SMURF2 predisposes cancer cell toward ferroptosis in GPX4-independent manners by promoting GSTP1 degradation.

Ferroptosis is a non-apoptotic form of regulated cell death. Glutathione (GSH) peroxidase 4 (GPX4) and GSH-independent ferroptosis suppressor protein 1 (FSP1) have been identified as major defenses. Here, we uncover a protective mechanism mediated by GSH S-transferase P1 (GSTP1) by monitoring proteinomic dynamics during ferroptosis. Dramatic downregulation of GSTP1 is caused by SMURF2-mediated GSTP1 ubiquitination and degradation at early stages of ferroptosis. Intriguingly, GSTP1 acts in GPX4- and FSP1-independent manners by catalyzing GSH conjugation of 4-hydroxynonenal and detoxifying lipid hydroperoxides via selenium-independent GSH peroxidase activity. Genetic modulation of the SMURF2/GSTP1 axis or the pharmacological inhibition of GSTP1's catalytic activity sensitized tumor responses to Food and Drug Administration (FDA)-approved ferroptosis-inducing drugs both in vitro and in vivo. GSTP1 expression also confers resistance to immune checkpoint inhibitors by blunting ferroptosis. Collectively, these findings demonstrate a GPX4/FSP1-independent cellular defense mechanism against ferroptosis and suggest that targeting SMURF2/GSTP1 to sensitize cancer cells to ferroptosis has potential as an anticancer therapy.

iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca2+ homeostasis and control tumor growth and drug resistance.

Ca2+ release from the endoplasmic reticulum (ER) is an essential event in the modulation of Ca2+ homeostasis, which is coordinated by multiple biological processes, ranging from cell proliferation to apoptosis. Deregulated Ca2+ homeostasis is linked with various cancer hallmarks; thus, uncovering the mechanisms underlying Ca2+ homeostasis dynamics may lead to new anticancer treatment strategies. Here, we demonstrate that a reported Ca2+-channel protein TMCO1 (transmembrane and coiled-coil domains 1) is overexpressed in colon cancer tissues at protein levels but not at messenger RNA levels in colon cancer. Further study revealed that TMCO1 is a substrate of ER-associated degradation E3 ligase Gp78. Intriguingly, Gp78-mediated TMCO1 degradation at K186 is under the control of the iASPP (inhibitor of apoptosis-stimulating protein of p53) oncogene. Mechanistically, iASPP robustly reduces ER Ca2+ stores, mainly by competitively binding with Gp78 and interfering with Gp78-mediated TMCO1 degradation. A positive correlation between iASPP and TMCO1 proteins is further validated in human colon tissues. Inhibition of iASPP-TMCO1 axis promotes cytosolic Ca2+ overload-induced apoptotic cell death, reducing tumor growth both in vitro and in vivo. Thus, iASPP-TMCO1 represents a promising anticancer treatment target by modulating Ca2+ homeostasis.

Mitochondria-localized lncRNA HITT inhibits fusion by attenuating formation of mitofusin-2 homotypic or heterotypic complexes.

Long noncoding RNAs (lncRNAs) are emerging as essential players in multiple biological processes. Mitochondrial dynamics, comprising the continuous cycle of fission and fusion, are required for healthy mitochondria that function properly. Despite long-term recognition of its significance in cell-fate control, the mechanism underlying mitochondrial fusion is not completely understood, particularly regarding the involvement of lncRNAs. Here, we show that the lncRNA HITT (HIF-1α inhibitor at translation level) can specifically localize in mitochondria. Cells expressing higher levels of HITT contain fragmented mitochondria. Conversely, we show that HITT knockdown cells have more tubular mitochondria than is present in control cells. Mechanistically, we demonstrate HITT directly binds mitofusin-2 (MFN2), a core component that mediates mitochondrial outer membrane fusion, by the in vitro RNA pull-down and UV-cross-linking RNA-IP assays. In doing so, we found HITT disturbs MFN2 homotypic or heterotypic complex formation, attenuating mitochondrial fusion. Under stress conditions, such as ultraviolet radiation, we in addition show HITT stability increases as a consequence of MiR-205 downregulation, inhibiting MFN2-mediated fusion and leading to apoptosis. Overall, our data provide significant insights into the roles of organelle (mitochondria)-specific resident lncRNAs in regulating mitochondrial fusion and also reveal how such a mechanism controls cellular sensitivity to UV radiation-induced apoptosis.

Mutational landscape of primary spinal cord astrocytoma.

Primary spinal cord astrocytoma (SCA) is a rare disease. Knowledge about the molecular profiles of SCAs mostly comes from intracranial glioma; the pattern of genetic alterations of SCAs is not well understood. Herein, we describe genome-sequencing analyses of primary SCAs, aiming to characterize the mutational landscape of primary SCAs. We utilized whole exome sequencing (WES) to analyze somatic nucleotide variants (SNVs) and copy number variants (CNVs) among 51 primary SCAs. Driver genes were searched using four algorithms. GISTIC2 was used to detect significant CNVs. Additionally, recurrently mutated pathways were also summarized. A total of 12 driver genes were identified. Of those, H3F3A (47.1%), TP53 (29.4%), NF1 (19.6%), ATRX (17.6%), and PPM1D (17.6%) were the most frequently mutated genes. Furthermore, three novel driver genes seldom reported in glioma were identified: HNRNPC, SYNE1, and RBM10. Several germline mutations, including three variants (SLC16A8 rs2235573, LMF1 rs3751667, FAM20C rs774848096) that were associated with risk of brain glioma, were frequently observed in SCAs. Moreover, 12q14.1 (13.7%) encompassing the oncogene CDK4 was recurrently amplified and negatively affected patient prognosis. Besides frequently mutated RTK/RAS pathway and PI3K pathway, the cell cycle pathway controlling the phosphorylation of retinoblastoma protein (RB) was mutated in 39.2% of patients. Overall, a considerable degree of the somatic mutation landscape is shared between SCAs and brainstem glioma. Our work provides a key insight into the molecular profiling of primary SCAs, which might represent candidate drug targets and complement the molecular atlas of glioma. © 2023 The Pathological Society of Great Britain and Ireland.

Diagnostic value of one-stop CT energy spectrum and perfusion for angiogenesis in colon and rectum cancer.

OBJECTIVE: Evaluation of the predictive value of one-stop energy spectrum and perfusion CT parameters for microvessel density (MVD) in colorectal cancer cancer foci. METHODS: Clinical and CT data of 82 patients with colorectal cancer confirmed by preoperative colonoscopy or surgical pathology in our hospital from September 2019 to November 2022 were collected and analyzed retrospectively. Energy spectrum CT images were measured using the Protocols general module of the GSI Viewer software of the GE AW 4.7 post-processing workstation to measure the CT values of the arterial and venous phase lesions and the neighboring normal intestinal wall in a single energy range of 40 kev∼140 kev, and the slopes of the energy spectrum curves (λ) were calculated between 40 kev-90 kev; Iodine concentration (IC), Water concentration (WC), Effective-Z (Eff-Z) and Normalized iodine concentration (NIC) were measured by placing a region of interest (ROI) on the iodine concentration map and water concentration map at the lesion and adjacent to the normal intestinal wall.Perfusion CT images were scanned continuously and dynamically using GSI Perfusion software and analyzed by applying CT Perfusion 4.0 software.Blood volume (BV), blood flow (BF), surface permeability (PS), time to peak (TTP), and mean transit time (MTT) were measured respectively in the lesion and adjacent normal colorectal wall. Based on the pathological findings, the tumors were divided into a low MVD group (MVD < 35/field of view, n = 52 cases) and a high MVD group (MVD ≥ 35/field of view, n = 30 cases) using a median of 35/field of view as the MVD grouping criterion. The collected data were statistically analyzed, the subjects' operating characteristic curve (ROC) was plotted, and the area under curve (AUC), sensitivity, specificity, and Yoden index were calculated for the predicted efficacy of each parameter of the energy spectrum and perfusion CT and the combined parameters. RESULTS: The CT values, IC, NIC, λ, Eff-Z of 40kev∼140kev single energy in the arterial and venous phase of colorectal cancer in the high MVD group were higher than those in the low MVD group, and the differences were all statistically significant (p < 0.05). The AUC of each single-energy CT value in the arterial phase from 40 kev to 120 kev for determining the high or low MVD of colorectal cancer was greater than 0.8, indicating that arterial stage has a good predictive value for high or low MVD in colorectal cancer; AUC for arterial IC, NIC and IC + NIC were all greater than 0.9, indicating that in arterial colorectal cancer, both single and combined parameters of spectral CT are highly effective in predicting the level of MVD. The AUC of 40 kev to 90 kev single-energy CT values in the intravenous phase was greater than 0.9, and its diagnostic efficacy was more representative; The AUC of IC and NIC in venous stage were greater than 0.8, which indicating that the IC and NIC energy spectrum parameters in venous stage colorectal cancer have a very good predictive value for the difference between high and low MVDs, with the greatest diagnostic efficacy in IC.The values of BV and BF in the high MVD group were higher than those in the low MVD group, and the differences were statistically significant (P < 0.05), and the AUC of BF, BV, and BV + BF were 0.991, 0.733, and 0.997, respectively, with the highest diagnostic efficacy for determining the level of MVD in colorectal cancer by BV + BF. CONCLUSION: One-stop CT energy spectrum and perfusion imaging technology can accurately reflect the MVD in living tumor tissues, which in turn reflects the tumor angiogenesis, and to a certain extent helps to determine the malignancy, invasion and metastasis of living colorectal cancer tumor tissues based on CT energy spectrum and perfusion parameters.

The Role of Preoperative CT Perfusion Imaging in Assessing Colorectal Cancer Angiogenesis and its Clinical Value.

Purpose: Angiogenesis, the formation of new blood vessels, plays a crucial role in tumor growth and metastasis. Understanding the vascular characteristics of colorectal cancer through preoperative computed tomography (CT) perfusion parameters can provide valuable insights into the tumor's aggressiveness and potential for spread. Additionally, exploring the correlation between these parameters and serum tumor marker levels may offer a comprehensive perspective on the disease's biological behavior. Methods: In this retrospective study, we investigated 42 colorectal cancer patients. Based on microvascular density (MVD) measured by immunohistochemistry (IHC), participants were categorized into either a high-density group (n = 24) with MVD ≥ 35/field of view or a low-density group (n = 18) with MVD < 35/field of view. Additionally, a control group comprised 25 patients with pathologically confirmed benign colorectal lesions. This study design allowed us to assess the correlation between MVD and colorectal cancer, differentiating between high and low microvascular density groups, while also comparing results to a control group for comprehensive analysis. Results: Colorectal cancer was associated with significantly higher levels of blood volume (BV; high-density group: 7.65±1.36 mL/100g; low-density group: 6.73±1.29 mL/100g), blood flow (BF; high-density group: 67.33±12.16 ml/(100g·min); low-density group: 52.84±11.43 ml/(100g·min)), permeability surface (PS; high-density group: 35.19±6.32 ml/(100g·min); low-density group: 22.27±4.85 ml/(100g·min)), serum glycoprotein antigen 19-9 (CA19-9; high-density group: 45.38±5.41 g/ml); low-density group: 23.43±3.59 g/ml), glycoprotein antigen 125 (CA125; high-density group: 27.56±3.73 g/ml); low-density group: 12.63±2.59 g/ml), and carcinoembryonic antigen (CEA; high-density group: 17.87±3.12 g/ml); low-density group: 8.51±2.87 g/ml) versus benign colorectal lesions, with more significant changes observed in the high-density group versus the low-density group (P ≤ .001). The three groups showed similar mean transit time (MTT). The AUCs under the ROC curves for BV, BF, PS, and TTP were 0.901, 0.898, 0.963, and 0.983, respectively. Pearson correlation analysis showed a positive correlation of patients' serum CA19-9 with BV, BF, and PS., Serum CA125 and CEA were positively correlated with BF and PS, and the above indicators were negatively correlated with TTP. Conclusions: In conclusion, our study highlights the potential of preoperative CT perfusion imaging as a valuable tool for evaluating angiogenesis in colorectal cancer and its correlation with serum tumor markers. The identified associations open avenues for further research to delve into specific aspects of angiogenesis and tumor markers. Future investigations could focus on elucidating the molecular mechanisms underlying the observed correlations, potentially identifying novel therapeutic targets. Additionally, exploring the dynamic changes in angiogenesis and tumor markers during different stages of colorectal cancer progression may provide a more comprehensive understanding. Moreover, assessing the prognostic value of these imaging and biomarker correlations in larger, diverse patient cohorts could enhance their clinical utility. Our findings lay the groundwork for these future research directions, emphasizing the need for continued exploration to advance our knowledge and improve clinical strategies for colorectal cancer management.

One-pot Synthesis of Phosphorus-modified ZSM-5 Zeolite by Solid-state Method and its MTO Catalytic Performance.

The traditional hydrothermal synthesis strategy of ZSM-5 zeolite is energy-consumption accompanying by pollution issues. Herein, phosphorus-modified layered ZSM-5 zeolites (PZ) were obtained by one-pot synthesis under solvent-free conditions. The synthesized samples were fully characterized by XRD, SEM, BET, NH3 -TPD and FTIR. The effect of phosphorus addition on the morphology and catalytic activity of ZSM-5 was investigated. The results showed that phosphorus-modified ZSM-5 zeolites exhibited higher light olefin (ethylene and propylene) selectivity (above 50 %) and longer catalytic lifetime (33 h) in methanol to olefin (MTO) reaction when the weight hourly space velocity was 4 h-1 . Phosphorus-modified ZSM-5 zeolite synthesized by in situ solvent-free method, which not only reduced the discharge of sewage but also showed a simple method to realize the introduction of phosphorous species, which provided a new idea for phosphorus modification of ZSM-5 zeolite.

A long noncoding RNA sensitizes genotoxic treatment by attenuating ATM activation and homologous recombination repair in cancers.

Ataxia-telangiectasia mutated (ATM) is an apical kinase of the DNA damage response following DNA double-strand breaks (DSBs); however, the mechanisms of ATM activation are not completely understood. Long noncoding RNAs (lncRNAs) are a class of regulatory molecules whose significant roles in DNA damage response have started to emerge. However, how lncRNA regulates ATM activity remains unknown. Here, we identify an inhibitor of ATM activation, lncRNA HITT (HIF-1α inhibitor at translation level). Mechanistically, HITT directly interacts with ATM at the HEAT repeat domain, blocking MRE11-RAD50-NBS1 complex-dependent ATM recruitment, leading to restrained homologous recombination repair and enhanced chemosensitization. Following DSBs, HITT is elevated mainly by the activation of Early Growth Response 1 (EGR1), resulting in retarded and restricted ATM activation. A reverse association between HITT and ATM activity was also detected in human colon cancer tissues. Furthermore, HITTs sensitize DNA damaging agent-induced cell death both in vitro and in vivo. These findings connect lncRNA directly to ATM activity regulation and reveal potential roles for HITT in sensitizing cancers to genotoxic treatment.

lncRNA HITT inhibits metastasis by attenuating Rab5-mediated endocytosis in lung adenocarcinoma.

Endocytosis of cell surface receptors is essential for cell migration and cancer metastasis. Rab5, a small GTPase of the Rab family, is a key regulator of endosome dynamics and thus cell migration. However, how its activity is regulated still remains to be addressed. Here, we identified a Rab5 inhibitor, a long non-coding RNA, namely HITT (HIF-1α inhibitor at translation level). Our data show that HITT expression is inversely associated with advanced stages and poor prognosis of lung adenocarcinoma patients with area under receiver operating characteristics (ROC) curve (AUC) 0.6473. Further study reveals that both endogenous and exogenous HITT inhibits single-cell migration by repressing ß1 integrin endocytosis in lung adenocarcinoma. Mechanistically, HITT is physically associated with Rab5 at switch I via 1248-1347 nt and suppresses ß1 integrin endocytosis and subsequent cancer metastasis by interfering with guanine nucleotide exchange factors (GEFs) for Rab5 binding. Collectively, these findings suggest that HITT directly participates in the regulation of Rab5 activity, leading to a decreased integrin internalization and cancer metastasis, which provides important insights into a mechanistic understanding of endocytosis and cancer metastasis.

Multi-Pathway Microenvironment Regulation for Atherosclerosis Therapy Based on Beta-Cyclodextrin/L-Arginine/Au Nanomotors with Dual-Mode Propulsion.

Most of the current non-pharmacological treatment strategies for atherosclerosis (AS) suffer from poor penetration into the plaque and only aim at a certain factor in its formation process, resulting in limited therapeutic effect. Herein, a kind of nanomotor with dual-mode propulsion is constructed, which is sensitive to higher reactive oxygen species (ROS) at the AS site and near-infrared (NIR) laser by the covalent binding and self-assembly of ß-cyclodextrin (ß-CD) and L-arginine (LA) with immobilization of Au nanoparticles. NIR laser irradiation can be used as a driving force and to ablate inflammatory macrophages through the photothermal effect. The nitric oxide (NO) released by the nanomotors can be used as another driving force and a therapeutic agent to promote endothelial repair in the plaque site. LA can eliminate ROS in the inflammatory site, and ß-CD can promote the removal of cholesterol from foam cells. In particular, the two driving modes of nanomotors synergistically promote their aggregation and penetration in the plaque. This kind of nanomotor can regulate the microenvironment of AS in multiple ways, including combination therapy for endothelial repair, lipid clearance, and reducing ROS, which is expected to become a potential non-pharmacological strategy in the treatment of AS.

Fluid shear stress-induced down-regulation of microRNA-140-5p promotes osteoblast proliferation by targeting VEGFA via the ERK5 pathway.

PURPOSE: Fluid shear stress (FSS) plays a critical role in osteoblast proliferation. However, the role of miRNA in osteoblast proliferation induced by FSS and the possible molecular mechanisms remain to be defined. The aim of the present study was to investigate whether miR-140-5p regulates osteoblast proliferation under FSS and its molecular mechanism. MATERIALS AND METHODS: miR-140-5p expression was measured by qRT-PCR. Western blot was used to measure the expressions of P-ERK1/2, ERK1/2, P-ERK5 and ERK5. The levels of VEGFA, PCNA, CDK4 and Cyclin D1 were identified through qRT-PCR and western blot, respectively. Cell proliferation was detected by CCK-8 assay and EdU labeling assay. Dual-luciferase reporter assay was used to validate the target of miR-140-5p. RESULTS: miR-140-5p was significantly down-regulated when MC3T3-E1 cells were exposed to FSS. We then confirmed that up-regulation of miR-140-5p inhibited and down-regulation of miR-140-5p promoted osteoblast proliferation. In addition, FSS promotes osteoblast proliferation via down-regulating miR-140-5p. Luciferase reporter assay demonstrated that VEGFA is a direct target of miR-140-5p. Furthermore, transfection of mimic-140-5p inhibited the up-regulation of VEGFA protein level induced by FSS, suggesting that FSS regulates VEGFA protein expression via miR-140-5p. Further investigations demonstrated that VEGFA could promote osteoblast proliferation. Lastly, we demonstrated that miR-140-5p regulates osteoblast proliferation and ERK5 activation through VEGFA. CONCLUSIONS: Our study demonstrates that FSS-induced the down-regulation of miR-140-5p promotes osteoblast proliferation through activing VEGFA/ERK5 signaling pathway. These findings may provide a novel mechanism of FSS-induced osteoblast proliferation and offer a new avenue to further investigate osteogenesis induced by mechanical loading.

Dural ossification associated with ossification of posterior longitudinal ligament in the cervical spine: a retrospective analysis.

OBJECTIVE: Dural ossification (DO) is common in patients with ossification of the posterior longitudinal ligament (OPLL). The existence of DO makes surgery challenging and increases the risk of complications. The aim of this study was to investigate the incidence, distribution and radiological characteristics of DO associated with OPLL. METHODS: From January 2017 to January 2019, 55 patients with cervical OPLL were treated in our single center using an anterior cervical approach microsurgery. Preoperative CT images of decompressed segments were evaluated to identify imaging signs of DO. The 'double-layer sign' (DLS), 'parenthese sign' (PS) and 'hook sign' (HS) were considered to be characteristic imaging findings of DO in OPLL. Two kinds of confusing signs (false double-layer) were identified. RESULTS: Nineteen segments from 15 patients with OPLL had DO related to OPLL. The incidence of DO in OPLL segments was 30.16% (19/63), and the incidence of DO in patients with OPLL was 27.27% (15/55). DO occurred at the intervertebral space level in 14 cases and at the posterior level of the vertebral body in 5 cases. The sensitivity and specificity of imaging diagnosis were 89.47% (17/19) and 81.82% (36/44), respectively. The positive predictive value was relatively low, 68.00% (17/25), due to the false-positive double-layer sign. The negative predictive value was 94.74% (36/38). CONCLUSION: DO was relatively common in cervical OPLL. DLS might be misdiagnosed. PS and HS can vividly and intuitively describe the imaging features of DO and have high diagnostic accuracy.

Three new tyrosol derivatives from Huangjing wine.

Phytochemical investigation on the concentrate of Huangjing wine, resulted in the isolation of three new tyrosol derivatives 4'''-hydroxyphenethyl 2-(R)-hydroxy-3-phenylpropionate (1), 4'''-hydroxyphenethyl(4'-hydroxy-3'-methoxyphenyl)propionate (2) and 4''-hydroxyphenethyl ethyl succinate (3), together with 5 known compounds, ferulic acid (4), L-phenyllactic acid (5), hydroxytyrosol (6), dihydroferulic acid (7), cyclo(L-Pro-D-Tyr) (8). Their structures were elucidated using spectroscopic analysis and by comparison with the literature data. All compounds displayed antioxidant effect in the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical. Among them, the new compound 2 exhibited obvious antioxidant effect, and new compounds 1 and 3 exhibited medium antioxidant effect.

Fluid shear stress regulates osteoblast proliferation and apoptosis via the lncRNA TUG1/miR-34a/FGFR1 axis.

LncRNAs and microRNAs play critical roles in osteoblast differentiation and bone formation. However, their exact roles in osteoblasts under fluid shear stress (FSS) and the possible mechanisms remain unclear. The aim of this study was to explore whether and how miR-34a regulates osteoblast proliferation and apoptosis under FSS. In this study, FSS down-regulated miR-34a levels of MC3T3-E1 cells. MiR-34a up-regulation attenuated FSS-induced promotion of proliferation and suppression of apoptosis. Luciferase reporter assay revealed that miR-34a directly targeted FGFR1. Moreover, miR-34a regulated osteoblast proliferation and apoptosis via FGFR1. Further, we validated that lncRNA TUG1 acted as a competing endogenous RNA (ceRNA) to interact with miR-34a and up-regulate FGFR1 protein expression. Furthermore, lncRNA TUG1 could promote proliferation and inhibit apoptosis. Taken together, our study revealed the key role of the lncRNA TUG1/miR-34a/FGFR1 axis in FSS-regulated osteoblast proliferation and apoptosis and may provide potential therapeutic targets for osteoporosis.

Deep Penetration of Nanolevel Drugs and Micrometer-Level T Cells Promoted by Nanomotors for Cancer Immunochemotherapy.

The ability of nanomotors to promote the deep penetration of themselves and the loaded drugs in diseased tissues has been proposed and confirmed. However, whether such motion behavior of the nanomotors can also promote deep penetration of micrometer-sized immune cells in the diseased microenvironment, which is important for the immunotherapy of some diseases, has not been mentioned. Herein, we construct a nitric oxide (NO)-driven nanomotor that can move in the tumor microenvironment, focusing on its motion behavior and the role of NO, the beneficial product released during movement from this kind of nanomotor, in regulating the infiltration behavior and activity of immune cells. It can be found that the drug-loaded nanomotors with both NO-releasing ability and motility can promote the normalization of the tumor vasculature system and the degradation of the intrinsic extracellular matrix (ECM), which can significantly improve the tumor infiltration ability of T cells in vivo. The efficiency of T-cell infiltration in tumor tissue in vivo increased from 2.1 to 28.2%. Both subcutaneous and intraperitoneal implantation tumor models can validate the excellent antitumor effect of drug-loaded NO-driven nanomotors. This combination of motility of the power source from nanomotors and their physiological function offers a design idea for therapeutic agents for the future immunotherapy of many diseases.

A novel classification and its clinical significance in Chiari I malformation with syringomyelia based on high-resolution MRI.

BACKGROUND: The existing classification in Chiari I malformation (CM-I) has limited significance for the selection of surgical methods. OBJECTIVE: The purpose of this study was to investigate the surgery of CM-I with syringomyelia based on the high-resolution MR imaging (HRMRI) findings. METHODS: Data from 115 patients were collected and retrospectively analyzed. For those with syringomyelia up to the level of C1, HRMRI was performed and according to the communication status between the fourth ventricle and the syringomyelia, patients can be divided into four types, namely Type A: classic communicating; Type B: partial communicating; Type C: non-communicating; Type D: atrophic. All operations were performed with Foramen magnum and Magendie dredging (FMMD), and all intradural factors that may have induced the obstruction of CSF circulation were recorded. The efficiency of operation on syringomyelia was evaluated by mJOA, imaging findings, and complications in the follow-up periods. RESULTS: The postoperative follow-up period was from 12 to 24 months, with an average of 14.3 months. At 1 year, the mJOA of 115 patients was significantly higher than that before the operations (before surgery 12.1 ± 2.3 vs. after surgery 14. 2 ± 1.4, P < 0.05). In addition, postoperative re-examination showed that the size of the syringomyelia was reduced or completely resolved in patients of Type A, 100% (2/2); Type B, 81% (9/11); Type C, 84% (81/97); and Type D, 20% (1/5). CONCLUSIONS: According to our new classification based on HRMRI, FMMD is the key to surgical treatment, especially for Type A and Type B patients.

The role of fibrinogen in predicting reinfection after DAIR for periprosthetic joint infections.

BACKGROUND: Fibrinogen (FIB) has been found to be a promising marker in diagnosing periprosthetic joint infection (PJI), however, the value of FIB in predicting reinfection of PJI is unknown. The purpose of this study was to evaluate the value of FIB in predicting reinfection after debridement, antibiotics, and implant retention (DAIR) for PJI. METHODS: We retrospectively analyzed the clinical data of patients who were diagnosed with PJI and underwent DAIR from 2013 to 2019. The levels of the FIB, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were measured before DAIR. After DAIR, patients were followed and reinfections were identified. For both acute and chronic PJI, the predictive value of FIB was evaluated by calculating the sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic curve (ROC), and was compared with traditional inflammatory markers including ESR and CRP. RESULTS: The expression of FIB differed between patients reinfected and those not reinfected in both acute and chronic PJI (p < 0.05). In patients who underwent DAIR for acute PJI, the sensitivity and specificity of FIB were 81.82 and 83.33%, respectively, which were significantly higher than that of CRP (sensitivity, 72.73%; specificity, 50%; p < 0.05), while the specificity was higher than that of ESR (specificity, 41.67%; p < 0.05). In patients who underwent DAIR for chronic PJI, the sensitivity and specificity of FIB were 80.00 and 66.66%, respectively, which were significantly higher than that of CRP (sensitivity, 53.33%; specificity, 66.66%; p < 0.05) and ESR (sensitivity was 66.00%; specificity, 16.66%; p < 0.05). The ROC curves showed that FIB demonstrated the highest AUC among the biomarkers in both acute and chronic PJI. CONCLUSION: FIB is a promising indicator in predicting reinfection after DAIR for both acute and chronic PJI, and it seems to perform better than ESR and CRP.

Tumor-Derived Exosomal eIF4E as a Biomarker for Survival Prediction in Patients with Non-Small Cell Lung Cancer.

BACKGROUND The aim of this study was to investigate the expression of tumor-derived exosomal RNA eIF4E (exo-eIF4E) in non-small cell lung cancer (NSCLC) and its correlation with prognosis. MATERIAL AND METHODS The Cancer Genome Atlas (TCGA) data was exacted to investigate the role of tissue eIF4E in NSCLC. We enrolled 99 NSCLC patients and 40 healthy volunteers with corresponding serum samples in this study. The levels of exo-eIF4E in the peripheral blood of each group were tested by quantitative polymerase chain reaction (PCR). The chi-squared test and the log-rank test were applied to analyze the correlation between the expression levels of exo-eIF4E and the patients' clinical-pathological data, including the overall survival. RESULTS TCGA data showed that increased eIF4E in NSCLC tissues was associated with late-stage disease (P=0.0497) and inferior overall survival (P=0.017). The expression of exo-eIF4E in the serum of the NSCLC group was significantly higher than that in healthy individuals (P<0.001). Furthermore, advanced TNM stage (P=0.003), distant metastasis (P=0.008), and serum positive cytokeratin fragment 19 (CYFRA21-1) (P=0.023) are more likely present in NSCLC patients with higher exo-eIF4E expression. Moreover, the multivariate combined with univariate analyses verified exo-eIF4E as an independent prognostic factor for shorter overall survival (P=0.01) and progression-free survival (P=0.005). Shorter overall survival (P=0.0005) and inferior progression-free survival (P=0.0017) are more likely present in NSCLC patients with higher exo-eIF4E. CONCLUSIONS Tumor-derived exo-eIF4E in serum can be a practical tool to predict the prognosis of NSCLC.

Predictors of mortality in patients with primary spinal cord glioblastoma.

PURPOSE: Primary spinal cord glioblastoma (GBM) is a rare and devastating disease. Little attention was ever paid to this rare disease. As a result, the standard treatment protocol and prognostic factors of primary spinal cord GBM were not well established. The aim of this study was to determine the predictors associated with survival in patients with primary spinal cord GBM. METHODS: A total of 122 patients with primary spinal cord GBM from Surveillance, Epidemiology, and End Results database and our institution were included in this retrospective analysis. Information about age, sex, race, tumor invasion, extent of resection, radiation, chemotherapy and year of diagnosis was collected. Univariate and multivariate accelerated failure time (AFT) regression model was performed to identify prognostic factors. RESULTS: Of the 122 patients, 102 (83.6%) expired at the time of data collection. Overall survival at 1 year, 2 years, 3 years and 5 years was 48.4%, 22.8%, 17.1% and 8.4%, respectively, and median survival time was 12 months. Only radiation was found to be associated with survival in the AFT regression model (time ratio 1.94, 95% CI 1.01-3.72, p < 0.05). Radiotherapy could improve survival slightly; patients who received RT survived approximately two times as long as patients who did not receive RT, but the advantage was short term. CONCLUSION: The survival of primary spinal cord GBM is poor in the current treatment strategy. Radiotherapy was associated with better survival, but the advantage was short term.

GNAS knockdown suppresses osteogenic differentiation of mesenchymal stem cells via activation of Hippo signaling pathway.

Bone marrow-derived mesenchymal stem cells (BMSCs) are a suitable option for cell-based tissue engineering therapies due to their ability to renew and differentiate into multiple different tissue types, such as bone. Over the last decade, the effect of GNAS on the regulation of osteoblast differentiation has attracted great attention. Herein, this study aimed to explore the role of GNAS in osteogenic differentiation of MSCs. A total of 85 GNASf/f male mice were selected for animal experiments and 10 GNASf/f male mice for BMSC isolation to conduct cell experiments. The mice and BMSCs were treated with Verteporfin (a Hippo signaling pathway inhibitor) to inhibit the Hippo signaling pathway or recombinant adenovirus-expressing Cre to knockout the GNAS expression. Next, computed tomography scan, Von Kossa staining, and alizarin red staining were performed to detect osteogenic differentiation ability. Moreover, immunohistochemistry and alkaline phosphatase (ALP) staining were used to assess the expression of Oc and Osx in femur tissues and ALP activity. At last, the expression of GNAS, osteogenic markers, and factors related to the Hippo signaling pathway was evaluated. Initially, the results displayed successful knockout of the GNAS gene from mice and BMSCs. Moreover, the data indicated that GNAS knockout inhibits expression of Oc, Osx, ALP, BMP-2, and Runx2, and ALP activity. Additionally, GNAS knockout promotes activation of the Hippo signaling pathway, so as to repress osteogenic differentiation. Collectively, depleted GNAS exerts an inhibitory role in osteogenic differentiation of MSCs by activating Hippo signaling pathway, providing a candidate mediator for osteoporosis.