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.Analysis and prediction of global burden due to cystic echinococcosis from 1990 to 2035
Zhen LAI ; Gang LIU ; Haili ZHAO ; Miaomiao QIU ; Jian CHEN ; En LUO ; Junguo XIN ; Xiaohong YANG
Chinese Journal of Schistosomiasis Control 2025;37(3):255-267
Objective To investigate the trends in the global burden due to cystic echinococcosis from 1990 to 2021, and to predict the global burden of cystic echinococcosis from 2022 to 2035, so as to provide insights into formulation of the cystic echinococcosis control strategy. Methods The global age-standardized prevalence, mortality, disability-adjusted life years (DALYs) rates and their 95% uncertainty intervals (UI) of cystic echinococcosis from 1990 to 2021 were captured from the Global Burden of Disease Study 2021 (GBD 2021) database, and the trends in the global burden of cystic echinococcosis from 1990 to 2021 were analyzed using the Joinpoint regression model. The associations between the global burden of cystic echinococcosis and socio-demographic index (SDI) were examined using a smoothing spline model and frontier analysis, and the global burden of cystic echinococcosis was projected from 2022 to 2035 using the Bayesian age-period-cohort (BAPC) model. Results The global agestandardized prevalence, mortality and DALYs rates of cystic echinococcosis were 7.69/105 [95% UI: (6.27/105, 9.51/105)], 0.02/105 [95% UI: (0.01/105, 0.02/105)], and 1.32/105 [95% UI: (0.99/105, 1.69/105)] in 2021. The global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a rise by 0.14% per year from 1990 to 2021, and the global age-standardized mortality and DALYs rates of cystic echinococcosis appeared a tendency towards a decline by 4.68% and 4.01% per year from 1990 to 2021, respectively. Joinpoint regression analysis showed that global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a decline from 1990 to 2000 [annual percent change (APC) = −0.66%, 95% confidence interval (CI): (−0.70%, −0.61%)] and from 2005 to 2015 [APC = −0.88%, 95% CI: (−0.93%, −0.82%)], and towards a rise from 2000 to 2005 [APC = 3.68%, 95% CI: (3.49%, 3.87%)] and from 2015 to 2021 [APC=0.30%, 95%CI: (0.19%, 0.40%)].Theagestandardized prevalence (r = −0.17, P < 0.05), mortality (r = −0.67, P < 0.05) and DALYs rates of cystic echinococcosis (r = −0.60, P < 0.05) all correlated negatively with SDI across 21 geographical regions from 1990 to 2021, and the age-standardized mortality (r = −0.61, P < 0.05) and DALYs rates (r = −0.44, P < 0.05) both correlated negatively with SDI across 204 countries and territories in 2021. Frontier analysis revealed that the age-standardized DALYs rate of cystic echinococcosis was still not in line with the frontier in some high-SDI countries or territories. In addition, the global age-standardized prevalence was projected with the BAPC model to appear a tendency towards a rise among both men [estimated annual percent change (EAPC) = 0.18%, 95% CI: (0.13%, 0.23%)] and women [EAPC = 0.29%, 95% CI: (0.24%, 0.34%)] from 2022 to 2035, and the global age-standardized mortality [men: EAPC = −4.71%, 95% CI: (−4.71%, −4.37%); women: EAPC = −4.74%, 95% CI: (−4.74%, −4.74%)] and DALYs rates [men: EAPC = −3.35%, 95% CI: (−3.36%, −3.34%); women: EAPC = −3.17%, 95% CI: (−3.18%, −3.16%)] were projected to appear a tendency towards a decline among both men and women. Conclusions The global burden of cystic echinococcosis appeared an overall tendency towards a decline from 1990 to 2021; however, the global prevalence of cystic echinococcosis is projected to appear a tendency towards a rise from 2022 to 2035. Intensified cystic echinococcosis control programmes are recommended.
3.Functional mechanism of curcumin inhibiting growth of malignant glioma by regulating TGF-β1/Smad signaling pathway
Gang ZHAO ; Guo-Dong ZHANG ; Li-Xiang WANG ; Yuan-Chao LI ; Hu ZHOU ; Zhen-Guo CHENG
Chinese Pharmacological Bulletin 2024;40(11):2113-2118
Aim To explore the effect of curcumin on the growth of malignant glioma and the possible mecha-nism.Methods Human glioblastoma cell U87 was taken as the study object.They were randomly separa-ted into the blank control group(without any interven-tion)and low,medium and high curcumin group(10,20 and 40 μmol·L-1),temozolomide group(40μmol·L-1),curcumin 40 μmol·L-1+LY210976110 μmol·L-1,curcumin 40 μmol·L-1+SRI-011381 10 μmol·L-1,then they were intervened for 48 h.The activity,migration and invasion ability of U87 cells in each group were measured by CCK-8 method and Transwell method.The cell cycle changes of U87 cells were measured by flow cytometry.The ex-pression levels of TGF-β1/Smad signaling pathway in U87 cells were measured by Western blotting.Results After 48 h intervention,the percentage of U87 cell activity,cell migration and invasion number in curcu-min group and temozolomide group were lower than those in the blank control group(P<0.05),and all decreased with the increase of curcumin dose(P<0.05).Compared with the blank control group,the number of cells increased in Sub-G0 stage in the curcu-min group and temozolomide group(P<0.05),and decreased in G2/M stage(P<0.05).The protein rel-ative expression levels of TGF-β1,p-Smad 3,N-cad-herin,matrix metalloproteinase(MMP)-2 and MMP-9 in U87 cells in high curcumin group and temozolomide group were lower than those in the blank control group(P<0.05),and the protein relative expression levels of Smad 7 and E-cadherin were higher than those in the blank control group(P<0.05).There was no statisti-cally significant difference between the high curcumin group and temozolomide group(P>0.05).Compared with the high curcumin group,inhibition of TGF-β1/Smad pathway could further inhibit the activity,migra-tion and invasion of U87 cells,reduce the relative ex-pression levels of TGF-β1,P-Smad 3,MMP-2 and MMP-9 proteins(P<0.05),and increase the relative expression levels of Smad 7 and E-cadherin protein(P<0.05),while the TGF-β1/Smad pathway activator was vice versa(P<0.05).Conclusions Curcumin can inhibit the growth of malignant glioma U87 cells,and the mechanism may be related to the regulation of TGF-β1/Smad signaling pathway.
4.Study on the basic characteristics and healthcare resource demand of elderly seasonal migrants in Hainan Province
Zhen-Yu SHI ; Cun-Ku WANG ; Ben-Guo YU ; Gang CHENG ; Qing-Yue MENG
Chinese Journal of Health Policy 2024;17(8):28-35
This study analyzed the characteristics of 118 738 seasonal migrants who were aged 65 and under management by the Health Statistics Center of Hainan Health Commission.Our study revealed that approximately 51.6%of elderly seasonal migrants were male,with around 75.2%aged below 75 years.Elderly seasonal migrants originating from the Northeast region constituted roughly 36.3%of the total,and the majority of them settled in Haikou,Chengmai and Dongfang(each representing over 10%of the total).Of the nine prevalent health conditions surveyed,about 27.6%of the elderly seasonal migrants suffered at least one condition.Haikou,Wanning,Qionghai,and Dongfang received more than 3 000 elderly seasonal migrants with health issues.Considering the availability of healthcare resources,there exists a negative correlation between the distribution of elderly seasonal migrants and the hospitalization service load of doctors in various destination areas.This study recommends Hainan Province further improving the seasonal migrants dynamic survey system,scientifically arranging healthcare resources and services,and systematically enhancing the health service experience of the seasonal migrants.
5.Application of China-made Toumai? Robot in laparoscopic radical prostatectomy
Zhi-Feng WEI ; Yu-Hao CHEN ; Ze-Peng ZHU ; Qi JIANG ; Yu XIONG ; Feng-Feng LU ; Zhen-Qian SONG ; Bin JIANG ; Xiao-Feng ZHU ; Tian-Hao FENG ; Xiao-Feng XU ; Gang YANG ; Wu WEI ; Ai-Bing YAO ; Jing-Ping GE
National Journal of Andrology 2024;30(8):696-700
Objective:To evaluate the safety and efficiency of China-made Toumai Robot-assisted laparoscopic radical prosta-tectomy(LRP).Methods:This study included 40 cases of PCa treated from January 2023 to May 2023 by robot-assisted LRP with preservation of the bladder neck and maximal functional urethral length,15 cases with the assistance of Toumai Robot(the TMR group)and the other 25 with the assistance of da Vinci Robot as controls(the DVR group).We recorded the docking time,laparo-scopic surgery time,vesico-urethral anastomosis time,intraoperative blood loss and postoperative urinary continence,and compared them between the two groups.Results:Operations were successfully completed in all the cases.No statistically significant differ-ences were observed between the TMR and DVR groups in the docking time(6 min vs 5 min,P>0.05)or intraoperative blood loss(200 ml vs 150 ml,P>0.05).The TMR group,compared with the DVR group,showed a significantly longer median laparoscopic surgery time(146 min vs 130 min,P<0.05)and median vesico-urethral anastomosis time(19 min vs 16 min,P<0.05).There were no statistically significant differences between the TMR and DVR groups in the rates of urinary continence recovery immediately af-ter surgery(60.0%[9/15]vs 64.0%[16/25],P>0.05)or at 1 month(80.0%[12/15])vs(76.0%[19/25],P>0.05),3 months(93.3%[14/15])vs(92.0%[23/25],P>0.05)and 6 months postoperatively(100%[15/15])vs(96%[24/25],P>0.05).Conclusion:China-made Toumai? Robot surgical system is safe and reliable for laparoscopic radical prosta-tectomy,with satisfactory postoperative recovery of urinary continence.
6.Expression of ZEB2 and CCL20 in glioma tissue and their correlation with prognosis
Shihe XIAO ; Gang LI ; Zhonghai LIU ; Zhen LIU
The Journal of Practical Medicine 2024;40(9):1262-1267
Objective To investigate the expression of zinc finger E-box-binding protein 2(ZEB2)and CC chemokine ligand 20(CCL20)in glioma tissue and their relationship with prognosis.Methods The tumor tissues of 156 patients with glioma were collected as tumor group and 52 normal brain tissues of the same period were collected as normal group.The expression of ZEB2 and CCL20 in tissues were detected by immunohistochemistry,and the relationship between the expression and survival was analyzed by Kaplan-Meier survival curve.Patients in the tumor group were followed up for three years and grouped into a poor prognosis group and a good prognosis group based on their survival status,and the prognostic factors were analyzed by COX regression.Results The positive expression rate of ZEB2 and CCL20 in the tumor group were higher than those in the normal group(P<0.05).The 3-year survival rate of 156 glioma patients was 69.87%.The survival rate of patients with positive ZEB2 and CCL20 expression was lower than that of patients with negative expression(P<0.001).Age,maximum tumor diameter,tumor pathological grade,and positive expression of ZEB2 and CCL20 were all risk factors for poor prog-nosis of patients with glioma(P<0.05),and preoperative KPS,postoperative radiotherapy,and course of temo-zolomide treatment were all protective factors(P<0.05).Conclusion The expression level of ZEB2 and CCL20 in tumor tissues of glioma patients is up-regulated,and related to the prognosis of patients.
7.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
8.The predictive value of peripheral blood-derived inflammatory markers SII and SIRI for in-hospital adverse cardiovascular events in patients with acute myocardial infarc-tion
Kai TANG ; Lei LIU ; Zhen TAN ; Gang ZHUANG ; Xuejun DENG ; Shiheng ZHOU
Chinese Journal of Arteriosclerosis 2024;32(7):606-612
Aim To investigate the relationship between systemic inflammatory immune index(SII)and systemic inflammatory response index(SIRI)and the risk of in-hospital major adverse cardiovascular events(MACE)in patients with acute myocardial infarction(AMI).Methods Retrospective analysis was conducted on AMI patients ad-mitted to the Second Cardiovascular Disease Area of Suining Central Hospital from February 2021 to May 2022.Based on inclusion and exclusion criteria,246 patients were finally enrolled.According to whether MACE occurred during hospital-ization,they were divided into event group and non-event group,and baseline data of the two groups were compared.All variables except SII and SIRI were included in a univariate-multivariate Logistic regression analysis to screen factors af-fecting the risk of MACE,and were used as significant covariates for adjustment to evaluate the relationship between SII and SIRI and the risk of MACE respectively.Results The results of multivariate Logistic regression analysis showed that emergency PCI,left ventricular ejection fraction,albumin level and age were significant factors affecting the risk of in-hos-pital MACE in AMI patients(OR=0.432,95%CI:0.194~0.960,P=0.038;OR=0.930,95%CI:0.890~0.969,P=0.001;OR=0.730,95%CI:0.621~0.845,P<0.001;OR=1.143,95%CI:1.070~1.228,P<0.001),and a basic model was established based on this.After adjusting for the significant covariates,SII and SIRI were both independ-ent risk factors for in-hospital MACE(OR=1.004,95%CI:1.001~1.008,P=0.002;OR=4.467,95%CI:2.597~8.142,P<0.001).The areas under the curves of SII and SIRI were 0.658 and 0.785,respectively,and the optimal cutoff values were 434.83 and 1.03.Restricted cubic spline analysis showed that SII(Nonlinear P=0.639)and SIRI(Nonlinear P=0.683)were linearly related to the risk of MACE after adjusting significant covariates.Threshold effect a-nalysis showed that when SIRI>0.93,the risk of MACE began to increase.Conclusion Elevated levels of SII and SI-RI are independent risk predictors for the occurrence of in-hospital MACE in AMI patients.
9.Development of A Model to Predict Mixed Cerebral Palsy in Infants with Periventricular White Matter Injury
Tingting HUANG ; Lan ZHANG ; Wei XING ; Zhen LI ; Fei WANG ; Gang ZHANG
Chinese Journal of Medical Imaging 2024;32(7):659-666
Purpose To development a model to predict mixed cerebral palsy(CP)in infants with periventricular white matter injury(PWMI).Materials and Methods This study retrospectively included infants with PWMI on MRI aged 6 to 24 months and were diagnosed as CP after age of 2 years in the First Affiliated Hospital of Henan University of Chinese Medicine,from September 2015 to October 2022.The eligible infants were divided into mixed group and spastic CP group.Multivariable Logistic regression model was used to select the MRI features associated with PWMI and mixed CP,and was internal validated by using the five-fold cross and repeated cross validation.Model performance was evaluated by the discrimination,calibration and decision curve.The correlation between independent MRI features and the gross motor function classification system levels was evaluated.Results A total of 135 infants with PWMI and CP were included in this study,100 with spastic CP,and 35 with mixed CP.Multivariable Logistic regression analysis found that the involvement of ventralateral of thalamus(OR=27.500,95%CI 8.293-90.942),posterior putamen(OR=13.700,95%CI 4.489-41.549),hippocampus(OR=7.200,95%CI 1.702-30.813)and caudate nucleus(OR 5.800,95%CI 1.973-16.950)were associated with PWMI and mixed CP.A prediction model was constructed using the above four MRI features.The model yielded an area under the receiver operating characteristic curve of 0.960(95%CI 0.934-0.988)and 0.95,0.96 in the five-fold cross and repeated cross validation,respectively.The model had good calibration(χ2=3.712,P=0.529)and clinical application.Furthermore,the four MRI variables were associated with gross motor function classification system levels(r=0.559,0.581,0.171,0.409,all P<0.05).Conclusion The model can early and accurately predict infants with PWMI at high risk of mixed CP.
10.Staged treatment of infectious femoral defects of Cierny-Mader type Ⅳ using bone transport combined with locking plating after En-Bloc resection debridement
Gang ZHAO ; Wenming LUO ; Baojie LI ; Zhen LIU ; Ping YU ; Xuecheng SUN
Chinese Journal of Orthopaedic Trauma 2024;26(7):597-603
Objective:To investigate the efficacy of staged treatment of infectious femoral defects of Cierny-Mader type Ⅳ using bone transport combined with locking plating after En-Bloc resection debridement.Methods:A retrospective analysis was conducted of the 10 patients with distal femoral traumatic bone infection who had been treated at Department of Orthopedics, The People's Hospital of Weifang from January 2020 to January 2023. There were 8 males and 2 females with an age of (48.5±11.4) years. All cases were classified as Cierny-Mader type Ⅳ. At the first stage, En-Bloc resection debridement was performed in all cases to remove previous internal fixation devices and fill the defects with antibiotic bone cement. After infection control, the second stage involved removal of bone cement, re-fixation with internal devices, and external fixation support for bone transport. After the bone segments met, freshening of the bone ends, minor bone grafting, and screw locking of the transported bone segments were performed. Outcomes observed included bone defect length, frame carrying time and index, bone healing time, limb function, and complications.Results:After the first stage of debridement, a bone defect of (9.1±2.1) cm was created in 10 patients. All patients were followed up for (19.8±6.6) months. The duration for carrying external fixation frame was (107.2±25.1) days, and the frame index (11.8±0.5) d/cm. No recurrence was observed postoperatively. Bone union was achieved in 9 patients within 8 months, but in 1 patient only after secondary bone grafting due to poor healing at the meeting ends. All patients returned to their previous life or physical labor with no complications like pain or re-fracture. Three patients experienced varying degrees of knee joint stiffness, but were able to meet needs of daily life; one requested joint release surgery which resulted in satisfactory therapeutic efficacy.Conclusion:Staged treatment of infectious femoral defects of Cierny-Mader type Ⅳ using bone transport combined with locking plating after En-Bloc resection debridement is simple and effective.

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