Explore the vast range of titles available.

To evaluate diffusion tensor imaging (DTI)-based functional neuronavigation in surgery of cerebral gliomas with pyramidal tract (PT) involvement with respect to both perioperative assessment and follow-up outcome. A prospective, randomized controlled study was conducted between 2001 and 2005. A consecutive series of 238 eligible patients with initial imaging diagnosis of cerebral gliomas involving PTs were randomized into study (n = 118) and control (n = 120) groups. The study cases underwent DTI and three-dimensional magnetic resonance imaging scans. The maps of fractional anisotropy were calculated for PT mapping. Both three-dimensional magnetic resonance imaging data sets and fractional anisotropy maps were integrated by rigid registration, after which the tumor and adjacent PT were segmented and reconstructed for presurgical planning and intraoperative guidance. The control cases were operated on using routine neuronavigation. There was a trend for high-grade gliomas (HGGs) in the study group to be more likely to achieve gross total resection (74.4 versus 33.3%, P < 0.001). There was no significant difference of low-grade gliomas resection between the two groups. Postoperative motor deterioration occurred in 32.8% of control cases, whereas it occurred in only 15.3% of the study cases (P < 0.001). The 6-month Karnofsky Performance Scale score of study cases was significantly higher than that of control cases (86 +/- 20 versus 74 +/- 28 overall, P < 0.001; 93 +/- 10 versus 86 +/- 17 for low-grade gliomas, P = 0.013; and 77 +/- 27 versus 53 +/- 32 for HGGs, P = 0.001). For 81 HGGs, the median survival of study cases was 21.2 months (95% confidence interval, 14.1-28.3 mo) compared with 14.0 months (95% confidence interval, 10.2-17.8 mo) of control cases (P = 0.048). The estimated hazard ratio for the effect of DTI-based functional neuronavigation was 0.570, representing a 43.0% reduction in the risk of death. DTI-based functional neuronavigation contributes to maximal safe resection of cerebral gliomas with PT involvement, thereby decreasing postoperative motor deficits for both HGGs and low-grade gliomas while increasing high-quality survival for HGGs.

Abstract OBJECTIVE To evaluate diffusion tensor imaging (DTI)-based functional neuronavigation in surgery of cerebral gliomas with pyramidal tract (PT) involvement with respect to both perioperative assessment and follow-up outcome. METHODS A prospective, randomized controlled study was conducted between 2001 and 2005. A consecutive series of 238 eligible patients with initial imaging diagnosis of cerebral gliomas involving PTs were randomized into study (n = 118) and control (n = 120) groups. The study cases underwent DTI and three-dimensional magnetic resonance imaging scans. The maps of fractional anisotropy were calculated for PT mapping. Both three-dimensional magnetic resonance imaging data sets and fractional anisotropy maps were integrated by rigid registration, after which the tumor and adjacent PT were segmented and reconstructed for presurgical planning and intraoperative guidance. The control cases were operated on using routine neuronavigation. RESULTS There was a trend for high-grade gliomas (HGGs) in the study group to be more likely to achieve gross total resection (74.4 versus 33.3%, P < 0.001). There was no significant difference of low-grade gliomas resection between the two groups. Postoperative motor deterioration occurred in 32.8% of control cases, whereas it occurred in only 15.3% of the study cases (P < 0.001). The 6-month Karnofsky Performance Scale score of study cases was significantly higher than that of control cases (86 ± 20 versus 74 ± 28 overall, P < 0.001; 93 ± 10 versus 86 ± 17 for low-grade gliomas, P = 0.013; and 77 ± 27 versus 53 ± 32 for HGGs, P = 0.001). For 81 HGGs, the median survival of study cases was 21.2 months (95% confidence interval, 14.1–28.3 mo) compared with 14.0 months (95% confidence interval, 10.2–17.8 mo) of control cases (P = 0.048). The estimated hazard ratio for the effect of DTI-based functional neuronavigation was 0.570, representing a 43.0% reduction in the risk of death. CONCLUSION DTI-based functional neuronavigation contributes to maximal safe resection of cerebral gliomas with PT involvement, thereby decreasing postoperative motor deficits for both HGGs and low-grade gliomas while increasing high-quality survival for HGGs.

Ulcerative colitis (UC) is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC). However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs) in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM), followed by repeated dextran sulfate sodium (DSS) ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP)-9 and neutrophil elastase (NE), accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer.

Osteoarthritis (OA) is a prevalent joint disease with a complex etiology, involving epigenetic alterations. Recent studies have suggested the potential of Oct4, Sox2 and Klf4 (OSK) in rejuvenating adult cells and facilitating tissue repair, but their specific role in OA pathophysiology and treatment remains unclear. Here we employed an adeno-associated virus (AAV) vector to achieve ectopic expression of OSK (AAV-OSK). Chondrocytes expressing OSK retained chondrocyte-specific markers with no increase in stemness-associated genes. AAV-OSK significantly preserved chondrocyte vitality in an inflammatory environment and counteracted the upregulation of osteogenic genes during OG differentiation. In OA murine models, AAV-OSK administration led to a notable improvement in cartilage integrity, a reduction in subchondral bone thickening and promoted the hyalinization of fibrocartilage. Furthermore, chondrocyte senescence and DNA methyltransferase expression were markedly diminished in the AAV-OSK group. Tet methylcytosine dioxygenase 2 was identified as a pivotal factor underlying the benefits of OSK-driven cartilage regeneration. Collectively, our study underscores that OSK expression within the knee joint modulates epigenetic alterations, mitigating OA progression and cartilage fibrosis through partial reprogramming, highlighting its therapeutic promise for comprehensive OA intervention. OSK expression reverses osteoarthritis through epigenetic modulation Osteoarthritis (OA) is a common joint disease that causes pain and stiffness. Here researchers explored a new approach using epigenetics to treat OA. They focused on three factors, Oct4, Sox2 and Klf4 (OSK), which can reprogram cells to a more youthful state. The study used adeno-associated virus vectors to deliver OSK into mouse joint tissues. This method aimed to reduce inflammation and prevent cell death in cartilage cells (chondrocytes). The researchers found that OSK helped maintain healthy cartilage by reducing harmful changes and promoting repair. The results showed that OSK could slow down OA progression by altering DNA methylation. This suggests that OSK might rejuvenate cartilage cells and improve joint health. The study concludes that OSK has potential as a new treatment for OA, with future research needed to refine this approach for human use. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Background: The presence of mild deficit is the most common reason for nonuse of intravenous alteplase in ischemic stroke. We analyzed within a national prospective cohort on whether patients with minor stroke can benefit from intravenous alteplase. Methods: This observational study included patients with acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score 0 to 5 at admission. The short-term outcomes at discharge and 3-month were analyzed including the modified Rankin Scale score, gait speed, Montreal Cognitive Assessment, Patient Health Questionnaire-9, General Anxiety Disorder-7 and Stroke Impact Scale-16. Multivariate regression models were performed to evaluate the association between intravenous thrombolysis and clinical outcomes. Results: A total of 1876 consecutive patients were included in the current analyses with 102 patients (5.4%) received alteplase and 1774 patients (94.5%) were in non-alteplase group. We found that 10.9% patients presented unfavorable functional outcome with a mRS [greater than or equal to] 2 at 3-month. Patients with alteplase treatment had a more favorable outcome in SIS-16 at discharge (OR, 5.45; 95% CI, 2.22-8.68) and 3-month after stroke (OR, 2.34; 95% CI, 0.17-4.50). There was an association of alteplase with better gait speed in the restricted sample of age >60 (OR,0.14; 95% CI, 0.02-0.25), while an unfavorable effect was found in anxiety (OR, 2.23; 95% CI, 2.23, 0.91-3.55) and depression (OR, 1.54; 95% CI, 0.17-2.91) in female. Conclusion: Alteplase showed a suggestive benefit in function and motor outcomes in patients with low NIHSS score of 0-5. Meanwhile, female seemed more inclined to post-stroke emotional problems after alteplase treatment, which should be further explored in the future. Keywords: alteplase, minor stroke, ischemic, outcomes

BackgroundGiven the swift advancements in artificial intelligence (AI), the utilisation of AI-based clinical decision support systems (AI-CDSSs) has become increasingly prevalent in the medical domain, particularly in the management of cerebrovascular disease.AimsTo describe the design, rationale and methods of a cluster-randomised multifaceted intervention trial aimed at investigating the effect of cerebrovascular disease AI-CDSS on the clinical outcomes of patients who had a stroke and on stroke care quality.DesignThe GOLDEN BRIDGE II trial is a multicentre, open-label, cluster-randomised multifaceted intervention study. A total of 80 hospitals in China were randomly assigned to the AI-CDSS intervention group or the control group. For eligible participants with acute ischaemic stroke in the AI-CDSS intervention group, cerebrovascular disease AI-CDSS will provide AI-assisted imaging analysis, auxiliary stroke aetiology and pathogenesis analysis, and guideline-based treatment recommendations. In the control group, patients will receive the usual care. The primary outcome is the occurrence of new vascular events (composite of ischaemic stroke, haemorrhagic stroke, myocardial infarction or vascular death) at 3 months after stroke onset. The sample size was estimated to be 21 689 with a 26% relative reduction in the incidence of new composite vascular events at 3 months by using multiple quality-improving interventions provided by AI-CDSS. All analyses will be performed according to the intention-to-treat principle and accounted for clustering using generalised estimating equations.ConclusionsOnce the effectiveness is verified, the cerebrovascular disease AI-CDSS could improve stroke care and outcomes in China.Trial registration number NCT04524624.

Osteosarcoma is a common malignant bone cancer easily to metastasize. Much safer and more efficient strategies are still needed to suppress osteosarcoma growth and lung metastasis. We recently presented a pure physical method to fabricate Ångstrom-scale silver particles (AgÅPs) and determined the anti-tumor efficacy of fructose-coated AgÅPs (F-AgÅPs) against lung and pancreatic cancer. Our study utilized an optimized method to obtain smaller F-AgÅPs and aimed to assess whether F-AgÅPs can be used as an efficient and safe agent for osteosarcoma therapy. We also investigated whether the induction of apoptosis by altering glucose metabolic phenotype contributes to the F-AgÅPs-induced anti-osteosarcoma effects. A modified method was developed to prepare smaller F-AgÅPs. The anti-tumor, anti-metastatic and pro-survival efficacy of F-AgÅPs and their toxicities on healthy tissues were compared with that of cisplatin (a first-line chemotherapeutic drug for osteosarcoma therapy) in subcutaneous or orthotopic osteosarcoma-bearing nude mice. The pharmacokinetics, biodistribution and excretion of F-AgÅPs were evaluated by testing the levels of silver in serum, tissues, urine and feces of mice. A series of assays were conducted to assess whether the induction of apoptosis mediates the killing effects of F-AgÅPs on osteosarcoma cells and whether the alteration of glucose metabolic phenotype contributes to F-AgÅPs-induced apoptosis. The newly obtained F-AgÅPs (9.38 ± 4.11 nm) had good stability in different biological media or aqueous solutions and were more effective than cisplatin in inhibiting tumor growth, improving survival, attenuating osteolysis and preventing lung metastasis in osteosarcoma-bearing nude mice after intravenous injection, but were well tolerated in normal tissues. One week after injection, about 68% of F-AgÅPs were excreted through feces. F-AgÅPs induced reactive oxygen species (ROS)-dependent apoptosis of osteosarcoma cells but not normal cells, owing to their ability to selectively shift glucose metabolism of osteosarcoma cells from glycolysis to mitochondrial oxidation by inhibiting pyruvate dehydrogenase kinase (PDK). Our study suggests the promising prospect of F-AgÅPs as a powerful selective anticancer agent for osteosarcoma therapy.

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)‐ or natural aging‐induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY‐abundant culture medium of osteocytes (OCY‐CM) from osteoarthritic mice possess pro‐inflammatory, pro‐osteoclastic, and pro‐neurite outgrowth effects, while OCY‐CM from the intermittent fasting‐treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM‐induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) to promote the development of osteoarthritis by directly or indirectly stimulating inflammation, osteoclast formation, and sensory nerve outgrowth. Intermittent fasting potently relieves osteoarthritis by suppressing the generation of osteocyte NPY and represents a promising nonpharmacological antiosteoarthritis strategy.

Recently, the gut microbiota (GM) has been shown to be a regulator of bone homeostasis and the mechanisms by which GM modulates bone mass are still being investigated. Here, it is found that colonization with GM from children (CGM) but not from the elderly (EGM) prevents decreases in bone mass and bone strength in conventionally raised, ovariectomy (OVX)‐induced osteoporotic mice. 16S rRNA gene sequencing reveals that CGM reverses the OVX‐induced reduction of Akkermansia muciniphila (Akk). Direct replenishment of Akk is sufficient to correct the OVX‐induced imbalanced bone metabolism and protect against osteoporosis. Mechanistic studies show that the secretion of extracellular vesicles (EVs) is required for the CGM‐ and Akk‐induced bone protective effects and these nanovesicles can enter and accumulate into bone tissues to attenuate the OVX‐induced osteoporotic phenotypes by augmenting osteogenic activity and inhibiting osteoclast formation. The study identifies that gut bacterium Akk mediates the CGM‐induced anti‐osteoporotic effects and presents a novel mechanism underlying the exchange of signals between GM and host bone. Colonization with gut microbiota from children (CGM) but not from the elderly (EGM) reverses the ovariectomy (OVX)‐induced reduction of Akkermansia muciniphila (Akk) and prevents OVX‐induced osteoporosis. Direct replenishment of Akk also induces bone benefits in OVX mice. Extracellular vesicles from CGM and Akk can enter into bone to directly attenuate the OVX‐induced osteoporotic phenotypes by augmenting osteogenesis and inhibiting osteoclastogenesis.