Objective:This study aims to investigate the role of fatty acid-binding protein 4 (FABP4) in endothelial-to-mesenchymal transition (EndMT) during the formation of idiopathic pulmonary fibrosis (IPF) and its possible mechanism, and to evaluate the therapeutic potential ofFABP4 inhibitor BMS309403.Methods:A bleomycin (BLM)-induced mouse model of pulmonary fibrosis was established for in vivo experiments.hematoxylin-eosin(HE)and Masson staining were used to assess the histopathological changes and collagen deposition in lung tissue, while western blotting (WB) was used to assess EndMT-related protein expression in lung tissue.In vitro, human umbilical vein endothelial cells (HUVEC) were treated with transforming growth factor-β (TGF-β) to induce the EndMT model.After intervention with FABP4 protein or BMS309403, the expression levels of EndMT related genes and peroxisome proliferator-activated receptor γ (PPAR γ) were detected.Results:BLM-induced mice showed significant pulmonary fibrosis, inflammatory infiltration, and EndMT (upregulated expression of Fibronectin and α-SMA proteins expression, downregulated expression of VE cadherin and CD31 proteins), and BMS309403 treatment significantly alleviated these pathological changes.In vitro experiments confirmed that TGF-β could successfully induce EndMT in HUVECs, FABP4 enhanced the induction effect of TGF-β on EndMT, and BMS309403 could effectively reverse this effect.The co-treatment with TGF-β and FABP4 significantly inhibited the expression of PPARγ, BMS309403 significantly alleviated these changes.Conclusions:FABP4 may promote pulmonary fibrosis progression by facilitating EndMT through the PPARγ signaling pathway.FABP4 may serve as a promising therapeutic target for IPF.

Aim To explore the mechanism of clar-ithromycin in treating inflammatory bowel disease(IBD)by inhibiting Kv1.3 channel protein in colonic epithelial cells.Methods A chronic IBD rat model was induced using dextran sulfate sodium(DSS)in vi-vo experiments,with clarithromycin intervention.The physical signs of each group of rats were observed,and the disease activity index(DAI)score and colonic mu-cosal damage index(CMDI)score were calculated.RT-qPCR was used to detect the levels of relevant cyto-kines in colonic tissue of rats.Flow cytometry was em-ployed to detect the relative proportions of immune cells in the peripheral blood and colonic tissue of each group of rats.Lipopolysaccharide(LPS)was used to establish an inflammation model of colon epithelial cells(NCM460)to clarify the inhibitory effect of clar-ithromycin on Kv1.3 channel protein.Results In vi-vo experiments:compared to the model group,the clar-ithromycin intervention group exhibited a reduced de-gree of weight loss(P＜0.01),and a significant de-crease in DAI scores(P＜0.01).There was an in-crease in colon length,a reduction in weight,and a de-crease in CMDI scores(P＜0.05).Levels of TNF-α,IL-1 β,and IL-6 in colon tissue were significantly re-duced(P＜0.01).The numbers of peripheral blood and colonic regulatory T lymphocytes(Th),cytotoxic T lymphocytes(CTL),natural killer cells(NK),B lym-phocytes(B),and dendritic cells(DC)were signifi-cantly decreased(P＜0.05).Clarithromycin reduced the expression of Kv1.3 channel protein in colon tissue(P＜0.05).In vitro experiments:compared to the model group,the clarithromycin group significantly pro-moted the proliferation of NCM460 cells(P＜0.01)and simultaneously significantly reduced the levels of TNF-α and IL-6 in cells(P＜0.05).Clarithromycin also reduced the expression of Kv1.3 channel protein in NCM460 cells(P＜0.05).Conclusions Clar-ithromycin may play an immunomodulatory role by in-hibiting the expression of Kv1.3 channel protein,re-ducing inflammation in the body,and playing a role in the treatment of IBD.

Aim To explore the mechanism of clar-ithromycin in treating inflammatory bowel disease(IBD)by inhibiting Kv1.3 channel protein in colonic epithelial cells.Methods A chronic IBD rat model was induced using dextran sulfate sodium(DSS)in vi-vo experiments,with clarithromycin intervention.The physical signs of each group of rats were observed,and the disease activity index(DAI)score and colonic mu-cosal damage index(CMDI)score were calculated.RT-qPCR was used to detect the levels of relevant cyto-kines in colonic tissue of rats.Flow cytometry was em-ployed to detect the relative proportions of immune cells in the peripheral blood and colonic tissue of each group of rats.Lipopolysaccharide(LPS)was used to establish an inflammation model of colon epithelial cells(NCM460)to clarify the inhibitory effect of clar-ithromycin on Kv1.3 channel protein.Results In vi-vo experiments:compared to the model group,the clar-ithromycin intervention group exhibited a reduced de-gree of weight loss(P＜0.01),and a significant de-crease in DAI scores(P＜0.01).There was an in-crease in colon length,a reduction in weight,and a de-crease in CMDI scores(P＜0.05).Levels of TNF-α,IL-1 β,and IL-6 in colon tissue were significantly re-duced(P＜0.01).The numbers of peripheral blood and colonic regulatory T lymphocytes(Th),cytotoxic T lymphocytes(CTL),natural killer cells(NK),B lym-phocytes(B),and dendritic cells(DC)were signifi-cantly decreased(P＜0.05).Clarithromycin reduced the expression of Kv1.3 channel protein in colon tissue(P＜0.05).In vitro experiments:compared to the model group,the clarithromycin group significantly pro-moted the proliferation of NCM460 cells(P＜0.01)and simultaneously significantly reduced the levels of TNF-α and IL-6 in cells(P＜0.05).Clarithromycin also reduced the expression of Kv1.3 channel protein in NCM460 cells(P＜0.05).Conclusions Clar-ithromycin may play an immunomodulatory role by in-hibiting the expression of Kv1.3 channel protein,re-ducing inflammation in the body,and playing a role in the treatment of IBD.

Objective:To analyze the correlation of ultrasonic shear wave elastography (SWE) and ultrasonic contrast with different molecular types of breast cancer was analyzed.Methods:A total of 100 patients with breast cancer admitted to our hospital from Jun. 2019 to Jun. 2024 were included, and general data of patients were collected. Patients were divided into lumen type, human epidermal growth factor receptor 2 (HER2) positive type and triple-negative type according to molecular classification. SWE imaging parameters [mean elastic modulus (Emean), maximum elastic modulus (Emax), standard deviation (Esd) ], quantitative parameters of contrast-enhanced ultrasound [peak intensity (PI), time to peak (TTP) ], qualitative parameters of ultrasonic contrast (enhancement speed, enhancement intensity, lesion expansion after enhancement, lesion margin, perfusion defect, vascular penetration) were compared. The correlation of ultrasonic SWE parameters, ultrasonic contrast parameters with different molecular types of breast cancer was analyzed.Results:Among 100 breast cancer patients, 48 were luminal type, 34 were HER2 overexpression type, and 18 were triple-negative type. There was no statistically significant difference in age, tumor diameter, tumor location, case cytology type, Emean, Esd, TTP, lesion expansion after enhancement, lesion margin, perfusion defect, or vascular penetration among three groups ( F=0.21, 1.28, 2.47, 0.91, x2=2.29, 0.62, 0.03, 4.88, 0.96, 0.64, 3.10, P > 0.05). Pathological grade, Emax, enhancement speed, enhancement intensity and PI among the three groups showed statistically significant differences, and the Emax and PI of luminal patients were significantly lower than those of HER2 overexpression type and triple-negative type ( χ2=13.28, 24.06, 17.90, F=11.65, 5.75, P < 0.05) ; Emax, enhancement velocity, enhancement intensity and PI in ultrasonic SWE parameters of breast cancer patients were correlated with different molecular types ( r=0.37, 0.40, 0.52, 0.32, P < 0.05) . Conclusions:Ultrasonic SWE and ultrasonic contrast have differences in different molecular types of breast cancer. There were significant differences in Emax, enhancement speed, enhancement intensity and PI among patients with different molecular types. The Emax and PI of HER2 overexpression type and triplenegative type are significantly higher, and Emax, enhancement speed, enhancement intensity and PI are significantly correlated with molecular typing of breast cancer.

STC is a kind of clinically common functional gastrointestinal disease.Its pathogenesis hasn't been completely clarified,and current diagnosis and treatment norms are certainly limited.In recent years,"Brain-Gut Axis"theory has unveiled the complex bidirectional regulation mechanism between brain and intestinal tract,rendering new perspective for the research and treatment of STC.TCM theory demonstrates that there is close connection between brain and gut,has formed abundant experience in discrimination and treatment of STC and formed unique diagnosis and treatment ideas.Based on the theory of"Brain-Gut Axis"and"excess syndrome is corresponding to Zhanyu,deficiency syndrome is corresponding to Zhengsheng"in the chapter on Yangming diseases in"Treatise on Febrile Diseases",this paper elaborates on the relationship between the"Brain-Gut Axis"and STC.Meanwhile,by combining the theory of"excess syndrome is corresponding to Zhanyu,deficiency syndrome is corresponding to Zhengsheng"with the"Brain-Gut Axis"theory,it analyzes the influence of the excess and deficiency of the Yangming meridian on the mental state as well as the regulatory mechanism of the"Brain-Gut Axis",and puts forward corresponding treatment methods according to different syndromes.By integrating the relevant provisions in"Treatise on Febrile Diseases"with the"Brain-Gut Axis"theory of modern medicine,this paper makes a preliminary exploration of the laws of differentiating and treating STC,aiming to provide a theoretical basis for promoting a more comprehensive understanding of the pathogenesis of STC and developing more effective treatment strategies.

Objective To investigate the effects of electroacupuncture at"Zusanli"(ST36)on type 3 innate lymphoid cells(ILC3s)secreting interleukin(IL)-22 and intestinal cholinergic neurons in the colon of mice with inflammatory bowel disease(IBD),and to explore the mechanisms underlying electroacupuncture-mediated amelioration of IBD.Methods Twenty-four male C57BL/6J mice were divided into a normal group(n=8)and a modeling group(n=16)using the random number table method.The modeling group received 4％dextran sulfate sodium solution ad libitum for 7 days to establish the IBD model.On the fourth day after modeling,the modeling group was divided into a model group and an electroacupuncture group using the random number table method,with eight mice per group.Electroacupuncture intervention was applied bilaterally at"Zusanli"(ST36)in mice of the electroacupuncture group,once daily for 20 min each time,for seven consecutive days.After intervention,stool characteristics and occult blood were assessed.The disease activity index(DAI)of mice in each group was scored,and colon length was measured.The morphology of the colon tissue in mice was observed using hematoxylin-eosin staining,and the histopathological score was determined.A cytometric bead array was used to detect the contents of IL-1β,tumor necrosis factor-α(TNF-α),and IL-6 in colon tissue.Flow cytometry was used to determine the IL-22+ILC3s proportion in lamina propria lymphocytes of colon tissue.The content of IL-22 in colon tissue was detected using an enzyme-linked immunosorbent assay.Immunofluorescence was used to detect the number of choline acetyltransferase(ChAT)+/cellular Fos(c-Fos)+co-labeled neurons in colon tissue.Results Compared with the normal group,mice in the model group exhibited different degrees of loose stools,strongly positive fecal occult blood test,elevated DAI scores,shortened colon length,increased colon histopathological score;increased contents of IL-1β,TNF-α,and IL-6 in colon tissue;and a decreased IL-22+ILC3s proportion in lamina propria lymphocytes of colon tissue(P＜0.05).Compared with the model group,mice in the electroacupuncture group exhibited improved fecal traits,weakly positive fecal occult blood test,decreased DAI score,increased colon length,reduced colon histopathological score;decreased contents of IL-1β,TNF-α,and IL-6 in colon tissues;an increased IL-22+ILC3s proportion in lamina propria lymphocytes of colon tissue;increased IL-22 content in colon tissue;and increased ChAT+/c-Fos+co-labeled neurons in colon tissue(P＜0.05).Conclusion Electroacupuncture at"Zusanli"(ST36)can significantly ameliorate colonic damage and reduce inflammatory responses in IBD mice,and its mechanism may be related to the activation of intestinal cholinergic neurons and the enhancement of colonic ILC3s function.

STC is a kind of clinically common functional gastrointestinal disease.Its pathogenesis hasn't been completely clarified,and current diagnosis and treatment norms are certainly limited.In recent years,"Brain-Gut Axis"theory has unveiled the complex bidirectional regulation mechanism between brain and intestinal tract,rendering new perspective for the research and treatment of STC.TCM theory demonstrates that there is close connection between brain and gut,has formed abundant experience in discrimination and treatment of STC and formed unique diagnosis and treatment ideas.Based on the theory of"Brain-Gut Axis"and"excess syndrome is corresponding to Zhanyu,deficiency syndrome is corresponding to Zhengsheng"in the chapter on Yangming diseases in"Treatise on Febrile Diseases",this paper elaborates on the relationship between the"Brain-Gut Axis"and STC.Meanwhile,by combining the theory of"excess syndrome is corresponding to Zhanyu,deficiency syndrome is corresponding to Zhengsheng"with the"Brain-Gut Axis"theory,it analyzes the influence of the excess and deficiency of the Yangming meridian on the mental state as well as the regulatory mechanism of the"Brain-Gut Axis",and puts forward corresponding treatment methods according to different syndromes.By integrating the relevant provisions in"Treatise on Febrile Diseases"with the"Brain-Gut Axis"theory of modern medicine,this paper makes a preliminary exploration of the laws of differentiating and treating STC,aiming to provide a theoretical basis for promoting a more comprehensive understanding of the pathogenesis of STC and developing more effective treatment strategies.

Objective To investigate the effects of electroacupuncture at"Zusanli"(ST36)on type 3 innate lymphoid cells(ILC3s)secreting interleukin(IL)-22 and intestinal cholinergic neurons in the colon of mice with inflammatory bowel disease(IBD),and to explore the mechanisms underlying electroacupuncture-mediated amelioration of IBD.Methods Twenty-four male C57BL/6J mice were divided into a normal group(n=8)and a modeling group(n=16)using the random number table method.The modeling group received 4％dextran sulfate sodium solution ad libitum for 7 days to establish the IBD model.On the fourth day after modeling,the modeling group was divided into a model group and an electroacupuncture group using the random number table method,with eight mice per group.Electroacupuncture intervention was applied bilaterally at"Zusanli"(ST36)in mice of the electroacupuncture group,once daily for 20 min each time,for seven consecutive days.After intervention,stool characteristics and occult blood were assessed.The disease activity index(DAI)of mice in each group was scored,and colon length was measured.The morphology of the colon tissue in mice was observed using hematoxylin-eosin staining,and the histopathological score was determined.A cytometric bead array was used to detect the contents of IL-1β,tumor necrosis factor-α(TNF-α),and IL-6 in colon tissue.Flow cytometry was used to determine the IL-22+ILC3s proportion in lamina propria lymphocytes of colon tissue.The content of IL-22 in colon tissue was detected using an enzyme-linked immunosorbent assay.Immunofluorescence was used to detect the number of choline acetyltransferase(ChAT)+/cellular Fos(c-Fos)+co-labeled neurons in colon tissue.Results Compared with the normal group,mice in the model group exhibited different degrees of loose stools,strongly positive fecal occult blood test,elevated DAI scores,shortened colon length,increased colon histopathological score;increased contents of IL-1β,TNF-α,and IL-6 in colon tissue;and a decreased IL-22+ILC3s proportion in lamina propria lymphocytes of colon tissue(P＜0.05).Compared with the model group,mice in the electroacupuncture group exhibited improved fecal traits,weakly positive fecal occult blood test,decreased DAI score,increased colon length,reduced colon histopathological score;decreased contents of IL-1β,TNF-α,and IL-6 in colon tissues;an increased IL-22+ILC3s proportion in lamina propria lymphocytes of colon tissue;increased IL-22 content in colon tissue;and increased ChAT+/c-Fos+co-labeled neurons in colon tissue(P＜0.05).Conclusion Electroacupuncture at"Zusanli"(ST36)can significantly ameliorate colonic damage and reduce inflammatory responses in IBD mice,and its mechanism may be related to the activation of intestinal cholinergic neurons and the enhancement of colonic ILC3s function.

Objective:To explore the protocol for handgrip exercise stress echocardiography by comparing different maximal voluntary contraction（MVC）handgrip groups with bicycle exercise stress.Methods:Forty-one healthy volunteers were enrolled prospectively from June to October 2024 in Tangdu Hospital and utilized a color Doppler echocardiography system，supine cycle ergometer，and handgrip dynamometer to collect echocardiographic data at baseline，during handgrip exercises at 20%（3 min），30%（3 min），and 40%（2 min）of MVC，and spine bicycle exercise stress at peak. Parameters measured included left ventricular ejection fraction（EF），stroke volume（SV），cardiac output（CO），mitral inflow E-wave and A-wave velocities，lateral and septal mitral annular e' velocities，E/A and E/e' ratios，global longitudinal strain（GLS），left atrial reservoir strain（LAS R），conduit strain（LAS CD），and contractile strain（LAS CT）. The non-invasive myocardial work indices were also assessed，including global work index（GWI），global constructive work（GCW），global wasted work（GWW），and global work efficiency（GWE）. Statistical analyses were performed using repeated measures analysis of variance，with corrected paired t-test for comparisons between two exercise stress states. Results:Compared with the baseline state，heart rate，blood pressure，CO、GWI、GCW、GWW and LAS CT gradually increased，while EF、E/A、GLS、GWE、LAS R and LAS CD gradually decreased under 20%，30% and 40% of MVC states. The changes were most obvious at 40% of MVC state，which was selected for the handgrip exercise stress echocardiography protocol.Compared with the peak of bicycle exercise，at 40% of MVC，heart rate was significantly lower［（81.2 ± 9.7）bpm vs.（164.6 ± 11.3）bpm， P<0.05）］，systolic blood pressure was slightly lower［（152.9 ± 13.2）mmHg vs.（165.1 ± 20.4）mmHg， P<0.05］，diastolic blood pressure was higher［（96.0 ± 9.5）mmHg vs.（89.5 ± 10.9）mmHg， P<0.05］，GLS was lower［（19.1 ± 1.5）% vs.（23.5 ± 1.7）%， P<0.05］，GWI was similar［（2 254.2 ± 417.3）mmHg% vs.（2 227.5 ± 389.0）mmHg%， P>0.05］，but GWE was higher［（95.3 ± 2.0）% vs.（93.7 ± 2.0）%， P<0.05］，and LAS R was lower［（39.4 ± 4.2）% vs.（43.9 ± 4.1）%， P<0.05］. Conclusions:The 40% of MVC lasting 2 min can cause the most significant handgrip-related changes in cardiac function and can be used as the standard protocol for handgrip exercise stress echocardiography. Handgrip stress exercise can cause significant changes in cardiac systole，diastole，and work performance，showing different characteristics compared with bicycle exercise stress.

Objective:To explore the diagnostic value of cardiac color Doppler ultrasonography for left ventricular hypertrophy(LVH)complicated left heart failure(LHF).Methods:A total of 117 LVH patients complicated LHF admitted in Ningde City Hospital Affiliated to Ningde Normal College between January 2019 and January 2023(heart failure group)and 100 healthy people(control group)who underwent general physical examination in our hospital simultaneously were selected for the study.Left ventricular ejection fraction(LVEF),left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd),early diastolic peak flow velocity/late diastolic peak flow velocity(E/A)were measured by cardiac color Doppler ultrasound in two groups.Receiver operating charac-teristic(ROC)curve was used to analyze the diagnostic value of cardiac color Doppler ultrasound indexes for LVH complicated LHF.In addition,the 117 patients with LVH and LHF were divided into mild group(n=54)and moderate to severe group(n=63)according to cardiac function class.Spearman correlation analysis was used to an-alyze the associationof cardiac color ultrasound parameters with cardiac function class.Results:Compared with par-ticipants in control group,those in heart failure group had significant lower LVEF[(47.88±4.75)％ vs.(69.81±5.64)％],and significant higher LAD[(44.03±4.88)mm vs.(27.56±2.76)mm vs.],LVEDd[(55.68±5.04)mm vs.(42.19±1.38)mm],E/A[(13.04±3.58)vs.(6.60±1.67)](P＜0.001 all).ROC analysis indicated that the area under the curve(AUC)of the combination of various parameters of cardiac ultrasound for diagnosing LVH with LHF was significantly higher than those of the single tests(Combined detection:AUC=0.901,95％CI 0.853～0.937 vs LVEF:AUC=0.644,95％CI 0.577～0.708,LAD:AUC=0.703,95％CI 0.637～0.763,LVEDd:AUC=0.633,95％CI 0.565～0.697,E/A:AUC=0.748,95％CI 0.685～0.804,Z=7.062,5.764,7.292,4.864,P＜0.001 all).Compared with patients in mild group,those in moderate to severe group had signifi-cant lower LVEF[(45.67±3.37)％ vs.(50.47±4.86)％],and significant higher LAD[(46.31±4.42)mm vs.(41.36±3.98)mm],LVEDd[(60.09±1.75)mm vs.(50.53±1.41)mm]and E/A[(13.99±2.96)vs.(11.93±3.92)](P＜0.01 all).Spearman correlation analysis indicated that LVEF was negatively correlated with cardiac function class(r=-0.474),while LAD(r=0.511),LVEDd(r=0.863),E/A(r=0.269)were positively corre-lated with cardiac function class(P＜0.01 all).Conclusion:Cardiac color Doppler ultrasound could better diagnose LVH complicated LHF,and also could effectively predict the cardiac function of patients with LVH and LHF.