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Immunotherapy targeting programmed cell death-1 (PD-1) and PD-L1 immune checkpoints has reshaped treatment paradigms across several cancers, including breast cancer. Combining PD-1/PD-L1 immune checkpoint blockade (ICB) with chemotherapy has shown promising efficacy in both early and metastatic triple-negative breast cancer, although only a subset of patients experiences durable responses. Identifying responders and optimizing immune drug selection are therefore critical. The effectiveness of PD-1/PD-L1 immunotherapy depends on both tumor-intrinsic factors and the extrinsic cell-cell interactions within the tumor microenvironment (TME). This review systematically summarizes the key findings from clinical trials of ICBs in breast cancer and examines the mechanisms underlying PD-L1 expression regulation. We also highlight recent advances in identifying potential biomarkers for PD-1/PD-L1 therapy and emerging evidence of TME alterations following treatment. Among these, the quantity, immunophenotype, and spatial distribution of tumor-infiltrating lymphocytes stand out as promising biomarkers. Additionally, we explore strategies to enhance the effectiveness of ICBs in breast cancer, aiming to support the development of personalized treatment approaches tailored to the unique characteristics of each patient’s tumor.

The evaluation and renovation of existing building envelope has important practical significance for energy conservation and emission reduction in the field of architecture. With the development of digital cities, 3D models with rich temperature information can realize the comprehensive and accurate detection and evaluation of the existing building envelope. However, the 3D model reconstructed from thermal infrared images has only relative temperature distribution and no temperature value of each location, so it is impossible to quantify the extent of the defect from it. To solve this issue, this paper develops a method to establish a 3D point cloud model with temperature information at selected points. The proposed 3D model is generated based on the thermal infrared images acquired by an unmanned aerial vehicle (UAV) equipped with an infrared camera. In the generated 3D thermal infrared model, we can not only get the relative temperature distribution of the building’s full envelope structure, but also obtain the exact temperature value of any selected point. This method has been verified by field measurements and the result shows that the deviation is within 5 °C. In addition to temperature information, the generated 3D model also has spatial and depth information, which can reflect the appearance information and 3D structure of the monitoring target more realistically. Thus, by using this method, it is possible to achieve a comprehensive, accurate, and efficient on-site assessment of the building envelope in the urban area.

Picroside II (P-II) is the main bioactive constituent of Picrorhiza Kurroa, a traditional Chinese herb of interest for its proven anti-inflammatory properties. Its beneficial effects have been noted across several physiological systems, including the nervous, circulatory, and digestive, capable of treating a wide range of diseases. Nevertheless, the potential of Picroside II to treat osteoarthritis (OA) and the mechanisms behind its efficacy remain largely unexplored. This study aims to evaluate the efficacy of Picroside II in the treatment of osteoarthritis and its potential molecular mechanisms. In vitro, we induced cellular inflammation in chondrocytes with lipopolysaccharide (LPS) and subsequently treated with Picroside II to assess protective effect on chondrocyte. We employed the Cell Counting Kit-8 (CCK-8) assay to assess the impact of Picroside II on cell viability and select the optimal Picroside II concentration for subsequent experiments. We explored the effect of Picroside II on chondrocyte pyroptosis and its underlying molecular mechanisms by qRT-PCR, Western blot (WB) and immunofluorescence. In vivo, we established the destabilization of the medial meniscus surgery to create an OA mouse model. The therapeutic effects of Picroside II were then assessed through Micro-CT scanning, Hematoxylin-eosin (H&E) staining, Safranin O-Fast Green (S&F) staining, immunohistochemistry and immunofluorescence. In in vitro studies, toluidine blue and CCK-8 results showed that a certain concentration of Picroside II had a restorative effect on the viability of chondrocytes inhibited by LPS. Picroside II notably suppressed the expression levels of caspase-1, IL-18, and IL-1β, which consequently led to the reduction of pyroptosis. Moreover, Picroside II was shown to decrease NLRP3 inflammasome activation, via the MAPK/NF-κB signaling pathway. In vivo studies have shown that Picroside II can effectively reduce subchondral bone destruction and osteophyte formation in the knee joint of mice after DMM surgery. Our research suggests that Picroside II can inhibit chondrocyte pyroptosis and ameliorate osteoarthritis progression by modulating the MAPK/NF-κB signaling pathway.

Background In recent years, programmed cell death protein-1 inhibitors, including sintilimab, have significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma (HCC); however, the cost-effectiveness of sintilimab is unclear. The aim of this study was to assess the cost-effectiveness of sintilimab plus bevacizumab biosimilar compared with lenvatinib as first-line treatment in patients with unresectable or metastatic HCC. Methods A lifetime partitioned survival model was developed to conduct a cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar vs. lenvatinib for advanced HCC from a Chinese healthcare system perspective. The clinical and safety data were derived from two recent randomized clinical trials, the ORIENT-32 and REFLECT studies. Utility data were obtained from previous studies. Long-term direct medical costs and quality-adjusted life-years (QALYs) were predicted. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of the model. Results Compared with lenvatinib, combination therapy with sintilimab and bevacizumab biosimilar yielded an additional 0.493 QALYs at a higher cost ($33,102 vs. $21,037) (2021 US dollars). This resulted in a deterministic incremental cost-effectiveness ratio (ICER) of $24,462 per QALY in the base-case analysis. The ICERs were sensitive to the utility of post-progression and the cost of bevacizumab biosimilar. A lower ICER was estimated when the dose of bevacizumab biosimilar decreased from 15 mg to 7.5 mg per kilogram in the scenario analysis. In the probabilistic sensitivity analysis, the probability of being cost-effective for sintilimab treatment at willingness-to-pay (WTP) thresholds of one ($12,516) and three times the gross domestic product per capita in China ($37,547) were 11.6% and 88.6%, respectively. Conclusion Sintilimab plus bevacizumab biosimilar is likely to be a cost-effective treatment option as a first-line treatment for unresectable or metastatic HCC in China when WTP threshold is over $23,650.

Iron homeostasis plays an essential role in joint health, while iron overload can cause damage and death of cartilage cells. Cardamonin (CAR) is a substance found in the fruit of the chasteberry plant and has anti-inflammatory and anti-tumor activities. We first administered iron dextran (500 mg/kg) intraperitoneally to establish an iron overload mouse model and surgically induced osteoarthritis. The extent of OA and iron deposition were assessed using Micro-ct, Safranin-O/fast green staining, H&E staining, and Prussian Blue 10 weeks later. We administered primary chondrocytes with Ferric Ammonium Citrate (FAC) to evaluate the chondrocyte changes. Chondrocytes were identified in vitro by toluidine blue staining, and chondrocyte viability was evaluated by CCK-8. The rate of apoptosis was determined by Annexin V-FITC/PI assay. The mechanism of action of CAR was verified by adding the SIRT1 inhibitor EX527, and the expression of SIRT1 and MAPK signaling pathways was detected by Western blot. Iron overload also promoted chondrocyte apoptosis, a process that was reversed by CAR. In addition, CAR reduced NLRP3 inflammasome production via the SIRT1-MAPK pathway, and the SIRT1 inhibitor EX527 inhibited the treatment of OA by CAR.CAR inhibited cartilage degeneration induced by iron overload both in vivo and in vitro. Besides, our study showed that iron overload not only inhibited type II collagen expression but also induced MMP expression by catalyzing the generation of NLRP3 inflammasome. Our results suggest that CAR can treat KOA by promoting SIRT1 expression and inhibiting p38MAPK pathway expression to reduce the production of NLRP3 inflammasome vesicles.

Secretory immunoglobulin A (SIgA) is one of the most abundant immunoglobulin subtypes among mucosa, which plays an indispensable role in the first-line protection against invading pathogens and antigens. Therefore, the role of respiratory SIgA in respiratory mucosal immune diseases has attracted more and more attention. Although the role of SIgA in intestinal mucosal immunity has been widely studied, the cell types responsible for SIgA and the interactions between cells are still unclear. Here, we conducted a wide search of relevant studies and sorted out the relationship between SIgA and some pulmonary diseases (COPD, asthma, tuberculosis, idiopathic pulmonary fibrosis, COVID-19, lung cancer), which found SIgA is involved in the pathogenesis and progression of various lung diseases, intending to provide new ideas for the prevention, diagnosis, and treatment of related lung diseases.

Atrial fibrillation (AF) is a common clinical arrhythmia, primarily associated with the risk of stroke and various thromboembolic events, imposing significant clinical and economic burdens on patients and societies. This study aimed to review the relevant pharmacoeconomic evaluations of novel oral anticoagulants (NOACs) compared to vitamin K antagonists (VKAs) in patients with AF and explore the influencing factors and general trends of economic evaluations. This review qualitatively analyzed the basic characteristics, model structure, and basic results of all included studies. Moreover, a cross-sectional and longitudinal comparative analysis of costs, health outcomes, and cost-effectiveness results of studies in the United States, China, and the United Kingdom was conducted. Additionally, this study employed multivariate binary logistic regression to explore the influencing factors and general trends of the cost-effectiveness between NOACs and VKAs across all included studies. A total of 103 studies were included, comprising 218 comparisons between NOACs and VKAs. Total costs and health outcomes measured in studies with different countries and baseline characteristics exhibited considerable variations. However, NOACs generally had higher total costs than VKAs and resulted in more health outcomes for patients. The binary logistic regression analysis revealed that the country's economic development level, study perspective, and cycle length significantly influenced cost-effectiveness results. In high-income countries, NOACs are generally considered cost-effective, while VKAs may remain an attractive strategy in middle- and low-income countries. Additionally, factors such as drug prices, patient baseline characteristics, and model settings could impact the costs, health outcomes, and cost-effectiveness results of studies. Conducting relevant pharmacoeconomic research based on specific populations and study contexts is essential.

The paper aims to investigate social commerce systems from a systems thinking perspective. It proposes to model the social commerce process and outlines how Following, Communicating, Purchasing, and Sharing are systematically connected with each other in the social commerce process. The paper describes an exploratory review study using the systematic literature review method, including 384 social commerce research papers, which were published from 2011 to 2021. The data are refined by documentary analysis, including Study Selection Criteria and Quality Assessment processes. The paper systematically develops a conceptual framework for understanding social commerce. Previous research on social commerce mainly focuses on one or more particular key success factors (such as trust) in social commerce, and a few of them investigate social commerce as an integral business system. This review provides a more comprehensive basis for future social commerce research.

Purpose Non-small cell lung cancer (NSCLC) constitutes a substantial global health challenge, with surgical resection serving as a principal therapeutic approach. Nevertheless, the frequency of exploratory thoracotomy without en-bloc resection remains significant, particularly in advanced-stage cases, thereby adversely affecting prognosis. This study aims to predict risk scores for exploratory thoracotomy and analyze postoperative survival in patients with central NSCLC, utilizing CT (computed tomography) imaging subsequent to neoadjuvant therapy. Methods Clinical and radiological data of central NSCLC patients who underwent R0 resection or exploratory thoracotomy from January 2017 to June 2023 were retrospectively reviewed. Independent risk factors for exploratory thoracotomy were identified through a multivariate regression analysis. Subsequently, a nomogram model was developed to assess the risk of exploratory thoracotomy, and was validated through internal and external cohorts. Postoperative disease-free survival (DFS) and overall survival (OS) were analyzed using a Cox regression model. Results A total of 78 who underwent R0 resection following neoadjuvant therapy and 32 patients who underwent exploratory thoracotomy were included in the analysis. The nomogram model derived from tumor area and vascular deformation both identified as independent risk factors for exploratory thoracotomy, exhibited robust predictive performance. Furthermore, a tumor area of less than 250 mm² at the critical CT slice was associated with better DFS and OS following neoadjuvant therapy and R0 resection. Postoperative immunotherapy has the potential to extend survival in cases where exploratory thoracotomy was performed. Conclusion CT imaging at the critical slice post-neoadjuvant therapy is crucial for predicting the risk of exploratory thoracotomy and postoperative survival in patients with central NSCLC.

Background In the present study, we attempted to develop and validate a participatory competency model for medical workers and then evaluate the current status of competency characteristics of Chinese medical workers. Methods The competency model was constructed in a multistage process, including literature review, expert consultation, critical incident and focus group interview. A pilot study was conducted to refine the initial model among 90 participators and the viability and reliability were evaluated by a questionnaire survey among 121 medical workers. Then, the current status of competency characteristics was measured based on the final version of competency model. Results In the pilot study, ten questionnaires were dropped for the poor quality and thus the eligible rate was 92% (138/150). KMO value was 0.785 and Bartlett test showed that the χ 2  = 6464.546 (df = 903) and p value < 0.001. Then , 10 items with double loading and factor loading < 0.4 were deleted. Finally, 33 items were retained with the lowest factor loading value of 0.465. The validity and reliability of competency model were determined with Cronbach’s α coefficient of 0.975 and ICC value of 0.933. Finally, a revised competency model with 5 dimensions and 31 items was obtained. The overall competencies of current medical workers were in a high level, except for emergency knowledge related competencies. Age was an independent factor affecting the competencies. Conclusions Our competency model was a reliable and validated tool for assessing the competences of medical staffs against public health emergencies, and the overall competencies of current medical workers in China were in a high level, except for emergency knowledge related competencies.