Objective To investigate the value of quantitative parameters of diffusion weighted imaging(DWI)based on mono-expo-nential model(MEM),diffusion kurtosis imaging(DKI)model,and stretched-exponential model(SEM)in predicting the efficacy of neoadjuvant therapy in locally advanced gastric cancer(LAGC).Methods Forty LAGC patients who underwent MRI examinations before neoadjuvant therapy and before radical surgery were prospectively enrolled.A radiologist delineated lesions on DWI images and acquired quantitative parameters before and after treatment,including lesion volume,apparent diffusion coefficient(ADC)of MEM,mean diffusivity(MD)and mean kurtosis(MK)of DKI model,distribution diffusion coefficient(DDC),and α of SEM.According to pathological tumor regression grade(TRG),the patients were stratified into good response group(TRG 0-1)and poor response group(TRG 2-3).The pre-treatment parameters and Δ of pre-and post-treatment parameters were compared between the two groups with Mann-Whitney U test;multivariate analysis was performed with binary logistic regression.Multiple DWI models and the combined model were established,and the prediction efficiency of each model was calculated.Results There was no significant differ-ence in each parameter before neoadjuvant therapy between the two groups(P>0.05).The delta of volume,ΔADC,ΔMD,and ΔDDC pre-and post-treatment were all statistically different between the two groups(P<0.05).The area under the curve(AUC)of ΔADC,ΔMD,and ΔDDC in predicting good response for LAGC were 0.900,0.806,and 0.762,respectively.The AUC of the combined model was 0.946.Conclusion Quantitative parameters of MEM,DKI model,and SEM can help predict the efficacy of neoadju-vant-treated LAGC patients.

Objective:To investigate the changes in serum levels of interleukin-1β (IL-1β) and hypoxia-inducible factor-2α (HIF-2α) in patients with intracranial aneurysms before and after surgery, and their relationship with clinical prognosis.Methods:A prospective research method was used, a total of 120 patients with intracranial aneurysms who underwent endovascular embolization treatment in Xi'an NO.9 Hospital from December 2019 to December 2022 were selected as the study subjects. According to the prognosis after one-year follow-up, they were divided into poor prognosis group and good prognosis group. The general data of the two groups and the changes of serum IL-1β and HIF-2α levels before and after surgery were compared and analyzed. The changes of serum IL-1β and HIF-2α before and after surgery in patients with intracranial aneurysms and their relationship with the prognosis of patients were analyzed.Results:Among the 120 patients, 98 (81.67%) had a good prognosis and 22 (18.33%) had a poor prognosis. The proportion of large and wide necked aneurysms in the poor prognosis group was higher than that in the good prognosis group: 40.91% (9/22) vs. 10.20% (10/98), 45.45% (10/22) vs. 20.41%(20/98), with statistical significant differences ( P<0.05). On postoperative day 7, the serum levels of IL-1 β and HIF-2 α in the poor prognosis group were higher than those in the good prognosis group: (62.58 ± 6.12) ng/L vs. (56.95 ± 5.33) ng/L, (101.62 ± 10.55) ng/L vs. (92.70 ± 7.82) ng/L, with statistical significant differences ( P<0.05). Multivariate Logistic regression analysis showed that the size of aneurysms, including giant aneurysms, wide necked aneurysms, and high levels of serum IL-1β and HIF-2α 7 d after surgery, were independent risk factors for clinical prognosis in patients with intracranial aneurysms ( P<0.05). The working characteristic curve of the subjects was drawn, and the results showed that serum IL-1β and HIF-2α had certain predictive value for the clinical prognosis of intracranial aneurysm patients 7 d after surgery, but their sensitivity was relatively low. The parallel experiment method was used to jointly predict the samples. The results showed that the area under the curve for predicting the clinical prognosis of intracranial aneurysm patients with serum IL-1β and HIF-2α at 7 d after surgery was 0.867, with sensitivity and specificity of 86.40% and 74.50%, respectively, indicating high predictive value. Conclusions:The levels of serum IL-1β and HIF-2α are significantly elevated in patients with intracranial aneurysms after surgery, and are closely related to their clinical prognosis, which can help predict the clinical prognosis of intracranial aneurysm patients.

Objective To investigate the value of quantitative parameters of diffusion weighted imaging(DWI)based on mono-expo-nential model(MEM),diffusion kurtosis imaging(DKI)model,and stretched-exponential model(SEM)in predicting the efficacy of neoadjuvant therapy in locally advanced gastric cancer(LAGC).Methods Forty LAGC patients who underwent MRI examinations before neoadjuvant therapy and before radical surgery were prospectively enrolled.A radiologist delineated lesions on DWI images and acquired quantitative parameters before and after treatment,including lesion volume,apparent diffusion coefficient(ADC)of MEM,mean diffusivity(MD)and mean kurtosis(MK)of DKI model,distribution diffusion coefficient(DDC),and α of SEM.According to pathological tumor regression grade(TRG),the patients were stratified into good response group(TRG 0-1)and poor response group(TRG 2-3).The pre-treatment parameters and Δ of pre-and post-treatment parameters were compared between the two groups with Mann-Whitney U test;multivariate analysis was performed with binary logistic regression.Multiple DWI models and the combined model were established,and the prediction efficiency of each model was calculated.Results There was no significant differ-ence in each parameter before neoadjuvant therapy between the two groups(P>0.05).The delta of volume,ΔADC,ΔMD,and ΔDDC pre-and post-treatment were all statistically different between the two groups(P<0.05).The area under the curve(AUC)of ΔADC,ΔMD,and ΔDDC in predicting good response for LAGC were 0.900,0.806,and 0.762,respectively.The AUC of the combined model was 0.946.Conclusion Quantitative parameters of MEM,DKI model,and SEM can help predict the efficacy of neoadju-vant-treated LAGC patients.

Objective:To investigate the changes in serum levels of interleukin-1β (IL-1β) and hypoxia-inducible factor-2α (HIF-2α) in patients with intracranial aneurysms before and after surgery, and their relationship with clinical prognosis.Methods:A prospective research method was used, a total of 120 patients with intracranial aneurysms who underwent endovascular embolization treatment in Xi'an NO.9 Hospital from December 2019 to December 2022 were selected as the study subjects. According to the prognosis after one-year follow-up, they were divided into poor prognosis group and good prognosis group. The general data of the two groups and the changes of serum IL-1β and HIF-2α levels before and after surgery were compared and analyzed. The changes of serum IL-1β and HIF-2α before and after surgery in patients with intracranial aneurysms and their relationship with the prognosis of patients were analyzed.Results:Among the 120 patients, 98 (81.67%) had a good prognosis and 22 (18.33%) had a poor prognosis. The proportion of large and wide necked aneurysms in the poor prognosis group was higher than that in the good prognosis group: 40.91% (9/22) vs. 10.20% (10/98), 45.45% (10/22) vs. 20.41%(20/98), with statistical significant differences ( P<0.05). On postoperative day 7, the serum levels of IL-1 β and HIF-2 α in the poor prognosis group were higher than those in the good prognosis group: (62.58 ± 6.12) ng/L vs. (56.95 ± 5.33) ng/L, (101.62 ± 10.55) ng/L vs. (92.70 ± 7.82) ng/L, with statistical significant differences ( P<0.05). Multivariate Logistic regression analysis showed that the size of aneurysms, including giant aneurysms, wide necked aneurysms, and high levels of serum IL-1β and HIF-2α 7 d after surgery, were independent risk factors for clinical prognosis in patients with intracranial aneurysms ( P<0.05). The working characteristic curve of the subjects was drawn, and the results showed that serum IL-1β and HIF-2α had certain predictive value for the clinical prognosis of intracranial aneurysm patients 7 d after surgery, but their sensitivity was relatively low. The parallel experiment method was used to jointly predict the samples. The results showed that the area under the curve for predicting the clinical prognosis of intracranial aneurysm patients with serum IL-1β and HIF-2α at 7 d after surgery was 0.867, with sensitivity and specificity of 86.40% and 74.50%, respectively, indicating high predictive value. Conclusions:The levels of serum IL-1β and HIF-2α are significantly elevated in patients with intracranial aneurysms after surgery, and are closely related to their clinical prognosis, which can help predict the clinical prognosis of intracranial aneurysm patients.

Objective:To investigate the diagnostic value of serum serine protease (Corin) in chronic renal failure (CRF) complicated with heart failure.Methods:A retrospective analysis was conducted on 120 patients, (64.05±13.89) years old, 77 male (64.17%), with chronic renal failure combined with heart failure admitted to Zhengzhou People′s Hospital from January 1, 2023, to December 31, 2023. The control group consisted of 87 patients, (60.59±8.78) years old, 54 male (62.07%), with simple chronic renal failure. Clinical information, laboratory test indicators and echocardiographic parameters were collected. Serum Corin concentration was measured using enzyme-linked immunosorbent assay (ELISA). The experimental group was divided into grade Ⅱ(31 cases), grade Ⅲ(47 cases) and grade Ⅳ(42 cases) according to the New York College of Cardiology heart function classification system. Serum Corin levels were compared between the experimental group and the control group and among different cardiac function grades. Spearman correlation analysis was performed to evaluate the relationship between serum Corin and brain natriuretic peptide (BNP), D-dimer. ROC analysis was conducted to assess the predictive value of serum Corin in CRF complicated with heart failure and cardiac function classification; Binary Logistic regression was used to construct a multi-index joint prediction model, the joint prediction probability was obtained, and ROC curve was drawn to compare the diagnostic value of serum Corin and BNP in CRF combined with heart failure and the diagnostic value of serum Corin combined with D-dimer and BNP in CRF combined with heart failure.Results:The serum Corin level[2 568.97±477.70 pg/ml vs. 1 727.81±480.60 pg/ml, t=12.47, P<0.001], BNP [700.00(256.00, 2 089.75) pg/ml compared with 88.00 (43.00, 230.00) pg/ml, Z=-9.00, P<0.001], D-dimer [1 150.00(643.00, 1 874.75)μg/L compared with 556.00 (301.00, 865.00)μg/L, Z=-6.57, P<0.001] in chronic renal failure complicated with heart failure group was higher than that in simple CRF group, and the difference was statistically significant. Among patients with CRF complicated with heart failure, serum Corin[2 231.74±311.39 pg/ml vs. 2 562.09±365.30 pg/ml vs. 2 825.57±536.83 pg/ml, F=74.33, P<0.001], BNP [234.00(168.00, 612.00) pg/ml compared with 514.00(260.00, 1 455.00) pg/ml compared with 2 200.00(640.50, 4 682.75) pg/ml, H=29.42, P<0.001], D-dimer [753.00(514.00, 1 280.00) μg/L compared with 1 187.00(590.00, 1 840.00) μg/L compared with 1 603.00(810.00, 3 313.25) μg/L, H=14.98, P<0.001] increased with the increase of cardiac function grade, and the difference was statistically significant. According to Spearman correlation analysis, serum Corin was positively correlated with BNP ( r=0.409) and D-dimer ( r=0.299), P<0.001. According to the ROC analysis, the AUC of serum Corin in the diagnosis of CRF complicated with heart failure and cardiac function grade Ⅱ, Ⅲ, Ⅳ were 0.890(95% CI 0.846-0.935), 0.807 (95% CI 0.728-0.885), 0.911 (95% CI 0.864-0.959), 0.927 (95% CI 0.882-0.972) respectively; the AUC of BNP in the diagnosis of CRF complicated with heart failure was 0.867 (95% CI 0.817-0.916), the AUC of serum Corin combined with D-dimer, BNP combined with D-dimer, serum Corin combined with D-dimer and BNP in the diagnosis of CRF complicated with heart failure were respectively 0.930 (95% CI 0.897-0.962), 0.892 (95% CI 0.847-0.936), 0.952 (95% CI 0.927-0.977). Conclusions:Serum Corin expression is elevated in patients with CRF complicated with heart failure, and the degree of elevation is related to cardiac function grade. Serum Corin has a good diagnostic value for CRF complicated with heart failure and its severity. Serum Corin is expected to become a new biomarker for diagnosis of CRF complicated with heart failure.

Total hip arthroplasty(THA)is an effective treatment for elderly femoral neck fractures,mid-to late-stage femoral head necrosis,and end-stage hip osteoarthritis.However,serious complications such as aseptic loosening of the prosthesis,peripheral fractures,and dislocation of the prosthesis still exist following THA,which makes the selection of the appropriate hip prosthesis type and placement position before THA an important challenge for surgeons.Currently,the commonly used preoperative planning methods for THA mainly rely on static images from two-dimensional(2D)X-ray or three-dimensional(3D)computed tomography(CT),which fail to adequately consider the hip joint in weight-bearing as well as motion,lumbar-hip joint changes,and prosthetic impingement during motion.Recently,the dual fluoroscopic imaging system,as a new in-vivo,dynamic radiological imaging technology,provides comprehensive and accurate dynamic 3D data for THA preoperative planning.However,the technical process and expert consensus on preoperative 3D planning of THA using a dual fluoroscopic imaging system have not yet been established,which affects the promotion and application of this technology.In light of the above,national orthopaedic experts and related professional representatives discussed and proposed seven consensus issues,and the'expert recommendation rate'and'strong recommendation rate'were obtained through a questionnaire survey on the recommendations of the participating experts.This consensus aims to provide guidance and reference for the standardised application of preoperative 3D planning of THA using the dual fluoroscopic imaging system.

Objective To explore the role of indole-3-propionic acid(IPA)in the pathogenesis of metabolic associated fatty liver disease(MAFLD)induced by high-fat diet(HFD)in order to reveal the role and related mechanism of adipose tissue metabolism in the process.Methods A mouse model of MAFLD was induced by HFD.Male C57BL/6J mice(6～7 weeks old)were randomly divided into control group(CON),HFD group,and HFD+IPA intervention group(HFD+IPA).The CON group was fed with control diet,and the HFD group and HFD+IPA group were fed with 60％of high-fat diet.The experiment period was 12 weeks,and IPA was administered at 20 mg/(kg·d)for 6 weeks starting from the 7th week.The body weight and food intake of each group were monitored weekly.After the intervention,the body composition of mice was detected by animal body composition analyzer.After the mice were euthanized,the morphological and structural changes in the liver and adipose tissues were observed by HE staining,the indicators relevant to lipid metabolism in the serum,l iver and adipose tissues were detected by automatic blood biochemical analyzer and biochemical kits,and the mRNA expression changes of lipid metabolism and inflammation related genes were detected by qRT-PCR.Results Compared with the CON group,the HFD group had significantly increased body weight and body fat percentage,obvious lipid deposition in the liver,obviously elevated serum alanine aminotransferase,aspartate aminotransferase,liver triglyceride and total cholesterol levels(P＜0.05),and raised mRNA levels of liver fatty acid transporter CD36(P＜0.05),while IPA intervention significantly reversed the above changes(P＜0.05).IPA intervention significantly inhibited the HFD-induced enlargement of visceral and brown fat cells,reduced the content of visceral adipose tissue(VAT)and serum level of free fatty acids(P＜0.05),and increased the mRNA expression levels of VAT lipolysis(HSL,CGI58),browning genes(Cidea,ND5,UCP1,Prdm16)(P＜0.05),as well as those of brown adipose tissue(BAT)lipolysis(HSL,ATGL)and fatty acid beta oxidation(Cpt1a,PPARα)genes(P＜0.05).Meanwhile,the mRNA levels of TNF-α,IL-1β,CXCL1 and CCL2 in VAT and BAT were decreased after IPA intervention(P＜0.05).Conclusion IPA can improve the occurrence of MAFLD induced by HFD,and its mechanism may be closely associated with its regulation of BAT and VAT morphology,and the mRNA expression of metabolic function and inflammation related genes.

Objective To explore the effect of chenodeoxycholic acid(CDCA)on the expression of glucagon-like peptide-1(GLP-1)in the intestine of mice induced by high-fat diet(HFD)through farnesoid X receptor(FXR),and investigate the related mechanism.Methods Forty C57BL/6 mice were divided into control group,HFD group,HFD+CDCA group,HFD+Z-Gug(FXR antagonist)group,and HFD+CDCA+Z-Gug group,with 8 animals in each group.During intervention for 8 weeks,body weight and 24-hour food intake were measured every week.At the 8th week,oral glucose tolerance test(OGTT)and intraperitoneal glucose tolerance test(IPGTT)were conducted.After the mice were sacrificed,the serum levels of GLu,TG,CHO,LDL-C and HDL-C were detected;the expression levels of GLP-1 and FXR in intestinal tissues were detected by immunofluorescence assay;and the mRNA levels of TNF-α,IL-6,IL-1β,Gcg and FXR were detected by RT-qPCR;the serum level of GLP-1 was detected by ELISA,and the proportion of intraepithelial lymphocytes(IELs)subsets and the expression of CD26/DPP4 were detected by flow cytometry.Results Compared with the control group,the HFD group had increased body weight,abnormal serum glucose and lipid metabolism,impaired oral glucose tolerance,and weakened secretion of gastrointestinal hormones(P＜0.05),enhanced FXR expression at mRNA and protein levels,declined Gcg mRNA level and GLP-1 secretion level(P＜0.05),increased mRNA levels of intestinal inflammatory factors TNF-α,IL-6 and IL-1β(P＜0.05),raised proportions of TCRαβ+IELs,TCRαβ+CD8αα+IELs,and TCRαβ+CD8αβ+IELs but reduced proportion of TCRγδ+IELs,and increased total CD26/DPP4 expression in IELs(P＜0.05).Compared with the HFD group,HFD+CDCA treatment resulted in significantly increased body weight,impaired oral glucose tolerance,decreased secretion of gastrointestinal hormones,increased FXR mRNA and protein expression,and decreased Gcg mRNA expression and GLP-1 secretion(P＜0.05);decreased proportions of TCRαβ+IELs,TCRαβ+CD8αα+IELs and TCRααβ+CD8αβ+IELs but increased proportion of TCRγδ+ cells in IELs,and increased expression of total CD26/DPP4 in IELs(P＜0.05),which were significantly improved after Z-Gug intervention(P＜0.05).Conclusion CDCA may inhibit the expression and secretion of GLP-1 in intestinal tissue by activating FXR,and reduce the secretion of GLP-1.At the same time,CDCA may inhibit the expression of related inflammatory factors,regulate the proportions of IELs subsets,up-regulate the expression level of CD26/DPP4,promote the degradation of GLP-1 and aggravate insulin resistance.

This study aimed to explore the roles of microRNAs (miRNAs) in the post-transcriptional regulation of cocaine- and amphetamine-regulated transcript (CART) peptide in the bovine hypothalamus and to screen key regulatory miRNAs. Targetscan was used to predict the potential miRNAs binding to CART 3' untranslated regions (3'UTR). Bioinformatics analysis predicted 7 miRNA binding sites in the bovine CART 3'UTR, which were bta-miR-377, bta-miR-331-3p, bta-miR-491, bta-miR-493, bta-miR-758, bta-miR-877, and bta-miR-381, respectively. Reverse transcription-PCR (RT-PCR) was carried out to determine the endogenous expression of CART and target miRNAs in the bovine hypothalamus. All the 7 target miRNAs and CART were endogenously expressed in the bovine hypothalamus. The dual-luciferase reporter gene assay was employed to detect the targeted binding relationship between CART 3'UTR and target miRNAs obtained from bioinformatics analysis. The dual-luciferase reporter gene assay confirmed that the 3'UTR of CART had a targeted binding relationship with the 7 target miRNAs. Cell experiments were conducted to examine the effects of target miRNAs on the messenger RNA (mRNA) and protein levels of exogenous CART and screen for key regulatory miRNAs. The results of cell experiments showed that the 7 miRNAs downregulated the mRNA level of CART, with bta-miR-491 demonstrating the strongest downregulating effect. Bta-miR-377, bta-miR-331-3p, bta-miR-491, bta-miR-493, and bta-miR-381 downregulated the protein level of CART, with bta-miR-381 exerting the strongest downregulating effect. Animal experiments were conducted to explore the effects of key regulatory miRNAs on the mRNA and protein levels of CART in the hypothalamus and the CART concentration in the serum. The results from animal experiments showed that miR-491 and miR-381 regulated the endogenous expression of CART in the hypothalamus and the concentration in the serum by binding to the CART 3'UTR. These results suggest that miR-491 and miR-381 are the main miRNAs regulating CART expression in the bovine hypothalamus, which can affect serum CART concentration by modulating endogenous CART expression.
Animals ; MicroRNAs/metabolism* ; Cattle ; Hypothalamus/metabolism* ; 3' Untranslated Regions/genetics* ; Nerve Tissue Proteins/metabolism* ; Gene Expression Regulation ; Binding Sites ; Base Sequence ; Computational Biology/methods* ; Cocaine- and Amphetamine-Regulated Transcript Protein

Macrophage-mediated inflammation plays a pivotal role in cardiovascular disease pathogenesis. However, current cell-based models lack a comprehensive understanding of crosstalk between macrophages and cardiomyocytes, hindering the discovery of effective therapeutic interventions. Here, a microfluidic model has been developed to facilitate the coculture of macrophages and cardiomyocytes, allowing for mapping key signaling pathways and screening potential therapeutic agents against inflammation-induced dynamic myocardial injury. Through metabolic profiling and bioinformatic enrichment analysis, the microchip model with dynamic cell-cell crosstalk reveals robust activation of inflammatory and oxidative stress-associated metabolic pathways, closely resembling metabolic profiles of myocardial infarction in both humans and rodents. Furthermore, an integrative screening strategy has been established to screen bioactive natural products precisely, identifying ginsenoside Rb₁ and protocatechualdehyde as promising cardioprotective candidates in vitro and in vivo. Taken together, the microfluidic coculture model advances mechanistic insight into macrophage-mediated cardio-immunology and may accelerate the discovery of therapeutics for myocardial injury.