Fatty infiltration in paraspinal muscles: Predicting the outcome of lumbar surgery and postoperative complications.

Lumbar spine disorders often cause lower back pain, lower limb radiating pain, restricted movement, and neurological dysfunction, which seriously affect the quality of life of middle-aged and older people. It has been found that pathological changes in the spine often cause changes in the morphology and function of the paraspinal muscles (PSMs). Fatty infiltration (FI) in PSMs is closely associated with disc degeneration and Modic changes. And FI causes inflammatory responses that exacerbate the progression of lumbar spine disease and disrupt postoperative recovery. Magnetic resonance imaging (MRI) can better distinguish between fat and muscle tissue with the threshold technique. Three-dimensional-MRI multi-echo imaging techniques such as water-fat separation and proton density are currently popular for studying FI. Muscle fat content obtained based on these imaging sequences has greater accuracy, visualization, acquisition speed, and utility. The proton density fat fraction calculated from these techniques has been shown to evaluate more subtle changes in PSMs. Magnetic resonance spectroscopy can accurately reflect the relationship between FI and the degeneration of PSMs by measuring intracellular and extracellular lipid values to quantify muscle fat. We have pooled and analyzed published studies and found that patients with spinal disorders often exhibit FI in PSMs. Some studies suggest an association between FI and adverse surgical outcomes, although conflicting results exist. These suggests that clinicians should consider FI when assessing surgical risks and outcomes. Future studies should focus on understanding the biological mechanisms underlying FI and its predictive value in spinal surgery, providing valuable insights for clinical decision-making.

Kaempferol Improves Exercise Performance by Regulating Glucose Uptake, Mitochondrial Biogenesis, and Protein Synthesis via PI3K/AKT and MAPK Signaling Pathways.

Kaempferol is a natural flavonoid with reported bioactivities found in many fruits, vegetables, and medicinal herbs. However, its effects on exercise performance and muscle metabolism remain inconclusive. The present study investigated kaempferol's effects on improving exercise performance and potential mechanisms in vivo and in vitro. The grip strength, exhaustive running time, and distance of mice were increased in the high-dose kaempferol group (p < 0.01). Also, kaempferol reduced fatigue-related biochemical markers and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) related to antioxidant capacity. Kaempferol also increased the glycogen and adenosine triphosphate (ATP) content in the liver and skeletal muscle, as well as glucose in the blood. In vitro, kaempferol promoted glucose uptake, protein synthesis, and mitochondrial function and decreased oxidative stress in both 2D and 3D C2C12 myotube cultures. Moreover, kaempferol activated the PI3K/AKT and MAPK signaling pathways in the C2C12 cells. It also upregulated the key targets of glucose uptake, mitochondrial function, and protein synthesis. These findings suggest that kaempferol improves exercise performance and alleviates physical fatigue by increasing glucose uptake, mitochondrial biogenesis, and protein synthesis and by decreasing ROS. Kaempferol's molecular mechanism may be related to the regulation of the PI3K/AKT and MAPK signaling pathways.

Peripheral blood MicroRNAs as biomarkers of schizophrenia: expectations from a meta-analysis that combines deep learning methods.

OBJECTIVES: This study aimed at identifying reliable differentially expressed miRNAs (DEMs) for schizophrenia in blood via meta-analyses combined with deep learning methods. METHODS: First, we meta-analysed published DEMs. Then, we enriched the pool of schizophrenia-associated miRNAs by applying two computational learning methods to identify candidate biomarkers and verified the results in external datasets. RESULTS: In total, 27 DEMs were found to be statistically significant (p < .05). Ten candidate schizophrenia-associated miRNAs were identified through computational learning methods. The diagnostic efficiency was verified on a blood-miRNA dataset (GSE54578) with a random forest (RF) model and achieved an area under the curve (AUC) of 0.83 ± 0.14. Moreover, 855 experimentally validated target genes for these candidate miRNAs were retrieved, and 11 hub genes were identified. Enrichment analysis revealed that the main functions in which the target genes were enriched were those related to cell signalling, prenatal infections, cancers, cell deaths, oxidative stress, endocrine disorders, transcription regulation, and kinase activities. The diagnostic ability of the hub genes was reflected in a comparably good average AUC of 0.77 ± 0.09 for an external dataset (GSE38484). CONCLUSIONS: A meta-analysis that combines computational and mathematical methods provides a reliable tool for identifying candidate biomarkers of schizophrenia.

FBXO28 promotes proliferation, invasion, and metastasis of pancreatic cancer cells through regulation of SMARCC2 ubiquitination.

The E3 ligase F-box only protein 28 (FBXO28) belongs to the F-box family of proteins that play a critical role in tumor development. However, the potential function of FBXO28 in pancreatic cancer (PC) and its molecular mechanism remain unclear. In this study, we examined FBXO28 expression in PC and its biological role and explored the mechanism of FBXO28-mediated proliferation, invasion, and metastasis of PC cells. Compared with paracancerous tissues and human normal pancreatic ductal epithelial cells, FBXO28 was highly expressed in PC tissues and cell lines. High expression of FBXO28 was negatively correlated with the survival prognosis of patients with PC. Functional assays indicated that FBXO28 promoted PC cell proliferation, invasion, and metastasis in vitro and in vivo. Furthermore, immunoprecipitation-mass spectrometry was used to identify SMARCC2 as the target of FBXO28; upregulation of SMARCC2 can reverse the effect of overexpression of FBXO28 on promoting the proliferation, invasion, and metastasis of PC cells. Mechanistically, FBXO28 inhibited SMARCC2 expression in post-translation by increasing SMARCC2 ubiquitination and protein degradation. In conclusion, FBXO28 has a potential role in PC, possibly promoting PC progression through SMARCC2 ubiquitination. Thus, FBXO28 might be a potential treatment target in PC.

The deubiquitinating enzyme MINDY2 promotes pancreatic cancer proliferation and metastasis by stabilizing ACTN4 expression and activating the PI3K/AKT/mTOR signaling pathway.

The pathogenic mechanisms of pancreatic cancer (PC) are still not fully understood. Ubiquitination modifications have a crucial role in tumorigenesis and progression. Yet, the role of MINDY2, a member of the motif interacting with Ub-containing novel DUB family (MINDY), as a newly identified deubiquitinating enzyme, in PC is still unclear. In this study, we found that MINDY2 expression is elevated in PC tissue (clinical samples) and was associated with poor prognosis. We also found that MINDY2 is associated with pro-carcinogenic factors such as epithelial-mesenchymal transition (EMT), inflammatory response, and angiogenesis; the ROC curve suggested that MINDY2 has a high diagnostic value in PC. Immunological correlation analysis suggested that MINDY2 is deeply involved in immune cell infiltration in PC and is associated with immune checkpoint-related genes. In vivo and in vitro experiments further suggested that elevated MINDY2 promotes PC proliferation, invasive metastasis, and EMT. Meanwhile, actinin alpha 4 (ACTN4) was identified as a MINDY2-interacting protein by mass spectrometry and other experiments, and ACTN4 protein levels were significantly correlated with MINDY2 expression. The ubiquitination assay confirmed that MINDY2 stabilizes the ACTN4 protein level by deubiquitination. The pro-oncogenic effect of MINDY2 was significantly inhibited by silencing ACTN4. Bioinformatics Analysis and Western blot experiments further confirmed that MINDY2 stabilizes ACTN4 through deubiquitination and thus activates the PI3K/AKT/mTOR signaling pathway. In conclusion, we identified the oncogenic role and mechanism of MINDY2 in PC, suggesting that MINDY2 is a viable candidate gene for PC and may be a therapeutic target and critical prognostic indicator.

Nucleotide-Binding Oligomerization Domain (NOD)-Like Receptor Subfamily C (NLRC) as a Prognostic Biomarker for Glioblastoma Multiforme Linked to Tumor Microenvironment: A Bioinformatics, Immunohistochemistry, and Machine Learning-Based Study.

Purpose: Glioblastoma multiforme (GBM) remains the deadliest primary brain tumor. We aimed to illuminate the role of nucleotide-binding oligomerization domain (NOD)-like receptor subfamily C (NLRC) in GBM. Patients and Methods: Based on public database data (mainly The Cancer Genome Atlas [TCGA]), we performed bioinformatics analysis to visually evaluate the role and mechanism of NLRCs in GBM. Then, we validated our findings in a glioma tissue microarray (TMA) by immunohistochemistry (IHC), and the prognostic value of NOD1 was assessed via random forest (RF) models. Results: In GBM tissues, the expression of NLRC members was significantly increased, which was related to the low survival rate of GBM. Additionally, Cox regression analysis revealed that the expression of NOD1 (among NLRCs) served as an independent prognostic marker. A nomogram based on multivariate analysis proved the effective predictive performance of NOD1 in GBM. Enrichment analysis showed that high expression of NOD1 could regulate extracellular structure, cell adhesion, and immune response to promote tumor progression. Then, immune infiltration analysis showed that NOD1 overexpression correlated with an enhanced immune response. Then, in a glioma TMA, the results of IHC revealed that the increase in NOD1 expression indicated high recurrence and poor prognosis of human glioma. Furthermore, the expression level of NOD1 showed good prognostic value in the TMA cohort via RF. Conclusion: The value of NOD1 as a biomarker for GBM was demonstrated. The possible mechanisms may lie in the regulatory role of NLRC-related pathways in the tumor microenvironment.

Predictive value of clinical characteristics on risk and prognosis of synchronous brain metastases in small-cell lung cancer patients: A population-based study.

BACKGROUND: Patients with small-cell lung cancer (SCLC) have a high incidence of synchronous brain metastases (SBM) and a poor prognosis, which causes a heavy burden of morbidity and mortality. A better understanding of the demographic and tumor-specific characteristics of these patients is critical to guiding clinical practice. The purpose of this study was to investigate the predictive and prognostic value of the clinical characteristics of SCLC patients with SBM at initial diagnosis. METHODS: This is a retrospective study based on the data in the latest Surveillance, Epidemiology, and End Results (SEER) version which was released in 2021 for patients diagnosed with SCLC in the presence or absence of SBM from 2010 to 2018. Multivariable logistic regression was performed to identify predictors of the presence of SBM at the initial diagnosis. Kaplan-Meier curves and multivariable Cox regression models were built to compare the prognosis of patients with different clinical characteristics and treatments. RESULTS: A total of 33,169 SCLC patients were enrolled in this study, including 5711 (17.2%) patients with SBM and 27,458 (82.8%) patients without SBM. Patients who are black(HR = 1.313, 95% CI = 1.167-1.478, p < 0.001), higher T stage (T2, HR = 1.193, 95%CI = 1.065-1.348, p = 0.005; T3, HR = 1.169, 95%CI = 1.029-1.327, p = 0.016; T4, HR = 1.259, 95%CI = 1.117-1.418, p < 0.001), lung metastases (HR = 1.434, 95%CI = 1.294-1.588, p < 0.001) and bone metastases (HR = 1.311, 95% CI = 1.205-1.426, p < 0.001) had greater odds of SBM at initial diagnosis. The median overall survival (OS) for SCLC patients with SBM was 5.0 months. Multivariable Cox regression revealed that age ≥ 65 (HR = 1.164, 95% CI = 1.086-1.247, p < 0.025), singled (HR = 1.095, 95% CI = 1.020-1.174, p = 0.012), higher T stage (T3, HR = 1.265, 95% CI = 1.123-1.425, p < 0.001; T4, HR = 1.192, 95% CI = 1.066-1.332, p = 0.002), higher N stage (N2, HR = 1.347, 95%CI = 1.214-1.494, p < 0.001; N3, HR = 1.452, 95%CI = 1.292-1.632, p < 0.001), liver metastases (HR = 1.415, 95%CI = 1.306-1.533, p < 0.001), and bone metastases (adjusted HR = 1.126, 95%CI = 1.039-1.221, p = 0.004). Analysis of treatment regimens showed that patients who received combinational treatment exhibited longer OS than chemotherapy or radiotherapy alone, and surgery combined with chemotherapy and radiotherapy exhibited the longest OS. CONCLUSIONS: In this study, we identified risk factors for SBM in SCLC patients and prognostic indicators among this patient population. We also found that patients who received different therapeutic strategies exhibited significant difference on OS, which will provide evidence-based support for treatment options.

Rare improperly treated traumatic vertical atlantoaxial dislocation: A case report and literature review.

BACKGROUND: Because of the severity and fatal outcome of traumatic vertical atlantoaxial dislocation (AAD), most patients may die in the early post-traumatic period. The post-injury management of patients with vertical AAD has been rarely reported. Improper treatment may lead to disastrous outcome and further aggravate the neurologic symptoms. CASE PRESENTATION: This report describes the perioperative management and outcome of a rare improperly treated patient with traumatic vertical AAD. The severe pulmonary infection of this patient prevented further surgery for vertical AAD. After placement of a halo vest, combined with effective antibiotic drug treatment, the patient's pulmonary infection was brought under control. The patient underwent atlantoaxial fusion using C1 lateral mass screws and C2 pedicle screws with the assistance of the halo vest. A computed tomography scan at 1 year follow-up indicated that the bone graft was fused and the patient was able to walk independently. CONCLUSION: Skull traction is contraindicated in patients with traumatic vertical AAD. Application of a halo vest can be used for temporary fixation of the cervical spine and atlantoaxial fixation should be performed to maintain the stability of atlantoaxial articulation.

Neural Stem Cells in the Treatment of Alzheimer's Disease: Current Status, Challenges, and Future Prospects.

Alzheimer's disease (AD), a progressive dementia, is one of the world's most dangerous and debilitating diseases. Clinical trial results of amyloid-ß (Aß) and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing. There are currently no effective strategies for slowing the progression of AD. Further understanding of the mechanisms underlying AD and the development of novel therapeutic options are critical. Neurogenesis is impaired in AD, which contributes to memory deficits. Transplanted neural stem cells (NSCs) can regenerate degraded cholinergic neurons, and new neurons derived from NSCs can form synaptic connections with neighboring neurons. In theory, employing NSCs to replace and restore damaged cholinergic neurons and brain connections may offer new treatment options for AD. However there remain barriers to surmount before NSC-based therapy can be used clinically. The objective of this article is to describe recent advances in the treatment of AD models and clinical trials involving NSCs. In addition, we discuss the challenges and prospects associated with cell transplant therapy for AD.

Individualized Functional Decompression Options for Adult Chiari Malformation With Syringomyelia and A Novel Scale for Syringomyelia Resolution: A Single-Center Experience.

OBJECTIVE: To compare outcomes of posterior fossa bony decompression alone (PFD) versus PFD with duraplasty (PFDD) versus PFDD with additional obex exploration (PFDDO) in patients with Chiari malformation type I (CMI) combining syringomyelia. METHODS: Clinical records of adult patients who underwent decompressions from 2014 to 2022 were retrospectively analyzed. The decompression procedure was individualized based on the cerebrospinal fluid pulse in the surgical field. The Chicago Chiari Outcome Scale (CCOS) was used to assess the prognosis of the patients and a novel syringomyelia resolution scale, based on 3-dimensional volume, was introduced. The percentage change in the cervical syrinx volume was classified as follows by resolution: ≥ 70%, 30%-70%, and < 30%. RESULTS: Seventy-eight individuals were enrolled, of which 22, 20, and 36 underwent PFD, PFDD, and PFDDO, respectively. The three decompression groups had no significant difference in the preoperative characteristics and postoperative prognosis. Multivariate analyses revealed that better CCOS was significantly correlated with younger age at surgery (p = 0.018), syrinx originated from lower cervical levels (p = 0.037), narrower preoperative cerebral aqueduct (p = 0.005), and better syrinx volume resolution (p = 0.004). Additionally, a better cervical syrinx volume resolution was significantly correlated with higher CCOS (p = 0.017), narrower cerebral aqueduct (p = 0.035), and better tonsillar descent resolution (p = 0.007). CONCLUSION: Individualized functional decompression induced an equal effect on CCOS and syrinx volume resolution for all CMI patients with syringomyelia. Our syringomyelia resolution scale facilitates communication and prediction of CMI prognosis.

Advances in research on fat infiltration and lumbar intervertebral disc degeneration.

Low back pain (LBP) is a disabling condition with no available cure, severely affecting patients' quality of life. Intervertebral disc degeneration (IVDD) is the leading cause of chronic low back pain (CLBP). IVDD is a common and recurrent condition in spine surgery. Disc degeneration is closely associated with intervertebral disc inflammation. The intervertebral disc is an avascular tissue in the human body. Transitioning from hematopoietic bone marrow to bone marrow fat may initiate an inflammatory response as we age, resulting in bone marrow lesions in vertebrae. In addition, the development of LBP is closely associated with spinal stability imbalance. An excellent functional state of paraspinal muscles (PSMs) plays a vital role in maintaining spinal stability. Studies have shown that the diminished function of PSMs is mainly associated with increased fat content, but whether the fat content of PSMs is related to the degree of disc degeneration is still under study. Given the vital role of PSMs lesions in CLBP, it is crucial to elucidate the interaction between PSMs changes and CLBP. Therefore, this article reviews the advances in the relationship and the underlying mechanisms between IVDD and PSMs fatty infiltration in patients with CLBP.

FBXW7 Reduces the Cancer Stem Cell-Like Properties of Hepatocellular Carcinoma by Regulating the Ubiquitination and Degradation of ACTL6A.

Cancer stem cells (CSCs) comprise a subset of tumor cells that can initiate tumorigenesis and promote tumor advance. A previous study showed that the expression of FBXW7 in hepatocellular carcinoma (HCC) clinical samples was lower than that in the adjacent nontumor tissues and was negatively correlated with the invasion and migration of HCC cells. However, the biological characteristics and the underlying molecular mechanisms of FBXW7 in HCC stemness are yet to be elucidated. In present study, we found that FBXW7 participates in the self-renewal, tumorigenicity, sorafenib therapy, and stem cell-like properties of HCC cells in vivo and in vitro. The upregulation of FBXW7 inhibited the stemness and reduced the tumorigenicity and drug resistance of HCC cells. Mechanistically, proteins binding to FBXW7 were identified by coimmunoprecipitation and protein colocalization assays. We confirmed ACTL6A as a novel downstream target for FBXW7. The in vivo ubiquitination assay showed that FBXW7 repressed HCC malignancy by regulating the oncogenic activity of ACTL6A in a ubiquitin-dependent manner. Furthermore, we found that ACTL6A overexpression inversed the self-renewal abilities and tumorigenic abilities depressed by overexpressing FBXW7. The current findings suggested that FBXW7 reduces the stemness of HCC cells by targeting and degrading ACTL6A and provides a novel target for the diagnosis and treatment of HCC.

Early prevention and risk factors analysis of portal vein system thrombosis after laparoscopic splenectomy and pericardial devascularization.

BACKGROUND: Portal vein system thrombosis (PVST) is a common postoperative complication brought by laparoscopic splenectomy and pericardial disconnection (LSD) among patients who suffered from portal hypertension and hypersplenism. This research lies mainly in probing into the risk factors of PVST and evaluating the effects of warfarin on PVST prevention. MATERIALS AND METHODS: We took 131 individuals who have carried out LSD from January 2015 to January 2021. Patients were divided into warfarin group (n = 68) and aspirin group (n = 63). Meanwhile, thrombosis factors were analyzed in PVST arm (n = 48) and non-PVST arm (n = 83). RESULTS: We analyzed the early postoperative anticoagulation effect, 20 patients (29.4%) in the warfarin group developed PVST, and 28 patients (44.4%) in the aspirin group. The chance to PVST during the first year after operation was lower in the warfarin group than in the aspirin group (F = 13.43, P = 0.006). Risk factors for PVST were analyzed, and diabetes, the diameter of the portal vein and splenic vein, and the velocity of portal blood flow were statistically significant between the PVST arm and non-PVST arm (P < < 0.05). Multiple logistic regression analyses have shown that diabetes, portal vein diameter, splenic vein diameter, and the velocity of portal blood flow were the risk factors of PVST. CONCLUSIONS: The portal vein diameter, splenic vein diameter, portal vein flow velocity, and diabetes are risk factors for the PVST after LSD. The prophylactic use of warfarin anticoagulation markedly decreases the probability of occurrence of the PVST in patients with portal hypertension after LSD compared to aspirin.

FAM126A interacted with ENO1 mediates proliferation and metastasis in pancreatic cancer via PI3K/AKT signaling pathway.

Pancreatic cancer (PC) is a common digestive system carcinoma with high mortality rate mostly due to aberrant growth and distant metastasis. Current researches demonstrated that Family Sequence Similarities (FAMs) have been involving in tumor development, and which subfamily has the function of promoting or inhibiting tumors and its in-depth molecular mechanism remains unclear. Based on the Gene Expression Omnibus (GEO), the Gene Expression Profiling Interactive Analysis (GEPIA2), we observed that FAM126A is in high expressed level among PC tissues and contributes to worse progression of PC, which was validated by PC tissue microarray. Function assay indicated that overexpression of FAM126A accelerates PC cell proliferation, invasion and migration in vitro, as well as liver cancer metastasis in vivo. Further, we found that FAM126A induces epithelial-mesenchymal transition (EMT), including the downregulation of E-cadherin epithelial marker expression, and the upregulation of N-cadherin, Vimentin, and Snail, mesenchymal marker expression. By co-localization and co-immunoprecipitation assays, we confirmed that FAM126A directly interacts with ENO1, which was a key activator of the PI3K/AKT signaling pathway. Furthermore, ENO1 knockdown reversed cell proliferation, migration, and invasion of PC cells promoted by FAM126A overexpression in vitro and in vivo. In general, these results verified FAM126A is an oncogene interacting with ENO1 in PC by activating PI3K/AKT signaling pathway.

The functional mechanism of bone marrow-derived mesenchymal stem cells in the treatment of animal models with Alzheimer's disease: crosstalk between autophagy and apoptosis.

The transplantation of bone marrow-derived mesenchymal stem cells (BMMSCs) alleviates neuropathology and improves cognitive deficits in animal models with Alzheimer's disease. However, the underlying mechanism remains undefined. Based on meta-analysis and comprehensive review, high-profile studies support the theory that transplanted BMMSCs activate autophagy, as evidenced by the expression levels of signal molecules such as Beclin-1, Atg5, LC3-II, and mTOR. Functional autophagy mitigates neuronal apoptosis, which is reflected by the alterations of IAPs, Bcl-2, caspase-3, and so forth. Moreover, the transplantation of BMMSCs can decrease aberrant amyloid-beta peptides as well as tau aggregates, inhibit neuroinflammation, and stimulate synaptogenesis. There is a signal crosstalk between autophagy and apoptosis, which may be regulated to produce synergistic effect on the preconditioning of stem cells. Forasmuch, the therapeutic effect of transplanted BMMSCs can be enhanced by autophagy and/or apoptosis modulators.

Multifaceted Roles of cAMP Signaling in the Repair Process of Spinal Cord Injury and Related Combination Treatments.

Spinal cord injury (SCI) results in multiple pathophysiological processes, including blood-spinal cord barrier disruption, hemorrhage/ischemia, oxidative stress, neuroinflammation, scar formation, and demyelination. These responses eventually lead to severe tissue destruction and an inhibitory environment for neural regeneration.cAMP signaling is vital for neurite outgrowth and axonal guidance. Stimulating intracellular cAMP activity significantly promotes neuronal survival and axonal regrowth after SCI.However, neuronal cAMP levels in adult CNS are relatively low and will further decrease after injury. Targeting cAMP signaling has become a promising strategy for neural regeneration over the past two decades. Furthermore, studies have revealed that cAMP signaling is involved in the regulation of glial cell function in the microenvironment of SCI, including macrophages/microglia, reactive astrocytes, and oligodendrocytes. cAMP-elevating agents in the post-injury milieu increase the cAMP levels in both neurons and glial cells and facilitate injury repair through the interplay between neurons and glial cells and ultimately contribute to better morphological and functional outcomes. In recent years, combination treatments associated with cAMP signaling have been shown to exert synergistic effects on the recovery of SCI. Agents carried by nanoparticles exhibit increased water solubility and capacity to cross the blood-spinal cord barrier. Implanted bioscaffolds and injected hydrogels are potential carriers to release agents locally to avoid systemic side effects. Cell transplantation may provide permissive matrices to synergize with the cAMP-enhanced growth capacity of neurons. cAMP can also induce the oriented differentiation of transplanted neural stem/progenitor cells into neurons and increase the survival rate of cell grafts. Emerging progress focused on cAMP compartmentation provides researchers with new perspectives to understand the complexity of downstream signaling, which may facilitate the clinical translation of strategies targeting cAMP signaling for SCI repair.

Photodynamic therapy during second surgery for recurrent gliomas improves survival.

BACKGROUND: Glioma accounts for most central nervous system tumors, and the degree of invasion and malignancy are higher in the recurrent glioma. Photodynamic therapy (PDT) is an effective strategy in glioma. This study aimed to explore the risk factors for re-recurrence after a second glioma surgery and the effects of PDT on re-recurrence. METHODS: This was a retrospective study in the Second Affiliated Hospital of Harbin Medical University in China, and 43 patients that received the secondary surgery for recurrent glioma were included. The Kaplan-Meier test and Cox proportional hazard method were used to analyze. RESULTS: The total re-recurrence rate after the second surgery for recurrent glioma was 48.84%. When the age increased by 1, the risk of re-recurrence increased 1.065 times (95% CI 1.000-1.134, P = 0.049). High matrix metalloproteinase (MMP) 2 expression was associated with a significantly higher risk of re-recurrence than low MMP2 expression (HR = 25.550, 95% CI 3.190-204.650, P = 0.002). Pathological grades IV and III were associated with a significantly higher risk of re-recurrence than pathological grade II (HR = 17.121, 95% CI 2.345-124.986, P = 0.005; HR = 2863.470, 95% CI 100.697-81,427.197, P < 0.001). PDT decreased the risk of re-recurrence (HR = 25.550, 95% CI 3.190-204.650, P = 0.002) and increased survival time (HR = 3.611, 95% CI 1.012-12.888, P = 0.048). CONCLUSION: The age, MMP2 expression, and pathological grade are independent risk factors for re-recurrence after a second surgery for recurrent glioma. PDT during the second surgery decreased the risk of re-recurrence and increased survival time.

Role of Hepatocyte- and Macrophage-Specific PPARγ in Hepatotoxicity Induced by Diethylhexyl Phthalate in Mice.

BACKGROUND: Phthalates may disturb metabolic homeostasis in the liver by interfering with the peroxisome proliferator-activated receptors (PPARs). However, the role of hepatic macrophages in the lipid metabolic dysregulation induced by diethylhexyl phthalate (DEHP) remains unclear. OBJECTIVES: We aimed to evaluate the respective role of hepatocyte- and macrophage-specific PPARγ in the hepatotoxicity induced by DEHP. METHODS: Wild-type (WT), hepatocyte-specific PPARγ knockout (Hep-KO), and macrophage-specific PPAR knockout (Mac-KO) mice were administered DEHP (625mg/kg body weight) by daily gavage for 28 d, followed by hepatotoxicity examination and macrophage analysis. RNA sequencing and lipid metabolomic analysis were used to characterize the molecular changes in mouse liver. Mouse bone marrow-derived macrophages (BMDMs) and human monocytic THP-1 cell-derived macrophages were used to investigate the mechanistic regulation of macrophages' polarization by DEHP and mono(2-ethylhexyl) phthalate (MEHP). RESULTS: The levels of hepatic steatosis and triglyceride were significantly higher in the mice treated with DEHP compared with the control mice in the WT and Hep-KO model. Lipid accumulation induced by DEHP was notably attenuated in the Mac-KO mice, but M2-polarization of hepatic macrophages in the Mac-KO mice was significantly higher compared with the WT mice under DEHP treatment. The M2-polarization of BMDMs and human macrophages was suppressed by DEHP and MEHP. Transcriptomic and lipidomic data suggested lower levels of lipid biosynthesis, fatty acid oxidation, and oxidative phosphorylation in the Mac-KO mice compared with the WT and Hep-KO mice under DEHP treatment. CONCLUSIONS: Our data suggested that the orchestrated activation of PPARα and PPARγ by MEHP may reprogram hepatic macrophages' polarization, thereby affecting lipid homeostasis in the mouse liver. Although this conclusion was based on studies conducted in mice and in vitro, these findings may aid in elucidating the health effect of environmental phthalate exposure. https://doi.org/10.1289/EHP9373.

Granulocytic sarcoma causing long spinal cord compression: Case report and literature review.

Context: Granulocytic sarcoma (GS) is an extramedullary form of proliferating myeloblasts. It is frequently reported in patients with acute myeloid leukemia (AML) but rarely in patients with chronic myeloid leukemia (CML). Spinal cord compression caused by CML-associated GS is exceedingly rare, with only few cases reported in the literature. To our knowledge, this is the first reported case in which GS caused such extensive compression.Findings: A 37-year-old man with CML suffered from back pain for 2 months. Notably, he had already achieved molecular remission (MR) after receiving imatinib mesylate for CML; bone marrow aspiration results were consistent with CML in chronic phase. Image examination revealed that developed GS occupied nearly the entire thoracic spinal canal, thereby causing extensive spinal cord compression. The tumor completely diminished after his treatment regimen was upgraded. He showed no signs of recurrence after 1-year follow-up.Conclusion: Extramedullary infiltration of CML should be taken into consideration when a mass lesion develops and compresses the spinal cord in a CML patient who has been receiving routine and standard treatment modalities; thus, a sudden and unexpected progression mandates a refinement and upgrade of treatment modality.