1.PCSK9 promotes mitochondrial dysfunction to accelerate the process of abdominal aortic aneurysm
Man LI ; Yanyu CHEN ; Mengdie XIA ; Qian XU ; Yating ZHOU ; Huayu ZHANG ; Lushan LIU ; Zhihan TANG ; Juan PENG
Chinese Journal of Arteriosclerosis 2025;33(3):209-218
Aim To explore the impact and mechanism of proprotein convertase subtilisin kexin 9(PCSK9)on the progression of abdominal aortic aneurysm(AAA).Methods 6~8 week old ApoE-/-mice were selected to estab-lish the AAA model.Angiotensin Ⅱ(Ang Ⅱ)was continuously infused through subcutaneous implantation of a micro-os-motic pump.The mice were fed with high-fat diet and killed after 28 days.The expression of PCSK9 in abdominal aor-tic smooth muscle cells was detected by immunohistochemistry and immunofluorescence in normal abdominal aortic blood vessels and AAA samples in human and mice.Primary cultured murine vascular smooth muscle cells(mVSMC)of C57BL/6 mice were treated with different concentrations of AngⅡ for 24 h,and the expression of PCSK9 mRNA and pro-tein was detected.PCSK9 overexpression and knockdown cell models were established,and mitochondrial reactive oxygen species(mtROS),mitochondrial membrane potential(MMP),mitochondrial permeability transition pore(MPTP)open-ing,and Z-DNA binding protein 1(ZBP1)protein expression were detected.Bioinformatics was used to analyze the dif-ferential expression of multiple single-cell sequencing datasets to obtain the key differentially expressed genes,and to study their expression and role in AAA.Results Immunohistochemistry and immunofluorescence results showed that PCSK9 expression in human and mouse AAA increased(P<0.01),and co-localized with smooth muscle.Ang Ⅱ promoted PCSK9 expression in mVSMC in a concentration-dependent manner,the 2.0 μmol/L Ang Ⅱ group showed a 2.9-fold and 1.1-fold increase in the expression of PCSK9 mRNA and protein,respectively(P<0.01),with the most significant effect observed.After successfully constructing PCSK9 overexpression and PCSK9 interference mVSMC models,PCSK9 overex-pression led to an increase in intracellular mtROS,a decrease in MMP,an increase in MPTP opening,and a decrease in cellular activity(P<0.01);PCSK9 knockdown could reduce Ang Ⅱ induced increase in mtROS,decrease in MMP and MPTP opening;compared with the siNC+Ang Ⅱ group,the siPCSK9+Ang Ⅱ group showed a decrease in mtROS and an in-crease in the fluorescence brightness of MMP and MPTP(P<0.05).Bioinformatics analysis revealed that ZBP1 was a core differentially expressed gene in AAA.Immunohistochemistry and immunofluorescence results showed that ZBP1 ex-pression in human and mouse AAA tissues increased,and co-localized with smooth muscle.Western blot results showed that PCSK9 overexpression or treatment with 2.0 μmol/L Ang Ⅱ could increase ZBP1 protein expression(P<0.01),while PCSK9 knockdown could alleviate the increased ZBP1 expression caused by AngⅡ(P<0.05).Conclusion PCSK9 may induce mitochondrial damage in smooth muscle cells,activate downstream molecule ZBP1 to cause cell damage,and promote the development of AAA.
2.PCSK9 promotes mitochondrial dysfunction to accelerate the process of abdominal aortic aneurysm
Man LI ; Yanyu CHEN ; Mengdie XIA ; Qian XU ; Yating ZHOU ; Huayu ZHANG ; Lushan LIU ; Zhihan TANG ; Juan PENG
Chinese Journal of Arteriosclerosis 2025;33(3):209-218
Aim To explore the impact and mechanism of proprotein convertase subtilisin kexin 9(PCSK9)on the progression of abdominal aortic aneurysm(AAA).Methods 6~8 week old ApoE-/-mice were selected to estab-lish the AAA model.Angiotensin Ⅱ(Ang Ⅱ)was continuously infused through subcutaneous implantation of a micro-os-motic pump.The mice were fed with high-fat diet and killed after 28 days.The expression of PCSK9 in abdominal aor-tic smooth muscle cells was detected by immunohistochemistry and immunofluorescence in normal abdominal aortic blood vessels and AAA samples in human and mice.Primary cultured murine vascular smooth muscle cells(mVSMC)of C57BL/6 mice were treated with different concentrations of AngⅡ for 24 h,and the expression of PCSK9 mRNA and pro-tein was detected.PCSK9 overexpression and knockdown cell models were established,and mitochondrial reactive oxygen species(mtROS),mitochondrial membrane potential(MMP),mitochondrial permeability transition pore(MPTP)open-ing,and Z-DNA binding protein 1(ZBP1)protein expression were detected.Bioinformatics was used to analyze the dif-ferential expression of multiple single-cell sequencing datasets to obtain the key differentially expressed genes,and to study their expression and role in AAA.Results Immunohistochemistry and immunofluorescence results showed that PCSK9 expression in human and mouse AAA increased(P<0.01),and co-localized with smooth muscle.Ang Ⅱ promoted PCSK9 expression in mVSMC in a concentration-dependent manner,the 2.0 μmol/L Ang Ⅱ group showed a 2.9-fold and 1.1-fold increase in the expression of PCSK9 mRNA and protein,respectively(P<0.01),with the most significant effect observed.After successfully constructing PCSK9 overexpression and PCSK9 interference mVSMC models,PCSK9 overex-pression led to an increase in intracellular mtROS,a decrease in MMP,an increase in MPTP opening,and a decrease in cellular activity(P<0.01);PCSK9 knockdown could reduce Ang Ⅱ induced increase in mtROS,decrease in MMP and MPTP opening;compared with the siNC+Ang Ⅱ group,the siPCSK9+Ang Ⅱ group showed a decrease in mtROS and an in-crease in the fluorescence brightness of MMP and MPTP(P<0.05).Bioinformatics analysis revealed that ZBP1 was a core differentially expressed gene in AAA.Immunohistochemistry and immunofluorescence results showed that ZBP1 ex-pression in human and mouse AAA tissues increased,and co-localized with smooth muscle.Western blot results showed that PCSK9 overexpression or treatment with 2.0 μmol/L Ang Ⅱ could increase ZBP1 protein expression(P<0.01),while PCSK9 knockdown could alleviate the increased ZBP1 expression caused by AngⅡ(P<0.05).Conclusion PCSK9 may induce mitochondrial damage in smooth muscle cells,activate downstream molecule ZBP1 to cause cell damage,and promote the development of AAA.
3.Epstein-Barr virus-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma:A report of 3 cases and literature review
Lushan PENG ; Xianchu PENG ; Saili DUAN ; Zhejia ZHANG
Journal of Central South University(Medical Sciences) 2024;49(2):319-329
Hepatic lymphoepithelioma-like carcinoma(LELC)is an extremely rare malignant tumor characterized by undifferentiated malignant epithelial cells and significant lymphatic infiltration.Hepatic LELC mainly includes lymphoepithelioma-like hepatocellular carcinoma(LEL-HCC)and lymphoepithelioma-like intrahepatic cholangiocarcinoma(LEL-CC).Epstein-Barr virus(EBV)infection is considered as an important factor in LELC carcinogenesis.Since 2005,Xiangya Hospital of Central South University has treated a total of 3 patients with EBV-associated LEL-CC,which all showed liver masses by CT scans.After surgical resection,the EBV encoded RNA(EBER)and CK19 expression in all 3 patients were positive,and pathological examination confirmed EBV-associated LEL-CC.Two patients had a good postoperative prognosis,while 1 patient received relevant immunotherapy and chemotherapy after surgery.Based on the analysis of existing literature,the author believes that hepatic LELC can be included in the classification of liver tumors,which will provide new ideas for the accurate diagnosis and treatment of hepatic LELC.
4.Clinical features and imaging manifestations for intravascular large B-cell lymphoma
Hong JIN ; Weihua LIAO ; Shuai YANG ; Lushan PENG ; Wu XING
Journal of Central South University(Medical Sciences) 2023;48(12):1920-1928
Objective:Intravascular large B-cell lymphomas are a rare group of extranodal non-Hodgkin's lymphomas with no apparent specificity of symptoms and often a poor prognosis.This study aims to investigate the clinical features and imaging manifestations of intravascular large B-cell lymphoma,to improve the awareness of clinicians and imaging physicians and to reduce the underdiagnosis and misdiagnosis of this disease. Methods:Five patients with pathologically confirmed intravascular large B-cell lymphoma diagnosed between December 2011 and February 2022 at Xiangya Hospital of Central South University were retrospectively analyzed for clinical features and imaging manifestations. Results:The age range for the 5 patients in this paper was 44-72 years at an average of(55.4±11.2)years,2 were male and 3 were female.There were 4 patients with fever,3 patients with cough,3 patients with fatigue,and 2 patients with neurological symptoms.The primary sites of lesions were bilateral adrenal glands(2 cases),liver(1 case),central nervous system(1 case),lung(1 case).Imaging of the corresponding site was performed in 5 cases.When the primary site is the adrenal gland,it appears as bilateral adrenal masses or bilateral adrenal thickening with clear contours.When the primary site is the liver,it appears as a hypodense lesion in the right lobe of the liver with"vascular floating sign".When the primary site is the central nervous system,it appears as multiple tumor-like lesions in the frontal-parietal-occipital lobe,right temporal lobe and bilateral cerebellar hemispheres with multiple hemorrhages within the lesions.When the primary site is the lung,it appears as multiple ground glass shadows and solid changes in both lungs with localized lobular septal thickening.The final pathological diagnosis was intravascular large B-cell lymphoma in all 5 patients,one of whom had a good prognosis after chemotherapy,2 of whom died within 3 days of discharge,and two of whom were lost to follow-up. Conclusion:Intravascular large B-cell lymphoma can involve multiple tissues and organs,and its prognosis is often poor,and its imaging manifestations possess certain specificity.When this disease is highly suspected,a biopsy of the corresponding organ should be performed as soon as possible to clarify the diagnosis.
5.Therapeutic Observation of Bloodletting Cupping at Dazhui (GV14) plus Scraping for Hordeolum
Juan CAO ; Junwei WANG ; Lushan WANG ; Li PENG
Shanghai Journal of Acupuncture and Moxibustion 2016;35(6):704-706
Objective To observe the clinical efficacy of bloodletting cupping at Dazhui (GV14) plus scraping in treating hordeolum. Method Forty-four patients with hordeolum were randomized into a control group and a treatment group, 22 cases in each group. The control group was intervened by bloodletting cupping at Dazhui, while the treatment group was by bloodletting cupping at Dazhui plus scraping. The size of the infection on eyelid was observed before and after treatment, and the recovery rate was calculated. Result The total effective rate was 81.8% in the control group versus 95.5% in the treatment group, and the total effective rate in the treatment group was higher than that in the control group (P<0.05); the sizes of the eyelid infection were significantly reduced in both groups after treatment (P<0.05), and the reduction in the treatment group was more significant than that in the control group (P<0.05). Conclusion Bloodletting cupping at Dazhui plus scraping can effectively improve the symptoms, reduce infection size, and enhance the clinical efficacy in treating hordeolum.
6.Observation on Therapeutic Effects of Acupuncture plus Psychological Intervention for Postpartum Depression
Hanling HUANG ; Li PENG ; Su ZHENG ; Lushan WANG
Journal of Acupuncture and Tuina Science 2014;(6):358-361
Objective: To observe the therapeutic effect of acupuncture plus psychological intervention for postpartum depression.
Methods: By random number table, 85 patients with postpartum depression were divided into a treatment group and a control group. Forty-three cases in the treatment group were treated by acupuncture plus psychological intervention, once every day, five sessions per week, and rest at weekend. Forty-two cases in the control group were treated by oral administration of Fluoxetine Hydrochloride, 20 mg, once per day. The two groups were treated continuously for six weeks. The change of the score in Hamilton depression scale (HAMD) was observed and the therapeutic effect was summarized.
Results:The total effective rate was 90.7%in the treatment group and 90.5% in the control group. The difference in the total effective rate between two groups was not statistically significant (P>0.05). In the intra-group comparisons of HAMD scores two, four and six weeks after treatment in both groups with those before treatment, the differences were statistically significant (all P<0.05). In comparison between the two groups at the same time point, the differences in HAMD scores were not statistically significant (all P>0.05). Regarding the adverse events, 5 cases had nausea, 3 cases had dizziness, and 6 cases had poor appetite in the control group; no obvious adverse events happened in the treatment group.
Conclusion:Acupuncture plus psychological intervention for postpartum depression is as same as oral administration of Fluoxetine Hydrochloride in therapeutic effects, but it does not have adverse reaction.

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