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1.
Artigo em Inglês | MEDLINE | ID: mdl-34389437

RESUMO

Among all psychiatric disorders, anorexia nervosa (AN) has the highest mortality rate. However, there is still no pharmacological therapy for AN. The human plasma proteome may be a great cornerstone for the development of new drugs against AN. Here we performed a Mendelian randomization (MR) analysis to identify causal risk proteins for AN. Exposure data were extracted from a large genome-wide association study (GWAS) of 2994 plasma proteins in 3301 subjects of European descent, while outcome data were obtained from another GWAS of AN (16,992 cases and 55,525 controls of European descent). MR analyses were performed using the inverse-variance weighted (IVW) method and other sensitivity analysis methods. Using single nucleotide polymorphisms as instruments, this study suggested that high TXNDC12 levels were associated with a higher risk of AN (IVW Odd's ratio [OR]: 1.12; 95% confidence interval [CI]: 1.08-1.16; P = 2.35 × 10-10), while another protein ADH1B showed the opposite effect (IVW OR: 0.89; 95% CI: 0.85-0.93; P = 2.99 × 10-7). The causal associations were robust in multivariable models, genome-wide significant models, and with additional MR methods. No pleiotropy was observed. Our findings suggest that TXNDC12 was associated with a high risk of AN, while AHD1B was associated with a low risk of AN. They might both have implications in AN by regulating the brain dopamine reward system. In combination with existing knowledge on AN, these proteins may be novel drug targets for AN treatment.

2.
Front Endocrinol (Lausanne) ; 12: 743202, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659125

RESUMO

Background and Aims: The heat shock protein (Hsp) 90α is induced by stress and regulates inflammation through multiple pathways. Elevated serum Hsp90α had been found in nonalcoholic steatohepatitis (NASH). Geranylgeranylacetone (GGA, also called teprenone) is a terpenoid derivative. It was reported to induce Hsp and alleviate insulin resistance. We aimed to evaluate the Hsp90α as a biomarker in predicting metabolic-associated fatty liver disease (MAFLD) and define the therapeutic effects of geranylgeranylacetone for the disease. Methods: A clinical study was conducted to analyze the elements associated with Hsp90α, and a predictive model of MAFLD was developed based on Hsp90α. The histopathological correlation between Hsp90α and MAFLD was investigated through a diet-induced mouse model. Furthermore, GGA was applied to the mouse model. Results: Serum Hsp90α was increased in patients with MAFLD. A positive linear relationship was found between age, glycosylated hemoglobin (HbA1c), MAFLD, and serum Hsp90α. Meanwhile, a negative linear relationship with body mass index (BMI) was found. A model using Hsp90α, BMI, HbA1c, and ALT was established for predicting MAFLD. The area under the receiver operating characteristic (ROC) curves was 0.94 (95% CI 0.909-0.971, p = 0.000). The sensitivity was 84.1%, and the specificity was 93.1%. In vitro experiments, GGA induced Hsp90α in steatosis cells. In the mice model, Hsp90α decreased in the GGA treatment group. Hepatic steatosis, inflammation, insulin resistance, and glucose intolerance were improved in the GGA-treated group. Serum Hsp90α was positively correlated with steatohepatitis activity according to hepatic histopathology. Conclusions: Serum Hsp90α was elevated in MAFLD, and a positive correlation between serum Hsp90α and the grade of activity of steatohepatitis was observed. The model using BMI, HbA1c, and alanine aminotransferase (ALT) had a good value to predict MAFLD. The findings also revealed the effectiveness of GGA in the treatment of MAFLD.

3.
Sci Total Environ ; 807(Pt 2): 150770, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34624283

RESUMO

Se unevenly distributed in soils due to variations of geology and anthropogenic input, which results in different effects on earthworms. The effects of Se were characterized by analyzing the growth and metabolism responses of earthworms after exposure to three different concentrations of Na2SeO3. The results showed that except the possible growth promotion at 5 mg/kg, low and middle-level exposure to Na2SeO3 (0.3-10 mg/kg) did not significantly affect the growth of earthworms. While a significant inhibition effect on growth was observed in the high-level exposure group (30-70 mg/kg). There was an inflection point for Se performing promotion to inhibition effects on earthworm growth. To investigate the metabolic response of earthworms, a novel HPLC-ESI-MS (High Performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry) method was used to determine sensitive biomarkers. Selenium exposure significantly altered the metabolism of seven essential amino acids, namely tyrosine, leucine, phenylalanine, valine, alanine, glycine, and lysine, and two selenoamino acids, namely selenomethionine and methylselenocysteine. The overall metabolism level of earthworms was not affected at low exposure concentrations, but was affected at medium and high exposure concentrations. The metabolic pathways that integrated the selenocompound metabolism and the tricarboxylic acid cycle from the perspective of energy supply and demand were affected by Na2SeO3 exposure. The derived reactive oxygen species at high exposure concentrations were probably the reason for the growth inhibition effect of Se on earthworms. This study provides biochemical insights into the effects of Na2SeO3 on earthworms and suggests that an Se concentration of about 2.3 mg/kg is appropriate for soil organism health.

4.
Acad Radiol ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34654623

RESUMO

RATIONALE AND OBJECTIVES: To investigate the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and texture parameters of primary lesions and lymph nodes for predicting pelvic lymph node metastasis in patients with cervical cancer. MATERIALS AND METHODS: A total of 143 patients with cervical cancer confirmed by surgical pathology were analyzed retrospectively and 125 patients were enrolled in primary lesions study, 83 patients and 134 lymph nodes were enrolled in lymph nodes study. Patients and lymph nodes were randomly divided into training group and test group at a ratio of 2: 1. The IVIM-DWI parameters and 3D texture features of primary lesions and lymph nodes of all patients were measured. The least absolute shrinkage and selection operator algorithm, spearman's correlation analysis, independent two-sample t-test and Mann-Whitney U-test were used to select texture parameters. Multivariate Logistic regression analysis and receiver operating characteristic curves were used to model and evaluate diagnostic performances. RESULTS: In primary lesions study, model 1 was constructed by combining f value, original_shape_Sphericity and original_firstorder_Mean of primary lesions. In lymph nodes study, model 2 was constructed by combining short diameter, circular enhancement and rough margin of lymph nodes. Model 3 was constructed by combining ADC, f value and original_glszm_Small Area Emphasis of lymph nodes. The areas under curve of model 1, 2 and 3 in training group and test group were 0.882, 0.798, 0.907 and 0.862, 0.771, 0.937 respectively. CONCLUSION: Models based on IVIM-DWI and texture parameters of primary lesions and lymph nodes both performed well in diagnosing pelvic lymph node metastasis of cervical cancer and were superior to morphological features of lymph nodes. Especially, parameters of lymph nodes showed higher diagnostic efficiency and clinical significance.

5.
Mol Cancer Res ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654722

RESUMO

Lymphatic metastasis is a common clinical symptom in nasopharyngeal carcinoma (NPC), the most common EBV-associated head and neck malignancy. However, the effect of EBV on NPC LN metastasis is still unclear. In this study, we demonstrated that EBV infection is strongly associated with advanced clinical N stage and lymphangiogenesis of NPC. We found that NPC cells infected with EBV promote LN metastasis by inducing cancer-associated lymphangiogenesis, whereas these changes were abolished upon clearance of EBV genomes. Mechanistically, EBV-induced VEGF-C contributed to lymphangiogenesis and LN metastasis, and PHLPP1, a target of miR-BART15, partially contributed to AKT/HIF-1a hyperactivity and subsequent VEGF-C transcriptional activation. Additionally, administration of anti-VEGF-C antibody or HIF-1α inhibitors attenuated the lymphangiogenesis and LN metastasis induced by EBV. Finally, we verified the clinical significance of this prometastatic EBV/VEGF-C axis by determining the expression of PHLPP1, AKT, HIF-1a and VEGF-C in NPC specimens with and without EBV. These results uncover a reasonable mechanism for the EBV-modulated LN metastasis microenvironment in NPC, indicating that EBV is a potential therapeutic target for NPC with lymphatic metastasis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34605989

RESUMO

PURPOSE: Although various papers have reported on the clinical performance of cup retention with cementation of a new liner and bone grafting in the management of well-fixed cups with polyethylene wear and periacetabular osteolysis after total hip arthroplasty (THA), no systematic review of this topic has been published to date. METHODS: Medline, EMBASE and Cochrane Library were searched for articles published from January 1999 to January 2019 using "osteolysis" AND "well-fixed", "osteolysis" AND "retro-acetabular", "bone graft" AND ("retention" OR "retained" OR "stable") AND "cup", and "cemented liner" AND "well-fixed". RESULTS: Nine articles were selected for review (186 cases, 76.1 months mean follow-up). The overall revision rate was 11.3% (21 hips) most commonly due to aseptic loosening (9/186 hips), dislocation (8/186 hips), and liner wear progression (2/186 cases). The reported square size of osteolytic lesions ranged from a mean of 465.84 mm2 to a max of 4,770 mm2. Almost all reported lesions treated with bone grafts resolved or did not progress 97% (72/74). All studies indicated improved pain and functional scores at follow-up. CONCLUSION: Cementation of a new liner with periacetabular bone grafting provides an alternative option to isolated liner exchange and cup revision for the management of periacetabular osteolysis in well-fixed cups with a disrupted locking mechanism or unavailable exchange liner. Further higher quality studies are required in order to examine if the use of highly cross-linked polyethylene, highly porous-coated cups, hydroxyapatite-coated cups, and small-diameter cups influence the clinical outcome of liner cementation in well-fixed cups with periacetabular osteolysis.

7.
Radiol Artif Intell ; 3(5): e200237, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34617025

RESUMO

Purpose: To develop and evaluate a diffusion-weighted imaging (DWI) deep learning framework based on the generative adversarial network (GAN) to generate synthetic high-b-value (b =1500 sec/mm2) DWI (SYNb1500) sets from acquired standard-b-value (b = 800 sec/mm2) DWI (ACQb800) and acquired standard-b-value (b = 1000 sec/mm2) DWI (ACQb1000) sets. Materials and Methods: This retrospective multicenter study included 395 patients who underwent prostate multiparametric MRI. This cohort was split into internal training (96 patients) and external testing (299 patients) datasets. To create SYNb1500 sets from ACQb800 and ACQb1000 sets, a deep learning model based on GAN (M0) was developed by using the internal dataset. M0 was trained and compared with a conventional model based on the cycle GAN (Mcyc). M0 was further optimized by using denoising and edge-enhancement techniques (optimized version of the M0 [Opt-M0]). The SYNb1500 sets were synthesized by using the M0 and the Opt-M0 were synthesized by using ACQb800 and ACQb1000 sets from the external testing dataset. For comparison, traditional calculated (b =1500 sec/mm2) DWI (CALb1500) sets were also obtained. Reader ratings for image quality and prostate cancer detection were performed on the acquired high-b-value (b = 1500 sec/mm2) DWI (ACQb1500), CALb1500, and SYNb1500 sets and the SYNb1500 set generated by the Opt-M0 (Opt-SYNb1500). Wilcoxon signed rank tests were used to compare the readers' scores. A multiple-reader multiple-case receiver operating characteristic curve was used to compare the diagnostic utility of each DWI set. Results: When compared with the Mcyc, the M0 yielded a lower mean squared difference and higher mean scores for the peak signal-to-noise ratio, structural similarity, and feature similarity (P < .001 for all). Opt-SYNb1500 resulted in significantly better image quality (P ≤ .001 for all) and a higher mean area under the curve than ACQb1500 and CALb1500 (P ≤ .042 for all). Conclusion: A deep learning framework based on GAN is a promising method to synthesize realistic high-b-value DWI sets with good image quality and accuracy in prostate cancer detection.Keywords: Prostate Cancer, Abdomen/GI, Diffusion-weighted Imaging, Deep Learning Framework, High b Value, Generative Adversarial Networks© RSNA, 2021 Supplemental material is available for this article.

8.
Curr Med Sci ; 41(5): 981-986, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34669115

RESUMO

OBJECTIVE: A diagnosis of drowning remains one of the most challenging issues in forensic science, especially for decomposed bodies. Diatom analysis is considered as an encouraging method for diagnosing drowning. In this study, we developed a drowned rat model using different diatom densities in water. METHODS: A total of 120 adult Sprague-Dawley rats were used and divided into six groups, wherein experimental groups 1-5 were drowned rats (group A) and postmortem submersion rats (group B) that were submerged in water with five different Cyclotella sp. diatom densities, while the remaining group was used as a blank control. The combination of microwave digestion and vacuum filtration method was used to accomplish efficient tissue digestion and ascertain higher accuracy of diatom determinations within organs. RESULTS: The abundances of diatoms in the lungs, livers, and kidneys were significantly different. The diatom abundances in the lungs, livers, and kidneys were directly proportional to the water diatom densities, and specific quantitative relationships could be approximated by separate regression equations for each organ type. However, the trends associated with the diatom increases among organs slightly differed. In addition, the diatom abundances in the lungs, livers, and kidneys were all positively correlated. Diatoms were not observed in the postmortem submersion groups nor in the blank control groups. CONCLUSION: The results of this study provide valuable information for establishing a quantitative diatom framework for informing future forensic medicine efforts.

9.
Front Oncol ; 11: 711206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540678

RESUMO

Objective: Inflammation plays a crucial role in tumorigenesis and progression. Our purpose was to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR), systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII), and develop a nomogram to predict the cancer-specific survival (CSS) and disease-free survival (DFS) of stage I lung adenocarcinoma patients. Methods: 1431 patients undergoing surgical resection with pathologically confirmed stage I lung adenocarcinoma were reviewed. The optimal cut-off values for NLR, SII, and SIRI were defined by the receiver operating characteristic (ROC) curve. Cox proportional hazards regression analyses were performed to recognize factors significantly correlated with CSS and DFS to construct the nomogram. The value of adjuvant chemotherapy on model-defined high-risk and low-risk patients was further explored. Results: The cohort had a median follow-up time of 63 months. Multivariate analysis revealed that higher NLR (≥2.606), higher SIRI (≥0.705), higher SII (≥580.671), later T stage, histological pattern with solid or micropapillary components and radiologic features with solid nodules were significantly associated with worse CSS and DFS. The concordance index (C-index) of the nomogram established by all these factors was higher than that of the TNM staging system both in CSS (validation set 0.778 vs 0.652) and DFS (validation set 0.758 vs 0.695). Furthermore, the value of the established nomogram on risk stratification in stage I lung adenocarcinoma patients was validated. Conclusions: Higher NLR, SII and SIRI pretreatment were associated with worse survival outcomes. A practical nomogram based on these three inflammatory biomarkers may help clinicians to precisely stratify stage I lung adenocarcinoma patients into high- and low-risk and implement individualized treatment.

10.
Mol Cell Biochem ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581942

RESUMO

Angiogenesis plays a key in the process of tissue repair and wound healing. Human adipose-derived mesenchymal stem cells (HADSCs) have been found to act a promotion role during angiogenesis. Moreover, miR-125a-3p in HADSCs could promote the angiogenesis of HUVECs, but their specific mechanism in wound healing needs further study. Western blotting and qRT-PCR were used for detecting the protein and mRNA level, respectively. Exosomes were isolated successfully, and transmission electron microscope was used to identify exosomes. Angiogenesis, cell migration, and proliferation were detected with tube formation, wound healing, and MTT assays. The interactions of miR-125a-3p and PTEN were validated using dual-luciferase reporter assay. Animal model was used to evaluate the effect of miR-125a-3p on wound healing. HADSCs-exosome remarkably promoted the viability, migration, and angiogenesis of HUVECs. Knockdown of miR-125a-3p in HADSCs could inhibit the effect of HADSCs-exosome, while overexpression of miR-125a-3p could further promote the effect of HADSCs-exosome on HUVECs. MiR-125a-3p from HADSCs-exosome inhibited the expression of PTEN in HUVECs. Knockdown of PTEN promoted the viability, migration, and angiogenesis of HUVECs and reversed the effect of miR-125a-3p knockdown on HUVECs. Finally, miR-125a-3p from HADSCs-exosome could promote wound healing and angiogenesis in mice by inhibiting PTEN in mice wound granulation tissues. MiR-125a-3p from the HADSCs-exosome promoted the wound healing and angiogenesis, and these effects were achieved through regulating PTEN. This study may provide a new thought for the treatment and prevention of tissue repair.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34562073

RESUMO

BACKGROUND: Self-reported low physical activity is a defining feature of phenotypic frailty but does not adequately capture physical activity performed throughout the day. This study examined associations between accelerometer-derived patterns of routine daily physical activity and frailty. METHODS: Wrist accelerometer and frailty data from 638 participants (mean age 77 (SD=5.5) years; 44% women) were used to derive five physical activity metrics: active minutes/day, sedentary minutes/day, total activity counts/day, activity fragmentation (reciprocal of the average active bout length) and sedentary fragmentation (reciprocal of the average sedentary bout length). Robust, pre-frail and frail statuses were identified using the physical frailty phenotype defined as having 0, 1-2, or ≥3 of the following criterion: weight loss, exhaustion, slowness, self-reported low activity, and weakness. Frailty was collapsed into not frail (robust and prefrail) and frail, and each frailty criteria was dichotomized. Multiple logistic regression was used to model each accelerometer metric. Separate frailty criteria and interactions with age and sex were also examined. RESULTS: With higher amounts and intensity of daily activity (more active minutes, fewer sedentary minutes, higher activity counts) and lower activity fragmentation, the odds of frailty were lower compared to robust/prefrail states (p<0.02 for all). For interactions, only an age by sedentary fragmentation interaction on the odds of frailty was observed (p=0.01). For each separate criteria, accelerometer metrics were associated with odds of slowness, low activity, and weakness. CONCLUSION: Less favorable patterns of objectively measured daily physical activity are associated with frailty and the components of slowness, low self-reported activity, and weakness.

12.
J Mol Cell Cardiol ; 162: 62-71, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34509499

RESUMO

Direct conversion of cardiac fibroblast into induced cardiomyocytes (iCMs) by forced expression of cardiac transcription factors, such as Mef2c, Gata4, and Tbx5 (MGT), holds great promise for regenerative medicine. The process of cardiac reprogramming consists of waves of transcriptome remodelling events. However, how this transcriptome remodelling is driven by the upstream chromatin landscape alteration is still unclear. In this study, we performed single-cell ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) on early reprogramming iCMs given the known epigenetic changes as early as day 3. This approach unveiled networks of transcription factors (TFs) involved in the early shift of chromatin accessibility during cardiac reprogramming. Combining our analysis with functional assays, we identified Smad3 to be a bimodal TF in cardiac reprogramming, a barrier in the initiation of reprogramming and a facilitator during the intermediate stage of reprogramming. Moreover, integrative analysis of scATAC-seq with scRNA-seq data led to the identification of active TFs important for iCM conversion. Finally, we discovered a global rewiring of cis-regulatory interactions of cardiac genes along the reprogramming trajectory. Collectively, our scATAC-seq study and the integrative analysis with scRNA-seq data provided valuable resources to understand the epigenomic heterogeneity and its alteration in relation to transcription changes during early stage of cardiac reprogramming.

13.
Nat Aging ; 1(1): 36-46, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34476409

RESUMO

Frailty in aging marks a state of decreased reserves resulting in increased vulnerability to adverse outcomes when exposed to stressors. This Perspective synthesizes the evidence on the aging-related pathophysiology underpinning the clinical presentation of physical frailty as a phenotype of a clinical syndrome that is distinct from the cumulative-deficit-based frailty index. We focus on integrating the converging evidence on the conceptualization of physical frailty as a state, largely independent of chronic diseases, that emerges when the dysregulation of multiple interconnected physiological and biological systems crosses a threshold to critical dysfunction, severely compromising homeostasis. Our exegesis posits that the physiology underlying frailty is a critically dysregulated complex dynamical system. This conceptual framework implies that interventions such as physical activity that have multisystem effects are more promising to remedy frailty than interventions targeted at replenishing single systems. We then consider how this framework can drive future research to further understanding, prevention and treatment of frailty, which will likely preserve health and resilience in aging populations.

14.
EMBO Rep ; : e52901, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523214

RESUMO

Cardiac regeneration occurs primarily through proliferation of existing cardiomyocytes, but also involves complex interactions between distinct cardiac cell types including non-cardiomyocytes (non-CMs). However, the subpopulations, distinguishing molecular features, cellular functions, and intercellular interactions of non-CMs in heart regeneration remain largely unexplored. Using the LIGER algorithm, we assemble an atlas of cell states from 61,977 individual non-CM scRNA-seq profiles isolated at multiple time points during regeneration. This analysis reveals extensive non-CM cell diversity, including multiple macrophage (MC), fibroblast (FB), and endothelial cell (EC) subpopulations with unique spatiotemporal distributions, and suggests an important role for MC in inducing the activated FB and EC subpopulations. Indeed, pharmacological perturbation of MC function compromises the induction of the unique FB and EC subpopulations. Furthermore, we developed computational algorithm Topologizer to map the topological relationships and dynamic transitions between functional states. We uncover dynamic transitions between MC functional states and identify factors involved in mRNA processing and transcriptional regulation associated with the transition. Together, our single-cell transcriptomic analysis of non-CMs during cardiac regeneration provides a blueprint for interrogating the molecular and cellular basis of this process.

15.
Water Res ; 203: 117539, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34407485

RESUMO

Red mud (RM) as waste of industrial aluminum production is piling up in huge ponds. RM could be a cost-effective adsorbent for heavy metals, but adsorption is vulnerable to pH changes, metal ions speciation and the occurrence of iron bearing minerals. In this study, the precipitation and elemental speciation transformation relevant to arsenic fate in responding to the addition of RM during arsenopyrite bio-oxidation by Sulfobacillus thermosulfidooxidans was investigated. The results show that the addition of RM significantly changed the arsenic precipitation and the solution chemistry and thus affected the arsenopyrite bio-oxidation and arsenic fate. An addition of a small amount (≤ 4 g/L) of RM substantially promoted arsenopyrite bio-oxidation with formation of SiO2 @ (As, Fe, Al, Si) spherical nanoparticles that can enhance the stability of the immobilized arsenic. The SiO2-based spherical nanoparticles precipitate was mainly composed of jarosites, amorphous ferric arsenate and crystalline scorodite, and its formation were controlled by Fe3+ concentration and solution pH. An addition of increased amount of RM (≥ 6 g/L) resulted in a significant increase of the solution pH and a decrease in the Fe2+ bio-oxidation activity, and spherical nanoparticles were not formed. Consequently, the dissolution of arsenopyrite was inhibited and the release of arsenic was blocked. This study suggests the applicability of RM in mitigation of arsenic pollution from bio-oxidation of As-bearing sulfide minerals.


Assuntos
Arsênio , Arsenicais , Clostridiales , Concentração de Íons de Hidrogênio , Ferro , Compostos de Ferro , Minerais , Oxirredução , Dióxido de Silício , Sulfetos
16.
J Am Heart Assoc ; 10(16): e020068, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34369204

RESUMO

Background We have previously reported the feasibility of noninvasive stereotactic body radiotherapy (SBRT) as a novel approach for renal denervation. Methods and Results Herein, from a translational point of view, we assessed the antihypertensive effect and chronological evolution of SBRT-induced renal nerve injury within 6 months in a hypertensive swine model. Hypertension was induced in swine by subcutaneous implantation of deoxycorticosterone acetate pellets in combination with a high-salt diet. A single dose of 25 Gy with SBRT was delivered for renal denervation in 9 swine within 3.4±1.0 minutes. Blood pressure levels at baseline and 1 and 6 months post-SBRT were comparable to control (n=5), whereas renal norepinephrine was significantly lower at 6 months (P<0.05). Abdominal computed tomography, performed before euthanasia and renal function assessment, remained normal. Standard semiquantitative histological assessment showed that compared with control (1.4±0.4), renal nerve injury was greater at 1 month post-SBRT (2.3±0.3) and peaked at 6 months post-SBRT (3.2±0.8) (P<0.05), along with a higher proportion of active caspase-3-positive nerves (P<0.05). Moreover, SBRT resulted in continuous dysfunction of renal sympathetic nerves and low level of nerve regeneration in 6 months by immunohistochemistry analysis. Conclusions SBRT delivering 25 Gy for renal denervation was safe and related to sustained reduction of sympathetic activity by aggravating nerve damage and inhibiting nerve regeneration up to 6 months; however, its translation to clinical trial should be cautious because of the negative blood pressure response in the deoxycorticosterone acetate-salt hypertensive swine model.

17.
BMC Geriatr ; 21(1): 448, 2021 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332530

RESUMO

BACKGROUNDS: Cardiovascular disease (CVD) risk factors are individually associated with frailty. This study examined whether Framingham CVD risk score (FRS) as an aggregate measure of CVD risk is associated with incident frailty among Chinese older adults. METHODS: This study used data from the China Health and Retirement Longitudinal Study. A sample of 3,618 participants aged 60 to 95 years and without CVD at baseline were followed for four years. FRS was calculated at baseline. Frailty status was defined as not-frail (0-2 criteria) or frail (3-5 criteria) based on the physical frailty phenotype consisting of five binary criteria (weakness, slowness, exhaustion, low activity level, and weight loss). After excluding subjects who were frail (n = 248) at baseline, discrete-time Cox regression was used to evaluate the relationship between FRS and incident frailty. RESULTS: During a median follow-up of 4.0 years, 323 (8 %) participants developed CVD and 318 (11 %) subjects had frailty onset. Higher FRS was associated with greater risk of incident frailty (HR: 1.03, 95 % CI: 1.00 to 1.06) after adjusting for education, marital status, obesity, comorbidity burden, and cognitive function. This association however was no longer significant (HR: 1.00, 95 % CI: 0.97 to 1.03) after additionally adjusting for age. These findings remained essentially unchanged after excluding subjects with depression (n = 590) at baseline or incident CVD (n = 323) during the 4-year follow-up. CONCLUSIONS: The FRS was not independently associated with incident frailty after adjusting for chronological age. More research is needed to assess the clinical utility of the FRS in predicting adverse health outcomes other than CVD in older adults.


Assuntos
Fragilidade , Idoso , Comorbidade , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Humanos , Estudos Longitudinais , Fatores de Risco
18.
World J Clin Cases ; 9(21): 6138-6144, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34368336

RESUMO

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is hard to diagnose because of nonspecific symptoms and signs. It is a general consensus that EPS is classified as primary and secondary. There have been several studies discovering some high-risk factors such as liver cirrhosis, of which AMA-M2 is a biomarker, and intra-abdominal surgery such as laparoscopic surgery. Imaging studies help to diagnose EPS and exploratory laparotomy might be an alternative if imaging fails. Nowadays, laparotomy plays a key role in treating EPS, especially when medical treatments do not work and medical therapy fails to ease patients' symptoms. CASE SUMMARY: A 58-year-old man complained of unexplained vomiting and abdominal distension 2 mo after laparoscopic cholecystectomy. Increased alkaline phosphatase and liver enzymes were discovered. An autoimmune liver disease test showed that AMA-M2 was positive. A gastroscopy revealed bile reflux gastritis. A magnetic resonance imaging scan showed a slight dilatation of the intrahepatic bile duct. A colonoscopy showed that there was a mucosal eminence lesion in the sigmoid colon (24 cm away from the anus), with a size of 3 cm × 3 cm and erosive surface. At last, the small intestine and the stomach were found to be encased in a cocoon-like membrane during the surgery. The membrane was dissected and adhesiolysis was done to release the trapped organs. The patient recovered and was discharged 44 d after the operation, and there was no recurrence during a follow-up period of 3 mo. CONCLUSION: AMA-M2 is a marker of primary biliary sclerosis and may help to make a preoperative diagnosis of EPS.

20.
Front Psychiatry ; 12: 717715, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456770

RESUMO

Purpose: To compare the efficacy and tolerability of different administration strategies of aripiprazole. Methods: We searched MEDLINE, EMBASE, the Cochrane Central, Web of Science, China National Knowledge Infrastructure(CNKI), and Wanfang Data Knowledge Service Platform(Wanfang) for randomized controlled trials (RCTs) of aripiprazole, using the terms: (aripiprazole) AND (schizophr* OR schizoaff*) AND ("syndrome scale" OR PANSS) AND (clini* OR trial). We retrieved study design, participant characteristics, comparison groups, and outcomes from each study. Results: In total, nine RCTs were selected for meta-analysis, which covered ~1,187 participants. We defined two treatment groups that represent different treatment strategies: (1) the high-dose group (the high-dose strategy) rapidly increased to doses higher than 15 mg/day in 2 weeks or began with doses higher than 15 mg/day, otherwise the group was defined as (2) the low-dose group (the low-dose strategy). If the initial or target doses of aripiprazole in a study were all higher than 15 mg/day, the high- and low-dose groups were created based on the relative level of the dose. The high-dose group showed significantly greater reductions in Positive and Negative Syndrome Scale (PANSS) total scores (standardized mean differences = -8.31, 95% confidence interval [CI] = -16.48, -0.13; P < 0.01; I 2 = 96%) than the low-dose group. The high-dose group showed superior effects compared with the low-dose group in long-term studies (more than 8 weeks) (standardized mean differences = -13.81, 95% CI = -25.07, -2.55; P < 0.01; I 2 = 96%). With exception of somnolence, we did not find significant differences in side effects or discontinuation due to adverse events. Sensitivity analyses produced similar results. Conclusion: The high-dose treatment strategy of aripiprazole for patients with schizophrenia or schizoaffective disorder may bring more benefits without obvious side effects.

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