Objective To investigate whether there exist differences in the improvement of left ventricular diastolic function between angiotensin receptor-neprilysin inhibitor(ARNI)and angiotensin-converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)in patients with hypertensive heart disease(HHD).Methods A retrospective cohort study was conducted on the HHD patients admitted in Department of Cardiovascular Diseases of our hospital from January 2021 to December 2024.The general information,echocardiographic parameters before and after treatment,and results of routine tests were collected.Finally,517 HHD patients were subjected,including 117 receiving ARNI treatment(ARNI group)and 400 getting ACEI/ARB treatment(ACEI/ARB group).A 1∶1 propensity score matching(PSM)was performed with a caliper value of 0.02,resulting in 89 matched cases for each group.Electrocardiography was performed to assess left ventricular diastolic dysfunction(LVDD),with various parameters,including left atrial volume index,early diastolic peak velocity at the interventricular septal portion of mitral annulus(septal e'),early diastolic peak velocity at the lateral wall portion of mitral annulus(lateral e'),tricuspid regurgitation velocity,and E/e'.These parameters were followed up and reassessed during the treatment period.Kaplan-Meier survival curve was plotted to compare the incidence of LVDD between the 2 groups.Multivariable logistic regression model was employed to identify the risk factors contributing to LVDD.Results The median follow-up time was 412(309,736)d in the whole cohort,and was 409(300,729)d for the patients after PSM.Kaplan-Meier survival analysis demonstrated that the incidence of LVDD was lower in the ARNI group than the ACEI/ARB group both before and after PSM(P<0.05).After treatment,the ARNI group obtained lower lateral e'[8.00(7.00,9.40)vs 9.00(7.10,10.30)cm/s,P<0.001],thinner left ventricular posterior wall thickness[12.20(10.80,12.80)vs 12.30(11.20,12.90)mm,P<0.048]when compared with the ACEI/ARB group.After adjusting for confounding factors,multivariable logistic regression analysis revealed that advanced age(OR=1.082,P<0.001),increased systolic blood pressure(OR=1.009,P=0.005),thicker left ventricular posterior wall thickness(OR=1.462,P<0.001),left atrial enlargement(OR=1.081,P<0.001),and use of calcium channel blocker(OR=1.548,P=0.006)were independent risk factors for LVDD,and positively correlated with the risk of LVDD.While,male(OR=0.709,P=0.043)and BMI(OR=0.933,P=0.006)were protective factors,which were negatively correlated with LVDD risk.Conclusion In HHD patients,ARNI is superior to ACEI/ARB in reducing the incidence of LVDD.

Objective:To explore the impact of tislelizumab on renal function in bladder cancer patients with hydronephrosisMethods:A retrospective analysis of 34 bladder cancer patients with hydronephrosis treated at the Second Hospital of Tianjin Medical University from July 2020 to September 2023. Among them, 27 were male, and 7 were female, with an average age of (67.41±11.06)years and a body mass index (BMI) of (29.00±7.34) kg/m 2. 18 patients (52.9%) had hypertension, 5 (14.7%) had diabetes, and 5 (14.7%) had coronary heart disease. The baseline serum creatinine (SCr) was 81.15(69.18, 108.90)μmol/L, and the estimated glomerular filtration rate (eGFR) was 73.86(62.17, 91.12)ml/(min·1.73m 2). Of these, 26 patients (76.5%) had eGFR ≥60 ml/(min·1.73m 2)(G60+ group), and 8 patients (23.5%) had eGFR <60 ml/(min·1.73m 2)(G60- group). 10 patients (29.4%) had non-muscle invasive bladder cancer (NMIBC), and 24(70.6%) had muscle-invasive bladder cancer (MIBC). Eleven patients received surgical interventions within 1 month before baseline data collection that might affect hydronephrosis. All 34 patients received tislelizumab (200 mg, intravenous infusion every 3 weeks) combined with albumin-paclitaxel (200 mg, intravenous infusion every 3 weeks). Serum creatinine values were recorded before cycles 1, 2, and 3, and 21 days after cycle 3 (Cr1, Cr2, Cr3, CrE), and corresponding eGFR values (eGFR1, eGFR2, eGFR3, eGFRE) were calculated. A reduction in eGFR >25% from baseline at any of these points was defined as a decline in renal function (DRF), and an increase in eGFR >25% was defined as improvement in renal function (IRF). Differences in renal function changes and IRF, DRF incidence rates were compared between baseline subgroups Results:After 3 cycles of tislelizumab treatment, there was no significant change in eGFR []eGFR1 vs. eGFRE, 73.86 (62.16, 91.12)ml/(min·1.73m 2) vs. 83.82 (60.32, 90.62) ml/(min·1.73m 2), P=0.197]. Subgroup analysis showed that patients with diabetes had a significant increase in CrE compared to Cr1 (88.90 μmol/L vs. 69.40 μmol/L, P=0.043) and a significant decrease in eGFRE compared to eGFR1 [76.47 ml/(min·1.73m 2) vs. 87.73 ml/(min·1.73m 2), P=0.043]. No significant differences were observed in the other subgroups for SCr and eGFR within or between groups. DRF occurred in 4 patients (11.8%), with 1 diagnosed with acute renal injury, but not immune-related. IRF occurred in 8 patients (22.9%). In the subgroup analysis, the IRF incidence was significantly higher in the G60-group compared to the G60+ group (50.0% vs. 15.4%, P=0.044). No other factors were found to be associated with DRF or IRF. Conclusions:Tislelizumab treatment is safe for renal function in bladder cancer patients with hydronephrosis. Most patients with baseline poor renal function or underlying conditions like hypertension, diabetes, or coronary heart disease showed stable renal function during treatment.

Objective:To explore the impact of tislelizumab on renal function in bladder cancer patients with hydronephrosisMethods:A retrospective analysis of 34 bladder cancer patients with hydronephrosis treated at the Second Hospital of Tianjin Medical University from July 2020 to September 2023. Among them, 27 were male, and 7 were female, with an average age of (67.41±11.06)years and a body mass index (BMI) of (29.00±7.34) kg/m 2. 18 patients (52.9%) had hypertension, 5 (14.7%) had diabetes, and 5 (14.7%) had coronary heart disease. The baseline serum creatinine (SCr) was 81.15(69.18, 108.90)μmol/L, and the estimated glomerular filtration rate (eGFR) was 73.86(62.17, 91.12)ml/(min·1.73m 2). Of these, 26 patients (76.5%) had eGFR ≥60 ml/(min·1.73m 2)(G60+ group), and 8 patients (23.5%) had eGFR <60 ml/(min·1.73m 2)(G60- group). 10 patients (29.4%) had non-muscle invasive bladder cancer (NMIBC), and 24(70.6%) had muscle-invasive bladder cancer (MIBC). Eleven patients received surgical interventions within 1 month before baseline data collection that might affect hydronephrosis. All 34 patients received tislelizumab (200 mg, intravenous infusion every 3 weeks) combined with albumin-paclitaxel (200 mg, intravenous infusion every 3 weeks). Serum creatinine values were recorded before cycles 1, 2, and 3, and 21 days after cycle 3 (Cr1, Cr2, Cr3, CrE), and corresponding eGFR values (eGFR1, eGFR2, eGFR3, eGFRE) were calculated. A reduction in eGFR >25% from baseline at any of these points was defined as a decline in renal function (DRF), and an increase in eGFR >25% was defined as improvement in renal function (IRF). Differences in renal function changes and IRF, DRF incidence rates were compared between baseline subgroups Results:After 3 cycles of tislelizumab treatment, there was no significant change in eGFR []eGFR1 vs. eGFRE, 73.86 (62.16, 91.12)ml/(min·1.73m 2) vs. 83.82 (60.32, 90.62) ml/(min·1.73m 2), P=0.197]. Subgroup analysis showed that patients with diabetes had a significant increase in CrE compared to Cr1 (88.90 μmol/L vs. 69.40 μmol/L, P=0.043) and a significant decrease in eGFRE compared to eGFR1 [76.47 ml/(min·1.73m 2) vs. 87.73 ml/(min·1.73m 2), P=0.043]. No significant differences were observed in the other subgroups for SCr and eGFR within or between groups. DRF occurred in 4 patients (11.8%), with 1 diagnosed with acute renal injury, but not immune-related. IRF occurred in 8 patients (22.9%). In the subgroup analysis, the IRF incidence was significantly higher in the G60-group compared to the G60+ group (50.0% vs. 15.4%, P=0.044). No other factors were found to be associated with DRF or IRF. Conclusions:Tislelizumab treatment is safe for renal function in bladder cancer patients with hydronephrosis. Most patients with baseline poor renal function or underlying conditions like hypertension, diabetes, or coronary heart disease showed stable renal function during treatment.

Objective: To investigate the effect of fusion protein tick anticoagulant peptide (TAP)-staphylococcus aureus superantigen-like protein 5 (SSL5) on the formation of atherosclerotic plaque in ApoE knockout (ApoE-/-) mice.Methods: Totally 21 male 12-week-old ApoE-/-mice were randomly divided into three groups: TAP-SSL5 (3 mg·kg-1·d-1) group, SSL5 (2 mg·kg-1·d-1) group and the blank control group (pH 7.4 phosphate buffer), ip, qd, for 12 weeks.The changes of body mass were observed.The mice were fed with high cholesterol diet for 12 weeks, and then the levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) in plasma were detected.The aorta of mice was subjected to paraffin section and routine HE staining.The formation of atherosclerotic plaque in the aortic root was analyzed.The distribution of atherosclerotic plaques was observed by oil red O staining of the aorta.Results: Compared with that of the blank control group, the increasement of body weight of TAP-SSL5 group and the level of TC significantly decreased (P <0.001), while TG, HDL-C and LDL-C did not change significantly.The HE staining results showed that the plaque area of root slice in the aorta in TAP-SSL5 group was significantly lower than that in the blank control group (P<0.05).The red O staining of aorta showed that the formation of atherosclerotic plaque in TAP-SSL5 group was significantly smaller than that in the blank control group.Conclusion: TAP-SSL5 can significantly inhibit the formation of atherosclerotic plaques in the arteries of ApoE-/-mice.

Objective To investigate the long-term toxicity of anti-inflammatory and anticoagulant tick anticoagulant peptide (TAP)-staphylococcal superantigen like protein-5 (SSL5) fusion protein in normal rats.MethodsSD rats were intraperitoneally injected with TAP-SSL5 (1mg/kg, every other day) for eight weeks and followed up for one week.The general behavior, weight, blood routine test, blood biochemistry and organ indexe were measured.ResultsOur results showed that there were no significantly difference between the TAP-SSL5 treated rats and the control on general behavior, weight, blood routine test, blood biochemistry, organ indexe and pathology.ConclusionThe fusion protein TAP-SSL5 with little long-term toxicity for rats is proved to be a safe drug.

AIM:Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions .Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles ( MVs) from macrophages .METHODS:HMGB1 was added to the medium of macrophages , the secretion of MVs in the supernatant was tested by flow cytometry analysis .The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining .Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs .Then we subcutaneous injection into mice with MVs to induce regional minera-lization.RESULTS:HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis .TNAP activity, considered as a marker of MVs maturation , was higher in HMGB1-induced MVs compared to the control-MVs.HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model .Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization .Mechanistic experiments revealed that HMGB 1 activated neutral sphingomyelinase 2 ( nSMase2 ) that involved the receptor for advanced glycation end products ( RAGE ) and p38 MAPK (upstream of nSMase2).Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and min-eral deposition .CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part , via the RAGE/p38 MAPK/nSMase2 signaling pathway .Our findings thus reveal a novel mechanism by which HMGB 1 may participated in the early calcification of atherosclerotic plaques .

AIM: To study the effect of tick anticoagulant peptide-staphylococcal superantigen like protein 5 (TAP-SSL5), an anti-inflammatory and anticoagulant fusion protein , on the binding of activated platelets to human lym-phocytes.METHODS:Human periphery lymphocytes were isolated by magnetic activated cell sorting (MACS).The toxic-ity of TAP-SSL5 on the viability of Jurkat cell was assessed by CCK-8 assay.Flow cytometry was applied to detect the ex-pression of CD162 (PSGL-1) on the Jurkat cells (human peripheral blood leukemia T lymphocyte cell line ) and the inhibi-tory effect of TAP-SSL5 on the binding of mouse anti-human CD162 monoclonal antibody (KPL-1) to Jurkat cells.Platelets were activated by ADP at concentration of 20μmol/L, the binding rates of activated platelets to Jurkat cells or human lym-phocytes were assayed by flow cytometry .RESULTS:The concentration of TAP-SSL5 below 30 mg/L didn’ t affect the vi-ability of Jurkat cells .TAP-SSL5 at 10 mg/L competitively inhibited KPL-1 binding to Jurkat cells .The binding rates of activated platelets to Jurkat cells or lymphocytes were (11.86 ±4.49)% and (8.32 ±1.00)%, respectively, which de-creased to (6.73 ±2.71)%and (5.51 ±0.70)%after the Jurkat cells and lymphocytes were pre-incubated with 10 mg/L TAP-SSL5 (P <0.05).CONCLUSION:TAP-SSL5 binds to PSGL-1 expressed on lymphocyte surface and directly in-hibits the binding of activated platelets to human lymphocytes , which may be one of the anti-inflammatory mechanisms of TAP-SSL5.

Adult ; Aneurysm, Dissecting ; diagnosis ; physiopathology ; Aneurysm, False ; Coronary Aneurysm ; diagnosis ; physiopathology ; Coronary Vessels ; pathology ; physiopathology ; Humans ; Male ; Myocardial Infarction ; diagnosis ; physiopathology ; Thoracic Injuries ; complications ; physiopathology ; Young Adult

Objective To systematically evaluate the clinical outcomes of patients with multivessel diseases treated by fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) or other forms of treatment .Methods Some keywords inclu-ding FFR or fractional flow reserve ,percutaneous coronary intervention or PCI ,multivessel coronary artery disease were used to search randomized control trails(RCT) ,which compared outcomes of patients with multivessel disease treated by FFR guided PCI with other forms of treatment ,in Chinese and English database including CNKI ,VIP ,Wanfang ,Pubmed ,EMBASE and the web of science .The quality of included studies was evaluated by Jadad quality score and all the data was analyzed by stata 10 .0 .Results A total of 7 english literatures accumulating 2024 cases in experimental group and 7 284 cases in control group were included in this study .Compared with other forms of treatment ,patients with multivessel diseases treated by FFR-guided PCI had significantly low-er risk of myocardial infarction (RR=0 .72 ,P=0 .008) .Although the risk of death and major adverse cardiovascular events were al-so be reduced ,there were no statistically significant difference .Conclusion FFR-guided PCI is an effective treatment for multivessel disease ,but it is still needs further verification for the application in Chinese population .

Objective To observe the curative effects of long term statins treatment on blood lipid and left ventriclar function of myocardial infarction patients. Methods 70 patients with myocardial infarction were randomly divided into two groups: Statins treatment group (n=37) and control group (n=33). The level of blood lipid, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF) were mearsured before and 2 years after the treatment. Results The long term applies of statins can bring statistically different (P<0.05) of TC and LDL-C to myocardial infarction patients. LVESD and LVEF were statistically different (P<0.05) before and after statins were used. Conclusion The long term applies of statins can improve the lipidic metabolism and left ventricular function after myocardial infarction.