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Background: Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic valve calcium (AVC) progression are limited, rendering its precise role in AVC ambiguous., Methods: From the Multi-Ethnic Study of Atherosclerosis database, we included 5597 individuals (61.8 ± 10.1 years and 47.5% men) without atherosclerotic cardiovascular disease at baseline for analysis. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), as estimated by the Martin/Hopkins equation. Using the adjusted Cox regression analyses, we examined the relationships between RC levels and AVC progression. Furthermore, we conducted discordance analyses to evaluate the relative AVC risk in RC versus LDL-C discordant/concordant groups., Results: During a median follow-up of 2.4 ± 0.9 years, 568 (10.1%) participants exhibited AVC progression. After adjusting for traditional cardiovascular risk factors, the HRs (95% CIs) for AVC progression comparing the second, third, and fourth quartiles of RC levels with the first quartile were 1.195 (0.925-1.545), 1.322 (1.028-1.701) and 1.546 (1.188-2.012), respectively. Notably, the discordant high RC/low LDL-C group demonstrated a significantly elevated risk of AVC progression compared to the concordant low RC/LDL-C group based on their medians (HR, 1.528 [95% CI 1.201-1.943]). This pattern persisted when clinical LDL-C threshold was set at 100 and 130 mg/dL. The association was consistently observed across various sensitivity analyses., Conclusions: In atherosclerotic cardiovascular disease-free individuals, elevated RC is identified as a residual risk for AVC progression, independent of traditional cardiovascular risk factors. The causal relationship of RC to AVC and the potential for targeted RC reduction in primary prevention require deeper exploration., (© 2023. The Author(s).)

Background: Conservative treatment is the recommended first-line treatment for degenerative disc diseases. Traction therapy has historically been one of the most common clinical methods to address this, but the clinical effect remains controversial., Methods: Forty-two six-month-old male Sprague-Dawley rats were randomly divided into six groups: the model group (Group A, four coccyx vertebrae (Co7-Co10) were fixed with customized external fixators, and the vertebral disc degeneration model was constructed by axial compression of the target segment Co8 - Co9 for 4 weeks), the experimental control group (Group B, after successful modeling, the external fixation device was removed and self-rehabilitation was performed) and four intervention groups (Groups C to F): Groups C and E: Co8 - Co9 vertebrae compressed for 4 weeks followed by two or 4 weeks of high tension traction (HTT), respectively, and Groups D and F: vertebrae compressed for 4 weeks followed by two or 4 weeks of low-tension traction (LTT), respectively. Imaging tests (X-ray and MRI) were performed to assess disc height and T2 signal intensity at each time point. After the experiment, the animals were euthanized, and the caudal vertebrae were collected for analysis of intervertebral disc histopathology, proteoglycan content, and micronanostructure of the annulus fibrosus, nucleus pulposus and bony endplate., Results: Signs of tissue regeneration were apparent in all four intervention groups. After two to 4 weeks of intervention (HTT and LTT), the morphology of pores in the bony endplate, their number, and diameter had recovered significantly compared with those in Group A. The LTT group was superior to the HTT group, and the 4w in situ group was significantly superior to the 2w group. Meanwhile, the histological scores of discs, the mean fibril diameter and modulus of annulus fibrosus were significantly improved compared with the control groups, and the LTT group was superior to HTT group., Conclusions: Low-tension traction better promotes active reconstruction of bony endplates and improves the elastic modulus and micro/nanostructure of the disc. Thus, it further promotes the regeneration and repair of intervertebral discs., (© 2022. The Author(s).)

Background: Articular cartilage has a high-weight-bearing area and a low-weight-bearing area, the macroscopic elastic moduli of the two regions are different. Chondrocytes are affected by the applied force at the microscopic level. Currently, the modulus of the two areas at the micro and nano levels is unknown, and studies on the relationship between macro-, micro- and nano-scale elastic moduli are limited. Such information may be important for further understanding of cartilage mechanics. Moreover, the surface morphology, proteoglycan content, and micro and nano structure of the two areas, which influences the mechanical properties of cartilage should be discussed., Methods: Safranin-O/Fast Green staining was used to evaluate the surface morphology and semi-quantify proteoglycan content of porcine femoral head cartilage between the two weight-bearing areas. The unconfined compression test was used to determine the macro elastic modulus. Atomic force microscope was used to measure the micro and nano compressive elastic modulus as well as the nano structure. Scanning electron microscope was employed to evaluate the micro structure., Results: No significant differences in the fibrillation index were observed between two areas (P = 0.5512). The Safranin-O index of the high-weight-bearing area was significantly higher than that of the low-weight-bearing area (P = 0.0387). The compressive elastic modulus of the high-weight-bearing area at the macro and micro level was significantly higher than that of the low-weight-bearing area (P = 0.0411 for macro-scale, and P = 0.0001 for micro-scale), while no statistically significant differences were observed in the elastic modulus of collagen fibrils at the nano level (P = 0.8544). The density of the collagen fibers was significantly lower in the high-weight-bearing area (P = 0.0177). No significant differences were observed in the structure and diameter of the collagen fibers between the two areas (P = 0.7361)., Conclusions: A higher proteoglycan content correlated with a higher compressive elastic modulus of the high-weight-bearing area at the micro level than that of the low-weight-bearing area, which was consistent with the trend observed from the macroscopic compressive elastic modulus. The weight-bearing level was not associated with the elastic modulus of individual collagen fibers and the diameter at the nano level. The micro structure of cartilage may influence the macro- and micro-scale elastic modulus.

Background: To retrospectively investigate the clinical characteristics, initial treatment, relapse, therapy outcome, and prognosis of Chinese patients with primary testicular lymphoma (PTL) through analysis of the cases of our institute., Methods: From December 2008 to July 2018, all patients with PTL were included in this study. Kaplan-Meier method was used to estimate PFS and OS. The Cox proportional hazards model was used to compare the survival times for groups of patients differing in terms of clinical and laboratory parameters., Results: All 28 PTL patients (24 DLBCL, three NK/T lymphomas, and one Burkkit's lymphoma) with a median age of 65.5 years were included in this study. Six patients were observed recurrence among all the 22 individuals evaluated. Following orchiectomy and systemic chemotherapy, with or without intrathecal prophylaxis, complete response was achieved in 15 (68%) patients. For DLBCL patients, the median progression-free survival (PFS) was 44.63 months (95% CI 17.71-71.56 months), and the median overall survival (OS) was 77.02 months (95% CI, 57.35-96.69 months). For all the DLBCL patients, the 5-year PFS and 5-year OS were 35.4% (95%CI, 14.8-56.0%) and 53.4% (95%CI, 30.1-76.7%). Without further chemotherapy following orchiectomy (HR = 3.4, P = 0.03) were associated with inferior PFS of DLBCL patients. Advanced Ann Arbor stage (HR =5.9, P = 0.009) and high (international prognostic index, IPI) score: 3-5 (HR =3.9, P = 0.04) were correlated with shorter OS of DLBCL patients., Conclusion: This study confirms that PTL is an aggressive malignant with a poor prognosis. Limited Ann Arbor stage, further chemotherapy following orchiectomy, and low IPI score (less than 2) are correlated with superior survival for DLBCL patients.

Background: Cervical spine fixation or immobilization has become a routine treatment for spinal fracture, dislocation, subluxation injuries, or spondylosis. The effects of immobilization of intervertebral discs of the cervical spine is unclear. The goal of this study was to evaluate the effects of long-segment in-situ immobilization of intervertebral discs of the caudal vertebra, thereby simulating human cervical spine immobilization., Methods: Thirty-five fully grown, male Sprague-Dawley rats were used. Rats were randomly assigned to one of five groups: Group A, which served as controls, and Groups B, C, D, and E, in which the caudal vertebrae were in-situ immobilized using a custom-made external device that fixed four caudal vertebrae (Co7-Co10). After 2 weeks, 4 weeks, 6 weeks, and 8 weeks of in-situ immobilization, the caudal vertebrae were harvested, and the disc height, the T2 signal intensity of the discs, disc morphology, the gene expression of discs, and the structure and the elastic modulus of discs was measured., Results: The intervertebral disc height progressively decreased, starting at the 6th week. At week 6 and week 8, disc degeneration was classified as grade III, according to the modified Pfirrmann grading system criteria. Long-segment immobilization altered the gene expression of discs. The nucleus pulposus showed a typical cell cluster phenomenon over time. The annulus fibrosus inner layer began to appear disordered with fissure formation. The elastic modulus of collagen fibrils within the nucleus pulposus was significantly decreased in rats in group E compared to rats in group A (p < 0.05). On the contrary, the elastic modulus within the annulus was significantly increased in rats in group E compared to rats in group A (p < 0.05)., Conclusion: Long-segment in-situ immobilization caused target disc degeneration, and positively correlated with fixation time. The degeneration was not only associated with changes at the macroscale and microscale, but also indicated changes in collagen fibrils at the nanoscale. Long-segment immobilization of the spine (cervical spine) does not seem to be an innocuous strategy for the treatment of spine-related diseases and may be a predisposing factor in the development of the symptomatic spine.

Background: Particulate matter (PM), which has adverse effects on citizen health, is a major air pollutant in Beijing city. PM 2.5 is an indicator of PM in urban areas and can cause serious damage to human health. Many epidemiological studies have shown that nuclear factor-kappa B (NF-κB) is involved in PM 2.5 -induced cell injury, but the exact mechanisms are not well understood., Methods: The cytotoxic effects of PM 2.5 at 25-1600 μg/ml for 24 h were determined by MTT assay in Chinese hamster ovary cells (CHO) cells. Flow cytometry was used to determine the apoptosis rate induced by PM 2.5 . The destabilized enhanced green fluorescent protein (d2EGFP) green fluorescent protein reporter system was used to determine the NF-κB activity induced by PM 2.5 . The expression of pro-apoptotic Bcl-2-associated death promoter (BAD) proteins induced by PM 2.5 was determined by western blotting to explore the relationship between PM 2.5 and the NF-κB signaling pathway and to determine the toxicological mechanisms of PM 2.5 ., Results: PM 2.5 collected in Beijing urban districts induces cytotoxic effects in CHO cells according to MTT assay with 72.28% cell viability rates even at 200 μg/ml PM 2.5 and flow cytometry assays with 26.97% apoptosis rates at 200 μg/ml PM 2.5 . PM 2.5 increases the activation levels of NF-κB, which have maintained for 24 h. 200 μg/ml PM 2.5 cause activation of NF-κB after exposure for 4 h, the activation peak appears after 13.5 h with a peak value of 25.41%. The average percentage of NF-κB activation in whole 24 h is up to 12.9% by 200 μg/ml PM 2.5 . In addition, PM 2.5 decreases the expression level of the pro-apoptotic protein BAD in a concentration-dependent manner., Conclusions: PM 2.5 induces NF-κB activation, which persists for 24 h. The expression of pro-apoptotic protein BAD decreased with increased concentrations of PM 2.5 . These findings suggest that PM 2.5 plays a major role in apoptosis by activating the NF-κB signaling pathway and reducing BAD protein expression.