Objective To evaluate the diagnostic value of myocardial work related parameters in coronary ischemia patients with coronary artery disease(CAD)coronary ischemia using non-invasive left ventricular pressure strain loop(PSL),taking fraction flow reservation(FFR)as the gold standard.Methods From December 2020 to December 2021,53 clinically suspected CAD patients were prospectively enrolled.All patients underwent echocardiography,invasive coronary angiography and FFR measurement.According to the results of coronary angiography,patients were divided into myocardial ischemia group(n=24,FFR≤0.80)and non-myocardial ischemia group(n=29,FFR＞0.80).PSL was used for off-line analysis to obtain the global work index(GWI),global constructive work(GCW),global wasted work(GWW),global work efficiency(GWE),global positive work(GPW),and global systolic constructive work(GSCW)and other myocardial work parameters.The differences of parameter values between the two groups were compared.The diagnostic efficacy of work parameters in myocardial ischemia was analyzed by ROC curve.Results Compared with the non-myocardial ischemia group,GWI,GCW,GPW and GSCW were significantly decreased in the myocardial ischemia group at the 18-,16-,and 12-segment levels(P＜0.001).The ROC curve showed that the AUC results of GWI,GCW,GPW,GSCW at the 18-segment level were 0.803(95％CI 0.679-0.927),0.807(95％CI 0.687-0.928),0.822(95％CI 0.708-0.936),0.819(95％CI 0.703-0.935).The optimal cut-off value of GWI was 1 676.3 mmHg％,and the sensitivity,specificity and accuracy of predicting myocardial ischemia were 70.8％,86.2％and 79.2％,respectively.The optimal cut-off value of GCW was 1 999.4 mmHg％,and the sensitivity,specificity and accuracy of predicting myocardial ischemia were 75.0％,82.8％and 79.2％,respectively.Conclusions Analyzing myocardial work using PSL has good significance for screening suspected myocardial ischemia in CAD patients.

Objective To investigate the effect of serum uric acid(SUA)on all-cause mortality and cardio-cerebrovascular diseases mortality in maintenance hemodialysis(MHD)patients.Methods Clinical data were retrospectively collected from MHD patients in Zhongshan Hospital,Fudan University from January 1,2015,to December 31,2016.The patients were categorized into low SUA group(SUA ≤ 399 μmol/L),medium SUA group(SUA 400-460 μmol/L),and high SUA group(SUA≥461 μmol/L)according to the tertiles of SUA level.The clinical data and laboratory examination results were compared among the three groups.The survival curves were plotted by Kaplan-Meier,and log-rank test were used to compare the survival rates among the three groups.Multivariate Cox regression was used to analyze the associations between SUA and all-cause mortality and cardio-cerebrovascular diseases mortality in MHD patients.Results A total of 436 MHD patients were enrolled,including 149 in low SUA group,144 in medium SUA group,and 143 in high SUA group.The median follow-up time was 59.7(38.4,60.9)months.During the follow-up,130 deaths were recorded,of which 90(69.2％)were due to cardio-cerebrovascular diseases.Kaplan-Meier survival analysis showed that the all-cause survival rate and cardio-cerebrovascular diseases survival rate of patients in low SUA group were lower than those in medium SUA group and high SUA group(P＜0.05).After adjusting for age,gender,comorbidities and other factors,the multivariate Cox regression analysis showed that the risk of all-cause mortality in patients decreased by 2.6％(HR=0.974,95％CI 0.952-0.996,P=0.022)and the risk of cardio-cerebrovascular diseases mortality decreased by 3.7％(HR=0.963,95％C1 0.937-0.991,P=0.008)for each 10 μmol/L increase in SUA level.The risks of all-cause mortality and cardio-cerebrovascular diseases mortality were significantly higher in low SUA group compared to high SUA group(HR=1.841,95％CI 1.138-2.979,P=0.013;HR=2.353,95％CI 1.288-4.300,P=0.005).Conclusions Low SUA level is independently associated with all-cause mortality and cardio-cerebrovascular diseases mortality in MHD patients.

Objective Two-sample Mendelian randomization(TSMR)method was used to explore the potential causal association between Hashimoto thyroiditis(HT)and primary biliary cholangitis(PBC).Methods The genome-wide association study(GWAS)data of HT and PBC from different research sources were obtained through the IEU OpenGWAS project database.Taking HT as the exposure factor and PBC as the outcome,single nucleotide polymorphisms(SNPs)significantly associated with exposure factor were selected as the instrumental variables(IVs),and inverse-variance weighed(IVW)was used as the main analysis method to explore the potential causal relationship between HT and PBC.Additionally,multiple sensitivity analyses such as heterogeneity test and horizontal multiple effect test were employed to evaluate the robustness and consistency of the findings.Results The results of random-effects inverse-variance weighted(rIVW)method indicated a significant association between HT and the development of PBC(OR=1.853,95％CI 1.241-2.768,P=0.003),and the results of the other four MR methods based on different assumptions were similar to the rIVW.Sensitivity analysis showed that the results were not affected by horizontal pleiotropy,and the robustness of the results was confirmed by leaving-one test.Reverse MR analysis,due to the presence of horizontal pleiotropy and failure to meet the criteria of the MR Egger test,could not establish a reverse causality of PBC on HT.Conclusions HT may be a risk factor for the occurrence of PBC,and there is no evidence to support reverse causality.This may potentially offer novel insights into the pathogenesis of both diseases,thereby providing avenues for further research,as well as clues for the prevention and treatment of these two conditions.

Objective To explore the correlation between malignant tumors and serum N-terminal pro-brain natriuretic peptide(NT-proBNP)levels.Methods A total of 336 patients with malignant tumors(cancer group)who were admitted to the Department of Cardiology,Chinese PLA General Hospital and underwent coronary angiography from January 1,2009 to December 31,2020,and were newly diagnosed and had not received any anti-tumor treatment were selected.They were matched with 1 008 patients(non-cancer group)in a 1:3 ratio using propensity score matching based on gender and age.Clinical data of the patients were collected,including age,gender,serum NT-proBNP,left ventricular ejection fraction(LVEF),SYNTAX score,serum creatinine,and tumor diagnosis information.The patients were divided into 4 groups based on the quartiles of NT-proBNP levels:low-level group(NT-proBNP ≤ 61.80 pg/mL),medium-level group(61.80 pg/mL＜NT-proBNP≤ 152.95 pg/mL),high-level group(152.95 pg/mL＜NT-proBNP≤470.10 pg/mL),and very high-level group(NT-proBNP＞470.10 pg/mL).Ordered logistic regression analysis was used to analyze the correlation between malignant tumors and serum NT-proBNP.Results A total of 1 344 patients were included,with an average age of(65.78±9.18)years old,1 003 males(74.63％),LVEF of 60.00％(55.00％,64.00％),SYNTAX score of(13.84±11.63)points,and creatinine level of 76.60(66.50,88.88)μmol/L.Among the 336 cancer patients,the top 3 types of cancer were lung cancer(84 cases,25.00％),colorectal cancer(58 cases,17.26％),and gastric cancer(52 cases,15.48％).The NT-proBNP levels in the cancer group were significantly higher than those in the non-cancer group(208.45[85.75,601.83]pg/mL vs 134.35[57.18,430.23]pg/mL,P＜0.001).Ordered logistic regression analysis showed that in the unadjusted model,malignant tumors were significantly associated with higher NT-proBNP levels(OR=1.561,95％CI 1.538-1.584,P＜0.001);after adjusting for relevant factors,malignant tumors remained significantly associated with higher serum NT-proBNP levels(OR=1.384,95％CI 1.070-1.791,P=0.013).Conclusions NT-proBNP in malignant tumor patients is higher than that in non-malignant tumor patients,and there is a significant correlation between malignant tumors and serum NT-proBNP levels.

Objective To prepare a novel photosensitive nanoparticle and to evaluate its physicochemical properties,and effect on the efficacy of photodynamic therapy.Methods 5,15-dibromo-10,20-diphenylporphine(DBN),tetrafluoroterephthalonitrile(TFN),and the amphiphilic polymer methoxy-polyethylene glycol-distearoylphosphatidylethanolamine(DSPE-MPEG2000,PEG)were dissolved in tetrahydrofuran(THF)by co-precipitation method to prepare novel photosensitive nanoparticles,named DBN/TFN@PEG.The physicochemical properties of DBN/TFN@PEG were characterized.Both novel and conventional nanoparticles were continuously irradiated with a 660 nm laser,and the fluorescence intensity of nanoparticles,representing reactive oxygen species(ROS)production levels,was measured using a fluorescence spectrophotometer at different irradiation times.Tumor cells were co-incubated with the nanoparticles and irradiated with a 660 nm laser.ROS levels within the tumor cells were detected using immunofluorescence,and the ratio of dead to live tumor cells was determined using PI/Calcein-AM staining.Results Prepared DBN/TFN@PEG nanoparticles with hydrated particle size of approximately 107.8 nm were uniformly distributed in the solution.Compared to conventional nanoparticles,the ROS production capacity of DBN/TFN@PEG was significantly higher(P＜0.01).Immunofluorescence results showed that the generation of ROS levels in the tumor cells of DBN/TFN@PEG group were significantly higher than in the conventional nanoparticles group under laser irradiation(P＜0.01).PI/Calcein-AM staining results indicated a significantly higher ratio of dead tumor cells in the DBN/TFN@PEG group compared to the conventional nanoparticle group(P＜0.01).Conclusions DBN/TFN@PEG has stable physicochemical properties and uniform distribution in the solution.As effective photosensitizers,DBN/TFN@PEG can exhibit stronger ability to induce ROS generation in tumor cells,and may enhance the efficacy of photodynamic therapy in cancer.

Objective To explore the feasibility and safety of submucosal tunneling endoscopic resection(STER)for the treatment of giant(long diameter≥3.5 cm)symptomatic submucosal tumors(SMT)originating from the esophageal and cardiac muscularis propria layer.Methods A retrospective analysis was conducted on patients with giant symptomatic SMT of the esophagus and cardia treated with STER at the Endoscopy Center of Zhongshan Hospital,Fudan University from January 2017 to January 2020.Clinical characteristics and follow-up data of patients were collected.The efficacy of STER was evaluated by complete resection rate,recurrence rate,and residual rate.The safety of the procedure was assessed by the occurrence of procedure-related complications.Results A total of 111 patients with SMT were included,including 65 males and 46 females,with an average age of(43.2±11.6)years old.Among them,11 patients(9.9％)presented with typical symptoms.Leiomyomas accounted for 105 cases,gastrointestinal stromal tumors for 2 cases,and schwannoma for 4 cases.The median long diameter of the tumors was 5 cm,and the median short diameter was 3 cm.The median operation time was 70 minutes,and the median time of hospital stay was 3 days.The success rate of STER was 100％,with a complete resection rate of 73.9％.Intraoperative mucosal injury was observed in 18 cases(16.2％),postoperative complications occurred in 16 cases(14.4％),including severe pneumothorax/pleural effusion requiring drainage in 10 cases(9.0％),delayed bleeding in 1 case(0.9％),moderate or severe fever in 4 cases(3.6％),and infection in tunnel in 1 case(0.9％).Follow-up at 1-18 months showed no tumor residue,recurrence,esophageal stenosis,diverticula or other long-term complications.Conclusions STER is a safe and effective treatment for giant symptomatic SMT of the esophagus and cardia.

Objective To construct a nomogram model to predict the risk of pressure injuries(PI)in mechanically ventilated patients in the intensive care unit(ICU).Methods Clinical data of mechanically ventilated patients in the ICU of Zhongshan Hospital,Fudan University from January 1,2020 to March 15,2023 were retrospectively collected as the training set,and data from ICU of the same hospital from October 1,2023 to December 11,2023 were collected as the external validation set.Risk variables for PI were selected using LASSO regression and Cox proportional hazards model,and a nomogram model was constructed.Receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate the model.Calibration curve and decision curve analysis(DCA)were used to assess the model's calibration and clinical applicability.The external validation was performed using the validation set data.Results A total of 580 mechanically ventilated patients were included in the training set,with 84 cases(14.5％)of PI.LASSO regression and Cox proportional hazards model selected 10 variables to construct the nomogram model.The ROC curve showed an AUC of 0.830 for predicting PI in mechanically ventilated patients.Calibration curve and DCA indicated good calibration and predictive performance of the model.The external validation set included 100 patients,with 12 cases of PI,and the AUC was 0.870.Calibration curve and DCA showed good model performance.Conclusions The nomogram model based on LASSO-Cox regression has good predictive performance and can be used to screen high-risk population for PI in mechanically ventilated patients.

Objective To explore the role and mechanism of cardiac resident macrophages in heart repair after myocardial infarction in mice.Methods Macrophage-specific Cre tool mice(CX3CR1CreER-YFP mice)with doubly transgenic mice(R26tdTomato/DTR mice)were hybridized to obtain cardiac resident macrophage-specific red fluorescent labels in mice.Sixty Cx3crlCreER-YFP:R26Td/DTR hybrid mice were randomly divided into 4 groups:Sham group,DT+Sham group,MI group,and DT+MI group,with 15 mice in each group.MI group and DT+MI group underwent myocardial infarction modeling by ligating the left anterior descending coronary artery.The DT+MI group mice were induced to deplete resident macrophages in the heart tissue using diphtheria toxin(DT)to establish a cardiac resident macrophage knockout model.On the 5th day after myocardial infarction modeling,heart tissue slices of mice were stained with H-E to observe inflammation infiltration and myocardial infarct size were calculated;on the 14th day of modeling,echocardiography was used to measure cardiac function-related parameters in mice,and mRNA expression levels of inflammatory cytokines were detected.Results Compared with the MI group,the DT+MI group mice showed a significant reduction in cardiac resident macrophages([53.75±4.62]vs[6.37±1.25],P＜0.05).On the 14th day after myocardial infarction modeling,compared with the Ml group,the DT+MI group mice had significantly increased left ventricular end-diastolic diameter([5.11±0.22]mm vs[5.92±0.26]mm,P＜0.05)and left ventricular end-systolic diameter([4.77±0.17]mm vs[5.38±0.16]mm,P＜0.05),while the ejection fraction significantly decreased([27.76±1.20]％vs[17.61±0.94]％,P＜0.05);in addition,the DT+MI group mice showed increased expression levels of inflammatory cytokines,increased inflammatory cell infiltration,and significantly larger myocardial infarct size.The protein expression levels of NF-KB/p-P65 in DT+MI group mice were significantly higher than those in the MI group([0.28±0.14]vs[1.09±0.12],P＜0.05).Conclusions Cardiac resident macrophages play an important role in heart tissue repair after myocardial infarction by reducing inflammation cell infiltration and myocardial infarct size.

Objective To investigate the therapeutic effect of chimeric antigen receptor(CAR)T cells on myocardial infarction(MI)and observe the impact of different administration routes on CAR-T cell cardiac toxicity.Methods Twenty-four SCID Beige immunodeficient mice,which successfully established a myocardial infarction model,were randomly divided into Hank's balanced salt solution(HBSS)group,CAR-TIM group,CAR-TIV group,and CAR-TIMIV group(n=6 for each group).In addition,a Sham group(n=6)was set up.The Sham group,HBSS group,CAR-TIM group,and CAR-TIMIV group were injected with HBSS or CAR-T cells via intramyocardial injection on the 7th day after modeling.The Sham group,HBSS group,CAR-TIV group,and CAR-TIMIV group were injected with HBSS or CAR-T cells via tail vein injection on the 7th day and 14th day after modeling.After 28 days of modeling,the electrical physiological indicators of the mice were observed,and the myocardial tissues were subjected to Masson staining to calculate the area of myocardial infarction.Results Compared with the Sham group,the HBSS group had significant increases in myocardial infarction size and incidence of arrhythmia(P＜0.05).Compared with HBSS group,different routes of CAR-T cell therapy significantly reduced the area of myocardial infarction(all P＜0.05)and significantly increased the incidence of arrhythmia(all P＜0.05).There was no significant difference in the effect of CAR-TIV and CAR-TIM groups on the area of myocardial infarction and the incidence of arrhythmia.Compared with the CAR-TIV group,the area of myocardial infarction significantly reduced in the CAR-TIMIV group(P＜0.05),with no significant difference in the incidence of arrhythmia between the two groups.Conclusions Intravenous and local myocardial injection of CAR-T cells can effectively reduce the myocardial infarction area but increase the incidence of arrhythmia.The mechanism needs further study.