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.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.
3.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.
4.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.
5.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.
6.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.
7.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.
8.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.
9.Analysis of VSIG4 expression in clear cell renal cell carcinoma and its correlation with tumor infiltrating immune cells
Hangfeng LIU ; Shenglu LIU ; Lianrui DUAN ; Likun ZAN ; Yanjie MA ; Lijun YANG
Chinese Journal of Immunology 2024;40(5):918-924
Objective:To explore expression of VSIG4 in clear cell renal cell carcinoma(ccRCC)and its correlation with immune cells infiltration and prognosis.Methods:RNA-seq data of ccRCC and corresponding clinical data of patients were downloaded from The Cancer Genome Atlas(TCGA)database.Wilcoxon rank-sum test was used to analyze VSIG4 mRNA expression in ccRCC and normal renal tissues.Correlation between VSIG4 expression and clinicopathological parameters was analyzed by Wilcoxon rank-sum or Kruskal-Wallis rank-sum test.Kaplan-Meier method was used to analyze the correlation between VSIG4 expression and progno-sis of patients.Gene set enrichment analysis(GSEA)was used to explore the signaling pathway of VSIG4 in ccRCC.Correlation between VSIG4 level and tumor infiltrating immune cells was analyzed via CIBERSORT in R software.Western blotting was used to detect VSIG4 protein level in human renal epithelial cell line 293T,and human renal carcinoma cell line ACHN,A498,786-O and OS-RC-2.Results:Expression level of VSIG4 in ccRCC was significantly higher than that in normal tissues(P<0.05).VSIG4 expression was significantly correlated with the stages of distant metastasis and lymph node metastasis(P<0.05).Overall survival rate of patients with high VSIG4 expression was significantly lower than that of patients with low expression(P<0.05).GSEA enrichment analysis showed that VSIG4 was mainly enriched in apoptosis,chemokine signaling pathway,cell adhesion molecules and other signaling path-ways.VSIG4 expression was negatively correlated with M1 macrophages(r<0,P<0.05),while positively correlated with M2 macro-phages(r>0,P<0.05).Western blotting results showed that expression of VSIG4 in renal cell carcinoma cells was higher than that in normal renal cells.Conclusion:VSIG4 is highly expressed in ccRCC,and is negatively associated with prognosis,which may become a prognostic biomarker for ccRCC patients.
10.Analysis of intestinal flora characteristics and influencing factors in patients with rheumatoid arthritis complicated with interstitial lung disease
Qingna CHEN ; Yanjie LIU ; Liangxiao LI ; Lina MA ; Ranran XIAO
Chinese Journal of Immunology 2024;40(11):2361-2367,2372
Objective:To explore characteristics of intestinal flora in patients with rheumatoid arthritis complicated with inter-stitial lung disease(RA-ILD),to analyze its influencing factors,and to explore improvement of intestinal flora in patients with RA-ILD by different treatment methods.Methods:A total of 100 patients with RA-ILD who visited Shijiazhuang People's Hospital from June 2021 to June 2022 were selected as research objects,and 100 healthy patients in Shijiazhuang People's Hospital during same pe-riod were selected as healthy group.High throughput sequencing was performed on intestinal flora of two groups,OTU flora abundance and α-Diversity,β-diversity,flora distribution and LEfSe difference were analyzed.Another 100 patients with RA-ILD were randomly divided into group A(n=50)and group B(n=50).Group A was treated with leflunomide+nidanib or pifenidone,and group B was treated with leflunomide+nidanib or pifenidone+bifidobacterium triad.Improvement of intestinal flora in two groups after treatment was analyzed.Correlation analysis was used to determine correlation between changes of intestinal flora and clinical characteristics and indicators in RA-ILD patients.Results:OTU flora abundance,α-diversity and β-diversity in RA-ILD patients were lower than that of healthy people.Abundance of Intestinibacter in RA-ILD group was higher than that in healthy group,and abundance of Lactobacillus,Escherichia coli,Klebsiella,Candidatus saccharimonas,Odoribacter and Enterococcus in RA-ILD group were lower than that in healthy group.After treatment,flora structure of group A and group B was improved.Group B was closer to healthy population,and cu-rative effect was significantly better than that of group A.Integinibacter bacteria level was positively correlated with age,RA course,DAS28,CRP,RF and KL-6(P<0.05),and negatively correlated with DLCO(P<0.05).Lactobacillus level was negatively correlated with course of RA,DAS28,CRP,RF,IL-6(P<0.05),and positively correlated with VC(P<0.05);Shigella coli level was negtively correlatied with RA course,ILD course,DAS28,ESR,RF,TNF-α(P<0.05).Klebsiella level was positively correlated with VC and DLCO(P<0.05);Bacterial level of Candida saccharimonas was negatively correlated with DAS28,ESR,CRP,RF,IL-6,TNF-α(P<0.05)and positive correlated with DLCO(P<0.05);Odoribacter bacteria level was negatively correlated with DAS28,CRP,RF,IL-6 and KL-6(P<0.05),and positively correlated with VC(P<0.05);Enterococcus level was negatively correlated with course of RA,ILD,DAS28,ESR,RF and KL-6(P<0.05),while positively correlated with DLCO(P<0.05).Conclusion:Intestinal microflora abundance of RA-ILD patients is significantly lower than that of healthy people,and there aree significant differences in some microflora,which are closely related to clinical characteristics and indicators.Using of bifidobacterium triad in clinical treatment is helpful to improve intestinal flora of RA-ILD patients.

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