1.GSTP1-mediated inhibition of ACSL4-dependent ferroptosis via JNK pathway in DOX-induced cardiomyopathy.
Mingbo WU ; Ye ZHAO ; Dong LI ; Xueli HU ; Jiaojiao ZHOU ; Siyi CHEN ; Xin YANG ; Zegang LI ; Xiaomiao RUAN ; Jingwen YANG ; Wenwu LING
Chinese Medical Journal 2025;138(19):2498-2510
BACKGROUND:
Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC.
METHODS:
A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms.
RESULTS:
Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC.
CONCLUSIONS
This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.
2.Clinical value of radiomics based on CT examination in preoperative differential diagnosis of pancreatic serous cystadenoma and mucinous cystadenoma
Wenjie LIANG ; Wuwei TIAN ; Yubizhuo WANG ; Jingwen XIA ; Shijian RUAN ; Jiayuan SHAO ; Zhihao FU ; Na LU ; Yong DING ; Wenbo XIAO ; Xueli BAI
Chinese Journal of Digestive Surgery 2021;20(5):555-563
Objective:To investigate the clinical value of radiomics based on computed tomography (CT) examination in preoperative differential diagnosis of pancreatic serous cystadenoma (SCA) and mucinous cystadenoma (MCA).Methods:The retrospective case-control study was conducted. The clinicopathological and imaging data of 154 patients with pancreatic cystic neoplasms who were admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2012 to December 2019 were collected. There were 24 males and 130 females, aged (50±13)years. Of the 154 patients, 99 cases were diagnosed as SCA and 55 cases were diagnosed as MCA. All the 154 patients underwent plain and enhanced CT scan of pancreas before operation. The clinical characteristics, radiology features and radiomics features of all patients were collected to construct the clinical characteristics model, radiology model, radiomics model and fused model. The receiver operating characteristic (ROC) curve of each model was drawn, and those constructed models were evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Based on the optimal model, the nomogram was constructed. Observation indicators: (1) establishment and validation of clinical characteristics model; (2) establishment and validation of radiology model; (3) establishment and validation of radiomics model; (4) establishment and validation of fused model; (5) nomogram of fused model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Results:(1) Establishment and validation of clinical characteristics model: 3 clinical characteristics, including age, symptoms and preoperative serum CA19-9, were selected using multinomial logistic linear regression analysis to construct the clinical characteristics model. Result of the multinomial logistic linear regression analysis was expressed by formula ①: clinical characteristics model score=0.635-0.007×age+0.054×clinical symptoms+0.108×preoperative serum CA19-9. The ROC curve for the test dataset of clinical characteristics model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of clinical characteristics model were 0.611(95% confidence interval as 0.488?0.734, P<0.05), 56.6%, 66.7%, 56.3%, 41.5%, 78.4% for the training dataset and 0.771(95% confidence interval as 0.624?0.919, P<0.05), 77.8%, 63.1%, 88.5%, 80.1%, 76.7% for the test dataset, respectively. (2) Establishment and validation of radiology model: 5 radiology characteristics, including tumor location, the number of tumors, tumor diameter of cross section, lobulated tumor and polycystic tumor (more than 6), were selected using multinomial logistic linear regression analysis to construct the radiology model. Result of the multinomial logistic linear regression analysis was expressed by formula ②: radiology model score=?0.034+0.300×tumor location+0.202×the number of tumors+0.014×tumor diameter of cross section?0.251×lobulated tumor?0.170×polycystic tumor (more than 6). The ROC curve for the test dataset of radiology model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of radiology model were 0.862(95% confidence interval as 0.791?0.932, P<0.05), 78.8%, 81.8%, 77.5%, 62.8%, 90.2% for the training dataset and 0.853(95% confidence interval as 0.713?0.994), P<0.05), 88.9%, 89.4%, 88.5%, 85.0%, 92.0% for the test dataset, respectively. (3) Establishment and validation of radiomics model: 4 categories of a total 1 067 radiomics features were extracted from 154 patients with pancreatic cystic neoplasms, including 7 first-order histogram features, 53 texture features, 848 wavelet features and 159 local binary pattern features. A total of 896 stable radiomics features were retained to construct the model, based on the condition of intraclass correlation coefficient >0.9. After selected by variance threshold and correlation coefficient threshold, 350 radiomics features were retained. Fifty synthetic radiomics features were constructed based on the original features in order to obtain potential radiomics features, and the total number of radiomics features was 400. After analyzed by the five-fold recursive feature elimination, 22 radiomics features were screened out, including 13 wavelet features, 7 synthetic radiomics features and 2 local binary pattern features. The support vector machine algorithm was used to construct the radiomics model. The penalty coefficient 'C' and parameter 'γ' of the radiomics model were 35.938 and 0.077, respectively. The kernel function of the radiomics model was 'radial basis function kernel'. The ROC curve of radiomics model using 5-fold cross validation was drawn. The average AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the radiomics model were 0.870 ( P<0.05), 83.1%, 81.8%, 83.8%, 73.8% and 89.2%, respectively. (4) Establishment and validation of fused model: the fused model was constructed after selecting the tumor location and lobulated tumor of radiology characteristics and radiomics score. Result of the multinomial logistic linear regression analysis was expressed by formula ③: fused model socre=?0.154+0.218×tumor location?0.223×lobulated tumor+0.621×radiomics score. The ROC curve for the test dataset of fused model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of fused model were 0.893(95% confidence interval as 0.828?0.958, P<0.05), 83.7%, 81.8%, 84.5%, 71.1%, 90.9% for the training dataset and 0.966(95% confidence interval as 0.921?0.999, P<0.05), 91.1%, 84.2%, 96.2%, 94.1%, 89.3% for the test dataset, respectively. (5) Nomogram of fused model: the nomogram of fused model was illustrated with the Youden index of 0.416. Conclusion:The prediction model based on the radiomics signature and radiological features extracted from preoperative CT examination can make the differential diagnosis of pancreatic SCA from MCA.
3.The effect of radial artery hemostat continuous compression time in patients undergoing transradial percutaneous coronary intervention
Jingwen HU ; Meili LIU ; Xiaojun BAI ; Huiqin RUAN
Chinese Journal of Practical Nursing 2018;34(27):2116-2119
Objective To investigate the effect of radial artery hemostat (TR Band) continuous compression time on bleeding of puncture point, thumb perception, palm swelling and subjective comfort in patients undergoing transradial percutaneous coronary intervention. Methods One hundred and fifty-five patients who underwent transradial percutaneous coronary intervention were randomly divided into two observation groups and a control group. All patients in the three groups were treated by TR Band patent hemostasis. All three groups received the consistent deflation schedule, except the TR Band was removed at the 12th hour post operation in the control group, and at the 6th hour in the 1st observation group and at the 4th hour in the 2nd observation group. Postoperative bleeding of puncture point, thumb perception, palm swelling and subjective comfort were observed in the three groups. Results The differences of postoperative bleeding of puncture point, thumb perception, palm swelling and subjective comfort among the three groups were statistically significant (χ2=6.31, P<0.05; F=5.26, 4.00, 14.69, P<0.01). In the 2nd observation group, palm swelling was the lowest, but perception, and comfort and bleeding rate is the highest among the three groups. In the 1st observation group, the overall indexes were medium among the three groups. Conclusions The optimal compression duration of TR Band post transradial percutaneous coronary intervention is 6 h, which does not increase the risk of bleeding, but also significantly improve local swelling and perceptual experience, and increase patient comfort.
4.Analysis on the atypical clinical accidents of acupuncture based on the individual factors in patients.
Guanheng HE ; Jingwen RUAN ; Xiaozhou LV ; Xinsheng LAI
Chinese Acupuncture & Moxibustion 2018;38(11):1245-1248
The hidden risk of acupuncture has become the factor of the high incidence of adverse reaction of acupuncture in clinical practice. The retrospective analysis and the typical cases analysis are especially important for the prevention from the hidden risk of acupuncture. In the paper, the relevant literatures were reviewed, the basic diseases were listed such as diabetes, hypertension and digestive gastric ulcer that were neglected by the physicians, and the adverse reactions induced by the therapeutic history and the body constitutions were analyzed. It was stated in the paper that because of the individual factors of patient, the risks of the atypical clinical accidents of acupuncture were extremely serious and easily neglected by the clinical acupuncture physicians. It is very necessary to remind the clinical acupuncture physicians to understand the basic diseases, basic treatment as well as the peculiarity of body constitution of the patients besides their chief complaints. Moreover, acupuncture should be applied very carefully after identifying the pulse condition and the contraindication so as to ensure the patient's safety and obtain the optimal efficacy.
Accidents
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Acupuncture Therapy
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Contraindications
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Humans
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Retrospective Studies
5.Design and clinical application of compression and fixation device for wound after permanent pacemaker implantation
Meili LIU ; Huiqin RUAN ; Jingwen HU
Chinese Journal of Practical Nursing 2017;33(26):2021-2023
Objective To evaluate effects of design of compression and fixation device for wound after permanent pacemaker implantation on compression hemostasis, working intensity of nursing staff and patients′ comfort. Methods Cotton cloth, Velcro tape and snap-fastener were used to design a compression and fixation device for wound after permanent pacemaker implantation. Sixty patients after permanent pacemaker implantation were randomly divided into compression and fixation device group (observation group), and traditional compression group (control group). In addition, the effects of postoperative complications, allergy to medical tape and working intensity of nursing staff for caring wound were evaluated. Results Comparing to the control group, there were significantly lower incidence rate of skin allergy (P<0.05) and shorter working hours needed for nursing staff to care wound (P<0.05).The complications of two groups have no significant differences (P>0.05). Conclusions This design of compression for wound after permanent pacemaker implantation is able to decrease working intensity of nursing staff, improve patients′comfort and show no effects on increasing postoperative complications.
6.Application of Case Teaching in Clinical Nursing Teaching and Medical Ethics Education in Cardiology Department
Jingwen HU ; Huiqin RUAN ; Yan GUO ; Meili LIU
Chinese Medical Ethics 2016;29(4):603-605
Objective:To explore the effect of case teaching in clinical nursing teaching and medical ethics ed-ucation in the department of cardiology. Methods: A sample of 75 nurse interns came to practice in November 2014 to April 2015 were allocated to the control group, while 96 nurse interns came in July 2015 to December 2015 were allocated to the experimental group. The interns in control group were taught according to the traditional teach-ing method, and the case teaching method was used in the experimental group. The scores of critical thinking abili-ty and the times of praise were compared between the two groups. Results:Both critical thinking ability and praise of the interns in the experimental group were better than those in the control group ( P<0 . 01 ) . Conclusion:In-troducing the case teaching method to clinical nursing teaching and moral education can improve nurse interns′clin-ical critical thinking ability and stimulate the enthusiasm for learning. Meanwhile, it is beneficial to cultivate nurse interns′medical humanistic spirit and improve the medical humanistic quality.
7.120 cases of non gonococcal urethritis mycoplasma and chlamydia infection and drug resistance status
Chinese Journal of Primary Medicine and Pharmacy 2016;23(11):1726-1729
Objective To investigate non gonococcal urethritis mycoplasma and chlamydia infection and drug sensitivity status.Methods From June 2014 to December 2014,120 cases of non gonococcal urethritis patients in our hospital were given chlamydia trachomatis,ureaplasma,mycoplasma detection and mycoplasma culture and drug sensitivity test of mycoplasma.Mycoplasma and chlamydia test results were compared between male and female patients.Positive drug sensitivity test results of ureaplasma urealyticum (Uu) and mycoplasma hominis (Mh) were observed.Results Among the 120 patients with positive detection,the proportion of Uu was the highest,up to 41.67% (50/120);the second was Mh,accounting for 31.67% (38/120).The detection rate of Uu in women (57.14%)was significantly higher than that in males (28.13%),and the difference was statistically significant (x2 =10.35,P < 0.05).The susceptibility of mycoplasma to pristinamycin susceptible rate highest,Uu and type mycoplasma reached 100.00%;followed by doxycycline,the susceptibility of Uu reached 98.00% and the susceptibility of Mh to 100.00%;sensitive rates of Uu and Mh to josamycin were 96.00% and 90.48%.The sensitive rates of Uu and Mh to tetracycline were 92.00% and 90.48% respectively.Conclusion The mycoplasma infection was mainly caused by Uu.Clinical treatment of mycoplasma infection can be based on the drug sensitivity test results to reasonably choose antibiotics,and sensitive rates of pristinamycin,doxycycline were higher.
8.Short-term and long-term efficacy analysis of acupoint catgut embedding at cervical Jiaji (EX-B 2) points combined with electroacupuncture at acupoints near ears for nervous tinnitus.
Xin ZHOU ; Jingwen RUAN ; Ziping LI ; Bingfeng XING
Chinese Acupuncture & Moxibustion 2015;35(1):32-35
OBJECTIVETo observe the efficacy differences between acupoint catgut embedding at cervical Jiaji (EX-B 2) points combined with electroacupuncture (EA) at acupoints near ear and simple EA for the treatment of nervous tinnitus.
METHODSSixty-three patients were randomly divided into an observation group (31 cases) and a control group (32 cases). The observation group was treated with acupoint catgut embedding at C4-C7 Jiaji (EXB 2) points on the affected side combined with EA at acupoints near ears, including Ermen (TE 21). Tinggong (SI 19), Tinghui (GB 2), etc.; the control group was treated with EA at regular acupoints near ears alone. The EA treatment was given five times per week, and the acupoint catgut embedding was given once every two weeks. All the treatment was given for 6 weeks. The Tinnitus severity score (TSS)was applied to assess the severity of tinnitus before the treatment, 2 weeks, 4 weeks and 6 weeks into treatment and one month after treat ment. Also the efficacy of two groups was compared.
RESULTSAfter the treatment, the severity of tinnitus was both improved in two groups at each time point (all P<0.05). which was more significant in the observation group (P<0.05, P<0.01). The cured and markedly effective rate was 77.4% (24/31) in the observation group, which was superior to 50.0% (16/32) in the control group (P<0.05).
CONCLUSIONThe short-term and long-term efficacy of acupoint catgut embedding at cervical Jiaji (EX-B 2) points combined with electroacupuncture are both superior to those of simple electroacupuncture for treatment of nervous tinnitus.
Acupuncture Points ; Acupuncture, Ear ; Adult ; Catgut ; Electroacupuncture ; Female ; Humans ; Male ; Middle Aged ; Tinnitus ; therapy
9.Comparison of general anesthesia of laryngeal mask and mask ventilation during bronchoscopy in elder patients
Bing LUO ; Xiangcai RUAN ; Lixin XU ; Shuquan WEI ; Yanlu YING ; Jingwen GUO
The Journal of Practical Medicine 2014;(16):2595-2598
Objective To evaluate the different effects of laryngeal mask and mask ventilation during bronchoscopy in elder patients. Methods 120 old patients (ASA I-III) were divided into three group according to the table of random number as following:surface anesthesia with autonomous respiration (group I);endoscope mask ventilation (group II);laryngeal mask airway ventilation (group III). Oxygen inhalation through nasal tube in groupⅠ,group II and group III was ventilated with endoscope mask and LMA respectively ,thenwe observed whether there were adverse effects or not during the procedure. Results The adverse reactions of group I were more than other groups. Compared with the group I, variance of MAP,HR, RR, SpO2 in the groupⅡand groupⅢ had less changes, the cases with severe bucking decreased significantly, and satisfaction degree increased markedly, (P <0.01or P<0.05 ) . The incidence rate of resp iratory depression and airway obstruction in groupⅡwas higher than that in groupⅢ (P<0.05). Conclusion Endoscope mask ventilation and LMA can both be adopted in analgesia bronchoscopy for old patient. LMA under general anesthesia to transbronchial lung biopsy would control respiration according to the demand at any time.LMA has more advantage in the operation for the stable respiration and hemodynamics and less complications.
10.Therapeutic Effect of Loosening Manipulation on Neck Tenderness Points for Cervicogenic Tinnitus
Shengqiang ZHANG ; Xin ZHOU ; Jingwen RUAN
Journal of Guangzhou University of Traditional Chinese Medicine 2014;(5):749-751
Objective To investigate the therapeutic effect of loosening manipulation on neck tenderness points for cervicogenic tinnitus . Methods Forty cervicogenic tinnitus patients were treated with loosening manipulation on neck tenderness points. Tinnitus grading was carried out before and after treatment by following Tinnitus Severity Grading Criteria for the evaluation of therapeutic effect. Results ( 1) Tinnitus was relieved after treatment for one week and 2 weeks, and at the end of treatment course (P<0.05 compared with that before treatment). (2) After treatment for 3 continuous weeks, the cure rate was 25.0% ( 10/40) , the markedly effective rate was 37.5% ( 15/40) , the effective rate was 27.5% ( 11/40) , the ineffective rate was 10.0% ( 4/40) , and the total effective rate was 90.0%. Conclusion Loosening manipulation on neck tenderness points is effective on relieving cervicogenic tinnitus.

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