1.Protective effect of novel phosphodiesterase 5 inhibitor CPD1 on promoting autophagy activation in hearts of rats with pathological myocardial hypertrophy
Xuedi ZHANG ; Huasui CUI ; Yeding SONG ; Haoyan CHEN ; Xiping CUI ; Fanghong LI ; Yunping MU ; Zijian ZHAO
Chinese Journal of Comparative Medicine 2025;35(8):29-38
Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180~200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P<0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P<0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.
2.Protective effect of novel phosphodiesterase 5 inhibitor CPD1 on promoting autophagy activation in hearts of rats with pathological myocardial hypertrophy
Xuedi ZHANG ; Huasui CUI ; Yeding SONG ; Haoyan CHEN ; Xiping CUI ; Fanghong LI ; Yunping MU ; Zijian ZHAO
Chinese Journal of Comparative Medicine 2025;35(8):29-38
Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180~200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P<0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P<0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.
3.Transcatheter arterial chemoembolization for hepatocellular carcinoma complicated by portal vein tumor thrombosis: prognostic analysis
Peng CUI ; Xiaoli DU ; Han ZHOU ; Qingwen LIU ; Yun GUO ; Chunmiao WU ; Xiping LIU
Journal of Interventional Radiology 2018;27(3):266-271
Objective To investigate the potential prognostic factors in patients with hepatocellular carcinoma (HCC) complicate by portal vein tumor thrombosis (PVTT) who are treated with transcatheter arterial chemoembolization (TACE). Methods The complete clinical data of a total of 46 patients with HCC complicate by PVTT, who were treated with TACE during the period from January 2010 to March 2016, were retrospectively analyzed. Clinical material database was established. Kaplan-Meier test was adopted to analyze the survival rate and the COX risk ratio model was used to screen out the independent prognostic factors. Life table method was employed to calculate the survival time. Results The 6-, 12-, 18- and 24-month survival rates were 51. 2%, 28. 9%, 23. 4% and 10. 2%, respectively. The median survival time was 6. 7 months. According to mRECIST standard, complete remission (CR) was obtained in one patient (2. 1%), partial remission (PR) in 11 patients (23. 9%), stable disease (SD) in 16 patients (34. 8%) and progress disease (PD) in 18 patients (39. 2%). Multivariate analysis indicated that local tumor response, ascites, cholinesterase, and arteriovenous fistula were the independent factors affecting the prognosis. Conclusion The independent prognostic factors that affect the survival time of HCC patient include local tumor response, ascites, cholinesterase and arteriovenous fistula. (J Intervent Radiol, 2018, 27: 266-271)
4.The association between smoking status and carotid artery plaque in rural areas of Eastern part of China.
Jing LUO ; Wei CUI ; Yu DING ; Binyan WANG ; Shanqun JIANG ; Genfu TANG ; Tonghua ZANG ; Xianhui QIN ; Yu WANG ; Yi WANG ; Fangfang FAN ; Yan ZHANG ; Jianping LI ; Yong HUO ; Xiping XU
Chinese Journal of Preventive Medicine 2015;49(3):243-247
OBJECTIVETo investigate the correlation between smoking status and carotid plaque in rural population residing in Eastern part of China.
METHODSBetween July and September of 2013, an epidemiological survey was carried out in residents aged 40 or above men who were enrolled randomly in rural areas of Anqing, Anhui province and Lianyungang, Jiangsu province. The data on epidemiological characteristics including smoking status, physical examination were collected using standardized protocol, and carotid ultrasonography was applied to examine the incidence of carotid plaque among never smokers, former smokers and current smokers. Logistic regress analysis was performed to determine the effect of smoking on carotid plaque.
RESULTSIn the study, a total of 625 male participants were included in the study. 51.4% (321 cases) were current smokers, 21.3% (133 cases) were former smokers, and 27.4% (171 cases) were never smokers. 32.0% (200/625) had carotid plaque. The incidence of carotid plaques was significantly higher in current smokers (35.2%, 113/321) than that in never smokers(23.4%,40/171) (χ(2) = 7.26, P = 0.007) and the incidence in former smokers (35.3%, 47/133) was also higher than that in never smokers (23.4%, 40/171) (χ(2) = 5.23, P = 0.022). Multiple logistic regression analysis showed that current cigarette smoking is significantly associated with the increased risk of carotid plaque (OR = 1.84, 95% CI: 1.13-2.98, P = 0.014) in comparison with never smokers, and there was an interaction between current smoking and age in association with carotid plaque. Compared with the young (≤60 years old) and never smoking group (8%, 3/40), prevalence of carotid plaque among the elderly (>70 years old) and smoking group (55%, 31/56) was significantly higher (OR = 8.06, 95% CI: 2.07-31.45) after adjusting for age, systolic blood pressure, diastolic blood pressure, blood glucose, total cholesterol, triglyceride high-density lipoprotein, body mass index, drinking and regional differences.
CONCLUSIONIt found that cigarette smoking was associated with increased risk of carotid plaque in rural elderly population residing in Eastern part of China.
Aged ; Alcohol Drinking ; Blood Glucose ; Blood Pressure ; Body Mass Index ; Carotid Stenosis ; China ; Cholesterol ; Humans ; Lipoproteins, HDL ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Rural Population ; Smoking ; Triglycerides
5.Effects of sevoflurane-remifentanil anesthesia on the balance between cerebral oxygen supply and demand during cerebral revascularization for ischemic moyamoya disease
Fa LIANG ; Weihua CUI ; Ying HE ; Xiping JIAO ; Rong WANG ; Dong ZHANG ; Ruquan HAN
Chinese Journal of Anesthesiology 2013;(2):167-170
Objective To evaluate the effects of sevoflurane-remifentanil anesthesia on the balance between cerebral oxygen supply and demand during cerebral revascularization for ischemic moyamoya disease by monitoring regional cerebral O2 saturation (rSO2) with near infrared spectroscopy.Methods Forty patients of both sexes aged 19-59 yr with a body mass index of 19-25 kg/m2 undergoing superficial temporal artery-middle cerebral artery anastomosis were randomly allocated into 2 groups (n =20 each):propofol-remifentanil group (group PR) and sevoflurane-remifentanil group (group SR).Radial artery was cannulated for direct BP monitoring and blood sampling.Near infrared spectroscopy probe was placed on the forehead.Anesthesia was induced with propofol TCI (Cp =5 μg/ml),fentanyl 3 μg/kg and rocuronium 0.6 mg/kg.The patients were mechanically ventilated after tracheal intubation (VT 8-10 ml/kg,RR 10-12 bpm,I∶ E 1∶2,FiO2 =1.0).PETCO2 was maintained at 35-40 mm Hg.Anesthesia was maintained with sevoflurane (end-tidal concentration 1.0%-1.7 %) or propofol TCI (Cp =3-4 μg/ml) in combination with remifentanil TCI (Cp =3.5 ng/ml) and intermittent iv boluses of rocuronium 0.3 mg/kg.BIS was maintained at 40-60 during operation.rSO2 was recorded before induction of anesthesia (T0),10 min before and 10 min after blood vessel was clamped (T1,T2) and 10 min after anastomosis was completed (T3).Results rSO2 was significantly increased on the operated side at T3 in PR group while in SR group bilateral rSO2 was significantly increased at T1-3 as compared with the baseline values at T0 (P < 0.05 or 0.01).rSO2 on the operated side was significantly higher at T1 in group SR than in PR group (P < 0.05).Conclusion The efficacy of sevoflurane-remifentanil anesthesia is similar to that of propofol-remifentanil anesthesia for revascularization for moyamoya disease in terms of maintence of the balance between cerebral oxygen supply and demand.
6.Clinical efficacy of three-dimensional conformal radiotherapy combined with thermochemotherapy in the treatment of locally advanced pancreatic cancer
Lingxin MENG ; Zhaojun DING ; Xiping CHEN ; Aili ZHANG ; Yingjie XUE ; Wen CUI ; Yuhua CHI
Journal of Chinese Physician 2012;(10):1327-1330
Objective To evaluate the clinical efficacy of three-dimensional conformal radiotherapy (3D-CRT) combined with thermochemotherapy in the treatment of locally advanced pancreatic cancer (LAPC).Methods From June 2008 to June 2011,70 patients with LAPC were divided into radiotherapy group (30 patients) and combination group (40 patients).Radiotherapy used 3D-CRT with a 90% to 95% isodose curve,a single dose of 1.8 to 2.OGy,and total radiation dose 50 ~ 70 Gy.The combination group patients received simultaneous thermotherapy at 41.5 ~43.5 ℃ (1 h/fraction,twice a week for 6 times),and hyperthermia given simultaneously injected using arsenic trioxide 20 mg,recombinant mutant human tumor necrosis factor(rmhTNF) intravenous infusion of 10 million U,4 to 6 times,or 3D-CRT at the same time and the treatment given after gemcitabine(0.6 ~ 1.0 g/m2) on Days dl and 8 and cisplatin (DDP) (20 ~ 30 mg/m2) on Days d1-3 intravenous infusion,repeated every 28 days for 3 ~ 6 cycles.Results At 3 months after treatment,the total response (complete remission and partial remission) rate was 70.0% (49/70),the efficiency of radiotherapy combined with chemotherapy,and radiotherapy combined with thermo-chemotherapy were 56.5% and 88.2%,and the radiotherapy alone group was 56.7%.There were significant difference in efficiency between radiotherapy combined with thermo-chemotherapy group compared to radiotherapy-chemotherapy group and radiotherapy group (x2 =4.68,4.98,P < 0.05),the last two groups showed no significant difference (P > 0.05).The 1-year and 2-year survival rate was 46.8% and 20.3%,respectively.The 1-year and 2-year survival rates were 52.4% and 26.7% in combination group,and 42.5% and 16.2% in radiotherapy group (x2 =14.17,P < 0.05 ; x2 =9.74,P < 0.05).No serious complications such as perforation,bleeding,and high fever were seen during treatment and follow-up.Conclusions 3D-CRT combined with thermochemotherapy is well tolerated and is relatively effective for the LAPC patients.
7.Preliminary study of tumor markers changes in the peripheral serum of pancreatic cancer patients treated by three-dimensional conformal radiotherapy combined with hyperthermia
Lingxin MENG ; Zhaojun DING ; Yingjie XUE ; Xiping CHEN ; Wen CUI ; Yuhua CHI
Journal of Chinese Physician 2011;13(12):1589-1592
ObjectiveTo determine the peripheral serum expressions and clinical value of carcinoembryonic antigen (CEA) and carbohydrate antigen CA19-9,CA242,CA72-4 and a single sialic acid ganglioside (CA50) antigen in advanced pancreatic cancer patients treated by three-dimensional conformal radiotherapy (3D-CRT) combined with endogenous field hyperthermia.Methods60 patients inoperable,advanced pancreatic cancer were treated by 3D-CRT combined with endogenous field hyperthermia.Radiation dose (DT) was 46 ~ 66 GY/23 ~ 33 F.Hyperthermia temperature was 41 ~ 43 ℃ 2 times/week,lasted 60 min each time.The expressions of CEA,CA19-9,CA242,CA72-4 and CA50 in peripheral serum were detected by Electrochemiluminescence immunoassay (ECLIA) every 2 weeks during treatment,and correlation were analyzed with tumor diameter,clinical stage,lymph node metastasis.Results From the 8th week,with 3D-CRT combined with endogenous field hyperthermia ongoing,CEA,CA19-9,CA50 andCA242 expression levels showed a gradual decline.CEA,CA19-9,CA50 and CA242 expression levels were (6.22 ± 2.71 ) μg/L,(43.44 ± 12.93 ) μg/L,(23.21 ± 7.71 )g/L and (24.26 ± 8.92) μg/L in 6 weeks,respectively.The difference was statistically significant among week 6 and week 0,week2,week 4 ( P <0.05),however there was no significant difference between week 6 and week 8 ( P > 0.05 ).The CA724 expression did not change significantly ( P > 0.05 ).There were positively correlation between CEA,CA199,CA50 and CA242 with pancreatic cancer tumor size,clinical stage and lymph node metastasis( respectively r =0.877,0.725,0.826,all P < 0.01 ),however CA72-4 had no correlations ( P > 0.05).ConclusionsCEA,CA19-9,CA50 and CA242 expressions in peripheral serum of pancreatic cancer patients were closely related to the treatment.Their joint detection can be served as independent objective evaluation reference information for the treatment efficacy and prognosis.

Result Analysis
Print
Save
E-mail