NUP43 promotes PD-L1/nPD-L1/PD-L1 feedback loop via TM4SF1/JAK/STAT3 pathway in colorectal cancer progression and metastatsis.

Programmed cell death-ligand 1 (PD-L1) has a significant role in tumor progression and metastasis, facilitating tumor cell evasion from immune surveillance. PD-L1 can be detected in the tumor cell nucleus and exert an oncogenic effect by nuclear translocation. Colorectal cancer (CRC) progression and liver metastasis (CCLM) are among the most lethal diseases worldwide, but the mechanism of PD-L1 nuclear translocation in CRC and CCLM remains to be fully understood. In this study, using CRISPR-Cas9-based genome-wide screening combined with RNA-seq, we found that the oncogenic factor NUP43 impacted the process of PD-L1 nuclear translocation by regulating the expression level of the PD-L1 chaperone protein IPO5. Subsequent investigation revealed that this process could stimulate the expression of tumor-promoting factor TM4SF1 and further activate the JAK/STAT3 signaling pathway, which ultimately enhanced the transcription of PD-L1, thus establishing a PD-L1-nPD-L1-PD-L1 feedback loop that ultimately promoted CRC progression and CCLM. In conclusion, our study reveals a novel role for nPD-L1 in CRC, identifies the PD-L1-nPD-L1-PD-L1 feedback loop in CRC, and provides a therapeutic strategy for CRC patients.

A Brillouin microscopy analysis of the crystalline lenses of Chinese adults with myopia.

To evaluate lenticular biomechanical and geometric parameters in Chinese adults with myopia and identify relevant factors using Brillouin microscopy (BM) and Pentacam. The biomechanical and geometric properties of the ocular lenses of Chinese adults with myopia were quantified using BM. Anterior segment images were acquired using a Pentacam. Correlated factors including age, sex, spherical equivalent (SE), intraocular pressure (IOP), axial length (AL), white-to-white ratio (WTW), central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) were analyzed. We studied 65 eyes from 65 participants (mean age, 25.23 ± 6.12 years). Width of Top Plateau (WTP), Width of Bottom Plateau (WBP), Slope of Anterior Cortex (SAC), Slope of Posterior Cortex (SPC), and Height of Plateau (Height) metrics obtained using BM showed mean values of 2.597 ± 0.393 mm, 4.310 ± 0.535 mm, 1.344 ± 0.549 GPa/mm, -1.343 ± 0.480 GPa/mm, and 3.373 ± 0.048 GPa, respectively. No significant correlation was found between these parameters and sex, SE, IOP, CCT, ACA, or Height. Interestingly, WBP (r = 0.467, P < 0.001), SAC (r = 0.412, P = 0.001), and SPC (r = -0.280, P = 0.024) were significantly associated with age, and an age-related increase of WBP (slope of 35.36 ± 10.08 µm per year) was identified. Both ACD and ACV showed significant correlations with SAC (r = 0.329 and 0.380, P = 0.008 and 0.002, respectively), but not with SPC. BM provided a novel perspective on lenticular biomechanical and geometric properties in Chinese adults with myopia, which correlated with age, AL, WTW, ACD, and ACV.

A bibliometric analysis of miRNAs in rheumatoid arthritis from 2001 to 2022: Research hotspots and trends.

BACKGROUND: MicroRNAs (miRNAs) are widely recognized in the pathogenesis of autoimmune disease. As a key regulatory factor, miRNAs have introduced new biomarkers for the early diagnosis of rheumatoid arthritis (RA) and provided a favorable research direction for the development of novel therapeutic targets. This study aimed to explore the hotspots of miRNA research related to RA published from different countries, organizations, and authors. METHODS: From 2001 to 2022, publications on miRNA related to RA were identified in the Web of Science database. The total and annual number of publishments, citations, impact factor, H-index, productive authors, and involved journals were collected for quantitative and qualitative comparisons. RESULTS: A total of 29 countries/regions in the world have participated in the research of miRNAs and RA over the past two decades, and China (760, 53.18%) and the United States (233, 16.31%) account for the majority of the total publications. China dominated in total citation (17881) and H-index (62). A total of 507 academic journals have published articles in related fields, and Frontiers in Immunology published the most (53, 3.71%). Chih-hsin Tang of the China Medical University has published the most papers (16, 1.2%). Stanczyk (2008) published the most cited article Altered expression of miRNAs in synovial fibroblasts and synovial tissue in rheumatoid arthritis in Arthritis and Rheumatism, with 660 citations. Inflammation is the high-frequency keyword outside of RA and miRNAs, and related researches have mainly focused on miR-146a and miR-155. CONCLUSIONS: In the past two decades, extensive and continuous research has been conducted to investigate the role of miRNAs in RA, and miRNAs are widely recognized in the pathogenesis of RA. Related research has mainly focused on miR-146a and miR-155 that have shown promising results as key factors in RA experimental models. Focusing on clinical applications and translational research may be the future research direction and hotspot based on molecular biology basic research and mechanism exploration.

Quantum nonlinear effect in a dissipatively coupled optomechanical system.

A full-quantum approach is used to study the quantum nonlinear properties of a compound Michelson-Sagnac interferometer optomechanical system. By deriving the effective Hamiltonian, we find that the reduced system exhibits a Kerr nonlinear term with a complex coefficient, entirely induced by the dissipative and dispersive couplings. Unexpectedly, the nonlinearities resulting from the dissipative coupling possess non-Hermitian Hamiltonian-like properties preserving the quantum nature of the dispersive coupling beyond the traditional system dissipation. This protective mechanism allows the system to exhibit strong quantum nonlinear effects when the detuning (the compound cavity detuning Δc and the auxiliary cavity detuning Δe) and the tunneling coupling strength (J) of two cavities satisfy the relation J2 = ΔcΔe. Moreover, the additive effects of dispersive and dissipative couplings can produce strong anti-bunching effects, which exist in both strong and weak coupling conditions. Our work may provide a new way to study and produce strong quantum nonlinear effects in dissipatively coupled optomechanical systems.

General Hyperspectral Image Super-Resolution via Meta-Transfer Learning.

Recent advances in deep learning-based methods have led to significant progress in the hyperspectral super-resolution (SR). However, the scarcity and the high dimension of data have hindered further development since deep models require sufficient data to learn stable patterns. Moreover, the huge domain differences between hyperspectral image (HSI) datasets pose a significant challenge in generalizability. To address these problems, we present a general hyperspectral SR framework via meta-transfer learning (MTL). We randomly sample various spectral ranges for SR tasks during MTL, allowing the model to accumulate diverse task experiences. Additionally, we implement a task schedule to gradually expand the number of bands, bridging the significant domain differences between datasets. By leveraging multiple datasets, we are able to achieve better performance and greater generalizability, making it applicable under various circumstances. Meanwhile, as a general framework, our scheme can be applied to existing methods to obtain performance improvements. In addition, we design an advanced network architecture based on the multifusion features to further improve the performance. Experiments demonstrate that our method not only achieves superior performance in both qualitative and quantitative terms but also can adapt robustly to a new and difficult sample, where few epochs can yield quite considerable results.

Additional suture augmentation to anterior cruciate ligament reconstruction with hamstring autografts bring no benefits to clinical results, graft maturation and graft-bone interface healing.

BACKGROUND: From the perspective of graft protection and early rehabilitation during the maturation and remodeling phases of graft healing, suture augmentation (SA) for anterior cruciate ligament reconstruction (ACLR) has attracted more and more attention. STUDY DESIGN: Retrospective study. PURPOSE: To determine whether the additional SA affects clinical results, graft maturation and graft-bone interface healing during two years follow-up after ACLR. METHODS: 20 ACLRs with additional SA (ACLR-SA group) and 20 ACLRs without additional SA (ACLR group) were performed between January 2020 and December 2021 by the same surgeon and were retrospectively analyzed. Pre- and postoperative International Knee Documentation Committee (IKDC) scores, Lysholm scores, graft failure and reoperation were evaluated. The signal/noise quotient (SNQ) of autografts and the signal intensity of graft-bone interface were analyzed. All 40 patients in ACLR-SA group and ACLR group completed 2-years follow-up. RESULTS: There was no patient in the two cohorts experienced graft failure and reoperation. The postoperative IKDC and Lysholm scores have been significantly improved compared with preoperative scored in both ACLR-SA group and ACLR group, however, there was no significant difference between two groups. The SNQ of proximal graft of ACLR-SA group (14.78 ± 8.62 vs. 8.1 ± 5.5, p = 0.041) was significantly greater while the grades of graft-bone interface healing of posterior tibial was significantly lower than that of ACLR group at 1-year postoperatively (p = 0.03), respectively. There were no significant differences between the two groups of the SNQ of proximal, distal medial graft segments, and the graft-bone interface healing grades of anterior femoral, posterior femoral, anterior tibial and posterior tibial at other time points (p>0.05). CONCLUSIONS: The additional SA in ACLR had no effect on IKDC scores, Lysholm scores, graft maturation and graft-bone interface healing at 2-year postoperatively. Our research does not support the routine use of SA in ACLR.

Osteoporosis and depression in perimenopausal women: From clinical association to genetic causality.

BACKGROUND: Osteoporosis and major depressive disorder (MDD) represent two significant health challenges globally, particularly among perimenopausal women. This study utilizes NHANES data and Mendelian randomization (MR) analysis to explore the link between them, aiming to provide a basis for intervention strategies for this group. METHODS: The study analyzed NHANES 2007-2018 data using weighted logistic regression in R software to evaluate the link between MDD and osteoporosis risk. Then, a two-sample MR analysis with GWAS summary statistics was performed, mainly using the IVW method. Additional validation included MR Egger, Weighted Median, Mode, and MR-PRESSO methods. RESULTS: The research analysis indicated a significant link between MDD and the risk of osteopenia/osteoporosis. Our analysis revealed a significant positive relationship between MDD and both femoral neck osteoporosis (OR = 6.942 [95 % CI, 1.692-28.485]) and trochanteric osteoporosis (OR = 4.140 [95 % CI, 1.699-10.089]). In analyses related to osteopenia, a significant positive correlation was observed between MDD and both total femoral osteopenia (OR = 3.309 [95 % CI, 1.577-6.942]) and trochanteric osteopenia (OR = 2.467 [95 % CI, 1.004-6.062]). Furthermore, in the MR analysis, genetically predicted MDD was causally associated with an increased risk of osteoporosis via the IVW method (P = 0.013). LIMITATIONS: Our study was limited by potential selection bias due to excluding subjects with missing data, and its applicability was primarily to European and American populations. CONCLUSION: Integrating NHANES and MR analyses, a robust correlation between MDD and osteoporosis was identified, emphasizing the significance of addressing this comorbidity within clinical practice and meriting further investigation.

[Medical emergency support for the snowboarding project during the Beijing Winter Olympics].

OBJECTIVE: To analyze and summarize the medical security situation of the snowmobile, sled, and steel frame snowmobile tracks at the National Sliding Centre, and to provide experience for future event hosting and medical security work for mass ice and snow sports. METHODS: Retrospective analysis of injuries and treatment of athletes participating in the International Training Week and World Cup for Ski, Sled, and Steel Frame Ski from October to November 2021(hereinafter referred to as "International Training Week"), as well as the Ski, Sled, and Steel Frame Ski events at the Beijing Winter Olympics in February 2022 (hereinafter referred to as the "Beijing Winter Olympics"). We referred to and drew on the "Medical Security Standards for Winter Snow Sports" to develop specific classification standards for analyzing injured areas, types of injuries, and accident locations. RESULTS: A total of 743 athletes participated in the International Training Week and the Beijing Winter Olympics. During the competition, there were 58 incidents of overturning, prying, and collision, of which 28 (28 athletes) were injured, accounting for 48.3% of the total accidents and 3.8% of the total number of athletes. Among them, there were 9 males (32.1%) and 19 females (67.9%), with an average age of (26.3 ± 4.7) years. Among the 28 injured athletes, 20 cases (71.4%) received on-site treatment for Class Ⅰ injuries, while 8 cases (28.6%) had more severe injuries, including Class Ⅱ injuries (7 cases) and Class Ⅲ injuries (1 case), which were referred to designated hospitals for further treatment. Among the 28 injured athletes, 3 cases (10.7%) experienced multiple injuries, including 2 cases of 2 injuries and 1 case of 3 injuries. The most common injuries were in the ankle and toes (10/32, 31.3%). Out of 28 injured athletes, one (3.6%) experienced two types of injuries simultaneously, with joint and/or ligament injuries being the most common (11/29, 37.9%). The most accident prone point on the track was the ninth curve (18/58, 31.0%). CONCLUSION: Through the analysis and summary of medical security work, it can provide better experience and reference for the future development of snowmobile, sled, and steel frame snowmobile sports in China, making the National Snowy and Ski Center truly a sustainable Olympic heritage.

Composite Hydrogel Containing Collagen-Modified Polylactic Acid-Hydroxylactic Acid Copolymer Microspheres Loaded with Tetramethylpyrazine Promotes Articular Cartilage Repair.

Articular cartilage defects pose a significant challenge due to the limited self-healing ability of cartilage. However, traditional techniques face limitations including autologous chondrocyte expansion issues. This study aims to investigate the effects of the polylactic acid-glycolic acid (PLGA) and collagen-surface modified polylactic acid-glycolic acid (CPLGA) microspheres loaded with tetramethylpyrazine (TMP) on two cell types and the regeneration potential of articular cartilage. CPLGA microspheres are prepared by Steglich reaction and characterized. They evaluated the effect of TMP-loaded microspheres on HUVECs (Human Umbilical Vein Endothelial Cells) and examined the compatibility of blank microspheres with BMSCs (Bone marrow mesenchymal stromal cells) and their potential to promote cartilage differentiation. Subcutaneous implant immune tests and cartilage defect treatment are conducted to assess biocompatibility and cartilage repair potential. The results highlight the efficacy of CPLGA microspheres in promoting tissue regeneration, attributed to improved hydrophilicity and collagen-induced mitigation of degradation. Under hypoxic conditions, both CPLGA and PLGA TMP-loaded microspheres exhibit inhibitory effects on HUVEC proliferation, migration, and angiogenesis. Notably, CPLGA microspheres show enhanced compatibility with BMSCs, facilitating chondrogenic differentiation. Moreover, the CPLGA microsphere-composite hydrogel exhibits potential for cartilage repair by modulating angiogenesis and promoting BMSC differentiation.

Physical breakdown of CH4 hydrate under stress: a molecular dynamics simulation study.

As a solid energy source, CH4 hydrate will inevitably break down physically as the result of geological movement or exploitation. Here, the molecular dynamics method was employed to simulate the uniaxial-deformation behavior of structure I (sI type) CH4 hydrate under stress. The stress increases regardless of whether the hydrate is stretched or squeezed, and other physical parameters also changed, such as hydrate cage numbers, order parameters, and the number of water molecules. A noticeable difference is observed between the two systems. Upon stretching, the stress immediately recovers to 0 GPa once the hydrate is completely stretched apart. During the squeeze process, the stress is ultimately not zero since solid and liquid are always in contact. When the hydrate is stretched apart, about 5% of water molecules change from solid to liquid, about 7.8% of CH4 molecules lose their shelter and become free due to the disintegration of water cages. While in the squeezing process, large cages (51262) are crushed more easily than small cages (512); in the end, about 93.5% of large cages and 73% of small cages are crushed, and approximately 87.5% CH4 is released from the cages. In mining CH4 hydrates, caution must be exercised, as if the hydrates break as a result of stress, a large release of CH4 may pose a security risk.

Good clinical outcomes of anterior cruciate ligament reconstruction in patients over 60 years of age.

PURPOSE: To evaluate the clinical outcomes following arthroscopic anterior cruciate ligament (ACL) reconstruction (ACLR) in patients over 60 years and to investigate the potential impact of preoperative osteoarthritis (OA) on these outcomes. METHODS: A retrospective study included ACL-injured patients over 60 years who underwent primary arthroscopic ACLR between 2010 and 2020. The Lysholm score and the International Knee Documentation Committee (IKDC) score were assessed preoperatively and at the final follow-up. The Tegner activity scale was performed to evaluate patients' activity levels. Data on return to sports, patient satisfaction, subsequent injuries and complications were collected. Preoperative radiographs were used to grade OA according to the Kellgrene-Lawrence classification. Correlation analysis between OA and clinical outcomes was performed. The rates of achieving the minimal clinically significant difference and patient-acceptable symptoms state were documented. RESULTS: A total of 37 patients were included in this study. The mean age at surgery was 62.3 ± 2.3 years, with a mean follow-up of 6.3 ± 3.2 years (range: 2.1-12.4). Patients showed statistically significant (all p < 0.001) improvements in the mean IKDC (38.9 ± 9.4-66.8 ± 12.5), Lysholm (48.8 ± 15.4-83.0 ± 12.8) and Tegner (1-3) scores. Fourteen patients (37.8%) returned to sports. No correlation was observed between the degree of preoperative OA and clinical outcomes (n.s.). CONCLUSION: Patients over 60 years with symptomatic ACL-deficient knees could benefit from ACLR, even when mild to moderate OA is present preoperatively. LEVEL OF EVIDENCE: Level IV.

Quantitative imaging for predicting hematoma expansion in intracerebral hemorrhage: A multimodel comparison.

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.

Triple-task mutual consistency for semi-supervised 3D medical image segmentation.

Semi-supervised deep learning algorithm is an effective means of medical image segmentation. Among these methods, multi-task learning with consistency regularization has achieved outstanding results. However, most of the existing methods usually simply embed the Signed Distance Map (SDM) task into the network, which underestimates the potential ability of SDM in edge awareness and leads to excessive dependence between tasks. In this work, we propose a novel triple-task mutual consistency (TTMC) framework to enhance shape and edge awareness capabilities, and overcome the task dependence problem underestimated in previous work. Specifically, we innovatively construct the Signed Attention Map (SAM), a novel fusion image with attention mechanism, and use it as an auxiliary task for segmentation to enhance the edge awareness ability. Then we implement a triple-task deep network, which jointly predicts the voxel-wise classification map, the Signed Distance Map and the Signed Attention Map. In our proposed framework, an optimized differentiable transformation layer associates SDM with voxel-wise classification map and SAM prediction, while task-level consistency regularization utilizes unlabeled data in an unsupervised manner. Evaluated on the public Left Atrium dataset and NIH Pancreas dataset, our proposed framework achieves significant performance gains by effectively utilizing unlabeled data, outperforming recent state-of-the-art semi-supervised segmentation methods. Code is available at https://github.com/Saocent/TTMC.

p-Smad3 differentially regulates the cytological behavior of osteoclasts before and after osteoblasts maturation.

BACKGROUND: A series of previous investigations have revealed that p-Smad3 plays a facilitative role in the differentiation and maturation of osteoblasts, while also regulating the expression of certain intercellular communication factors. However, the effects of p-Smad3 in osteoblasts before and after maturation on the proliferation, migration, differentiation, apoptosis and other cellular behaviors of osteoclasts have not been reported. METHODS: MC3T3-E1 cells were cultured in osteogenic induction medium for varying durations, After that, the corresponding conditioned medium was collected and the osteoclast lineage cells were treated. To elucidate the regulatory role of p-Smad3 within osteoblasts, we applied the activator TGF-ß1 and inhibitor SIS3 to immature and mature osteoblasts and collected corresponding conditioned media for osteoclast intervention. RESULTS: We observed an elevation of p-Smad3 and Smad3 during the early stage of osteoblast differentiation, followed by a decline in the later stage. we discovered that as osteoblasts mature, their conditioned media inhibit osteoclasts differentiation and the osteoclast-coupled osteogenic effect. However, it promotes apoptosis in osteoclasts and the angiogenesis coupled with osteoclasts. p-Smad3 in immature osteoblasts, through paracrine effects, promotes the migration, differentiation, and osteoclast-coupled osteogenic effects of osteoclast lineage cells. For mature osteoblasts, p-Smad3 facilitates osteoclast apoptosis and the angiogenesis coupled with osteoclasts. CONCLUSIONS: As pre-osteoblasts undergo maturation, p-Smad3 mediated a paracrine effect that transitions osteoclast cellular behaviors from inducing differentiation and stimulating bone formation to promoting apoptosis and coupling angiogenesis.

The Utilization of Metal-Organic Frameworks and Their Derivatives Composite in Supercapacitor Electrodes.

Up to now, the mainstream adoption of renewable energy has brought about substantial transformations in the electricity and energy sector. This shift has garnered considerable attention within the scientific community. Supercapacitors, known for their exceptional performance metrics like good charge/discharge capability, strong power density, as well as extended cycle longevity, have gained widespread traction across various sectors, including transportation and aviation. Metal-organic frameworks (MOFs) with unique traits including adaptable structure, highly customizable synthetic methods, and high specific surface area, have emerged as strong candidates for electrode materials. For enhancing the performance, MOFs are commonly compounded with other conducting materials to increase capacitance. This paper provides a detailed analysis of various common preparation strategies and characteristics of MOFs. It summarizes the recent application of MOFs and their derivatives as supercapacitor electrodes alongside other carbon materials, metal compounds, and conductive polymers. Additionally, the challenges encountered by MOFs in the realm of supercapacitor applications are thoroughly discussed. Compared to previous reviews, the content of this paper is more comprehensive, offering readers a deeper understanding of the diverse applications of MOFs. Furthermore, it provides valuable suggestions and guidance for future progress and development in the field of MOFs.

The relationship between healthy lifestyles and cognitive function in Chinese older adults: the mediating effect of depressive symptoms.

BACKGROUND: Previous studies have proven the positive relationship between healthy lifestyles and cognitive function in older adults. However, the specific impacts and mechanisms require further investigation. Therefore, this study aimed to investigate whether healthy lifestyles and cognitive function were associated with Chinese older adults and whether depressive symptoms mediated their association. METHODS: 8272 valid samples were included using the latest data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Pearson's test was applied to investigate the relationship between the key variables. Regression models were employed to examine the mediating effects of healthy lifestyles, using Sobel's test and the bootstrap method to confirm path effects. RESULTS: There was a significant correlation between healthy lifestyles, depressive symptoms, and cognitive function (p < 0.01). Healthy lifestyles directly impact cognitive function (ß = 0.162, p < 0.01). Healthy lifestyles had a significant effect on depressive symptoms (ß=-0.301, p < 0.01), while depressive symptoms have a significant impact on cognitive function (ß=-0.108, p < 0.01). Depressive symptoms partially mediated the effect of healthy lifestyles on cognitive function (ß = 0.032, p < 0.01). The Sobel and bootstrap tests confirmed the robustness of the regression analysis results. CONCLUSION: Depressive symptoms mediate the relationship between healthy lifestyles and cognitive function. Our findings suggest that prevention strategies for cognitive impairment in older adults should focus on healthy lifestyles and mental health.

Icariin ameliorates osteoporosis in ovariectomized rats by targeting Cullin 3/Nrf2/OH pathway for osteoclast inhibition.

Osteoporosis, characterized by low bone mass and bone microarchitecture breakdown, has become a growing public health problem. The increase in oxidative stress could lead to an imbalance between osteoblasts-mediated osteogenesis and osteoclast-mediated bone resorption, which gives rise to osteoporosis. Nrf2 is a master transcription factor that regulates oxidative stress and has recently been reported to take part in the development of osteoporosis. Icariin, a leading active flavonoid in herbal Epimedium pubescens, has significant antioxidant activity in and is widely applied for treating bone diseases. In this study, we aimed to explore the effect of icariin on osteoclastogenesis and its potential mechanism from the perspective of oxidative stress inhibition, using ovariectomized (OVX) rats and RANKL-induced RAW264.7 cells. Our results demonstrated that icariin-treated OVX rats exhibited higher bone density, fewer tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and lower ROS levels in bone tissues than vehicle-treated OVX rats. Also, icariin suppressed osteoclast differentiation and inhibited the expression of osteoclastogenesis-related genes, such as NFATc1, Ctsk, Trap, and c-Fos, in RANKL-induced RAW264.7 cells. Icariin also reduced intracellular ROS levels by increasing the expression of nuclear Nrf2 and HO-1. Further mechanistic studies showed icariin inhibited Cullin 3 expression and could delay Nrf2 degradation by reducing the ubiquitination of endogenous Nrf2 in RANKL-stimulated RAW264.7 cells, and these effects were markedly reversed by cullin three overexpression. These findings suggest icariin alleviated osteoporosis by suppressing osteoclastogenesis via targeting the Cullin 3/Nrf2/OH signaling pathway. Our study implied that icariin may be a potential candidate to treat osteoporosis.

FGF21 protects against ischaemia reperfusion injury in normal and fatty livers.

BACKGROUND: Liver ischaemia/reperfusion (I/R) injury, which is an inevitable clinical problem of liver resection, liver transplantation and haemorrhagic shock. Fibroblast growth factor 21 (FGF21) was intimately coupled with multiple metabolic processes and proved to protect against apoptosis and inflammatory response in hepatocytes during hepatic I/R injury. However, the regulatory mechanisms of FGF21 in hepatic I/R injury remains unknown. Therefore, we hypothesize that FGF21 protects hepatic tissues from I/R injury. METHODS: Blood samples were available from haemangiomas patients undergoing hepatectomy and murine liver I/R model and used to further evaluate the serum levels of FGF21 both in humans and mice. We further explored the regulatory mechanisms of FGF21 in murine liver I/R model by using FGF21-knockout mice (FGF21-KO mice) and FGF21-overexpression transgenic mice (FGF21-OE mice) fed a high-fat or ketogenic diet. RESULTS: Our results show that the circulating levels of FGF21 were robustly decreased after liver I/R in both humans and mice. Silencing FGF21 expression with FGF21-KO mice aggravates liver injury at 6 h after 75 min of partial liver ischaemia, while FGF21-OE mice display alleviated hepatic I/R injury and inflammatory response. Compared with chow diet mice, exogenous FGF21 decreases the levels of aminotransferase, histological changes, apoptosis and inflammatory response in hepatic I/R injury treatment mice with a high-fat diet. Meanwhile, ketogenic diet mice are not sensitive to hepatic I/R injury. CONCLUSIONS: The circulating contents of FGF21 are decreased during liver warm I/R injury and exogenous FGF21 exerts hepatoprotective effects on hepatic I/R injury. Thus, FGF21 regulates hepatic I/R injury and may be a key therapeutic target.

Nomogram prediction model for the risk of intracranial hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke.

Background: Hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) might worsen the clinical outcomes, and a reliable predictive system is needed to identify the risk of hemorrhagic transformation after IVT. Methods: Retrospective collection of patients with acute cerebral infarction treated with intravenous thrombolysis in our hospital from 2018 to 2022. 197 patients were included in the research study. Multivariate logistic regression analysis was used to screen the factors in the predictive nomogram. The performance of nomogram was assessed on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots and decision curve analysis (DCA). Results: A total of 197 patients were recruited, of whom 24 (12.1%) developed HT. In multivariate logistic regression model National Institute of Health Stroke Scale (NIHSS) (OR, 1.362; 95% CI, 1.161-1.652; p = 0.001), N-terminal pro-brain natriuretic peptide (NT-pro BNP) (OR, 1.012; 95% CI, 1.004-1.020; p = 0.003), neutrophil to lymphocyte ratio (NLR) (OR, 3.430; 95% CI, 2.082-6.262; p < 0.001), systolic blood pressure (SBP) (OR, 1.039; 95% CI, 1.009-1.075; p = 0.016) were the independent predictors of HT which were used to generate nomogram. The nomogram showed good discrimination due to AUC-ROC values. Calibration plot showed good calibration. DCA showed that nomogram is clinically useful. Conclusion: Nomogram consisting of NIHSS, NT-pro BNP, NLR, SBP scores predict the risk of HT in AIS patients treated with IVT.

A nomogram for predicting the risk of cerebral vasospasm after neurosurgical clipping in patients with aneurysmal subarachnoid hemorrhage.

Purpose: Cerebral vasospasm (CVS) is a common complication that occurs after neurosurgical clipping of intracranial aneurysms in patients with aSAH. This complication can lead to clinical deterioration and a poor prognosis. The aim of this study is to explore the risk factors for CVS in aSAH patients who have undergone neurosurgical clipping, develop a nomogram for CVS, and evaluate its performance. Methods: Patients with aSAH who underwent neurosurgical clipping in the Department of Neurosurgery from January 2018 to January 2023 were selected as the subjects of this research. The clinical data of these patients were retrospectively analyzed. Logistic multivariate regression analysis was employed to identify the independent risk factors of CVS. A clinical prediction model in the form of a nomogram for CVS was developed using the R programming language and subsequently evaluated for its performance and quality. Results: A total of 156 patients with aSAH were included in the analysis, comprising 109 patients in the training set and 47 patients in the validation set. In the training cohort, 27 patients (24.77%) developed CVS after neurosurgical clipping, while in the validation cohort, 15 patients (31.91%) experienced CVS. Multivariate regression analysis revealed that age, Hcy, WBC, glucose/potassium ratio, aneurysm location, and modified Fisher grade were independent risk factors for CVS. The nomogram exhibited excellent discriminative performance in both the training set (AUC = 0.885) and the validation set (AUC = 0.906). Conclusion: CVS was a prevalent complication following neurosurgical clipping in patients with aSAH, with a highly intricate pathogenesis and pathophysiological course. Early prediction of CVS represented a significant challenge in clinical practice. In this study, age, Hcy, WBC, glucose/potassium ratio, aneurysm location, and modified Fisher grade emerged as independent risk factors for CVS. The resulting nomogram demonstrated substantial predictive value.