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Lower extremity arteriosclerosis obliterans (LEASO) is a vascular disease that may result in adult limb loss worldwide. CD4+T cell-mediated immunity plays a significant role in LEASO. The T cell immunoglobulin and mucin domain 3 (Tim-3) and inhibitory receptor programmed cell death-1 (PD-1) are well-known immune checkpoints that play crucial roles in regulating CD4+T cell activation or tolerance. In this study, blood mononuclear cells were isolated from the blood samples of healthy controls and patients who were diagnosed with LEASO for the first time [stage III or IV according to the Fontaine classification system and had not received drugs (except for heparin) or surgery treatment]. We concluded the higher proportion of Tim-3+PD-1+CD4+T cells in human higher stage LEASO, and oxidized low-density lipoprotein increased Tim-3 and PD-1 co-expression by activating CD4+T cells in a dose- dependent manner. Tim-3+PD-1+CD4+T cells displayed a more active status and produced more anti-atherogenic cytokines compared to Tim-3-PD-1-CD4+T cells. Apart from the increased frequency, the altered function of Tim-3+PD-1+CD4+T cells was also observed in LEASO compared to those from healthy controls. These in vitro results indicated that Tim-3 and PD-1 might be promising early warning targets of higher stage LEASO. In addition, the blockade of Tim-3 and PD-1 signaling pathways aggravated the pro-atherogenic Th1 responses in LEASO, further suggesting that the cardiovascular safety must be a criterion considered in using immune checkpoint inhibitors to reverse T cell exhaustion during tumors and chronic viral infections. [ABSTRACT FROM AUTHOR]

Background: Patients aged 40-60 years who require total hip arthroplasty (THA) often first receive unindicated hip arthroscopy or magnetic resonance imaging (MRI). Our objective was to identify potentially inappropriate resource utilization before THA, specifically reporting on the proportion of patients aged 40-60 years who underwent hip arthroscopy or MRI in the year before THA., Methods: We conducted a retrospective, population-based study at the provincial level. We retrieved data from the Canadian Institute for Health Information (CIHI). We included all Ontario residents who underwent an elective, primary THA for osteoarthritis between Apr. 1, 2004, and Mar. 31, 2016. We identified the rates and timing of patients who underwent an MRI or hip arthroscopy before their index THA., Results: The percentage of patients who underwent an MRI before THA increased significantly over the study period, from 8.7% in 2004 to 23.8% in 2015. There was also a significant but variable trend in the percentage of patients who underwent a hip arthroscopy before THA., Conclusion: Our results demonstrate a high, gradually increasing proportion of patients who received a hip MRI and a low but increasing proportion of patients who received hip arthroscopy in close proximity to THA. Multidisciplinary collaboration may improve knowledge translation and help reduce the rate of clinically unnecessary diagnostic and therapeutic interventions in this population of patients who require THA., Competing Interests: Competing interests:: None declared., (© 2024 CMA Impact Inc. or its licensors.)

Lower extremity arteriosclerosis obliterans (LEASO) is a vascular disease that may result in adult limb loss worldwide. CD4 + T cell-mediated immunity plays a significant role in LEASO. The T cell immunoglobulin and mucin domain 3 (Tim-3) and inhibitory receptor programmed cell death-1 (PD-1) are well-known immune checkpoints that play crucial roles in regulating CD4 + T cell activation or tolerance. In this study, blood mononuclear cells were isolated from the blood samples of healthy controls and patients who were diagnosed with LEASO for the first time [stage III or IV according to the Fontaine classification system and had not received drugs (except for heparin) or surgery treatment]. We concluded the higher proportion of Tim-3 + PD-1 + CD4 + T cells in human higher stage LEASO, and oxidized low-density lipoprotein increased Tim-3 and PD-1 co-expression by activating CD4 + T cells in a dose- dependent manner. Tim-3 + PD-1 + CD4 + T cells displayed a more active status and produced more anti-atherogenic cytokines compared to Tim-3 - PD-1 - CD4 + T cells. Apart from the increased frequency, the altered function of Tim-3 + PD-1 + CD4 + T cells was also observed in LEASO compared to those from healthy controls. These in vitro results indicated that Tim-3 and PD-1 might be promising early warning targets of higher stage LEASO. In addition, the blockade of Tim-3 and PD-1 signaling pathways aggravated the pro-atherogenic Th1 responses in LEASO, further suggesting that the cardiovascular safety must be a criterion considered in using immune checkpoint inhibitors to reverse T cell exhaustion during tumors and chronic viral infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cui, Chen, Dai, Ou, Qiu and Wang.)

Decidual CD4 + T (dCD4 + T) cells play pivotal roles in inducing and maintaining maternal-fetal tolerance. Dysfunctional dCD4 + T cells are associated with miscarriage. In the present study, we demonstrated that the T-box transcription factor protein eomesodermin (Eomes) was involved in the functional regulation of dCD4 + T cells during early pregnancy. We concluded the higher Eomes expression dCD4 + T cells during normal pregnancy, and the Eomes + dCD4 + T cells displayed an active status and produced more Th2- and Treg type cytokines. Decreased number and altered function of Eomes + dCD4 + T cells were observed in miscarriage. Progesterone, the traditional treatment for miscarriage, had no effect on Eomes expression by dCD4 + T cells from normal pregnancy, but increased Eomes expression by dCD4 + T cells from miscarriage. We also found the higher frequency of Eomes + dCD4 + T cells from miscarriage in response to cyclosporine, tacrolimus, Trophoblasts, and HTR8/SVneo cell line, might provide new strategy for therapy to promote maternal-fetal tolerance and prevent pregnancy loss. These results indicated that Eomes might be promising early warming targets of miscarriage, though further studies are required to determine that the altered number and function of Eomes + dCD4 + T cells are the cause or consequence of miscarriage., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Postmenopausal osteoporosis affected most elderly women with co-existence of lipid and bone metabolism disorders. However, the cellular and molecular mechanisms underlying the parallel progression and cross-talk of these systems remained unclear. In the present study, low-density lipoprotein receptor knockout (LDLR -/- ) mice were chosen to elucidate the effect of LDLR in regulating the differentiation of osteoblasts, which were responsible for bone formation and modulation of osteoclastogenesis. Primary osteoblasts were isolated from the calvarium of newborn LDLR -/- or wild-type mice followed by osteoblastic differentiation culture in vitro. Alkaline phosphatase activity was significantly decreased in LDLR -/- osteoblasts compared to wild-type controls, combined with calcium deposit formation delay, implying impaired osteoblastogenesis in vitro. Consistent with these findings, the expression of runt-related transcription factor 2 (Runx2) was decreased 3 days after differentiation in LDLR -/- osteoblasts compared to wild-type controls. Moreover, the expression of Osterix was decreased 7 days after differentiation in LDLR -/- osteoblasts compared to wild-type controls, later than Runx2.However, the osteoclastogenesis modulation role of osteoblasts was unaffected by the LDLR deficiency, evidenced by the same level of osteoprotegerin (OPG)/receptor activator of nuclear factor-κ B ligand (RANKL) axis between LDLR -/- and wild-type control osteoblasts. Our results provide a novel insight into the role of LDLR during osteoblastic differentiation and improve understanding of cross-talk between bone and lipid metabolisms.

The aim of this study was to evaluate primitively whether the extent and component of astigmatism influences regression in degree of spherical (DS) and the best corrected visual acuity (BCVA) of children with hyperopia of +5.00 diopters (D) or greater. Children were screened from the outpatient refraction database in the Wenling No. 1 People's Hospital in Zhejiang province and in Eye & ENT Hospital of Fudan University between June 2005 and December 2015. Eligible eyes were divided into three groups according to the extent of astigmatism: group of astigmatism ≤ -2 D of cylinder, group without astigmatism or with astigmatism ≥ -0.5 D of cylinder, and the group with astigmatism ≥ -0.75 D and ≤ -1.75 D of cylinder. For the component of astigmatism, eyes with astigmatism as ≤ -0.75 D of cylinder were divided into 3 groups: with the rule (WTR), against the rule (ATR) and the group with the oblique. Differences in the changes of BCVA and refractive error (RE) during follow-up terms were compared within and among groups. Differences in the mean DS or BCVA were not statistically significant between groups according to the extent of the astigmatism at the last visit (p = 0.2396 and p = 0.2131, respectively). As for the component of astigmatism, the group with oblique astigmatism had more severe hyperopia than the group of WTR (p < 0.0001) and mean BCVA in the group of ATR were better than that of the other two groups (p < 0.0001) at the first visit. However, the among-group changes were not significant at the end of the observation (p > 0.1). The regression of DS and improvement of the BCVA in children with hyperopia of +5.00D or greater may be irrespective of the component and the extent of astigmatism.