Objective To comprehensively analyze the current epidemic characteristics and disease burden of brucellosis in Tongliao City, and to provide a basis for the prevention and control strategy of brucellosis in Tongliao City. Methods The report data of brucellosis in Tongliao City from 2018 to 2023 were collected. Descriptive methods were used for data analysis, and the disability-adjusted life years and indirect economic losses were calculated. Results From 2018 to 2023, a total of 22 034 cases were reported in Tongliao City, with an average annual incidence of 136.17/100 000. The incidence was statistically different between men and women ( χ²=12.23, P=0.032). The majority of cases were farmers (94.25%), followed by herdsmen (1.67%). The age group was concentrated between 30-60 years old (79.30%), among which the majority of cases were in the 40-50 years group (6 883/22 034). The onset time had seasonal characteristics, and the peak period was from March to August (the seasonal index was between 115.40%-151.29%). In terms of regional distribution, cases were reported in all counties (banners). The average annual incidence was highest in Kulun Banner (233.85/100 000) and Zalut Banner (210.13/100 000), and lowest in Keerqin District (42.28/100 000) and Holingol City (31.87/100 000). The analysis of disease burden showed that a total of 677.55 person-years (YLD) were lost from 2018 to 2023, with an average annual loss of 112.92 person-years. The total indirect economic loss was 59.3576 million yuan, with an average annual loss of 9.892 9 million yuan, and the people over 60 years old had the lowest annual loss. Conclusion The overall brucellosis epidemic in Tongliao City has shown a fluctuating downward trend. The epidemic prevention and control should be strengthened in farmers, people aged 40-50 years old, and areas such as Zalut Banner and Kulun Banner to further control the epidemic of brucellosis.

By reviewing the physical biological research on the activation of acupoint effects by acupuncture， this paper explains the activation mechanism from the perspective of the generation and transmission of mechanical signals caused by acupuncture， and reveals the physical-chemical coupling processes in the acupoint microenvironment. Future research should focus on locally mechanosensitive cells， further exploring how acupuncture mechanical signals trigger dynamic changes in cells and molecules in the acupoints， and the physical-chemical information transduction mechanism， which will provide scientific evidence for the acupoint activation during acupuncture. Related studies will contribute to a deeper understanding of the scientific principles behind acupuncture and promote its clinical application and development.

Objective:This study aims to investigate the differences in hemostatic efficacy and patient comfort between an innovative domestically produced biodegradable nasal packing sponge and a traditional absorbent sponge following endoscopic nasal surgery. Methods:A prospective, randomized controlled trial design was utilized, including 30 patients who were divided into two groups according to random allocation, each receiving one of the two types of nasal packing. The study assessed the hemostatic efficacy, comfort, and safety of the materials by comparing the rates of no bleeding within 24 hours after packing, re-bleeding rates after 48 hours, pain ratings in the head and nasal areas, scores on a visual analog scale for nasal ocular symptoms, and safety indicators between the two groups. Results:The rates of no bleeding within 24 hours post-packing were 73.33% for both the experimental and control groups, with a no-bleeding rate of 100% after 48 hours in both groups. The pain rating in the head and nasal areas at various times post-packing was Grade Ⅰ（100%） in both groups, with no statistically significant difference（P=1.000）. The experimental groups sneezing score on the day of packing was（0.73±1.03）, lower than the control groups（2.27±1.67）, （P=0.007）; after 48 hours, the experimental groups sneezing score was（0.67±0.98）, also lower than the control groups（1.67±1.18）, （P=0.019）. There was no significant difference between the two groups in the Lund-Kennedy scoring during endoscopic examinations at the screening period, 7 days, 1 month, and 3 months post-packing（P>0.05）. Laboratory tests for other examination indicators were normal in both groups. Conclusion:The innovative domestically produced biodegradable nasal packing sponge not only provides hemostatic efficacy comparable to imported materials but also significantly improves patient comfort after surgery. It represents an economical and effective choice for nasal packing materials.
Humans ; Prospective Studies ; Surgical Sponges ; Endoscopy/methods* ; Male ; Female ; Epistaxis/prevention & control* ; Middle Aged ; Nasal Surgical Procedures/methods* ; Adult

Head and neck tumors are one of the major diseases that threaten human health. Targeted chemotherapy is an important treatment for head and neck tumors. However, many anti-cancer drugs are difficult to reach effective concentrations in tumors and can cause damage to normal tissues. Therefore, the efficient delivery of anti-tumor drugs, improvement of their therapeutic effects, and reduction of their adverse effects on the whole body and locally are urgent issues in targeted drug research. Liposomes have been widely studied due to their unique characteristics, including amphiphilicity, biocompatibility, biodegradability, and low toxicity. This article outlines the current applications and prospects of liposome drug delivery systems in different treatment modalities for head and neck tumors in recent years, aiming to provide more options for the treatment of head and neck tumors.
Humans ; Liposomes ; Head and Neck Neoplasms/drug therapy* ; Drug Delivery Systems ; Antineoplastic Agents/administration & dosage*

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo, showing huge promise for the active treatment of biofilm-associated infections.

Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

OBJECTIVES: To investigate the mechanism by which transforming growth factor‑β (TGF‑β) regulates major histocompatibility complex class I (MHC-I) expression in hepatocellular carcinoma (HCC) cells and its role in immune evasion of HCC. METHODS: HCC cells treated with TGF‑β alone or in combination with SB-431542 (a TGF-β type I receptor inhibitor) were examined for changes in MHC-I expression using RT-qPCR and Western blotting. A RNA interference experiment was used to explore the role of miR-23a-3p/IRF1 signaling in TGF‑β‑mediated regulation of MHC-I. HCC cells with different treatments were co-cultured with human peripheral blood mononuclear cells (PBMCs), and the changes in HCC cell proliferation was assessed using CCK-8 and colony formation assays. T-cell cytotoxicity in the co-culture systems was assessed with lactate dehydrogenase (LDH) release and JC-1 mitochondrial membrane potential assays, and T-cell activation was evaluated by flow cytometric analysis of CD69 cells and ELISA for TNF-α secretion. RESULTS: TGF‑β treatment significantly suppressed MHC-I expression in HCC cells and reduced T-cell activation, leading to increased tumor cell proliferation and decreased HCC cell death in the co-culture systems. Mechanistically, TGF-β upregulated miR-23a-3p, which directly targeted IRF1 to inhibit MHC-I transcription. Overexpression of miR-23a-3p phenocopied TGF‑β‑induced suppression of IRF1 and MHC-I. CONCLUSIONS We reveal a novel immune escape mechanism of HCC, in which TGF‑β attenuates T cell-mediated antitumor immunity by suppressing MHC-I expression through the miR-23a-3p/IRF1 signaling axis.
Humans ; MicroRNAs/genetics* ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Interferon Regulatory Factor-1/metabolism* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Histocompatibility Antigens Class I/metabolism* ; Cell Line, Tumor ; Tumor Escape ; Coculture Techniques

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China