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Chromosome 8q gain is associated with poor clinical outcomes in prostate cancer, but the underlying biological mechanisms remain to be clarified. CSN5, a putative androgen receptor (AR) partner that is located on chromosome 8q, is the key subunit of the COP9 signalosome, which deactivates ubiquitin ligases. Deregulation of CSN5 could affect diverse cellular functions that contribute to tumor development, but there has been no comprehensive study of its function in prostate cancer. The clinical significance of CSN5 amplification/overexpression was evaluated in 16 prostate cancer clinical cohorts. Its oncogenic activity was assessed by genetic and pharmacologic perturbations of CSN5 activity in prostate cancer cell lines. The molecular mechanisms of CSN5 function were assessed, as was the efficacy of the CSN5 inhibitor CSN5i-3 in vitro and in vivo. Finally, the transcription cofactor activity of CSN5 in prostate cancer cells was determined. The prognostic significance of CSN5 amplification and overexpression in prostate cancer was independent of MYC amplification. Inhibition of CSN5 inhibited its oncogenic function by targeting AR signaling, DNA repair, multiple oncogenic pathways, and spliceosome regulation. Furthermore, inhibition of CSN5 repressed metabolic pathways, including oxidative phosphorylation and glycolysis in AR-negative prostate cancer cells. Targeting CSN5 with CSN5i-3 showed potent antitumor activity in vitro and in vivo. Importantly, CSN5i-3 synergizes with PARP inhibitors to inhibit prostate cancer cell growth. CSN5 functions as a transcription cofactor to cooperate with multiple transcription factors in prostate cancer. Inhibiting CSN5 strongly attenuates prostate cancer progression and could enhance PARP inhibition efficacy in the treatment of prostate cancer.
In women, metabolic health deteriorates after menopause, and the role of physical activity (PA) in mitigating the change is not completely understood. This study investigates the changes in indicators of metabolic health around menopause and evaluates whether PA modulates these changes.

Longitudinal data of 298 women aged 48-55 years at baseline participating in the ERMA and EsmiRs studies was used. Mean follow-up time was 3.8 (SD 0.1) years. Studied indicators of metabolic health were total and android fat mass, waist circumference, waist-to-hip ratio (WHR), systolic (SBP) and diastolic (DBP) blood pressure, blood glucose, triglycerides, serum total cholesterol, and high- (HDL-C) and low-density (LDL-C) lipoprotein cholesterol. PA was assessed by accelerometers and questionnaires. The participants were categorized into three menopausal groups PRE-PRE (pre- or perimenopausal at both timepoints, n = 56), PRE-POST (pre- or perimenopausal at baseline, postmenopausal at follow-up, n = 149), and POST-POST (posddle-aged women, menopause may accelerate the changes in multiple indicators of metabolic health. PA associates with healthier blood lipid profile and body composition in middle-aged women but does not seem to modulate the changes in most of the studied metabolic health indicators during the menopausal transition.BACKGROUND The purpose of this observational cohort study was to assess patient and operator-dependent factors which could have an impact on total fluoroscopy time during ultrasound and fluoroscopy-guided percutaneous transhepatic biliary drainage (PTBD). MATERIAL AND METHODS Between October 2016 and November 2020, 127 patients with malignant biliary obstruction underwent ultrasound- and fluoroscopy-guided PTBD with the right-sided intercostal approach. The initial bile duct puncture was ultrasound-guided in all patients, and the puncture angle was measured by ultrasound. Any subsequent steps of the procedure were performed under continuous fluoroscopy (15 fps). The patients were divided in 2 groups based on the puncture angle ≤30° (group I) and >30° (group II). In a retrospective analysis, both groups were compared for inter- and intragroup variability, technical success, total fluoroscopy time, and complications. RESULTS In group II, the recorded total fluoroscopy time (232.20±140.94 s) was significantly longer than that in group I (83.44±52.61 s) (P less then 0.001). In both groups, total fluoroscopy time was significantly longer in cases with a lesser degree of bile duct dilatation, intrahepatic bile duct tortuosity, presence of liver metastases, and multiple intrahepatic bile duct strictures. CONCLUSIONS The initial bile duct puncture angle was identified as an operator-dependent factor with the possible impact on total fluoroscopy time. The puncture angle of less than 30° was positively correlated with overall procedure efficacy and total fluoroscopy time reduction.BACKGROUND Kikuchi-Fujimoto disease (KFD) is a rare benign and usually local lymphadenopathy that typically occurs in young women. Patients with it usually have non-specific symptoms, such as fever in the afternoon, cervical lymphadenitis, and weight loss. Posterior cervical lymphadenopathy is the most common manifestation of KFD. The symptoms often last for a few weeks and then resolve spontaneously. The cause of KFD is unknown; however, it is considered to be related to some infectious agents, as well as several autoimmune diseases. Because of the non-specific symptoms and the rarity of KFD, the cervical lymphadenopathy associated with it can be misdiagnosed as coming from a more common condition. Making a correct diagnosis requires histology of the affected lymph nodes. CASE REPORT Here, we describe the case of a 25-year-old Vietnamese woman who presented with mild fever in the afternoons and enlarged cervical lymph nodes with no local sign of inflammation. She was initially believed to have tubercular lymphadenitis because of her symptoms and the high prevalence of tuberculosis in Vietnam. However, she had no respiratory symptoms and tested negative on QuantiFERON-TB Gold. Pathology from the patient's lymph node specimen showed an abnormal inflammatory reaction in the tissue. Her lesions were suspected to have been caused by KFD and she was treated successfully with nonsteroidal anti-inflammatory drug (NSAID) therapy. CONCLUSIONS KFD is a benign disease that manifests with common symptoms. The diagnosis is based on biopsy of a specimen and pathology results. No treatment is required in patients who have no symptoms. Patients with symptoms usually respond well to a short course of NSAID therapy.
A controlled laboratory study.

The aim of this study was to examine bone damage caused by irradiation to spinal vertebrae in rats.

Radiotherapy is widely used in the treatment of malignant spine tumors. However, a few studies have reported vertebral fractures following radiotherapy as an adverse reaction. There are no reports on irradiation-induced changes in bone fragility, mechanical and structural changes focusing on the spine, and the mechanism of irradiation-induced bone osteoporosis.

Eighty-four female Wistar rats were randomly allocated to the 20 Gy irradiated or the nonirradiated (control) group. see more The lumbar vertebrae were irradiated with an external focal radiation dose of 20 Gy. Biomechanical, structural, and histological analyses were performed at 0, 2, 4, 6, 8, 12, and 24 weeks after irradiation. Structural analysis and bone density measurement of vertebral trabecular bone were performed by μCT. Histopathological evaluation was performed by hematoxylin and eosin staining and immunostaining.

The bone strength at 2 weeks after irradiation (311 ± 23 N) was 22% lower than that before irradiation (398 ± 34 N) (P < 0.05). The trabecular spacing increased, and trabecular connectivity and width decreased significantly in the irradiated group compared with those in the non-irradiated group. The three-dimensional structure model became coarse, and the trabecular structure continued to thin and disrupt after irradiation. There was no significant change in the bone mineral density in both groups.

A decrease in bone strength was observed 2 weeks after irradiation. Bone mineral density remained unaltered, whereas the microstructure of trabecular bone changed, suggesting bone damage by irradiation.Level of Evidence N/A.
A decrease in bone strength was observed 2 weeks after irradiation. Bone mineral density remained unaltered, whereas the microstructure of trabecular bone changed, suggesting bone damage by irradiation.Level of Evidence N/A.
Cross-sectional study.

This study aimed to objectively evaluate spastic gait and reveal its novel characteristics via analysis of gait in patients with cervical myelopathy (CM) using the Timed Up and Go (TUG) test with a laser range sensor.

Among patients with CM, spastic gait is a common diagnostic symptom; thus, objective assessments of spastic gait would be useful for the diagnosis of CM and recognition of disease status. link2 Although spastic gait has been objectively evaluated in previous studies, the methods employed in those studies are not suitable for clinical settings.

In total, 37 and 24 participants were recruited for a control group and CM group, respectively. CM was diagnosed by spine surgeons. We developed a laser TUG test, in which the position and velocity of both the legs were captured. The parameter values for both groups were statistically compared, and odds ratios were calculated using logistic regression analyses.

The total TUG test time, time to stand up, time to first step, numberigher if the individual took longer than 9 seconds to complete the TUG test.Level of Evidence 4.
Basic science study.

The aim of this study was to examine whether epidural fat tissue (EFT) transplantation can prevent epidural adhesion after laminectomy more efficiently than subcutaneous fat tissue (SFT) transplantation.

Epidural adhesion is almost inevitable after laminectomy. Although many materials have been used to prevent adhesion, none has been widely accepted. As EFT is an ectopic fat tissue located on the dura mater and there is no adhesion between EFT and the dura mater, we focused on the efficacy of EFT for adhesion prevention.

We examined the differences in histology and gene expression between EFT and SFT of mice. We performed laminectomy at the 10th thoracic level and immediately transplanted EFT or SFT to the dura mater in mice. At six weeks after transplantation, we performed histological and gene expression analyses and evaluated the adhesion tenacity. In addition, we examined the characteristic differences between human EFT and SFT.

The adipocytes of EFT were significantly smallafter laminectomy in a mouse model.Level of Evidence N/A.
Randomized controlled trial.

To evaluate the efficacy of adjunctive topical tranexamic acid (tTXA) in reducing postoperative blood loss and packed red cell (PRC) transfusion in patients who underwent palliative decompressive spinal metastasis surgery for malignant epidural spinal cord compression.

Palliative decompressive spinal metastasis surgery is associated with massive postoperative blood loss and increased transfusion rate. tTXA reduces blood loss in traumatic or degenerative spinal surgery; however, the role of topical TXA in decompressive spinal metastasis surgery remains controversial.

A total of 65 patients who underwent palliative decompressive thoracolumbar spinal metastasis surgery were included in this study. link3 In 33 patients, 1 g of tTXA (20 mL) was soaked in an absorbable gelatin sponge and placed lateral to the decompressive site. The remaining 32 patients in the control group received the same procedures with normal saline at the same volume, instead of TXA. All of the patients received standard 1 g intravenous TXA, just before initiating the operation.
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