1.Effect of Tongmai Kaiqiao Pills on Mitochondrial Biogenesis of Hippocampal Neurons in Rats with Vascular Cognitive Impairment Based on AMPK/PGC-1α Signaling Pathway
Luyao MA ; Yanjie LI ; Haoyuan LIU ; Yanjie BAI ; Ruoxing XING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):125-134
ObjectiveTo observe the effects of Tongmai Kaiqiao pills on AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) signaling pathway and mitochondrial biogenesis in hippocampal tissue of rats with vascular cognitive impairment (VCI) and to investigate the potential mechanism of Tongmai Kaiqiao pills in improving cognitive impairment in rats with VCI. MethodsTwelve of 72 male SD rats were selected as the sham operation group, and the remaining rats were modelled using the modified 2VO method. The rats that were successfully modelled were divided into the model group, the high-dose group of Tongmai Kaiqiao pills (27.6 g·kg-1), the low-dose group of Tongmai Kaiqiao pills (13.8 g·kg-1), the combination group (27.6 g·kg-1 Tongmai Kaiqiao pills + 25 mg·kg-1 dorsomorphin), and the donepezil hydrochloride group (0.45 g·kg-1) according to the random number table method. After four weeks of continuous intraperitoneal injection of the corresponding drugs, the Morris water maze test was used to test the learning and memory ability of rats. Hematoxylin-eosin (HE) staining and Nissl staining were used to detect pathological changes in the hippocampus of the rats. The content of mitochondrial adenosine triphosphate (ATP) in the brain hippocampus was detected by colorimetry, and reactive oxygen species (ROS) level was detected in rat mitochondria by MitoSOX Red assay. Mitochondrial DNA copy number was detected by real-time fluorescent quantitative PCR (Real-time PCR). Pathological changes in mitochondria were observed by transmission electron microscopy (TEM), and AMPK, PGC-1α, phosphorylated AMP-activated protein kinase (p-AMPK), nuclear respiratory factor 1 (Nrf1), and mitochondrial transcription factor A (TFAM) protein expression in the hippocampus of the rats were detected by Western blot. ResultsCompared with those in the sham operation group, rats in the model group had a reduced number of platform crossings (P<0.01), significantly prolonged evasion latency (P<0.01), disorganized neuronal arrangement in the hippocampal region, widened gaps, and blurred nucleus membrane and nucleolus boundaries. The emergence of necrotic cells was visible. The color of the nissl bodies was light, and the number was reduced with severe loss. Mitochondria were atrophied, and cristae were lost. Severe damage was observed. The content of ROS was increased, and the level of ATP was decreased. mtDNA copy number decreased significantly (P<0.01), and the protein expression of p-AMPK, PGC-1α, Nrf1, and TFAM decreased (P<0.05, P<0.01). Compared with those in the model group, rats in the high-dose group of Tongmai Kaiqiao pills and donepezil hydrochloride group showed a shorter time to find the platform (P<0.01), increased number of platform crossings (P<0.01), restored mitochondrial morphology and structure of the hippocampal neurons, alleviated neuronal death, increased number of nissl bodies, weaken degree of injury, lower content of ROS, and significantly increased levels of ATP and number of copies of mtDNA (P<0.05, P<0.01). In addition, there was increased protein expression of p-AMPK, PGC-1α, Nrf1, and TFAM (P<0.05, P<0.01). Compared with the model group, the evasion latency was shortened in the low-dose group of Tongmai Kaiqiao pills (P<0.01), and the number of platform crossings was increased, but the difference was not statistically significant. The mitochondria were swollen and deformed, and the cristae became shorter and partially disappeared. The degree of damage did not improve significantly, and the number of nissl bodies was increased but not statistically significant. The ROS content decreased (P<0.01), but there was no significant difference in ATP level and mtDNA copy number. The protein expression of PGC-1α was increased (P<0.05), but there was no significant difference in the protein expression of p-AMPK, Nrf1, and TFAM, and the results were not statistically significant. Compared with the donepezil hydrochloride group, there was no significant change in the results of each assay in the high-dose group of Tongmai Kaiqiao pills, and the difference was not statistically significant. Compared with the high-dose group of Tongmai Kaiqiao pills, rats in the combination group had a significantly lower number of platform crossings (P<0.01), a significantly longer evasion latency (P<0.01), a reduced number of neuronal cells, disorganized tissue structure, swollen and blurred cell outlines, a significant reduction in the number of nissl bodies. Moreover, there was an increase in the content of ROS, a decrease in the level of ATP and the number of mtDNA copies (P<0.01), and a decrease in the expression of p-AMPK, PGC-1α, Nrf1, and TFAM (P<0.05). ConclusionTongmai Kaiqiao pills is able to improve cognitive function in rats by activating the AMPK/PGC-1α signaling pathway, promoting mitochondrial biogenesis, and attenuating pathological damage to neurons in the hippocampal region, thereby demonstrating its therapeutic potential.
2.Mechanism of action of dysregulated mitochondrial quality control system mediating Parkinson's disease
Juan LIU ; Yanjie LI ; Hewei QIN ; Luyao MA ; Nannan ZHAO ; Huimin DING
The Journal of Practical Medicine 2024;40(11):1479-1482
Parkinson's disease(PD)is a common neurodegenerative disease with a complex pathogenesis,and a large number of studies have shown that mitochondrial dysfunction is an important causative factor for PD,whereas dysregulation of mitochondrial quality control is a key factor leading to mitochondrial dysfunction,and that aberrant mitochondrial biogenesis,fusion/fission imbalance,and mitochondrial hyperautophagy are closely associated with the onset of PD,but the role of the mitochondrial quality control system in the progression of PD is unclear.Therefore,this paper reviews the mechanism of mitochondrial quality control system in PD,with the aim of providing new ideas and theoretical basis for the clinical prevention and treatment of PD.
3.Association between prenatal exposure to PM 2.5 and fetal growth: a prospective cohort study
Lei HUANG ; Hong LYU ; Xin XU ; Tianyu SUN ; Yiyuan CHEN ; Yanjie ZHANG ; Bo YANG ; Qun LU ; Yangqian JIANG ; Tao JIANG ; Jiangbo DU ; Xiaoyan WANG ; Hongxia MA ; Zhibin HU ; Yuan LIN
Chinese Journal of Epidemiology 2024;45(6):794-801
Objective:To investigate the association of exposure to PM 2.5 and its constituents during pregnancy and fetal growth and to further identify critical windows of exposure for fetal growth. Methods:We included 4 089 mother-child pairs from the Jiangsu Birth Cohort Study between January 2016 and October 2019. Data of general characteristics, clinical information, daily average PM 2.5 exposure, and its constituents during pregnancy were collected. Fetal growth parameters, including head circumference (HC), abdominal circumference (AC), and femur length (FL), were measured by ultrasound after 20 weeks of gestation, and then estimated fetal weight (EFW) was calculated. Generalized linear mixed models were adopted to examine the associations of prenatal exposure to PM 2.5 and its constituents with fetal growth. Distributed lag nonlinear models were used to identify critical exposure windows for each outcome. Results:A 10 μg/m 3 increase in PM 2.5 exposure during pregnancy was associated with a decrease of 0.025 ( β=-0.025, 95% CI: -0.048- -0.001) in HC Z-score, 0.026 ( β=-0.026, 95% CI: -0.049- -0.003) in AC Z-score, and 0.028 ( β=-0.028, 95% CI:-0.052--0.004) in EFW Z-score, along with an increased risk of 8.5% ( RR=1.085, 95% CI: 1.010-1.165) and 13.5% ( RR=1.135, 95% CI: 1.016-1.268) for undergrowth of HC and EFW, respectively. Regarding PM 2.5 constituents, prenatal exposure to black carbon, organic matter, nitrate, sulfate (SO 42-) and ammonium consistently correlated with decreased HC Z-score. SO 42- exposure was also associated with decreased FL Z-scores. In addition, we found that gestational weeks 2-5 were critical windows for HC, weeks 4-13 and 19-40 for AC, weeks 4-13 and 23-37 for FL, and weeks 4-12 and 20-40 for EFW. Conclusions:Our findings demonstrated that exposure to PM 2.5 and its constituents during pregnancy could adversely affect fetal growth and the critical windows for different fetal growth parameters are not completely consistent.
4.Research advances in visualized microspheres
Yanjie YANG ; Jingqin MA ; Zhiping YAN
Journal of Interventional Radiology 2024;33(2):115-121
Microspheres are commonly used as embolic materials in vascular interventional operations.However,due to the limitation of materials,almost all microspheres cannot be detected by imaging equipment in vivo.The visualization of microspheres refers to the addition of various materials to the microspheres that enable the microspheres to be displayed on the images of imaging equipment.In order to optimize the embolization process and facilitate postoperative follow-up,a lot of visualized microspheres have been reported so far,such as X-ray visualized microspheres,MRI visualized microspheres,ultrasonic visualized microspheres,etc.Clinical experience has shown that these microspheres can provide true spatial distribution and real-time intraoperative feedback,which contributes to the optimization,personalization,and improvement of vascular embolization technology.This paper aims to make a comprehensive review about the recent advances in researches about the above mentioned visualized microspheres.
5.Correlation between genes associated with serum alpha-fetoprotein positive gastric cancer and prognosis
Shunli LU ; Qinjun SU ; Jianping YU ; Ruiyu TAO ; Youwei MA ; Yanjie LI ; Hongtao LI ; Li LIN ; Xiaopeng HAN
Chinese Journal of General Surgery 2024;39(2):92-98
Objective:To analyse the differences of related genes between serum alpha-fetoprotein (AFP) positive gastric cancer and AFP negative gastric cancer, and the relationship between related genes and prognosis of serum AFP positive gastric cancer.Methods:A total of 1 144 gastric cancer patients undergoing surgery at the 940th Hospital , Joint Logistic Support Force, People's Liberation Army from Jan 2013 to Dec 2018 were retrospectively analyzed. Of them, 47 cases were of AFP positive gastric cancer, and 47 serum AFP negative case were obtained by proper matching method.Results:Forty-seven patients with serum AFP positive gastric cancer, accounting for 4.1% of all gastric cancer patients during the same period. The prognosis of serum AFP negative gastric cancer is better than that of serum AFP positive gastric cancer. The 1-, 3- and 5-year cumulative survival rates were 95.6% vs. 63.8%, 48.9% vs. 23.4% and 26.7% vs. 14.9%, respectively. There were statistical differences in the immunohistochemistry of AFP, HER2, VEGF, GPC3, SALL4, P53 and Ki67 between the two groups ( χ2=67.758, P<0.001; χ2=4.004, P=0.044; χ2=19.299, P<0.001; χ2=5.232, P=0.022; χ2=6.359, P=0.012; χ2=6.224, P=0.013; χ2=5.232, P=0.022). The more co-positive expressions of AFP, GPC3, VEGF and SALL4, the more likely they were to affect pTNM stage, vascular invasion and liver metastasis ( χ2=5.328, P=0.021; P=0.013; χ2=5.887, P=0.015; χ2=3.923, P=0.048). Univariate and multivariate survival analysis of serum AFP positive gastric cancer showed:AFP, GPC3, VEGF and SALL4 were risk factors for AFP positive gastric cancer ( HR=3.700, P=0.036; HR=4.237, P=0.003; HR=3.916, P=0.004; HR=3.412, P=0.001). Conclusions:Serum AFP positive gastric cancer is a rare and highly invasive special type of gastric cancer. AFP, GPC3, VEGF and SALL4 are overexpressed in serum AFP positive gastric cancer, which is correlated with tumor stage, vascular invasion and liver metastasis. The final diagnosis of serum AFP positive gastric cancer still needs immunohistochemical examination. Preoperative serum AFP level is an important basis for AFP positive gastric cancer screening and AFP immunohistochemical examination.
6.Advances in the mechanism-of-action of circRNA in Parkinson's disease
Juan LIU ; Yanjie LI ; Hewei QIN ; Luyao MA ; Nannan ZHAO ; Zhenhua XU
Chinese Journal of Comparative Medicine 2024;34(2):161-166
PD is a neurodegenerative disease characterized by degenerative death of dopaminergic neurons in the substantia nigra,exhibiting a range of motor and non-motor symptoms with serious effects on quality of life.circRNA is a covalently closed-loop non-coding RNA that plays a major role in PD progression.This article reviews the involvement of circRNA in oxidative stress,regulation of transcription,neuroinflammation,autophagy,and α-synuclein.
7.Construction and analysis of early warning and prediction model for risk factors of sepsis-associated encephalopathy
Li ZHANG ; Xiangyou YU ; Long MA ; Yi WANG ; Xiang LI ; Yanjie YANG
Chinese Critical Care Medicine 2024;36(2):124-130
Objective:To investigate the epidemiological characteristics of sepsis-associated encephalopathy (SAE) in patients with sepsis, analyze its risk factors and build a prediction model, which provides evidence for early clinical identification of SAE patients and improvement of clinical outcomes.Methods:A retrospective observational study was conducted. Sepsis patients admitted to the critical care medical center of the First Affiliated Hospital of Xinjiang Medical University from February 2022 to February 2023 were enrolled. According to whether SAE occurred, the patients were divided into sepsis group and SAE group. The 24 patients without sepsis in the same period were used as controls (non-sepsis group). Demographic data, relevant scores and laboratory test indicators at admission to intensive care unit (ICU), and prognostic indicators were collected. Univariate and multivariate Logistic regression analysis was used to analyze the risk factors for sepsis and SAE. Receiver operator characteristic curve (ROC curve) was drawn. The predictive value of each risk factor for sepsis and SAE.Results:A total of 130 patients with sepsis were included, of which 52 had SAE, and the incidence of SAE was 40.00%. There were significant differences in the length of ICU stay and total length of stay among all groups, while there were no significant differences in hospitalization cost and mechanical ventilation time. Multivariate Logistic regression analysis showed that pulmonary infection [odds ratio ( OR) = 46.817, 95% confidence interval (95% CI) was 5.624-389.757, P = 0.000], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ: OR = 1.184, 95% CI was 1.032-1.358, P = 0.016), sequential organ failure assessment (SOFA: OR = 9.717, 95% CI was 2.618-36.068, P = 0.001), Charson comorbidity index (CCI: OR = 4.836, 95% CI was 1.860-12.577, P = 0.001), hemoglobin (Hb: OR = 0.893, 95% CI was 0.826-0.966, P = 0.005), glutamyltranspeptidase ( OR = 1.026, 95% CI was 1.008-1.045, P = 0.006) were independent risk factors for sepsis in ICU patients. Pulmonary infection ( OR = 28.795, 95% CI was 3.296-251.553, P = 0.002), APACHEⅡ score ( OR = 1.273, 95% CI was 1.104-1.467, P = 0.001), SOFA score ( OR = 8.670, 95% CI was 2.330-32.261, P = 0.001), CCI ( OR = 5.141, 95% CI was 1.961-13.475, P = 0.001), Hb ( OR = 0.922, 95% CI was 0.857-0.993, P = 0.031), glutamyltranspeptidase ( OR = 1.020, 95% CI was 1.002-1.038, P = 0.030) were independent risk factors for SAE in sepsis patients. ROC curve analysis showed that the area under the curve (AUC) of pulmonary infection, APACHEⅡ score, SOFA score, CCI, Hb, and glutamyltranspeptidase for predicting sepsis were 0.792, 0.728, 0.987, 0.933, 0.720, and 0.699, respectively; the AUC of the combined prediction of the above 6 variables for sepsis was 1.000, with a sensitivity of 100% and a specificity of 100%. The AUC predicted by pulmonary infection, APACHEⅡ score, SOFA score, CCI, and Hb for SAE were 0.776, 0.810, 0.907, 0.917, and 0.758, respectively; the AUC of the combined prediction of the above 5 variables for SAE was 0.975, with a sensitivity of 97.3% and a specificity of 93.1%. Conclusions:Sepsis is more severe when accompanied by encephalopathy. Pulmonary infection, Hb, APACHEⅡ score, SOFA score and CCI were independent risk factors of SAE. The combination of the above five indicators has good predictive value for early screening and prevention of the disease.
8.Intervention study of lung cancer patients undergoing postoperative chemotherapy based on sentinel symptoms
Jingshuang MA ; Aiping WANG ; Yanjie WANG ; Wei LI ; Yanxia LIU
Chinese Journal of Nursing 2024;59(2):133-141
Objective Based on sentinel symptoms,a nursing intervention program for gastrointestinal symptom group of postoperative chemotherapy for lung cancer was constructed and its application effect was evaluated.Methods The nursing intervention program of gastrointestinal symptom group was constructed on the basis of ref-erence guidelines,qualitative interview and expert consultation.From January 2021 to January 2022,a total of 330 patients with postoperative chemotherapy for lung cancer in a tertiary hospital in Shenyang were selected as re-search subjects.The experimental group received the gastrointestinal symptoms group nursing intervention program on the basis of routine nursing,and the control group received routine care.Patients were investigated with the M.D.Anderson Symptom Inventory and the MOS 36-Item Short-Form Health Survey before 1st chemotherapy(T1),3rd chemotherapy(T2)and 5th chemotherapy(T3).Results After the intervention,the total scores of the 2 groups and the total scores of each symptom in T2 and T3 were statistically significant(P<0.05),and the score of the experi-mental group was lower than that of the control group.For the scores of 6 dimensions of physiological function,physical pain,overall health,vitality,emotional function,mental health in 2 groups between different time points,the differences are statistically significant(P<0.05).Conclusion The nursing intervention program of the gastroin-testinal symptom group based on sentinel symptoms is beneficial to reduce the severity of the gastrointestinal symp-tom group and improve the quality of life for postoperative chemotherapy for lung cancer patients.
9.Progress of echocardiographic parameters in patients with different severity of aortic stenosis
Jia MA ; Liwei ZHANG ; Yongjiang MA ; Mate GUO ; Shimin SUN ; Meiqing ZHANG ; Qiushuang WANG ; Yanjie SONG ; Chan SHI ; Feifei YANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(11):1253-1257
Objective To investigate the progress of two-dimensional echocardiographic parameters in patients with different severity of aortic stenosis.Methods A retrospective analysis was per-formed on 96 patients diagnosed with aortic stenosis with at least 2 times of transthoracic echo-cardiography(interval ≥1 year)in Department of Cardiology,Fourth Medical Center of Chinese PLA General Hospital from March 2017 to December 2023.According to aortic stenosis severity,they were divided into a mild group(72 cases),a moderate group(14 cases)and a severe group(10 cases).Peak pressure gradient(PPG)across aortic valve,Vmax,mean aortic valve pressure gradient(ΔPm),pulmonary artery systolic pressure(PASP)were collected,and the changes and annual progress of these echocardiographic parameters at baseline and before and after follow-up were analyzed.Results The values of IVST,LVPWT,Vmax,aortic valve PPG and ΔPm were sig-nificantly increased in the mild,moderate and severe stenosis groups in turn(P<0.05,P<0.01).The values of Vmax,PPG and ΔPm were significantly lower in the mild stenosis group than the moderate and severe stenosis groups,and the LVPWT value was obviously lower in the mild ste-nosis group than the severe stenosis group(P<0.05).The aortic valve PPG and ΔPm values at follow-up were significantly higher than those before the follow-up in the three stenosis groups(P<0.05,P<0.01).After follow-up,the Vmax values in mild and moderate stenosis groups were notably higher than before(P<0.01).The PASP value at follow-up was significantly higher than before in the severe stenosis group(P<0.05).The annual progression rate of Vmax,PASP,LVEF were gradually increased in the mild,moderate,and severe stenosis groups(P>0.05).The annual progression rate of ΔPm was gradually increased in the three groups in turn(2.30±1.77 mm Hg/year vs 2.40±1.18 mm Hg/year vs 6.08±1.70 mm Hg/year,P<0.05).Conclusion As the severity of baseline aortic stenosis increases,obvious changes are observed in cardiac structure and function.Before and after follow-up,the serious the aortic stenosis severity is,the faster the annual progression rates of Vmax,PPG,LVEF and PASP are.
10.The efficacy and impact on quality of life in the elderly patients with proximal ureteral stones larger than 1 cm who reciveing minimally invasive percutaneous nephrolithotomy and retrograde intrarenal surgery
Yanjie MA ; Wei ZHANG ; Changjian ZHAO ; Dongwen WANG ; Lijuan REN
Chinese Journal of Geriatrics 2024;43(8):1007-1012
Objective:To compare the efficacy and impact on the quality of life of elderly patients of minimally invasive percutaneous nephrolithotomy(MPCNL)and retrograde intrarenal surgery(RIRS)in the treatment of unilateral upper ureteral calculi larger than 1.0 cm in diameter.Methods:A total of 104 patients were prospectively collected from January 2021 to December 2022 in the First Hospital of Shanxi Medical University.Based on the inclusion and exclusion criteria, 88 patients were finally included, 32 patients in the MPCNL group and 56 patients in the RIRS group, and the independent samples t-test, χ2 test, or Fisher's exact probability method were used to compare the differences in the general information, stone characteristics, and intraoperative and postoperative indexes between the two groups, and the quality-of-life scores were applied with the SF-36 Health Survey form. Results:There were no significant differences in age[(67.52±7.41)years and(67.38±7.25)years], gender[male/female: 19/13 cases and 36/20 cases], body mass index[(23.74±2.93)kg/m 2 and(23.70±2.57)], stone location(left/right: 20/12 cases and 38/18 cases), degree of hydronephrosis(mild/moderate/severe: 9/20/3 cases and 16/38/2 cases), stone maximum diameter[(14.12±3.69)mm and(13.34±2.99)mm], stone CT values[(1 035.7±275.7)HU and(973.3±253.8)HU]and postoperative complications[15.6%(5/32)and 14.3%(8/56)]between the two groups of patients( P>0.05).However, there were significant difference in stone clearance rate[96.9%(31/32) vs.80.4%(45/56)], and the operation time[(44.44±9.91)min vs.(54.69±11.94)min]between the two groups.The hospital stay in the RIRS group was shorter than that in the MPCNL group[(5.27±2.27)d vs.(8.00±2.19)d, P<0.05].There was no significant difference in the scores of eight dimensions between the two groups before surgery( P<0.05).At the day of discharge, patients in the MPCNL group had significantly lower mean scores than the RIRS group on six different subscales of the SF-36 questionnaire, namely, physical functioning, role-physical, bodily pain, social functioning, role-emotional and mental health.No differences in the mean scores for general health and vitality between the two groups were noted.In terms of SF-36 scores at one month after operation, the MPCNL group had lower scores in physical pain and social function than the RIRS group and the difference was statistically significant( P<0.05).No differences in the mean scores for other domains at one month after operation between patients undergoing MPCNL and those undergoing RIRS were noted. Conclusions:For patients with unilateral upper ureteral calculi larger than 1.0 cm in diameter, MPCNL has higher stone-free rate and shorter operation time than RIRS, but longer hospitalization time, and MPCNL has a greater impact on the quality of life of patients with ureteral calculi than RIRS in many aspects.

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