Clinical observation of 10-mm endoscopic minimally invasive interlaminar decompression in the treatment of ossified lumbar spinal stenosis.

PURPOSE: This study aims to observe the safety and effectiveness of 10-mm endoscopic minimally invasive interlaminar decompression in the treatment of ossified lumbar spinal stenosis. METHODS: The clinical data of 50 consecutive patients with ossified lumbar spinal stenosis were retrospectively analyzed. All patients underwent minimally invasive interlaminar decompression with 10-mm endoscope. Patient demographics, perioperative data, and clinical outcomes were recorded. Visual analog scale (VAS) scores, Oswestry disability index (ODI) scores, and modified Macnab criteria were used to assess clinical outcomes. The lateral recess angle, real spinal canal area and effective intervertebral foramen area were used to assess the effect of decompression. RESULTS: The mean age of all patients was 59.0±12.3 years. The mean operative time and intraoperative blood loss were 43.7±8.7 minutes and <20ml, respectively. Two years after surgery, the leg pain VAS score decreased from 7.4 ± 1.0 to 1.6 ± 0.6 (P < 0.05) and the ODI score decreased from 63.8 ± 7.6 to 21.7 ± 3.4 (P < 0.05). The lateral recess angle, real spinal canal area and effective intervertebral foramen area were significantly larger than before surgery (P < 0.05). The overall excellent and good rate at the last follow-up was 92.0% according to the modified Macnab criteria. CONCLUSION: The 10-mm endoscopic minimally invasive interlaminar decompression can safely and effectively remove the ossification in the spinal canal and achieve adequate decompression in patients with ossified lumbar spinal stenosis.

Cross-Layer Contrastive Learning of Latent Semantics for Facial Expression Recognition.

Convolutional neural networks (CNNs) have achieved significant improvement for the task of facial expression recognition. However, current training still suffers from the inconsistent learning intensities among different layers, i.e., the feature representations in the shallow layers are not sufficiently learned compared with those in deep layers. To this end, this work proposes a contrastive learning framework to align the feature semantics of shallow and deep layers, followed by an attention module for representing the multi-scale features in the weight-adaptive manner. The proposed algorithm has three main merits. First, the learning intensity, defined as the magnitude of the backpropagation gradient, of the features on the shallow layer is enhanced by cross-layer contrastive learning. Second, the latent semantics in the shallow-layer and deep-layer features are explored and aligned in the contrastive learning, and thus the fine-grained characteristics of expressions can be taken into account for the feature representation learning. Third, by integrating the multi-scale features from multiple layers with an attention module, our algorithm achieved the state-of-the-art performances, i.e. 92.21%, 89.50%, 62.82%, on three in-the-wild expression databases, i.e. RAF-DB, FERPlus, SFEW, and the second best performance, i.e. 65.29% on AffectNet dataset. Our codes will be made publicly available.

M2 macrophage­derived exosomes alleviate KCa3.1 channel expression in rapidly paced HL­1 myocytes via the NF­κB (p65)/STAT3 signaling pathway.

The present study was designed to explore the role of M2 macrophage­derived exosomes (M2­exos) on the KCa3.1 channel in a cellular atrial fibrillation (AF) model using rapidly paced HL­1 myocytes. M2 macrophages and M2­exos were isolated and identified. MicroRNA (miR)­146a­5p levels in M2 macrophages and M2­exos were quantified using reverse transcription­quantitative PCR (RT­qPCR). HL­1 myocytes were randomly divided into six groups: Control group, pacing group, pacing + coculture group (pacing HL­1 cells cocultured with M2­exos), pacing + mimic­miR­146a­5p group, pacing + NC­miR­146a­5p group and pacing + pyrrolidine dithiocarbamate (PDTC; a special blocker of the NF­κB signaling pathway) group. Transmission electron microscopy, nanoparticle tracking analysis, western blotting, RT­qPCR and immunohistochemistry were performed in the present study. A whole­cell clamp was also applied to record the current density of KCa3.1 and action potential duration (APD) in each group. The results revealed that miR­146a­5p was highly expressed in both M2 macrophages and M2­exos. Pacing HL­1 cells led to a shorter APD, an increased KCa3.1 current density and higher protein levels of KCa3.1, phosphorylated (p­)NF­κB p65, p­STAT3 and IL­1ß compared with the control group. M2­exos, miR­146a­5p­mimic and PDTC both reduced the protein expression of KCa3.1, p­NF­κB p65, p­STAT3 and IL­1ß and the current density of KCa3.1, resulting in a longer APD in the pacing HL­1 cells. In conclusion, M2­exos and their cargo, which comprised miR­146a­5p, decreased KCa3.1 expression and IL­1ß secretion in pacing HL­1 cells via the NF­κB/STAT3 signaling pathway, limiting the shorter APD caused by rapid pacing.

COVID-19 as WATER? The functions of WATER metaphors in the metaphorical representation of COVID-19.

Previous studies have examined WATER metaphors in different discourses, yet there has been limited focus on understanding the functions of these metaphors in constructing discourses. To address this research gap, the present paper utilised the metaphor identification procedure developed by the Pragglejaz Group and the Weak Differentiating Model to investigate WATER metaphors in the Coronavirus Corpus. The study reveals that WATER metaphors can be used flexibly for multiple purposes. These include explaining the many pandemic stages, describing the occurrence and performance of the pandemic, explaining how COVID-19 affects human life, rallying the public to take precautions against contagion, and communicating risk. This research highlights the diverse functions that WATER metaphors served in conveying intricate information and influencing public perceptions throughout the COVID-19 pandemic.

A proteomic and phosphoproteomic landscape of spinal cord injury.

Spinal cord injury (SCI) is a devastating trauma of the central nervous system, with high levels of morbidity, disability, and mortality. To explore the underlying mechanism of SCI, we analyzed the proteome and phosphoproteome of rats at one week after SCI. We identified 465 up-regulated and 129 down-regulated differentially expressed proteins (DEPs), as well as 184 up-regulated and 40 down-regulated differentially expressed phosphoproteins (DEPPs). Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we identified the biological characteristics of these proteins from the perspectives of cell component, biological process, and molecular function. We also found a lot of enriched functional pathways such as GABAergic synapse pathway, ErbB signaling pathway, tight junction, adherens junction. The integrated analysis of proteomics and phosphoproteomics yielded 22 differently expressed co-identified proteins of DEPs and DEPPs, which revealed strongly correlative patterns. These findings may help clarify the potential mechanisms of trauma and repair in SCI and may guide the development of novel treatments.

Clinical Results of 10-mm Endoscopic Minimally Invasive Interlaminar Decompression in the Treatment of Lumbar Spinal Stenosis with Degenerative Lumbar Scoliosis and Simple Lumbar Spinal Stenosis.

Purpose: The number of patients with lumbar spinal stenosis (LSS) with degenerative lumbar scoliosis (DLS) is gradually increasing as the population ages. The purpose of this study was to evaluate the clinical outcomes of 10-mm endoscopic minimally invasive interlaminar decompression for LSS with DLS and simple LSS. Material and Methods: The clinical data of 175 consecutive elderly patients with LSS were retrospectively analyzed. They were divided into LSS group and LSS with DLS group based on whether they were accompanied by DLS. Patient demographics, perioperative indicators, and clinical outcomes were recorded. Lumbar spine stability was assessed by imaging data. Meanwhile, visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores, and the modified Macnab criteria were used to assess clinical outcomes. Results: There were 129 patients in the LSS group and 46 patients in the LSS with DLS group. Both groups had similar VAS and ODI scores preoperatively, and both were significantly lower postoperatively (P < 0.05). However, patients combined with DLS showed higher VAS scores for low back pain at 3 months and 1 year postoperatively (P < 0.05). In addition, postoperative LL and PI-LL were significantly improved in both groups (P < 0.05). However, patients in LSS with DLS group showed higher PT, PI and PI-LL before and after surgery. According to the modified Macnab criteria, the excellent and good rates were 92.25% and 89.13% in the LSS group and LSS with DLS group at the last follow-up, respectively. Conclusion: 10-mm endoscopic minimally invasive interlaminar decompression for LSS with or without DLS has shown satisfactory clinical outcomes. However, patients with DLS may have higher residual low back pain after surgery.

Seasonal associations between air pollutants and influenza in 10 cities of southern China.

Few studies have explored the associations between air pollutants and influenza across seasons, especially at large scales. This study aimed to evaluate seasons' modifying effects on associations between air pollutants and influenza from 10 cities of southern China. Through scientific evidence, it provides mitigation and adaptation strategies with practical guidelines to local health authorities and environmental protection agencies. Daily influenza incidence, meteorological, and air pollutants data from 2016 to 2019 were collected. Quasi-Poisson regression with a distributed lag nonlinear model was used to evaluate city-specific air pollutants and influenza associations. Meta-analysis was used to pool site-specific estimates. Attributable fractions (AFs) of influenza incidence due to pollutants were calculated. Stratified analyses were conducted by season, sex, and age. Overall, the cumulative relative risk (CRR) of influenza incidence for a 10-unit increase in PM2.5, PM10, SO2, NO2, and CO was 1.45 (95% CI: 1.25, 1.68), 1.53 (95% CI: 1.29, 1.81), 1.87 (95% CI: 1.40, 2.48), 1.74 (95% CI: 1.49, 2.03), and 1.19 (95% CI: 1.04, 1.36), respectively. Children aged 0-17 were more sensitive to air pollutants in spring and winter. PM10 had greater effect on influenza than PM2.5 in autumn, winter, and overall, lesser in spring. The overall AF due to PM2.5, PM10, SO2, NO2, and CO was 4.46% (95% eCI: 2.43%, 6.43%), 5.03% (95% eCI: 2.33%, 7.56%), 5.36% (95% eCI: 3.12%, 7.58%), 24.88% (95% eCI: 18.02%, 31.67%), and 23.22% (95% eCI: 17.56%, 28.61%), respectively. AF due to O3 was 10.00% (95% eCI: 4.76%, 14.95%) and 3.65% (95% eCI: 0.50%, 6.59%) in spring and summer, respectively. The seasonal variations in the associations between air pollutants and influenza in southern China would provide evidence to service providers for tailored intervention, especially for vulnerable populations.

SARS-CoV-2 Surveillance Through China Influenza Surveillance Information System - China, December 1, 2022 to February 12, 2023.

Introduction: The World Health Organization (WHO) proposed using influenza surveillance systems to carry out coronavirus disease 2019 (COVID-19) surveillance due to the similarity between the two diseases in some respiratory symptoms. To assess the prevalence of COVID-19, we analyzed the influenza-like illness (ILI) and positive rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detections in ILI patients reported to the influenza Surveillance Information System (CNISIS) since late 2022. Methods: Data related to ILI were reported by national surveillance sentinel hospitals. Positive testing for SARS-CoV-2 and influenza viruses was conducted using real-time reverse transcription polymerase chain reaction (rRT-PCR) detection by the national influenza surveillance network laboratories. Surveillance data were reported to CNISIS. Results: Beginning on December 12, 2022 (Week 50), the ILI percentage increased dramatically, peaking in Week 51 at 12.1%. Subsequently, the ILI percentage began to decline rapidly from Week 52, 2022, and by Week 6, 2023 (February 6-12), the ILI and ILI percentage had returned to the levels observed at the beginning of December 2022. From December 1, 2022 to February 12, 2023, 115,844 specimens were tested for both SARS-CoV-2 and influenza virus. Of these, 30,381 (26.2%) were positive for SARS-CoV-2 and 1,763 (1.5%) were positive for influenza virus. The positive rate of SARS-CoV-2 tests peaked at 74.1% around December 23 and 25. Conclusions: Sentinel-based surveillance, previously established for influenza, is an effective way to track the circulation trend of SARS-CoV-2 during community-level epidemics. There was no co-prevalence of SARS-CoV-2 and influenza virus during the outbreak of SARS-CoV-2, even during the winter influenza season. However, it is important to remain vigilant for the potential rise of influenza activities following the COVID-19 epidemic.

Curcumin-Primed Umbilical Cord Mesenchymal Stem Cells-Derived Extracellular Vesicles Improve Motor Functional Recovery of Mice with Complete Spinal Cord Injury by Reducing Inflammation and Enhancing Axonal Regeneration.

Background Transplantation of extracellular vesicles (EVs) from stem cells is a feasible scheme for traumatic spinal cord injury (SCI). However, there is no relevant report about stem cells derived EVs loaded with curcumin for SCI treatment. Methods Mouse umbilical cord mesenchymal stem cells (MUMSCs) were incubated in the medium containing curcumin (20 µM) for 48 h. Extracellular vesicles (EVs) and curcumin-primed EVs (Cur-EVs) were collected by ultracentrifugation. Characterizations of EVs/Cur-EVs were analyzed by western blotting with CD9 and CD81 antibodies, transmission electron microscopy and nano-tracking analysis. Curcumin in the Cur-EVs was analyzed by high performance liquid phase chromatography at 430 nm wavelength. Immunofluorescence and in vivo imaging methods were used to confirm biocompatibility of EVs/Cur-EVs in vitro and in vivo. Mice with complete SCI were treated with EVs/Cur-EVs to compare the differences of locomotor function, inflammation, histological changes and remyelination. Results The isolated EVs and Cur-EVs from MUMSCs have good biocompatibility. Compared with the model mice, the locomotor function, inflammation and axonal regeneration of mice were significantly improved after injection of Cur-EVs/EVs. Furthermore, it is more effective for structural and functional recovery of complete SCI after the Cur-EVs treatment compared with the EVs treatment. In the lesioned regions, the macrophage polarization from M1 to M2 phenotype and axonal regeneration were significantly improved in the Cur-EVs group compared with the EVs group. Conclusions Our data suggested that EVs from MUMSCs might be a promising drug delivery vehicle of curcumin for the efficient and biocompatible treatment of severe SCI.

Marked distinctions in syntactic complexity: A case of second language university learners' and native speakers' syntactic constructions.

Existing research on syntactic complexity tends to examine diversity and complexity embedded in grammatical employments which may well be witnessed in formulations of different syntactic structures. Conceivably, the subject syntactic complexity seems to be exercised mostly by non-native speakers and writers. The present study employs pseudo-longitudinal data: essays written by undergraduate students in different levels collected at the same time. Hence, it aims at investigating the mechanism involved in the L2 production of L2 learners in terms of syntactic complexity by analyzing a corpus of non-native English-speaking learners. The research inquiry is mainly focused on investigation of significant differences in terms of syntactic complexity between writing of Japanese university students and that of native speakers, probing further into the particular dimension and level of difference. The study also traces marked variations in syntactic complexity employed by Japanese university students in different grades. Nagoya Interlanguage Corpus of English (NICE) developed by Sugiura in 2015 was employed to conduct the entire research proceedings. The corpus of the subject study comprises 339 essays written by L2 EFL learners studying in a Japanese university employing a judicious selection of quantitative measures of syntactic complexity. The results exhibited a considerable statistical difference between the writing of Japanese learners and native English writers. The findings of this study provide meaningful pedagogical implications for English teachers and textbook compilers. Japanese university students in higher grades are found to be employing more complicated and diverse syntactic structures. Conforming to the already conducted research studies with almost similar objectives, this study demonstrates the significance of using both general and more particular complexity metrics to assess syntactic development in L2.

Bibliometric assessment of world scholars' international publications related to conceptual metaphor.

Research on metaphor has gained increasing attention of world's scholars since the publication of Lakoff and Johnson's collaborated book Metaphors We Live By in 1980. The present study comprises a pioneering review of publications on Conceptual Metaphor Theory (CMT). It aimed to use the CiteSpace software to provide a clear overview of international research in relation to CMT. In total, 4,458 bibliometric recordings ranging from 1980 to 2022 were collected from the Web of Science (WOS) Core Collection. The descriptive analysis presents the trend of annual publications, the top 10 most prolific journals and the top 10 most productive authors. A document co-citation analysis was conducted via CiteSpace to navigate the key documents in this field. A visualization of keywords and its cluster analysis were conducted to show the research fields and dominant topics. The top 5 keywords with high frequency were language, comprehension, conceptual metaphor, discourse, and figurative language. The most prominent 5 clusters are labeled as right hemisphere, self, time, teacher education, and corpus linguistics. The present review through CiteSpace flags the need for more investigations of CMT from more aspects or interdisciplinary studies, such as metaphor translation, metaphor in literature, metaphor and corpus linguistics, etc.

Epidemiological and etiological characteristics of mild hand, foot and mouth disease in children under 7 years old, Nanjing, China, 2010-2019.

BACKGROUND: Mild hand, foot and mouth disease (HFMD) cases make up a relatively high proportion of HFMD while have often been overlooked. This study aimed to investigate the epidemiological and etiological characteristics of mild HFMD in Nanjing. METHODS: Data on mild HFMD cases, during 2010-2019 in Nanjing, were collected from the China Information System for Disease Control and Prevention. This study mainly focused on mild cases aged < 7 years. Descriptive analysis was used to summarize epidemiological and etiological characteristics of mild cases. Flexible spatial scan statistic was used to detect spatial clusters of mild cases. RESULTS: A total of 175,339 mild cases aged < 7 years were reported, accounting for 94.4% of all mild cases. There was a higher average annual incidence of mild HFMD in children aged < 7 years (4,428 cases/100,000) compared with children aged ≥ 7 years (14 cases/100,000, P < 0.001), and especially children aged 1-year-old (7,908 cases/100,000). Mild cases showed semi-annual peaks of activity, including a major peak (April to July) and a minor peak (September to November). The average annual incidence was higher in males (5,040 cases/100,000) than females (3,755 cases/100,000). Based on the cumulative reported cases, the most likely cluster was detected, including Yuhuatai District, Jiangning District, Jiangbei new Area, and Pukou District. The annual distribution of enterovirus serotypes showed a significant difference. During 2010-2016, Enterovirus 71 (EV71), Coxsackievirus A16 (Cox A16), and other non-EV71/Cox A16 EVs, accounted for 29.1%, 34.6%, 36.3% of all the enterovirus test positive cases, respectively. Moreover, during 2017-2019, Cox A6, Cox A16, EV71, and other non-EV71/Cox A16/Cox A6 EVs, accounted for 47.3%, 32.5%, 10.7%, 9.5%, respectively. CONCLUSIONS: Children under 7 years old are at higher risk of mild HFMD. Regions with high risk are mainly concentrated in the areas surrounding central urban areas. Cox A16 and Cox A6 became the dominant serotypes and they alternated or were co-epidemic. Our findings could provide valuable information for improving the regional surveillance, prevention and control strategies of HFMD.

Temperature and influenza transmission: Risk assessment and attributable burden estimation among 30 cities in China.

BACKGROUND: Many studies have explored the epidemiological characteristics of influenza. However, most previous studies were conducted in a specific region without a national picture which is important to develop targeted strategies and measures on influenza control and prevention. OBJECTIVES: To explore the association between ambient temperature and incidence of influenza, to estimate the attributable risk from temperature in 30 Chinese cities with different climatic characteristics for a national picture, and to identify the vulnerable populations for national preventative policy development. METHODS: Daily meteorological and influenza incidence data from the 30 Chinese cities over the period 2016-19 were collected. We estimated the city-specific association between daily mean temperature and influenza incidence using a distributed lag non-linear model and evaluated the pooled effects using multivariate meta-analysis. The attributable fractions compared with reference temperature were calculated. Stratified analyses were performed by region, sex and age. RESULTS: Overall, an N-shape relationship between temperature and influenza incidence was found in China. The cumulative relative risk of the peak risk temperature (5.1 °C) was 2.13 (95%CI: 1.41, 3.22). And 60% (95%eCI: 54.3%, 64.3%) of influenza incidence was attributed to ambient temperature during the days with sensitive temperatures (1.6°C-14.4 °C). The ranges of sensitive temperatures and the attributable disease burden due to temperatures varied for different populations and regions. The residents in South China and the children aged ≤5 and 6-17 years had higher fractions attributable to sensitive temperatures. CONCLUSIONS: Tailored preventions targeting on most vulnerable populations and regions should be developed to reduce influenza burden from sensitive temperatures.

A bibliometric analysis of linguistic research on COVID-19.

Research on COVID-19 has drawn the attention of scholars around the world since the outbreak of the pandemic. Several literature reviews of research topics and themes based on scientometric indicators or bibliometric analyses have already been conducted. However, topics and themes in linguistic-specific research on COVID-19 remain under-studied. With the help of the CiteSpace software, the present study reviewed linguistic research published in SSCI and A&HCI journals to address the identified gap in the literature. The overall performance of the documents was described and document co-citations, keyword co-occurrence, and keyword clusters were visualized via CiteSpace. The main topic areas identified in the reviewed studies ranged from the influences of COVID-19 on language education, and speech-language pathology to crisis communication. The results of the study indicate not only that COVID-19-related linguistic research is topically limited but also that insufficient attention has been accorded by linguistic researchers to Conceptual Metaphor Theory, Critical Discourse Analysis, Pragmatics, and Corpus-based discourse analysis in exploring pandemic discourses and texts.

Characterization of influenza seasonality in China, 2010-2018: Implications for seasonal influenza vaccination timing.

BACKGROUND: Optimizing the timing of influenza vaccination based on regional temporal seasonal influenza illness patterns may make seasonal influenza vaccination more effective in China. METHODS: We obtained provincial weekly influenza surveillance data for 30 of 31 provinces in mainland China from the Chinese Center for Disease Control and Prevention for the years 2010-2018. Influenza epidemiological regions were constructed by clustering analysis. For each region, we calculated onset date, end date, and duration of seasonal influenza epidemics by the modified mean threshold method. To help identify initial vaccination target populations, we acquired weekly influenza surveillance data for four age groups (0-4, 5-18, 19-59, and ≥60 years) in each region and in 171 cities of wide-ranging size. We used linear regression analyses to explore the association of epidemic onset dates by age group, city, and epidemiological region and provide evidence for initial target populations for seasonal influenza vaccination. RESULTS: We determined that northern, mid, southwestern, southeast regions of mainland China have distinct seasonal influenza epidemic patterns. We found significant regional, temporal, and spatial heterogeneity of seasonal influenza epidemics. There were significant differences by age group and city size in the interval between epidemic onset in the city or age group and regional spread (epidemic lead time), with longer epidemic lead times for 5- to 18-year-old children and larger cities. CONCLUSIONS: Knowledge of influenza epidemic characteristics may help optimize local influenza vaccination timing and identify initial target groups for seasonal influenza vaccination in mainland China. Similar analyses may help inform seasonal influenza vaccination strategies in other regions and countries.

Self-Assembling Imageable Silk Hydrogels for the Focal Treatment of Osteosarcoma.

Background: The standard treatment for osteosarcoma comprises complete surgical resection and neoadjuvant chemotherapy, which may cause serious side effects and partial or total limb loss. Therefore, to avoid the disadvantages of traditional treatment, we developed self-assembling imageable silk hydrogels for osteosarcoma. Methods: We analysed whether iodine induced apoptosis in MG-63 and Saos-2 cells by using CCK-8 and flow cytometry assays and transmission electron microscopy. Western blotting was used to analyse the pathway of iodine-induced apoptosis in osteosarcoma cells. PEG400, silk fibroin solution, polyvinylpyrrolidone iodine (PVP-I), and meglumine diatrizoate (MD) were mixed to produce an imageable hydrogel. A nude mouse model of osteosarcoma was established, and the hydrogel was injected locally into the interior of the osteosarcoma with X-ray guidance. The therapeutic effect and biosafety of the hydrogel were evaluated. Results: Iodine treatment at 18 and 20 µM for 12 h resulted in cell survival rate reduced to 50 ± 2.1% and 50.5 ± 2.7% for MG-63 and Sao-2 cells, respectively (p < 0.01). The proportion of apoptotic cells was significantly higher in the iodine-treatment group than in the control group (p < 0.05), and apoptotic bodies were observed by transmission electron microscopy. Iodine could regulate the death receptor pathway and induce MG-63 and Saos-2 cell apoptosis. The hydrogels were simple to assemble, and gels could be formed within 38 min. A force of less than 50 N was required to inject the gels with a syringe. The hydrogels were readily loaded and led to sustained iodine release over 1 week. The osteosarcoma volume in the PEG-iodine-silk/MD hydrogel group was significantly smaller than that in the other three groups (p < 0.001). Caspase-3 and poly (ADP-ribose) polymerase (PARP) expression levels were significantly higher in the PEG-iodine-silk/MD hydrogel group than in the other three groups (p < 0.001). Haematoxylin and eosin (H&E) staining showed no abnormalities in the heart, liver, spleen, lung, kidney, pancreas or thyroid in any group. Conclusions: Self-assembling imageable silk hydrogels could be injected locally into osteosarcoma tissues with X-ray assistance. With the advantages of good biosafety, low systemic toxicity and minimal invasiveness, self-assembling imageable silk hydrogels provide a promising approach for improving the locoregional control of osteosarcoma.

Monoamine oxidase A attenuates chondrocyte loss and extracellular matrix degradation in osteoarthritis by inducing autophagy.

OBJECTIVES: Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage destruction and extracellular matrix (ECM) degeneration. Here, we studied the potential function of monoamine oxidase A (MAOA) in OA pathogenesis. METHODS: Cartilage tissue samples were collected from 33 patients with knee OA and nine normal healthy controls. Sprague-Dawley rats with anterior cruciate ligament transection (ACLT) and primary chondrocytes treated with interleukin (IL)-1ß were used as OA animal and cell models, respectively. The effects of adenovirus-mediated MAOA overexpression in OA models were studied using Safranin-O staining, immunohistochemistry, CCK-8 assay, EdU assay, flow cytometry, qRT-PCR, western blotting, and immunofluorescence. RESULTS: MAOA was identified as an overlapping downregulating gene in the GSE82107, GSE1919, GSE169077, and GSE29746 datasets. MAOA expression was negatively correlated with OA severity. MAOA downregulation was confirmed in ACLT rats and IL-1ß-treated chondrocytes. Notably, MAOA overexpression significantly inhibited ACLT-induced OA pathogenesis in rats, as was evidenced by the reduced Osteoarthritis Research Society International (OARSI) score and serum crosslinked C-telopeptides of type II collagen (CTX-II) and cartilage oligomeric matrix protein (COMP) levels. These findings show that MAOA overexpression inhibits extracellular matrix (ECM) degradation and promotes ACLT-induced autophagy. The effects of MAOA on ECM degradation and autophagy were also confirmed in IL-1ß-treated primary chondrocytes. Additionally, MAOA protects chondrocytes against IL-1ß-induced apoptosis. Furthermore, treating chondrocytes with 3-MA significantly attenuated the protective effects of MAOA. CONCLUSION: MAOA was identified as a downregulated gene in OA. Restoring MAOA expression protects against chondrocyte loss and ECM degradation through autophagy regulation.

Cannabidiol promotes apoptosis of osteosarcoma cells in vitro and in vivo by activating the SP1-CBX2 axis.

Osteosarcoma is the most common primary malignant bone tumor that often occurs in children, adolescents, and young adults. Cannabidiol plays an essential role in cancer treatment. However, its effects on osteosarcoma have not yet been addressed. In the present study, we investigated the pharmacological effects of cannabidiol on osteosarcoma. We found that cannabidiol effectively suppressed the proliferation and colony formation of osteosarcoma cells. Further studies showed that cannabidiol significantly promoted cell apoptosis and changes in cell apoptosis-related gene proteins in vitro. In addition, cannabidiol administration inhibited tumor growth and promoted the apoptosis of osteosarcoma cells in a mouse xenograft model. The in vitro study also demonstrated that SP1 contributes to chromobox protein homolog 2 (CBX2) reduction in cannabidiol-treated MG63 and HOS cells, and that cannabidiol may recruit SP1 into the CBX2 promoter regions to downregulate CBX2 expression at the transcriptional level and promote osteosarcoma cell apoptosis. Further, the result showed that cannabidiol suppressed osteosarcoma cell migration. In summary, cannabidiol effectively promoted the apoptosis of osteosarcoma cells in vitro and in vivo and suppressed tumor growth in a mouse xenograft model by regulating the SP1-CBX2 axis. This finding provides novel therapeutic strategies for osteosarcoma in the clinic.