1.Human umbilical cord mesenchymal stem cell-derived exosomes attenuate renal ischemia-reperfusion injury by up-regulating ATF3 to inhibit the TLR4/NF-κB pathway
Xingyu* WAN ; Yujia LIU ; Ruiyan WANG ; Hao WANG ; Yi ZHAO ; Lu GUO ; Zhihua YANG ; Xinghua LÜ
Organ Transplantation 2026;17(2):275-286
Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.
2.Analysis of the characteristics and influencing factors of mirtazapine steady-state trough concentration and concentration-to-dose ratio
Ze ZHANG ; Mengqiang ZHAO ; Ruiyan YU ; Yiyuan WANG ; Yuanyuan ZHAO ; Jing YU ; Chunhua ZHOU
China Pharmacy 2026;37(6):776-781
OBJECTIVE To analyze the distribution characteristics of mirtazapine steady-state trough concentration and concentration-to-dose ratio ( C / D ), and to investigate the influence of clinical and genetic factors on C / D . METHODS A retrospective study was conducted on hospitalized patients with depression who received mirtazapine treatment and underwent therapeutic drug monitoring at the First Hospital of Hebei Medical University from May 2022 to May 2025. The collected data included patients’ gender, age, body mass index, daily dose, steady-state trough concentration, smoking status, history of liver disease, drug type, concomitant medications, and CYP2D6 metabolic phenotype. The C / D was calculated. Spearman rank correlation was used to analyze the relationship between mirtazapine steady-state trough concentration and daily dose. Univariate analysis and multiple linear regression model were employed to screen the factors potentially influencing the C / D of mirtazapine. RESULTS A total of 226 patients were included. The daily dose of mirtazapine was 25.00 (24.82, 30.00) mg/d, the steady-state trough concentration was 44.46 (20.00, 70.00) ng/mL, and the C / D was 1.83 (1.00, 2.00) (ng·d)/(mL·mg). Steady-state trough concentrations were within the reference range (30-80 ng/mL) in 121 patients (53.54%), below the lower limit in 80 patients (35.40%), and above the upper limit in 25 patients (11.06%). A positive correlation was observed between mirtazapine steady-state trough concentration and daily dose (coefficient of determination was 0.320 8, P <0.001). Gender, smoking status, and CYP2D6 metabolic phenotype were significantly associated with the mirtazapine C / D ( P <0.05). CONCLUSIONS Significant interindividual variability exists in mirtazapine steady-state trough concentrations. Gender, smoking status, and CYP2D6 metabolic phenotype are identified as independent influencing factors for the mirtazapine C / D , with higher C / D ratios observed in females, non-smokers, and intermediate metabolizers.
3.Clinical study on improving diagnostic accuracy of focal prostate cancer based on 18F-PSMA-1007 PET/CT radiomics
Ruxi CHANG ; Liang LUO ; Ruiyan WANG ; Weixuan DONG ; Xiaoyi DUAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(2):339-344
Objective To construct a radiomics model to improve the discriminatory ability of 18 F-PSMA-1007 PET/CT for focal prostate cancer.Methods We retrospectively collected data from 74 patients diagnosed with prostate cancer by biopsy at The First Affiliated Hospital of Xi'an Jiaotong University between July 2020 and April 2024.These patients had focal radionuclide accumulation observed on 18F-PSMA-1007 PET/CT,with the median age of 71 years.Among them,42 patients had a Gleason score<8 and 32 patients had a Gleason score ≥8.An external validation set was randomly selected based on the timing of examination,while the remaining patients were randomly divided into training and test sets at a 7∶3 ratio.Region of interest(ROI)were semi-automatically drawn on registered images,manually adjusted,and symmetrically shifted to contralateral non-tumor tissue.We made variance and correlation analyses to choose features,and built models with Logistic regression and compared the results with those of visual evaluation.Receiver operating characteristics(ROC)curves were drawn to compare model performance,and subgroup analysis was performed to identify optimal features for distinguishing tumor tissue,based on Gleason score,serum total prostate specific antigen(tPSA)levels,and lesion location.Results A total of eight features were selected.The area under the curve(AUC)for visual evaluation,testing set,and external validation set were 0.858,0.933,and 0.891,respectively.The sensitivity was 0.757,0.800 and 0.917;the specificity was 0.960,0.800 and 0.792,respectively.Subgroup analysis showed that the radiomic features 10percentile and skewness had a high value in tumor differentiation.In tumor tissues,the 10percentile values were higher than in non-tumor tissues across all groups(P-values were 0.012,0.002,<0.001,<0.001,<0.001,and<0.001).When tPSA≤10 ng/mL and Gleason score ≥8,there was no statistically significant difference in skewness between tumor and non-tumor tissues(P=0.08).When tPSA ≥20 ng/mL,the skewness of non-tumor tissue was slightly higher than that of tumor tissue,but the difference was not statistically significant(P-values were 0.285 and 0.791).When the tumor was located in the posterior part of the prostate(left posterior and right posterior),the skewness was significantly higher in tumor tissue than in non-tumor tissue(P-values<0.001 for both).Conclusion The radiomics model had better sensitivity and accuracy than visual evaluation in distinguishing focal prostate cancer tumors from non-tumor tissues,but visual evaluation had higher specificity.Skewness and 10percentile had a high value in differential diagnosis.
4.Epidemiological characteristics of newly diagnosed occupational diseases among workers from other provinces in Guangdong Province from 2006 to 2023
Shanyu ZHOU ; Xianzhong WEN ; Yongshun HUANG ; Bing XIA ; Shu WANG ; Lang HUANG ; Ruiyan HUANG ; Xudong LI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(3):212-216
Objective:To investigate the epidemiological characteristics and source distribution of newly diagnosed occupational diseases among workers from other provinces in Guangdong Province from 2006 to 2023, providing a basis for occupational health risk assessment and government decision-making.Methods:In July 2024, through the Occupational Disease Report Card of the Occupational Disease and Health Hazard Monitoring Information System of the China Disease Prevention and Control Information System, the basic information of newly diagnosed occupational disease cases reported online in Guangdong Province from 2006 to 2023 was collected, and the epidemiological characteristics of new occupational diseases among workers from other provinces were described. The locations of employment units and their source provinces of different cases were analyzed. Counting data were described by component ratio (%) and compared by Pearson χ2 test. Results:From 2006 to 2023, 9763 cases of newly diagnosed occupational diseases among workers from other provinces in Guangdong Province were reported, accounting for 78.82% (9763/12387) of the total number of occupational diseases in the province. The cases of occupational diseases were mainly concentrated in the Pearl River Delta region (94.93%, 9268/9763) and the manufacturing industry (86.97%, 8491/9763), and the domestic enterprises accounted for 57.35% (5593/9753). Newly diagnosed occupational disease cases were mainly from province A in Central China (2767 cases, 28.34%), province A in Southwest China (2323 cases, 23.79%) and a province in South China (1070 cases, 10.96%) .Conclusion:The proportion of newly diagnosed occupational diseases among workers from other provinces in Guangdong Province is relatively high, and the cases are concentrated in the regions, industries and source provinces.
5.Efficacy of 18F-fluorodeoxyglucose PET/CT parameters in differentiating benign and malignant pulmonary nodules after propensity score matching
Ruxi CHANG ; Liang LUO ; Ruiyan WANG ; Weishan ZHANG ; Jungang GAO ; Wang YUAN ; Xiaoyi DUAN
Journal of Practical Radiology 2025;41(5):762-766
Objective To include patients with clinical data matched by propensity scores and to explore the value of 18F-fluorode-oxyglucose(18F-FDG)PET/CT metabolic parameters and radiomics in differentiating benign and malignant solitary pulmonary nod-ule(SPN).Methods A total of 54 patients with SPN(27 benign and 27 malignant)were retrospectively selected,all of them under-went 18F-FDG PET/CT scans.Then the metabolic parameters were analyzed,and the metabolic parameters model was established.After delineating the lesion,imaging features were selected through variance and correlation analysis.The logistic regression was used to build the model,and balance accuracy(bACC)was used to compare the performance of the models.The correlation between meta-bolic parameters and radiomics features was analyzed.Results The maximum standardized uptake value(SUVmax),total lesion uptake(TLU),and coefficient of variation(COV)of malignant were higher than those of benign(P<0.05).SUVmax and COV had positive predictive value for malignant lesions[odds ratio(OR)>1,P<0.05].There was no statistical difference between the performance of the metabolic parameters model and the radiomics model(P>0.05).There was a strong correlation between radiomics features and metabolic parameters.Conclusion After propensity score matching,metabolic parameters and radiomics show no statistical difference in differentiating benign from malignant SPN.
6.Diagnostic value of 18F-PSMA-1007 PET/CT in patients with PI-RADS 1-3 prostate cancer lesions on multi-parametric MRI
Liang LUO ; Ruiyan WANG ; Jungang GAO ; Yang LI ; Xiang LIU ; Xiaoyi DUAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(10):595-599
Objective:To evaluate the diagnostic efficacy of 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT in patients with prostate imaging reporting and data system (PI-RADS) 1-3 lesions on multi-parametric MRI (mpMRI) and pathologically confirmed prostate cancer. Methods:Clinical, pathological, and imaging data of 59 patients (age (67.8±7.6) years) with PI-RADS 1-3 lesions on mpMRI in the First Affiliated Hospital of Xi′an Jiaotong University between December 2021 and March 2024 were retrospectively collected. Those patients also underwent 18F-PSMA-1007 PET/CT and prostate biopsy during the same period due to an elevated prostate specific antigen (PSA) level. The diagnostic performances of 18F-PSMA-1007 PET/CT for PI-RADS 1-3 prostate cancer and clinically significant prostate cancer were evaluated by using pathological results as the standard. Mann-Whitney U test was used to compare differences in clinical characteristics and PET parameters between PET-positive and PET-negative groups, and logistic regression analysis was performed to select independent influencing factors for the PET/CT diagnosis of prostate cancer. Results:Of the included 59 patients, 7, 27, and 25 had PI-RADS scores of 1, 2, and 3 respectively. Benign prostate hyperplasia was pathologically confirmed in 8 patients, and prostate cancer was confirmed in 51 patients, of which 37 had clinically significant prostate cancer. The sensitivity of 18F-PSMA-1007 PET/CT in diagnosing prostate cancer was 86.3%(44/51), the specificity was 2/8, the accuracy was 78.0%(46/59), the positive predictive value was 88.0%(44/50), and the negative predictive value was 2/9. For patients with clinically significant prostate cancer, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 91.9%(34/37), 27.3%(6/22), 67.8%(40/59), 68.0%(34/50), and 6/9, respectively. SUV max was significantly higher in the PET-positive group ( n=44) than that in the PET-negative group ( n=7; 12.8(9.1, 23.5) vs 5.1(5.0, 6.2); Z=-4.16, P=0.001). Logistic regression analysis showed that SUV max was an independent influencing factor for the diagnosis of prostate cancer by 18F-PSMA-1007 PET/CT (odds ratio ( OR)=6.01, 95% CI: 1.57-23.00, P=0.009). Conclusions:18F-PSMA-1007 PET/CT has a high sensitivity and positive predictive value in prostate cancer patients with PI-RADS 1-3 on mpMRI. It can be used as a supplementary modality to mpMRI to guide clinical decision for patients with PI-RADS 1-3 and clinically suspected prostate cancer lesions.
7.The predictive value of 18F-PSMA-1007 PET/CT for positive surgical margins after radical prostatectomy
Ruiyan WANG ; Liang LUO ; Ruxi CHANG ; Bo WANG ; Jungang GAO ; Xiaoyi DUAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(3):486-490
Objective The application of 18F-PSMA-1007 PET/CT in the precise diagnosis and treatment of prostate cancer(PCa)is gradually increasing.This study aimed to explore the predictive value of 18F-PSMA-1007 PET/CT for positive surgical margins after radical prostatectomy(RP).Methods A total of 173 PCa patients who were pathologically confirmed and underwent RP in our hospital from July 2020 to August 2023 were retrospectively recruited.All patients underwent 18F-PSMA-1007 PET/CT whole-body imaging before surgery.According to the postoperative pathological results,they were divided into a negative surgical margin group with 83 cases and a positive surgical margin group with 90 cases.The differences in age,SUVmax,SUVmean,preoperative total prostate specific antigen(tPSA),prostate specific antigen density(PSAD),prostate volume,Gleason score,and clinical T staging between the groups were compared,and the risk factors were further analyzed by Logistic regression.Results The preoperative tPSA(Z=-3.252,P=0.001),SUVmax(Z=2.531,P=0.011),and clinical T staging(P=0.018)were all lower in the negative surgical margin group than in the positive surgical margin group.PSAD(OR=3.492,95%CI:1.095-11.133,P=0.035),SUVmax(OR=1.036,95%CI:1.003-1.070,P=0.034),and clinical T staging(OR=3.364,95%CI:1.117-10.133,P=0.045)were independent risk factors for positive surgical margins.Conclusion 18F-PSMA-1007 PET/CT has certain predictive value for positive surgical margins after RP in PCa patients.High PSAD,high SUVmax and high clinical T stage were independent risk factors for predicting positive margin after PR surgery,thus providing some reference for the clinical treatment strategy of PCa patients.
8.The effect and mechanism of Huangkui capsule pretreatment of human umbilical cord mesenchymal stem cell-derived exosomes on improving renal ischemia-reperfusion injury
Yawei YAO ; Jiahui HE ; Hao WANG ; Yutong WANG ; Ruiyan WANG ; Xingyu WAN ; Yujia LIU ; Xinghua LÜ
Organ Transplantation 2025;16(2):237-245
Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cell (HUC-MSC)-derived exosomes (Exo) pretreated with Huangkui capsules on renal ischemia-reperfusion injury (IRI). Methods HUC-MSCs were cultured in media containing different concentrations of Huangkui capsules for 24 hours to determine cell viability and select an appropriate concentration for subsequent experiments. HUC-MSCs were pretreated with 50 μg/mL Huangkui capsules for 24 hours, and Exo were extracted using an exosome extraction kit. The morphology was observed under a transmission electron microscope, particle size was measured by nanoparticle tracking analysis, and the expression of exosomal membrane surface marker proteins was detected by Western blot. Human renal tubular epithelial cells (HK-2 cells) were randomly divided into hypoxia/reoxygenation group (M group), hypoxia/reoxygenation + Exo group (E group), and hypoxia/reoxygenation + Huangkui capsules pretreated Exo group (H group). Western blotting was used to measure the expression of endoplasmic reticulum stress (ERS)-related proteins, and real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to measure the expression of ERS-related gene messenger RNA (mRNA). Mice were randomly divided into sham operation group (Sham group), ischemia-reperfusion group (I/R group), ischemia-reperfusion + Exo group (E group), and ischemia-reperfusion + Huangkui capsules pretreated Exo group (H group). Renal histological assessment, serum creatinine (Scr), blood urea nitrogen (BUN) measurement and inflammatory factor detection were performed 24 hours later. Results Both Exo and Huangkui capsules prereated Exo had a bilayer membrane structure and a cup-shaped morphology; their average particle sizes were 116.8 nm and 81.3 nm, respectively. Both expressed CD9, CD63, TSG101. Compared with the M group, the E group had decreased relative expression of transcription factor 6 (ATF6) and protein kinase R-like endoplasmic reticulum kinase (PERK) proteins, increased mRNA relative expression, increased relative expression of C/EBP homologous protein (CHOP) protein, and decreased mRNA relative expression. Compared with the E group, the H group had decreased relative expression of ATF6, PERK, CHOP proteins, and decreased mRNA relative expression of ATF6 and PERK (all P<0.05). Animal experimental results showed that compared with the Sham group, the I/R group had increased renal tubular injury scores, Scr, BUN, interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor (TNF)-α levels. Compared with the I/R group, the E and H groups had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels. Compared with the E group, the H group had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels (all P<0.05). Conclusions Huangkui capsules pretreatment HUC-MSC-derived Exo may alleviate renal IRI by inhibiting ERS.
9.The application progress of music intervention in nursing of patients with psychiatric disorders
Haijiao LI ; Dongshuai WEI ; Ruiyan WANG ; Rongxun LIU ; Chaofeng ZHANG ; Jie JIA ; Yange WEI
Chinese Journal of Nursing 2025;60(6):764-768
Music intervention is an innovative nursing method that integrates music,medicine,and psychology.It is safe,effective,and easy for implemention.It has demonstrated positive effects in alleviating psychotic symptoms,stabilizing emotions,and improving sleep,and it is gradually being applied in psychiatric disorders.This article provides a review of the theoretical basis and current research status of music intervention,and offers a perspective on future applications,with the aim of providing a reference for the application of music intervention in the rehabilitation nursing of mental illnesses.
10.Association between insulin resistance and left ventricular remodeling after STEMI in patients without a history of diabetes mellitus
Chendie YANG ; Changqing HU ; He YUAN ; TAY Guan POH ; Abulikemu AMUTI ; Ruiyan ZHANG ; Xiaoqun WANG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(3):292-300
Objective·To investigate the association of insulin resistance with left ventricular(LV)remodeling after ST-segment elevation myocardial infarction(STEMI)in patients without a history of diabetes mellitus.Methods·This study consecutively enrolled STEMI patients without a history of diabetes mellitus who underwent percutaneous coronary intervention in the Department of Cardiology of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from January 2014 to December 2022.The patients were followed up for 6 months.Age,gender,smoking status,blood pressure,body mass index,biochemical indexes(liver function,kidney function,lipid profiles,glycemic levels and peak troponin levels,etc.)and pharmacological treatment were recorded.Homeostasis model assessment of insulin resistance(HOMA-IR)was used to evaluate insulin resistance and mean values of visit-to-visit HOMA-IR were calculated.Patients were divided into 4 groups(low-level group,low-to-medium-level group,medium-to-high-level group,and high-level group)according to the quartiles of mean HOMA-IR levels.Echocardiography was performed at baseline and during follow-up.Then the association between mean values of insulin resistance and post-infarction LV remodeling was analyzed.Results·A total of 219 patients were finally included,with an average age of(62.7±11.9)years,and male patients accounted for 85.4%(187 cases).The average follow-up time was(6.4±1.8)months.During follow-up,the average number of HOMA-IR measurements was(4.32±2.18),and the mean value of visit-to-visit HOMA-IR was 2.41(1.58,3.98),which was higher than normal range.The results showed that post-infarction LV end-diastolic diameter(P=0.027)and LV end-diastolic volume index(P=0.013)generally showed a trend for dilation with increasing mean HOMA-IR levels.Pearson correlation analysis revealed the mean values of visit-to-visit HOMA-IR were positively correlated to changes in LV dimensions(△ LV end-diastolic volume index:r=0.20,P=0.003;△ LV end-diastolic diameter:r=0.21,P=0.002).Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI,even after adjusting for age,gender,traditional risk factors(history of hypertension,body mass index,smoking status,renal function and lipid profiles),pharmacological treatment,baseline LV ejection fraction and peak troponin levels.Compared with patients with the lowest quartile of HOMA-IR,those with the highest HOMA-IR quartile exhibited a 7.727 mL/m2 increase in LV end-diastolic volume index(P<0.001).Conclusion·This study reveals that insulin resistance is prevalent in STEMI patients without a history of diabetes mellitus.Insulin resistance is an independent predictor of adverse LV remodeling in this population.

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