1.YTHDF1 regulation of Fis1 on the activation and proliferation and migration ability of hepatic stellate cells
Lin Jia ; Feng Sun ; Qiqi Dong ; Jingjing Yang ; Renpeng Zhou ; Wei Hu ; Chao Lu
Acta Universitatis Medicinalis Anhui 2025;60(1):49-58
Objective:
To explore the effect of YTH domain family protein 1(YTHDF1) on the activation, proliferation and migration of hepatic stellate cells(HSCs) by regulating mitochondrial fission mediated by mitochondrial fission protein 1(Fis1).
Methods:
The mouse hepatic stellate cell line JS-1 was treated with 5 ng/ml TGF-β1 for 24 h to induce its activation and proliferation, andYTHDF1-siRNA was used to construct aYTHDF1silencing model.The experiment was divided into Control group, TGF-β1 group, TGF-β1+si-NC group and TGF-β1+si-YTHDF1 group.Expression changes ofYTHDF1,Fis1and key indicators of fibrosis, type Ⅰ collagen(CollagenⅠ) and α-smooth muscle actin(α-SMA) were detected through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot; CCK-8 was used to detect cell proliferation ability; Transwell migration assay and cell scratch assay were used to detect cell migration ability; immunofluorescence staining experiment was used to detect the effect ofYTHDF1onFis1-mediated mitochondrial fission; finally, JC-1 staining was used to experimentally detect the effect ofYTHDF1on mitochondrial membrane potential.
Results:
Compared with the Control group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1increased in the TGF-β1 group(P<0.05,P<0.01;P<0.000 1), as well as the fibrosis markersCollagenⅠand the expression level of α-SMA increased(P<0.01;P<0.001,P<0.000 1); while adding CCK-8, the experimental results showed that the proliferation ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); Transwell experimental results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.01); the cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); the immunofluorescence experiment results showed that the TGF-β1 group Mito-Tracker Red staining andFis1co-localization signal increased(P<0.05); JC-1 staining experiment results showed that the mitochondrial membrane potential increased in the TGF-β1 group(P<0.01). Compared with the TGF-β1+si-NC group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1in the TGF-β1+si-YTHDF1 group was reduced(P<0.01;P<0.001), and fibrosis markers the levels ofCollagenⅠandα-SMAwere reduced(P<0.01;P<0.001,P<0.01).CCK-8 experimental results showed that the proliferation ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); Transwell experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.001); cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); immunofluorescence experiment results showed that the Mito-Tracker Red staining andFis1co-localization signal decreased in the TGF-β1+si-YTHDF1 group(P<0.01); JC-1 staining experiment results showed that mitochondrial membrane potential decreased in the TGF-β1+si-YTHDF1 group(P<0.05).
Conclusion
YTHDF1promotes the activation, proliferation and migration capabilities of HSCs by positively regulatingFis1-mediated mitochondrial fission. This suggests thatYTHDF1may be a key gene involved in regulating the activation, proliferation and migration of HSCs.
2.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
3.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
4.The relationship between D-loop region single nucleotide polymorphism and copy number of mitochondrial DNA with the risk of developing dermatomyositis
Zirui Tan ; Jingjing Zhang ; Yuanyuan Jia ; Chenxing Peng ; Yufe Zhao
Acta Universitatis Medicinalis Anhui 2025;60(1):130-135
Objective :
To explore the relationship between single nucleotide polymorphisms ( SNPs) in D-loop region of mitochondrial DNA ( mtDNA) and mtDNA copy number and the risk of dermatomyositis ( DM) ,and its in- fluencing factors.
Methods :
74 patients with DM and 92 healthy controls were included in the study. Genomic DNA was extracted from peripheral blood and the target fragment of mtDNA D-loop region was amplified by PCR technique,and the products were subsequently sequenced.Serum levels of ROS were assessed using a high-sensi- tivity reactive oxygen species detection kit.The expression levels of cytokines,interleukin ( IL) -5,IL-13,inter- feron-γ ( IFN-γ) ,IL-2,IL-6,IL-10,tumor necrosis factor-α ( TNF-α) and IL-4 were measured using Flow Fluo- rescence Immunmicrobeads Assay.Wilcoxon rank-sum test was used to assess the potential correlation between cy- tokines and SNPs associated with DM risk.The relative copy number of mtDNA was measured using quantitative re- al-time polymerase chain reaction ( qPCR) analysis.
Results :
Two SNPs ( 16304T / C,16519T / C) were found to be associated with the risk of developing DM,and alleles 16304C ( χ2 = 4. 937,P = 0. 026) and 16519C ( χ2 = 4. 405,P = 0. 036) in the mitochondrial D-loop region were confirmed to be associated with DM development risk. The DM risk-associated allele 16304C was significantly associated with lower IL-4 expression ( P = 0. 016) .The mtDNA copy number was significantly higher in DM patients than in controls ( P <0. 001) .
Conclusion
Mitochondrial D-loop SNPs can be potential biomarkers for DM risk,and SNPs may be involved in DM by influencing cytokines.DM shows high expression of mtDNA copy number,and the increase in mtDNA copy number may lead to mitochondrial dysfunction,which triggers the pathogenesis of DM.
5.Effect of group exercise therapy on improving sleep quality in patients with mild to moderate depressive disorder during the acute phase
Ruinan LI ; Jianjun GUO ; Wenyang LIU ; Yu QIAO ; Lu TIAN ; Shengtao JIA ; Jingjing ZHOU
Sichuan Mental Health 2024;37(6):492-496
BackgroundPatients with depressive disorder commonly experience sleep disturbances. Previous studies have indicated that group exercise therapy is beneficial in alleviating depressive symptom among patients with depressive disorder. However, there is a lack of research on the impact of group exercise therapy on improving sleep quality in patients with depressive disorder. ObjectiveTo explore the impact of group exercise therapy on sleep quality in patients with acute mild-to-moderate depression during the acute phase, so as to provide references for clinically improving the sleep quality of patients with mild to moderate depressive disorder during the acute phase. MethodsFrom December 2018 to July 2021, patients with mild-to-moderate depressive disorder during the acute phase (n=40), who met the diagnostic criteria for depressive disorder according to International Classification of Diseases, tenth edition (ICD-10) ,were recruited from the outpatient clinic of Beijing Anding Hospital, Capital Medical University. All participants underwent an 8-week moderate-intensity group exercise therapy program comprising three sessions per week, each lasting 60 minutes. Assessments were conducted at baseline and after 2, 4, 6 and 8 weeks of intervention using Visual Analogue Scale (VAS), Hamilton Depression Scale-17 item (HAMD-17) and Pittsburgh Sleep Quality Index (PSQI). The reduction scores at each time point relative to baseline treated as the dependent variables, time as the independent variable, baseline scores as covariates, with time as a fixed effect and baseline values as random effects. Data were analyzed using a linear mixed-effects model. ResultsThe PSQI scores of patients at baseline, 2, 4 , 6 and 8 weeks after the intervention were (10.62±5.12), (9.07±3.58), (7.39±3.66), (6.54±3.84) and (5.50±3.41), respectively. The results of linear mixed effect model analysis showed that after 2, 4, 6 and 8 weeks of intervention, patients scored lower than baseline, with statistically significant differences observed in all cases (P<0.01). The HAMD-17 sleep fcctor scores at baseline, 2, 4, 6 and 8 weeks were (2.25±1.56), (2.06±1.49), (1.36±1.27), (1.22±1.46) and (0.97±1.34), respectively. The results of linear mixed effects model analysis showed that the HAMD-17 sleep factor scores of 4, 6 and 8 weeks of intervention were lower than that of baseline, and the difference was statistically significant (P<0.05 or 0.01). The VAS scores at baseline, 2, 4, 6 and 8 weeks after the intervention were (3.18±2.17), (4.74±2.22), (6.01±2.31), (6.54±2.16) and (7.90±1.64), respectively. The results of linear mixed effect model analysis showed that VAS scores of 2, 4, 6 and 8 weeks of intervention were higher than baseline,and the difference was statistically significant (P<0.01). ConclusionGroup exercise therapy may improve sleep quality and alleviate depressive symptoms in patients with mild-to-moderate depressive disorder during the acute phase. [Funded by National Key Research and Development Plan Project (number, 2016YFC1307200); Beijing Municipal Hospital Scientific Research and Cultivation Plan Project (number, PX2024070)]
6.Establishment and practice of hospital medical consumable admission decision-making system based on expert heuristics
Lei GAO ; Rui MAO ; Xiaoli HE ; Yubin YE ; Jingjing JIA ; Lin WEN
China Medical Equipment 2024;21(10):155-160
Objective:To construct a rapid admission evaluation model for medical consumables of same category,and to achieve a balance between scientificity,efficiency and practicality in the management of medical consumables.Methods:Based on the mini health technology assessment(Mini-HTA)model,combined with expert heuristics,a rapid qualitative analysis of the intended use and technical characteristics of the same category of medical consumables were conducted.Expert opinions were solicited through the Delphi method,and a rapid admission evaluation model of same category of medical consumables was constructed.A total of 80 high-value medical consumables of 10 categories in clinical use in Sichuan Provincial People's Hospital from June 2023 to March 2024 were selected,and the traditional admission process method and expert heuristics optimization method were used to make admission decisions for medical consumables,with 40 high-value medical consumables for each method.The differences in the decision-making process and approval time between the two different admission methods were compared and analyzed.Results:The admission decision-making system indicators of the rapid admission evaluation model of medical consumables of same category included 6 primary indicators of clinical efficacy,reliability,economics,values and aspirations,hospital management and corporate services,and 25 secondary indicators.The approval process for medical consumables admission decision-making using the rapid admission evaluation model of medical consumables of same category had been reduced from 10 in the traditional admission process to 2,and the approval time had been shortened from an average of 7.03 days to 2.43 days.Conclusion:The rapid admission evaluation model for the approval of medical consumables of same category based on expert heuristics can significantly optimize the admission approval process of medical consumables,improve the comprehensiveness and transparency of medical consumables admission decisions,and improve the management efficiency of medical consumables.
7.Predictive value of CALLY index for depression after ischemic stroke
Jingjing ZHANG ; Wendong ZHAO ; Yuan ZHAO ; Qingxia ZHANG ; Jia DU ; Yanxia LIU
Tianjin Medical Journal 2024;52(12):1300-1304
Objective To investigate the predictive value of CALLY index for ischemic post-stroke depression(PSD).Methods The clinical data of 179 patients with ischemic stroke were included,and the demographic information,medical history,stroke severity and laboratory indicators at admission were collected.After 6 months of follow-up,all patients were assessed for depressive symptoms using the 17-item Hamilton Depression Scale(HAMD-17).Patients were divided into the PSD group(48 cases)and the non-PSD group(131 cases).Differences in clinical characteristics were compared between the PSD group and the non-PSD group.CALLY index was calculated from C-reactive protein(CRP),albumin(ALB)and lymphocyte counts.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of CALLY index to PSD.Spearman correlation analysis was used for the correlation between CALLY index and neurological and cognitive function in PSD patients.K-M curve and Cox regression were used for analyzing the influence of CALLY index on PSD.Results The CALLY index of 179 patients ranged from 0.54 to 1.79,with a median of 1.08.ROC curve analysis showed that the optimal critical value of CALLY index to predict PSD was 1.09,and the area under ROC curve was 0.757(95%CI:0.687-0.818).Compared with the non-PSD group,the proportion of females was higher in the PSD group,and the proportion of patients with hyperlipidemia was increased with shorter years of education.The serum C-reactive protein(CRP)was higher,and albumin(ALB)and CALLY index were lower(P<0.05).The K-M curve showed that the incidence of PSD was significantly higher in the low CALLY index group(CALLY≤1.08)than that in the higher CALLY index group(CALLY>1.08,33.0%vs.20.5%,Log rank χ2=8.553,P=0.004).Cox regression analysis showed that after adjusting for other covariates,the decreased CALLY index was an independent risk factor for PSD(HR=2.651,95%CI:1.269-5.540,P<0.05).Conclusion CALLY index has a certain predictive value for PSD in acute ischemic stroke patients,which is helpful for early identification and timely intervention to improve the prognosis of patients.
8.Research progress of shared decision-making in treatment decision-making of breast cancer patients
Yuzhu LIU ; Chuhan HUANG ; Yingjie CAI ; Jingjing JIA ; Tieying SHI
Chinese Journal of Modern Nursing 2024;30(3):406-411
As the largest cancer in the world, breast cancer has both benefits and risks from its diversified treatments. Shared decision-making can respect the patient's right to information and autonomy, consider their preferences and value orientations, and help patients obtain the most suitable treatment plan, it also can reduce their decision-making difficulties and improve their disease knowledge awareness and decision-making satisfaction. This paper reviews the definition of shared decision-making, the influencing factors, steps, tools and clinical effects of shared decision-making in the treatment decision-making of breast cancer patients, in order to provide reference for the research of shared decision-making in breast cancer patients in China.
9.Effects of intelligent multifunctional rehabilitation instrument for lower limb diseases on preventing deep vein thrombosis in stroke patients with hemiplegia
Bing LI ; Rufu JIA ; Zhijing WANG ; Haiyue LI ; Cuijie WANG ; Mianlei DING ; Tao HUANG ; Jingjing WU
Chinese Journal of Modern Nursing 2024;30(7):950-953
Objective:To explore the effectiveness of intelligent multifunctional rehabilitation instrument for lower limb diseases in preventing deep vein thrombosis in stroke patients with hemiplegia.Methods:From September 2022 to September 2023, convenience sampling was used to select 121 stroke patients with hemiplegia admitted to the Department of Neurology, Neurosurgery, and Rehabilitation of Cangzhou Central Hospital as the study subject. The study subjects were divided into a control group ( n=58) and an observation group ( n=63) using the random number table method. The control group was treated with standard medication and routine rehabilitation nursing, while the observation group was treated with the intelligent multifunctional rehabilitation instrument for lower limb diseases on the basis of the control group. The intervention time was four weeks for both groups. This study compared the incidence of clinical symptoms of lower limbs (swelling, pain, skin temperature, gastrocnemius test results) and deep vein thrombosis in the lower limbs between two groups of patients after intervention. The plasma D-dimer levels, femoral vein blood flow velocity, and blood flow of the two groups of patients before and after intervention were also compared. Results:After intervention, the number of cases of lower limb clinical symptoms (swelling, pain, elevated skin temperature, positive results of gastrocnemius muscle test) and deep vein thrombosis in the observation group was lower than that in the control group ( P<0.05). In the observation group, the plasma D-dimer levels of patients were lower than those of the control group ( P<0.05), and the femoral vein blood flow velocity and blood flow were higher than those of the control group ( P<0.05) . Conclusions:The intelligent multifunctional rehabilitation instrument for lower limb diseases can effectively prevent the occurrence of deep vein thrombosis in stroke patients with hemiplegia.
10.Construction of risk prediction model for fear of disease progression in stroke patients
Jingjing JIA ; Xinping WANG ; Jia LIU ; Yuanyuan GUI ; Hongmin LIU
Chinese Journal of Modern Nursing 2024;30(20):2737-2743
Objective:To explore influencing factors of the occurrence of fear of disease progression (FoP) in stroke patients and to construct a risk prediction nomogram model.Methods:A total of 201 stroke patients of the First Affiliated Hospital of Qiqihar Medical University and the Third Affiliated Hospital of Qiqihar Medical University from July to December 2023 were selected as the survey objects by the convenient sampling method. Baseline data questionnaire, Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Chinese version of Perceived Stress Scale (CPSS), Social Support Rating Scale (SSRS) and Fatigue Severity Scale (FSS) were used to investigate of patients FoP occurrence, stress perception, social support level and fatigue level of stroke patients. The influencing factors of FoP occurrence in stroke patients were explored and R 4.3.2 was used to construct a risk prediction nomogram model for FoP occurrence in stroke patients. The performance of the model was evaluated using receiver operating characteristic curve, calibration curve, and clinical decision curve from the perspectives of discrimination, calibration and clinical practicality.Results:In this study, a total of 201 questionnaires were collected, 199 were valid, and the effective rate was 99%. The FOP-Q-SF score of 199 patients was (29.64±9.50), of which 71 patients (35.7%) developed FoP. Educational level, complications, self-care ability, social support, stress perception and fatigue were the influencing factors of FoP in stroke patients ( P<0.05). A risk prediction nomogram model for FoP in stroke patients was constructed based on the results of binary Logistic regression analysis. The Hosmer-Lemeshow results showed that the nomogram model fitted well (χ 2=10.466, P=0.234). The area under ROC curve was 0.912 (95% CI: 0.871-0.952). The clinical decision curve showed that when the threshold probability ranged from 4% to 99%, choosing this model to predict the risk of FoP could benefit stroke clinically. Conclusions:Educational level, complications, self-care ability, social support, stress perception and fatigue are the influencing factors for fear of disease progression in stroke patients. The risk nomogram model based on multiple evaluation indexes has certain clinical value.


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