KAP1 stabilizes MYCN mRNA and promotes neuroblastoma tumorigenicity by protecting the RNA m6A reader YTHDC1 protein degradation.

BACKGROUND: Neuroblastoma (NB) patients with amplified MYCN often face a grim prognosis and are resistant to existing therapies, yet MYCN protein is considered undruggable. KAP1 (also named TRIM28) plays a crucial role in multiple biological activities. This study aimed to investigate the relationship between KAP1 and MYCN in NB. METHODS: Transcriptome analyses and luciferase reporter assay identified that KAP1 was a downstream target of MYCN. The effects of KAP1 on cancer cell proliferation and colony formation were explored using the loss-of-function assays in vitro and in vivo. RNA stability detection was used to examine the influence of KAP1 on MYCN expression. The mechanisms of KAP1 to maintain MYCN mRNA stabilization were mainly investigated by mass spectrum, immunoprecipitation, RIP-qPCR, and western blotting. In addition, a xenograft mouse model was used to reveal the antitumor effect of STM2457 on NB. RESULTS: Here we identified KAP1 as a critical regulator of MYCN mRNA stability by protecting the RNA N6-methyladenosine (m6A) reader YTHDC1 protein degradation. KAP1 was highly expressed in clinical MYCN-amplified NB and was upregulated by MYCN. Reciprocally, KAP1 knockdown reduced MYCN mRNA stability and inhibited MYCN-amplified NB progression. Mechanistically, KAP1 regulated the stability of MYCN mRNA in an m6A-dependent manner. KAP1 formed a complex with YTHDC1 and RNA m6A writer METTL3 to regulate m6A-modified MYCN mRNA stability. KAP1 depletion decreased YTHDC1 protein stability and promoted MYCN mRNA degradation. Inhibiting MYCN mRNA m6A modification synergized with chemotherapy to restrain tumor progression in MYCN-amplified NB. CONCLUSIONS: Our research demonstrates that KAP1, transcriptionally activated by MYCN, forms a complex with YTHDC1 and METTL3, which in turn maintain the stabilization of MYCN mRNA in an m6A-dependent manner. Targeting m6A modification by STM2457, a small-molecule inhibitor of METTL3, could downregulate MYCN expression and attenuate tumor proliferation. This finding provides a new alternative putative therapeutic strategy for MYCN-amplified NB.

Should we perform sigmoidoscopy for colorectal cancer screening in people under 45 years?

BACKGROUND: The strategy for preventing colorectal cancer is screening by colonoscopy, which offers a direct way for detection and removal of adenomatous polyps (APs). American College of Gastroenterology guidelines recommend that people aged ≥ 45 years should undergo colonoscopy; however, how to deal with people aged ≤ 45 years is still unknown. AIM: To compare the prevalence of APs and high-grade neoplasia between the left and right colon in patients ≤ 45 years. METHODS: A retrospective observational study was conducted at a single tertiary III hospital in China. This study included patients aged 18-45 years with undergoing initial colonoscopy dissection and pathological diagnosis AP or high-grade neoplasia between February 2014 and January 2021. The number of APs in the entire colon while screening and post-polypectomy surveillance in following 1-3 years were evaluated. RESULTS: A total of 3053 cases were included. The prevalence of APs in the left and right colon was 55.0% and 41.6%, respectively (OR 1.7, 95%CI 1.6-2.4; P < 0.05). For APs with high-grade neoplasia, the prevalence was 2.7% and 0.9%, respectively (OR 3.0, 95%CI 2.0-4.6; P < 0.05). Therefore, the prevalence of APs and high-grade neoplasia in the left colon was significantly higher than in the right colon in patients aged ≤ 45 years. There were 327 patients who voluntarily participated in post-polypectomy surveillance in following 1-3 years, and APs were found in 216 cases (66.1%); 170 cases had 1-3 polyps (52.0%) and 46 cases had > 3 polyps (14.1%; OR 0.3, 95%CI 0.1-0.6; P < 0.05). CONCLUSION: This study suggests that flexible sigmoidoscopy would be an optimal approach for initial screening in people aged ≤ 45 years and would be a more cost-effective and safe strategy.

[Recent advances in the genetic etiology of central precocious puberty]. / é—ä¼ ç¼ºé™·è‡´ä¸­æž¢æ€§æ€§æ—©ç†Ÿç— å› å­¦çš„ç ”ç©¶æ–°è¿›å±•.

Central precocious puberty (CPP) is a developmental disorder caused by early activation of the hypothalamic-pituitary-gonadal axis. The incidence of CPP is rapidly increasing, but the underlying mechanisms are not fully understood. Previous studies have shown that gain-of-function mutations in the KISS1R and KISS1 genes and loss-of-function mutations in the MKRN3, LIN28, and DLK1 genes may lead to early initiation of pubertal development. Recent research has also revealed the significant role of epigenetic factors such as DNA methylation and microRNAs in the regulation of gonadotropin-releasing hormone neurons, as well as the modulating effect of gene networks involving multiple variant genes on pubertal initiation. This review summarizes the genetic etiology and pathogenic mechanisms underlying CPP.

The association between different physical activity (PA) patterns and cardiometabolic index (CMI) in US adult population from NHANES (2007-2016).

Background: Physical activity (PA) is widely recommended for preventing and combating obesity, but the most effective PA pattern for treating obesity remains unclear. Cardiometabolic index (CMI), derived from waist height ratio and triglycerides to high-density lipoprotein-cholesterol ratio, is a novel indicator for evaluating obesity. However, the relationship between different PA patterns and CMI remains unelucidated. Objective: This study aimed to explore the association between different PA patterns and CMI in U.S. adults. Methods: Participants with complete information in CMI, PA patterns, and other covariates in the National Health and Nutrition Examination Survey database (2007-2016) were included in this study. Multivariate linear regression models were utilized to explore the relationship between PA patterns and CMI. Moreover, stratified analyses, interaction tests and restricted cubic spline (RCS) regression analysis were used to investigate the stability and nonlinearity of the association, respectively. Results: A total of 16,442 adults were included in this study. After adjusting for all potential covariates, only the regularly active group was significantly associated with CMI reduction (ß = -0.13, 95% CI: 0.19 to -0.07, P < 0.0001), while the weekend warriors group did not achieve equivalent CMI reduction (ß = -0.09, 95% CI: 0.32 to 0.14, P = 0.4204). Subgroup analyses and interaction tests revealed that the CMI-PA association was more pronounced in the subgroup with age≤45 or >60, with higher education level, and who are current drinkers. Furthermore, RCS analysis indicated that total PA in a week was significantly, nonlinearly associated with CMI in non-inactive adults, and that a total of PA more than 330 min can reap favorable CMI reduction. Conclusion: Being regularly active is associated with significant CMI reduction, while being weekend warriors and insufficiently active do not achieve equivalent benefits. For non-inactive individuals, engaging in PA for more than 330 min weekly helps to reduce CMI effectively.

Bibliometric analysis of worldwide research on Polycythemia Vera in the 21st century.

Polycythemia vera (PV) is a myeloproliferative tumor with low incidence and complex symptoms, affecting patients' quality of life and shortening their life span. Since the beginning of the 21st century, there has been an update but a need for uniform consensus regarding diagnosing and treating PV. With the continued interest of researchers in this field, a bibliometric study of PV is necessary. This paper aims to analyze articles on PV through bibliometric software to provide collaborative information and new ideas for researchers in this field. We collected PV-related publications in the Web of Science Core Collection database from 2000 to 2023. The included literature was analyzed using Citespace (6.2.R2), VOSviewer (1.6.19), and Bibliometrix. The study included country/region, institution, authors, journals, keywords, and references, and a visual knowledge network diagram was constructed. Microsoft Excel 2013 was also used for statistical analysis. A total of 1,093 articles were eventually included. The number of PV-related publications has steadily increased from 2000 to the present, with great potential for future growth. The US and US institutions have contributed more to this field, with the US ranking first in the number of publications, total citations, and centrality. Alessandro M. Vannucchi is the most published author. Tefferi, Ayalew is the most cited author. And BLOOD has the most publications, topping the list of the eleven high-productivity core source journals. The most cited article was "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders" (Baxter, EJ, 2005). By examining the keywords, we found that the diagnosis and typing of true erythrocytosis, the use of ruxolitinib, and the tyrosine kinase JAK2 are the research hotspots in the field; genetic and molecular research in the field of true erythrocytosis is a cutting-edge topic in the field; and risk factors for true erythrocytosis is a cutting-edge hotspot issue in the field. The fruitful research in this century has laid the foundation for developing the field of PV. The information in this article will provide researchers with current hotspots and future potential in the discipline, helping the field achieve more extraordinary breakthroughs. Currently, research should focus on increasing global multicenter collaborative research in diagnosis and treatment to develop scientifically recognized diagnostic and treatment protocols and new clinical drug research. Our proposed model of global innovation collaboration will provide strong support for future research.

[Clinical manifestation and imaging diagnostic analysis of fat embolism syndrome].

OBJECTIVE: To explore characteristics of clinical and imaging findings in patients with fat embolism syndrome. METHODS: From January 2021 to October 2022,clinical manifestations of 13 patients with fat embolism due to fracture or orthopaedic surgery were retrospectively analyzed,including 11 males and 2 females,aged from 17 to 60 years old. Mental and respiratory abnormalities and changes in vital signs occurred after admission or after surgery,and patient's chest and brain imaging results were abnormal. The patient's mental and respiratory abnormalities,vital signs,chest and brain imaging results were continuously monitored. RESULTS: The main clinical manifestations of fat embolism syndrome were abnormal pulmonary respiration in 13 patients,abnormal central nervous function in 7 patients,and spotted rash in 2 patients. Chest CT showed diffuse distribution of ground glass shadows in 13 patients,and severe symptoms were "snowstorm". Nine patients with ground glass fusion consolidation,5 patients with multiple nodules and 4 patients accompanied by bilateral pleural effusion. Head CT findings of 5 patients were negative,and head MRI findings of 1 patient showed multiple T1WI low signal,T2WI high signal shadow,DWI high signal shadow,and "starry sky sign" in basal ganglia,radiative crown,hemioval center,thalamus,frontal parietal cortex and subcortex. CONCLUSION: Fat embolism syndrome has a high mortality rate. Clinical manifestations of respiratory system and nervous system are not specific,and the skin spot rash has a characteristic manifestation. The "blizzard" sign is the specific manifestation of chest X-ray and CT examination of fat embolism,and the "starry sky" sign is the typical manifestation of diffusion-weighted sequence of brain MRI examination of fat embolism.

LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling.

BACKGROUND: Cancer stem-like cell is a key barrier for therapeutic resistance and metastasis in various cancers, including breast cancer, yet the underlying mechanisms are still elusive. Through a genome-wide lncRNA expression profiling, we identified that LINC00115 is robustly upregulated in chemoresistant breast cancer stem-like cells (BCSCs). METHODS: LncRNA microarray assay was performed to document abundance changes of lncRNAs in paclitaxel (PTX)-resistant MDA-MB-231 BCSC (ALDH+) and non-BCSC (ALDH-). RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to determine the binding proteins of LINC00115. The clinical significance of the LINC00115 pathway was examined in TNBC metastatic lymph node tissues. The biological function of LINC00115 was investigated through gain- and loss-of-function studies. The molecular mechanism was explored through RNA sequencing, mass spectrometry, and the CRISPR/Cas9-knockout system. The therapeutic potential of LINC00115 was examined through xenograft animal models. RESULTS: LINC00115 functions as a scaffold lncRNA to link SETDB1 and PLK3, leading to enhanced SETDB1 methylation of PLK3 at both K106 and K200 in drug-resistant BCSC. PLK3 methylation decreases PLK3 phosphorylation of HIF1α and thereby increases HIF1α stability. HIF1α, in turn, upregulates ALKBH5 to reduce m6A modification of LINC00115, resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1α are prognostic for clinical triple-negative breast cancers. CONCLUSIONS: Our findings uncover LINC00115 as a critical regulator of BCSC and highlight targeting LINC00115 and SETDB1 as a potential therapeutic strategy for chemotherapeutic resistant breast cancer.

Pan-cancer integrated analysis of ANKRD1 expression, prognostic value, and potential implications in cancer.

There is substantial evidence demonstrating the crucial role of inflammation in oncogenesis. ANKRD1 has been identified as an anti-inflammatory factor and is related to tumor drug resistance. However, there have been no studies investigating the prognostic value and molecular function of ANKRD1 in pan-cancer. In this study, we utilized the TCGA, GTEx, GSCALite, ENCORI, CTRP, DAVID, AmiGO 2, and KEGG databases as well as R language, to explore and visualize the role of ANKRD1 in tumors. We employed the ROC curve to explore its diagnostic significance, while the Kaplan-Meier survival curve and Cox regression analysis were used to investigate its prognostic value. Additionally, we performed Pearson correlation analysis to evaluate the association between ANKRD1 expression and DNA methylation, immune cell infiltration, immune checkpoints, TMB, MSI, MMR, and GSVA. Our findings indicate that ANKRD1 expression is dysregulated in pan-cancer. The ROC curve revealed that ANKRD1 expression is highly sensitive and specific in diagnosing CHOL, LUAD, LUSC, PAAD, SKCM, and UCS (AUC > 85.0%, P < 0.001). Higher ANKRD1 expression was related to higher overall survival (OS) in LGG, but with lower OS in COAD and STAD (P < 0.001). Moreover, Cox regression and nomogram analyzes suggested that ANKRD1 is an independent factor for COAD, GBM, HNSC, and LUSC. Dysregulation of ANKRD1 expression in pan-cancer involves DNA methylation and microRNA regulation. Using the CTRP database, we discovered that ANKRD1 may influence the half-maximal inhibitory concentration (IC50) of several anti-tumor drugs. ANKRD1 expression showed significant correlations with immune cell infiltration (including cancer-associated fibroblast and M2 macrophages), immune checkpoints, TMB, MSI, and MMR. Furthermore, ANKRD1 is involved in various inflammatory and immune pathways in COAD, GBM, and LUSC, as well as cardiac functions in HNSC. In vitro experiments demonstrated that ANKRD1 promotes migration, and invasion activity, while inhibiting apoptosis in colorectal cancer cell lines (Caco2, SW480). In summary, ANKRD1 represents a potential prognostic biomarker and therapeutic target in human cancers, particularly in COAD.

Relationship between paravertebral muscle function, pelvic incidence, and health-related quality of life in patients with degenerative spinal deformity.

BACKGROUND: Patients with degenerative spinal deformity often experience symptoms that seriously affect their quality of life, such as low back pain and dysfunction. This study aimed to investigate the relationship between paravertebral muscle function and pelvic incidence (PI) and their effect on health-related quality of life (HRQL) in patients with degenerative spinal deformity. METHODS: A total of 112 patients with degenerative spinal deformity in Southwest Hospital (Chongqing, China) were enrolled. They were divided into groups according to PI angle: high (PI > 60°, n = 37), normal (PI 50°-60°, n = 31), and low (PI < 50°, n = 44). Paravertebral muscle strength and endurance were assessed using the prone external fixation test frame. The sagittal vertical axis (SVA) was measured on X-rays of the spine in an anterolateral position, and all subjects were assessed with the Oswestry Disability Index (ODI), Roland-Morris questionnaire (RMQ), and 36-Item Short Form Health Survey (SF-36). Pearson or Spearman coefficients were used to assess the relationship of paravertebral muscle function with SVA, PI, and health-related quality of life. RESULTS: Maximal voluntary exercise (MVE) in the high-PI group was significantly lower than the MVE of both the normal- and low-PI groups (p < 0.05). There was no significant difference in MVE between the normal- and low-PI groups (p > 0.05). There was no significant difference in endurance time, SVA, ODI, RMQ, and SF-36 among the three groups. Paravertebral muscle MVE was negatively correlated with PI, SVA, ODI, and RMQ (r = - 0.193, - 0.210, - 0.283, - 0.277, p < 0.05). Endurance time of paravertebral muscle was also negatively correlated with SVA, ODI, and RMQ (r = - 0.200, - 0.420, - 0.348, p < 0.05) and positively correlated with SF-36 (r = 0.245, p < 0.05). In addition, paravertebral muscle MVE was positively correlated with the physical functioning score of the SF-36 (r = 0.251, p < 0.05), and the endurance time of paravertebral muscle was positively correlated with the physical functioning, physical role, bodily pain, and social function scores of the SF-36 (r = 0.342, 0.230, 0.209, 0.256, p < 0.05). CONCLUSIONS: High PI may serve as a risk factor for decreased paraspinal muscle strength in patients with degenerative spinal deformities. Early and targeted exercises focusing on paraspinal muscle strength and endurance could potentially be of positive significance in slowing down the progression of sagittal imbalance, alleviating functional disorders, and increasing health-related quality of life in patients with degenerative spinal deformity.

Identification of potential biomarkers in the peripheral blood of neonates with bronchopulmonary dysplasia using WGCNA and machine learning algorithms.

Bronchopulmonary dysplasia (BPD) is often seen as a pulmonary complication of extreme preterm birth, resulting in persistent respiratory symptoms and diminished lung function. Unfortunately, current diagnostic and treatment options for this condition are insufficient. Hence, this study aimed to identify potential biomarkers in the peripheral blood of neonates affected by BPD. The Gene Expression Omnibus provided the expression dataset GSE32472 for BPD. Initially, using this database, we identified differentially expressed genes (DEGs) in GSE32472. Subsequently, we conducted gene set enrichment analysis on the DEGs and employed weighted gene co-expression network analysis (WGCNA) to screen the most relevant modules for BPD. We then mapped the DEGs to the WGCNA module genes, resulting in a gene intersection. We conducted detailed functional enrichment analyses on these overlapping genes. To identify hub genes, we used 3 machine learning algorithms, including SVM-RFE, LASSO, and Random Forest. We constructed a diagnostic nomogram model for predicting BPD based on the hub genes. Additionally, we carried out transcription factor analysis to predict the regulatory mechanisms and identify drugs associated with these biomarkers. We used differential analysis to obtain 470 DEGs and conducted WGCNA analysis to identify 1351 significant genes. The intersection of these 2 approaches yielded 273 common genes. Using machine learning algorithms, we identified CYYR1, GALNT14, and OLAH as potential biomarkers for BPD. Moreover, we predicted flunisolide, budesonide, and beclomethasone as potential anti-BPD drugs. The genes CYYR1, GALNT14, and OLAH have the potential to serve as diagnostic biomarkers for BPD. This may prove beneficial in clinical diagnosis and prevention of BPD.

Seawater pearl hydrolysate inhibits photoaging via decreasing oxidative stress, autophagy and apoptosis of Ultraviolet B-induced human skin keratinocytes.

BACKGROUND: Ultraviolet (UV) is the main reason to cause photoaging skin which not only hinders beauty, brings the patients with psychological burden, but also pathologically leads to the occurrence of tumors in skin. OBJECTIVE: This study goes into the inhibitory effect and mechanism of seawater pearl hydrolysate (SPH) to address human skin keratinocytes photoaging induced by UVB. METHODS: The photoaging model of Hacat cell was constructed by UVB irradiation, the levels of oxidative stress, apoptosis, aging, autophagy and autophagy-related protein and signal pathway expression were assessed to characterize the inhibitory effect and mechanism of SPH on photoaging Hacat cell. RESULTS: Seawater pearl hydrolysate significantly accelerated (p < 0.05) the activities of superoxide dismutase, catalase, and glutathione peroxidase, and markedly reduced (p < 0.05) the contents of reactive oxygen species (ROS), malondialdehyde, protein carbonyl compound and nitrosylated tyrosine protein, aging level, apoptosis rate in Hacat cell induced by 200 mJ cm-2 UVB after 24 and 48 h of culture; high dose SPH significantly raised (p < 0.05) relative expression level of p-Akt, p-mTOR proteins, and markedly decreased (p < 0.05) relative expression level of LC3II protein, p-AMPK, and autophagy level in Hacat cell induced by 200 mJ cm-2 UVB, or in combination with the intervention of PI3K inhibitor or AMPK overexpression after 48 h of culture. CONCLUSION: Seawater pearl hydrolysate can effectively inhibit 200 mJ cm-2 UVB-induced photoaging of Hacat cells. The mechanism indicates removing the excessive ROS through increasing the antioxidation of photoaging Hacat cells. Once redundant ROS is eliminated, SPH works to reduce AMPK, increase PI3K-Akt pathway expression, activate mTOR pathway to lowdown autophagy level, and as a result, inhibit apoptosis and aging in photoaging Hacat cells.

Effects of physical activity on the levels of remnant cholesterol: A population-based study.

Physical activity (PA) has the potential to bring about favourable changes in plasma lipid profile. However, the relationship between PA and remnant cholesterol (RC) remains unclear. We aimed to study the link between PA and RC using the database of the 2007-2020 National Health and Nutrition Examination Survey (NHANES). PA was categorized based on Physical Activity Guidelines for Americans. A multivariate linear regression model was used to determine the correlations between PA and RC. The study involved a total of 18,396 participants and revealed that individuals whose PA met the guidelines by engaging in moderate-intensity PA at least 150 min per week had lower body mass index and showed decreased levels of triglyceride, TC, and haemoglobin A1c compared to those who were physically inactive, exercising <150 min per week. Participants whose intensity of PA meets PA guidelines had a lower level of RC than those who did not met PA guidelines (ß = -1.3, 95% confidence interval [CI]: -1.9 to -0.7, p < 0.001), even after adjusting for confounders. During subgroup analysis, we observed that race (pinteraction = 0.0089) emerged as a significant factor of interaction.

The association of statin therapy and cancer: a meta-analysis.

BACKGROUND: Statins are routinely prescribed to lower cholesterol and have been demonstrated to have significant benefits in atherosclerotic cardiovascular disease. However, whether statin therapy has effects on cancer risk remains controversial. In this study, we investigated the influence of statin therapy on cancer incidence and mortality by conducting a comprehensive meta-analysis of randomized controlled trials. METHODS: Systematic searches by Cochrane, Embase, Medline, and PubMed were performed to locate data from eligible randomized controlled trials related to statin therapy and oncology. Our main endpoints were cancer incidence and mortality. Fixed-effects models were used in this study. RESULTS: This meta-analysis comprised thirty-five randomized controlled studies. Twenty-eight included studies reported cancer incidence, and eighteen reported cancer mortality. The pooled results indicated no reduction in cancer incidence with statins compared to placebo [OR = 0.99, 95% CI (0.95, 1.03)]. In addition, statins did not decrease cancer mortality [OR = 0.99, 95% CI (0.91, 1.07)]. This study also performed a number of subgroup analyses, which showed no effect of statins on cancer subtypes such as genitourinary and breast cancer. Neither the type of statin nor long-term treatment with statins had an effect on cancer incidence and mortality. CONCLUSION: Through comprehensive analysis, we found that statin therapy does not reduce cancer incidence or mortality while protecting the cardiovascular system. TRIAL REGISTRATION: Prospero CRD42022377871.

Efficacy of Frontline Chemotherapy for Extranodal Natural Killer/T-Cell Lymphoma: A Systematic Review and Network Meta-Analysis.

Background: Treatment with non-anthracycline (ANT)-based chemotherapy has increased survival in patients with extranodal natural killer/T-cell lymphoma (ENKTCL). However, the relative efficacy of various drug combinations has been contentious. We aimed to identify the most effective chemotherapy regimens for newly diagnosed ENKTCL. Methods: A network meta-analysis was performed to evaluate the differences in survival and treatment responses across various regimens. The primary objective was overall survival (OS), while secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and complete response (CR). We utilized a Bayesian framework to perform the network meta-analysis. Rank probabilities were assessed by the surface under the cumulative ranking curve (SUCRA). Node-splitting method was used to assess the inconsistency. Results: A total of 1,113 patients were enrolled across 10 studies. Chemotherapy regimens were grouped into five modalities, for which six types of direct comparisons were available. We identified the asparaginase (ASP)/gemcitabine (GEM)-based regimens superiority over ANT-based, non-ASP/ANT-based and ASP/methotrexate (MTX)-based regimens on OS. Although no significant differences were observed compared with ASP/not otherwise specified-based, ASP/GEM-based regimens were still the best option chemotherapy for OS. Moreover, the ASP/GEM-based regimens demonstrated advantages in PFS, ORR and CR. Conclusions: According to our network meta-analysis, it appears that ASP/GEM-based regimens could potentially serve as the most effective frontline chemotherapy option for ENKTCL.

Replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis.

The interleukin 6 (IL6) signaling pathway plays pleiotropic roles in regulating the inflammatory milieu that contributes to arthritis development. Here, we show that activation of IL6 trans-signaling induces phenotypic transitions in tissue-resident cells toward an inflammatory state. The establishment of arthritis increases the serum number of extracellular vesicles (EVs), while these EVs express more IL6 signal transducer (IL6ST, also known as gp130) on their surface. Transferring these EVs can block IL6 trans-signaling in vitro by acting as decoys that trap hyper IL6 and prevent inflammatory amplification in recipient arthritic mice. By genetically fusing EV-sorting domains with extracellular domains of receptors, we engineered EVs that harbor a higher quantity of signaling-incompetent decoy receptors. These exogenous decoy EVs exhibit significant potential in eliciting efficient anti-inflammatory effects in vivo. Our findings suggest an inherent resistance of decoy EVs against inflammation, highlighting the therapeutic potential of efficient decoy EVs in treating inflammatory diseases.

Neuroendoscopy surgery for hypertensive intracerebral hemorrhage with concurrent brain herniation: a retrospective study of comparison with craniotomy.

Background: Hypertensive intracerebral hemorrhage combined with cerebral hernia (HIH-CH) is a serious condition. Neuroendoscopy can effectively remove intracranial hematoma, but there is no relevant research support for its utility in patients with HIH-CH. The purpose of this study is to investigate the efficacy and safety of neuroendoscopy in patients with HIH-CH. Methods: Patients with HIH-CH who received craniotomy or neuroendoscopy treatment were included. The patients were divided into craniotomy (CHE) group and neuroendoscopy (NEHE) group. Clinical data and follow-up outcome of the two groups were collected. The primary outcome was hematoma clearance. Results: The hematoma clearance rate (%) of patients in NEHE group was 97.65 (92.75, 100.00), and that of patients in CHE group was 95.00 (90.00, 100.00), p > 0.05. The operation time and intraoperative bleeding volume of patients in NEHE group were significantly less than those in CHE group (p < 0.05). There was no significant difference in the volume of residual hematoma and the incidence of rebleeding between the two groups (p > 0.05). The length of stay in ICU in NEHE group was significantly shorter than that in CHE group (p < 0.05). Conclusion: Neuroendoscopy can safely and effectively remove the intracranial hematoma in patients with hypertensive intracerebral hemorrhage and cerebral hernia, significantly shorten the operation time, reduce the amount of intraoperative hemorrhage, shorten the ICU stay.

Reverse Lumbar Pedicle Screw in Oblique Lateral Interbody Fusion: A Novel Concept to Restrict Cage Subsidence.

OBJECTIVE: Cage subsidence is a common morbidity after oblique lumbar interbody fusion (OLIF), with risk of compromising clinical and radiographic outcomes. The study aims to describe an innovative reverse lumbar pedicle screw (RLPS) technique in OLIF and compare its effect on restricting cage subsidence with classical lateral fixation (LF) in radiological and clinical evaluation. METHOD: Consecutive patients having undergone single-level OLIF-LF/RLPS from 2018 to 2020 were retrospectively reviewed. In OLIF-RLPS, the upper entry point was determined at the intersection between one horizontal line (1 cm above inferior endplate) and one vertical line (dissecting anterior and middle thirds of the vertebra) while the inferior entry point between one horizontal line (5 mm below superior endplate) and the same vertical line. Trajectories were from vertebrae reverse into contralateral pedicle. Radiological evaluation included disc height (DH) and segmental lordosis (SL); cage subsidence was evaluated by DH loss. Clinical assessment included visual analogue scale (VAS) and Oswestry disability index (ODI). Student t or Mann-Whitney U test was used for continuous variation according to normality analysis while Chi-square test for category variation. RESULTS: A total of 29 patients had been enrolled in the study including 14 cases in the RLPS group and 15 cases in the LF group. The DH in the OLIF-RLPS group had increased from the preoperative 9.07 ± 1.73 mm to 13.73 ± 1.83 mm postoperatively, without significant difference compared with the OLIF-LF group during the perioperative, but decreased to 12.53 ± 1.74 mm in 3 months and maintained at 12.00 ± 1.45 mm in 12 months, significantly higher than the OLIF-LF group (p < 0.05). At the last follow-up, 7.1% (1/14) cases in the OLIF-RLPS group had shown subsidence of grade I, significantly less than 46.7% (7/15) cases in the OLIF-LF group. Pain and disability had improved similarly in two groups, without significant difference detected between two groups at the last follow-up. CONCLUSION: RLPS technique with modified entry points and prolonged trajectory could effectively restrict cage subsidence in OLIF postoperatively compared with traditional lateral fixation.