1.Mitochondial-located miRNAs in The Regulation of mtDNA Expression
Peng-Xiao WANG ; Le-Rong CHEN ; Zhen WANG ; Jian-Gang LONG ; Yun-Hua PENG
Progress in Biochemistry and Biophysics 2025;52(7):1649-1660
Mitochondria, functioning not only as the central hub of cellular energy metabolism but also as semi-autonomous organelles, orchestrate cellular fate decisions through their endogenous mitochondrial DNA (mtDNA), which encodes core components of the electron transport chain. Emerging research has identified microRNAs localized within mitochondria, termed mitochondria-located microRNAs (mitomiRs). Recent studies have revealed that mitomiRs are transcribed from nuclear DNA (nDNA), processed and matured in the cytoplasm, and subsequently transported into mitochondria. mitomiRs regulate mtDNA through diverse mechanisms, including modulation of mtDNA expression at the translational level and direct binding to mtDNA to influence transcription. Aberrant expression of mitomiRs leads to mitochondrial dysfunction and contributes to the pathogenesis of metabolic diseases. Restoring mitomiR expression to physiological levels using mitomiRs mimics or inhibitors has been shown to improve mitochondrial function and alleviate related diseases. Consequently, the regulatory mechanisms of mitomiRs have become a major focus in mitochondrial research. Given that mitomiRs are located in mitochondria, targeted delivery strategies designed for mtDNA can be adapted for the delivery of mitomiRs mimics or inhibitors. However, numerous intracellular and extracellular barriers remain, highlighting the need for more precise and efficient delivery systems in the future. The regulation of mtDNA expression mediated by mitomiRs not only expands our understanding of miRNA functions in post-transcriptional gene regulation but also provides promising molecular targets for the treatment of mitochondrial-related diseases. This review systematically summarizes recent research progress on mitomiRs in regulating mtDNA expression and discusses the underlying mechanisms of mitomiRs-mtDNA interactions. Additionally, it provides new perspectives on precision therapeutic strategies, with a particular emphasis on mitomiRs-based regulation of mitochondrial function in mitochondrial-related diseases.
2.Short- to medium-term safety and efficacy of the implantable Corheart 6 left ventricular assist system in patients with end-stage heart failure
Zhibing QIU ; Xiaochun SONG ; Liangpeng LI ; Hongwei SHI ; Liqiong XIAO ; Yunzhang WU ; Xiaosong RONG ; Jidan FAN ; Liang WEI ; Xin CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):639-645
Objective To investigate the efficacy and safety of the Corheart 6 left ventricular assist system in patients with end-stage heart failure. Methods A retrospective study was conducted on patients with end-stage heart failure who were treated with Corheart 6 left ventricular assist system from March 2022 to June 2024 in 4 hospitals in Jiangsu Province. The efficacy of the device was evaluated by comparing changes in clinical indicators at preoperative, discharge, 3-month postoperative, and 6-month postoperative timepoints, including the New York Heart Association (NYHA) functional classification, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic diameter (LVEDD). The safety of the device was assessed by analyzing the intraoperative position and orientation of the blood pump inlet cannula, as well as the incidence of adverse events. Results In this study, 39 patients were collected, including 34 males and 5 females with a mean age of (56.4±12.5) years, ranging from 20 to 75 years. There was no operative death. There was no death in postoperative 3 months with a survival rate of 100.0%. There were 3 deaths in 6 months postoperatively, with a survival rate of 92.3%. All patients had a preoperative NYHA cardiac function classification of class Ⅳ. The NYHA cardiac function class of the patients improved (P<0.05) at discharge, 3 and 6 months after surgery when compared to the preoperative period. LVEF was significantly higher at 3 months after surgery than that during the preoperative period (P<0.05). LVEDD was significantly smaller at discharge, 3 and 6 months after surgery than that during the preoperative period (P<0.05). The safety evaluation's findings demonstrated that all 39 patients' intraoperative blood pump inlet tubes were oriented correctly, the artificial blood vessel suture sites were appropriate, there were no instances of device malfunction or pump thrombosis, or instances of bleeding or hemolysis, and the rate of the remaining adverse events was low. Conclusion With a low rate of adverse events and an excellent safety profile, the Corheart 6 left ventricular assist system can efficiently enhance cardiac function in patients with end-stage heart failure. It also has considerable clinical uses.
3.Cardamomine attenuates cardiotoxicity induced by anthracyclines in rats by regulating Notch/NF-κB signal pathway mediated pyroptosis
Xiao-Lei YU ; Wen-Xin LI ; Pan-Pan CHEN ; Yun-Fei LIANG ; Yan-Rong CUI ; Hai-Jing JIAO ; Fan XU
The Chinese Journal of Clinical Pharmacology 2024;40(9):1277-1281
Objective To investigate the protective effect of cardamomine(CAR)on anthracycline-induced cardiotoxicity in rats by regulating the pyroptosis mediated by Notch/nuclear factor-κB(NF-κB)signal pathway.Methods The rat model of cardiotoxicity was established by intraperitoneal injection of doxorubicin(DOX).The model rats were randomly divided into DOX group,CAR-L group,CAR-H group and Jagged1 group.Another 10 rats were taken as the control group.The control group and the DOX group were given the same amount of 0.9%NaCl.The CAR-L group and CAR-H group were given 40 and 80 mg·kg-1 CAR by gavage,respectively.The Jagged1 group was given 80 mg·kg-1 CAR+and 25 ng·kg-1 Jagged1 by gavage once a day for 4 weeks.Myocardial injury markers creatine kinase isoenzyme(CK-MB)and troponin Ⅰ(cTn Ⅰ)were detected by kit.The expression of pyroptosis protein Nod-like receptor protein 3(NLRP3)and desquamate D(GSDM-D)were observed by immunohistochemistry.The expression of Notch1 and phosphorylated NF-κB p65(p-NF-κB p65)protein in myocardial tissue was detected by Western blotting.Results The levels of CK-MB in control group,DOX group,CAR-L group,CAR-H group and Jagged1 group were(48.51±5.39),(175.93±13.27),(106.83±9.73),(83.71±8.39)and(126.08±9.74)U·L-1;the levels of cTn Ⅰ were(1.95±0.18),(12.46±1.83),(7.15±0.64),(4.13±0.38)and(8.01±0.78)ng·mL-1;the average optical density of NLRP3 protein were 0.19±0.07,0.36±0.05,0.25±0.05,0.21±0.03 and 0.31±0.06;the average optical density of GSDM-D were 0.18±0.04,0.43±0.06,0.24±0.03,0.19±0.04 and 0.32±0.05.There were significant differences in the above indexes between DOX group and control group(all P<0.05).There were significant differences in the above indexes between CAR-L group,CAR-H group and DOX group(all P<0.05),and there were significant differences between CAR-L group and CAR-H group(all P<0.05).The above indexes in Jagged1 group were significantly different from those in CAR-H group(all P<0.05).Conclusion CAR can improve myocardial injury in DOX cardiotoxic rats,reduce oxidative stress,inflammatory reaction and pyroptosis,and its mechanism may be related to the inhibition of Notch/NF-κB pathway.
4.Effects of total flavonoids of Oxytropis falcata Bunge on CCl4-induced liver fibrosis in rats
Tian-Yan YANG ; Xin-Huan MA ; Zhi-Wei XU ; Rong-Kun LI ; Fang-Xiong MA ; Bao-Feng HE ; Liang CHEN ; Xiao-Qing CHEN ; Jun ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(14):2073-2077
Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9%NaCl),model group(intraperitoneal injection of 40%CC14 peanut oil solution induced HF model,intragastric administration of 0.9%NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P<0.05,P<0.01,P<0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.
5.Bioequivalence study of pyrazinamide tablets in Chinese healthy subjects
Li-Bing YE ; Chong YAO ; Ying-Rong CHEN ; Lu-Yuan TONG ; Tao YANG ; Xiao LU ; Min XU ; Qiu-Yue JIN ; Shui-Xin YANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2236-2240
Objective To evaluate the bioequivalence and safety of two pyrazinamide tablets in healthy Chinese subjects.Methods An open,randomized,single-dose,two-sequence,two-cycle,double-cross trial design was used.All 48 healthy subjects(24 in fasting and 24 in fed trial)were randomized to receive a single oral dose of a 0.5 g pyrazinamide tablet(test or reference)per cycle.The plasma concentration of the drug was determined by liquid chromatography coupled to tandem mass spectrometry method.The pharmacokinetic parameters were calculated by WinNonlin v8.2,and the bioequivalence was evaluated by SAS 9.4.Results In the fasting group,the Cmax of the test and reference preparation of pyrazinamide tablets were(13.28±2.82)and(12.88±4.49)μg·mL-1,the AUC0-t were(139.17±26.58)and(138.63±28.92)h·μg·mL-1,the AUC0-∞ were(148.96±33.65)and(148.71±36.97)h·μg·mL-1 respectively.In the fed group,the Cmax of the test and reference preparation of pyrazinamide tablets were(11.89±1.96)and(11.99±1.92)μg·mL-1,the AUC0-t were(138.22±37.21)and(141.68±25.80)h·μg·mL-1,the AUC0-∞ were(152.20±32.41)and(151.04±28.05)h·μg·mL-,respectively.The 90%confidence intervals of Cmax,AUC0-t and AUC0-∞ geometric mean ratios of the test and reference preparation were all within 80.00%to 125.00%.The incidence of adverse events was 16.70%for both the test and reference preparation in the fasting group and 8.30%for both the test and reference preparation in the fed group,all of which were mild in severity.Conclusion The test and reference preparation of pyrazinamide tablets were bioequivalent,safe and well tolerated in healthy Chinese subjects under fasting and fed conditions.
6.Construction of a whole business process supervision and management system: based on management information system of blood banks
Weidong HE ; Zhiquan RONG ; Chen XIAO ; Junlei HUANG ; Na HU ; Xuefeng LIANG ; Liyue JIANG ; Caina LI ; Wei WEI ; Yan LIU
Chinese Journal of Blood Transfusion 2024;37(4):455-461
【Objective】 To achieve supervision and management of the whole business process of blood center, raise productivity and ensure blood quality by enabling blood center managers comprehensively grasp the key business operation situation of the whole process at anytime and anywhere. 【Methods】 A whole business process supervision and management system was established covering background of preparation, business scope, content of position supervision and management, overall framework design, interface design of management and supervision management, physical database design, program development and online debugging, and was integrated with the blood bank management information system. The display and management were through a mobile APP to record key indicators of business process from blood collection to blood supply timely and comprehensively. Statistical analysis was conducted on total collection volume, total preparation volume and total supply volume, as well as discarding rate of test unqualified and of non-test unqualified (lipemic blood excluded) in 2023 and 2022. 【Results】 We established a mobile APP based on a blood bank management information system for business supervision and management of whole process, and achieved management by phones. After its implementation in 2023, the total collection volume, total preparation volume and total supply volume in 2023 were all higher than those in 2022, with growth rates of 5.88% (13 247/225 454 U), 4.73% (24 156/510 698 U), and 6.70% (34 814/519 914 U), respectively. The discarding rate in 2023 was lower than that in 2022 (0.54%, 2 868/534 854 U) vs (0.60%, 3 047/510 698 U) (P<0.01), and the non-test unqualified discarding rate (lipemic blood excluded) in 2023 was significantly lower than that in 2022(0.12%, 649/534 854 U) vs (0.19%, 991/510 698 U)(P<0.01). 【Conclusion】 The construction of supervision and management system of a whole business process based on blood bank management information system can meet the standardized service needs of managers at anytime and anywhere, continuously raise productivity and the standardization and scientific level of blood bank management, thus ensuring blood supply.
7.Altered gray matter volume and resting-state functional connectivity in migraine patients without aura
Zhengwei CHEN ; Cunxin LIN ; Yueji LIU ; Dan LIU ; Liangqun RONG ; Xiue WEI ; Lijie XIAO ; Haiyan LIU
Chinese Journal of Neurology 2024;57(4):366-374
Objective:To investigate the underlying neuroimaging mechanism of migraine without aura (MwoA) by using methods of voxel-based morphometry (VBM) and resting-state functional connectivity (FC).Methods:Twenty-five MwoA patients admitted to Department of Neurology, the Second Affiliated Hospital of Xuzhou Medical University from September 2020 to June 2023 were recruited as MwoA group, and 22 volunteers were recruited as healthy control (HC) group. Demographic, clinical characteristics, scores of Hamilton Anxiety Scale (HAMA), Hamilton Depression Rating Scale (HAMD) and Montreal Cognitive Assessment (MoCA) of all subjects were collected; MwoA patients also received Migraine Disability Assessment Questionnaire, Headache Impact Test-6 and headache Visual Analogue Scale assessments. All subjects underwent high-resolution 3D-T 1 and resting-state functional magnetic resonance imaging scanning. The SPM12 software was used to compare the difference in gray matter volume (GMV) between the 2 groups by VBM method. The GRETNA software was adopted to calculate the whole brain FC with anatomical automatic labeling 90 as the regions of interest, and the difference in FC between the 2 groups was statistically analyzed by two-sample t-test. Pearson partial correlation was used to analyze the correlation between brain GMV and FC changes and clinical features and scale scores of MwoA patients. Results:There existed no statistically significant difference between the 2 groups in age, gender, education, scores of HAMA, HAMD and MoCA (all P>0.05). Migraine Disability Assessment Questionnaire, Headache Impact Test-6 and headache Visua Analogue Scale scores of MwoA patients were (8.86±4.55), (50.27±6.35) and (6.68±1.73). Compared with the HC group, GMV was significantly decreased in the right superior frontal gyrus (SFG), right cingulate gyrus (CG) and left thalamus in the MwoA group ( P<0.05, false discovery rate corrected). In addition, the MwoA group showed decreased FC between left thalamus and right cuneus, left lingual gyrus (LG) and bilateral precuneus; decreased FC between right thalamus and right cuneus, right LG and right precuneus; decreased FC between right cuneus and left precuneus and right SFG; decreased FC between left LG and bilateral precuneus, decreased FC between right LG and right precuneus and left SFG; decreased FC between left precuneus and bilateral SFG, and between right precuneus and right SFG (edge P<0.001, component P<0.05, network-based statistics correction, interation=2 000). In MwoA patients, the FC (z-value) between left thalamus and right cuneus was negatively correlated with the duration of disease ( r=-0.530, P=0.011). Conclusions:MwoA patients showed decreased GMV in right SFG, CG and left thalamus. In MwoA patients, FC between thalamus and visual network (VN) and default mode network (DMN) was significantly decreased, and FC among VN, DMN and executive control network was significantly decreased. These changes in brain structure and function may be an adaptive change in the central sensitivity and responsiveness to pain stimuli, and may be an important neuroimaging mechanism of MwoA.
8.Preparation of scutellarin solid dispersion based on deep eutectic solvents
Yong-jing LIU ; Li LOU ; Dong-ting HUANG ; Li-rong CHEN ; Xiao-ying WANG
Acta Pharmaceutica Sinica 2024;59(9):2665-2672
In this study, deep eutectic solvents (DESs) were used as excipients to prepare solid dispersion (SD) of scutellarin. The SD of scutellarin were prepared by melting method with cumulative dissolution rate as the index of investigation. The preparation conditions of SD of scutellarin were optimized by single factor experiment, which investigated the type of the carrier material, the type of DESs, and the ratio of the drug to the carrier. The optimum preparation conditions of DESs-SD were as follows: using Poloxamer 407 as the carrier material, PEG 200/urea (2∶1) as the DESs system, and the ratio of carrier, DESs, and drug was 6∶1∶1. The drug loading capacity of scutellarin in SD was 12.53% under the optimum preparation conditions. Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray powder diffraction and scanning electron microscope exhibited that scutellarin was amorphous form in the SD system. Furthermore, the stability of the DESs-based SD of scutellarin was evaluated by high temperature, high humidity, and strong light tests, which showed that the cumulative dissolution rate and scutellarin content of SD decreased with time under these conditions. Finally, the result of pharmacokinetic studies indicated that the oral absorption of the scutellarin could be increased using DESs as an excipient in the preparation of SD. The animal experiment was approved by the Experimental Animal Ethics Committee of Fujian University of Traditional Chinese Medicine (approval number: FJTCMIACUC 2023048). Consequently, this research offers a novel and effective approach for using DESs to enhance the oral bioavailability of active substances with low water solubility.
9.Visualization Analysis of Artificial Intelligence Literature in Forensic Research
Yi-Ming DONG ; Chun-Mei ZHAO ; Nian-Nian CHEN ; Li LUO ; Zhan-Peng LI ; Li-Kai WANG ; Xiao-Qian LI ; Ting-Gan REN ; Cai-Rong GAO ; Xiang-Jie GUO
Journal of Forensic Medicine 2024;40(1):1-14
Objective To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database,to explore research hotspots and developmen-tal trends.Methods A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the litera-ture measuring tool CiteSpace.The authors,institution,country(region),title,journal,keywords,cited references and other information of relevant literatures were analyzed.Results A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries(regions)were identi-fied,with the number of articles published showing an increasing trend year by year.Among them,the United States had the highest number of publications and China ranked the second.Academy of Forensic Science had the highest number of publications among the institutions.Forensic Science Inter-national,Journal of Forensic Sciences,International Journal of Legal Medicine ranked high in publica-tion and citation frequency.Through the analysis of keywords,it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technol-ogy for sex and age estimation,cause of death analysis,postmortem interval estimation,individual identification and so on.Conclusion It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research.Exploring the combination of advanced ar-tificial intelligence technologies with forensic research will be a hotspot and direction for future re-search.
10.Application of scaffolding-based flipped classroom in Infectious Disease Nursing
Fei ZHAO ; Zhiyan BAO ; Rong CHEN ; Leyao XIAO ; Fenlian ZENG ; Xia LIU ; Chunmei YAO ; Kangyan LIU ; Shuozhen CHEN ; Song LI ; Ping YANG
Chinese Journal of Medical Education Research 2024;23(3):401-405
Objective:To explore the effects of the scaffolding-based flipped classroom approach in the teaching of Infectious Disease Nursing. Methods:We assigned 152 students of nursing and midwifery majors of grade 2018 (experimental group) to be taught using the scaffolding-based flipped classroom approach and 182 students of grade 2017 (control group) to be taught using the traditional lecture method. Teaching effects were evaluated through students' exam performance and a questionnaire survey. Numerical data were analyzed using the χ2 test and t test with the use of SPSS 18.0, and text data were processed using NVivo 11 for thematic analysis. Results:The experimental group and control group showed significant differences in the interim exam score (83.19±7.96 vs. 79.62±3.14, P<0.001) and final exam score (78.47±6.92 vs. 73.16±8.24, P<0.001). The students of grade 2018 had a high level of participation in online learning. The questionnaire results showed that the scaffolding-based flipped classroom was well recognized in terms of students' overall perception, perceived course quality, perceived value of learning, and satisfaction and the open-ended question, with low scores for learner complaints and loyalty. Conclusions:The scaffolding-based flipped classroom is feasible in the teaching of Infectious Disease Nursing, which can improve students' academic performance and overall competence.

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