorities, healthcare workers, and customers to screen formaldehyde contamination easily. Also, the cost-saving strategy is appropriate for low-income areas, where there is a lack of laboratories, funds, and trained experts.

19.
Hum Cell ; 35(1): 199-213, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34628623

RESUMO

The immune context of the tumor microenvironment (TME) is critical for effective immunotherapy. Nonetheless, DNA-based biomarkers for the immune-sensitive TME and the identification of immune checkpoint inhibitor (ICI) responders are under-explored. This study aims to comprehensively landscape the homologous recombination deficiency (HRD) score, an emerging hallmark for tumor genome instability that triggers immune responsiveness across major cancer types, and to unveil their link to the TME and immunotherapeutic response. The HRD-associated genomic scars were characterized in 9088 tumor samples across 32 cancer types from TCGA. We evaluated the HRD score's performance in classifying ICI responders using an independent breast cancer cohort (GSE87049) and 11 in vivo murine mammary tumor models treated with anti-PD1/CTLA4 regimen (GSE124821). This study revealed a broad association between HRD-high genotype and neoantigenesis in the major cancer types including bladder cancer, breast cancer, head and neck squamous carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, ovarian cancer, and sarcoma. Tumors with high HRD score bears increased leukocyte infiltration and lymphocyte fraction and demonstrated immune-sensitive microenvironment. The tumor immune dysfunction and exclusion (TIDE) model further confirmed HRD score-high genotype as a potential predictor for ICI immunotherapy responders in breast cancer. In conclusion, tumors with high HRD score exhibit an immune-sensitive TME. The HRD-high genotype is a promising marker for identifying ICI therapy responders among breast cancer patients.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Recombinação Homóloga/genética , Imunoterapia , Animais , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Modelos Animais de Doenças , Feminino , Instabilidade Genômica , Genótipo , Recombinação Homóloga/imunologia , Humanos , Imunoterapia/métodos , Leucócitos/patologia , Linfócitos/patologia , Camundongos , Microambiente Tumoral/imunologia
20.
Ann Vasc Surg ; 78: 379.e1-379.e5, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34481882

RESUMO

BACKGROUND: To describe a retrograde recanalization for the proximal occluded lesion in right renal artery (RRA) in young patient with fibromuscular dysplasia (FMD). METHODS: A 10-year-old girl presented to our hospital with proximal RRA occlusion and refractory hypertension though she took anti-hypertension medicines. Her renin and aldosterone were beyond the normal level in both base state and excited state. Her glomerular filtration rate at right kidney was only 18.4 ml/min. Angiography revealed proximal RRA occlusion and a compensated collateral artery (CCA) from the infrarenal aorta to the RRA. She was thus diagnosed with focal FMD. A retrograde recanalization was performed through this CCA. RESULTS: Angioplasty and stenting were successfully performed to treat the proximal RRA occlusion. Postoperatively, the glomerular filtration rate in the right kidney improved. One-year follow-up revealed that, the blood pressure maintained at normal range without any antihypertensive agents. No other discomfort was complained. CONCLUSIONS: It is feasible to establish a working pathway with patient's compensated collateral artery to treat the renal artery occlusion.


Assuntos
Angioplastia com Balão , Circulação Colateral , Displasia Fibromuscular/complicações , Hipertensão Renovascular/terapia , Obstrução da Artéria Renal/terapia , Circulação Renal , Angioplastia com Balão/instrumentação , Pressão Sanguínea , Criança , Feminino , Displasia Fibromuscular/diagnóstico , Displasia Fibromuscular/fisiopatologia , Humanos , Hipertensão Renovascular/diagnóstico , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/fisiopatologia , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/etiologia , Obstrução da Artéria Renal/fisiopatologia , Stents , Resultado do Tratamento
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