ObjectiveTo investigate the effects of targeted silencing of Runt-related Transcription Factor 3 （RUNX3） on the proliferation and migration of Mouse Hepatic Stellate Cells （HSCs）， as well as subsequent collagen deposition. MethodsMouse hepatic stellate cell line （JS-1） was selected and then morphologically observed and identified under a microscope. After the cells had fully adhered， they were treated with 5 ng/mL of transforming growth factor beta 1 （TGF-β₁） for 24 hours to induce hepatic stellate cell activation. Furthermore， a RUNX3 silencing model was established using RUNX3 lentiviral infection. The experiment was divided into four groups： Control group， TGF-β₁ group， TGF-β₁+siRNA-NC group， and TGF-β₁+siRNA-RUNX3 group. Protein expression changes of RUNX3， alpha-smooth muscle actin （α-SMA）， and Alpha 1 type I collagen （Collagen I） were detected using Western blot method. Cellular immunofluorescence assays were employed to investigate the deposition changes of α-SMA and RUNX3 in hepatic stellate cells. RT-qPCR was utilized to examine the mRNA expression changes of RUNX3， α-SMA， and Collagen I. The proliferative capacity of hepatic stellate cells was assessed using Edu staining. The migratory ability of hepatic stellate cells was evaluated through wound healing assays and Transwell migration experiments. ResultsCompared with Control group， a significant elevation in RUNX3 was observed in the TGF-β₁-induced activated HSCs （P<0.01）. Meanwhile， the protein and mRNA levels of fibrosis-related markers and α-SMA and Collagen I were significantly upregulated （P<0.001）. Additionally， the proliferation and migration capabilities of HSCs were significantly enhanced （P<0.001）. In contrast， when compared to TGF-β₁+siRNA-NC group， TGF-β₁+siRNA-RUNX3 group exhibited a notable decrease in RUNX3 and other related indicators， such as the protein and mRNA levels of α-SMA and Collagen I （P<0.05）. Concurrently， the proliferation and migration capabilities of HSCs were significantly inhibited in TGF-β₁+siRNA-RUNX3 group （P<0.01）. ConclusionSilencing RUNX3 can inhibit the deposition of collagen and the proliferation and migration of hepatic stellate cells. Conversely， RUNX3 promotes the proliferation and migration capabilities of HSCs， thereby facilitating the activation of HSC.

Objective To explore the correlation between serum circularRNA-HOMER1(circHOMER1),microRNA(miR)-23a-3p levels with clinical stages and oxidative stress in patients with diabetic retinopathy(DR).Methods From January 2023 to July 2024,75 DR patients treated in Handan Central Hospital were included as the DR group.According to the clinical staging of DR,they were divided into non proliferative DR(NPDR group,n=43)and proliferative DR(PDR group,n=32).In addition,75 patients with simple type 2 diabetes who came to Handan Central Hospital were included as non DR group.The levels of serum circHOMER1,miR-23a-3p,malondialdehyde(MDA),superoxide dismutase(SOD),and reduced glutathione(GSH)were detect-ed.Clinical data of the subjects were collected.The TargetScan website was used to predict the targeting relationship between circHOMER1 and miR-23a-3p.Pearson method was used to analyze the correlation between serum circHOMER1,miR-23a-3p and MDA,SOD,GSH.Univariate and multivariate Logistic regression were used to analyze the influencing factors of progression of DR in type 2 diabetes patients.Receiver operating characteristic(ROC)carve was used to analyze the predictive value of serum circHOMER1 and miR-23a-3p in the progression of DR in patients with type 2 diabetes.Results There was a targeted relationship between circHOMER1 and miR-23a-3p.The serum MDA(28.66±4.52ng/ml)and circHOMER1(1.24±0.16)levels in the DR group were higher than those in the non DR group(16.95±3.27ng/ml,1.02±0.11),while SOD(45.39±7.84U/L),GSH(135.82±21.23μg/mL)and miR-23a-3p(0.88±0.07)levels were lower than those in the non DR group(81.65±11.47U/L,207.44±25.95μg/mL,1.01±0.09),and differences were statistically significant(t=9.813～22.602,all P<0.001).The serum MDA(33.28±4.96ng/ml)and circHOMER1(1.36±0.20)levels in the PDR group were higher than those in the NPDR group(25.23±3.58ng/ml,1.15±0.17),while SOD(34.39±7.15U/L),GSH(113.50±20.17μg/ml)and miR-23a-3p(0.79±0.07)levels were lower than those in the NPDR group(53.27±8.44U/L,152.43±23.99μg/ml,0.94±0.08),and the differences were statistically significant(t=4.906～10.376,all P<0.001).Spearman analysis showed that serum MDA and circHOMER1 were positively correlated with the severity of DR(r=0.533,0.473,all P<0.001),while SOD,GSH,miR-23a-3p were negatively correlated with the severity of DR(r=-0.552,-0.515,-0.529,all P<0.001).Pearson analysis showed that serum circHOMER1 was negatively correlated with miR-23a-3p,SOD,GSH,and positively correlated with MDA(r=-0.475,-0.460,-0.455,0.462,all P<0.001).Serum miR-23a-3p was positively correlated with SOD and GSH,and negatively correlated with MDA(r=0.428,0.437,-0.439,all P<0.001).Logistic regression analysis showed that high MDA,low SOD,low GSH,high circHOMER1,low miR-23a-3p,high FPG and high HbA1c were the risk factors of progression of DR in type 2 diabetes patients(OR=0.214～3.556,all P<0.05).The area under curve(AUC)of serum circHOMER1 and miR-23a-3p alone and jointhy predicting the progression of DR in type 2 diabetes patients were 0.751,0.797 and 0.903 respectively.The combined prediction was higher than that of serum circHOMER1 and miR-23a-3p alone(Z=3.179,2.335,P=0.002,0.020).Conclusion Serum MDA and circHOMER1 levels are higher in DR patients,while serum SOD,GSH and miR-23a-3p levels are lower.Abnormal expression of circHOMER1 and miR-23a-3p in serum is associated with progression of DR and oxidative stress.Combined detection of circHOMER1 and miR-23a-3p in serum can predict the progression of DR in patients with type 2 diabetes.

Objective To explore the relationship between the M1/M2 macrophages and severity of diabetic retinopathy(DR).Methods This retrospective study included 42 patients with or without DR who had type 2 diabetes mellitus(T2DM)and 19 healthy individuals undergoing cataract intraocular surgery without systemic or ocular diseases from Handan Central Hospital between April 2022 and November 2023.Patients with T2DM were divided into three groups:diabetes mellitus with non-dominant diabetic retinopathy(T2DM non-DR group,n=20),mild and moderate non-proliferative diabetic retinopathy(NPDR)(n=10)and severe NPDR/proliferative diabetic retinopathy(PDR)(n=12).Peripheral blood and aqueous humor were obtained at surgery initiation.The levels of VEGF-A,IL-8,Elafin and TGF-β in the samples were analyzed using kits,and the ratio of M1 macrophages to M2 macrophages was analyzed by flow cytometry.Results Among patients with T2DM,there were significant differences in the duration of diabetes,insulin and metformin use among the three groups(P<0.05).Aqueous humor levels of VEGF-A,IL-8,Elafin,M1 ratio,M2 ratio and TGF-β of each group were significantly different(F=17.40,9.492,4.792,11.32,5.768 and 20.38,all P<0.01).The levels of VEGF-A,IL-8,Elafin,M1 ratio,VD86 and TGF-β in severe NPDR/PDR group were significantly higher than those in healthy control group and T2DM non-DR group(P<0.05),and the levels of VEGF-A,IL-8 and Elafin in severe NPDR/PDR group were significantly higher than those in mild and moderate NPDR group(P<0.05).The levels of M1 proportion and TGF-β in aqueous humor of the mild to moderate NPDR group were significantly higher than those in healthy control group and T2DM non-DR group(P<0.05).The level of M1 in aqueous humor was positively correlated with the levels of M2,Elafin,TGF-β and VEGF-A(r=0.260,0.411,0.726 and 0.304,all P<0.05),and the level of M2 was positively correlated with the levels of Elafin and TGF-β(r=0.865,0.552,all P<0.01).Conclusion The elevation of IL-8 and M1 macrophages in the aqueous humor may promote the occurrence of DR,while the increase of Elafin and M2 macrophages may be a compensatory regulation to chronic inflammation,which is involved in the regulation of local microvascular lesions and fibrosis.

Objective To explore the correlation between serum circularRNA-HOMER1(circHOMER1),microRNA(miR)-23a-3p levels with clinical stages and oxidative stress in patients with diabetic retinopathy(DR).Methods From January 2023 to July 2024,75 DR patients treated in Handan Central Hospital were included as the DR group.According to the clinical staging of DR,they were divided into non proliferative DR(NPDR group,n=43)and proliferative DR(PDR group,n=32).In addition,75 patients with simple type 2 diabetes who came to Handan Central Hospital were included as non DR group.The levels of serum circHOMER1,miR-23a-3p,malondialdehyde(MDA),superoxide dismutase(SOD),and reduced glutathione(GSH)were detect-ed.Clinical data of the subjects were collected.The TargetScan website was used to predict the targeting relationship between circHOMER1 and miR-23a-3p.Pearson method was used to analyze the correlation between serum circHOMER1,miR-23a-3p and MDA,SOD,GSH.Univariate and multivariate Logistic regression were used to analyze the influencing factors of progression of DR in type 2 diabetes patients.Receiver operating characteristic(ROC)carve was used to analyze the predictive value of serum circHOMER1 and miR-23a-3p in the progression of DR in patients with type 2 diabetes.Results There was a targeted relationship between circHOMER1 and miR-23a-3p.The serum MDA(28.66±4.52ng/ml)and circHOMER1(1.24±0.16)levels in the DR group were higher than those in the non DR group(16.95±3.27ng/ml,1.02±0.11),while SOD(45.39±7.84U/L),GSH(135.82±21.23μg/mL)and miR-23a-3p(0.88±0.07)levels were lower than those in the non DR group(81.65±11.47U/L,207.44±25.95μg/mL,1.01±0.09),and differences were statistically significant(t=9.813～22.602,all P<0.001).The serum MDA(33.28±4.96ng/ml)and circHOMER1(1.36±0.20)levels in the PDR group were higher than those in the NPDR group(25.23±3.58ng/ml,1.15±0.17),while SOD(34.39±7.15U/L),GSH(113.50±20.17μg/ml)and miR-23a-3p(0.79±0.07)levels were lower than those in the NPDR group(53.27±8.44U/L,152.43±23.99μg/ml,0.94±0.08),and the differences were statistically significant(t=4.906～10.376,all P<0.001).Spearman analysis showed that serum MDA and circHOMER1 were positively correlated with the severity of DR(r=0.533,0.473,all P<0.001),while SOD,GSH,miR-23a-3p were negatively correlated with the severity of DR(r=-0.552,-0.515,-0.529,all P<0.001).Pearson analysis showed that serum circHOMER1 was negatively correlated with miR-23a-3p,SOD,GSH,and positively correlated with MDA(r=-0.475,-0.460,-0.455,0.462,all P<0.001).Serum miR-23a-3p was positively correlated with SOD and GSH,and negatively correlated with MDA(r=0.428,0.437,-0.439,all P<0.001).Logistic regression analysis showed that high MDA,low SOD,low GSH,high circHOMER1,low miR-23a-3p,high FPG and high HbA1c were the risk factors of progression of DR in type 2 diabetes patients(OR=0.214～3.556,all P<0.05).The area under curve(AUC)of serum circHOMER1 and miR-23a-3p alone and jointhy predicting the progression of DR in type 2 diabetes patients were 0.751,0.797 and 0.903 respectively.The combined prediction was higher than that of serum circHOMER1 and miR-23a-3p alone(Z=3.179,2.335,P=0.002,0.020).Conclusion Serum MDA and circHOMER1 levels are higher in DR patients,while serum SOD,GSH and miR-23a-3p levels are lower.Abnormal expression of circHOMER1 and miR-23a-3p in serum is associated with progression of DR and oxidative stress.Combined detection of circHOMER1 and miR-23a-3p in serum can predict the progression of DR in patients with type 2 diabetes.

One of its primary surgical treatments of tricuspid regurgitation is tricuspid valve biological valve replacement. Catheter tricuspid valve-in-valve implantation is a novel interventional alternative for biological valve failure. The non-invasive lung fluid measuring device remote dielectric sensing (ReDSTM) has been increasingly incorporated into clinical practice as a means of monitoring chronic heart failure in recent years. This report describes the process and outcomes of the first instance of perioperative lung fluid volume evaluation following transcatheter tricuspid valve implantation utilizing ReDSTM technology. The patient has a short-term, substantial increase in postoperative lung fluid volume as compared to baseline.

Objective:To study the value of coronary flow reserve (CFR) via dynamic single photon emission computed tomography (D-SPECT) in evaluating coronary microcirculation dysfunction (CMD) in patients with heart failure.Methods:A prospective research method was adopted. One hundred and ninety-four patients with heart failure from September 2019 to September 2020 in Zhongshan Hospital, Fudan University were selected. The patients were tested for CFR using D-SPECT, and CFR<2 was defined as CMD. The general data were recorded, including age, gender, body mass index (BMI), blood pressure, heart rate, smoking history, New York Heart Association (NYHA) heart function classification, comorbidities and medication situation. The laboratory test results were recorded, including blood urea nitrogen, blood creatinine, blood uric acid, estimated glomerular filtration rate (eGFR), high-sensitivity C-reactive protein (hs-CRP), cardiac troponin T (cTnT) and N terminal pro B type natriuretic peptide (NT-proBNP). The left atrial diameter (LAD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), interventricular septal thickness (IVST), pulmonary artery systolic pressure (PASP) and left ventricular ejection fraction (LVEF) were measured by cardiac ultrasound. After discharge, patients were followed up in outpatient or telephone contact, with the primary endpoint event being a composite endpoint consisting of cardiovascular death and heart failure readmission. Multiple linear regression analysis was used to analyze the risk factors of CFR. The Kaplan-Meier survival curve was draw, and the log-rank test was used to evaluate the effect of CFR on prognosis.Results:Among 194 patients, 133 patients had CMD (CMD group), and the incidence of CMD was 68.56%; 61 patients did not have CMD (non-CMD group). There were no statistical differences in gender composition, BMI, smoking history proportion, blood pressure, heart rate, hypertension rate, atrial fibrillation rate, diabetes mellitus rate, renal dysfunction rate, medication situation, LAD, LVEDD, IVST, PASP, blood urea nitrogen, blood creatinine, blood uric acid, eGFR and hs-CRP between two groups ( P>0.05). The age, rate of NYHA heart function classification Ⅲ to Ⅳ grade, rate of myocardial infarction or revascularization history, LVESD, cTnT and NT-proBNP in CMD group were significantly higher than those in non-CMD group: (60.7 ± 14.0) years old vs. (55.9 ± 15.8) years old, 54.89% (73/133) vs. 26.23% (16/61), 22.56% (30/133) vs. 1.64% (1/61), (48.8 ± 13.1) mm vs. (44.6 ± 11.4) mm, 0.023 (0.015, 0.046) μg/L vs. 0.015 (0.010, 0.023) μg/L and 1 591 (751, 3 409) ng/L vs. 1 132 (288, 1 860) ng/L, the LVEF was significantly lower than that in non-CMD group: (40.9 ± 14.2)% vs. (45.5 ± 14.1)%, and there were statistical differences ( P<0.05 or <0.01). Multiple linear regression analysis result showed that the cTnT was an risk factor of CFR ( β = - 0.18, 95% CI - 0.82 to - 0.06, P = 0.025). The median followed up time was 230 (136 to 330) d, 10 patients were lost to follow-up, with 58 patients in CMD group completing follow-up and 126 patients in the non-CMD group. The incidences of primary endpoint event and heart failure readmission in CMD group were significantly higher than those in non-CMD group: 23.02% (29/126) vs. 3.45% (2/58) and 15.87% (20/126) vs. 3.45% (2/58), and there were statistical differences ( P<0.01); there was no statistical difference in incidence of cardiovascular death between two groups ( P>0.05). Kaplan-Meier survival curve analysis result showed that the event free survival rate in CMD group was significantly lower than that in non-CMD group, and there was statistical difference (log-rank χ2 = 11.92, P<0.01). Conclusions:CMD is highly prevalent in patients with heart failure, and it is associated with poor prognosis. Improving CMD for improving coronary microcirculation may be potential targets for the treatment of heart failure.

In this paper, we prepared a dual functional system based on dextrin-coated silver nanoparticles which were further attached with iron oxide nanoparticles and cell penetrating peptide (Tat), producing Tat-modified Ag-FeO nanocomposites (Tat-FeAgNPs). To load drugs, an -SH containing linker, 3-mercaptopropanohydrazide, was designed and synthesized. It enabled the silver carriers to load and release doxorubicin (Dox) in a pH-sensitive pattern. The delivery efficiency of this system was assessed using MCF-7 cells, and using null BalB/c mice bearing MCF-7 xenograft tumors. Our results demonstrated that both Tat and externally applied magnetic field could promote cellular uptake and consequently the cytotoxicity of doxorubicin-loaded nanoparticles, with the IC of Tat-FeAgNP-Dox to be 0.63 µmol/L. The delivery efficiency of Tat-FeAgNP carrying Cy5 to the mouse tumor was analyzed using the optical imaging tests, in which Tat-FeAgNP-Cy5 yielded the most efficient accumulation in the tumor (6.7±2.4% ID of Tat-FeAgNPs). Anti-tumor assessment also demonstrated that Tat-FeAgNP-Dox displayed the most significant tumor-inhibiting effects and reduced the specific growth rate of tumor by 29.6% ( = 0.009), which could be attributed to its superior performance in tumor drug delivery in comparison with the control nanovehicles.

Objective To investigate the in vivo radioprotective effect of adenosine triphosphate (ATP) on radiation damage induced by high dose γ-ray ionizing radiation(IR) in mice.Methods Specific pathogen-free C57BL/6 female mice were randomly divided into IR group and IR+ATP group by body weight,with 10 mice in each group.All the mice were treated with a 8 Gy one-time and high-dose whole body γ-ray irradiation.Within 6 h after irradiation,mice were injected intramuscular injection of 150 pl sodium chloride solution (9 g/L) for IR group,and 150 μl ATP solution (6 mg/kg) for IR+ATP group,respectively.The drug was administered once a day until the death of the animal.The mean survival days,survival rate,body weight and major organ coefficients in both groups were measured.Results The average survival days of mice in IR group and IR +ATP group were 6.5 d and 9.6 d,respectively.The survival rate of the mice in IR+ATP group was higher than that in IR group (P＜0.01).The body weight values of the mice in IR+ATP group was higher than that in IR group on the after the 4th day post-irradiation,and the differences were statistically significant (all P＜0.05).Except for heart and stomach,the organ coefficients of liver,spleen,lung,and kidney in IR +ATP mice were higher than those in IR group,and the differences were statistically significant (all P＜0.05).Conclusion ATP has certain radiation protection effect,and it can reduce the radiation damage of mice induced by high-dose (8 Gy) γ-ray IR so as to increase the survival rate.

China ; Heart Failure ; epidemiology ; Humans

Objective To assess the effect of ultrasound contrast agent SonoVue on the dimensions and systolic function of left and right ventricle in pigs. Methods Sixteen pigs were randomly assigned to two groups. Intravenous injection of 1 ml of SonoVue were given in study group, and repeated 20 min later. The control group was given the same doses of saline. Before and after the administration of contrast agent, the end-diastolic dimension (LVEDD, RVEDD). end-systolic dimension ( LVESD, RVESD) and fractional shortening(LVFS,RVFS) of left and right ventricle were measured. The time to reach the extreme value of these parameters and the time to return to the baseline were recorded. Results There was no significant difference regarding the parameters at baseline between the two groups. After injection of SonoVue,RVEDD significantly increased from (25. 88 ± 1. 38) mm at baseline to its maximum of (33. 26 ± 0. 99)mm( P < 0. 05). Accordingly,RVFS significantly increased from (26. 90 ± 1. 92) % to (33. 92 ± 2. 53) % ( P <0. 05). Meanwhile,LVEDD remarkably decreased from (38.10 ± 1. 39)mm at baseline to its minimum of (26.25 ± 0. 65)mm( P <0. 05) and LVFS remarkably decreased from (36. 24 ± 1. 93) % to (29.13 ± 3.00) % ( P < 0. 05). There was no change in the control group after administration of the saline. When SonoVue was given repeatedly, the maximum RVEDD and RVFS was (29. 98 ± 1. 23) mm and (31. 09 + 1.90) % , respectively, which had less increase compared to the first time. Minimum LVEDD and LVFS was (31. 91 ± 1, 64)mm and (32. 17 ± 2. 31)%,respectively,with less decrease compared with which at first injection. It took (10. 15±0. 59) min for the right and left ventricle to reach the extreme value and (9.00± 0. 56) min to return to the baseline at the first injection. The time used for the right and left ventricle to reach its peak change and back to baseline after second injection of SonoVue were shorter [(8.73± 0.55) min and (6.89± 0.43) min, respectively,both P <0.05]. Conclusions Administration of SonoVue was associated with acute, transient dilation of right ventricle and compression of left ventricle. The influence of SonoVue on the right and left ventricle became less at it second injection.