Clinical distribution of carbapenem genotypes and resistance to ceftazidime-avibactam in Enterobacteriaceae bacteria.

Introduction: Bacterial resistance is a major threat to public health worldwide. To gain an understanding of the clinical infection distribution, drug resistance information, and genotype of CRE in Dongguan, China, as well as the resistance of relevant genotypes to CAZ-AVI, this research aims to improve drug resistance monitoring information in Dongguan and provide a reliable basis for the clinical control and treatment of CRE infection. Methods: VITEK-2 Compact automatic analyzer was utilized to identify 516 strains of CRE collected from January 2017 to June 2023. To determine drug sensitivity, the K-B method, E-test, and MIC methods were used. From June 2022 to June 2023, 80 CRE strains were selected, and GeneXpert Carba-R was used to detect and identify the genotype of the carbapenemase present in the collected CRE strains. An in-depth analysis was conducted on the CAZ-AVI in vitro drug sensitivity activity of various genotypes of CRE, and the results were statistically evaluated using SPSS 23.0 and WHONET 5.6 software. Results: This study identified 516 CRE strains, with the majority (70.16%) being K.pneumoniae, followed by E.coli (18.99%). Respiratory specimens had highest detection rate with 53.77% identified, whereas urine specimens had the second highest detection rate with 17.99%. From June 2022 to June 2023, 95% of the strains tested using the CRE GeneXpert Carba-R assay possessed carbapenemase genes, of which 32.5% were blaNDM strains and 61.25% blaKPC strains. The results showed that CRE strains containing blaKPC had a significantly higher rate of resistance to amikacin, cefepime, and aztreonam than those harboring blaNDM. Conclusions: The CRE strains isolated from Dongguan region demonstrated a high resistance rate to various antibiotics used in clinical practice but a low resistance rate to tigecycline. These strains produce Class A serine carbapenemases and Class B metals ß-lactamases, with the majority of them carrying blaNDM and blaKPC. Notably, CRE strains with blaKPC and blaNDM had significantly lower resistance rates to tigecycline. CAZ-AVI showed a good sensitivity rate with no resistance to CRE strains carrying blaKPC. Therefore, CAZ-AVI and tigecycline should be used as a guide for rational use of antibiotics in clinical practice to effectively treat CRE.

An in Vivo, Three-Dimensional (3D), Functional Centers of Rotation of the Healthy Cervical Spine.

OBJECTIVE: This study examined cervical center of rotation (COR) positions in 7 postures using validated cone beam computed tomography (CBCT) combined with 3D-3D registration in healthy volunteers. METHODS: CBCT scans were performed on 20 healthy volunteers in 7 functional positions, constructing a three-dimensional (3D) model. Images were registered to the neutral position using 3D-3D registration, allowing analysis of kinematic differences and rotational axes. COR measurements were obtained for each segment (C2/3 to C6/7) in each posture. RESULTS: The CORs of C2/3 to C6/7 were predominantly posterior (-5.3 ± 3.8 ∼ -0.6 ± 1.2 mm) and superior (16.5 ± 6.0 ∼ 23.6 ± 3.2 mm) to the intervertebral disc's geometric center (GC) in flexion and extension. However, the C4/5 segment's COR was anterior to the GC (2.0 ± 9.8 mm) during flexion and close to it in the right-left direction. During left-right twisting, the CORs of C2/3-C6/7 were posterior (-21.8 ± 10.5 ∼-0.9 ± 0.8 mm) and superior (3.1 ± 7.5 ∼23.2 ± 3.6 mm) to the GCs in anterior-posterior and superior-inferior directions, without consistent right-left directionality. During left-right bending, each segment's COR was predominantly posterior (-25.2 ± 13.1 ∼-6.5 ± 9.9 mm) and superior (0.3 ± 12.5 ∼12.1 ± 5.1 mm) to the GC in anterior-posterior and superior-inferior directions, except for the C2/3 segment, located inferiorly (-5.9 ± 4.1 mm) in left bending. The right-left COR position varied across segments. CONCLUSIONS: Our findings reveal segment-specific and posture-dependent COR variations. Notably, the CORs of C3/4, C4/5, and C5/6 consistently align near the intervertebral disc's GC at different postures, supporting their suitability for total disc replacement surgery within the C3/4 to C5/6 segments.

Innovating from the ground up: the impact of key technological advancements on collaborative carbon and haze governance.

Strengthening the synergistic management of carbon and haze is an important means to realize China's "carbon peaking and carbon neutrality goals" and green development. In this paper, the entropy method is used to measure the key core technology innovation level of 30 provinces in China from 2011 to 2021, and the fixed-effect model is used to empirically test the impact of key core technology innovation on carbon haze synergistic governance and the internal mechanism. The study found that (1) key core technological innovation helps to promote carbon haze synergistic governance. (2) The mechanism test shows that key core technology innovation promotes the synergistic management of carbon haze by improving the clean energy structure. (3) The moderating effect shows that both market incentives and government environmental regulations will strengthen the positive relationship between key core technology innovation and carbon haze synergistic governance. The main contribution of this paper is to reveal the influence mechanism of key core technology innovation on carbon haze synergistic governance, and also to provide theoretical basis for the mechanism and law of carbon haze synergistic governance.

Dominant Contribution of NO3 Radical to NO3- Formation during Heavy Haze Episodes: Insights from High-Time Resolution of Dual Isotopes Δ17O and δ18O.

δ18O is widely used to track nitrate (NO3-) formation but overlooks NO3 radical reactions with hydrocarbons (HCs), particularly in heavily emitting hazes. This study introduces high-time resolution Δ17O-NO3- as a powerful tool to quantify NO3- formation during five hazes in three cities. Results show significant differences between Δ17O-NO3- and δ18O-NO3- in identifying NO3- formation. δ18O-NO3- results suggested N2O5 hydrolysis (62.0-88.4%) as the major pathway of NO3- formation, while Δ17O-NO3- shows the NO3- formation contributions of NO2 + OH (17.7-66.3%), NO3 + HC (10.8-49.6%), and N2O5 hydrolysis (22.9-33.3%), revealing significant NO3 + HC contribution (41.7-56%) under severe pollution. Furthermore, NO3- formation varies with temperatures, NOx oxidation rate (NOR), and pollution levels. Higher NO2 + OH contribution and lower NO3 + HC contribution were observed at higher temperatures, except for low NOR haze where higher NO2 + OH contributions were observed at low temperatures (T ← 10 °C). This emphasizes the significance of NO2 + OH in emission-dominated haze. Contributions of NO2 + OH and NO3 + HC relate to NOR as positive (fP1 = 3.0*NOR2 - 2.4*NOR + 0.8) and negative (fP2 = -2.3*NOR2 + 1.8*NOR) quadratic functions, respectively, with min/max values at NOR = 0.4. At mild pollution, NO2 + OH (58.1 ± 22.2%) dominated NO3- formation, shifting to NO3 + HC (35.5 ± 16.3%) during severe pollution. Additionally, high-time resolution Δ17O-NO3- reveals that morning-evening rush hours and high temperatures at noon promote the contributions of NO3 + HC and NO2 + OH, respectively. Our results suggested that the differences in the NO3- pathway are attributed to temperatures, NOR, and pollution levels. Furthermore, high-time resolution Δ17O-NO3- is vital for quantifying NO3 + HC contribution during severe hazes.

Influence of Polycyclic Aromatic Compounds and Oxidation States of Soot Organics on the Metabolome of Human-Lung Cells (A549): Implications for Vehicle Fuel Selection.

Decades of research have established the toxicity of soot particles resulting from incomplete combustion. However, the unique chemical compounds responsible for adverse health effects have remained uncertain. This study utilized mass spectrometry to analyze the chemical composition of extracted soot organics at three oxidation states, aiming to establish quantitative relationships between potentially toxic chemicals and their impact on human alveolar basal epithelial cells (A549) through metabolomics-based evaluations. Targeted analysis using MS/MS indicated that particles with a medium oxidation state contained the highest total abundance of compounds, particularly oxygen-containing polycyclic aromatic hydrocarbons (OPAHs) composed of fused benzene rings and unsaturated carbonyls, which may cause oxidative stress, characterized by the upregulation of three specific metabolites. Further investigation focused on three specific OPAH standards: 1,4-naphthoquinone, 9-fluorenone, and anthranone. Pathway analysis indicated that exposure to these compounds affected transcriptional functions, the tricarboxylic acid cycle, cell proliferation, and the oxidative stress response. Biodiesel combustion emissions had higher concentrations of PAHs, OPAHs, and nitrogen-containing PAHs (NPAHs) compared with other fuels. Quinones and 9,10-anthraquinone were identified as the dominant compounds within the OPAH category. This knowledge enhances our understanding of the compounds contributing to adverse health effects observed in epidemiological studies and highlights the role of aerosol composition in toxicity.

Reliability and validity of simplified Chinese version of Spinal Cord Injury Pain Instrument in patients with spinal cord injury in mainland China.

PURPOSE: To cross-culturally adapt the Spinal Cord Injury Pain Instrument (SCIPI) into a simplified Chinese version (SC-SCIPI) and verify reliability and validity in screening for neuropathic pain in SCI patients. METHODS: A preliminary validation study was conducted to screen for neuropathic pain after SCI using SCIPI. A total of 130 patients with SCI treated at Shanghai Changhai Hospital were enrolled. Results for internal consistency, reliability and construct validity were compared with those of the Douleur Neuropathique (DN4), Leeds Assessment of Neuropathic Pain Questionnaire (LANSS), Neuropathic Pain Questionnaire (NPQ), ID Pain scale and VAS pain scale. RESULTS: The SCIPI was successfully translated into Chinese and expert consensus was reached on final adapted version of SC-SCIPI. For test-retest, SC-SCIPI total score was 2.35 ± 1.75 in first round and 2.35 ± 1.76 in second round. Cronbach α coefficient of SC-SCIPI was 0.909, indicating good internal consistency. Pearson correlation coefficient (r) showed that SC-SCIPI correlated well with LANSS, DN4, NPQ and ID pain; and correlated fairly well with VAS, indicating good construct validity. CONCLUSION: SC-SCIPI demonstrates excellent internal consistency, reliability and good construct validity in Chinese patients with neuropathic pain, suggesting that SC-SCIPI is applicable in clinical practice to screen patients for neuropathic pain. IMPLICATION FOR REHABILITATIONThe Spinal Cord Injury pain Instrument has been cross-culturally adapted into a simplified Chinese version (SC-SCIPI).The SC-SCIPI showed excellent test-retest reliability and good construct validity.The 4-item SC-SCIPI is quite convenient to complete and it might be a useful instrument for routine application in patients with SCI for rehabilitation.

Influence of C/N ratio and ammonia on nitrogen removal and N2O emissions from one-stage partial denitrification coupled with anammox.

The development of low carbon treatment processes is an important issue worldwide. Partial denitrification coupled with anammox (PD/A) is a novel strategy to remove nitrogen and reduce N2O emissions. The influence of C/N ratio and NH4+ concentration on nitrogen removal and N2O emissions was investigated in batch reactors filled with PD/A coupled sludge. A C/N ratio of 2.1 was effective for nitrogen removal and N2O reduction; higher ammonia concentration might make anammox more active and indirectly reduce N2O emissions. Long-term operation further confirmed that a C/N ratio of 2.1 resulted in a minimum effluent N2O concentration (mean value of 0.94 µmol L-1); as the influent NH4+ concentration decreased to 50 mg L-1 (NH4+-N/NO3--N: 1), the nitrogen removal rate increased to 82.41%. Microbial analysis showed that anammox bacteria (Candidatus Jettenia and Ca. Brocadia) were enriched in the PD/A system and Ca. Brocadia gradually dominated the anammox community, with the relative abundance increasing from 1.69% to 18.44% between days 97 and 141. Finally, functional gene analysis indicated that the abundance of nirS/K and hao involved in partial denitrification and anammox, respectively, increased during long-term operation of the reactor; this change benefitted nitrogen metabolism in anammox, which could indirectly reduce N2O emissions.

Research progress in nucleus-targeted tumor therapy.

The nucleus is considered the most important organelle in the cell as it plays a central role in controlling cell reproduction, metabolism, and the cell cycle. The successful delivery of drugs into the nucleus can achieve excellent therapeutic effects, which reveals the potential of nucleus-targeted therapy in precision medicine. However, the transportation of therapeutics into the nucleus remains a significant challenge due to various biological barriers. Herein, we summarize the recent progress in the nucleus-targeted drug delivery system (NDDS). The structures of the nucleus and nuclear envelope are first described in order to understand the mechanisms by which drugs cross the nuclear envelope. Then, various drug delivery strategies based on the mechanisms and their applications are discussed. Finally, the challenges and solutions in the field of nucleus-targeted drug delivery are raised for developing a more efficient NDDS and promoting its clinical transformation.

Nucleus-selective self-augmenting cascade nanoassemblies for targeted synergistic photo-chemo therapy of tumors.

A nucleus-targeted enzyme prodrug nanocomposite, assembled from ß-cyclodextrin-lysine (CL), catalase (CAT), Pt(IV) and chlorin e6 (Ce6), was developed for self-augmenting cascade photo-chemo therapy of tumors. It can effectively transport through the cytoplasm and accumulate in the nucleus, thereby significantly inhibiting tumor growth and lung metastasis.

Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury.

The miRNA-181 (miR-181) family regulates neuronal persistence during cerebral ischemia/reperfusion injury (CI/RI). Since the effect of miR-181d on CI/RI has never been studied, the current work sought to determine the involvement of miR-181d in neuronal apoptosis after brain I/R injury. To replicate in vivo and in vitro CI/RI, a transient middle cerebral artery occlusion (tMCAO) model in rats and an oxygen-glucose deficiency/reoxygenation (OGD/R) model in neuro 2A cells were developed. In both in vivo and in vitro stroke models, the expression of miR-181d was considerably higher. miR-181d suppression reduced apoptosis and oxidative stress in OGD/R-treated neuroblastoma cells, but miR-181d overexpression increased both. Furthermore, it was observed that miR-181d has a direct target in dedicator of cytokinesis 4 (DOCK4). The overexpression of DOCK4 partially overcame cell apoptosis and oxidative stress induced by miR-181d upregulation and OGD/R injury. Furthermore, the DOCK4 rs2074130 mutation was related to lower DOCK4 levels in ischemic stroke (IS) peripheral blood and higher susceptibility to IS. These findings suggest that downregulating miR-181d protects neurons from ischemic damage by targeting DOCK4, implying that the miR-181d/DOCK4 axis might be a novel therapeutic target for IS.

Cross-Interference of VOCs in SnO2-Based NO Sensors.

In this work, we studied the influence of cross-interference effects between VOCs and NO on the performance of SnO2 and Pt-SnO2-based gas sensors. Sensing films were fabricated by screen printing. The results show that the response of the SnO2 sensors to NO under air is higher than that of Pt-SnO2, but the response to VOCs is lower than that of Pt-SnO2. The Pt-SnO2 sensor was significantly more responsive to VOCs in the NO background than in air. In the traditional single-component gas test, the pure SnO2 sensor showed good selectivity to VOCs and NO at 300 °C and 150 °C, respectively. Loading noble metal Pt improved the sensitivity to VOCs at high temperature, but also significantly increased the interference to NO sensitivity at low temperature. The explanation for this phenomenon is that the noble metal Pt can catalyze the reaction between NO and VOCs to generate more O-, which further promotes the adsorption of VOCs. Therefore, selectivity cannot be simply determined by single-component gas testing alone. Mutual interference between mixed gases needs to be taken into account.

Global trends in research of fibroblasts associated with rheumatoid diseases in the 21st century: A bibliometric analysis.

Background: Rheumatoid Diseases (RDs) are a group of systemic auto-immune diseases that are characterized by chronic synovitis, and fibroblast-like synoviocytes (FLSs) play an important role in the occurrence and progression of synovitis. Our study is the first to adopt bibliometric analysis to identify the global scientific production and visualize its current distribution in the 21st century, providing insights for future research through the analysis of themes and keywords. Methods: We obtained scientific publications from the core collection of the Web of Science (WoS) database, and the bibliometric analysis and visualization were conducted by Biblioshiny software based on R-bibliometrix. Results: From 2000 to 2022, a total of 3,391 publications were reviewed. China is the most prolific country (n = 2601), and the USA is the most cited country (cited 7225 times). The Center of Experimental Rheumatology at University Hospital Zürich supported the maximum number of articles (n = 40). Steffen Gay published 85 records with 6263 total citations, perhaps making him the most impactful researcher. Arthritis and Rheumatism, Annals of Rheumatic Diseases, and Rheumatology are the top three journals. Conclusion: The current study revealed that rheumatoid disease (RD)-related fibroblast studies are growing. Based on the bibliometric analysis, we summarized three important topics: activation of different subsets of fibroblasts; regulation of fibroblast function; and in vitro validation of existing discoveries. They are all valuable directions, which provide reference and guidance for researchers and clinicians engaged in the research of RDs and fibroblasts.

The Recurrent-Specific Regulation Network of Prognostic Stemness-Related Signatures in Low-Grade Glioma.

Gliomas including astrocytomas, oligodendrogliomas, mixed oligoastrocytic, and mixed glioneuronal tumors are an important group of brain tumors. Based on the 2016 WHO classification for tumors in the central nervous system, gliomas were classified into four grades, from I to IV, and brain lower grade glioma (LGG) consists of grade II and grade III. Patients with LGG may undergo recurrence, which makes clinical treatment tough. Stem cell-like features of cancer cells play a key role in tumor's biological behaviors, including tumorigenesis, development, and clinical prognosis. In this article, we quantified the stemness feature of cancer cells using the mRNA stemness index (mRNAsi) and identified stemness-related key genes based on correlation with mRNAsi. Besides, hallmark gene sets and translate factors (TFs) which were highly related to stemness-related key genes were identified. Therefore, a recurrency-specific network was constructed and a potential regulation pathway was identified. Several online databases, assay for transposase-accessible chromatin using sequencing (ATAC-seq), single-cell sequencing analysis, and immunohistochemistry were utilized to validate the scientific hypothesis. Finally, we proposed that aurora kinase A (AURKA), positively regulated by Non-SMC Condensin I Complex Subunit G (NCAPG), promoted E2F target pathway in LGG, which played an important role in LGG recurrence.

Measurement Properties of the Simplified Chinese Version of the Lumbar Spine Instability Questionnaire for Patients With Low Back Pain in Mainland China.

STUDY DESIGN: A prospective study. OBJECTIVE: To develop a simplified Chinese version of Lumbar Spine Instability Questionnaire (SC-LSIQ) and test its measurement properties. SUMMARY OF BACKGROUND DATA: The LSIQ has been translated into several languages. Different versions of LSIQ have proved good reliability and validity in evaluating patients with low back pain. However, there is no simplified Chinese version of LSIQ (SC-LSIQ). MATERIALS AND METHODS: The SC-LSIQ has been translated into a simplified Chinese version according to a standard procedure. A total of 155 patients with low back pain completed the SC-LSIQ along with Oswestry Disability Index, Roland-Morris disability questionnaire, Tampa Scale for Kinesiophobia, and visual analogue scale (VAS). The internal consistency, test-retest reliability, and validity of SC-LSIQ were then calculated to evaluate the measurement properties of SC-LSIQ. RESULTS: The results of SC-LSIQ demonstrated that there was no ceiling or floor effect detected. The Cronbach α coefficient of 0.911 determined a well internal consistency. The intraclass correlation coefficient (0.98) presented an excellent reliability of SC-LSIQ. The Pearson correlation coefficient (r) showed that the SC-LSIQ was excellent correlated to Oswestry Disability Index (r=0.809), Roland-Morris disability questionnaire (r=0.870), and Tampa Scale for Kinesiophobia (r=0.945,). Furthermore, it moderately correlated to visual analogue scale (r=0.586). CONCLUSION: The SC-LSIQ features good internal consistency, reliability, and validity for evaluating Chinese patients with LBP. Results suggest that the SC-LSIQ can be appropriately applied to patients with LBP in routine clinical practice.

Convex Temporal Convolutional Network-Based Distributed Cooperative Learning Control for Multiagent Systems.

Due to its great efficiency, scalability, and inclusivity, distributed cooperative learning control has gotten a lot of attention. For complex uncertain multiagent systems, it is challenging to model the uncertainties and exploit the cooperative learning ability of the systems. To address these issues, we proposed a novel convex temporal convolutional network-based distributed cooperative learning control for uncertain discrete-time nonlinear multiagent systems. A new concept of using a convex temporal convolutional network (CTCNet) is proposed for estimating the uncertain agent dynamics in a cooperative way. Unlike previous methods that require adjustment of network weights for different control tasks, the proposed CTCNet can map the high-dimensional input-output space into a deep space spanned by basis features that represent the inherent properties of the system, so it has good robustness for different tasks. Consequently, to improve the control performance, a CTCNet-based distributed cooperative learning control method that shares learned knowledge through the communication topology among adaptive laws of CTCNet is proposed. Furthermore, the asymptotic convergence of system tracking errors to an arbitrarily small neighborhood of the origin is strictly proved. Finally, the simulation results are given to illustrate that our suggested method has higher control accuracy, stronger robustness, and anti-interference ability than the existing methods.

Bibliometric analysis of research on gene expression in spinal cord injury.

Background: Spinal cord injury (SCI) is a severe disease with motor and sensory function being destroyed, which leads to a poor prognosis and a serious financial burden. It is urgent to figure out the molecular and pathological mechanisms of SCI to develop feasible therapeutic strategies. This article aims to review documents focused on gene expression in SCI and summarize research hotspots and the development process in this field. Methods: Publications of SCI-related studies from 2000 to 2022 were retrieved from the Web of Science Core Collection database. Biblioshiny was used to evaluate the research performance, core authors, journals and contributed countries, together with trend topics, hotspots in the field, and keyword co-occurrence analysis. Visualized images were obtained to help comprehension. Results: Among 351 documents, it was found that the number of annual publications increased in general. The most productive country was China, followed by the United States with the highest influence and the most international cooperation. Plos One was the journal of the maximum publications, while Journal of Neuroscience was the most influential one. According to keyword co-occurrence and trend topics analysis, these articles mainly focused on molecular and pathological mechanisms as well as novel therapies for SCI. Neuropathic pain, axonal regeneration and messenger RNA are significant and promising research areas. Conclusion: As the first bibliometric study focused on gene expression in SCI, we demonstrated the evolution of the field and provided future research directions like mechanisms and treatments of SCI with great innovativeness and clinical value. Further studies are recommended to develop more viable therapeutic methods for SCI.

Repression of enhancer RNA PHLDA1 promotes tumorigenesis and progression of Ewing sarcoma via decreasing infiltrating T-lymphocytes: A bioinformatic analysis.

Background: The molecular mechanisms of EWS-FLI-mediating target genes and downstream pathways may provide a new way in the targeted therapy of Ewing sarcoma. Meanwhile, enhancers transcript non-coding RNAs, known as enhancer RNAs (eRNAs), which may serve as potential diagnosis markers and therapeutic targets in Ewing sarcoma. Materials and methods: Differentially expressed genes (DEGs) were identified between 85 Ewing sarcoma samples downloaded from the Treehouse database and 3 normal bone samples downloaded from the Sequence Read Archive database. Included in DEGs, differentially expressed eRNAs (DEeRNAs) and target genes corresponding to DEeRNAs (DETGs), as well as the differentially expressed TFs, were annotated. Then, cell type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) was used to infer portions of infiltrating immune cells in Ewing sarcoma and normal bone samples. To evaluate the prognostic value of DEeRNAs and immune function, cross validation, independent prognosis analysis, and Kaplan-Meier survival analysis were implemented using sarcoma samples from the Cancer Genome Atlas database. Next, hallmarks of cancer by gene set variation analysis (GSVA) and immune gene sets by single-sample gene set enrichment analysis (ssGSEA) were identified to be significantly associated with Ewing sarcoma. After screening by co-expression analysis, most significant DEeRNAs, DETGs and DETFs, immune cells, immune gene sets, and hallmarks of cancer were merged to construct a co-expression regulatory network to eventually identify the key DEeRNAs in tumorigenesis of Ewing sarcoma. Moreover, Connectivity Map Analysis was utilized to identify small molecules targeting Ewing sarcoma. External validation based on multidimensional online databases and scRNA-seq analysis were used to verify our key findings. Results: A six-different-dimension regulatory network was constructed based on 17 DEeRNAs, 29 DETFs, 9 DETGs, 5 immune cells, 24 immune gene sets, and 8 hallmarks of cancer. Four key DEeRNAs (CCR1, CD3D, PHLDA1, and RASD1) showed significant co-expression relationships in the network. Connectivity Map Analysis screened two candidate compounds, MS-275 and pyrvinium, that might target Ewing sarcoma. PHLDA1 (key DEeRNA) was extensively expressed in cancer stem cells of Ewing sarcoma, which might play a critical role in the tumorigenesis of Ewing sarcoma. Conclusion: PHLDA1 is a key regulator in the tumorigenesis and progression of Ewing sarcoma. PHLDA1 is directly repressed by EWS/FLI1 protein and low expression of FOSL2, resulting in the deregulation of FOX proteins and CC chemokine receptors. The decrease of infiltrating T-lymphocytes and TNFA signaling may promote tumorigenesis and progression of Ewing sarcoma.

KRAS as a Key Oncogene in the Clinical Precision Diagnosis and Treatment of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors, with a 5-year survival rate of less than 10%. At present, the comprehensive treatment based on surgery, radiotherapy and chemotherapy has encountered a bottleneck, and targeted immunotherapy turns to be the direction of future development. About 90% of PDAC patients have KRAS mutations, and KRAS has been widely used in the diagnosis, treatment, and prognosis of PDAC in recent years. With the development of liquid biopsy and gene testing, KRAS is expected to become a new biomarker to assist the stratification and prognosis of PDAC patients. An increasing number of small molecule inhibitors acting on the KRAS pathway are being developed and put into the clinic, providing more options for PDAC patients.

Sagittal imaging study of the lumbar spine with the short rod technique.

PURPOSE: The short rod technique (SRT) is a novel method for lumbar pedicle screw placement to reduce surgical trauma and avoid damage to the facet joint and articular surface. The core concept is to change the entry point and angle of the screw on the vertebrae at both ends in the sagittal plane to shorten the length of the longitudinal rods. The purpose of this study is to determine the sagittal screw angle (SSA) and its safe Maximum (MAX) value on each lumbar vertebra for the SRT and to observe the shortening effect on the longitudinal rods. METHODS: A total of 152 healthy adults were investigated by measuring the lumbar spine lateral view images. The SSA and MAX-SSA were measured with SRT as reference to the conventional placement technique method. The distance between the entry points of the proximal and distal vertebrae was measured to compare the changes in the length of the longitudinal rods using the two screw placement techniques. RESULTS: + SSA increased from L1 to L4, and -SSA increased from L2 to L5, in which the -SSA of L2, L3, and L4 were significantly greater than those of + SSA (P < 0.05). + MAX-SSA at L1-L4 was 23.26 ± 3.54°, 23.68 ± 3.37°, 24.12 ± 3.29°, and 24.26 ± 3.42°, respectively. -MAX-SSA at L2-L5 was 36.25 ± 3.26°, 38.26 ± 3.73°, 38.62 ± 3.63° and 37.33 ± 3.31°, respectively. Theoretical reductions by calculation for the 2-segment lumbar pedicles were: L1-2: 9 mm, L2-3: 9.29 mm, L3-4: 6.23 mm, and L4-5: 7.08 mm; And the 3-segment lumbar pedicles were: L1-3: 16.97 mm, L2-4: 16.73 mm, L3-5, and 18.24 mm, respectively. CONCLUSIONS: The application of the SRT to lumbar pedicles is a safe screw placement method that can significantly shorten the length of the used longitudinal rods.

Construction of the prognostic enhancer RNA regulatory network in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a common malignant tumor in osteoarticular system, the 5-year overall survival of which is poor. Enhancer RNAs (eRNAs) have been implicated in the tumorigenesis of various cancer types, whereas their roles in OS tumorigenesis remains largely unclear. METHODS: Differentially expressed eRNAs (DEEs), transcription factors (DETFs), target genes (DETGs) were identified using limma (Linear Models for Microarray Analysis) package. Prognosis-related DEEs were accessed by univariate Cox regression analysis. A multivariate model was constructed to evaluate the prognosis of OS samples. Prognosis-related DEEs, DETFs, DETGs, immune cells, and hallmark gene sets were co-analyzed to construct an regulatory network. Specific inhibitors were also filtered by connectivity Map analysis. External validation and scRNA-seq analysis were performed to verify our key findings. RESULTS: 3,981 DETGs, 468 DEEs, 51 DETFs, and 27 differentially expressed hallmark gene sets were identified. A total of Multivariate risk predicting model based on 18 prognosis-related DEEs showed a high accuracy (area under curve (AUC) = 0.896). GW-8510 was the candidate inhibitor targeting prognosis-related DEEs (mean = 0.670, p < 0.001). Based on the OS tumorigenesis-related regulation network, we identified that CCAAT enhancer binding protein alpha (CEBPA, DETF) may regulate CD8A molecule (CD8A, DEE), thereby promoting the transcription of CD3E molecule (CD3E, DETG), which may affect allograft rejection based on CD8+ T cells. CONCLUSION: We constructed an eRNA-based prognostic model for predicting the OS patients' prognosis and explored the potential regulation network for OS tumorigenesis by an integrated bioinformatics analysis, providing promising therapeutic targets for OS patients.