Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective:To establish a nomogram for preoperative differentiating intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) based on clinical, ultrasound, and contrast-enhanced ultrasound (CEUS) data.Methods:A retrospective analysis was conducted on ultrasound and CEUS data of 462 patients who underwent hepatectomy in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2016 to December 2023, including 262 cases of HCC (56.7%) and 200 cases of ICC (43.3%). The data were randomly divided into training set ( n=324) and validation set ( n=138) in a 7∶3 ratio. Univariate analysis was used to initially screen for variables with statistically significant differences between HCC and ICC groups in the training set, and LASSO regression was performed to select the variables with higher coefficients. Logistic regression analyses were then used to predict independent risk factors for ICC. A nomogram was drawn using R software. The performance of the nomogram was then validated using ROC curve, calibration curve, and decision curve analysis (DCA). Results:Univariate analysis showed that there were significant differences in age, gender, liver cirrhosis, HBsAg (+ ), ALP >185 U/L, CA19-9 >27 kU/L, CA242>10 kU/L, irregular shape, border, cholangiectasis, portal vein tumor thrombus, enhanced pattern in arterial phase, clearance time <60 s, intra-tumoral vein between ICC and HCC groups (all P<0.05). The top 10 features were selected for LASSO regression analysis. Logistic regression analysis revealed that gender, cirrhosis, CA19-9>27 kU/L, CA242>10 kU/L, cholangiectasis, clearance time <60 s, intra-tumoral vein and enhanced pattern in arterial phase were risk factors for ICC (all P<0.05). The area under the ROC curve in the training and validation groups were 0.963 and 0.914, respectively. In the training group, the specificity and sensitivity of the nomogram were 0.926 and 0.917, respectively, and in the validation group, they were 0.875 and 0.871, respectively. The calibration curve showed that the prediction effect of the model was in good agreement with the actual situation. DCA showed that the nomogram could increase the net benefit to the different diagnosis of ICC in patients. Conclusions:The nomogram based on clinical, ultrasound and CEUS features has a good predictive value for preoperative identification of ICC and provides reliable evidence for clinical practice.

Objective:To investigate the predictive value of the ratio of tricuspid annulus plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) in the progression of heart failure with reduced ejection fraction (HFrEF) patients.Methods:A total of 172 patients with HFrEF in the First Affiliated Hospital of Zhengzhou University from January to December 2022 were prospectively selected. All participants underwent routine echocardiography, the routine cardiac ultrasound parameters, left atrial volume index (LAVi), right ventricular fractional area change (RVFAC) were measured. The ratio of early diastolic velocity E peak of the mitral valve orifice to the early diastolic mean velocity e′ of the mitral valve annulus (E/e′) and TAPSE/PASP were calculated. The online quantitative analysis software of the ultrasound instrument were used to obtain the left ventricular global longitudinal strain (LVGLS), left atrial reservior strain (LASr), left atrial conduit strain (LAScd), left atrial contraction strain (LASct), right ventricular global systolic strain (RVGLS), and right ventricular free wall strain (RVFWS). According to the median of TAPSE/PASP, the patients were divided into TAPSE/PASP≥0.50 mm/mmHg group(group 1, 85 cases) and TAPSE/PASP<0.50 mm/mmHg group(group 2, 87 cases). The endpoint events were recorded. The differences of the above parameters in two groups were compared, the correlation analysis was used to analyze the correlations between myocardial mechanical parameters and TAPSE/PASP. The Kaplan-Merier method was used to draw survival curves, and the Log-rank method was used to compare the differences in survival curves in the two groups. The univariate and multivariate Cox regression models were used to analyze the predictive value of TAPSE/PASP for end-point events.Results:There were no significant differences in age, gender, body mass index, complications and left ventricular end-diastolic volume (LVEDV) between the two groups (all P>0.05). Compared with group 1, patients in group 2 showed a significant decrease in RVFAC and TAPSE (all P<0.05), while the LAVi, left ventricular end-systolic volume (LVESV), right ventricular end-diastolic diameter (RVDd-base), E/e′ and PASP were increased (all P<0.05), the absolute values of LVGLS, LASr, LASct, RVGLS, and RVFWS were significantly decreased (all P<0.05). Correlation analysis showed that LVGLS, LASr, RVGLS, RVFAC and 6-min walking distance were linearly correlated with TAPSE/PASP ( r/ rs=-0.176, 0.181, -0.496, 0.472, 0.421; all P<0.05). The follow-up time was (11.71±1.80) months, and the incidence of death events in group 2 (28.73%) was higher than that in group 1 (10.61%), with a significant difference ( P<0.05). The results of multivariate Cox regression analysis showed that TAPAE/PASP was one of the independent predictive factors for endpoint events in HFrEF patients, with adjusted HR: 0.306, 95% CI=0.141-0.663, P=0.003. Conclusions:TAPSE/PASP can monitor the progression of chronic heart failure and is one of the independent predictive factors, providing a new reference indicator for clinical diagnosis and treatment.

Objective:To establish and evaluate a clinical and ultrasound parameters-based nomogram for the preoperative differentiating diagnosis of intrahepatic cholangiocarcinoma (ICC).Methods:A total of 723 patients undergoing hepatectomy in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2016 to August 2022 were retrospectively screened. A total of 399 patients with hepatocellular carcinoma (HCC, 198 cases) or ICC (201 cases) were enrolled in this study, including 284 males and 115 females, aged (60.5±10.5) years. Through random sampling using computer-generated random numbers, patients were divided into training ( n=279) and validation groups ( n=120) in a ratio of 7∶3. Univariate and multivariate logistic regression were performed to identify factors differentiating ICC, and a nomogram was established using R software based on independent risk factors for ICC. The accuracy of the nomogram was evaluated by receiver operating characteristic curve and calibration curves. Decision curve analysis was performed to assess the net benefit of the model. Results:Multivariate logistic regression analysis showed that irregular shape, cholangiectasis, female, cirrhosis, carbohydrate antigen 242 >10 U/ml, carbohydrate antigen 125 >30 U/ml and alpha-fetoprotein >10 μg/L were independent differentiating factors for ICC (all P<0.05). A nomogram was constructed based on those factors. The nomogram showed a better discrimination between ICC and HCC. The area under the curve of the training group and the validation group were 0.966 and 0.956, respectively. The calibration curve showed that the prediction effect of the model is in good agreement with the actual situation. Decision curve analysis showed that the nomogram was more effective than diagnosing all patients as either HCC or ICC, which yielded a net benefit at the most reasonable threshold probabilities. Conclusion:The nomogram for the preoperative diagnosis of ICC based on clinical and ultrasound features showed a good diagnostic performance.

Objective:To compare the efficacy and safety of Castor single-branch stent and in vitro fenestration stent in treating thoracic aortic diseases with insufficient landing zone.Methods:The clinical data of patients with thoracic aortic diseases treated with Castor single-branch stent or in vitro fenestrated stent between December 2017 and June 2021 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. A total of 184 patients were included, 99 patients were treated with Castor branch stent, and 85 patients with in vitro fenestration stent. All patients′ general clinical data, surgical data, perioperative and follow-up clinical and imaging data, and postoperative complications were collected. The χ2 test was used to compare the incidence of complications between the two groups, and the Kaplan-Meier method was used to plot the survival rate without adverse events between the two groups. Results:Stent placement was successful in all patients, and the success rate of the technique was 100%. Other branches were reconstructed in 2 patients in the Castor group and double fenestrated stent were reconstructed in 12 patients in the fenestrated group. The mean operation time of the Castor group was significantly shorter than that of the fenestrated group, the number of patients who received local anesthesia was significantly lower than that of the fenestrated group, and the endoleak rate during follow-up was significantly lower than that of the fenestrated group ( P<0.05). There was no significant difference in the postoperative hospital stay, the incidence rate of perioperative complications, mortality, the incidence rate of neurological complications, new dissection or aneurysm rate, branch stent stenosis rate, second surgical intervention rate, and false lumen thrombosis between the two groups ( P>0.05). The adverse event-free survival rate of the Castor group was slightly higher than that of the fenestrated group, but its difference was not statistically significant ( P>0.05). Conclusion:Castor branch stent and in vitro fenestration stent have good short-term and mid-term efficacy in the treatment of aortic diseases with insufficient landing zone, which are safe and effective options for reconstruction of LSA and other branch arteries.

Objective:To investigate the effect of mid-ventricular obstruction (MVO) on left ventricular systolic function in patients with hypertrophic cardiomyopathy(HCM) by four-dimensional automatic left ventricular quantitation technology(4D Auto LVQ).Methods:Fifty-seven hypertrophic obstructive cardiomyopathy patients were selected from December 2020 to October 2022 in the First Affiliated Hospital of Zhengzhou University. According to the presence of MVO, HCM patients were divided into two groups: HCM 1 group, HCM without MVO ( n=34); HCM 2 group, HCM with MVO ( n=23). In addition, 25 healthy subjects in the same period were selected as the control group. Conventional ultrasound parameters were collected, and 4D Auto LVQ technology was used to obtain the mechanical parameters of left ventricular myocardium, including left ventricular longitudinal strain (GLS), circumferential strain (GCS), area strain (GAS), radial strain (GRS), segmental longitudinal strain (SLS) and area strain (SAS). The differences of these parameters among the three groups were compared. Results:①Compared with the control group, the thickness of the maximum basal segment of interventricular septum, the thickness of the middle segment of the maximum interventricular septum, the thickness of the apical segment of the interventricular septum, the thickness of the left ventricular posterior wall and left atrium diameter were significantly increased. Six-minute walk distance and the left ventricular end-diastolic diameter was decreased in the two groups of HCM(all P<0.05). Left ventricular outflow tract gradients in HCM 1 group was higher than HCM 2 group( P<0.05), but there was no significant difference in left ventricular ejection fraction among the three groups( P>0.05). There was significant difference in the incidence of left ventricular apical aneurysm among the three groups( P<0.05). ②Compared with the control group, the GLS in both HCM groups was lower, and it was lower in the HCM 2 group than in the HCM 1 group(all P<0.05) the GRS and GAS in both HCM groups were lower than in the control group ( P<0.05), and there was no significant difference between the two groups of HCM, and there was no significant difference in GCS among the three groups(all P>0.05). ③Compared with the control group, the SLS of basal segment, middle segment, apical cap, posterior septum, inferior wall and lateral wall in HCM group were significantly lower than those in control group. The SLS of apical segment of posterior septum, anterior septum, anterior wall, posterior wall, inferior wall and apical segment of posterior septum, lateral wall and inferior wall in HCM 2 group were significantly lower than HCM 1 group(all P<0.05), but there was no significant difference in SLS of posterior septum, anterior septum, anterior wall, lateral wall and inferior wall between the two groups(all P>0.05). ④Compared with the control group, the SAS of posterior septal basal segment, middle segment, anterior septal middle segment, anterior wall basal segment, middle segment, apical segment, lateral wall basal segment, middle segment, apical segment, posterior wall basal segment, middle segment, inferior wall basal segment, middle segment and apical cap in HCM groups were significantly lower than the control group(all P<0.05), but there was no significant difference in SAS between the two groups of HCM( P>0.05). Conclusions:4D Auto LVQ can quantitatively evaluate the damage of MVO on the left ventricular systolic function in patients with HCM, especially for the evaluation of local myocardial function damage in the medial segment and apical segment.

Objective:To explore the value in differentiating Borrmann Ⅳ type gastric cancer (BT4-GC) from gastric diffuse large B-cell lymphoma (DLBCL) using a nomogram based on CT texture analysis (CTTA) and morphological characteristics.Methods:From June 2011 to December 2020, a total of 60 patients with BT4-GC and 24 patients with DLBCL were retrospectively collected in Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University. Morphological characteristics were evaluated, including major location, long axis range, circumferential range, mucosal line status, and perigastric enlarged lymph nodes. CTTA parameters were calculated using venous CT images with a manual region of interest. The morphological characteristics and CTTA parameters between BT4-GC and DLBCL were compared by χ 2 test, Fisher exact test or Mann-Whitney U test. The multivariate binary logistic regression analysis was used to filter factors into the diagnostic model and construct a nomogram. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of CTTA parameters and the diagnostic model in differentiating BT4-GC from DLBCL. Results:For morphological characteristics, mucosal line status showed a significant difference between BT4-GC and DLBCL (χ 2=12.99, P<0.001). For CTTA parameters, 16 parameters showed significant differences between BT4-GC and DLBCL (all P<0.05). The area under the ROC curve (AUC) of 16 CTTA parameters in differentiating BT4-GC from DLBCL was 0.662-0.833. Percentile 90 showed the highest AUC of 0.833 (95%CI 0.736-0.906). The mucosal line status (OR 4.82, 95%CI 1.21-19.25, P=0.026) and percentile 90 (OR 1.09, 95%CI 1.04-1.15, P=0.001) were brought into the diagnostic model and constructed a nomogram. The AUC of the model in differentiating BT4-GC from DLBCL was 0.898 (95%CI 0.813-0.953), sensitivity was 0.833, and specificity was 0.817. Conclusions:The nomogram based on CTTA percentile 90 and morphological characteristics mucosal line status can effectively distinguish BT4-GC from DLBCL and shows high diagnostic efficacy.

Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKβ has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKβ is constitutively activated in healthy donors and healthy Ikkβ ^C46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKβ-IκBα-NF-κB signaling activation. These indicate that IKKβ activation probably plays homeostatic role instead of causing inflammation. Compared to Ikkβ ^WT littermates, lipopolysaccharides (LPS) could induce high mortality rate in Ikkβ ^C46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5' adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKβ kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKβ helix-loop-helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKβ simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKβ could substantially rescue LPS-induced mortality in Ikkβ ^C46A mice by rebuilding the homeostasis. We conclude that IKKβ activates AMPK to restrict inflammation and IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.

Objective:To explore the safety and efficacy of Castor branched stent-graft exclusion in the treatment of aortic dissection and aneurysm involving left subclavian artery.Methods:The clinical and imaging data of 88 patients with aortic dissection or aneurysm involving left subclavian artery diagnosed by CTA or DSA in our hospital from December 2017 to December 2019 were collected retrospectively, including 67 aorta dissections, 7 thoracic aortic aneurysms and 14 aorta penetrating ulcer. All patients were treated with branched stent-graft under the guidance of DSA. The postoperative curative effect and complications were observed. The paired t test was used to compare the maximum aortic diameter of the lesion before and 6 months after the operation. Results:Eighty-eight patients were successfully treated with integrated stent, the success rate of operation was 100%, and the disease-related symptoms of all patients were basically or completely relieved. The mortality rate within 1 month after the operation was 2.7% (2/88). The two deaths were complicated with other serious diseases before the operation, and the cause of death was not related the operation. All patients were followed up except 4 patients who lost contact after discharge. During the follow-up, there were 1 case of retrograde type A dissection, 1 case of new aneurysm of aortic arch, 2 cases of in-stent stenosis of left subclavian artery branch, 3 cases of mild stroke, no persistent endoleak and no death or other serious complications. The mean maximum aortic diameter at 6 months after operation [(34±4)mm] was significantly lower than that before operation [(38±6 mm)] ( t=6.63, P<0.05). Conclusion:Castor branched stent-graft is simple, mini-invasive and effective in the treatment of aortic dissection and aneurysms involving the left subclavian artery.

Objective To evaluate the feasibility and clinical outcomes of interventional treatment of Budd-Chiari syndrome (BCS) associated with simultaneous upper gastrointestinal hemorrhage.Methods The clinical data of 32 patients of BCS with upper gastrointestinal hemorrhage from October 2015 to April 2008 in First Affiliated Hospital of Zhengzhou University were analyzed retrospectively.Variceal embolization and inferior vena cave (IVC) and/or hepatic veins (HV) angioplasty were performed simultaneously.Perioperative complications were observed.Portal vein pressures were measured through catheterization preand post-operation.Restenosis of IVC and HV,upper gastrointestinal hemorrhage were observed on followup.Results Percutaneous transluminal balloon angioplasty were successfully carried out in all patients:16 patients with IVC and 17 patients with HV stenosis underwent angioplasty without stent placement.Portography indicated one esophageal and gastric varices in 17 patients and two in 15 patients.All the varices were embolized successfully.The portal vein pressure reduced from (35.7±2.9) cmH2O to (31.2±2.5) cmH2O (P ＜ 0.05,1 cmH2O =0.098 kPa).Portal vein pressure reduced from (35.8± 3.0) cmH2O to (30.7±2.3) cmH2O in HV type BCS post-operation,and reduce from (35.6±3.0) cmH2O to (31.8±2.6) cmH2O in HV and IVC involved type,which indicated that portal vein pressure decreased more obviously after HV recanalization.On follow-up for 3 to 32 months (mean 11.7 ±7.8 months),7 patients with IVC and 5 patients with HV stenosis developed restenosis.Transluminal balloon angioplasty was performed.No upper gastrointestinal hemorrhage occurred during the follow-up period.Conclusion One-stage interventional treatment of BCS with upper gastrointestinal hemorrhage was safe and effective,and had satisfactory mediumlong term outcomes.