1.Molecular Mechanisms of Huangjing Zanyu Capsule in Treating Oligoasthenospermia:A Study Based on AMPK-Mediated Mitophagy
Yuan GAO ; Yiyang GUO ; Mohan WU ; Yanfei ZHENG
Journal of Sichuan University (Medical Sciences) 2025;56(1):74-82
Objective To investigate the molecular mechanism of Huangjing Zanyu Capsule(HJZY),a new class-Ⅲ traditional Chinese medicine for the treatment of male infertility developed by Wang Qi,an academician of the Chinese Academy of Engineering,based on AMPK-mediated mitophagy in the treatment of oligoasthenospermia.Methods Acrolein(ACR)was used to treat GC-2spd(ts)mouse spermatocytes to establish a cell model of oligoasthenospermia.The optimal ACR concentration and exposure time for subsequent modeling were determined by CCK8 cell viability assay.After successful modeling,the cells were cultured in complete medium containing different concentrations of HJZY.Then,cell viability was assessed by CCK8 assay after 24 hours,and the subsequent treatment concentration was determined based on the cell viability.After the GC-2spd cells adhered to the wall,they were divided into a normal control(NC)group,a modeling group,and an ACR+HJZY treatment group.The effect of HJZY on mitophagy was observed by confocal fluorescence microscopy.The three groups of cells were transfected with siRNA-NC and siRNA-AMPK,respectively,and divided into six groups,including siRNA-NC+control,siRNA-NC+ACR,siRNA-NC+ACR+HJZY,siRNA-AMPK+control,siRNA-AMPK+ACR,and siRNA-AMPK+ACR+HJZY groups.Western blot was performed to validate the regulatory effect of HJZY on mitophagy-related proteins,such as p-AMPK,LC3B,P62,PINK1,Parkin,TBK1,and ULK1,which were all proteins mediated by AMPK.Results Through the cell viability assay,34 μmol/L was selected as the the modeling concentration of ACR,and 20 minutes was selected as the modeling time The treatment concentration of HJZY was 160 μmol/L.Confocal fluorescence microscopy showed that HJZY had,to a certain degree,a positive regulatory effect on the mitochondrial membrane potential of damaged spermatogenic cells.The mitochondrial membrane potential of the model group decreased significantly compared with that of the NC group.After exposure to treatment,the cell membrane potential of the ACR+HJZY treatment group increased compared with that of the model group,and the difference was statistically significant(P<0.05).Western blot results showed that the expression levels of p-AMPK/AMPK and PINK1 proteins in the siRNA-NC+ACR group were significantly lower than those in the siRNA-NC+control group(P<0.001).The level of Parkin protein in the siRNA-NC+ACR group was lower than that in the siRNA-NC+control group,but the difference was not statistically significant.After the administration of HJZY,the levels of these 3 proteins increased,and those in the siRNA-NC+ACR+HJZY group were higher than those in the siRNA-NC+ACR group(P<0.001).The expression levels of LC3B,P62,TBK1,and ULK1 proteins in the siRNA-NC+ACR group were higher than those in the siRNA-NC+control group(P<0.01),and those in the siRNA-NC+ACR+HJZY group were lower than those in the siRNA-NC+ACR group(P<0.05).After transfection with the gene-silencing siRNA-AMPK,the expression levels of p-AMPK/AMPK,PINK1,and Parkin proteins in the siRNA-AMPK+ACR group were lower than those in the siRNA-AMPK+control group(P<0.01).After the administration of HJZY,there was no significant difference in the levels of these three proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-AMPK+ACR group.The expression level of LC3B protein in the siRNA-AMPK+ACR+HJZY group was still lower than that in the siRNA-AMPK+ACR group(P<0.01).There was no significant difference in the levels of P62,TBK1,and ULK1 proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-AMPK+ACR group.Compared with the siRNA-NC+control group,the siRNA-AMPK+control group showed significantly decreased expression levels of p-AMPK/AMPK,ULK1,and TBK1 proteins(P<0.001),decreased expression of PINK1 protein(P<0.05),and increased expression of P62 protein(P<0.001).Compared with the siRNA-NC+ACR group,the siRNA-AMPK+ACR group showed decreased expression of TBK1 protein(P<0.001),decreased expression of LC3B protein(P<0.01),and decreased expression of ULK1 protein(P<0.05).The expression levels of PINK1 and Parkin proteins in the siRNA-AMPK+ACR group were lower than those in the siRNA-NC+ACR group,but the difference was not statistically significant.Compared with the siRNA-NC+ACR+HJZY group,the siRNA-AMPK+ACR+HJZY group showed decreased expression of p-AMPK/AMPK,PINK1,and Parkin proteins(P<0.05),decreased expression of LC3B protein(P<0.01),and increased expression of P62 protein(P<0.001).There was no significant difference in the levels of TBK1 and ULK1 proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-NC+ACR+HJZY group.Conclusion HJZY may exert its therapeutic effect on oligoasthenospermia by regulating AMPK-mediated mitophagy.
2.Analysis of the factors influencing the efficacy of conventional Western medicine treatment on patients with acute exacerbation of COPD
Xiaoxue GAO ; Yanfei LI ; Baozhu LIU
China Pharmacist 2024;27(7):1248-1256
Objective To explore the factors influencing the efficacy of conventional Western medicine treatment for patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD),and to provide a basis for individualized clinical treatment.Methods 100 patients with AECOPD were prospectively included in this study,and all of them were given standard treatment plans according to the guidelines.After 3 months of follow-up observation,53 cases were evaluated as effective and included in the effective group;47 cases were evaluated as having no significant effect and included in the ineffective group.Differences in basic characteristics between the two groups in terms of age,duration of COPD,respiratory rate,lung function and consolidated malignancy were compared,and pre-treatment laboratory test indexes and blood gas analysis data were collected for comparison.Results There were significant differences between the two groups in terms of age,duration of COPD,respiratory rate,ratio of forced expiratory volume in one second to forced vital capacity(FEV1/FVC%),consolidated malignancy,hemoglobin,lymphocytes,C-reactive protein,glutamic-pyruvic transaminase and PaCO2(P<0.05).Univariate logistic regression analysis showed that older age,prolonged COPD duration,increased respiratory rate,decreased FEV1/FVC%,consolidated malignancy,decreased hemoglobin,decreased lymphocyte count,increased C-reactive protein,increased glutamic-pyruvic transaminase,increased lactate,and increased PaCO2 were risk factors for poor treatment outcome in AECOPD.Further multifactorial logistic regression analysis showed that age(P=0.007,OR=1.240),FEV1/FVC%(P=0.014,OR=0.757),hemoglobin(P=0.038,OR=0.954),lymphocyte count(P=0.007,OR=0.488),and lactate(P=0.002 OR=9.964)were independent risk factors affecting the efficacy of AECOPD treatment.ROC curve analysis showed that the AUCs for age,FEV1/FVC%,hemoglobin,lymphocyte count and lactate were 0.728[95%CI(0.627,0.829)],0.681[95%CI(0.576,0.785)],0.686[95%CI(0.582,0.790)],0.629[95%CI(0.520,0.737)]and 0.823[95%CI(0.744,0.902)],respectively,and the combined AUC of the five risk factors for predicting a poor AECOPD treatment outcome was 0.957[95%CI(0.923,0.991).Conclusion Age,FEV1/FVC%,hemoglobin,lymphocyte count and lactate are independent risk factors that influence the treatment outcome of AECOPD patients.The comprehensive analysis of these risk factors can predict the treatment effect of AECOPD more accurately,help clinicians adjust the treatment plan in time,and improve the treatment effect and prognosis.
3.Diagnostic and intervention value of implantable cardiac monitor in patients over 60 years of age with unexplained syncope
Rui WANG ; Yanfei ZHANG ; Hongchao ZHANG ; Jia WANG ; Shuhui SHEN ; Jiabin TONG ; Junpeng LIU ; You LYU ; Jia CHONG ; Zhilei WANG ; Xin JIN ; Lin SUN ; Xu GAO ; Yan DAI ; Jing LIANG ; Haitao LI ; Tong ZOU ; Jiefu YANG
Chinese Journal of Cardiology 2024;52(7):784-790
Objective:To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.
4.Efficacy and safety of hybrid surgery for the recanalization of carotid artery occlusion after stenting
Zhengyu WANG ; Guangdong LU ; Tao WANG ; Wenlong XU ; Xia LU ; Fei CHEN ; Bin YANG ; Peng GAO ; Yabing WANG ; Yanfei CHEN ; Yan MA ; Liqun JIAO
Chinese Journal of Cerebrovascular Diseases 2024;21(8):505-513
Objective To investigate the efficacy and safety of hybrid surgery for the recanalization of carotid artery occlusion after stenting.Methods Clinical data and results of 17 patients with occlusion after carotid artery stenting and treated with hybrid surgery from June 2016 to April 2023 at the Department of Neurosurgery Cerebral Blood Flow Reconstruction Center of Xuanwu Hospital,Capital Medical University were retrospectively analyzed.According to whether the recanalization was successful,17 patients were divided into the the successful recanalization group and the failed recanalization group.Successful recanalization was defined as achieving modified thrombolysis in cerebral infarction(mTICI)grade ≥2b and residual stenosis<50%.Baseline data(age,sex,body mass index,smoking history,alcohol consumption history,hypertension history,diabetes history,hyperlipidemia history,coronary heart disease history),clinical data(National Institutes of Health Stroke Scale[NIHSS]score at admission,fasting blood glucose,low density lipoprotein,high density lipoprotein,total cholesterol,triglyceride,occlusion side and segment,combination with severe stenosis or occlusion of the contralateral carotid artery,opening of the anterior communicating artery,opening of the posterior communicating artery,compensation of the external and internal carotid artery,compensation of the pia artery,stump morphology,and time from imaging diagnosis of occlusion to recanalization)were documented and compared between groups.The recanalization of occlusive vessels and perioperative complications were recorded.Imaging and clinical follow-up were performed 3,6 months and≥1 year after surgery.Results Among the 17 patients,the ratio of successful recanalization was 13/17.One patient had re-occlusion after operation,which was re-opened after thrombolysis,but neck hematoma with dyspnea occurred,and recovered after emergency operation.There was no postoperative stroke or death.The incidence of perioperative complications was 1/17.Compared with the successful recanalization group,the levels of high density lipoprotein and total cholesterol in the failed recanalization group were higher,and the differences between the groups were statistically significant(high density lipoprotein[1.3±0.3]mmol/L vs.[0.9±0.3]mmol/L,t=-2.139;total cholesterol:[4.2±0.8]mmol/L vs.[3.1±0.7]mmol/L,t=-2.649;both P<0.05);There were no significant differences in other baseline data and clinical data(all P>0.05).Imaging follow-up was completed in 9 of the 13 patients in the successful recanalization group,and the follow-up time was 3.8-36.9 months,with a median follow-up time of 22.8(12.8,34.7)months.Among them,1 patient(1/9)developed restenosis of recanalization vessels at 33.0 months after surgery and underwent stent implantation again.Conclusions The preliminary analysis showed that the occlusion after carotid artery stenting had better recanalization success and lower perioperative complications.In patients with chronic occlusion after carotid stenting,the application of a hybrid surgery for opening may be attempted under multimodal imaging assessment.
5.The correlation between cortical thickness alteration and cognitive dysfunction in Parkinson's Disease
Yongyun ZHU ; Chao GAO ; Yanfei HU ; Kangfu YIN ; Weifang YIN ; Fang WANG ; Chuanbin ZHOU ; Hui REN ; Baiyuan YANG ; Xinglong YANG
Chinese Journal of Geriatrics 2023;42(8):897-903
Objective:This study investigated the changes of cortical thickness in patients with Parkinson's cognitive dysfunction.Methods:In this cross-sectional study, general clinical data and head magnetic resonance imaging data were collected from Parkinson's disease(PD)patients and healthy controls who were hospitalized or outpatient in the Department of Geriatric Neurology of the First Affiliated Hospital of Kunming Medical University from January 2019 to December 2020.We observed the changes of cortical thickness in each group, and analyzed the correlation between cortical thickness and cognitive dysfunction in PD.Results:Compared with PD normal cognitive group, the cortical thickness of the left superiortemporal gyrus[(2.7±0.1)mm, (2.4±0.1)mm, t=-4.194], left supramarginal[(2.4±0.1)mm, (2.2±0.1)mm, t=-4.845], right insula[(3.0±0.1)mm, (2.7±0.1)mm, t=-4.170], left parahippocampal[(2.8±0.3)mm, (2.4±0.3)mm, t=-4.164]decreased in PD cognitive impairment group(all P<0.05), and cortical thickness of the right parsorbitalis[(2.5±0.2)mm, (2.4±0.2)mm, t=-4.226], left entorhinal[(3.5±0.3)mm, (3.1±0.4)mm, t=-4.583], left inferiortemporal[(2.7±0.2)mm, (2.5±0.1)mm, t=-6.229], left supramarginal[(2.4±0.1)mm, (2.1±0.1)mm, t=-3.236], right fusiform[(2.8±0.1)mm, (2.5±0.1)mm, t=-5.364], right lingual[(2.0±0.1)mm, (1.9±0.1)mm, t=-3.887], right insula[(3.0±0.1)mm, (2.7±0.2)mm, t=-5.326], right isthmuscingulate[(2.6±0.2)mm, (2.3±0.2)mm, t=-3.743]decreased in PD severe cognitive impairment group, the statistical difference was significant(all P<0.05). The cerebral cortex thickness was positively correlated with Mini-Mental State Examination and different cognitive areas, and negatively correlated with Hoehn-Yahrr grading. Conclusions:Local cortical thinning was observed in PD patients with cognitive impairment, whereas cortical involvement was more extensive in PD patients with severe cognitive impairment.
6.Copy number variant sequencing for chromosome analysis in 487 fetuses with increased nuchal translucency
Zhi GAO ; Tianyuan ZHANG ; Wei HUANG ; Yanfei WANG ; Panlai SHI ; Xiangdong KONG
Chinese Journal of Perinatal Medicine 2022;25(3):186-191
Objective:To analyze the genetic etiology of 487 fetuses with increased nuchal translucency (NT) using copy number variant sequencing (CNV-seq) and explore the relationship between increased NT and chromosomal abnormality.Methods:A retrospective study was performed on 487 fetuses with increased NT who received CNV-seq in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020. These fetuses either had NT of ≥3.0-<3.5 mm (Group A, n=129) or ≥3.5 mm (Group B, n=358), the distribution and incidence of chromosomal abnormalities in the two sets of fetuses were analyzed using Chi square test or Fisher's exact test. Results:Fetuses with abnormal chromosomes accounted for 25.9%(126/487) of cases, including 107 with chromosome aneuploidy (22.0%) and 19 with pathogenic or likely pathogenic copy number variation (CNV, 3.9%). The detection rate of fetal aneuploidy in Group B was higher than that in Group A [14.0% (18/129) vs 24.9% (89/358), χ2=6.58, P=0.010]. However, no significant difference was observed regarding the detection rate of pathogenic or likely pathogenic CNV between the two groups ( χ2=0.30, P=0.584). Conclusions:The risk of fetal chromosome aneuploidy increased with NT thickness, but not with pathogenic or likely pathogenic CNV, which needed further verification due to the small sample size. CNV-seq is an option to detect the conventional detection methods for the genetic etiology of NT thickening fetuses.
7.Research on the Communication Strategy of Strengthening Socialist Ideology in Hospitals in All-media Era
Ping ZHANG ; Litao JIA ; Fei GAO ; Xiaodan ZHANG ; Wei WANG ; Yanfei WANG ; Cuifeng GAO
Chinese Medical Ethics 2022;35(9):1050-1052
In the all-media era, communication channels are increasingly diversified and the modes of communication are undergoing profound changes. Same medical institutions ignore the development of all media, which lead to rigid and backward communication situation, affect the healthy development of medical and health undertakings. Mastering and making good use of the advantages and characteristics of communication in the all-media era will also provide more motivation and possibilities for strengthening ideological work. This paper expounded the significance of strengthening the dissemination of socialist ideology in hospitals, proposed the opportunities and challenges faced by hospitals in strengthening the dissemination of socialist ideology in the all-media era, and then put forward specific coping strategies combined with the actual situation of hospitals.
8.Single-cell Sequencing Reveals Clearance of Blastula Chromosomal Mosaicism in In Vitro Fertilization Babies
Gao YUAN ; Zhang JINNING ; Liu ZHENYU ; Qi SHUYUE ; Guo XINMENG ; Wang HUI ; Cheng YANFEI ; Tian SHUANG ; Ma MINYUE ; Peng HONGMEI ; Wen LU ; Tang FUCHOU ; Yao YUANQING
Genomics, Proteomics & Bioinformatics 2022;(6):1224-1231
Although chromosomal mosaic embryos detected by trophectoderm(TE)biopsy offer healthy embryos available for transfer,high-resolution postnatal karyotyping and chromosome testing of the transferred embryos are insufficient.Here,we applied single-cell multi-omics sequenc-ing for seven infants with blastula chromosomal mosaicism detected by TE biopsy.The chromo-some ploidy was examined by single-cell genome analysis,with the cellular identity being identified by single-cell transcriptome analysis.A total of 1616 peripheral leukocytes from seven infants with embryonic chromosomal mosaicism and three control ones with euploid TE biopsy were analyzed.A small number of blood cells showed copy number alterations(CNAs)on seem-ingly random locations at a frequency of 0%-2.5%per infant.However,none of the cells showed CNAs that were the same as those of the corresponding TE biopsies.The blastula chromosomal mosaicism may be fully self-corrected,probably through the selective loss of the aneuploid cells dur-ing development,and the transferred embryos can be born as euploid infants without mosaic CNAs corresponding to the TE biopsies.The results provide a new reference for the evaluations of trans-ferring chromosomal mosaic embryos in certain situations.
9.Analysis of results of prenatal diagnosis for 67 pedigrees affected with Duchenne muscular dystrophy in the central plain region of China
Zhi GAO ; Li'na LIU ; Yanli WANG ; Yanfei WANG ; Wei HUANG ; Xiangdong KONG
Chinese Journal of Medical Genetics 2022;39(7):669-673
Objective:To retrospectively analyze the results of prenatal diagnosis for 67 pedigrees affected with Duchenne muscular dystrophy (DMD) from the Central Plain Region of China and explore the optimal diagnostic strategy.Methods:Probands from the 67 pedigrees were subjected to multiplex ligation-dependent probe amplification (MLPA), next-generation sequencing (NGS) and Sanger sequencing to attain the diagnosis. The fetuses were subjected to prenatal diagnosis, and the results were verified with short tandem repeat (STR) analysis.Results:Among the 67 probands, large deletions, duplications and small mutations have accounted for 73.13% (49/67), 10.45% (7/67), and 16.42% (11/67), respectively. A hotspot deletion has involved exons 45 to 52. There were 11 small mutations, among which four were unreported previously. De novo mutations have accounted for 41.80% (28/67), of which 27 were novel large fragment deletions. Prenatal diagnosis was provided to 39 women who have carried the DMD gene mutations, 10 fetuses were identified as male patients and 7 fetuses were female carriers. Among the prenatal diagnosis results of 28 non-carrier pregnancies, one fetus was a male patient with the same mutation site as the proband. Conclusion:For the prenatal diagnosis of DMD, in addition to known pathogenic mutations, deletion of large fragments should also be excluded. Mothers of probands who do not carry the DMD mutation should also undergo prenatal diagnosis to rule out gonadal mosaicism.
10.Analysis of frailty and its related factors in elderly patients with stage 3-5 non-dialysis chronic kidney disease
Yun GAO ; Jing CHANG ; Yanfei WANG ; Xiangyang FANG ; Wenwen HOU ; Qianmei SUN
Chinese Journal of Geriatrics 2021;40(1):82-86
Objective:To investigate the prevalence of frailty in elderly patients with stage 3-5 non-dialysis chronic kidney disease(ND-CKD)and to analyze its related factors.Methods:A cross-sectional study was conducted.Patients ≥65 years old with stage 3-5 CKD who had never undergone dialysis in the nephrology department and the internal medicine department of our hospital between October 2017 to September 2018 were enrolled.Patients were divided into the non-frail group and the frail group according to the Fried frailty phenotype.Clinical data and laboratory results were collected and comprehensive geriatric assessment was carried out to evaluate participants' medication, comorbidities, daily living ability, nutritional status, depression, cognitive and physical performance.The relevant factors for frailty were analyzed.Results:A total of 193 elderly patients with stage 3-5 ND-CKD were enrolled, 106 male and 87 female, including 68 outpatients and 125 inpatients, with a median age of 79.00(73.00, 85.00)years.There were 143 frailty patients(74.1%), including 41 outpatients and 102 inpatients, accounting for 60.3% and 81.6% of the eligible outpatients and inpatients respectively.Multivariable Logistic regression analysis showed that CKD stage( OR=9.74, 95% CI: 1.12-84.54)and polypharmacy( OR=3.69, 95% CI: 1.09-12.42)were associated with frailty in outpatients, and CKD stage( OR=11.75, 95% CI: 1.38-99.99)and malnourishment or risk of malnutrition( OR=4.22, 95% CI: 1.40-12.74)were correlated with frailty in inpatients. Conclusions:The prevalence of frailty is high in elderly patients with stage 3-5 ND-CKD.CKD stage, polypharmacy and malnourishment or the risk of malnutrition are closely correlated with frailty.

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