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Objective: Losartan and activation of the peroxisome proliferator-activated receptor-γ (PPARγ) have been previously reported to alleviate the progression of osteoarthritis (OA). However, the nature of the interaction between losartan and PPARγ in OA remains elusive. Therefore, we aimed to investigate the mechanism of the regulation of PPARγ by losartan in the context of OA. Methods: Clinical samples of OA patients were collected and the chondrocytes were further isolated, and used to construct OA chondrocyte model via induction with IL-1β. An OA mouse model was developed by the surgical destabilization of the medial meniscus (DMM). OA chondrocytes were treated with losartan, PPARγ siRNA and the PPAR-γ agonist GW1929 alone or in combination. Furthermore, the OA mice were treated with varying doses of losartan to determine the best mode of administration and treatment dose. Subsequently, the DMM mice were treated with losartan and GW9662. Expression of PPARγ, key proteins of the transforming growth factor-beta1 (TGF-β1) signaling pathway and the markers of OA degeneration were evaluated by the Western blot analysis, while effects on OA inflammatory factors were determined by ELISA. Results: The downregulation of PPARγ and the upregulation of TGF-β1 signaling pathway were detected in the OA cartilage tissues and chondrocytes. Losartan treatment or PPARγ activation contributes to reduced levels of IL-6, IL-1β, TNF-α, and COX-2, expression of TGF-β1, MMP-13, ADAMTS-4, ADAMTS-5, HtrA1, and iNOS, along with reduced Smad2 and Smad3 phosphorylation, but elevated PPARγ and Collagen II expression in vivo and in vitro. Additionally, the intraarticular injection of losartan into the knee joint proved to be the best mode of administration, and 10 ​mg/mL being the optimal treatment concentration. Conclusion: Our results show that losartan could arrest the progression of OA by upregulating PPARγ expression and inactivating the TGF-β1 signaling pathway.The translational potential of this article: Our results provide a biological rationale for the use of losartan as a potential candidate for OA treatment.

Extra-articular synovial chondromatosis is a rare entity in the foot and ankle. We present a case of a 49-year-old female who presented for evaluation of a palpable concern following trauma; which was found to represent synovial chondromatosis. This case demonstrates the multimodality imaging findings, including ultrasound and MRI, with histopathologic correlation. Keywords: Synovial chondromatosis, Extra-articular, Ankle, MRI, Ultrasound, Pathology

Introduction: A novel type of a disposable circumcision suture device (DCSD) has been proved to be effective and safe; however, a few cases of severe bleeding took place after circumcisions. Aim: To evaluate the effectiveness of a modified double-layer pressure dressing to avoid severe bleeding after circumcision with the DCSD, in our department in a prospective randomized controlled study, and discuss the mechanism of bleeding with DCSD. Methods: Patients with redundant foreskin or phimosis were included between September 2018 and November 2019 and divided into 2 groups: In group A, the conventional pressure dressing was performed; in group B, an modified double-layer pressure dressing was performed. Main Outcome Measure: The main outcomes and complications (surgical time, incidence of glans ischemia, severe bleeding rate, infection rate, pain level, total cost, and overall satisfaction) were collected and analyzed. Results: A total of 624 patients were recruited for this study. There was no difference in the average age and body mass index between 2 groups. No patient suffered obvious glans ischemia. In group B, lower pain level, lower incidences of severe bleeding, and better satisfaction were recorded. Conclusion: The mechanism of bleeding with the DCSD was discussed in this study, and the modified pressure dressing was proved effective, safe, and easy to perform.W Jiang, J-li Fu, W-l Guo, et al. A Modified Pressure Dressing to Avoid Severe Bleeding After Circumcision With a Disposable Circumcision Suture Device and a Discussion on the Mechanism of Bleeding With the Disposable Circumcision Suture Device. Sex Med 2021;9:100288.

Purpose Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) planning can present challenges. This study examines the influence of head tilt angles on the dosimetric characteristics of target and organs at risk (OARs), aiming to identify the optimal tilt angle that yields optimal dosimetric outcomes using tomotherapy (TOMO). Methods Eight patients diagnosed with brain metastases underwent CT scans at five tilt angles: [0°, 10°), [10°, 20°), [20°, 30°), [30°, 40°), and [40°, 45°]. Treatment plans were generated using TOMO and volumetric modulated arc therapy (VMAT). Dosimetric parameters including conformity index (CI), homogeneity index (HI), D 2cc , D 98% , and D mean of PTV, as well as D max , and D mean of OARs were analyzed. Furthermore, a comparison was made between the dosimetric parameters of TOMO and VMAT plans. Finally, delivery efficiency of TOMO plans were assessed. Results For the PTV, [40°, 45°] tilt angle demonstrated significantly better conformity, homogeneity, lower D 2cc , and lower D mean for the PTV. Regarding the OARs, the [40°, 45°] head tilt angle demonstrated significantly lower D max and D mean in hippocampus, eyes, optic chiasm, and optic nerves. The [40°, 45°] tilt angle also showed significantly lower D max for brainstem and cochleas, as well as a lower D mean for lens. In the [40°,45°] tilt angle for HA-WBRT, TOMO showed superior performance over VMAT for the PTV. TOMO achieved lower D max for brainstem, cochleas, optic nerves, and optic chiasm, as well as a lower D mean for hippocampus. Furthermore, a significant correlation was found between delivery time and the PTV projection length in the sagittal plane. Conclusion The TOMO plan utilizing a tilt angle range of [40°, 45°] demonstrated superior PTV conformity and uniformity, along with enhanced OARs sparing. Furthermore, it exhibited a dosimetric advantage over VMAT for PTV and most OARs at the same angle range.

Sepsis-induced coagulopathy (SIC) is a critical condition in sepsis patients, with varying outcomes depending on the type of infection. This study aims to analyze the prognosis of different infections in SIC cohort. A retrospective cohort study was conducted on 525 patients diagnosed with SIC in the intensive care unit from December 2013 to December 2022. These patients were divided into four groups: a non-pneumonia or bacteremia group, a severe pneumonia group, a bacteremia group, and a severe pneumonia concomitant with bacteremia group. The 28-day mortality was 18% (49/271) in the other infections group, 31% (33/106) in the lung infections group, 23% (29/126) in the blood infections group and 36% (8/36) in the lung and blood co-infections group, respectively. Pearson correlation analysis showed that procalcitonin (PCT) correlated strongly with all detected hemostatic markers ( p

Backgrounds: Microfibril-associated protein 2 (MFAP2) is an extracellular matrix protein that regulates the function of microfibrils by interacting with fibrillin. MFAP2 has been reported to play an important role in metabolic diseases and has been shown to be significantly overexpressed in head and neck squamous cell carcinoma and Hepatocellular carcinoma (HCC). However, the molecular function and prognostic value of MFAP2 have never been reported in HCC or other tumors. Methods: In the present study, expression characteristics of MFAP2 in HCC, its influence on the development of HCC, as well as its function and potential mechanism in HCC were verified by Quantitative reverse transcription-polymerase chain reaction, bioinformatics data mining and in vitro cell experiments. Results: MFAP2 was prominently high-expressed in HCC and associated with cancer stages. HCC patients with higher MFAP2 expression displayed lower overall survival (OS) and disease-specific survival(DSS), while there was no significant difference in recurrence-free survival (RFS). In vitro experiments showed that downregulation of MFAP2 inhibited proliferation, migration level of HCC cells. Transcription factors, DNA methyltransferases, immune factors may interact with MFAP2 mRNA to promote tumor progression in HCC. Conclusion: These findings suggest that MFAP2 may play a key role in the development of HCC. Therefore, MFAP2 may be a valuable prognostic marker and an effective anticancer target in HCC.