Objective:To evaluate the effect of sevoflurane on Ca 2+ transporter expression in cardiomyocytes during right ventricular remodeling in rats with pulmonary arterial hypertension. Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) by the random number table method: control group (CM group), sevoflurane group (CS group), monocrotaline group (M group) and sevoflurane + monocrotaline group (S group). Monocrotaline 60 mg/kg was intraperitoneally injected in group M and group S, and monocrotaline lysate was intraperitoneally injected in group CM. The rats in S and CS groups inhaled 2.5% sevoflurane for 1 h, twice a week, at an interval of 3 days starting from the first day after injection of monocrotaline. Pulmonary artery acceleration time and pulmonary artery ejection time were measured by transthoracic echocardiography at 6 weeks after monocrotaline injection. The chest was exposed under 3% sevoflurane anesthesia, the heart was perfused, and the pulmonary artery branch and right ventricular myocardial tissues were retained. The wall thickness of pulmonary arterioles and cross-section area of right ventricular cardiomyocytes were observed by HE staining. The expression of Ca 2+ transporter in right ventricular cardiomyocytes was detected by Western blot. Results:Compared with CM group, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly decreased, the cross-section area of right ventricular cardiomyocytes was increased, the wall thickness of pulmonary arteriole was increased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was up-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was down-regulated in M group ( P<0.01). Compared with group M, the ratio of pulmonary artery acceleration time to pulmonary artery ejection time was significantly increased, the cross-section area of right ventricular cardiomyocytes was decreased, the wall thickness of pulmonary arteriole was decreased, the expression of type 1 sodium-calcium exchange and inositol triphosphate receptor was down-regulated, and the expression of voltage-dependent L-type calcium channel α1C subunit, type 2 ryanodine receptor, sarcoplasmic reticulum calcium pump 2α and proteinphilin-2 was up-regulated in group S ( P<0.01). Conclusions:The mechanism by which sevoflurane improves right ventricular remodeling is related to regulating the expression of Ca 2+ transporter in cardiomyocytes of rats with pulmonary arterial hypertension.

Myocardial infarction is one of the leading causes of mortality globally.Currently, the pleiotropic inflammatory cytokine interleukin-6 (IL-6) is considered to be intimately related to the severity of myocardial injury during myocardial infarction. Interventions targeting IL-6 are a promising therapeutic option for myocardial infarction, but the underlying molecular mechanisms are not well understood. Here, we report the novel role of IL-6 in regulating adverse cardiac remodeling mediated by fibroblasts in a mouse model of myocardial infarction. It was found that the elevated expression of IL-6 in myocardium and cardiac fibroblasts was observed after myocardial infarction. Further, fibroblast-specific knockdown of Il6 significantly attenuated cardiac fibrosis and adverse cardiac remodeling and preserved cardiac function induced by myocardial infarction. Mechanistically, the role of Il6 contributing to cardiac fibrosis depends on signal transduction and activation of transcription (STAT)3 signaling activation. Additionally, Stat3 binds to the Il11 promoter region and contributes to the increased expression of Il11, which exacerbates cardiac fibrosis. In conclusion, these results suggest a novel role for IL-6 derived from fibroblasts in mediating Stat3 activation and substantially augmented Il11 expression in promoting cardiac fibrosis, highlighting its potential as a therapeutic target for cardiac fibrosis.

Objective:This study aimed to systematically evaluate the efficacy and safety of ivabradine in patients with dilated cardiomyopathy, and to provide evidence-based reference for clinical treatment.Methods:We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wan Fang, VIP databases from inception to 1 September 2021 for randomized controlled trials (RCTs) that compared conventional therapies and ivabradine with conventional therapies in dilated cardiomyopathy patients. Studies meeting the inclusion criteria were included and analyzed. After data extraction and literature quality evaluation, we use the Review Manager 5.4 to perform the meta-analysis and publication bias test.Results:5 studies enrolling 494 patients were included. Compared with conventional therapies (control group), ivabradine and conventional therapies (observation group) significantly reduced resting heart rate [ MD=-7.58, 95% CI(-12.40, -2.76), Z=3.08, P=0.002], left ventricular end diastolic diameter (LVEDD) [ MD=-4.48, 95% CI(-7.33, -1.64), Z=3.09, P=0.002], left ventricular end systolic diameter (LVESD) [ MD=-4.94, 95% CI(-7.29, -2.59), Z=4.12, P<0.001], B-type natriuretic peptide (BNP) [ MD=-212.39, 95% CI(-230.55, -194.23), Z=22.92, P<0.001], New York Heart Association (NYHA) class [ MD=-0.36, 95% CI(-0.44, -0.27), Z=8.46, P<0.001] and Minnesota Questionnaire Score [ MD=-10.43, 95% CI(-15.72, -5.13), Z=3.86, P=0.001]. The left ventricular ejection fraction (LVEF) levels [ MD=1.31, 95% CI(0.64, 1.97), Z=3.85, P=0.001], 6-minute walk test level (6MWT) [ MD=54.83, 95% CI(40.58, 69.08), Z=7.54, P<0.001], systolic blood pressure [ MD=4.72, 95% CI(0.91, 8.54), Z=2.43, P=0.02], the incidence of visual symptoms (phosphene) [ OR=7.22, 95% CI(1.32, 45.00), P=0.02] and symptomatic bradycardia [ OR=8.90, 95% CI(1.21, 65.75), P=0.03] in the observation group were higher than those in the control group after treatment. In addition, there were no significant difference in the incidence of acute event between the two groups [ OR=0.72, 95% CI(0.12, 4.29), P=0.72]. Conclusions:Meta analysis showed that ivabradine combined β receptor blockers can effectively reduce resting heart rate and improve cardiac function in patients with dilated cardiomyopathy, but may increase the incidence of hallucinations and symptomatic bradycardia.

Objective:This study aimed to systematically evaluate the efficacy of Chinese medicine injection (CMI) in the treatment of heart failure (HF) after acute myocardial infarction (AMI).Methods:China National Knowledge Infrastructure (CNKI), WanFang Data, VIP, The Cochrane Library, PubMed, and EMbase databases were electronically searched from inception to October 2021 to identify randomized controlled trials (RCTs) on CMI for treating HF after AMI. Two reviewers independently screened literature, extracted data, and evaluated the bias risk of included studies. Network meta-analysis was then performed by ADDIS1.16.6 software and Stata 16.0 software.Results:A total of 55 studies were included involving 4 760 patients with HF after AMI and 3 types of CMIs, including Shenmai, Shenfu, Xinmailong injections. The results of network meta-analysis showed that Xinmailong injection was superior to Shenmai injection and Shenfu injection in improving the total effective rate and reducing left ventricular end diastolic diameter (LVEDD); Shenmai injection was superior to Xinmailong injection and Shenfu injection in reducing B-type natriuretic peptide (BNP); Shenfu injection was superior to Shenmai injection and Xinmailong injection in increasing left ventricular ejection fraction (LVEF) and reducing heart rate (HR).Conclusions:The combined 3 types of CMIs for treating HF after AMI can improve the clinical efficacy when compared with conventional Western medicine treatment. Among them, Xinmailong injection is better in improving the total effective rate and reducing LVEDD, Shenmai injection is more advantageous in reducing BNP, and Shenfu injection has the best efficacy in improving LVEF and reducing HR.

Objective:To evaluate the effects of sevoflurane on right ventricular myocardial fibrosis caused by pulmonary arterial hypertension (PAH) in rats.Methods:Eighteen SPF healthy adult male Wistar rats, weighing 260-300 g, were divided into 3 groups ( n=6 each) by a random number table method: control group (group C), group PAH and PAH plus sevoflurane group (group PS). The PAH model was established by single intraperitoneal injection of monocrotaline 60 mg/kg in group PAH and group PS, while the equal volume of normal saline was intraperitoneally injected in group C. Sevoflurane 1.5 MAC was inhaled for 1 h starting from the end of injection, twice a week for 6 weeks in total, in group PS.Echocardiography was performed at the end of 6th week to measure right ventricular end-diastolic diameter (RVEDD), right ventricular anterior wall end-diastolic thickness (RVWTd), interventricular septal end-diastolic thickness (IVSTd), pulmonary artery inner diameter (PAID) and pulmonary valve orifice maximum peak velocity (PV). At the end of 6th week, the hearts were taken to measure the weight of right ventricle, interventricular septum and left ventricle, and Fulton′s index was calculated, and the tissue of the lower lobe of the right lung was taken, the outer diameter and inner diameter of the vascular wall were measured to calculate the vascular wall thickness index (WT), and total vascular area and lumen area were measured to calculate the vascular wall area index (WA) after HE staining.The myocardial tissue of the right ventricle was obtained to observe the degree of myocardial fibrosis (with a light microscope after Masson staining) and to detect the expression of TGF-β1 (after immunofluorescence staining) and expression of TGF-β1, phosphorylated Smad3 (p-SMad3) and Smad7 (by Western blot). Results:Compared with group C, Fulton′s index, RVEDD, RVWTd, IVSTd, PAID, WT and WA were significantly increased, PV was decreased, the expression of TGF-β1 and pSmad3 in right ventricular myocardial tissues was up-regulated, the expression of Smad7 was down-regulated( P<0.01), and myocardial fibrosis occurred in group PAH.Compared with group PAH, Fulton′s index, RVEDD, RVWTd, IVSTd, PAID, WT and WA were significantly decreased, PV was increased, the expression of TGF-β1 and pSmad3 in right ventricular myocardial tissues was down-regulated, the expression of Smad7 was up-regulated ( P<0.05 or 0.01), and myocardial fibrosis was significantly improved in group PS. Conclusion:Sevoflurane can improve the myocardial fibrosis in right ventricle induced by PAH in rats, and the mechanism may be related to inhibiting activation of TGF-β1/Smad3 signaling pathway.

Objective To study the effect on renal function about repeated use of contrast media , and whether alprostadil has protective effect towards contrast-induced nephropathy ( CIN) .Methods 80 adult patients who had ever received contrast examination and scheduled to have PCI within 1 month were randomly divided into two groups: the simple hydration group and the hydration plus alprostadil therapy group.The serum level of creati-nine,urea, Cystatin C, Urineβ-microglobulin and creatinine clearance were recorded and compared between the two groups , and were observed before and after repeated exposure of contrast medium.The incidence of CIN was analyzed .Results Compared with pre-contrast levels , serum levels of urea, creatinin, Cystatin C and Urine β-microglobulin all elevated after single and repeated contrast media use in patients in the simple hydration group ( P<0.05 ) .The incidence of CIN did not differ after single or repeated contrast used (2.5%vs.15.0%, P>0.05).After repeated contrast exposure compared with patients with simple hydration , patients in the alprostadil group had repeated serum levels of urea [(7.4 ±2.3) mmol/L vs.(9.1 ±2.6) mmol/L], creatinia [(87.2 ±25.6) μmol/L vs.(96.9 ± 25.8) μmol/L], Cystatin C [(0.8 ±0.3) mg/L vs.(1.4 ±0.3) mg/L] and Urine β-microglobulin [(207.0 ±31.9 ) μg/L vs.(279.3 ±37.3 ) μg/L] were all lower with higher creatinin clearance [(92.2 ±24.2) ml/min vs.(78.2 ±27.5) ml/min](all P<0.05).The incidence of CIN in patients with alprostadil did not differ after single or repeated contrast used (2.5%vs.7.5%, P>0.05).The incidence of CIN in patients treated with alprostadil had no difference compared with patients with simple hydration after repeated contract (7.5% vs.15.0%, χ2 =0.501,P=0.479).Conclusions Contrast media can cause damage to renal function .Short-term repeated use of contrast media can further worsen renal function without significant increase in CIN rates .Alprostadil may have renoprotective effect towards CIN .

To establish a simple and sensitive LC-MS/MS method for simultaneous determination of the concentration for L-tryptophan(L-Try)and L-kynurenine(L-Kyn)in rat plasma. The changesin the process of the liver tumors formation may provide a basis for the diagnosis of liver cancer. 3-Nitro-L-tyrosine(3-NT)were added as the internal standard for the determination of two active substances and the chromatographic analysis was performed on a RRHD Eclipse Plus C18 column(3. 0 mm×100 mm, 1. 8 μm). The mobile phase was composed of water and acetonitrile(containing 0. 1%formic acid)(90 ∶10)at a flow rate of 0. 25 mL/min, and the injection volume is 5 μL. Detection and quantification were performed by mass spectrometry in multiple reaction monitoring mode with m/z 205. 12→146. 10(L-Try), m/z 209. 09 →146. 10(L-Kyn), m/z 227. 09→181. 10(3-NT), respectively. The results show that thelinear ranges were 9. 670-9 670 ng/mL for L-Try, and 9. 973-9973 ng/mL for L-Kyn(r2≥0. 9990). The limit of quantitation were 9. 670 ng/mL for L-Try, and 9. 973 ng/mL for L-Kyn, respectively. The intra- and inter-day precisions were all less than15%; the recoveries ofthe two analytes were more than 81. 17% and severe matrix effect was not observed. The ratio of L-Try/L-Kyn determined by LC-MS/MS in rat plasma showed an overall downward trend, which could used effectively for the drug metabolism studies and researches on the action mechanism of medicine on liver cancer. A rapid, simple, sensitive and specific LC-MS/MS method has been successfully developed and could also be used effectively for the drug metabolism studies and researches on the action mechanism of medicine on liver cancer.

Aim To study the effect of adiponectin ( APN) on myocardial ischemia reperfusion( IR) injury in diabetic rats and to explore the role of oxidation-an-tioxidation system. Methods Male Sprague Dawley rats were randomly divided into control group( NS) , IR group ( NIR ) , diabetes group ( DS ) , DS + IR group (DIR), DS +APN +IR group(APN). Experimental diabetes was induced in the animals by a single intrap-eritoneal injection of streptozotocin at a dose of 55 mg ·kg-1 . The IR and NIR group were subjected to myo-cardial I/R injury. APN group was administered APN through intravenous injection 10 min before the reper-fusion, the others were administered normal saline. The rats were considered diabetic and used for the study only if their glucose levels were higher than 15 mmol·L-1. Results All the diabetic rats exhibited increased levels of blood glucose and reduction of body weight ( P <0. 05 ) . Compared with those of NS and DS groups, the myocardial infarct size, cardiomyocyte apoptosis, MDA concentration and ROS in NIR and DIR groups were remarkably increased, activities of SOD and NO were decreased(P<0. 05 or P<0. 01). APN decreased oxidative stress product generation and myocardial apoptosis induced by diabetic myocardial I/R injury ( P <0. 05 ) . Conclusion APN exerts pro-tective effect on myocardial I/R injury in diabetic rats through anti-oxidative mechanism.

Objective To explore the activity of thioredoxin reductase (TrxR) in chronic myeloid leukemia cell line K562 and the anti-leukemia effect of BBSKE (a novel inhibitor of TrxR) in vitro. Methods The activity of TrxR on K562 cell lineage and fresh bone marrow cell from healthy adult was analyzed by insulin reduction assay. The inhibition of proliferation was measured by CCK-8 assay. The anti-leukemia effect of BBSKE was detected by laser scanning confocal microscope,agarose gel electrophoresis and flow cytometry with Annexin V -FITC/PI staining. Results TrxR activity of K562 cell lineage was significantly higher than that of normal bone marrow mononuclear cells. The apoptosis of K562 cells could be induced at concentrations of 10 μmol/L BBSKE after treated for 24 hours. The typical DNA ladder bans were observed by agarose gel electrophoresis. The apoptotic rates of K562 cells were (10.28±2.74) %. Application of 10 μmol/L BBSKE for 48 hours could also induce apoptosis of fresh bone marrow cell from chronic myeloid leukemia patients, and the apoptotic rates were (5.70±0.48) %. Conclusion TrxR activity in chronic myeloid leukemia cells was significantly higher than that of normal cells. BBSKE inhibits the TrxR activity and the proliferation of K562 by inducing apoptosis.It might be a potential medication for chronic myeloid leukemia.

Objective To induce adipose-derived mesenchymal stem cells (ADMSCs) differentiation into cardiomyocytes, so as to provide stem cells for myocardial regeneration.Method ADMSCs were isolated and cultured from adult adipose tissue in vitro.They were induced with 10μmol/L 5-azacytidine (5Aza) for 24h.At the 7th, 14th, 21st days after induction, the expression of α-sarcomeric actin, and myosin heavy chain were repeatedly detected by immunocytochemistry.The expression of ANP was detected by RT-PCR.Results At the 7th day after induction, there was no expression of α-sarcomeric actin and MHC.At the 14th day, there was a little expression of α-sarcomeric actin and MHC that could be seen in cells.At the 21st day, there was increased expression of α-sarcomeric and MHC, and the expression of ANP was positive results detected by RT-PCR.Conclusions 5-Aza can induced ADMSCs to differentiate into cardiomyocytes.ADMSCs might be a potential source of cell transplantation for myocardial.