1.NAT10 inhibition alleviates astrocyte autophagy by impeding ac4C acetylation of Timp1 mRNA in ischemic stroke.
Li YANG ; Xiaotong LI ; Yaxuan ZHAO ; Hao CHEN ; Can WANG ; Angrong WU ; Xintong GUO ; Yue HUANG ; Qihui WANG ; Lingyun HAO ; Xiaowen LI ; Ying JI ; Jin BAN ; Guangtian WANG ; Junli CAO ; Zhiqiang PAN
Acta Pharmaceutica Sinica B 2025;15(5):2575-2592
Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.
2.Differential effects of hypoxia and oxidative stress on paracrine of mesenchymal stem cells from different sources
Xiaoying PAN ; Yongde XU ; Zhiqiang LIU ; Xiaowen XING ; Yong YANG
Chinese Journal of Tissue Engineering Research 2024;28(19):3024-3030
BACKGROUND:The biological behavior of mesenchymal stem cells is influenced by the survival microenvironment.Pre-treatment of the microenvironment is an important means of regulating the function of mesenchymal stem cells. OBJECTIVE:To compare the differences in paracrine function of umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells under oxidative stress and hypoxia,and to provide a theoretical basis for selecting appropriate pretreatment of mesenchymal stem cells to treat different diseases. METHODS:Umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells were cultured by H2O2 or O2 oxygen,respectively,and cell morphology,proliferation,viability and paracrine factor expression were examined. RESULTS AND CONCLUSION:(1)The expression levels of brain-derived neurotrophic factor and transforming growth factor-β were higher in umbilical cord mesenchymal stem cells than in adipose mesenchymal stem cells under a normal culture environment,while the expressions of stromal cell-derived factor-1α and tumor necrosis factor stimulating factor-6 in the adipose mesenchymal stem cells were significantly higher than those in the umbilical cord mesenchymal stem cells.(2)There was no significant difference in the effect of low and moderate levels(≤100 μmol/L)of H2O2 on the viability of the two mesenchymal stem cells.However,increasing the H2O2 concentration from 50 μmol/L to 100 μmol/L resulted in a distinct increase in vascular endothelial growth factor expression in umbilical cord mesenchymal stem cells.The expression of basic fibroblast growth factor,vascular endothelial growth factor,stromal cell-derived factor-1α and interleukin-10 in adipose mesenchymal stem cells was greatly increased by increasing H2O2 concentration in this range.(3)1%O2 hypoxia promoted mesenchymal stem cell proliferation.After 24 hours of culture in 1%O2,gene expression levels were elevated in both mesenchymal stem cells,but the expression levels of vascular endothelial growth factor,interleukin-10 and tumor necrosis factor stimulating factor-6 were significantly higher in adipose mesenchymal stem cells than in umbilical cord mesenchymal stem cells.(4)It is concluded that hypoxia and oxidative stress preconditioning enhances the paracrine function of mesenchymal stem cells.However,mesenchymal stem cells respond differently to hypoxia and oxidative stress.Treating diseases can choose suitable mesenchymal stem cells for appropriate pretreatment to further enhance their therapeutic potential.
3.Diagnostic value of MRI using proton density-weighted fat-saturated sequence for bone marrow edema in osteoarticular injury
Yan GAO ; Xiaowen PAN ; Wanting DONG ; Peng XIAO
Chinese Journal of Medical Physics 2024;41(2):181-184
Objective To analyze the value of magnetic resonance proton density-weighted fat-saturated(PDWI-FS)sequence in the diagnosis of bone marrow edema(BME)in osteoarticular injury.Methods A total of 150 patients with bone and joint trauma were enrolled in the study.All patients underwent sagittal PDWI-FS sequence scan and conventional MRI sequence scan.The BME detection,signal intensity,image quality,and the signal-to-noise ratio and contrast-to-noise ratio of the lesions were compared between two methods.Results Both methods revealed that there were 225 sites of BME signs in 134 out of the 150 patients,with a higher prevalence in knee joint trauma patients.The signal intensity of the lesions was mainly grade 3 on PDWI-FS sequence and grade 2 on conventional MRI sequence,accounting for 97.78%(220/225)and 43.11%(97/225),indicating that the two methods graded signal intensity differently(Z=15.919,P<0.05).PDWI-FS sequence and conventional sequence had scores of 4.09±0.45 vs 3.88±0.39,3.65±0.42 vs 3.41±0.36,3.25±0.37 vs 3.14±0.35 and 4.21±0.38 vs 3.97±0.34 on lesion clarity,spatial resolution,anamorphosis and diagnostic confidence,and the former scored higher(t=4.319,5.314,2.645,5.765;P<0.05).The signal-to-noise ratio and contrast-to-noise ratio of the lesions on PDWI-FS sequence were 2.07±0.23 and 5.52±0.64,higher than 2.01±0.22 and 5.17±0.59 on conventional sequence,and the differences were statistically significant(t=2.309,4.925;P<0.05).Conclusion Compared with conventional MRI sequence,magnetic resonance PDWI-FS sequence can effectively enhance image quality and display lesions more clearly,providing more accurate information for the diagnosis of BME in osteoarticular injury.
4.Effects of paroxetine combined with aniracetam on the treatment of senile depression and the levels of serotonin, cortisol and cystatin C
Meiqin XU ; Yong YANG ; Xiaowen XU ; Mingzhi PAN
Journal of Chinese Physician 2024;26(11):1632-1636
Objective:To analyze the effects of paroxetine combined with aniracetam on the treatment of senile depression and the levels of 5-hydroxytryptamine (5-HT), cortisol and cystatin C(CysC).Methods:A total of 80 patients admitted to the psychiatric Department of Psychiatry, Suzhou City Guangji Hospital from January 2020 to January 2023 were selected and divided into two groups by random number table method: control group (40 cases) and observation group (40 cases). The control group was treated with oral paroxetine hydrochloride tablets, and the observation group was treated with oral paroxetine hydrochloride combined with aniracetam tablets. Negative emotions were assessed by Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) before and after treatment, and sleep quality was assessed by Pittsburgh Sleep Quality Scale (PSQI). Serum levels of central neurotransmitters [norepinephrine (NE) and 5-HT], neurotrophic factor (BDNF), oxidative stress [cortisol and malondialdehyde (MDA)] and amino acid metabolism [cysteine (Hcy) and CysC] were measured before and after treatment.Results:After treatment, SAS and SDS scores in both groups were significantly decreased (all P<0.05), and SAS and SDS scores in the observation group were significantly lower than those in the control group (all P<0.05). After treatment, the sleep quality, sleep time, sleep time, sleep efficiency, sleep disorders, hypnotic drugs, daytime function scores and PSQI total scores of the two groups were significantly decreased (all P<0.05), and the above scores of the observation group were significantly lower than those of the control group ( P<0.05). After treatment, the serum levels of NE, 5-HT and BDNF in 2 groups were significantly increased, and the serum levels of NE, 5-HT and BDNF in the observation group were significantly higher than those in control group (all P<0.05). After treatment, the levels of serum cortisol and MDA in both groups were significantly decreased, and the levels of serum cortisol and MDA in the observation group were significantly lower than those in the control group (all P<0.05). After treatment, the serum Hcy and CysC levels in 2 groups were significantly decreased, and the serum Hcy and CysC levels in the observation group were significantly lower than those in the control group (all P<0.05). Conclusions:Paroxetine combined with aniracetam is more effective than paroxetine alone in the treatment of senile depression, which can effectively relieve anxiety and depression symptoms, improve sleep quality, and have positive effects on serum neurotransmitters, neurotrophic factors, oxidative stress and amino acid metabolism levels of patients.
5.Clinical and MRI nomogram model for predicting simultaneous liver metastasis of rectal cancer
Yudie PAN ; Shuxing WANG ; Xiaowen LIU ; Ting XU ; Changsi JIANG ; Xue TANG ; Yan LUO ; Jingshan GONG
Chinese Journal of Medical Imaging Technology 2024;40(9):1361-1365
Objective To explore the value of nomogram model based on clinical data and MRI findings for predicting simultaneous liver metastasis(SLM)of rectal cancer.Methods Clinical and MRI data of 356 patients with rectal cancer were randomly divided into training set(n=249,45 cases of SLM)and validation set(n=107,27 cases of SLM)at a ratio of 7∶3.Logistic regression analysis were used to screen the independent factors for predicting SLM of rectal cancer.The nomogram model was then constructed,and the efficacy of this model was evaluated.Results Tumor N-stage,serum carcinoembryonic antigen,carbohydrate antigen 19-9 and involvement of mesorectal fascia(MRF)or not were all independent factors for predicting SLM of rectal cancer.The area under the curve(AUC)of this nomogram model for predicting rectal cancer SLM in training set and validation set was 0.834(95%CI[0.776,0.893])and 0.769(95%CI[0.662,0.877]),respectively.The calibration curve showed good consistency between the predicted values and the measured values,and the decision curve analysis showed that the nomogram model had good clinical practicality.Conclusion The nomogram model based on clinical data and MRI findings could be used to predict SLM of rectal cancer.
6.Application value of observed tumor enhancement characteristics by dynamic enhancement MRI in assessing blood supply of small hepatocellular cancer
Yang SUN ; Tingting ZHANG ; Xiaowen HU ; Mengli WANG ; Xiaolong PAN ; Guorong LI
China Medical Equipment 2024;21(11):51-56
Objective:To explore application value of observed tumor enhancement characteristics by dynamic enhancement magnetic resonance imaging(MRI)in assessing blood supply of small hepatocellular cancer.Methods:The cases data of 80 patients with suspected small hepatocellular cancer who admitted to Yichang Central People's Hospital from January 2019 to January 2023 were retrospectively analyzed.The enhancement characteristics of tumors of all patients were real-timely observed by MRI scanner,which included the relative enhancement degree(RSI),enhancement mode,time-signal intensity curve,etc.The enhanced characteristics of the tumors were recorded,which were combined with a series of variables included disease history,tumor type,tumor size,the number of tumor,liver function status of patients to conduct analysis.The receiver operating characteristics(ROC)curve was adopted to analyze the application value of the observed tumor enhancement characteristics by dynamic enhancement MRI in assessing the status of blood supply of small hepatocellular cancer.Results:There were statistically significant differences in the RSI(F=40.151,P<0.05),enhancement degree(x2=27.374,P<0.05),and time-signal intensity curve(x2=20.950,P<0.05)of dynamic enhanced MRI among different stages of small hepatocellular cancer.The differences in medical history(F=17.844,P<0.05),tumor type(x2=11.219,P<0.05),tumor size(x2=14.081,P<0.05),and the number of tumor(x2=74.310,P<0.05)among different enhancement degrees of arterial phase were also statistically significant.With the enhancement degree increased,the asymptomatic period increased,and the number of malignant tumors increased,and tumor size increased.The differences in liver function status among different time-signal intensity curves were statistically significant(F=330.182,325.872,216.689,P<0.05).The area under curve(AUC)value of the ROC of the RSI of observed tumor enhancement characteristics by dynamic enhancement MRI was 0.582(95%CI:0.493-0.670)in assessing blood supply of small hepatocellular cancer.Conclusion:Dynamic enhancement MRI can observe the vascular generation and hemodynamic changes of small hepatocellular cancer,which has a certain application value in assessing blood supply of small hepatocellular cancer,and it can help doctors to choose appropriate treatment plan and assess treatment effect.
7.The Reliability and Validity of the Chinese Version of the Visually Induced Motion Sickness Susceptibility Questionnaire
Jiamei LU ; Linyao SHI ; Chuanjing QIU ; Fan WANG ; Xiaowen LI ; Shuai PAN ; Jing ZHAO ; Shengguang YAN ; Zhanguo JIN
Journal of Audiology and Speech Pathology 2024;32(3):193-199
Objective To sinicize the long and short forms of the English version of the visually induced mo-tion sickness susceptibility questionnaire(VIMSSQ)and to test the validity and reliability of the Chinese version of the questionnaire among college students.Methods The Chinese version of the VIMSSQ was sinicized using Brislin's translation model,the translated scale was cross-culturally adapted through expert consultation.At last,the Chinese version of the questionnaire survey was conducted among 757 college students,and 80 college students were selected to fill out the simulator sickness questionnaire(SSQ)at the same time to do a correlation analysis in order to verify the predictive efficacy of the scale,and the reliability and validity results of the scale were analyzed to form the Chinese version of the VIMSSQ.Results The total Cronbach's alpha coefficient of the long form question-naire was 0.94,and the alpha coefficients of the five factors were 0.85,0.85,0.85,0.84,and 0.83 respectively.The total retest reliability was 0.79,and the retest reliabilities of the five factors were 0.73,0.77,0.76,0.66,and 0.62 respectively.The split-half reliability was 0.84.The total Cronbach's alpha coefficient of the short form ques-tionnaire was 0.83,and the retest reliability was 0.81,and the split-half reliability was 0.77.The item-level con-tent validity index(I-CVI)for the long and short forms and the average scale-level content validity(scale-level con-tent validity index/average,S-CVI/Ave)were both 1.VIMSSQ scores for both the long and short forms were sig-nificantly correlated with the SSQ,with r=0.76(P<0.001)between the long form and the SSQ,and with r=0.77(P<0.001)between the short form and the SSQ.Conclusion The Chinese version of the VIMSSQ has good reliability and validity among college students,and can be used as a measurement tool to evaluate college students'susceptibility to visually induced motion sickness.
8.Cerebral Hyperperfusion Syndrome
Furong LI ; Shuhan LIU ; Weiwei DONG ; Ya'nan ZHANG ; Xin PAN ; Xiaowen SUI ; Hongling ZHAO
International Journal of Cerebrovascular Diseases 2024;32(4):297-302
Cerebral hyperperfusion syndrome (CHS) is a rare but serious complication after cerebral revascularization, which may lead to catastrophic consequences. The mechanism of CHS is not fully understood, and it may be related to cerebral autoregulation dysfunction and the increase of blood pressure after operation. Timely detection and treatment of cerebral hyperperfusion can avoid CHS. This article reviews the pathogenesis, diagnosis, clinical manifestations, prevention and treatment of CHS.
9.To investigate the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation in mild stenosis of the carotid artery
Xin PAN ; Yanan ZHANG ; Shubei MA ; Shuhan LIU ; Xiaowen SUI ; Haibin LIU ; Furong LI ; Zusheng LI ; Hongling ZHAO
Chinese Journal of Postgraduates of Medicine 2024;47(8):694-699
Objective:To investigate the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation in patients with mild carotid artery stenosis.Methods:A retrospective study was conducted to select 30 cases of patients with unilateral mild carotid artery stenosis and moderate intensity aerobic exercise for more than 1 year in the Central Hospital of Dalian University of Technology from July 2022 to November 2023 as the exercise group (study group), and 30 cases of patients with unilateral mild carotid artery stenosis without exercise habits matched by age, gender and other factors as the non-exercise group (control group). Transcranial Doppler ultrasound (TCD) examination was performed in both groups, and the recumbent-upright-test, breath holding test and breath exchange test were performed to calculate the occurrence rate of "w" wave in recumbent-upright position, the slope of "w" wave in recubitus position, the change rate of pulse index (PI) before and after breath holding, resistance index (RI), breath holding index (BHI), and cerebral blood flow velocity before and after breath exchange. The blood pressure and heart rate difference in the recumbent-upright position were calculated, and the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation function in patients with mild carotid artery stenosis was evaluated by statistical analysis. The correlation analysis between the exercise years and BHI in the study group was carried out to explore the relationship between the exercise years and cerebrovascular reactivity.Results:The occurrence rate and slope of "w" wave in the study group were higher than those in the control group: 93.3%(28/30) vs. 86.7%(26/30), 2.27 ± 1.14 vs. 1.28 ± 0.23, 2.67 ± 0.63 vs. 1.41 ± 0.69, there were statistically significant ( P<0.05). The change rates of PI and RI before and after breath holding and ventilation in the study group were higher than those in the control group: 21.23 ± 7.67 vs. 13.89 ± 9.67, 14.62 ± 6.63 vs. 11.17 ± 1.78 and 26.26 ± 12.46 vs. 18.36 ± 12.13, 14.91 ± 4.91 vs. 10.83 ± 2.35, and the average cerebral blood flow velocity before and after ventilation was higher than that in the control group: (31.26 ± 4.92) cm/s vs. (24.89 ± 6.34) cm/s, there were statistically significant ( P<0.01). The exercise years of the study group was negatively correlated with the breath holding index. Conclusions:Moderate intensity exercise is associated with cerebral blood flow regulation in patients with mild carotid artery stenosis. Exercise years are negatively correlated with cerebral blood flow regulation. Impaired cerebral blood flow regulation may be one of the potential mechanisms of poor prognosis of stroke in carotid artery stenosis population.
10.The mediating role of intrinsic motivation between challenge-hindrance stressors and thriving at work among clinical nurses
Cuicui LI ; Xiaowen CUI ; Ying XIN ; Yarui ZHAO ; Weiwei PAN ; Yun ZHU
Chinese Journal of Practical Nursing 2023;39(21):1665-1670
Objective:To explore the relationship between challenge-hindrance stressors and thriving at work in clinical nurses, and to analyze the mediating role of intrinsic motivation.Methods:This was a cross-sectional survey. A total of 319 nurses from the Provincial Hospital Affiliated to Shandong First Medical University, Qilu Hospital of Shandong University, Shandong Provincial Qianfoshan Hospital from May to June 2022 were investigated by general data questionnaire, Challenge-Hindrance Stressors Scale, Intrinsic Motivation Scale and Thriving At Work Scale. Pearson was used to analyze the correlation between various variables, and Amos 23.0 was used to construct a structural equation model to analyze the mediating role of intrinsic motivation between challenging stressors, hindrance stressors, and thriving at work.Results:The score for challenging stressors was (21.22 ± 4.42) points, the score for hindrance stressors was (13.51 ± 3.59) points, the score for intrinsic motivation was (78.96 ± 11.52) points, and the score for thriving at work was (51.27 ± 8.03) points. Challenging stressors was positively associated with intrinsic motivation and thriving at work ( r=0.222, 0.221, both P<0.01), hindrance stressors was negatively associated with intrinsic motivation and thriving at work ( r=-0.152, -0.337, both P<0.01), intrinsic motivation was positively correlated with thriving at work ( r=0.564, P<0.01). Intrinsic motivation was partially mediated between challenging stressors, hindrance stressors and thriving at work, respectively accounting for 16.02% and 13.79%. Conclusions:Challenging stressors and hindrance stressors can indirectly influence their thriving at work through intrinsic motivation. Nursing managers should help nurses treat different stressors correctly to enhance their intrinsic motivation and promote their thriving at work.

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