1.PCBP1-mediated regulation of iron homeostasis suppresses ferroptosis against cadmium-induced neurotoxicity in mouse neuroblastoma cells
Sheng JIE ; Rui TIAN ; Yuchen QU ; Li TIAN ; Jia XIE ; Mengyan CHEN ; Mindi HE ; Zhengping YU ; Huifeng PI ; Ping DENG
Journal of Army Medical University 2025;47(19):2315-2326
Objective To investigate the role of poly(rC)-binding protein 1(PCBP1)in cadmium(Cd)-induced ferroptosis in mouse neuroblastoma Neuro-2a(N2A)cells.Methods N2A cells were exposed to a concentration gradient of CdCl?(0,1,2,4 μmol/L)for 72 h.Cell viability was assessed by trypan blue staining.Western blotting was employed to detect the expression of ferroptosis-related proteins(GPX4,HMOX1,ACSL4)and PCBP1.Intracellular Fe2? level and lipid peroxidation were detected using FerroOrange and BODIPY581/591 C11 probes,respectively.Ferrostatin-1(Fer-1),a ferroptosis inhibitor,was applied to confirm the critical role of ferroptosis in Cd-induced cytotoxicity.Molecular docking was performed to elucidate the interaction between PCBP1 and ferritin,as well as the binding sites of Cd2?.PCBP1 overexpression plasmid was further constructed for functional validation.Results Cd exposure suppressed cell viability in N2A cells in a dose-dependent manner(P<0.01),significantly down-regulated GPX4 expression(P<0.05),up-regulated HMOX1 expression(P<0.01),and induced Fe2? overload and lipid peroxidation(P<0.01).Molecular docking revealed that Cd2? directly bound to the KH2 domain of PCBP1 and then co-localized on the outer surface of ferritin heavy chain.Overexpression of PCBP1 markedly reversed Cd-induced Fe2? accumulation,GPX4 down-regulation,lipid peroxidation,and cell death.Conclusion Cd exposure disrupts PCBP1-mediated iron homeostasis via transcriptional suppression and competitive displacement of metal ions,and then synergistically drives Fe2? overload-triggered ferroptosis cascades,ultimately leading to neurotoxicity.Targeting PCBP1-mediated iron homeostasis can effectively mitigate Cd-induced neurotoxicity,and may serve as a novel therapeutic strategy.
2.Application value of dual-layer spectral CT 45 keV single energy image in follow up after TACE for hepatocellular carcinoma
Yan JIANG ; Jie TANG ; Zhihao FU ; Yuting TIAN ; Daixin LI ; Zhengping XIE
Journal of Practical Radiology 2024;40(3):483-486
Objective To investigate the application value of dual-layer spectral computed tomography(DLCT)45 keV single energy image in follow up after transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC).Methods The DLCT images of 60 patients with HCC after TACE treatment were analyzed retrospectively.The CT value and standard deviation(SD)value of the lesion region of interest(ROI)and surrounding normal liver parenchyma on two kinds of images with 45 keV energy spectrum CT and 120 kVp conventional CT were measured respectively,then the contrast-to-noise ratio(CNR)between the lesions and surrounding normal liver parenchyma was calculated,and their differences were compared.The image quality of the two kinds of images was scored subjectively with the 3-point method,and the patients were divided into different groups according to the enhance-ment degree and tumor staining.The receiver operating characteristic(ROC)curve was also drawn.Results(1)There was no signif-icant difference in CNR between arterial phase,portal phase,and delayed phase of 120 kVp conventional CT(Hc=1.128,P>0.05).The CNR of 45 keV energy spectrum CT was higher than that of 120 kVp conventional CT,with a statistically significant difference(Z=5.060,P<0.05).(2)The subjective score of 45 keV energy spectrum CT was higher than that of 120 kVp conventional CT,and the difference was statistically significant(Z=5.335,P<0.05).ROC curve analysis showed that 45 keV energy spectrum CT had a larger area under the curve(AUC)than 120 kVp conventional CT,and the difference was statistically significant(Z=4.136,P<0.001).Conclusion 45 keV energy spectrum CT image can significantly improve the CNR between tumor and normal liver parenchyma,and it has the better image quality and higher diagnostic efficiency.
3.Surgical prognosis and influencing factors in 406 patients with primary aldosteronism
Yixin ZHANG ; Ying SONG ; Jinbo HU ; Shumin YANG ; Zhengping FENG ; Wenwen HE ; Qifu LI ; Wenrui ZHAO
Chinese Journal of Endocrinology and Metabolism 2024;40(3):228-234
Objective:To evaluate postoperative biochemical and clinical remission rates in patients with unilateral primary aldosteronism and analyze related influencing factors.Methods:A total of 406 patients of primary aldosteronism with confirmed subtyping, who underwent adrenalectomy and completed follow-up in the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to March 2022 were retrospectively enrolled. Clinical and biochemical data were recorded. Postoperative clinical and biochemical outcomes were assessed according to Primary Aldosteronism Surgery Outcome(PASO) consensus.Results:Complete biochemical success was achieved in 391(96.31%) of 406 primary aldosteronism patients, while partial and absent biochemical success in only 4(0.99%) and 11(2.71%) primary aldosteronism patients; Complete clinical success was seen in 217(53.45%) patients, and partial clinical success in 189(46.55%) patients. Compared to the partial clinical success group, the complete clinical success group was younger, had a greater proportion of women, a smaller body mass index, a shorter duration of hypertension, a smaller daily defined dose value for antihypertensive medication, a higher estimated glomerular filtration rate(eGFR), and a lower proportion of family history of hypertension and diabetes mellitus. Multifactorial logistic regression analysis further showed that gender( OR=2.49, 95% CI 1.42-4.35, P=0.001), body mass index( OR=1.16, 95% CI 1.05-1.28, P=0.003), antihypertensive drug daily defined dose( OR=1.83, 95% CI 1.37-2.44, P<0.001), family history of hypertension( OR=2.16, 95% CI 1.22-3.83, P=0.008), history of diabetes( OR=2.47, 95% CI 1.15-5.29, P=0.021), and eGFR( OR=0.98, 95% CI 0.97-0.99, P=0.001) were independent factors influencing clinical prognosis of primary aldosteronism. Conclusion:The postoperative complete biochemical success is higher in patients with unilateral primary aldosteronism, but only about half of all patients achieve complete clinical success.
4.Study of appropriate cut-off for diagnosis of primary aldosteronism by seated saline suppression test based on liquid chromatography with tandem mass spectrometry
Yixin ZHANG ; Ying SONG ; Jinbo HU ; Shumin YANG ; Zhengping FENG ; Wenwen HE ; Qifu LI ; Yifan HE
Chinese Journal of Internal Medicine 2024;63(1):66-73
Objective:To investigate the appropriate cut-off for diagnosis of primary aldosteronism (PA) by seated saline suppression test (SSST) based on liquid chromatography with tandem mass spectrometry (LC-MS/MS).Methods:In this cross-sectional study, patients who underwent SSST for suspected PA in the First Affiliated Hospital of Chongqing Medical University from January 2018 to March 2022 were evaluated. Briefly, 300 patients with PA and 119 with essential hypertension (EH) were included. Plasma aldosterone concentration (PAC) after SSST was determined by LC-MS/MS. Primary aldosteronism confirmatory testing (PACT) score was used as the reference standard for diagnosis of PA, and receiver operating characteristic (ROC) curve was used to explore the cut-off value.Results:The average age of the PA group was (50.8±10.5) years, and males accounted for 53.00% ( n=159); the average age of the EH group was (49.4±11.2) years, and males accounted for 26.89% ( n=32). The area under the ROC curve of PAC post-SSST was 0.819 (95% CI 0.775-0.862). When 40 pg/ml (110.8 pmol/L) was selected as the appropriate cut-off for diagnosis of PA, the sensitivity was 83.67% (95% CI 78.88%-87.56%) and specificity was 60.50% (95% CI 51.10%-69.21%). Thus, 95.09% (155/163) of patients with unilateral PA could be identified. Conclusion:PAC after SSST determined by LC-MS/MS has high efficacy for diagnosis of PA, and 40 pg/ml is recommended as the appropriate cut-off value.
5.Jinshu Liujun Decoction Ameliorates Airway Lesions in COPD Mice by Correcting Oxidative Stress Mediated CFTR Acquired Defects
Zhen ZHANG ; Yiran YANG ; Hui WANG ; Jianqing LI ; Aiping LI ; Zhengping BAI ; Yu LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(7):1793-1801
Objective To observe the effect of Jinshui Liujun decoction on airway lesions in mice with COPD and explore its possible mechanism.Methods 48 C57BL/6 mice were randomly divided into blank group,model group,Jinshui Liujun decoction group and NAC group,with 12 in each group.The COPD mouse model was established by intranasal drip of LPS and smoking,and the corresponding drugs were given intragastric administration for 14 days after the model was established.Observe the general condition of the mice,measure the MV,PEF and PIF of the mice with the small animal lung function instrument,semi quantitatively evaluate the inflammation of the lung tissue,the thickness of the alveolar septum and the thickness of the airway wall with HE staining,and observe the airway mucus secretion and goblet cell proliferation with PAS staining.The content of MPO,SA and Urea in BALF was detected by the kit,and the ratio of SA and Urea was calculated.The content of MUC5AC in BALF was detected by ELISA.The levels of ROS,GSH,GSSG and GR in lung tissue were detected with the kit,and the ratio of GSH and GSSG was calculated.The expression level of CFTR mRNA in lung tissue was detected by qRT-PCR.Western blot was used to detect the expression level of CFTR protein in lung tissue.Results Compared with the control group,the growth of mice in the model group was poor.The body weight at each time point during the modeling period decreased(P<0.01),and the indexes of MV,PEF and PIF decreased(P<0.01).The lung tissue pathological score,alveolar septal thickness,airway wall thickness,airway mucus and goblet cell increased(P<0.01).The levels of SA,SA/Urea,MUC5AC and MPO in BALF increased(P<0.01),and the level of Urea decreased(P<0.01),The levels of ROS and GSSG in lung tissue increased(P<0.01),and the levels of GSH,GSH/GSSG,and GR decreased(P<0.01).The expression levels of CFTR mRNA and protein in lung tissue decreased(P<0.01).Compared with the model group,the growth condition of COPD mice improved,the body weight increased at each time point during the modeling period(P<0.05,P<0.01),the indexes of MV,PEF and PIF improved significantly(P<0.01),the pathological score of lung tissue,the thickness of alveolar septa,the thickness of airway wall,airway mucus and goblet cell decreased(P<0.01,P<0.05),and the levels of SA,SA/Urea,MUC5AC and MPO in BALF decreased(P<0.01),And an increase in Urea levels(P<0.01),a decrease in ROS and GSSG levels in lung tissue(P<0.01),and an increase in GSH,GSH/GSSG,and GR levels(P<0.01).The expression levels of CFTR mRNA and protein in lung tissue increased(P<0.01).Conclusion Jinshui Liujun decoction can correct CFTR acquired defects through antioxidant effects to improve airway lesions in COPD.
6.Research on the rheological properties of terbinafine hydrochloride cream
Qianqian CHEN ; Zhengping LIU ; Shuolei LI ; Song XUE ; Dawei LI
China Pharmacist 2024;27(8):1296-1302
Objective To study the rheological properties of terbinafine hydrochloride cream,and provide a research basis for the consistency of this product.Methods The Kinexus rheometer was used to determine the dynamic and steady rheological parameters of terbinafine hydrochloride cream.Comparative studies on the rheological curves,yield stress,viscosity measurement,linear viscoelasticity and creep recovery of original and generic terbinafine hydrochloride cream were carried out.Results The original and generic terbinafine hydrochloride cream were both non-Newtonian fluid with shear thinning.The yield stress of three generic were similar to the original.The linear viscoelastic region of three generic were similar to the original,and the ranges of linear viscoelastic were both 0.01%-1%,the elastic moduli were all greater than the viscosity moduli and were viscoelastic materials.It could be seen from the creep recovery curve that the creep behavior of three generic were basically the same with the original.Conclusion Among the six terbinafine hydrochloride creams measured experimentally,the rheological properties of most generic drugs are basically the same as the original.
7.CT radiomics nomogram for predicting Ki-67 expression of thymus epithelial tumors
Zhengping ZHANG ; Xiaojing HOU ; Zijin LIU ; Kede MI ; Zhitao WANG ; Shuping MENG ; Xingcang TIAN ; Li ZHU
Chinese Journal of Medical Imaging Technology 2024;40(11):1693-1697
Objective To observe the value of CT radiomics nomogram for predicting Ki-67 expression of thymus epithelial tumors.Methods Totally 163 patients with thymus epithelial tumor,including 114 patients in training set and 49 patients in validation set were retrospectively enrolled.The patients were further divided into low expression(<50%)and high expression(≥50%)subgroups according to Ki-67 index.Multivariate logistic regression analysis was performed to screen independent predicting factors of Ki-67 expression in thymus epithelial tumors,and clinical-CT model was constructed.The optimal radiomics features were extracted and screened based on chest plain and venous phase enhanced CT images,respectively.Then radiomics modelplain and radiomics modelenhanced were constructed,and Radscoreplain and Radscoreenhanced were calculated,respectively.The nomogram model was constructed based on clinical-CT model,Radscoreplain and Radscoreenhanced.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting Ki-67 expression of thymus epithelial tumors.Results Patient's gender and enhanced CT value of lesion were both independent predicting factors of Ki-67 expression in thymus epithelial tumors(both P<0.05).The AUC of clinical-CT model,radiomics modelplain,radiomics modelenhanced and nomogram model for predicting Ki-67 expression was 0.736,0.814,0.836 and 0.857 in training set,which was 0.746,0.746,0.750 and 0.799 in validation set,respectively.Conclusion CT radiomics nomogram could be used to predict Ki-6 7 expression of thymus epithelial tumors.
8.Research progress on ALSP caused by CSF1R gene mutations
Zhengping HUANG ; Jiawei JIANG ; Shufen LIU ; Xiaofang YE ; Mimi LI ; Jianlong ZHUANG ; Lichao YE ; Chunnuan CHEN
Chinese Journal of Nervous and Mental Diseases 2024;50(3):173-178
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP)is a clinically rare autosomal dominant genetic disease,and its specific pathogenesis is not yet clear.The colony-stimulating factor 1 receptor(CSF1R)is a transmembrane tyrosine kinase receptor on the cell surface and mutations in the gene encoding it have been identified as potential pathogenic factors for ALSP.However,the specific mechanisms by which CSF1R gene mutations lead to the onset of ALSP are still unclear.After reviewing the mutation sites and pathogenic mechanisms of CSF1R in the pathogenesis of ALSP,CSF1R mutations have been shown to cause microglial dysfunction through mechanisms such as dominant-negative effects,loss of function,haploinsufficiency,and gain of function,thereby leading to the onset of ALSP.A deeper understanding of the causes of ALSP will help in exploring potential treatment methods.
9.Effect of Whole-Course Empowerment Health Intervention on Psychological Resilience and Self-care Ability in Older Patients With Severe Pneumonia
Chun FENG ; Ai ZHANG ; Huaicong LONG ; Zhengping TANG ; Kaixiu LI ; Jing GUAN
Journal of Sichuan University (Medical Sciences) 2024;55(6):1587-1592
Objective To investigate the effect of whole-course empowerment health intervention on the psychological resilience and self-care ability of older patients with severe pneumonia.Methods A total of 210 older patients with severe pneumonia admitted to Sichuan Provincial People's Hospital between January 2020 and December 2023 were enrolled.The patients were sequentially numbered according to the order of admission.Then,they were assigned to a conventional care group(105 cases)and a whole-course empowerment group(105 cases)by a 1∶1 ratio using a random number table.The conventional care group received conventional clinical intervention,while the whole-course empowerment group received the whole-course empowerment health intervention regimen in addition to the intervention administered in the conventional care group.Psychological resilience was assessed with the Connor-Davidson Resilience Scale(CD-RISC),self-care ability with Exercise of Self-Care Agency Scale(ESCA),and quality of life with the World Health Organization Quality of Life Brief Version(WHOQOL-BREF).The evaluation results obtained before and after the interventions were compared.Results After intervention,the scores for all dimensions of CD-RISC in the whole-course empowerment group were higher than those in the conventional care group(t=10.326,P<0.001;t=6.386,P<0.001;t=9.581,P<0.001).The scores for all dimensions of ESCA after intervention were higher in whole-course empowerment group than those in the conventional care group(t=1 1.599,P<0.001;t=9.072,P<0.001;t=4.353,P<0.001;t=16.646,P<0.001).After intervention,the scores for all dimensions of WHOQOL-BREF in the whole-course empowerment group were higher than those in the conventional care group(t=9.164,P<0.001;t=13.809,P<0.001;t=5.001,P<0.001;t=6.695,P<0.001).Conclusion Whole-course empowerment health intervention significantly enhances psychological resilience,self-care capacity,and quality of life in older patients with severe pneumonia.
10.Association Between Metabolic Risk Factors and Cognitive Impairment in Schizophrenia Based on Sex
Hongna HUANG ; Lizhao DU ; Zhengping PU ; Yuan SHI ; Zifan XIAO ; Xi CHEN ; Shun YAO ; Lijun WANG ; Zezhi LI ; Ting XUE ; Donghong CUI
Psychiatry Investigation 2023;20(10):930-939
Objective:
Sex differences have been observed in many aspects of schizophrenia, including cognitive deficits. Despite extensive research into the relationship between metabolic factors and cognitive deficits in schizophrenia, few studies have explored the potential sex difference in their association.
Methods:
We recruited 358 schizophrenia patients and 231 healthy controls. The participants underwent measurements of body mass index (BMI), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. Metabolic risk factors included abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. A collection of these metabolic risk factors has been defined as metabolic syndrome. These diagnoses were based on the criteria of the National Cholesterol Education Program’s Adult Treatment Panel III. Cognitive performance was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A descriptive analysis, difference analysis, and linear regression model were used to identify the metabolic risk factors for cognitive function in schizophrenia.
Results:
Our findings revealed sex differences in the rate of abdominal obesity and hypertension in schizophrenic patients. Additionally, we observed sex differences in the association between metabolic risk factors and cognitive impairment in schizophrenia. Specifically, hyperglycemia was associated with the immediate memory index score of RBANS in male patients, while dyslipidemia was associated with language, attention, delayed memory index scores, and RBANS total score in female patients.
Conclusion
Our results suggest that sex should be considered when evaluating the impact of metabolic disorders on the cognitive function of schizophrenic patients. Moreover, our study identifies hyperglycemia and dyslipidemia as potential targets for precise treatment by sex stratification, which could benefit the improvement of cognitive impairment in schizophrenic patients.

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