OBJECTIVE: To investigate the effect of manual acupuncture manipulations (MAMs) on subcutaneous muscle tissue, by developing quantitative models of "lifting and thrusting" and "twisting and rotating", based on machine learning techniques. METHODS: A depth camera was used to capture the acupuncture operator's hand movements during "lifting and thrusting" and "twisting and rotating" of needle. Simultaneously, the ultrasound imaging was employed to record the muscle tissue responses of the participants. Amplitude and angular features were extracted from the movement data of operators, and muscle fascicle slope features were derived from the data of ultrasound images. The dynamic time warping barycenter averaging algorithm was adopted to align the dual-source data. Various machine learning techniques were applied to build quantitative models, and the performance of each model was compared. The most optimal model was further analyzed for its interpretability. RESULTS: Among the quantitative models built for the two types of MAMs, the random forest model demonstrated the best performance. For the quantitative model of the "lifting and thrusting" technique, the coefficient of determination (R²) was 0.825. For the "twisting and rotating" technique, R² reached 0.872. CONCLUSION Machine learning can be used to effectively develop the models and quantify the effects of MAMs on subcutaneous muscle tissue. It provides a new perspective to understand the mechanism of acupuncture therapy and lays a foundation for optimizing acupuncture technology and designing personalized treatment regimen in the future.
Humans ; Acupuncture Therapy/methods* ; Machine Learning ; Male ; Adult ; Female ; Subcutaneous Tissue/diagnostic imaging* ; Young Adult

Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

Background Ozone (O₃), a key air pollutant, significantly contributes to cardiovascular disease (CVD)-related mortality, with particularly pronounced effects in the elderly. Objective To explore the association between acute O₃ exposure and mortality from CVD and its subtypes in the elderly population in Jinan, and to investigate the modifying effects of gender,age, and seasonal factors on O₃-related effects, as well as to clarify the interaction with other air pollutants. Methods Daily mortality data for CVD, air pollutants, and meteorological parameters were collected in Jinan from 2015 to 2023. Generalized additive models (GAM) combined with distributed lag nonlinear models (DLNM) were used to analyze the lag effects of acute O₃ exposure on mortalities from CVD, ischemic heart disease (IHD), and stroke in elderly individuals aged ≥60 years. Subgroup analyses were conducted to explore effect differences by gender (male vs. female), age (non-high-aged elderly<80 years vs. high-aged elderly ≥80 years), and season (warm season: April–September vs. cold season: October–March of the following year). Relative excess risk due to interaction (RERI), attributable proportion of interaction (API), and Synergy index (SI) were used to assess the interactions of O₃ with PM_2.5 and NO₂. Results During the study period, the mean daily concentration of ozone reached (105.01 ± 54.18) μg·m⁻³, exceeding the Grade I limit value specified in Ambient Air Quality Standard (GB 3095–2012). Among the 203834 CVD deaths, IHD (53.07%) and stroke (33.33%) were the predominant mortality subtypes. The single-day lag analysis revealed peak excess risk (ER) for CVD mortality at lag0 (ER=0.64%, 95%CI: 0.29%, 1.00%) per 10 μg·m⁻³ O₃ increase. The cumulative effects peaked at lag04 (ER=1.61%, 95%CI: 0.77%, 2.46%). The subtype-specific analyses showed the maximal single-day effects at lag0 were identified for both IHD (ER=0.61%, 95%CI: 0.20%, 1.03%) and stroke (ER=0.65%, 95%CI: 0.19%, 1.11%), while the cumulative risks peaked at lag04 for IHD (ER=1.54%, 95%CI: 0.56%, 2.54%) and lag03 for stroke (ER=1.74%, 95%CI: 0.76%, 2.73%). The gender subgroup analyses suggested that both male and female subgroups showed the most significant impact on CVD mortality at lag0, with ER values of 0.53% (95%CI: 0.11%, 0.95%) and 0.75% (95%CI: 0.33%, 1.18%), respectively, but the differences were not statistically significant (P>0.05). No statistically significant difference in effect values was found between high-aged and non-high-aged elderly (P>0.05) after age subgroup analyses. The seasonal subgroup analyses indicated that the effects of O₃ on CVD and its subtypes in the warm season were significantly higher than those in the cold season (P<0.05). At lag0 in the warm season, the ER values for CVD, IHD, and stroke mortality were 0.86% (95%CI: 0.57%, 1.14%), 0.84% (95%CI: 0.49%, 1.19%), and 0.84% (95%CI: 0.43%, 1.26%), respectively. The interaction analyses revealed an antagonistic effect between O₃ and PM_2.5 on stroke mortality in the elderly [RERI=−4.64% (95%CI: −9.27%, −0.01%), API=−4.39% (95%CI: −8.77%, −0.01%), SI=0.55 (95%CI: 0.26, 0.84)]. The O₃ effect remained robust in the multi-pollutant models (P<0.05). Conclusion Acute O₃ exposure increases the risk of mortality from CVD and its subtypes in the elderly, and this effect is amplified in the warm season. Additionally, O₃ and PM_2.5 have an antagonistic effect on stroke mortality in the elderly.

Objective To explore the regulatory effect of miR-6838-5p on DDR1 gene expression and proliferation of breast cancer cells.Methods The expression levels of miR-6838-5p in normal breast epithelial cells and breast cancer cells were detected using qRT-PCR,and the potential target genes of miR-6838-5p was predicted using TargetscanV 8.0.Double luciferase reporter gene experiment was performed to verify the binding between miR-6838-5p and DDR1.Breast cancer MCF-7 cells were transfected via liposome,miR-6838-5p mimic,miR-6838-5p inhibitor,DDR1 siRNA,DDR1-overexpresisng vector,or both miR-6838-5p mimic and DDR1-overexpressing vector,and the changes in cell proliferation were examined with CCK-8 and EdU assays;Western blotting was used to detect the expression of DDR1.The mediating role of DDR1 in miR-6838-5p overexpression-induced inhibition of MCF-7 cell proliferation was verified in a nude mouse model bearing MCF-7 cell xenografts.Results The expression of miR-6838-5p was significantly lower in breast cancer cells than in normal breast epithelial cells.In MCF-7 cells,miR-6838-5p overexpression induced significant inhibition of cell proliferation.Dual luciferase reporter gene experiment demonstrated a binding relationship between miR-6838-5p and DDR1(P<0.01).Western blotting showed that miR-6838-5p overexpression significantly lowered DDR1 expression in MCF-7 cells,and DDR1 overexpression promoted proliferation of the cells;co-transfection of the cells with DDR1-overexpressing vector significantly attenuated the inhibitory effect of miR-6838-5p mimic on cell proliferation.In the tumor-bearing nude mice,the xenografts overexpressing miR-6838-5p showed a significantly smaller volum with obviously the expression of DDR1.Conclusion Overexpression of miR-6838-5p inhibits breast cancer cell proliferation by regulating DDR1 expression.

Objective To explore the regulatory effect of miR-6838-5p on DDR1 gene expression and proliferation of breast cancer cells.Methods The expression levels of miR-6838-5p in normal breast epithelial cells and breast cancer cells were detected using qRT-PCR,and the potential target genes of miR-6838-5p was predicted using TargetscanV 8.0.Double luciferase reporter gene experiment was performed to verify the binding between miR-6838-5p and DDR1.Breast cancer MCF-7 cells were transfected via liposome,miR-6838-5p mimic,miR-6838-5p inhibitor,DDR1 siRNA,DDR1-overexpresisng vector,or both miR-6838-5p mimic and DDR1-overexpressing vector,and the changes in cell proliferation were examined with CCK-8 and EdU assays;Western blotting was used to detect the expression of DDR1.The mediating role of DDR1 in miR-6838-5p overexpression-induced inhibition of MCF-7 cell proliferation was verified in a nude mouse model bearing MCF-7 cell xenografts.Results The expression of miR-6838-5p was significantly lower in breast cancer cells than in normal breast epithelial cells.In MCF-7 cells,miR-6838-5p overexpression induced significant inhibition of cell proliferation.Dual luciferase reporter gene experiment demonstrated a binding relationship between miR-6838-5p and DDR1(P<0.01).Western blotting showed that miR-6838-5p overexpression significantly lowered DDR1 expression in MCF-7 cells,and DDR1 overexpression promoted proliferation of the cells;co-transfection of the cells with DDR1-overexpressing vector significantly attenuated the inhibitory effect of miR-6838-5p mimic on cell proliferation.In the tumor-bearing nude mice,the xenografts overexpressing miR-6838-5p showed a significantly smaller volum with obviously the expression of DDR1.Conclusion Overexpression of miR-6838-5p inhibits breast cancer cell proliferation by regulating DDR1 expression.

Objective To investigate the protective effect of Toll-like receptor (TLR)2/TLR9 agonists,Pam2 CSK4(Pam)and CpG ODN (CpG)on mice infected with Acinetobacter baumannii (Ab)in the lungs.Methods Female C57 mice (6～8 weeks old)were randomly divided into PBS,Pam,CpG and Pam+CpG groups.In 24 h after intranasal immunization with different doses of the corresponding agonists,the mice were given a lethal dose of Ab infection in the lungs,and the survival rates of the mice were observed.A sublethal dose lung infection model of Ab was then established,and the bacterial colonization in the blood,lungs,liver,kidneys and spleen was measured respectively in the mice after infection.HE staining was used to observe the pathological damages in the lungs and kidneys.The protective effect of the agonists in the immunized mice against Ab was examined at 1,3 and 7 d after immunization to explore the protective time window.Pam+CpG was used to stimulate A549 cells and RAW264.7 cells to investigate the killing or phagocytic effects on Ab.Results Compared to PBS,Pam+CpG treatment significantly improved the survival rate of the mice after a lethal dose of Ab lung infection (P<0.05,P<0.01 ),reduced bacterial colonization in the blood (P<0.01 ),lungs (P<0.01 ),liver (P<0.01 ),kidneys (P<0.01 )and spleen (P<0.01 )in the mice after sublethal challenge,and alleviated pathological damage caused by infection. Immunization at 1 or 3 d before infection significantly improved the survival rate (P<0.05 ),and the protective effect was the best in 3 d after immunization.Furthermore,compared to single PBS,Pam and CpG immunization,Pam+CpG significantly promoted the killing and phagocytic effects of A549 epithelial cells and RAW264.7 cells,respectively,against Ab (P<0.01 ).Conclusion Combined application of TLR2/TLR9 agonists exerts a significant protective effect on both lethal and sublethal infections of Ab,which might be by its promoting the killing or phagocytic effect of lung epithelial cells and macrophages against Ab.

Objective To construct lipid nanoparticles(lipopeptide-lipid nanoparticle,LP-LNP)with novel lipopeptides as adjuvants,and initially explore their synergistic effect on mRNA vaccines.Methods Two novel lipopeptides,SS-10 and SQ18,were designed and synthesized.Microfluidic technology was used to encapsulate lipopeptides in different proportions,as well as mRNAs encoding enhanced green fluorescent protein(eGFP),firefly luciferase(F-luc),and ovalbumin(OVA)into lipid nanoparticles to construct an mRNA delivery system with novel lipopeptides as adjuvants(LP-LNP).The particle size and polydispersity coefficient of LP-LNP were measured using dynamic light scattering.The activation effect on Toll-like receptors 2(TLR2)was detected using HEK-BlueTM mTLR2 reporter cells to screen the optimal lipopeptide ratio.The preferred LP-LNP-eGFP-mRNA was transfected into HEK293T cells,and the expression of eGFP was observed under a fluorescence microscope.In vivo imaging was used to investigate the expression level of LP-LNP-F-luc-mRNA in mice.Flow cytometry was used to evaluate the ability of LP-LNP-OVA-mRNA to induce the maturation of dendritic cells(DCs)in draining lymph nodes and cross-presentation of antigens after immunization.Results Lipopeptides SQ18 and SS-10 were incorporated into LNP at 0.50％and 0.75％molar ratios,respectively,to obtain LP-LNP with uniform particle size,high encapsulation efficiency,and good in vitro safety.The ability of this formulation to activate TLR2 was significantly stronger than the positive control Pam2CSK4(P＜0.01).The preferred LP-LNP obtained effective in vitro transfection,and LP-LNP prepared with SQ18 at 0.50％molar ratio had significantly better in vivo transfection efficiency than traditional LNP(P＜0.01),and significantly promoted the maturation of DCs in draining lymph nodes and cross-presentation of antigens(P＜0.05).Conclusion LP-LNP with novel lipopeptides as adjuvants can enhance the delivery capacity of mRNA and further improve the immune effect of mRNA vaccines.

Objective This study aimed to investigate the physical activity status of liver transplant patients,explore the relevant influencing factors,and provide a basis for developing a physical activity management program for this population.Methods A convenience sampling method was used from January to May 2023 to investigate 250 liver transplant patients in a tertiary hospital in Guangzhou,using a general situation questionnaire,international physical activity questionnaire,exercise fear scale,and organ transplant patient symptom and happiness scale.Ordinal logistic regression analysis was used to analyze the relevant influencing factors of physical activity in liver transplant patients.Results 240 valid questionnaires were collected,and the median total metabolic equivalent of physical activity in liver transplant patients was 2 433(506,30263)MET-min/week patients.Ordinal logistic regression analysis revealed that body mass index(BMI),time to transplantation,postoperative follow-up,fear of exercise,and quality of life were significant factors influencing physical activity in liver transplant patients(P＜0.05).Conclusion Liver transplant patients have lower levels of physical activity,mainly with light activity intensity such as walking.Medical staff need to pay attention to the management of physical activity in liver transplant patients,especially for obese and low-quality of life patients.Postoperative follow-up should be strengthened to improve their fear of exercise and promote early and regular exercise.

AIM:To investigate of the effect of Shenqifuzheng injection(SFI)combined with PD-L1 antibody on tumor immune microenvironment and its efficacy.METHODS:A subcutaneous transplanta-tion tumor model for B16F10-LUC melanoma was created.The expression of Ki67,CD31,CD8,CD16,CD163,FOXP3,LY6C,LY6G with labeling antibodies was used to detect CD8+T cells,Treg cells,NK cells,MDSCs cells,centrocytes,and granulocytes in the tumor tissues via immunohistochemistry.Flow cy-tometry was used to measure the ratios of CD11c+,IA/IE+,and CD80+cells in splenic tissue,as well as the ratios of CD8+T,CD4+T,and Treg cells in tumor tissue.Additionally,granulocyte count and NK cell expression were analyzed.RESULTS:The immuno-histochemistry results indicate that the drug admin-istration group effectively suppressed tumor angio-genesis and cell proliferation,while decreasing the expression level of immunosuppressive cytokines CD4+T cells,Treg cells,MDSCs and centroblasts.Ad-ditionally,CD8 and NK cell infiltration was promot-ed compared to the control group.The results of the flow analysis demonstrated a significant in-crease in the expression level of CD8+T cells within tumor tissues,as well as inhibition of CD4+T,Treg,and DC cell infiltration within the spleen in the drug administration group.Additionally,the tumor volume analysis indicated that the drug administra-tion group effectively inhibited tumor growth.The flow results illustrate that the group administering treatment exhibited significant increases in CD8+T cell expression levels in tumor tissue and DC cells in the spleen.Furthermore,the treatment effec-tively inhibited the infiltration of CD4+T and Treg cells.The results also indicate that the treatment significantly reduced tumor growth,with the tumor inhibition rate being better with PD-L1 antibody alone than with the SFI group.Additionally,combin-ing drugs resulted in superior results compared to the PD-L1 antibody group alone.CONCLUSION:SFI combined with a PD-L1 antibody can have synergis-tic anti-tumor effects,potentially enhancing DC cell infiltration and promoting T cell activation.Immu-nohistochemistry results indicate a positive impact on the tumor immune microenvironment.

Objective To discuss the efficacy and safety of transarterial chemoembolization(TACE)and hepatic arterial infusion chemotherapy(HAIC)combined with tyrosine kinase inhibitors(TKI)and immune checkpoint inhibitors(ICI)for advanced hepatocellular carcinoma(HCC).Methods A total of 101 patients with unresectable HCC,who were admitted to the Affiliated Cancer Hospital of Harbin Medical University of China between January 2021 and October 2022 to receive treatment,were enrolled in this study.Of the 101 patients,50 received TACE+TKI+ICI therapy(TACE+TKI+ICI group)and 51 received HAIC+TKI+ICI therapy(HAIC+TKI+ICI group).The overall survival(OS)and the progression-free survival(PFS)were compared between the two groups,and the adverse events were analyzed to assess the safety of the therapeutic scheme.Results The median PFS in the TACE+TKI+ICI group was 12.0 months,which in the HAIC+TKI+ICI group was 11.0 months(P=0.030).The median OS was not achieved in the TACE+TKI+ICI group,which in the HAIC+TKI+ICI group was 14.6 months(P=0.005).The most common adverse effects in the TACE+TKI+ICI group were the elevation of total bilirubin(46.0％)and hepatic function injury(26.0％),which in the HAIC+TKI+ICI group were the decrease of albumin level(62.7％),fatigue(39.2％),and gastrointestinal reactions(31.4％).Conclusion For the treatment of advanced HCC,the therapeutic scheme of TACE+TKI+ICI has a better long-term survival benefits and the therapeutic scheme of HAIC+TKI+ICI can better maintain the liver function reserve of the patients.Neither therapeutic scheme shows any unexpected toxicity,and both therapeutic schemes have high clinical safety.(J Intervent Radiol,2024,33:543-548)