1.Danggui Shaoyaosan Regulates Nrf2/SLC7A11/GPX4 Signaling Pathway to Inhibit Ferroptosis in Rat Model of Non-alcoholic Fatty Liver Disease
Xinqiao CHU ; Yaning BIAO ; Ying GU ; Meng LI ; Tiantong JIANG ; Yuan DING ; Xiaping TAO ; Shaoli WANG ; Ziheng WEI ; Zhen LIU ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):35-42
ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease (NAFLD) and explore the underlying mechanism based on the nuclear factor E2-related factor 2 (Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows: control, model, Yishanfu (0.144 g·kg-1), and low-, medium-, and high-dose (2.44, 4.88, and 9.76 g·kg-1, respectively) Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling, rats were treated with corresponding agents for 4 weeks. Then, the body weight and liver weight were measured, and the liver index was calculated. At the same time, serum and liver samples were collected. The levels or activities of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fe2+ in the serum and TC, TG, free fatty acids (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and Fe2+ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species (ROS) content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2, SLC7A11, GPX4, transferrin receptor 1 (TFR1), and divalent metal transporter 1 (DMT1) in the liver were determined by Western blot. ResultsCompared with the control group, the model group showed increases in the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), and decreases in the activities of SOD, GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.05, P<0.01). Meanwhile, the liver tissue in the model group presented steatosis, iron deposition, mitochondrial shrinkage, and blurred or swollen mitochondrial cristae. Compared with the model group, all doses of Danggui Shaoyaosan reduced the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), while increasing the activities of SOD and GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.01). Furthermore, Danggui Shaoyaosan alleviated steatosis, iron deposition, and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.
2.Clinicopathological analysis of gonadal differentiation of sex development disorder
Hua JIN ; Zhenhua LIU ; Yixin DING ; Lin LI ; Hai HU ; Aijun LIU
Chinese Journal of Pathology 2024;53(2):162-167
Objective:To investigate pathological features and differential diagnosis in the gonads with disorder of sex development.Methods:Thirty-six cases of clinically diagnosed hermaphroditism with gonadal biopsy in the Department of Pathology, the Seventh Medical Center of People′s Liberation Army General Hospital from April 2007 to July 2021, were collected. All biopsy pathological sections were reviewed, and the gonadal cases with abnormal pathological morphology were screened out. The clinical and imaging data and karyotype of these cases were reviewed. Additional immunohistochemical staining was performed and relevant literature was reviewed.Results:Seven cases of ovotesticular disorder of sex development (OTDSD) were identified, which were characterized by the presence of testicular and ovarian differentiation in the same individual. All patients were under 15 years old and presented with abnormal appearance of external genitalia, and the ratio of male to female was 2∶5. Ultrasonography showed testicular structure in all female patients and cryptorchidism in all male patients. The most common karyotype was 46, XX. One case with undifferentiated gonadal tissue (UGT) and one case with streak gonads were screened out. UGT germ cells were neither in seminiferous tubules nor in follicles, but randomly distributed in an ovarial-type interstitial background, sometimes accompanied by immature sex cords. Streak gonads resembled UGT without germ cells. FOXL2 was positive in granulosa cells, but negative in Sertoli cells. SOX9 expression was opposite. OCT4 was weakly positively/negatively expressed in oocytes and positively expressed in the germ nuclei of UGT.Conclusions:Four differentiation patterns need to be identified in the gonadal biopsy: ovarian differentiation, testicular differentiation, undifferentiated gonadal tissue and streak gonad. The positive expression of SOX9 indicates testicular differentiation, while the positive expression of FOXL2 confirms ovarian differentiation, and the expression of both markers in the same tissue indicates ovotestis differentiation. It is very important to identify UGT, because that has a high probability of developing into gonadoblastoma in the future.
3.Status risk factors and prevention and control strategies of familial aggregation of Helicobacter pylori infection
Lihua SONG ; Sijing HAN ; Shuqin REN ; Wen YANG ; Sihong DING ; Yixin ZHONG ; Yao QIN ; Huiyue ZHANG ; Yang ZHANG
Journal of Public Health and Preventive Medicine 2024;35(2):148-151
Objective To investigate the status of familial aggregation of Helicobacter pylori (Hp) infection in Jinniu District, Chengdu, and analyze its risk factors so as to provide a basis for developing prevention and control strategies of family aggregation of Hp infection. Methods A total of 172 subjects in the Second Affiliated Hospital of Chengdu Medical College · 416 Hospital of Nuclear Industry from January 2022 to January 2023 were selected as the research subjects. All subjects underwent 13C-urea breath test (13C-UBT) to diagnose whether there was Hp infection. Analyze the current situation of family aggregation of Hp infection in the region, collect general data of survey subjects, analyze the relevant factors affecting Hp family aggregation infection, and develop prevention and control strategies based on this. Results A total of 242 people from 97 households were surveyed, and the Hp family aggregation rate was 29.33%. Univariate analysis showed that there were statistically significant differences in family aggregation of Hp infection in terms of different age groups (χ2=9.719, P=0.008), marital status (χ2=8.496, P=0.014), occupations (χ2=19.462, P<0.001), frequencies of dining out (χ2=5.457, P=0.019), previous Hp test results (χ2 =4.131, P=0.042) and test results after treatment (χ2=12.000, P=0.001), with statistical significance (P<0.05). Multivariate logistic regression analysis showed that the frequency of dining out 2 days or more per week and a positive Hp test results in the past were risk factors for family aggregation of Hp infection, while the occupation of teachers/medical staff/management/technology personnel and a negative Hp results after treatment were protective factors (P<0.05). Conclusion Family aggregation of Hp infection is related to family members' occupation, frequency of dining out, previous Hp test results and Hp test results after eradication, which deserves attention in clinical practice.
4.Construction of an immune-related LncRNA prognostic risk model for gastric cancer based on bioinformatics
Huaji JIANG ; Wei DING ; Yulin TAN ; Lin ZHUANG ; Cheng XI ; Yixin XU ; Yibo WANG ; Xuezhong XU
Chinese Journal of Immunology 2024;40(6):1203-1209
Objective:Based on bioinformatics,new immune-related LncRNAs related to the prognosis of gastric cancer were screened,and a prognostic risk model of immune-related LncRNA was further constructed,in order to be used as a new indicator for early diagnosis and prognostic status of gastric cancer.Methods:The gastric cancer transcriptome data and corresponding clinical prog-nosis data were downloaded from multiple data platforms,and the immune-related LncRNAs of gastric cancer were screened by bioin-formatics methods.Cox regression analysis was used to screen LncRNAs related to immune prognosis in gastric cancer,and LncRNAs related to immune prognosis with independent prognostic significance were identified to construct a prognostic risk model,and the risk score of each patient was calculated.Patients were divided into low-risk and high-risk groups according to the cutpoint.Kaplan-Meier analysis was performed for survival analysis and survival curves were drawn,nomograms were drawn and internal validation was per-formed,and univariate and multivariate Cox regression analysis was performed to analyze the relationship between risk scores and clin-icopathological characteristics and survival prognosis of gastric cancer patients.Results:Three immune prognosis-related LncRNAs(UCA1,MIR4435-1HG,RP11-617F23.1)were identified by Cox regression analysis,and a predictive scoring model was constructed to divide the patients into high-risk group and low-risk group according to the prognosis score.There was a statistically significant dif-ference in the prognosis of patients between the two groups(P<0.05).The multivariate Cox regression analysis risk score was an inde-pendent risk factor for the prognosis of gastric cancer,and the internal verification of the nomogram showed good reliability.Conclu-sion:Three immune-related LncRNAs in gastric cancer are significantly correlated with the prognosis of gastric cancer patients,and the predictive scoring model constructed based on them can effectively predict the prognosis and can be used as their independent prog-nostic biomarkers.
5.The application of transcervical non-inflatable endoscopic posterior inferior sternocleidomastoid approach in thyroid surgery.
Yixin JING ; Yiming DING ; Jing ZHOU ; Jun WU ; Hongfei LIU ; Junwei HUANG ; Xiao CHEN ; Zhigang HUANG ; Xiaohong CHEN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(9):691-694
Objective:To investigate the clinical efficacy and safety of transcervical non-inflatable endoscopic thyroidectomy through the posterior inferior sternocleidomastoid approach. Methods:From December 2022 to May 2023, the clinical data of 35 patients with papillary thyroid carcinoma treated by transcervical non-inflatable endoscopic surgery via posterior inferior sternocleidomastoid approach were retrospectively analyzed. There were 14 males and 21 females, with an average age of 44.7 years. The operation time, bleeding volume, postoperative recovery, complications and follow-up were recorded. Results:All 35 patients successfully completed the surgery, with an average operation time of 4 hours and 7 minutes, an average bleeding volume of 14 ml, and an average postoperative hospital stay of 3.5 days. There were no serious complications and no obvious neck discomfort during postoperative follow-up. Conclusion:Transcervical non-inflatable endoscopic thyroidectomy via posterior inferior sternocleidomastoid approach is safe and effective, with fast postoperative recovery,high appearance satisfaction and good neck comfort.
Female
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Male
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Humans
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Adult
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Retrospective Studies
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Neck
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Neck Muscles/surgery*
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Thyroid Neoplasms/surgery*
6.A novel cuproptosis-related gene signature for prediction of prognosis, drug sensitivity and immunotherapy response in patients with hepatocellular carcinoma
Ruili DING ; Chuanbing ZHAO ; Yixin JING ; Rong CHEN ; Qingtao MENG
Chinese Journal of Hepatobiliary Surgery 2023;29(6):449-454
Objective:To construct a novel cuproptosis-related gene signature (CRGS) for prediction of prognosis, immunotherapy response and drug sensitivity in patients with hepatocellular carcinoma (HCC).Methods:Data materials for this study were obtained from the international cancer genome consortium (ICGC), the cancer genome atlas (TCGA) database and Migort210 database, and protein expression profiles were obtained from the human protein atlas image classification database. Based on the TCGA cohort, the least absolute shrinkage and selection operator algorithm was applied to construct the CRGS and calculate the risk score for each HCC patient. HCC patients were grouped according to the median risk score: HCC patients in the TCGA cohort were divided into a high-risk group TCGA and a low-risk group TCGA with 184 cases in each group; HCC patients in the ICGC cohort were divided into a high-risk group ICGC and a low-risk group ICGC with 116 cases in each group. Patients in the Migort210 cohort were divided into a responder group ( n=68) and a non-responder group ( n=230) based on their response to immunotherapy. We assessed the value of CRGS in predicting the prognosis of HCC patients in the TCGA cohort and validated whether CRGS could be used to predict the prognosis of HCC patients in the ICGC dataset. To explore the role of CRGS in predicting immunotherapy response and drug sensitivity in HCC patients based on data from the TCGA cohort, and to apply the Migort210 immunotherapy cohort to validate the clinical value of CRGS in predicting immunotherapy in malignant tumors. Results:CRGS consists of four copper death-related genes: GLS, CDKN2A, LIPT1, and DLAT. Patients in the high-risk group TCGA had lower overall survival (OS), disease-specifical survival, and progression-free interval than those in the low-risk group TCGA (all P<0.01). OS of patients in the high-risk group ICGC was lower than that in the low-risk group ICGC ( P=0.022). Multivariate Cox regression analysis showed that CRGS was an independent risk factor for poor prognosis in HCC patients (TCGA: HR=2.991, 95% CI: 1.781-5.049, P<0.001; ICGC: HR=4.621, 95% CI: 1.685-12.674, P=0.033). Risk scores were positively correlated with the expression levels of CTLA4, PDCD1, CD80 and HLLA2 (all P<0.001). Patients in the high-risk group TCGA had lower tumor immune dysfunction and rejection scores than those in the low-risk group TCGA [-0.04(-0.07, -0.02) vs. -0.02(-0.04, 0) points], and the difference was statistically significant ( P<0.001). Patients in the responder group had a higher risk score than the non-responder group [1.70 (1.56, 1.90) vs. 1.63 (1.52, 1.80)], with a statistically significant difference ( P<0.05). The half-inhibitory concentrations (IC 50) for sunitinib, rapamycin and etanercept were higher in the high-risk group TCGA than that in the low-risk group TCGA, while the IC 50 for erlotinib was lower than that in the low-risk group TCGA, and the differences were all statistically significant (all P<0.001). Conclusion:The CRGS might be served as a potential biomarker to predict the prognoses, immunotherapy response, and drug sensitivity of patients with HCC.
7.Ethics considerations on brain-computer interface technology.
Zhe ZHANG ; Xu ZHAO ; Yixin MA ; Peng DING ; Wenya NAN ; Anmin GONG ; Yunfa FU
Journal of Biomedical Engineering 2023;40(2):358-364
The development and potential application of brain-computer interface (BCI) technology is closely related to the human brain, so that the ethical regulation of BCI has become an important issue attracting the consideration of society. Existing literatures have discussed the ethical norms of BCI technology from the perspectives of non-BCI developers and scientific ethics, while few discussions have been launched from the perspective of BCI developers. Therefore, there is a great need to study and discuss the ethical norms of BCI technology from the perspective of BCI developers. In this paper, we present the user-centered and non-harmful BCI technology ethics, and then discuss and look forward on them. This paper argues that human beings can cope with the ethical issues arising from BCI technology, and as BCI technology develops, its ethical norms will be improved continuously. It is expected that this paper can provide thoughts and references for the formulation of ethical norms related to BCI technology.
Humans
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Brain-Computer Interfaces
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Technology
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Brain
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User-Computer Interface
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Electroencephalography
8.Establishment and validation of risk prediction model for bone metastasis of NSCLC
Chunxiao Hu ; Yafeng Liu ; Yixin Su ; Jianqiang Guo ; Wenting Zhang ; Xueqin Wang ; Jun Xie ; Wanfa Hu ; Jing Wu ; Yingru Xing ; Dong Hu ; Xuansheng Ding
Acta Universitatis Medicinalis Anhui 2022;57(5):832-836
Objective:
To construct nomogram to predict the risk of bone metastasis in patients with non-small cell lung cancer(NSCLC).
Methods:
The clinical data of NSCLC patients diagnosed in the hospital were retrospectively analyzed, including the occurrence of bone metastasis, age, gender, pathological type, smoking status, PS score, TN stage, metastasis of other sites before bone metastasis, carcinoembryonic antigen(CEA) level, alpha fetoprotein(AFP) level, serum calcium(Ca2+), serum phosphorus(P), alkaline phosphatase(ALP) level, which were determined by univariate and multivariate logistic regression analysis. Receiver operating characteristic curve(ROC) and decision curve analysis were used, DCA was used to verify the accuracy and clinical benefit of the model, and nomogram was used to visualize the model.
Results:
Area under the ROC curve(AUC) showed that in the modeling group(n=138) and the validation group(n=92), the AUC value predicted by combined indicators(age, gender, pathological type, CEA, ALP)(modeling group=0.792, validation group=0.629) was higher than that predicted by single indicator.
Conclusion
The prediction model constructed in this study has good effect and can provide reference for clinical screening of high-risk patients with bone metastasis of NSCLC.
9.The value of deb-tace as down-stage therapy for hepatocellular carcinoma before liver transplantation
Hao WANG ; Guang CHEN ; Haijun GAO ; Zhengjia YI ; Lianfang WEN ; Penghui WANG ; Yixin YANG ; Li ZHANG ; Qingchan DING
Chinese Journal of General Surgery 2019;34(5):410-412
Objective To evaluate the drug-eluting-beads (DEB)-TACE as down-stage therapy for hepatocellular carcinoma before liver transplantation.Methods Inclusion criteria:the hepatocellular carcinoma exceeding the standard of Milan criteria.From Jan 2016 to Jan 2018,30 patients received DEB-TACE as down-stage therapy for hepatocellular carcinoma before liver transplantation.4 weeks after DEB-TACE,the imaging examination was performed.The patients who received the liver transplantation,the pathological conditions were recorded and the tumor free survival of the patients was followed up.Results 30 patients received 30 times DEB-TACE successfully.76.7% (23/30) patients was down-staged to meet UCSF criteria,53.3% (16/30) patients was down-staged to meet Milan criteria.13 patients had being given liver transplantation,pathology showed that DEB-TACE achieved complete necrosis in 30.8 % (4/13)cases.No significant treatment related complications were observed.After liver transplantation 12 patients are alive with no tumor recurrence.The tumor recurrence rate after liver transplantation was 7.7%.Conclusion DEB-TACE is safe and effective as down-stage therapy for hepatocellular carcinoma before liver transplantation.
10.Efficacy analysis of drug-eluting beads chemoembolization in the treatment of liver cancer patients who are waiting for fiver transplantation
Hao WANG ; Guang CHEN ; Haijun GAO ; Lianfang WEN ; Penghui WANG ; Yixin YANG ; Li ZHANG ; Qingchan DING
Chinese Journal of Hepatobiliary Surgery 2019;25(4):246-248
Objective To evaluate the value of DEB-TACE before liver transplantation for hepatocellular carcinoma patients.Methods From Jan.2016 to Jan.2018,23 patients received DEB-TACE before liver transplantation for hepatocellular carcinoma were induced.Complications evaluation was followed up after interventional therapy.4 weeks after the intervention,the imaging examination was performed to examine the tumor response rate depond on mRECIST,the pathological conditions and tumor free survival were studied in the patients who received liver transplantation.Results The achievement ration of operation was 100% in 23 patients.23 patients received 24 times successfully,1 patient received DEB-TACE twice,and the remaining 22 patients received DEB-TACE once.No serious complications occurred.Eighteen patients (78.3%,18/23) had postembolic syndrome after interventional therapy,mainly fever and pain.Four weeks after DEB-TACE,the complete response rate was 47.8% (11/23),partial response rate was 30.4% (7/23),disease stability rate was 21.7% (5/23).All the 23 patients were included in the waiting list for transplantation.Among them,15 cases received liver transplantation.Pathological results showed that the total necrosis rate was 53.3% (8/15),and the tumour necrosis rate in 4 of them was less than 50%.The average tumour necrosis rate of the neoplasm was 75.0%.The 15 patients who received liver transplantation were alive with no tumor recurrence.Conclusion DEB-TACE is a safe and effective treatment for patients suffered from hepatocellular carcinoma in waiting for liver transplantation.However,due to the short time of DEBs in China,further research is needed.


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