1.Exercise Regulates Structural Plasticity and Neurogenesis of Hippocampal Neurons and Improves Memory Impairment in High-fat Diet-induced Obese Mice
Meng-Si YAN ; Lin-Jie SHU ; Chao-Ge WANG ; Ran CHENG ; Lian-Wei MU ; Jing-Wen LIAO
Progress in Biochemistry and Biophysics 2025;52(4):995-1007
ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.
2.Association between coronary artery stenosis and myocardial injury in patients with acute pulmonary embolism: A case-control study
Yinjian YANG ; Chao LIU ; Jieling MA ; Xijie ZHU ; Jingsi MA ; Dan LU ; Xinxin YAN ; Xuan GAO ; Jia WANG ; Liting WANG ; Sijin ZHANG ; Xianmei LI ; Bingxiang WU ; Kai SUN ; Yimin MAO ; Xiqi XU ; Tianyu LIAN ; Chunyan CHENG ; Zhicheng JING
Chinese Medical Journal 2024;137(16):1965-1972
Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.
3.Value of Pretreatment Inflammation-nutrition Score to Predict Non-response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer.
Guo Chao ZHANG ; Yan Yan XU ; Ying Chao WU ; Nuo CHENG ; Rui LIAN ; Xin WANG
Biomedical and Environmental Sciences 2023;36(10):940-948
OBJECTIVE:
To investigate the value of pretreatment inflammatory-nutritional biomarkers in predicting the pathological response of locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (nCT).
METHODS:
This retrospective study included eligible participants who underwent nCT followed by radical surgery. Pretreatment inflammatory nutritional biomarkers were calculated within one week prior to nCT. Correlations between biomarkers and pathological responses were analyzed. The cut-off values of the pretreatment biomarkers for predicting non-response were determined using receiver operating characteristic (ROC) curve analysis. The inflammation-nutrition score was calculated using the lymphocyte level, neutrophil-to-lymphocyte ratio (NLR), and prognostic nutritional index (PNI).
RESULTS:
A total of 235 patients were retrospectively recruited between January 2017 and September 2022. Lower lymphocyte levels, lymphocyte monocyte ratio (LMR), and PNI, and higher NLR and platelet-to-lymphocyte ratio (PLR) were observed in patients without response. Multivariate logistic regression analysis revealed that NLR could independently predict non-response to nCT in patients with LARC. The sensitivity and specificity of the inflammation-nutrition score for predicting nonresponse were 71.2% and 61.7%, respectively.
CONCLUSION
The pretreatment inflammation-nutrition score is a practical parameter for predicting non-response to nCT in patients with LARC. Patients with high scores were more likely to respond poorly to nCT.
Humans
;
Retrospective Studies
;
Neoadjuvant Therapy
;
Lymphocytes
;
Biomarkers
;
Rectal Neoplasms/pathology*
5.Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.
Ying-Ying JIANG ; Fang-Chao LIU ; Chong SHEN ; Jian-Xin LI ; Ke-Yong HUANG ; Xue-Li YANG ; Ji-Chun CHEN ; Xiao-Qing LIU ; Jie CAO ; Shu-Feng CHEN ; Ling YU ; Ying-Xin ZHAO ; Xian-Ping WU ; Lian-Cheng ZHAO ; Ying LI ; Dong-Sheng HU ; Jian-Feng HUANG ; Xiang-Feng LU ; Dong-Feng GU
Journal of Geriatric Cardiology 2023;20(11):779-787
BACKGROUND:
The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).
METHODS:
A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.
RESULTS:
A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).
CONCLUSIONS
Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.
6.Association of cardiovascular diseases with milk intake among general Chinese adults.
Xin-Yan WANG ; Fang-Chao LIU ; Xue-Li YANG ; Jian-Xin LI ; Jie CAO ; Xiang-Feng LU ; Jian-Feng HUANG ; Ying LI ; Ji-Chun CHEN ; Lian-Cheng ZHAO ; Chong SHEN ; Dong-Sheng HU ; Ying-Xin ZHAO ; Ling YU ; Xiao-Qing LIU ; Xian-Ping WU ; Dong-Feng GU
Chinese Medical Journal 2020;133(10):1144-1154
BACKGROUND:
The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults.
METHODS:
A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations.
RESULTS:
Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86-1.03) (P > 0.05), 0.77 (0.66-0.89) (P < 0.05), and 0.59 (0.40-0.89) (P < 0.05), respectively; each 100 g increase of daily milk intake was associated with 11% lower risk of CVD incidence (HR, 0.89; 95% CI: 0.85-0.94; P < 0.001), and 11% lower risk of CVD mortality (HR, 0.89; 95% CI: 0.82-0.97; P = 0.008) after adjustment for age, sex, residential area, geographic region, education level, family history of CVD, smoking, alcohol drinking, physical activity level, body mass index, and healthy diet status (ideal or not). RCS analyses also showed a linear dose-response relationship with CVD (P for overall significance of the curve <0.001; P for non-linearity = 0.979; P for linearity <0.001) and stroke (P for overall significance of the curve = 0.010; P for non-linearity = 0.998; P for linearity = 0.002) incidence, and CVD mortality (P for overall significance of the curve = 0.045; P for non-linearity = 0.768; P for linearity = 0.014) within the current range of daily milk intake.
CONCLUSIONS
Daily milk intake was associated with lower risk of CVD incidence and mortality in a linear inverse relationship. The findings provide new evidence for dietary recommendations in CVD prevention among Chinese adults and people with similar dietary pattern in other countries.
7.Mechanism action of Chinese herbal compound and target network pharmacology of
Min LI ; Xiao-Lin SHI ; Chao XU ; Lian-Guo WU ; Bin HE ; Yan-Hua LI ; Bo-Cheng LIANG
China Journal of Orthopaedics and Traumatology 2020;33(10):933-937
OBJECTIVE:
To explore compounds, targets and mechanism of
METHODS:
The known effective Chinese herbal compound of YG pill was searched from traditional Chinese medicine integrated database(TCMID). Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN-TCM) was used to predict target of components;DisGeNET and artificial literature reading were used to obtain targets of osteoporosis and bone remodeling;Cytoscape 3.7.1 software and its plug-ins BiN-GO and ClueGO were used to enrich the GO annotation and pathwaysof the related targets, and validation of the predicted target of YG pill were validated by 87 differentially expressed proteins in postmenopausal osteoporosis and postmenopausal osteoporosis disease models in postmenopausal patients with normal bone mass from the previous serum proteomics data.
RESULTS:
Totally 392 compounds were retrieved from YG pill, including 83 sovereign drugs (monkshood, cinnamon, deerhorn gelatin), 127 ministerial drugs (prepared rehmannia root, dogwood, wolfberry fruit and Chinese yam) and 182 supplementary drugs (cuscuta chinensis, eucommia ulmoides and Chinese angelica). Among them, there were 4 same compounds between sovereign drug and ministerial drug, 1 same compound between sovereign drug and supplementary drug, and 14 same compounds between ministerial drug and supplementary drug. Totally 2 112 trusted targets were identified, included 775 sovereign drugs, 1 483 ministerial drugs and 1 491 supplementary drugs;227 targets were selected from YG pill for treating osteoporosis, which participate in nearly 20 process of metabolic process, cell differentiation and biology, and data mining revealed that the process involved bone remodeling and bone mineralization. Acting site of cell mainly inclded 9 kinds of cell which had 13 molecular function. Results of KEGG metabolic pathway enrichment analysis showed 137 signal passages were obviously enriched. Among them, classical osteoclast differentiation signal passages and relative estrogen regulates signaling pathways of menopause were widely distributed in 27 signal passages. Sixtargets were screened by target validation, such as AGT, FGA, APOE, DKK3, P4HB and RAB7A.
CONCLUSION
The characteristics of multi-targets and multi-pathways of YG pill for the treatment of osteoporosis were clarified, which provided a clear direction for the in-depth research. The pharmacodynamic components of YG pill include 36 compounds, and their main action targets include FGA, AGT, APOE, DKK3, P4HB and RAB7A.
Drugs, Chinese Herbal
;
Female
;
Humans
;
Medicine, Chinese Traditional
;
Osteoporosis/drug therapy*
;
Osteoporosis, Postmenopausal
8.Impact of different admission ways on treatment efficiency in patients with acute ST-segment elevation myocardial infarction.
Cai Yan CUI ; Ming Gang ZHOU ; An Fang CHEN ; Lian Chao CHENG ; Cui ZHANG ; Han Xiong LIU ; Lin CAI
Chinese Journal of Cardiology 2020;48(4):302-307
Objective: To analyze the impact of different admission ways on the timeliness of percutaneous coronary intervention and in-hospital mortality in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: A total of 1 044 patients with STEMI, who received primary percutaneous coronary intervention (PPCI) in 9 hospitals in Chengdu from January 2017 to June 2019, were retrospectively enrolled. According to the admission ways, patients were divided into ambulance group (n=100), self-transport group (n=584) and transferred group (n=360). Timeliness and in-hospital mortality were compared among the groups. Indicators of timeliness included the time from symptoms onset to arrive at the hospital, the time from arrive at the hospital to balloon and the total myocardial ischemia time (the time from symptoms to balloon). Multivariate logistic regression analysis was used to verify whether the admission ways was the determinant for in-hospital death in STEMI patients receiving PPCI. Results: The median total myocardial ischemic time in the ambulance group was significantly shorter than that in the self-transport group (180.0 (135.0, 282.0) minutes vs. 278.0 (177.8, 478.5) minutes, P<0.05) and the transferred group (180.0 (135.0, 282.0) minutes vs. 301.0 (204.3, 520.8) minutes, P<0.05). The median time from symptoms to door was as follows: ambulance group
Humans
;
Percutaneous Coronary Intervention
;
Retrospective Studies
;
ST Elevation Myocardial Infarction
;
Time Factors
;
Treatment Outcome
9. Quality Control of Zhenqi Fuzheng Granule Based on Multi-component Determination
Cheng-tao REN ; Lian-chao TIAN ; Yun LI ; Chun LI ; Hong YI ; Dong ZHANG ; Xia-xia FENG ; Wen-wen ZHANG ; Xiao-qian LIU ; Zhi-min WANG
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(9):150-158
Objective: To estimate the overall quality characteristics of Zhenqi Fuzheng granules (ZQFZ),which were composed of Ligustri Lucidi Fructus and Astragali Radix and collected from different manufacturers (their final preparations included two types,contained sugar and sugar free) by established HPLC methods,in order to propose an appropriate quality-control strategy for promoting the quality control specification of ZQFZ.Method: The quantification of the 6 components (rhodioloside,calycosin-7-O-β-D-glucoside,specnuezhenide,ononin,calycosin and astragaloside IV) were performed on a C18 column with two chromatographic systems.Chromatographic system Ⅰ:methanol and water were adopted as mobile phase with gradient elution,the flow rate was 1.0 mL·min-1,and optimum detection waves were at 224,250 and 275 nm respectively.Chromatographic system Ⅱ:methanol and water (80:20) were adopted as mobile phase with gradient elution at the flow rate of 1.0 mL·min-1,and the detector parameters were set as follows:the drift tube temperature was 75℃,and the carrier gas flow rate was 1.5 L·min-1.Both column temperatures were at 30℃.All of the 80 batches of ZQFZ from different manufacturers were determined and analyzed.Result: All of the six markers could be detected in 80 batches of ZQFZ,but their contents were quite different.The results of the one-way ANOVA showed significant differences between manufacturer 4 and other three manufacturers in sugar-containing preparations (P <0.05).And for sugar-free preparations,manufacturer 3 was significant different from other manufacturers (P<0.05).The differences were concentrated in components of rhodioloside and specnuezhenide derived from crude maternal of Ligustri Lucidi Fructus.Conclusion: It is of great significance to increase relevant quality control markers of Ligustri Lucidi Fructus in ZQFZ,such as rhodioloside and specnuezhenide,for standardizing production and improving quality level.
10.TEE guided minimally invasive transthoracic device closure of ventricular septal defect versus convention-al thoracotomy: a comparative study of propensity score matching
Yong CAO ; Bo CHEN ; Lian HU ; Chao LIU ; Huasen CHENG ; Guoxiong WEI ; Fanwu CHI ; Guanshui YU
The Journal of Practical Medicine 2018;34(5):796-799
Objective To compare the difference between transthoracic device closure of ventricular sep-tal defect and conventional thoracotomy and examine the effect and safety of transesophageal echocardiography (TEE) guided minimally invasive transthoracic device closure of ventricular septal defect. Methods Three hun-dred and sixty-eight patients underwent isolated ventricular septal defect surgery in our hospital from May 2014 to May 2016. There were 40 patients in group A underwent TEE guided minimally invasive transthoracic device clo-sure of ventricular septal defect and 328 patients in group B underwent conventional thoracotomy surgery.By using the method of propensity score matching,we selected 40 conventional thoracotomy patients as a control group in our study. Results All patients were survived after surgery without death and other serious complications. Compared with conventional thoracotomy surgery,patient with transthoracic device closure of ventricular septal defect had sta-tistical improvement in surgery time(1.97 ± 0.48 vs. 3.55 ± 1.95)h, ICU stayed time(21.15 ± 30.52 vs. 38.37 ± 10.91)h,volume of thoracic drainag(28.39 ± 32.67 vs.174.84 ± 85.36)mL,surgery incision length(2.98 ± 0.72 vs. 11.76 ± 2.89)cm.There were no significant differences in postoperative valvular regurgitation,arrhythmia and resid-ual shunt between the two groups.Conclusion TEE guided minimally invasive transthoracic device closure of ven-tricular septal defect is safe,effective,feasible,less trauma,less bleeding,faster recovery and etc.

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