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Hepatic fibrosis is a pathological response of the liver to a variety of chronic stimuli. Hepatic stellate cells (HSCs) are the major source of myofibroblasts in the liver. Follistatin like 1 (Fstl1) is a secreted glycoprotein induced by transforming growth factor-β1 (TGF-β1). However, the precise functions and regulation mechanisms of Fstl1 in liver fibrogenesis remains unclear.

Hepatic stellate cell (HSC) line LX-2 stimulated by TGF-β1, primary culture of mouse HSCs and a model of liver fibrosis induced by CCl4 in mice was used to assess the effect of Fstl1 in vitro and in vivo.

Here, we found that Fstl1 was significantly up regulated in human and mouse fibrotic livers, as well as activated HSCs. Haplodeficiency of Fstl1 or blockage of Fstl1 with a neutralizing antibody 22B6 attenuated CCl

-induced liver fibrosis in vivo. Fstl1 modulates TGF-β1 classic Samd2 and non-classic JNK signaling pathways. Knockdown of Fstl1 in HSCs significantly ameliorated cell activation, cell migration, chemokines C-C Motif Chemokine Ligand 2 (CCL2) and C-X-C Motif Chemokine Ligand 8 (CXCL8) secretion and extracellular matrix (ECM) production, and also modulated microRNA-29a (miR29a) expression. Furthermore, we identified that Fstl1 was a target gene of miR29a. And TGF-β1 induction of Fstl1 expression was partially through down regulation of miR29a in HSCs.

Our data suggests TGF-β1-miR29a-Fstl1 regulatory circuit plays a key role in regulation the HSC activation and ECM production, and targeting Fstl1 may be a strategy for the treatment of liver fibrosis. Video Abstract.

Our data suggests TGF-β1-miR29a-Fstl1 regulatory circuit plays a key role in regulation the HSC activation and ECM production, and targeting Fstl1 may be a strategy for the treatment of liver fibrosis. Video Abstract.

In this study, we employed a gated recurrent unit (GRU)-based recurrent neural network (RNN) using dosimetric information induced by individual beam to predict the dose-volume histogram (DVH) and investigated the feasibility and usefulness of this method in biologically related models for nasopharyngeal carcinomas (NPC) treatment planning.

One hundred patients with NPC undergoing volumetric modulated arc therapy (VMAT) between 2018 and 2019 were randomly selected for this study. All the VMAT plans were created using the Monaco treatment planning system (Elekta, Sweden) and clinically approved > 98% of PGTVnx received the prescribed doses of 70 Gy, > 98% of PGTVnd received the prescribed doses of 66 Gy and > 98% of PCTV received 60 Gy. Of these, the data from 80 patients were used to train the GRU-RNN, and the data from the other 20 patients were used for testing. For each NPC patient, the DVHs of different organs at risk were predicted by a trained GRU-based RNN using the information given by ind1.67 Gy dose reduction in EPs on average.

The GRU-RNN-based DVH prediction method was capable of accurate DVH prediction. The regenerated plans guided by the predicted EUDs were not inferior to the manual plans, had better consistency in PTVs and better dose sparing in critical OARs, indicating the usefulness and effectiveness of biologically related model in knowledge-based planning.

The GRU-RNN-based DVH prediction method was capable of accurate DVH prediction. The regenerated plans guided by the predicted EUDs were not inferior to the manual plans, had better consistency in PTVs and better dose sparing in critical OARs, indicating the usefulness and effectiveness of biologically related model in knowledge-based planning.

High body mass index (BMI) is a risk factor for type 2 diabetes and cardiovascular disease. However, its relationships with indices of carotid stiffness and plaque volume are unclear. We investigated associations of long-term measurements of BMI with indices of carotid stiffness and atherosclerosis among non-demented diabetes patients from the Israel Diabetes and Cognitive Decline (IDCD) study.

Carotid ultrasound indices [carotid intima media thickness (cIMT), distensibility, elastography and plaque volume] were assessed in N = 471 participants. Mean BMI across all MHS diabetes registry measurements and trajectories of BMI were calculated. BMI was categorized into three trajectory groups representing a relatively stable normal weight (n = 185, 44%), overweight trajectory (n = 188, 44.8%) and a trajectory of obesity (n = 47, 11.2%). Linear and logistic regressions estimated associations of carotid indices with mean BMI and BMI trajectories.

Compared to the normal weight trajectory, an obesity trajectory was associated with carotid distensibility (β = - 3.078, p = 0.037), cIMT (β = 0.095, p = 0.004), and carotid elastography (β = 0.181, p = 0.004) but not with plaque volume (β = 0.066, p = 0.858). Compared with the normal weight trajectory, an obesity trajectory was associated with increased odds for impaired carotid distensibility (OR = 2.790, p = 0.033), impaired cIMT (OR = 5.277, p = 0.001) and large carotid plaque volume (OR = 8.456, p = 0.013) but not with carotid elastography (OR = 1.956, p = 0.140). PFI2 Mean BMI was linearly associated with Distensibility (β = - 0.275, p = 0.005) and cIMT (β = 0.005, p = 0.026).

Long-term measurements of adiposity are associated with indices of carotid stiffness and plaque volume among older type 2 diabetes adults.

Long-term measurements of adiposity are associated with indices of carotid stiffness and plaque volume among older type 2 diabetes adults.

Ultrahypofractionation using stereotactic body radiotherapy (SBRT) is an increasingly utilized technique for men with prostate cancer (PC). The comparative efficacy of SBRT plus androgen deprivation therapy (ADT) compared to fractionated radiotherapy (EBRT) plus ADT in higher-risk prostate cancer is unknown.

Men > 40 years old with localized PC treated with external beam radiation and concomitant ADT for curative intent between 2004 and 2016 were analyzed from the National Cancer Database. Patients who lacked ADT or risk stratification data were excluded. 558 men treated with SBRT versus 40,797 men treated with conventional or moderately hypofractionated EBRT were included. Patients were stratified by unfavorable intermediate (UIR) and high (HR) risk using NCCN criteria. Kaplan Meier and Cox proportional hazards were used to compare overall survival (OS) between RT modality, adjusting for age, race, and comorbidity index.

With a median follow up of 74 months, there was no difference in estimated 6-year OS between men treated with SBRT versus EBRT regardless of risk group.

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