Breast cancer has become the malignant tumor with the highest incidence rate among women， seriously threatening the life and health of women all over the world. The pathogenic factors and development mechanisms of breast cancer are complex and diverse. The development of breast cells from ordinary hyperplasia to atypical hyperplasia， and from pre-cancerous lesions to cancerous lesions， is a long-term progressive process. Therefore， early screening and prevention of breast cancer is particularly important. Western medicine has a relatively mature treatment program for breast cancer， which is mainly based on surgery and systemic treatment， whereas the ensuing complications and adverse reactions often bring a heavy burden to patients. For the precancerous lesions of breast cancer， surgery is also the mainstay of treatment. In recent years， traditional Chinese medicine （TCM） has increasingly highlighted its advantages in the prevention and treatment of breast cancer. Increasing studies have shown that in the prevention and treatment of breast cancer and pre-cancerous lesions， TCM compound prescriptions， single herbs or herb pairs， and active components are able to regulate a variety of intracellular signaling pathways through multi-targets to inhibit the proliferation and invasion， promote the apoptosis and autophagy of tumor cells， and regulate the cell cycle and the immune microenvironment， thus exerting anti-tumor effects. At the same time， they can significantly attenuate the toxic side effects of radiotherapy and drug resistance of patients. However， the specific mechanisms of TCM in the prevention and treatment of breast cancer and precancerous lesions have not been fully clarified. The available studies are tanglesome regarding the TCM inhibition of tumor development through the regulation of classical signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Wnt/β-catenin， and Notch， which still need to be verified by a large number of clinical and experimental studies. Therefore， this paper reviews the research progress in the prevention and treatment of breast cancer and precancerous lesions by TCM through interfering with the relevant signaling pathways in recent years， aiming to summarize the possible mechanisms of TCM in the prevention and treatment of breast cancer and provide references for subsequent studies.

Objective To systematically review international research on health communication, and to provide valuable insights and reference for China's health communication research and practice. Methods This study included 693 articles published from January 2023 to April 2024 in two authoritative academic journals in the field of health communication, ^“Health Communication^” and the ^“Journal of Health Communication^”. A systematic review was conducted on the themes, theoretical foundations, research methods, and populations of international health communication research. Results The findings in this study revealed that international health communication research topics were diverse, with hotspots including social media, health information behavior, health misinformation, stigmatization, trust, and risk perception. The results showed that 34% of the articles were based on theoretical foundations, and 93.3% employed research methods, focusing on adolescents, parents, women, and other key populations. Conclusion Domestic health communication research can expand its perspective from ^“information transmission^” to ^“social interaction^”, innovate theories and methods from ^“single paradigm" to ^“multi-integration^” and shift focus from a ^“mass perspective^” to ^“targeted care^” for the health of all populations. Domestic health communication practice can delve into the localization of social media health communication practices, the comprehensive management of health misinformation, and the critical application of new technologies.

OBJECTIVE To analyze the distribution characteristics of mirtazapine steady-state trough concentration and concentration-to-dose ratio （ C / D ）， and to investigate the influence of clinical and genetic factors on C / D . METHODS A retrospective study was conducted on hospitalized patients with depression who received mirtazapine treatment and underwent therapeutic drug monitoring at the First Hospital of Hebei Medical University from May 2022 to May 2025. The collected data included patients’ gender， age， body mass index， daily dose， steady-state trough concentration， smoking status， history of liver disease， drug type， concomitant medications， and CYP2D6 metabolic phenotype. The C / D was calculated. Spearman rank correlation was used to analyze the relationship between mirtazapine steady-state trough concentration and daily dose. Univariate analysis and multiple linear regression model were employed to screen the factors potentially influencing the C / D of mirtazapine. RESULTS A total of 226 patients were included. The daily dose of mirtazapine was 25.00 （24.82， 30.00） mg/d， the steady-state trough concentration was 44.46 （20.00， 70.00） ng/mL， and the C / D was 1.83 （1.00， 2.00） （ng·d）/（mL·mg）. Steady-state trough concentrations were within the reference range （30-80 ng/mL） in 121 patients （53.54%）， below the lower limit in 80 patients （35.40%）， and above the upper limit in 25 patients （11.06%）. A positive correlation was observed between mirtazapine steady-state trough concentration and daily dose （coefficient of determination was 0.320 8， P ＜0.001）. Gender， smoking status， and CYP2D6 metabolic phenotype were significantly associated with the mirtazapine C / D （ P ＜0.05）. CONCLUSIONS Significant interindividual variability exists in mirtazapine steady-state trough concentrations. Gender， smoking status， and CYP2D6 metabolic phenotype are identified as independent influencing factors for the mirtazapine C / D ， with higher C / D ratios observed in females， non-smokers， and intermediate metabolizers.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

OBJECTIVE: To observe the clinical efficacy of different acupuncture methods in the treatment of ankylosing spondylitis (AS) at different stages. METHODS: Thirty-two patients with AS were treated with acupuncture at ashi points (tendon focus), triple acupuncture method was used in the acute phase, accompanied needling method was used in the remission phase, once a day, 5 times a week for 4 weeks. The Bath ankylosing spondylitis disease activity index (BASDAI) score, Bath ankylosing spondylitis functional index (BASFI) score and TCM symptom grade quantitative standard score before and after treatment were observed, and the efficacy was evaluated. RESULTS: After treatment, the BASDAI score, BASFI score and TCM symptom grade quantitative standard score were reduced compared with those before treatment (P<0.01), the effective rate was 96.9% (31/32). CONCLUSION Different acupuncture methods in the treatment of AS at different stages could improve signs and symptoms, such as pain, activity limitation and morning stiffness.
Humans ; Spondylitis, Ankylosing/physiopathology* ; Acupuncture Therapy/methods* ; Male ; Female ; Adult ; Middle Aged ; Young Adult ; Acupuncture Points ; Treatment Outcome

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the intestinal flora in rats with chronic obstructive pulmonary disease (COPD) and explore its possible mechanism based on the gut-lung axis theory. METHODS: A total of 30 male SD rats of SPF grade were randomly divided into a normal control (NC) group, a model group and an EA group, 10 rats in each one. In the model group and the EA group, COPD model was established by intratracheal instillation of lipopolysaccharide combined with cigarette fumigation. In the EA group, EA was applied at bilateral "Feishu" (BL13) and "Zusanli" (ST36), with disperse-dense waves, in frequency of 4 Hz/20 Hz, current of 1-3 mA, 20 min a time, once a day for 14 days continuously. Before and after modeling, as well as after intervention, body weight was observed; after intervention, the lung function indexes (forced expiratory volume in 0.1 second [FEV_0.1], FEV_0.1/forced vital capacity [FVC]%, forced expiratory volume in 0.3 second [FEV_0.3] and FEV_0.3/FVC%) were measured, serum levels of inflammatory factors (tumor necrosis factor-α[TNF-α], interleukin-6[IL-6], interleukin-1β[IL-1β] and interleukin-10[IL-10]) were detected by ELISA, histopathology of lung and colon tissues was observed by HE staining, the intestinal flora were analyzed by 16S rRNA, and the correlations between lung function and intestinal flora were analyzed. RESULTS: Compared with the NC group, in the COPD group, the body weight and lung function indexes were reduced (P<0.01); the lung and colon tissues were damaged, the mean linear intercept (MLI) of alveolus and inflammatory cell numbers of 100 μm² in lung tissue were increased (P<0.01); the serum levels of TNF-α, IL-6 and IL-1β were increased (P<0.01, P<0.05), and the serum level of IL-10 was decreased (P<0.01); α-diversity indexes of intestinal flora were increased (P<0.01); the relative abundance of Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus was increased (P<0.01), the relative abundance of Firmicutes, Actinobacteria, Tenericutes, TM7 and Lactobacillus, Allobaculum, Bifidobacterium, YRC22 was decreased (P<0.01, P<0.05); 31 different expressed metabolic pathways were identified between the two groups. Compared with the COPD group, in the EA group, the body weight and lung function indexes were increased (P<0.01); the damage of lung and colon tissues was improved, the MLI of alveolus was decreased (P<0.05); the serum levels of TNF-α, IL-6 and IL-1β were decreased (P<0.05), and the serum level of IL-10 was increased (P<0.05); α-diversity indexes of intestinal flora were decreased (P<0.01); the relative abundance of Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus was decreased (P<0.01, P<0.05), the relative abundance of Firmicutes, Actinobacteria, Tenericutes, TM7 and Lactobacillus, Allobaculum, Bifidobacterium, YRC22 was increased (P<0.01); 35 different expressed metabolic pathways were identified between the two groups. The lung function was positive related with Actinobacteria, Tenericutes, TM7 and YRC22, and was negative related with Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus. CONCLUSION EA may ameliorate lung function and tissue injury of COPD by regulating intestinal flora dysbiosis and inflammatory response, suggesting an anti-inflammatory effect mediated via "gut-lung" axis.
Animals ; Pulmonary Disease, Chronic Obstructive/genetics* ; Male ; Electroacupuncture ; Rats ; Rats, Sprague-Dawley ; Lung/metabolism* ; Gastrointestinal Microbiome ; Humans ; Interleukin-6/immunology* ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/microbiology* ; Interleukin-10/immunology*

BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome