Search

Abstract Background Insomnia disorder (ID) is one of the most common sleep problems, usually accompanied by anxiety and depression symptoms. Functional magnetic resonance imaging (fMRI) study suggests that both poor sleep quality and negative emotion are linked to the dysregulation of brain network related to emotion processing in ID patients. Acupuncture therapy has been proven effective in improving sleep quality and mood of ID patients, but the involved neurobiological mechanism remains unclear. We aimed to investigate the modulation effect of acupuncture on resting-state functional connectivity (rsFC) of the emotional network (EN) in patients experiencing insomnia. Methods A total of 30 healthy controls (HCs) and 60 ID patients were enrolled in this study. Sixty ID patients were randomly assigned to real and sham acupuncture groups and attended resting-state fMRI scans before and after 4 weeks of acupuncture treatment. HCs completed an MRI/fMRI scan at baseline. The rsFC values within EN were calculated, and Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), Hyperarousal Scale (HAS), and actigraphy data were collected for clinical efficacy evaluation. Results Resting-state FC analysis showed abnormalities in rsFC centered on the thalamus and dorsolateral prefrontal cortex within EN of ID patients compared to HCs. After real acupuncture treatment, rsFC of the anterior cingulate cortex, hippocampus, and amygdala were increased compared with the sham acupuncture group (p

Abstract Pazopanib (PAZ), an oral multi-tyrosine kinase inhibitor, demonstrates promising cytostatic activities against various human cancers. However, its clinical utility is limited by substantial side effects and therapeutic resistance. We developed a nanoplatform capable of delivering PAZ for enhanced anti-breast cancer therapy. Nanometer-sized PAZ@Fe-MOF, compared to free PAZ, demonstrated increased anti-tumor therapeutic activities in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. High-throughput single-cell RNA sequencing (scRNAseq) revealed that PAZ@Fe-MOF significantly reduced pro-tumorigenic M2-like macrophage populations at tumor sites and suppressed M2-type signaling pathways, such as ATF6-TGFBR1-SMAD3, as well as chemokines including CCL17, CCL22, and CCL24. PAZ@Fe-MOF reprogramed the inhibitory immune microenvironment and curbed tumorigenicity by blocking the polarization of M2 phenotype macrophages. This platform offers a promising and new strategy for improving the cytotoxicity of PAZ against breast cancers. It provides a method to evaluate the immunological response of tumor cells to PAZ-mediated treatment.

Macrophage polarization facilitates the inflammatory response and intensified fibrosis in the silicosis microenvironment by a mechanism related to macrophage pyroptosis, although the upstream target remains poorly defined. Currently, there are few reports on the development of drugs that alleviate macrophage polarization by dampening pyroptosis. The present study aims to explore the mechanics of silica mediating macrophage polarization and to investigate whether quercetin (Que) can depolarize macrophages with this mechanism. Silica processing led to prominent M1 polarization of macrophages. Additionally, significant macrophage polarization could be detected in the lung tissue of mice with airway-perfused silica. Further investigation turned out that pronounced mitochondria damage, mtDNA cytoplasmic ectomy, and pyroptosis occurred in response to silica. Nevertheless, Que treatment could effectively attenuate silica-induced mitochondria damage and pyroptosis as demonstrated in vitro and in vivo. Further exploration presented Que could bind to TOM70 and restore silica-induced mitochondrial damage. More importantly, the M1 polarization of macrophage was depressed with the co-treatment of Que and silica, wherein the inflammatory response and pulmonary fibrosis were also mitigated without obvious damage to vital organs. In conclusion, these findings proved that silica leads to mitochondrial damage, thereby evoking pyroptosis and promoting macrophage M1 polarization. Que could bind to TOM70 and restore its function, suppressing mitochondrial damage and pyroptosis, and depolarizing macrophages to reduce fibrosis, which provides a promising strategy for silicosis treatment in the future.

Abstract Chemotherapeutic agents can inhibit the proliferation of malignant cells due to their cytotoxicity, which is limited by collateral damage. Dihydroartemisinin (DHA), has a selective anti-cancer effect, whose target and mechanism remain uncovered. The present work aims to examine the selective inhibitory effect of DHA as well as the mechanisms involved. The findings revealed that the Lewis cell line (LLC) and A549 cell line (A549) had an extremely rapid proliferation rate compared with the 16HBE cell line (16HBE). LLC and A549 showed an increased expression of NRAS compared with 16HBE. Interestingly, DHA was found to inhibit the proliferation and facilitate the apoptosis of LLC and A549 with significant anti-cancer efficacy and down-regulation of NRAS. Results from molecular docking and cellular thermal shift assay revealed that DHA could bind to epidermal growth factor receptor (EGFR) molecules, attenuating the EGF binding and thus driving the suppressive effect. LLC and A549 also exhibited obvious DNA damage in response to DHA. Further results demonstrated that over-expression of NRAS abated DHA-induced blockage of NRAS. Moreover, not only the DNA damage was impaired, but the proliferation of lung cancer cells was also revitalized while NRAS was over-expression. Taken together, DHA could induce selective anti-lung cancer efficacy through binding to EGFR and thereby abolishing the NRAS signaling pathway, thus leading to DNA damage, which provides a novel theoretical basis for phytomedicine molecular therapy of malignant tumors.

Abstract B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb–defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb–defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb–defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage–associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb–defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.

ObjectiveThe World Health Organization advocated for enhanced integration of traditional medicine and complementary medicine into national healthcare systems across all countries. This study aims to explore the progress and challenges in integrated traditional Chinese and western medicine (ITCWM) in China over 20 years using nationwide data.MethodsThis cross-sectional study examined various facets of ITCWM in China in terms of policies, resources, services, and funding. National policy documents from 2009 onwards were retrieved from official websites of the Chinese government. Data on ITCWM resources, services and subsidies from 2002 to 2021 were extracted from the China Statistical Yearbooks of Chinese Medicine and China Health Statistical Yearbooks. Research fund projects with the ITCWM discipline were collected from the database of National Natural Science Foundation of China. A mixed method of both quantitative and qualitative approaches was employed to present a comprehensive overview of the collected data.ResultsThis study presented five key findings. First, despite the issuance of 17 national policies by the Chinese government since 2009 to promote the development of traditional Chinese medicine (TCM), only three of them were specifically tailored for ITCWM. Second, although the average annual growth rates of ITCWM institutions, beds, and practitioners reached 0.35%, 10.56%, and 10.88% from 2002 to 2021, with more equitable allocation of ITCWM resources, the overall proportion of ITCWM remained below 5% in 2021. Third, progress has been made in ITCWM practices, yet service efficiency requires further enhancement. In 2021, ITCWM hospitals accounted for 2% of outpatient and emergency visits and 1.57% of hospital admissions among all hospitals, and 9.82% of delivered services were preventive healthcare services. Fourth, ITCWM served a crucial role in primary healthcare services, but its service capabilities need improvement. From 2007 to 2021, the average growth rates of ITCWM clinics, outpatient departments, and practitioners in outpatient departments were 13.30%, 2.57%, and 12.14%, respectively, while the proportion within TCM hospitals dropped. Lastly, despite the Chinese government’s emphasis on financial investment and related project funding for ITCWM, it remained lower than that allocated to TCM and western medicine.ConclusionITCWM played a pivotal role in China’s healthcare system to advance individuals’ health and well-being across the lifespan. In the future, China will provide further support to enhance ITCWM health resources and improve service capability, and the strategic integration of ITCWM into the broader healthcare system will play a crucial role in achieving universal health coverage and the Sustainable Development Goals.

Background: Chordoma is a rare congenital low-grade malignant tumor characterized by infiltrative growth. It often tends to compress important intracranial nerves and blood vessels, making its surgical treatment extremely difficult. Besides, the efficacy of radiotherapy and chemotherapy is limited. The photosensitizer hematoporphyrin derivative (HPD) can emit red fluorescence under 405 nm excitation and produce reactive oxygen species for tumor therapy under 630 nm excitation. Herein, we investigated the effects of the photosensitizer hematoporphyrin derivative (HPD) on different cell lines of chordoma and xenograft tumors under 405 nm and 630 nm excitation. Methods: The photosensitizer hematoporphyrin derivative (HPD) and Two different chordoma cell lines (U-CH1, JHC7) were used for the test. The in vitro experiments were as follows: (1) the fluorescence intensity emitted by chordoma cells excited by different 405 nm light intensities was observed under a confocal microscope; (2) the Cell Counting Kit-8 (CCK-8) assay was performed to detect the effects of different photosensitizer concentrations and 630 nm light energy densities on the activity of chordoma cells. In the in vivo experiments, (3) Fluorescence visualization of chordoma xenograft tumors injected with photosensitizer via tail vein under 405 nm excitation; (4) Impact of 630 nm excitation of photosensitizer on the growth of chordoma xenograft tumors. Results: (1) The photosensitizers in chordoma cells and chordoma xenografts of nude mice were excited by 405 nm to emit red fluorescence; (2) 630 nm excitation photosensitizer reduces chordoma cell activity and inhibits chordoma xenograft tumor growth in chordoma nude mice. Conclusion: Photodynamic techniques mediated by the photosensitizer hematoporphyrin derivatives can be used for the diagnosis and treatment of chordoma.

Abstract Background The overall comprehensive consideration of the factors influencing the recommendations in the traditional Chinese medicine (TCM) guidelines remains poorly studied. This study systematically evaluate the factors influencing recommendations formation in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) clinical practice guidelines (CPGs) and TCM CPGs. Methods This was a methodological review in which we searched six databases and multiple related websites. The GRADE CPGs were identified as the guidelines developed by the GRADE Working Group or the two Co-Chairs. For the TCM CPGs, we randomly selected guidelines that were published by the TCM or integrative medicine academic societies from China mainland (published by the TCM or integrative medicine academic societies of China mainland). Two reviewers independently screened and extracted data. We included CPGs published in 2018–2022. We extracted information on the influencing factors of evidence to recommendation and conducted the analyses using descriptive statistics and calculated the proportion of relevant items by IBM SPSS Statistics and Microsoft Excel to compare the differences between the GRADE CPGs and the TCM CPGs. Results Forty-five GRADE CPGs (including 912 recommendations) and 88 TCM CPGs (including 2452 recommendations) were included. TCM recommendations mainly considered the four key determinants of desirable anticipated effects, undesirable anticipated effects, balance between desirable and undesirable effects, certainty of evidence, with less than 20% of other dimensions. And TCM CPGs presented more strong recommendations (for or against) and inappropriate discordant recommendations than GRADE CPGs. GRADE CPGs were more comprehensive considered about the factors affecting the recommendations, and considered more than 70% of all factors in the evidence to recommendation. Conclusions The TCM CPGs lack a comprehensive consideration of multiple influencing determinants from evidence to recommendations. In the future, the correct application of the GRADE approaches should be emphasized.

Environmental pollution, including air pollution, plastic contamination, and heavy metal exposure, is a pressing global issue. This crisis contributes significantly to pollution-related diseases and is a critical risk factor for chronic health conditions, including cancer. Mounting evidence underscores the pivotal role of N6-methyladenosine (m6A) as a crucial regulatory mechanism in pathological processes and cancer progression. Governed by m6A writers, erasers, and readers, m6A orchestrates alterations in target gene expression, consequently playing a vital role in a spectrum of RNA processes, covering mRNA processing, translation, degradation, splicing, nuclear export, and folding. Thus, there is a growing need to pinpoint specific m6A-regulated targets in environmental pollutant-induced carcinogenesis, an emerging area of research in cancer prevention. This review consolidates the understanding of m6A modification in environmental pollutant-induced tumorigenesis, explicitly examining its implications in lung, skin, and bladder cancer. We also investigate the biological mechanisms that underlie carcinogenesis originating from pollution. Specific m6A methylation pathways, such as the HIF1A/METTL3/IGF2BP3/BIRC5 network, METTL3/YTHDF1-mediated m6A modification of IL 24, METTL3/YTHDF2 dynamically catalyzed m6A modification of AKT1, METTL3-mediated m6A-modified oxidative stress, METTL16-mediated m6A modification, site-specific ATG13 methylation-mediated autophagy, and the role of m6A in up-regulating ribosome biogenesis, all come into play in this intricate process. Furthermore, we discuss the direction regarding the interplay between pollutants and RNA metabolism, particularly in immune response, providing new information on RNA modifications for future exploration.

ObjectiveAcupuncture, acknowledged as a potent non-pharmacological therapy, is frequently employed to alleviate pain. Despite its widespread use, there has been a lack of overarching bibliometric analysis of clinical research on acupuncture analgesia. We aimed to summarize current patterns, hotspots, and development trends in this field through bibliometric analysis.MethodsThis study evaluates academic publications retrieved from the Web of Science database (2010.01–2023.09) concerning acupuncture analgesia in clinical settings. All primary and secondary studies on humans were included. To track global developmental trends, we employed several software for analyzing annual publication volumes, countries/regions, institutions, authors, cited authors, journals, cited journals, references, and keywords and to draw collaborative networks and reference co-citation network maps.ResultsThe final search encompassed 7,190 relevant studies, including 1,263 randomized controlled trials (RCTs) and 1,293 systematic reviews and meta-analyses. The results indicated a gradual increase in the number of annual publications on acupuncture analgesia in clinical practice. Among countries and institutions, China (2,139) and Chengdu University of Traditional Chinese Medicine (258) ranked first. Liang FR (89 articles) was the most prolific author, while MacPherson H (604) was the most cited author. MEDICINE (455) was the most productive journal, and Pain (2,473/0.20) ranked first in both the frequency and centrality of cited journals. Notably, the most frequently cited reference was a systematic review of individual patient data on acupuncture carried out for chronic pain that was published by Vickers Andrew J in 2012 (156). Burst analysis identified frontier research areas for 2010–2020, encompassing network meta-analysis, case reports, dry needling, lumbar disc herniation, cancer, post-herpetic neuralgia, insomnia, and bibliometric analysis.ConclusionThis study outlines current trends and potential future research hotspots in clinical acupuncture analgesia over the past decade. Findings emphasize the necessity for enhanced international collaboration to improve research output and translation.

Abstract Background Treatment options for pregnant women with immune thrombocytopenia (ITP) who do not respond to first-line treatment are limited. Few studies have reported the use of recombinant human thrombopoietin (rhTPO) for this subset of patients. Aims To investigate the efficacy and safety of rhTPO in ITP during pregnancy and determine obstetric outcomes and predictors of treatment response. Methods From July 2013 to October 2022, the data of 81 pregnant women with ITP and a platelet count 0.05, both). Compared with controls, rhTPO patients had higher platelet counts (median [interquartile range]: 42 [21.5–67.5] vs. 25 [19–29] × 109/L, P = 0.002), lower bleeding rate (6.1% vs. 25%, P = 0.027), and lower platelet transfusion rate before delivery (57.6% vs. 97.9%, P 0.05). No liver or renal function impairment or thrombosis cases were observed in the rhTPO group. GEE analysis revealed that the baseline mean platelet volume (MPV) (odds ratio [OR]: 0.522, P = 0.002) and platelet-to-lymphocyte ratio (PLR) (OR: 1.214, P = 0.025) were predictors of response to rhTPO treatment. Conclusion rhTPO may be an effective and safe treatment option for pregnancies with ITP that do not respond to first-line treatment; it may have slightly prolonged the gestational age of delivery. Patients with a low baseline MPV and high baseline PLR may be more responsive to rhTPO treatment. The present study serves as a foundation for future research.