Direct contact between tumor cells and platelets initiates a FAK-dependent F3/TGF-ß positive feedback loop that promotes tumor progression and EMT in osteosarcoma.

Platelets have received growing attention for their roles in hematogenous tumor metastasis. However, the tumor-platelet interaction in osteosarcoma (OS) remains poorly understood. Here, using platelet-specific focal adhesion kinase (FAK)-deficient mice, we uncover a FAK-dependent F3/TGF-ß positive feedback loop in OS. Disruption of the feedback loop by inhibition of F3, TGF-ß, or FAK significantly suppresses OS progression. We demonstrate that OS F3 initiated the feedback loop by increasing platelet TGF-ß secretion, and platelet-derived TGF-ß promoted OS F3 expression in turn and modulated OS EMT process. Immunofluorescence results indicate platelet infiltration in OS niche and we verified it was mediated by platelet FAK. In addition, platelet FAK was proved to mediate platelet adhesion to OS cells, which was vital for the initiation of F3/TGF-ß feedback loop. Collectively, these findings provide a rationale for novel therapeutic strategies targeting tumor-platelet interplay in metastatic OS.

Extracellular vesicles as a new frontier of diagnostic biomarkers in osteosarcoma diseases: a bibliometric and visualized study.

The use of liquid biopsy in cancer research has grown exponentially, offering potential for early detection, treatment stratification, and monitoring residual disease and recurrence. Exosomes, released by cancer cells, contain tumor-derived materials and are stable in biofluids, making them valuable biomarkers for clinical evaluation. Bibliometric research on osteosarcoma (OS) and exosome-derived diagnostic biomarkers is scarce. Therefore, we aimed to conduct a bibliometric evaluation of studies on OS and exosome-derived biomarkers. Using the Web of Science Core Collection database, Microsoft Excel, the R "Bibliometrix" package, CiteSpace, and VOSviewer software, quantitative analyses of the country, author, annual publications, journals, institutions, and keywords of studies on exosome-derived biomarkers for OS from 1995 to 2023 were performed. High-quality records (average citation rate ≥ 10/year) were filtered. The corresponding authors were mainly from China, the USA, Australia, and Canada. The University of Kansas Medical Center, National Cancer Center, Japan, and University of Kansas were major institutions, with limited cooperation reported by the University of Kansas Medical Center. Keyword analysis revealed a shift from cancer progression to mesenchymal stem cells, exosome expression, biogenesis, and prognostic biomarkers. Qualitative analysis highlighted exosome cargo, including miRNAs, circRNAs, lncRNAs, and proteins, as potential diagnostic OS biomarkers. This research emphasizes the rapid enhancement of exosomes as a diagnostic frontier, offering guidance for the clinical application of exosome-based liquid biopsy in OS, contributing to the evolving landscape of cancer diagnosis.

Application of additively manufactured bone scaffold: a systematic review.

The application of additive manufacturing (AM) technology plays a significant role in various fields, incorporating a wide range of cutting-edge technologies such as aerospace, medical treatment, electronic information, and materials. It is currently widely adopted for medical services, national defense, and industrial manufacturing. In recent years, AM has also been extensively employed to produce bone scaffolds and implant materials. Through AM, products can be manufactured without being constrained by complex internal structures. AM is particularly advantageous in the production of macroscopically irregular and microscopically porous biomimetic bone scaffolds, with short production cycles required. In this paper, AM commonly used to produce bone scaffolds and orthopedic implants is overviewed to analyze the different materials and structures adopted for AM. The applications of antibacterial bone scaffolds and bone scaffolds in biologically relevant animal models are discussed. Also, the influence on the comprehensive performance of product mechanics, mass transfer, and biology is explored. By identifying the reasons for the limited application of existing AM in the biomedical field, the solutions are proposed. This study provides an important reference for the future development of AM in the field of orthopedic healthcare. In conclusion, various AM technologies, the requirements of bone scaffolds and the important role of AM in building bridges between biomaterials, additives, and bone tissue engineering scaffolds are described and highlighted. Nevertheless, more caution should be exercised when designing bone scaffolds and conducting in vivo trials, due to the lack of standardized processes, which prevents the accuracy of results and reduces the reliability of information.

Design and Optimization of Heat Treatment Process Parameters for High-Molybdenum-Vanadium High-Speed Steel for Rolls.

High-molybdenum-vanadium high-speed steel is a new type of high-hardenability tool steel with excellent wear resistance, castability, and high-temperature red hardness. This paper proposes a composition design of high-molybdenum-vanadium high-speed steel for rolls, and its specific chemical composition is as follows (wt.%): C2%, Mo7.0%, V7.0%, Si0.3%, Mn0.3%, Ni0.4%, Cr3.0%, and the rest of the iron. This design is characterized by the increase in molybdenum and vanadium in high-speed steel to replace traditional high-speed steel rolls with the tungsten element in order to reduce the heavy elements' tungsten-specific gravity segregation caused by centrifugal casting so that the roll performance is uniform and the stability of use is improved. JMatPro (version 7.0) simulation software is used for the composition design of high-molybdenum-vanadium high-speed steel. The phase composition diagram is analyzed under different temperatures. The content of different phases of the organization in different temperatures is also studied. The martensitic transformation temperature and different tempering temperatures with the different types of compounds and grain sizes are calculated. The process parameters of heat treatment of high-molybdenum-vanadium high-speed steel are optimized. The selection of carbon content and the temperature of M50 are calculated and optimized, and the results show that the range of pouring temperatures, quenching temperatures, annealing temperatures, and tempering temperatures are 1360~1410 °C, 1190~1200 °C, 818~838 °C, and 550~600 °C, respectively. Scanning electron microscope (SEM) analysis of the samples obtained by using the above heat treatment parameters is consistent with the simulation results, which indicates that the simulation has important reference significance for guiding the actual production.

The role of tumor immune microenvironment in chordoma: promising immunotherapy strategies.

Chordoma is a rare malignant bone tumor with limited therapeutic options, which is resistant to conventional chemotherapy and radiotherapy, and targeted therapy is also shown with little efficacy. The long-standing delay in researching its mechanisms of occurrence and development has resulted in the dilemma of no effective treatment targets and no available drugs in clinical practice. In recent years, the role of the tumor immune microenvironment in driving tumor growth has become a hot and challenging topic in the field of cancer research. Immunotherapy has shown promising results in the treatment of various tumors. However, the study of the immune microenvironment of chordoma is still in its infancy. In this review, we aim to present a comprehensive reveal of previous exploration on the chordoma immune microenvironment and propose promising immunotherapy strategies for chordoma based on these characteristics.

Tocilizumab (monoclonal anti-IL-6R antibody) reverses anlotinib resistance in osteosarcoma.

Purpose: Anlotinib, a tyrosine kinase inhibitor (TKI) has been in clinical application to inhibit malignant cell growth and lung metastasis in osteosarcoma (OS). However, a variety of drug resistance phenomena have been observed in the treatment. We aim to explore the new target to reverse anlotinib resistance in OS. Materials and Methods: In this study, we established four OS anlotinib-resistant cell lines, and RNA-sequence was performed to evaluate differentially expressed genes. We verified the results of RNA-sequence by PCR, western blot and ELISA assay. We further explored the effects of tocilizumab (anti- IL-6 receptor), either alone or in combined with anlotinib, on the inhibition of anlotinib-resistant OS cells malignant viability by CCK8, EDU, colony formation, apoptosis, transwell, wound healing, Cytoskeletal stain assays, and xenograft nude mouse model. The expression of IL-6 in 104 osteosarcoma samples was tested by IHC. Results: We found IL-6 and its downstream pathway STAT3 were activated in anlotinib-resistant osteosarcoma. Tocilizumab impaired the tumor progression of anlotinib-resistant OS cells, and combined treatment with anlotinib augmented these effects by inhibiting STAT3 expressions. IL-6 was highly expressed in patients with OS and correlated with poor prognosis. Conclusion: Tocilizumab could reverse anlotinib resistance in OS by IL-6/STAT3 pathway and the combination treatment with anlotinib rationalized further studies and clinical treatment of OS.

Research on Characterization of Nylon Composites Functional Material Filled with Al2O3 Particle.

This study revolves around the issues raised by the current semiconductor device metal casings (mainly composed of aluminum and its alloys), such as resource and energy consumption, complexity of the production process, and environmental pollution. To address these issues, researchers have proposed an eco-friendly and high-performance alternative material-Al2O3 particle-filled nylon composite functional material. This research conducted detailed characterization and analysis of the composite material through scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The results show that the Al2O3 particle-filled nylon composite material has a significantly superior thermal conductivity, about twice as high as that of pure nylon material. Meanwhile, the composite material has good thermal stability, maintaining its performance in high-temperature environments above 240 °C. This performance is attributed to the tight bonding interface between the Al2O3 particles and the nylon matrix, which not only improves the heat transfer efficiency but also significantly enhances the material's mechanical properties, with a strength of up to 53 MPa. This study is of great significance, aiming to provide a high-performance composite material that can alleviate resource consumption and environmental pollution issues, with excellent polishability, thermal conductivity, and moldability, which is expected to play a positive role in reducing resource consumption and environmental pollution problems. In terms of potential applications, Al2O3/PA6 composite material can be widely used in heat dissipation components for LED semiconductor lighting and other high-temperature heat dissipation components, thereby improving product performance and service life, reducing energy consumption and environmental burden, and laying a solid foundation for the development and application of future high-performance eco-friendly materials.

Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma.

Tumor thrombus of bone sarcomas represents a unique reservoir for various types of cancer and immune cells, however, the investigation of tumor thrombus at a single-cell level is very limited. And it is still an open question to identify the thrombus-specific tumor microenvironment that is associated with the tumor-adaptive immune response. Here, by analyzing bulk tissue and single-cell level transcriptome from the paired thrombus and primary tumor samples of osteosarcoma (OS) patients, we define the immunostimulatory microenvironment in tumor thrombus of OS with a higher proportion of tumor-associated macrophages with M1-like states (TAM-M1) and TAM-M1 with high expression of CCL4. OS tumor thrombus is found to have upregulated IFN-γ and TGF-ß signalings that are related to immune surveillance of circulating tumor cells in blood circulation. Further multiplexed immunofluorescence staining of the CD3/CD4/CD8A/CD68/CCL4 markers validates the immune-activated state in the tumor thrombus samples. Our study first reports the transcriptome differences at a single-cell level between tumor thrombus and primary tumor in sarcoma.

Chordoma recruits and polarizes tumor-associated macrophages via secreting CCL5 to promote malignant progression.

BACKGROUND: Chordoma is an extremely rare, locally aggressive malignant bone tumor originating from undifferentiated embryonic remnants. There are no effective therapeutic strategies for chordoma. Herein, we aimed to explore cellular interactions within the chordoma immune microenvironment and provide new therapeutic targets. METHODS: Spectrum flow cytometry and multiplex immunofluorescence (IF) staining were used to investigate the immune microenvironment of chordoma. Cell Counting Kit-8, Edu, clone formation, Transwell, and healing assays were used to validate tumor functions. Flow cytometry and Transwell assays were used to analyze macrophage phenotype and chemotaxis alterations. Immunohistochemistry, IF, western blot, PCR, and ELISA assays were used to analyze molecular expression. An organoid model and a xenograft mouse model were constructed to investigate the efficacy of maraviroc (MVC). RESULTS: The chordoma immune microenvironment landscape was characterized, and we observed that chordoma exhibits a typical immune exclusion phenotype. However, macrophages infiltrating the tumor zone were also noted. Through functional assays, we demonstrated that chordoma-secreted CCL5 significantly promoted malignancy progression, macrophage recruitment, and M2 polarization. In turn, M2 macrophages markedly enhanced the proliferation, invasion, and migration viability of chordoma. CCL5 knockdown and MVC (CCL5/CCR5 inhibitor) treatment both significantly inhibited chordoma malignant progression and M2 macrophage polarization. We established chordoma patient-derived organoids, wherein MVC exhibited antitumor effects, especially in patient 4, with robust killing effect. MVC inhibits chordoma growth and lung metastasis in vivo. CONCLUSIONS: Our study implicates that the CCL5-CCR5 axis plays an important role in the malignant progression of chordoma and the regulation of macrophages, and that the CCL5-CCR5 axis is a potential therapeutic target in chordoma.

Denosumab in pediatric bone disorders and the role of RANKL blockade: a narrative review.

Background and Objective: Denosumab is a valuable and safe therapy for skeletal disorders in adults and has received regulatory approval to treat osteoporosis and bone metastases. However, denosumab is not licensed for pediatric use due to a lack of high-quality prospective research on children. This study aimed to describe and discuss the benefits and disadvantages of denosumab in treating bone diseases in children and to summarize the current understanding of the role of denosumab therapy in children. Methods: A narrative review was conducted using the literature retrieved from the PubMed, Embase, and Cochrane Library databases. Key Content and Findings: In children with type 6 osteogenesis imperfecta (OI), juvenile Paget disease (JPD), and secondary osteoporosis who show poor response to bisphosphonate, the use of denosumab has been reported to improve osteoporosis and increase bone mineral density (BMD). Moreover, for those with relapse, progressive and refractory aneurysmal bone cyst (ABC), fibrous dysplasia (FD), giant cell tumor of bone (GCTB), and central giant cell granuloma (CGCG) lesions, denosumab can improve pain symptoms, control disease progression, and reduce serious adverse events. Although there have been sporadic reports of adverse events such as hypocalcemia during medication and rebound hypercalcemia after discontinuation, early prevention, monitoring, and timely intervention can prevent children from experiencing severe adverse events. Conclusions: The published data indicate that denosumab has efficacy in alleviating disease in multiple refractory bone lesions in children.

The role of tumor-platelet interplay and micro tumor thrombi during hematogenous tumor metastasis.

BACKGROUND: In addition to their pivotal roles in coagulation and thrombosis, platelets are crucial in tumor progression, with plenty of clinical and experimental data demonstrating that the interplay of platelets and tumor cells is essential for hematogenous tumor metastasis. After detach from primary sites, tumor cells intravasate into the blood circulation becoming circulating tumor cells and induce platelet activation, aggregation and encasement around tumor cells to form micro tumor thrombi, which create a permissive tumor microenvironment for metastasis. Platelets in micro tumor thrombi protect tumor cells from immune surveillance and anoikis (detachment-triggered apoptosis) through various pathways, which are significant for tumor cell survival in the bloodstream. Moreover, platelets can facilitate tumor metastasis by expediting epithelial-mesenchymal transition (EMT), adhesion to the endothelium, angiogenesis, tumor proliferation processes and platelet-derived microvesicle (PMV) formation. CONCLUSIONS: Here, we provide a synopsis of the current understanding of the formation of micro tumor thrombi and the role of micro tumor thrombi in tumor hematogenous metastasis based on the tumor-platelet interplay. We also highlight potential therapeutic strategies targeting platelets for tumor treatment, including cancer-associated platelet-targeted nanomedicines.

Current progress and open challenges for applying tyrosine kinase inhibitors in osteosarcoma.

Osteosarcoma (OS) is a mesenchymal-origin tumor that constitutes the most common primary malignant bone tumor. The survival rate of the patients has significantly improved since the introduction of neoadjuvant chemotherapy and extensive resection, but it has stagnated in recent 40 years. Tyrosine kinase inhibitors (TKIs) have played a key part in the treatment of malignant tumors. In advanced OS, TKIs including anlotinib, apatinib, sorafenib, etc. have significantly improved the progression-free survival of patients, while the overall survival remains unchanged. The main reason is the rapid and inevitable progress of acquired drug resistance of OS. However, as the application of TKIs in OS and other tumors is still in the exploratory phase, its drug resistance mechanism and corresponding solutions are rarely reported. Hence, in this review, we summarize knowledge of the applications of TKIs, the mechanism of TKIs resistance, and the attempts to overcome TKIs resistance in OS, which are the three potentially novel insights of TKIs in OS. Because most evidence is derived from studies using animal and cell models, we also reviewed clinical trials and related bioinformatics data available in public databases, which partially improved our understanding of TKIs applications.

Simultaneous detection of genomic imbalance in patients receiving preimplantation genetic testing for monogenic diseases (PGT-M).

Background: Preimplantation genetic test for monogenic disorders (PGT-M) has been used to select genetic disease-free embryos for implantation during in vitro fertilization (IVF) treatment. However, embryos tested by PGT-M have risks of harboring chromosomal aneuploidy. Hence, a universal method to detect monogenic diseases and genomic imbalances is required. Methods: Here, we report a novel PGT-A/M procedure allowing simultaneous detection of monogenic diseases and genomic imbalances in one experiment. Library was prepared in a special way that multiplex polymerase chain reaction (PCR) was integrated into the process of whole genome amplification. The resulting library was used for one-step low-pass whole genome sequencing (WGS) and high-depth target enrichment sequencing (TES). Results: The TAGs-seq PGT-A/M was first validated with genomic DNA (gDNA) and the multiple displacement amplification (MDA) products of a cell line. Over 90% of sequencing reads covered the whole-genome region with around 0.3-0.4 × depth, while around 5.4%-7.3% of reads covered target genes with >10000 × depth. Then, for clinical validation, 54 embryos from 8 women receiving PGT-M of ß-thalassemia were tested by the TAGs-seq PGT-A/M. In each embryo, an average of 20.0 million reads with 0.3 × depth of the whole-genome region was analyzed for genomic imbalance, while an average of 0.9 million reads with 11260.0 × depth of the target gene HBB were analyzed for ß-thalassemia. Eventually, 18 embryos were identified with genomic imbalance with 81.1% consistency to karyomapping results. 10 embryos contained ß-thalassemia with 100% consistency to conventional PGT-M method. Conclusion: TAGs-seq PGT-A/M simultaneously detected genomic imbalance and monogenic disease in embryos without dramatic increase of sequencing data output.

Characteristics of IgG4-related disease complicated with allergic rhinitis or chronic rhinosinusitis: a large cross-sectional cohort study.

In clinical practice, we found that IgG4-related disease (IgG4-RD) patients complicated with allergic rhinitis (AR)/chronic rhinosinusitis (CRS) seemed to have unique characteristics different from patients with IgG4-RD alone. In this study, demographic, clinical and laboratory characteristics of IgG4-RD patients complicated with AR/CRS were investigated. We retrospectively analyzed 756 IgG4-RD patients who were recruited in four medical centers from 2009 to 2021. We divided 756 IgG4-RD patients into 2 groups: the case group included IgG4-RD patients complicated with AR/CRS, and the control group included IgG4-RD patients without AR/CRS. 411 patients were complicated with AR/CRS among 756 IgG4-RD patients. Multiple organs involvement (≥ 3, p < 0.0001, OR 3.585 (95% CI 2.655-4.839)) and other types of allergic disease (p < 0.0001, OR 2.007 (95% CI 1.490-2.693)) were more common in the case group. Patients in the case group had a higher level of serum IgG4 (650 mg/dL vs 385 mg/dL, p < 0.0001), IgE (347 mg/dL vs 98 mg/dL, p < 0.0001) and ESR (14 mm/h vs 12 mm/h, p < 0.05). High IgE level (p < 0.01, OR 1.003 (95% CI 1.001-1.005)) and other types of allergic disease (p < 0.05, OR 3.196 (95% CI 1.146-8.908)) were risk factors for patients in the case group, in which most patients had nasal manifestations before the diagnosis of IgG4-RD. The median time interval from nasal symptoms appearance to IgG4-RD diagnosis was - 120 and - 90 months for patients complicated with AR and CRS, respectively. IgG4-RD patients are often complicated with AR/CRS and have distinct characteristics, which appear to be a subgroup of IgG4-RD. The data suggests a pathogenic association of IgG4-RD and AR/CRS.

Clinical characteristics of IgG4-related respiratory disease patients: a large Chinese cohort study.

OBJECTIVES: IgG4-related disease (IgG4-RD) is an autoimmune disorder and frequently involves multiple organs. The respiratory tract is one of the most frequently affected sites. In this study, we aimed to compare the demographic and clinical characteristics between IgG4 related respiratory disease (IgG4-RRD+) and extra-thoracic IgG4-related disease (IgG4-RRD-) in a large cohort. METHODS: A total of 448 cases of IgG4-RD (104 IgG4-RRD+ patients and 344 IgG4-RRD- patients) diagnosed at Peking University People's Hospital during 2003 to 2020 were included in our study. Patients' demographic data, clinical characteristics, laboratory parameters and imaging features were analysed. RESULTS: IgG4-RRD+ patients had an older age at disease onset and diagnosis. Multiorgan involvement and hypocomplementaemia were more common in IgG4-RRD+. Besides, the level of ESR, IgG and IgG4 were higher in IgG4-RRD+ patients. In IgG4-RRD+ group, salivary gland, lacrimal gland, lymph nodes, biliary system and kidney were more commonly involved than those in the IgG4-RRD- group. Also, more organ involvement eosinophilia and biliary involvement were independent risk factors for the development of IgG4-RRD+. CONCLUSIONS: Our study revealed demographic, clinical and laboratory differences between the two phenotypes, in addition to describing the imaging features of IgG4-RRD+, which will be helpful for understanding of the disease.

Disparities between IgG4-related kidney disease and extrarenal IgG4-related disease in a case-control study based on 450 patients.

We aimed to compare the demographic, clinical and laboratory characteristics between IgG4-related kidney disease (IgG4-RKD+) and extrarenal IgG4-related disease (IgG4-RKD-) in a large Chinese cohort, as well as describing the radiological and pathological features of IgG4-RKD+. We retrospectively analyzed the medical records of 470 IgG4-related disease (IgG4-RD) patients at Peking University People's Hospital from January 2004 to January 2020. The demographic, clinical, laboratory, radiological and pathological characteristics between IgG4-RKD+ and IgG4-RKD- were compared. Twenty IgG4-RD patients who had definite etiology of renal impairment including diabetes, hypertension and etc. were excluded. Among the remained 450 IgG4-RD patients, 53 were diagnosed with IgG4-RKD+ . IgG4-RKD+ patients had older age at onset and at diagnosis. Male to female ratio of IgG4-RKD+ patients is significantly higher. In the IgG4-RKD+ group, the most commonly involved organs were salivary gland, lymph nodes and pancreas. It was found that renal function was impaired in approximately 40% of IgG4-RKD+ patients. The most common imaging finding is multiple, often bilateral, hypodense lesions. Male sex, more than three organs involved, and low serum C3 level were risk factors for IgG4-RKD+ in IgG4-RD patients. These findings indicate potential differences in pathogenesis of these two phenotypes.

Impact of COVID-19 on Anxiety, Stress, and Coping Styles in Nurses in Emergency Departments and Fever Clinics: A Cross-Sectional Survey.

BACKGROUND: During the Coronavirus Disease 2019 (COVID-19) pandemic, emergency departments and fever clinics nurses acted as gatekeepers to the health care system. To manage the psychological problems that these nurses experience, we should develop appropriate training and intervention programs. OBJECTIVE: To identify the impact of COVID-19 on the psychology of Chinese nurses in emergency departments and fever clinics and to identify associated factors. METHODS: This online cross-sectional study recruited participants through snowball sampling between 13 February and 20 February 2020. Nurses self-administered the online questionnaires, including a general information questionnaire, the Self-Rating Anxiety Scale, the Perceived Stress Scale-14, and the Simplified Coping Style Questionnaire. RESULTS: We obtained 481 responses, of which 453 were valid, an effective response rate of 94.18%. Participants who had the following characteristics had more mental health problems: female gender, fear of infection among family members, regretting being a nurse, less rest time, more night shifts, having children, lack of confidence in fighting transmission, not having emergency protection training, and negative professional attitude. CONCLUSION: Effective measures are necessary to preserve mental health of nurses in emergency departments and fever clinics. These include strengthening protective training, reducing night shifts, ensuring adequate rest time, and timely updating the latest pandemic situation.

Delayed postoperative radiotherapy increases the incidence of radiographic local tumor progression before radiotherapy and leads to poor prognosis in spinal metastases.

BACKGROUND: Most previous studies focused on the minimum interval between surgery and radiotherapy in spinal metastases, leaving the maximum interval under-investigated. However, in real world, limited radiotherapist and equipment cannot meet the needs of a large patient population to obtain timely radiotherapy after the index spine surgery in developing countries. This study aimed to estimate the clinical risks of delayed radiotherapy after surgery in patients with spinal metastases in developing country. METHODS: Data from 89 patients who underwent surgery and postoperative radiotherapy at a single site in a developing country were retrospectively reviewed. Patients were divided into the progression before radiotherapy (PBR) and no progression before radiotherapy (NPBR) groups. Kaplan-Meier analysis and log-rank tests were used to compare the local control (LC) and overall survival (OS) between groups. RESULTS: Within 1 month after surgery, only 20.2% of patients underwent radiotherapy. Risk of local progression before radiotherapy at 1, 3, and 6 months was 1.2%, 24.1%, and 45.1%, respectively. The LC rate at 1 year was lower in the PBR group than in the NPBR group (53.3% vs. 76.3%, P = 0.040). The OS rate at 1 year was 61.9% and 79.6% in the PBR and NPBR groups, respectively (P = 0.001). The Karnofsky performance status significantly improved only in the NPBR group (52.5 ± 17.6 vs. 66.8 ± 26.3, P < 0.001). The sphincter dysfunction significantly improved in the NPBR group (0.3 ± 0.5 vs. 0.1 ± 0.3, P = 0.007) but it tended to be deteriorated in the PBR group (0.1 ± 0.4 vs. 0.3 ± 0.5, P = 0.500). CONCLUSIONS: In real world, about 80% of patients had delayed radiotherapy 1 month after spine surgery for metastases in our developing country. Patients had a higher risk for radiographic local progression before radiotherapy and poorer LC, OS, and quality of life as time to radiotherapy increased.

The Role of Autophagy in the Pathogenesis of Ischemic Stroke.

Autophagy is a strictly regulated process that degrades and recycles long-lived or misfolded proteins and damaged organelles for the maintenance of energy and function homeostasis of cells. Insufficient oxygen and glucose supply caused by cerebral ischemia lead to a higher ratio of AMP/ATP, which will activate the AMPK pathway to initiate the process of autophagy. Accumulating evidence shows that autophagy participates in the pathogenesis of ischemic stroke as a double- edged sword. However, the exact role of autophagy in the pathogenesis of ischemic stroke is controversial and yet to be elucidated. In this review, the autophagy pathway, both in physiological conditions and in ischemic stroke, is expounded. The focus was also on discussing the doubleedged sword effect of autophagy in brain ischemia and its underlying mechanisms. In addition, potential therapeutic strategies for ischemic stroke targeting autophagy pathway were also reviewed.

Experiences and Psychological Adjustments of Nurses Who Voluntarily Supported COVID-19 Patients in Hubei Province, China.

BACKGROUND: The COVID-19 pandemic poses a major threat to global public health and economic development. Moreover, it has put considerable psychological pressure on nurses, who have played a vital role in the prevention and control of the epidemic. OBJECTIVE: This qualitative study aimed at exploring the experiences and psychological adjustments of nurses who voluntarily traveled to Hubei Province in China to provide support during the COVID-19 epidemic. METHODS: We conducted semi-structured, face-to-face interviews with twelve nurses recruited from three hospitals in Jiangsu Province and performed qualitative content analysis of the interview data. RESULTS: The following themes emerged from the analysis: (1) motivations for supporting the hardest-hit areas (professional commitment, family support, and media propaganda); (2) challenges faced during the support missions (heavy workloads, changes in working patterns, communication barriers, and barriers associated with wearing personal protective equipment); (3) psychological experiences (a sense of uncertainty, fear of infection, loneliness, stressful events, and sleep disorders); (4) psychological adjustments (adequate training and personal protective equipment, positive responses to stress, and social support); and (5) personal and professional growth (a strong professional identity, a positive work attitude, a perception of expanded possibilities, realization of the value of learning, and cherishing life). CONCLUSIONS AND RECOMMENDATIONS: Policy makers and nursing managers should implement effective measures for supporting nurses. They include ensuring adequate workforce preparedness for nurses, strengthening protection training, including professional psychologists in support teams, encouraging nurses to apply self-regulation methods, such as exercising and listening to music, and seeking social support to promote mental health.