1.Effects of autophagy on myocardial injury in rats with common bile duct ligation.
Xiaoyu WANG ; Lin LYU ; Aijie LIU ; Lei LUN ; Wenli BI ; He DONG
Chinese Critical Care Medicine 2025;37(1):59-64
OBJECTIVE:
To investigate the impact of autophagy on cardiac tissue injury following common bile duct ligation (CBDL) in rats.
METHODS:
Twenty-four SPF grade healthy adult male Sprague-Dawley (SD) rats were randomly divided into four groups, with 6 rats in each group. The sham-operated (Sham) group underwent only dissection of the common bile duct without ligation. The CBDL group underwent CBDL to simulate jaundice-induced myocardial injury. The autophagy inhibitor 3-methyladenine (3-MA)+CBDL group was intraperitoneally injected with 15 mg/kg 3-MA 2 hours before modeling, and then injected once every other day. The CBDL+autophagy enhancer rapamycin (Rapa) group was intraperitoneally injected with Rapa 1 mg/kg 0.5 hour after modeling, and then injected once every other day. The rats in each group were sacrificed 2 weeks after surgery, and blood was taken from the inferior vena cava. Serum total bilirubin (TBil), alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and MB isoenzyme of creatine kinase (CK-MB) were detected by using a fully automated animal biochemical analyzer. Serum oxidative stress marker superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by colorimetric assay. The heart tissues of rats were taken and pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining. Transmission electron microscope was used to observe autophagosomes after double staining with uranyl acetate and lead citrate. The expressions of autophagy-related proteins were detected using Western blotting.
RESULTS:
Compared with the Sham group, the serum SOD activity of rats in the CBDL group was significantly decreased, while the serum MDA, TBil, ALT, AST, LDH, and CK-MB were significantly increased; the expressions of autophagy-related proteins Beclin-1 and microtubule-associated protein 1 light chain 3-II/I (LC3-II/I) were significantly increased, and p62 protein expression was significantly decreased. Autophagosomes were seen under electron microscopy in the CBDL group, and cardiac histopathological morphology showed focal necrosis in the myocardium as well as infiltration of inflammatory cells, dilatation of small interstitial blood vessels, and myocardial fiber degeneration. Compared with the CBDL group, cardiac tissue injury in rats was attenuated by pretreatment with the autophagy inhibitor 3-MA, with a decrease in inflammatory cell infiltration in myocardial tissue, a reduction in interstitial vasodilatation, and a decrease in the area of myocardial fibrosis; a decrease in the number of autophagosomes by electron microscopy; and a further rise in the viability of serum TBil, ALT, and AST [TBil (μmol/L): 184.40±6.74 vs. 120.70±16.93, ALT (U/L): 501.10±62.18 vs. 178.80±22.30, AST (U/L): 806.50±76.92 vs. 275.50±55.81, all P < 0.01], as well as a decrease in the levels of serum SOD, MDA, LDH, and CK-MB [SOD (kU/L): 85.00±5.29 vs. 107.50±7.86, MDA (μmol/L): 10.72±0.93 vs. 15.06±1.88, LDH (U/L): 387.40±119.50 vs. 831.30±84.35, CK-MB (U/L): 320.10±14.04 vs. 814.70±75.66, all P < 0.05]. The expressions of the autophagy-related proteins Beclin-1 and LC3-II/I in cardiac tissues were significantly decreased [Beclin-1 protein (Beclin-1/GAPDH): 0.67±0.04 vs. 0.89±0.01, LC3-II/I ratio: 0.93±0.03 vs. 1.09±0.01, both P < 0.01], and p62 protein expression was significantly increased (p62/GAPDH: 0.99±0.01 vs. 0.60±0.01, P < 0.01). In contrast, compared with the CBDL group, after administration of the autophagy enhancer Rapa, the rats showed increased cardiac tissue injury, increased inflammatory cell infiltration in myocardial tissues, increased interstitial vasodilatation, and increased area of myocardial fibrosis; an increase in autophagosomes was seen by electron microscopy; the change tendency of serum biochemical indicators and proteins in myocardial tissues were opposite with autophagy inhibition group with a decrease in serum TBil, ALT, and AST [TBil (μmol/L): 22.00±3.21 vs. 120.70±16.93, ALT (U/L): 72.13±5.97 vs. 178.80±22.30, AST (U/L): 135.20±12.95 vs. 275.50±55.81, all P < 0.05], as well as a increase in the levels of serum SOD, MDA, LDH, and CK-MB [SOD (kU/L): 208.00±2.65 vs. 107.50±7.86, MDA (μmol/L): 20.38±0.40 vs. 15.06±1.88, LDH (U/L): 1 268.00±210.90 vs. 831.30±84.35, CK-MB (U/L): 1 150.00±158.70 vs. 814.70±75.66, all P < 0.05]. The protein expressions of Beclin-1 and LC3-II/I in cardiac tissues were significantly increased [Beclin-1 protein (Beclin-1/GAPDH): 0.96±0.01 vs. 0.89±0.01, LC3-II/I ratio: 1.19±0.01 vs. 1.09±0.01, both P < 0.05], and p62 protein expression was significantly decreased (p62/GAPDH: 0.19±0.02 vs. 0.60±0.01, P < 0.01).
CONCLUSIONS
Activation of autophagy in CBDL rats led to myocardial tissue injury and reduced cardiac function. Inhibition of autophagy improved cardiac tissue injury in CBDL rats, while increasing autophagy exacerbated myocardial tissue injury.
Animals
;
Autophagy
;
Rats, Sprague-Dawley
;
Male
;
Ligation
;
Rats
;
Common Bile Duct/surgery*
;
Myocardium/pathology*
;
Adenine/pharmacology*
2.Syndrome Differentiation and Treatment of Tic Disorders in Children from the Theory of Qi Movement of Zang-Fu Organs Based on “Manifestation-Body and Spirit-Qi”
Wenbo LIU ; Wenli SHI ; Juan DONG ; Yunxia ZHAO ; Mengting ZHAO ; Bingxiang MA
Journal of Traditional Chinese Medicine 2024;65(6):582-586
Based on the theory of “manifestation-body and spirit-qi”, it is considered that the pathogenesis of tic disorders (TD) involves three manifestations of “wind, phlegm and fire”, with wind as the leading factor and phlegm and fire as the accompanying factors. It is advocated to identify the abnormality of body and spirit, summarize the evolution of manifestation, and prescribe flexibly based on qi movement of zang-fu organs. Among them, the common symptoms related to tics are mostly belong to wind symptoms, which originated from lung qi failing to purify and liver qi over-ascent. The method of soothing liver wood and purifying lung gold is adopted, and modified Xiaochaihu Decoction (小柴胡汤) and Cangerzi Powder (苍耳子散) are recommended; Patients with prolonged illness and strange symptoms are often mixed with phlegm, which stemmed from the fact that spleen failing to rise clear and stomach failing to downward turbid. The method of raising spleen-earth and lowering stomach-earth is adopted, and modified Yigong Powder (异功散) and Erchen Decoction (二陈汤) are recommended; Patients with severe symptoms are often mixed with fire symptoms, which originated from discordance of water and fire and hyperactivity of heart fire. The method of interacting heart and kidney and coordinating water and fire is adopted, and modified Xiegan Pill (泻肝丸) and Liuwei Dihuang Pill (六味地黄丸) are recommended, in order to regulate qi movement, harmonize body and spirit, and improve the symptoms.
3.Influencing Factors of Inter-arm Systolic Blood Pressure Differences in Hypertensive Population Aged 40 Years and Younger
Qihuan CAO ; Yinan SU ; Ying ZHU ; Wenli DONG ; Yuxi WANG ; Jing GE ; Shouling WU
Chinese Circulation Journal 2024;39(2):164-170
Objectives:To explore the influencing factors of inter-arm systolic blood pressure difference(sIAD)in young hypertensive population. Methods:A total of 12 895 young Kailuan employees aged≤40 years,who participated in the physical examination from 2010 to 2020,were enrolled in this study.All of them underwent blood pressure measurements of four limbs in supine position.Young hypertensive group(n=3 584)and young non-hypertensive group(n=3 584)were 1∶1 matched by sex and age(±1 year),and participants were further divided into sIAD<10 mmHg(1 mmHg=0.133 kPa)and sIAD≥10 mmHg subgroups.A stepwise multivariate logistic regression model was established to analyze the determinants of sIAD≥10 mmHg. Results:The detection rate of sIAD≥10 mmHg was significantly higher in the young hypertensive group than in the young non-hypertensive group(31.72%vs.27.76%,P<0.001).Stepwise multivariate logistic regression analysis showed that in young hypertensive population,ankle-brachial index(ABI)<0.9,male,obesity,overweight,elevated low density lipoprotein cholesterol(LDL-C)level,and systolic blood pressure were positively associated with sIAD≥10 mmHg,while college education or above,physical exercise were negatively correlated with sIAD≥10 mmHg(all P<0.05).In the young non-hypertensive population,ABI<0.9,systolic blood pressure were positively correlated with sIAD≥10 mmHg,while age was negatively associated with sIAD≥10 mmHg(all P<0.05). Conclusions:The detection rate of sIAD≥10 mmHg is higher in young hypertensive population than in young non-hypertensive population.Decreased ABI,male sex,obesity,overweight,increased LDL-C level,systolic blood pressure,college education and above,and physical exercise are the influencing factors of sIAD≥10 mmHg in young hypertensive population.
4.Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China
Yufei LUO ; Yuan WEI ; Xiaochen WANG ; Yi ZHANG ; Wenli ZHANG ; Bing WU ; Zhengxiong YANG ; Xiaojie DONG ; Ruiting HAO ; Yifu LU ; Xiaoshuang FU ; Ziyue ZHU ; Ying ZHU ; Yuebin LYU ; Dongqun XU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2024;58(6):839-846
Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.
5.Choice of extraction media for Ni release risk evaluation on nickel-titanium alloys cardiovascular stents
Bin LIU ; Yang QIN ; Xiaoman ZHANG ; Changyan WU ; Dongwei WANG ; Wenli LI ; Cheng JIN ; Yunfan DONG ; Yiwei ZHAO ; Lili LIU ; Wei XIONG
International Journal of Biomedical Engineering 2024;47(2):156-161
Objective:To determine the content of the released nickel ion through the 7 extraction media to extract the Ni-Ti wires and to plot the curve of the released nickel ion so as to identify a leaching medium that can be substituted for blood for in vitro Ni release evaluation. Methods:The release of Ni through microwave digestion/inductively coupled plasma mass spectrometry (ICP-MS) in the goat serum was determined. Because of the high content of Ni release, it could be determined by diluting the extraction medium, and other extraction media could be determined directly. Ni release standard curves were plotted by the release amount and different time point variables. Though the different extraction media Ni release curves confirm the specificity of extraction media instead of blood.Results:By analyzing the Ni release curves of seven leaching media, it was found that none of these seven extraction media was suitable for the evaluation of Ni release in in vitro leaching media. Considering the safety of the leaching medium and the simplicity of preparation, hydrochloric acid solution was chosen as the leaching medium, but the concentration needed to be diluted accordingly. Finally, a hydrochloric acid solution was created as an alternative to blood for the in vitro study of Ni release from Ni-Ti alloy cardiovascular products, with a volume fraction of 0.005%. Conclusions:The in vitro leaching medium that can replace blood was found to be hydrochloric acid for the time being, but its concentration was too high, resulting in too much Ni release as well, which deviated from the actual situation. Therefore, the hydrochloric acid solution was diluted step by step, and the Ni release curve was examined until it was close to the clinical release level, and the actual concentration was determined, thus laying a solid foundation for the subsequent evaluation of the safety and risk.
6.Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China
Yufei LUO ; Yuan WEI ; Xiaochen WANG ; Yi ZHANG ; Wenli ZHANG ; Bing WU ; Zhengxiong YANG ; Xiaojie DONG ; Ruiting HAO ; Yifu LU ; Xiaoshuang FU ; Ziyue ZHU ; Ying ZHU ; Yuebin LYU ; Dongqun XU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2024;58(6):839-846
Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.
7.Three-dimensional evaluation of changes in the upper airway,natural head position and hyoid bone position in skeletal Class Ⅲ patients after bimaxillary surgery
Yao ZHENG ; Shaoyang YU ; Wenli HUANG ; Lirong DONG ; Qiang ZHANG ; Xiao YUAN
STOMATOLOGY 2024;44(8):590-595
Objective To assess short-and long-term changes in the upper airway,natural head position and hyoid bone position in skeletal Class Ⅲ patients after bimaxillary surgery.Methods In this retrospective study,the cone-beam computed tomography(CBCT)of skeletal Class Ⅲ patients was taken before surgery(T0),3 months after surgery(T1)and 2 years after surgery(T2).Three-dimensional images were created to assess postoperative changes and the correlation between the upper airway,natural head posi-tion and hyoid bone was analyzed.Results Thirty skeletal Class Ⅲ patients(13 men and 17 women)who underwent bimaxillary sur-gery with a mean(SD)age of 21 years(a range of 17-30 years)were evaluated.A significant decrease was observed in the volume of palatopharynx,glossopharynx and total airway after T1 and T2.There was a significant correlation between changes in the position of the mandible and changes in the volume of the upper airway(P<0.05).The NSL/OPT angle and the NSL/CVT angle were greater after Tl and T2.The change in the NSL/CVT angle was positively correlated with the change in palatopharyngeal and glossopharyngeal volume(P<0.05).Conclusion Bimaxillary surgery may cause a decrease in upper airway volume,an increase in the cranio-cervical angle,and a downward and backward movement of the hyoid bone.Changes in the cranio-cervical angle may cause changes in the upper air-way.
8.Mechanism of microglia ferroptosis in smoke inhalation-induced brain injury
Bin LIU ; Long YANG ; Wenli LI ; Ningning SHAO ; Jinrui DONG
Tianjin Medical Journal 2024;52(8):791-797
Objective To investigate the underlying mechanism of microglia ferroptosis in smoke inhalation-induced(SII)brain injury.Methods Twenty SPF-grade male C57BL/6 mice were randomly divided into the control group,the SII group,the ferrostatin-1 group(Fer-1,2.5 mmol/kg)and the deferoxamine group(DFO,200 mg/kg),with 5 mice in each group.Mice in the Fer-1 group and the DFO group were intraperitoneally injected with Fer-1 and DFO 1,3 and 5 day after smoke exposure,respectively.The pathological changes of brain tissue were examined by HE staining and Prussian blue staining on the 6th day after smoke exposure.RT-qPCR was used to detect levels of inflammatory factors,brain tissue damage markers and ferroptosis markers.The contents of iron in mouse brain tissue were determined by double pyridine colorimetric assay.The contents of malondialdehyde(MDA)and lipid peroxide(LPO)in mouse brain tissue were determined by thiobarbituric acid(TBA)colorimetric assay.Superoxide dismutase(SOD)activity in mouse brain tissue was measured by xanthine oxidase assay kit.The contents of glutathione(GSH)in mouse brain tissue were determined by direct method of dithiodinitrobenzoic acid(DTNB)assay.BV2 cells were cultured in complete DMEM medium and divided into the control group,the erastin group(10 μmol/L),the Fer-1 group(erastinc stimulation combined with 5 mmol/L Fer-1 treatment)and the DFO group(erastinc stimulation combined with 50 mmol/L DFO treatment).After 24 h,cell viability was detected by CCK-8 assay,cell apoptosis was detected by Annexin V-FITC/PI flow cytometry,intracellular reactive oxygen species(ROS)production was detected by DCFDA staining,and mitochondrial membrane potential was detected by MitoTracker Red CMXRos staining.Results Compared with the control group,enhanced iron deposition and inflammation in brain tissue,elevated mRNA expression of inflammatory markers and damage markers in brain tissue,up-regulated ACSL4 and NCOA4 mRNA levels,down-regulated GPX4 and SLC7A11 mRNA levels,decreased GSH and SOD contents,and increased LPO and MDA contents were observed in brain tissue of the SII group(P<0.05).The mRNA expression level of 7 member of solute carrier family 11(SLC7A11)was decreased in mice of the SII group.The contents of GSH and SOD were decreased,and the contents of LPO and MDA were increased(P<0.05).Compared with the SII group,all the above parameters were reversed in the Fer-1 group and the DFO group,and the damage of mouse brain tissue was alleviated(P<0.05).In BV2 cell experiments,compared with the control group,decreased survival rate of BV2 cells and increased apoptosis rate were found in the erastin group(P<0.05),and increased intracellular ROS level and decreased mitochondrial membrane potential were also observed in the erastin-stimulated BV2 cells.The above parameters were opposite to those of the erastin group in the Fer-1 group and the DFO group(P<0.05),and the oxidative damage of BV2 cells was alleviated.Conclusion The ferroptosis inhibitors Fer-1 and DFO can inhibit microglia ferroptosis and alleviate smoke inhalation-induced brain injury.
9.Practice and reflection on strengthening ideological and political work in public hospitals from the per-spective of high-quality development
Jing JIAO ; Chun GUAN ; Lin DONG ; Xin LUO ; Li HUANG ; Xi WU ; Wenli DUAN
Modern Hospital 2024;24(7):1031-1033
Ideological and political work is the fine tradition,distinct characteristic,and political advantage of the Com-munist Party of China,and it is the lifeline of all work.This article,based on literature research and practical experience,ex-pounds the important significance of ideological and political work for the high-quality development of public hospitals,analyzes the weaknesses of current ideological and political work,focuses on strengthening ideals and beliefs,sharpening the initial aspira-tion of serving the people,and cultivating high-quality talents,and explores the practical path of strengthening ideological and po-litical work in hospitals in the new era.It summarizes the working methods of"three focuses,three combinations,and three unifi-cations,"providing strong impetus for the high-quality development of hospitals.
10.Clinical characteristics and prognoses of 13 patients with Morvan syndrome with obvious electromyography characteristics
Zeqin DONG ; Wenli MEI ; Shaomin ZUO ; Jiajia XU ; Lipin YUAN ; Wei LI ; Huiqin LIU
Chinese Journal of Neuromedicine 2024;23(5):471-477
Objective:To summarize the clinical manifestations, neuroelectrophysiological characteristics and prognoses of Movan syndrome (MoS), and provide references for early diagnoses and prognoses.Methods:A retrospective analysis was performed. The clinical data, such as clinical symptoms, treatments and prognoses, laboratory test results and electrophysiological test results, of 13 patients with confirmed MoS in Department of Neurology, He'nan Provincial People's Hospital from January 2018 to October 2023 were collected.Results:Ten male MoS patients and 3 female ones were included. Main clinical manifestations of 13 patients with MoS included myokymia, pain, numbness of limbs, itching all over the body, hyperhidrosis, urinary and defecation disorder, tachycardia, insomnia, anxiety and depression. Ten patients completed the autoimmune encephalitis antibody detection: 3 only had positive anti-contactin-associated protein-like 2 (CASPR2) antibody, 2 only had positive anti-leucine-rich glioma-inactivated protein1 (LGI1) antibody, and 2 had both positive anti-CASPR2 antibody and anti-LGI1 antibody. Eleven patients completed tumor screening and 4 tumors (thymoma [ n=2], lung squamous cell carcinoma [ n=1] and adrenal non-Hodgkin's lymphoma [ n=1]) were noted. Ten patients completed electrocardiogram, including 3 patients with resting tachycardia and 2 patients with ST segment elevation. All patients completed the electromyographic examination; 12 patients showed abnormal motor unit potential, including myokymia potential, fasciculation potential and neuromyotonic potential; F-wave and/or M-wave post-discharge potentials were found in all patients. Follow up was performed for 1-12 months; in 9 non-tumor patients, 5 were improved in 6 patients accepted immunotherapy and one was improved in 3 patients received symptomatic treatment; in 4 tumor patients, only one was improved in 3 received immunotherapy. Conclusion:Myokymia, pain, urinary and defecation disorder, and severe insomnia are typical symptoms for MoS patients; serum anti-CASPR2/LGI1 antibody and electromyography results provide evidences for MoS diagnosis; early immunotherapy can improve the MoS prognosis, and MoS patients combined with tumors have poor clinical prognosis.

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