Atherosclerosis （AS） is the main pathological basis of cardiovascular diseases and seriously threatens human quality of life. Its prevention and treatment urgently need breakthroughs. The inflammatory response， which runs through the physiological and pathological evolution process of AS， is one of the important mechanisms for AS occurrence. Currently， the treatment methods for AS in Western medicine are relatively mature. However， they have adverse reactions such as abnormal liver and kidney function， drug tolerance， target vessel restenosis， and stent thrombosis， which remain the key bottleneck restricting clinical efficacy. Traditional Chinese medicine （TCM）， characterized by multiple components， multiple targets， and multi-pathway synergy， shows unique clinical application potential and efficacy advantages in the intervention of AS. This article reviewed the research progress of TCM in intervening in AS by regulating inflammatory-related signaling pathways， such as nuclear factor-κB （NF-κB）， Toll-like receptors （TLRs）， mitogen-activated protein kinase （MAPK）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）， in the past five years. It summarized the combined mechanism of action of TCM monomers， TCM pairs， and compound preparations in inhibiting the inflammatory cascade reaction through multiple targets， regulating lipid metabolism disorders， and improving vascular endothelial dysfunction and the imbalance of the microenvironment. It deepened the research on the molecular mechanism of TCM in anti-AS， so as to provide a scientific basis for the clinical transformation application and related theoretical research of TCM in anti-AS.

Atherosclerosis （AS） is the main pathological basis of cardiovascular diseases and seriously threatens human quality of life. Its prevention and treatment urgently need breakthroughs. The inflammatory response， which runs through the physiological and pathological evolution process of AS， is one of the important mechanisms for AS occurrence. Currently， the treatment methods for AS in Western medicine are relatively mature. However， they have adverse reactions such as abnormal liver and kidney function， drug tolerance， target vessel restenosis， and stent thrombosis， which remain the key bottleneck restricting clinical efficacy. Traditional Chinese medicine （TCM）， characterized by multiple components， multiple targets， and multi-pathway synergy， shows unique clinical application potential and efficacy advantages in the intervention of AS. This article reviewed the research progress of TCM in intervening in AS by regulating inflammatory-related signaling pathways， such as nuclear factor-κB （NF-κB）， Toll-like receptors （TLRs）， mitogen-activated protein kinase （MAPK）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）， in the past five years. It summarized the combined mechanism of action of TCM monomers， TCM pairs， and compound preparations in inhibiting the inflammatory cascade reaction through multiple targets， regulating lipid metabolism disorders， and improving vascular endothelial dysfunction and the imbalance of the microenvironment. It deepened the research on the molecular mechanism of TCM in anti-AS， so as to provide a scientific basis for the clinical transformation application and related theoretical research of TCM in anti-AS.

Background/Aims: Non-pharmacological treatments are crucial for managing irritable bowel syndrome (IBS), yet patient engagement remains a challenge. Understanding patients' knowledge, attitudes, and practices regarding these treatments is essential for improving care. Methods: A cross-sectional study was conducted across 5 hospitals, from October 2023 to February 2024. A self-designed knowledge, attitudes, and practices questionnaire along with the IBS quality of life and IBS severity scoring system was administered, and 496 valid responses were analyzed. Statistical analyses included correlation tests, multivariate linear regression, and mediation effect analysis. Results: The median scores for knowledge, attitude, and practice were 28, 25.5, and 21, respectively. Significant positive correlations were found between knowledge-attitude (r = 0.195), knowledge-practice (r = 0.364), and attitude-practice (r = 0.151). The multivariate linear regression analysis further indicated that knowledge (β = 0.399, P < 0.001) and attitude (β = 0.219, P = 0.022) positively correlated with the practical performance. SEM revealed that knowledge had a significant direct effect on both attitude (β = 0.186, P = 0.013) and practice (β = 0.356, P = 0.006). However, the direct effect of attitude on practice was not significant, and attitude did not mediate the relationship between knowledge and practice. Conclusions IBS patients exhibit a significant gap between their positive attitudes and their actual practices concerning non-pharmacological treatments. Knowledge is a direct driver of practice, but positive attitudes alone are insufficient to translate into behavior. Healthcare providers must move beyond simply fostering positive attitudes and focus on targeted educational interventions that provide actionable knowledge and skills to improve patient outcomes.

Objective:To explore the potential mechanism underlying IL-6 production through the TLR7 signaling pathway,which regulates Th17 cell differentiation in the context of Coxsackievirus B3(CVB3)-induced acute viral myocarditis(AVMC).Meth-ods:A total of 110 patients diagnosed with AVMC were admitted to Quanzhou First Hospital,Fujian between January 2020 and Janu-ary 2023,alongside 93 healthy volunteers.CD4+T cells were isolated from the subjects'blood,and the levels of CVB3 and the number of Th17 cells were assessed.Subsequently,CD4+T cells were infected with CVB3,and the levels of Th17 cells,IL-17,IL-21,and TNF-α were measured.After knockdown of TLR7 or treatment with TLR7 inhibitors,the differentiation of CVB3-infected CD4+T cells into Th17 cells was observed.Results:In comparison to healthy controls,AVMC patients exhibited elevated plasma levels of hsCRP,IL-17,IL-21,and TNF-α(P<0.05).The levels of CVB3 mRNA in CD4+T cells were also notably higher in AVMC patients compared to healthy controls(P<0.05).The mean viral titer in AVMC patients measured 230 PFU/ml,while no detectable virus was found in healthy volunteers(P<0.05).In CD4+T cells,the count of Th17 cells was significantly increased in AVMC patients compared to healthy volunteers(P<0.05).Moreover,the number of Th17 cells in peripheral blood CD4+T cells of AVMC patients showed a positive correlation with CVB3 virus titer(P<0.05).Following CVB3 infection,the number of Th17 cells increased compared with the control group(P<0.05),accompanied by elevated levels of IL-17,IL-21,and TNF-α in the supernatant(P<0.05).Knockdown of TLR7 and CVB3 infection in CD4+T cells significantly reduced the levels of Th17 cells(P<0.05),while the expression level of phosphorylated-activated TLR7 increased significantly after CVB3 infection of CD4+T cells compared to the control group(P<0.05).Treatment with the TLR7 inhibitor M5049 and CVB3 infection led to a significant decrease in Th17 cell levels(P<0.05).The secretion of IL-6 in CD4+T cells increased after CVB3 infection(P<0.05),and this increase was mitigated by TLR7 knockdown and CVB3 infection(P<0.05)as well as TLR7 inhibitor M5049 treatment and CVB3 infection(P<0.05).Conclusion:CVB3 activates TLR7 via phosphoryla-tion,prompting CD4+T cells to release IL-6 and undergo differentiation into Th17 cells.Consequently,TLR7 emerges as a promising therapeutic target for AVMC.

Objective:To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes.Methods:The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis.Results:A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells ( t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage ( t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability ( t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells ( t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions:By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation.

Objective To observe the value of right ventricular free wall longitudinal strain(RVFWLS)to pulmonary artery systolic pressure(PASP)ratio(RVFWLS/PASP)for evaluating systolic function of right ventricle(RV)in patients with hypertrophic cardiomyopathy(HCM).Methods Fifty-two HCM patients were retrospectively collected and divided into group A(RVFWLS/PASP≤0.75,n=26)and B(RVFWLS/PASP＞0.75,n=26)according to median RVFWLS/PASP.Meanwhile,26 healthy individuals were included as control group.Parameters of echocardiography and speckle tracking imaging(STI)were obtained and compared among 3 groups.The correlations of RVFWLS/PASP and other parameters were analyzed with linear regression.Results In group A and B,left ventricular ejection fraction(LVEF),RV septal longitudinal strain(RVSepLS),RVFWLS,RV end-diastolic volume index(RVEDVi),RV stroke volume(RVSV),RV fractional area change(RVFAC)and left ventricular global longitudinal strain(LVGLS)were all lower,while the ratio of peak E blood flow velocity at mitral orifice diastole to early mitral intervalal annulus diastole velocity(E/e′)were higher than those in control group(all adjusted P＜0.05).Compared with group B and control group,group A had higher PASP but lower RV ejection fraction(RVEF)(all adjusted P＜0.05).Furthermore,RVFWLS and LVGLS were both lower in group A than in group B(both adjusted P＜0.05).Linear regression analysis showed that RVSepLS and RVEF were independently linearly related to RVFWLS/PASP(both P＜0.05).Conclusion RVFWLS/PASP could be used to monitor changes of RV systoic function in HCM patients at early stage.

Objective:To explore the potential mechanism underlying IL-6 production through the TLR7 signaling pathway,which regulates Th17 cell differentiation in the context of Coxsackievirus B3(CVB3)-induced acute viral myocarditis(AVMC).Meth-ods:A total of 110 patients diagnosed with AVMC were admitted to Quanzhou First Hospital,Fujian between January 2020 and Janu-ary 2023,alongside 93 healthy volunteers.CD4+T cells were isolated from the subjects'blood,and the levels of CVB3 and the number of Th17 cells were assessed.Subsequently,CD4+T cells were infected with CVB3,and the levels of Th17 cells,IL-17,IL-21,and TNF-α were measured.After knockdown of TLR7 or treatment with TLR7 inhibitors,the differentiation of CVB3-infected CD4+T cells into Th17 cells was observed.Results:In comparison to healthy controls,AVMC patients exhibited elevated plasma levels of hsCRP,IL-17,IL-21,and TNF-α(P<0.05).The levels of CVB3 mRNA in CD4+T cells were also notably higher in AVMC patients compared to healthy controls(P<0.05).The mean viral titer in AVMC patients measured 230 PFU/ml,while no detectable virus was found in healthy volunteers(P<0.05).In CD4+T cells,the count of Th17 cells was significantly increased in AVMC patients compared to healthy volunteers(P<0.05).Moreover,the number of Th17 cells in peripheral blood CD4+T cells of AVMC patients showed a positive correlation with CVB3 virus titer(P<0.05).Following CVB3 infection,the number of Th17 cells increased compared with the control group(P<0.05),accompanied by elevated levels of IL-17,IL-21,and TNF-α in the supernatant(P<0.05).Knockdown of TLR7 and CVB3 infection in CD4+T cells significantly reduced the levels of Th17 cells(P<0.05),while the expression level of phosphorylated-activated TLR7 increased significantly after CVB3 infection of CD4+T cells compared to the control group(P<0.05).Treatment with the TLR7 inhibitor M5049 and CVB3 infection led to a significant decrease in Th17 cell levels(P<0.05).The secretion of IL-6 in CD4+T cells increased after CVB3 infection(P<0.05),and this increase was mitigated by TLR7 knockdown and CVB3 infection(P<0.05)as well as TLR7 inhibitor M5049 treatment and CVB3 infection(P<0.05).Conclusion:CVB3 activates TLR7 via phosphoryla-tion,prompting CD4+T cells to release IL-6 and undergo differentiation into Th17 cells.Consequently,TLR7 emerges as a promising therapeutic target for AVMC.

Objective To observe the effects of electroacupuncture at"Neiguan"and"Gongsun"on autophagy and apoptosis related indexes of interstitial cells of Cajal(ICC)in rats with functional dyspepsia(FD);To explore its possible mechanism on improving gastrointestinal motility of FD.Methods Totally 32 SPF grade SD rats were randomly divided into blank group,model group,electroacupuncture group and Western medicine group,with 8 rats in each group.An FD model was constructed using a composite etiology modeling method.The electroacupuncture group received electroacupuncture at"Neiguan"and"Gongsun",while the Western medicine group received oral administration of mosapride once a day for 7 consecutive days.The general condition,body mass and average daily intake of rats were observed every week,and gastric emptying rate and small intestine propulsion rate were detected,transmission electron microscopy was used to observe the structure of gastric antrum ICC,Western blot was used to observe the expressions of c-kit,Beclin1,LC3Ⅱ/Ⅰ,p62,Caspase-3 protein in gastric antrum tissue,qPCR was used to observe the mRNA expressions of Beclin1,LC3Ⅱ/Ⅰ,p62 and c-kit in gastric antrum tissue,TUNEL staining was used to detect the apoptosis rate of cells in gastric antrum tissue.Results Compared with the blank group,the model group rats were mentally lethargic,clustered and curled up,with reduced activity,rough and dull hair,loose and unformed feces,reduced body mass and daily food intake(P<0.05),and gastric emptying rate and small intestine propulsion rate decreased(P<0.01),ICC mitochondria swelled and dissolved,with varying degrees of vacuolar formation,rough endoplasmic reticulum dilation and destruction,and a large number of autophagosomes,the expressions of Beclin1 and LC3 Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue increased(P<0.01),the expressions of p62,c-kit protein and mRNA decreased(P<0.01),while Caspase-3 protein expression increased(P<0.01),and the apoptosis rate of gastric antral tissue cells increased(P<0.01).Compared with the model group,the condition of rats in electroacupuncture group and the Western medicine group were improved,with increased responsiveness,increased mobility,neat hair,formed feces,increased body mass and daily food intake(P<0.01),and gastric emptying rate and small intestine propulsion rate increase(P<0.01),a normal ICC structure,and a small amount of autophagosomes were still visible,the expressions of Beclin1,LC3Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue decreased(P<0.01),the expressions of p62,c-kit protein and mRNA increased(P<0.01),while Caspase-3 protein expression decreased(P<0.01),and the apoptosis rate of gastric antral tissue cells decreased(P<0.01).There was no statistically significant difference in various indicators between electroacupuncture group and Western medicine group(P>0.05).Conclusion Electroacupuncture at"Neiguan"and"Gongsun"can restore the number and structure of ICC and improve gastrointestinal motility,and its mechanism may be related to the inhibition of autophagy and apoptosis levels.

Objective To explore the characteristics of the inhibitory effect of Evodiamine on the proliferation of activated T cells. Methods Mononuclear cells from peripheral blood (PBMCs) were obtained from healthy donors through density gradient centrifugation, and T cells were subsequently purified by using immunomagnetic bead separation. T cell activation was induced by employing anti-human CD3 and anti-human CD28 antibodies. T cells were treated with different concentrations of EVO (0.37, 1.11, 3.33, and 10)μmol/L. Flow cytometry was applied to evaluate the proliferation index, apoptosis rate, viability, CD25 expression levels, and cell cycle distribution of T cells. The expression levels of cytokines IL-2, IL-17A, IL-4, and IL-10 were quantified by using ELISA. Results 1.11, 3.33 and 10 μmol/L EVO effectively inhibited the proliferation of activated T cells, with an IC₅₀ of (1.5±0.3)μmol/L. EVO did not induce apoptosis in activated T cells and affect the survival rate of resting T cells. EVO did not affect the expression of CD25 and the secretion of IL-2 in activated T cells. EVO arrested the T cell cycle at the G2/M phase, resulting in an increase in G2/M phase cells, and exhibited a concentration-dependent effect. EVO did not affect the secretion of IL-4, IL-10 by activated T cells, but significantly inhibited the secretion of IL-17A. Conclusion EVO did not significantly affect the activation process of T cells but inhibited T cell proliferation by arresting the cell cycle at the G2/M phase and significantly suppressed the secretion of the pro-inflammatory cytokine IL-17A, which suggests that EVO has the potential to serve as a lead compound for the development of low-toxicity and high-efficiency immunosuppressants and elucidates the mechanisms underlying the anti-inflammatory and immunomodulatory effects of the traditional Chinese medicine Evodia rutaecarpa.
Humans ; Cell Proliferation/drug effects* ; Quinazolines/pharmacology* ; T-Lymphocytes/metabolism* ; Lymphocyte Activation/drug effects* ; Apoptosis/drug effects* ; Interleukin-4/metabolism* ; Interleukin-10/metabolism* ; Interleukin-2 Receptor alpha Subunit/metabolism* ; Interleukin-17/metabolism* ; Interleukin-2/metabolism* ; Cell Cycle/drug effects* ; Cells, Cultured

Objectives:To evaluate the outcomes of cochlear implantation in prelingually deafened late-implanted patients with regular cochlear implant use and to analyze the influencing factors of rehabilitation effects.Methods:This before-after self-controlled study design included 60 subjects, comprising 36 males and 24 females, who had received cochlear implantation at Chinese PLA General Hospital. Post-implantation, all patients demonstrated continuous and regular use of cochlear implants (≥8 hours daily). Rehabilitation outcomes were evaluated by using the Categories of Auditory Performance scale (CAP), Meaningful Auditory Integration Scale (MAIS), Speech Intelligibility of Rating scale (SIR), Meaningful Use of Speech Scale (MUSS) and speech recognition score (SRS) in 2018 and 2023. 9 potential risk factors were analyzed by univariate analysis with SPSS 25.0. The influencing factors associated with outcomes were evaluated through multivariate logistic regression.Results:Longitudinal data of 60 participants followed-up in 2018 and 2023 were analyzed. The average duration of cochlear implant use for all patients was (11.3±3.0) years. The mean score of CAP, SIR and MUSS improved significantly over time. The mean CAP score before surgery was (1.0±0.9). From 2018 to 2023, the mean CAP score improved from (5.1±1.4) to (5.9±1.6), with a statistical significance ( P<0.01); the mean SIR score before surgery was (1.3±0.5), and the mean SIR score improved from (2.7±1.1) to (3.2±1.3), with a statistical significance ( P<0.01); the mean MUSS score increased from (16.8±9.7) to (21.1±10.9) between the two follow-ups, with a statistical significance ( P<0.01); the MAIS was only initiated in the 2023 follow-up, with a mean score of (31.0±10.2). The speech recognition score for monosyllabic words increased from (23.9±16.0)% to (25.2±13.0)%, with no statistically significant difference ( P=0.66). Preoperative residual hearing significantly predicted rehabilitation outcomes at univariate analysis ( P<0.05), but the statistical significance was lost at multivariate analysis ( P>0.05). Age at implantation was identified as an independent predictive factor by both univariate and multivariate analysis (Hazard Ratio, 0.88; 95% Confidence Interval 0.79-0.97; P=0.014). The cut-off point for predicting further rehabilitation effects was 19.2 years old. In the correlation analysis of different scales, the CAP score was positively correlated with the total score of MAIS. So were the SIR score and the total score of MUSS. Conclusions:For prelingually deafened late-implanted patients with regular CI use, there was still potential for further improvement of auditory and speech abilities even after 10 years post-implantation. Age at implantation was an independent predictive factor and the cut-off point was 19.2 years old.