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Objective: Triple-negative breast cancer (TNBC) poses a significant challenge for treatment efficacy. CD8+ T cells, which are pivotal immune cells, can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology. By leveraging these genes, our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy., Methods: Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases. In the initial stage, we identified 67 differentially expressed genes associated with immune response in CD8+ T cells. Subsequently, we narrowed our focus to three key genes, namely CXCL13 , GBP2 , and GZMB , which were used to construct a prognostic model. The accuracy of the model was assessed using the validation set data and receiver operating characteristic (ROC) curves. Furthermore, we employed various methods, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, immune infiltration, and correlation analyses with CD274 (PD-L1) to explore the model's predictive efficacy in immunotherapeutic responses. Additionally, we investigated the potential underlying biological pathways that contribute to divergent treatment responses., Results: We successfully developed a model capable of predicting the prognosis of patients with TNBC. The areas under the curve (AUC) values for the 1-, 3-, and 5-year survival predictions were 0.618, 0.652, and 0.826, respectively. Employing this risk model, we stratified the samples into high- and low-risk groups. Through KEGG enrichment analysis, we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism, whereas the low-risk group demonstrated significant enrichment in cytokine pathways. Furthermore, immune landscape analysis revealed noteworthy variations between (PD-L1) expression and risk scores, indicating that our model effectively predicted the response of patients to immune-based treatments., Conclusion: Our study demonstrates the potential of CXCL13, GBP2, and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC. These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: Cuproptosis is a new modality of cell death regulation that is currently considered as a new cancer treatment strategy. Nevertheless, the prognostic predictive value of cuproptosis-related lncRNAs in breast cancer (BC) remains unknown. Using cuproptosis-related lncRNAs, this study aims to predict the immune microenvironment and prognosis of BC patients. and develop new therapeutic strategies that target the disease., Methods: The Cancer Genome Atlas (TCGA) database provided the RNA-seq data along with the corresponding clinical and prognostic information. Univariate and multivariate Cox regression analyses were performed to acquire lncRNAs associated with cuproptosis to establish predictive features. The Kaplan-Meier method was used to calculate the overall survival rate (OS) in the high-risk and low-risk groups. High risk and low risk gene sets were enriched to explore functional discrepancies among risk teams. The mutation data were analyzed using the "MAFTools" r-package. The ties of predictive characteristics and immune status had been explored by single sample gene set enrichment analysis (ssGSEA). Last, the correlation between predictive features and treatment condition in patients with BC was analyzed. Based on prognostic risk models, we assessed associations between risk subgroups and immune scores and immune checkpoints. In addition, drug responses in at-risk populations were predicted., Results: We identified a set of 11 Cuproptosis-Related lncRNAs (GORAB-AS1, AC 079922.2, AL 589765.4, AC 005696.4, Cytor, ZNF 197-AS1, AC 002398.1, AL 451085.3, YTH DF 3-AS1, AC 008771.1, LINC 02446), based on which to construct the risk model. In comparison to the high-risk group, the low-risk patients lived longer (p < 0.001). Moreover, cuproptosis-related lncRNA profiles can independently predict prognosis in BC patients. The AUC values for receiver operating characteristics (ROC) of 1-, 3-, and 5-year risk were 0.849, 0.779, and 0.794, respectively. Patients in the high-risk group had lower OS than those in the low-risk group when they were divided into groups based on various clinicopathological variables. The tumor burden mutations (TMB) correlation analysis showed that high TMB had a worse prognosis than low-TMB, and gene mutations were found to be different in high and low TMB groups, such as PIK3CA (36% versus 32%), SYNE1 (4% versus 6%). Gene enrichment analysis indicated that the differential genes were significantly concentrated in immune-related pathways. The predictive traits were significantly correlated with the immune status of BC patients, according to ssGSEA results. Finally, high-risk patients showed high sensitivity in anti-CD276 immunotherapy and conventional chemotherapeutic drugs such as imatinib, lapatinib, and pazopanib., Conclusion: We successfully constructed of a cuproptosis-related lncRNA signature, which can independently predict the prognosis of BC patients and can be used to estimate OS and clinical treatment outcomes in BRCA patients. It will serve as a foundation for further research into the mechanism of cuproptosis-related lncRNAs in breast cancer, as well as for the development of new markers and therapeutic targets for the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Yang, Jin, Yi, Bing, Zhou and Yang.)

Ischaemic stroke is a common condition leading to human disability and death. Previous studies have shown that oleanolic acid (OA) ameliorates oxidative injury and cerebral ischaemic damage, and miR-186-5p is verified to be elevated in serum from ischaemic stroke patients. Herein, we investigated whether OA regulates miR-186-5p expression to control neuroglobin (Ngb) levels, thereby inhibiting neuronal pyroptosis in ischaemic stroke. Three concentrations of OA (0.5, 2, or 8 μM) were added to primary hippocampal neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R), a cell model of ischaemic stroke. We found that OA treatment markedly inhibited pyroptosis. qRT-PCR and western blot revealed that OA suppressed the expression of pyroptosis-associated genes. Furthermore, OA inhibited LDH and proinflammatory cytokine release. In addition, miR-186-5p was downregulated while Ngb was upregulated in OA-treated OGD/R neurons. MiR-186-5p knockdown repressed OGD/R-induced pyroptosis and suppressed LDH and inflammatory cytokine release. In addition, a dual luciferase reporter assay confirmed that miR-186-5p directly targeted Ngb. OA reduced miR-186-5p to regulate Ngb levels, thereby inhibiting pyroptosis in both OGD/R-treated neurons and MCAO mice. In conclusion, OA alleviates pyroptosis in vivo and in vitro by downregulating miR-186-5p and upregulating Ngb expression, which provides a novel theoretical basis illustrating that OA can be considered a drug for ischaemic stroke.

Isoquercitrin (ISO), an extract from Chinese traditional herb, exhibits potent neuroprotective roles in various disease models. However, its role in stroke is not fully understood. We established oxygen-glucose deprivation and reoxygenation (OGD/R) model in SH-SY5Y cell to study the roles of ISO in stroke. In the experiment, the changes of LDH level and cell viability (MTT) were analyzed. Apoptotic cells stained with anti-Annexin V antibody and propidium iodide (PI) were detected by flow cytometry. The mRNA and protein level of aldolase C (ALDOC) and nuclear factor erythroid 2-related factor (Nrf2) was determined by real-time quantitative polymerase chain reaction (qPCR) and Western blotting assay, respectively. The localization of Nrf2 was investigated by immunofluorescent assay. OGD/R reduced cell viability via inducing cell apoptosis, while ISO treatment reduced the level of apoptosis in OGD/R-treated SH-SY5Y cells ISO rescued OGD/R-treated cells. Mechanistically, the expression of Nrf2 and ALDOC was upregulated upon ISO treatment, while knockdown of ALDOC diminished the activation of autophagy and hence inhibited ISO-mediated protective activity. We further demonstrated that ISO enhanced ALDOC transcription by promoting nuclear translocation of Nrf2, and suppression of Nrf2 decreased the expression of ALDOC. Our data revealed that ISO exhibited neuroprotective activity in OGD/R model through Nrf2-ALDOC-autopagy axis and highlighted the potential application of ISO in stroke treatment., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study compared outcomes of plating distal radius (DR) fractures using wide-awake local anesthesia no tourniquet (WALANT) versus general anesthesia (GA)., Methods: From March 2018 to March 2019, 20 patients with DR fracture underwent plating using WALANT whereas 20 patients who underwent plating under GA were used as controls. Outcomes evaluated were pain control, waiting time for the operation, hemodynamic changes, blood loss, the occurrence of adverse effects of medications used in WALANT and GA, and the duration of postoperative stay., Results: The WALANT group experienced a significantly shorter waiting time for surgery (6 vs 20 days; P < .001) and a shorter postoperative stay (1 vs 2 days; P  = .009) compared with the GA group. They also reported mild to no pain during surgery. The groups were similar with regard to blood pressure, blood loss, and operative time. None in the WALANT group required conversion to GA during surgery and no adverse effects were reported., Conclusions: The WALANT approach is a viable alternative to GA for plating of DR fractures., Type of Study/level of Evidence: Therapeutic III., (© 2020 The Authors.)

Fractures of the distal radius are one of the most common types of injuries encountered in hand surgery. Plate osteosynthesis is recommended for unstable fractures. Because distal radius fracture fixation is usually performed under general or regional anesthesia with the use of a tourniquet, this exposes patients, especially elderly people with extensive comorbidities, to adverse effects commonly associated with these forms of anesthesia. As such, many of these patients are unable to undergo surgery in a timely manner until they are deemed medically fit for surgery or anesthesia, and some may still be treated nonsurgically. Injecting local anesthetic of lidocaine and epinephrine into the surgical field and without using a tourniquet is known to be advantageous for various surgical procedures of the hand. However, this approach, also known as wide-awake local anesthesia no tourniquet (WALANT), has not been used in the fixation of fractures beyond the wrist. Using the WALANT approach as an alternative anesthetic for plating of distal radius fractures may enable patients who are normally denied surgery owing to their age or medical comorbidities to undergo plate fixation for the fractures. This article outlines the WALANT approach used for a single case of fixation of distal end radius fracture with a detailed description of the technique of administering local anesthesia., (Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD), the most common dementia, is characterized by potentially neurotoxic aggregation of Aβ peptide and tau protein, and their deposition as amyloid plaques and neurofibrillary tangles (NFTs). Tau aggregation also occurs in other common neurodegenerative diseases. Frontotemporal dementia (FTD) can be caused by tau mutations that increase the susceptibility of tau to hyperphosphorylation and aggregation, which may cause neuronal dysfunction and deposition of NFTs. 17-allylamino-17-demethoxygeldanamycin (17-AAG) is a potent inhibitor of heat shock protein 90 (Hsp90), a cytosolic chaperone implicated in the proper folding and functions of a repertoire of client proteins. 17-AAG binds to Hsp90 and enhances degradation of Hsp90 client protein. We sought to determine whether 17-AAG can reduce Aβ and tau pathology in the brains of AD and FTD model mice expressing Aβ or P301L mutant tau, respectively. Mice were randomized to receive 25, 5, or 0 mg/kg 17-AAG thrice weekly from age eight to 11 months. Analysis was performed by rotarod test on motor function, on the area occupied by plaques in hippocampus or NFTs in medulla tissue sections, and on mortality. A high dose of 17-AAG tended to decrease NFTs in male mice (p = 0.08). Further studies are required to confirm the effect of 17-AAG in diseases of tau aggregation.

Background: This study aimed to determine knowledge of medication use, to investigate the treatment-seeking pattern and to identify factors affecting the use of public health clinics among the study population., Methods: A survey was conducted in Mantin Town of Malaysia using a structured questionnaire based on a literature review. Households were recruited through a three-stage sampling technique., Results: Of 183 respondents (mean age 44.6 [±16.9] years; 115 [62.8%] women), 157 (85.8%) did not know about the term 'generic name' and 159 (86.9%) were not sure about the difference in price between a generic medicine and a branded medicine. The majority sought healthcare from the public health clinics (102/183; 55.7%). In the multivariate analysis, higher education level of respondents (p = 0.028), good quality of services in public health clinics (p = 0.001) and short distances between their residences and the public health clinics (p<0.001) were the significant variables for predicting the use of a public health clinic., Conclusion: This study highlights that health education on the use of generic drugs needs to be scaled up. These findings are important to the health policy makers who may need to consider addressing factors such as quality of care and physical distance to the clinic in the design and implementation of health facilities and the selection of the catchment areas.

Laboratory incubation test was conducted to study the effects of temperature on the CH4 emission from the leaves of subtropical common tree species Castanopsis carlesii, Schima superb, Cinnamomum chekiangense, Castsanopsis fabri, Cunninghamia lanceolata, and Citrus reticulata. Among the six tree species, only S. superb, C. reticulate, and C. fabri emitted CH4 at 10 degrees C. At above 20 degrees C, all the six species emitted CH4, and the average CH4 emission rate at above 30 degrees C (1.010 ng CH4 x g(-1) DM x h(-1)) was 2.96 times higher than that at 10-30 degrees C (0.255 ng CH4 x g(-1) DM x h(-1)). Moreover, increasing temperature had much more effects on the CH4 emission rate of C. reticulata and C. lanceolata than on that of the other four tree species. Incubation time affected the CH4 emission rate of all test tree species significantly, suggesting that the effects of temperature stress on the CH4 emission could be controlled by plant activity. Dry leaves could not emit CH4 no matter the temperature was very high or low. It was suggested that high temperature stress had important effects on the CH4 emission from subtropical tree leaves, and global warming could increase the CH4 emission from plants.

Five ternary complexes were synthesized from europium with aromatic carboxylic acid (p-methylbenzoic acid, methoxybenzoic acid, m-chlorobenzoic acid and benzoic acid, p-hydroxylbenzoic acid) and acrylonitrile, and characterized by means of elemental analysis, thermal analysis, FTIR spectra and UV spectra. The fluorescence spectra show that five ternary complexes have good luminescence properties, and the sequence of the ability of the aromatic carboxylic acids to transfer light energy to europium ion is as follows: p-methylbenzoic acid>benzoic acid>m-chlorobenzoic acid>p-hydroxylbenzoic acid>methoxybenzoic acid. Meanwhile, the ternary europium complexes containing a reactive ligand acrylonitrile will possibly have a potential application to the fabrication of bonding-type europium polymer luminescent materials.