1.Mitochondria: The Target of Ionizing Radiation Damage
Lian-Chen TIAN ; Ya-Yi YUAN ; Xu-Hong DANG
Progress in Biochemistry and Biophysics 2025;52(4):836-844
In recent years, due to the development of radiotherapy technology and nuclear energy, people have paid more and more attention to the various effects of ionizing radiation on organisms. Ionizing radiation can induce protein, DNA and other biological macromolecules to damage, resulting in apoptosis, senescence, cancer and a series of changes. For a long time, it has been believed that the main target of ionizing radiation damage is DNA in the nucleus. However, it has been reported in recent years that ionizing radiation has both direct and indirect effects, and the theory of ROS damage in the indirect effects believes that ionizing radiation has target uncertainty, so it is not comprehensive enough to evaluate only the DNA damage in the nucleus. It has been reported that ionizing radiation can cause damage to organelles as well as damage to cells. Mitochondria are important damaged organelles because mitochondria occupy as much as 30% of the entire cell volume in the cytoplasm, which contains DNA and related enzymes that are closely related to cellular ATP synthesis, aerobic respiration and other life activities. What is more noteworthy is that mitochondria are the only organelles in which DNA exists in the human body, which makes researchers pay attention to various damage to mitochondrial DNA caused by ionizing radiation (such as double-strand breaks, base mismatching, and fragment loss). Although these damages also occur in the nucleus, mitochondrial DNA is more severely damaged than nuclear DNA due to its lack of histone protection, so mitochondria are important targets of ionizing radiation damage in addition to the nucleus. Mitochondrial DNA is not protected by histones and has little repair ability. When exposed to ionizing radiation, common deletions occur at an increased frequency and are passed on to offspring. For large-scale mitochondrial DNA damage, mitochondria indirectly compensate for the amount of damaged DNA by increasing the number of DNA copies and maintaining the normal function of mitochondrial DNA. Mitochondria are in a state of oxidative stress after exposure to ionizing radiation, and this oxidative stress will promote the change in mitochondrial function. When mitochondria are damaged, the activity of proteins related to aerobic respiration decreases, and oxidative respiration is inhibited to a certain extent. At the same time, a large amount of active superoxide anions are continuously produced to stimulate mitochondrial oxidative stress, and the signal of such damage is transmitted to the surrounding mitochondria, resulting in a cascade of damage reaction, which further activates the signalling pathway between mitochondria and nucleus. The cell nucleus is also in a state of oxidative stress, and finally, the level of free radicals is high, causing secondary damage to the genetic material DNA of mitochondria and nucleus. In this paper, the damage effects of ionizing radiation on mitochondria are reviewed, to provide a new idea for radiation protection.
2.Research on multi antigen extended matching transfusion in RhCE alloantibody positive patients with blood diseases
Pin YI ; Mingming WANG ; Yi ZHU ; Xintang DANG ; Ziyu OU ; Fan WU ; Chaopeng SHAO ; Changlin WU
Chinese Journal of Blood Transfusion 2025;38(5):678-683
Objective: To analyze the changes in homologous immunity after RhCE-matched transfusion in positive patients with RhCE blood group antibodies, and to provide precise transfusion strategies for chronic anemia patients. Methods: Patients with chronic anemia in our hospital from January 2020 to March 2024 (continuously receiving blood transfusions for more than 6 months) were enrolled, and 63 cases of unexpected antibody screening positive and identified as RhCE blood group antibodies were selected as the research subjects. The changes in unexpected antibody yield rate after ABO and RhCcDEe isotype blood transfusion were observed. Patients with MNS, Kidd, or Lewis blood group antibodies were screened for corresponding negative donors using monoclonal antibodies for extended typing transfusion based on RhCcEe typing, and the changes in unexpected antibody yield rate after transfusion were observed. Blood group genotyping was performed when serological techniques failed to resolve discrepancies or detect abnormal antigen expression. Results: After RhCcDEe-matched transfusions, RhCE antibodies disappeared in 62 patients, while 1 patient developed anti-Ce. The latter did not develop blood type isotype immunity after receiving RhccEE donor blood. Among the 62 patients, 9 developed unexpected antibodies against other systems: anti-M (4 cases), anti-Mur (2), anti-S (1), anti-Jka (1), and anti-Lea (1). No additional alloimmunization occurred after extended antigen-matched transfusions. A patient with serologically weak e phenotype was genotyped as DCe/DcE, with gene sequencing revealing an 827C>A mutation in exon 6 of the RHCE gene, forming the RHCE
01.31 allele. Conclusion: Precise transfusion strategies incorporating RhCE, MNS, Kidd, and Lewis blood group antigen typing can reduce the probability of blood group homologous immunity. RhCE complex antibodies and RhCE variants pose difficulties for clinical RhCE typing transfusion, which can be addressed through cross-matching and genetic analysis.
3.Relationship between type 2 diabetes mellitus and cognitive decline:a 4-year prospective cohort study
Liangjun DANG ; Yi ZHAO ; Ling GAO ; Shan WEI ; Chen CHEN ; Junlong FENG ; Jin WANG ; Kang HUO ; Qiumin QU ; Suhang SHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(5):749-754
Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2%)were free of T2DM,158(11.7%)already had T2DM at baseline,and 96(7.1%)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0%of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7%vs.20.9%vs.26.0%,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95%CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95%CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.
4.Relationships between plasma homocysteine levels and cognitive impairment:a cross-sectional study based on the rural population aged 40 years old and above in Xi'an,China
Yi ZHAO ; Chunyu LI ; Liangjun DANG ; Suhang SHANG ; Jingyi WANG ; Jin WANG ; Qiumin QU ; Wenhui LU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(5):755-762
Objective To investigate the relationship between plasma homocysteine(Hcy)levels and cognitive impairment(CI).Methods From November 2018 to January 2019,baseline data and cognitive function were collected from the participants aged≥40 years who lived in two villages in Huyi District,Xi'an,China.Their global cognitive function was assessed by Mini-Mental State Examination(MMSE)and the diagnosis of cognitive impairment was based on international guidelines.Fasting blood was collected in the morning,and plasma Hcy level was measured by the chemiluminometric assay.Multivariate Logistic regression analysis,subgroup analysis,and interaction analysis were performed to investigate the relationship between plasma Hcy and CI.Results A total of 1 805 subjects were included in the analysis.There were 1 056 females(58.5%),age ranged from 40 to 88 years[mean(58.99±9.52)years],and 145 participants(8.0%)were diagnosed as CI.The median plasma Hcy level in the overall population was 14.1(11.6,17.8)μmol/L.There were 729(40.4%)subjects in the HHcy group(>15.0 μmol/L)and 1 076(59.6%)in the normal group(≤15.0 μmol/L).Univariate analysis showed that the prevalence of CI was higher in the HHcy group than in the normal Hcy group(11.4%vs.5.8%,P<0.001).In multivariable Logistic regression fully adjusted for potential confounders,each 1 μmol/L increase in plasma Hcy level was associated with a 3.0%increased risk of CI(OR=1.030,95%CI:1.012-1.048,P=0.001).Interaction analysis indicated that sex,age,BMI,systolic blood pressure,history of stroke,and diabetes did not significantly modify this association.Conclusion Elevated plasma Hcy levels are associated with an increased risk of CI in people aged≥40 years.This indicates that HHcy may be a risk factor for CI.
5.Serum AGR2 and TMAO levels and their correlation with gut microbiota in children with inflammatory bowel disease
Qinghua DANG ; Lifang GU ; Xianxia ZHANG ; Yi ZHANG ; Ning ZENG
Tianjin Medical Journal 2025;53(2):156-160
Objective To explore the relationship between serum levels of anterior gradient 2(AGR2)and trimethylamine N-oxide(TMAO)and gut microbiota in children with inflammatory bowel disease(IBD).Methods A total of 145 IBD children were selected as the observation group,and children were divided into the ulcerative colitis group(64 cases)and the Crohn's disease group(81 cases)according to the disease type.Meanwhile,140 healthy children underwent physical examination in our hospital were included as the control group.Serum AGR2 and TMAO levels were detected by enzyme-linked immunosorbent assay(ELISA).The disease activity of ulcerative colitis and Crohn's disease were evaluated using the modified Mayo score and the Crohn's Disease Activity Index(CDAI)score,and patients were divided into the active group(75 cases)and the remission group(70 cases)according to the disease activity.Fecal samples were collected for identification and count of intestinal flora.Receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of serum AGR2 and TMAO levels in ulcerative colitis and Crohn's disease.The correlation between serum AGR2 and TMAO levels and intestinal flora was analyzed by Pearson test.Logistic regression was used to analyze the relationship between serum AGR2 and TMAO levels and the disease stage of children with IBD.Results The serum AGR2 level was lower in the ulcerative colitis group and the Crohn's disease group than that in the control group,and the serum TMAO level was higher than that in the control group(P<0.05).The areas under the curve(AUC)of serum AGR2 and TMAO levels were 0.835,0.836 and 0.896 for diagnosis of ulcerative colitis alone and 0.859,0.864 and 0.964 for diagnosis of Crohn's disease.The serum AGR2 level and numbers of lactobacillus and bifidobacterium were significantly lower in the active group than those in the remission group,and the serum TMAO level and numbers of Escherichia coli,enterococcus,Helicobacter pylori and streptococcus were significantly higher in the active group than those in the remission group(P<0.05).Serum AGR2 levels in IBD children were positively correlated with numbers of lactobacillus and bifidobacterium,and negatively correlated with numbers of Escherichia coli,Enterococcus,Helicobacter pylori and streptococcus(P<0.05).Serum TMAO level was negatively correlated with numbers of lactobacillus and bifidobacterium,and positively correlated with numbers of Escherichia coli,Enterococcus,Helicobacter pylori and streptococcus(P<0.05).The decreased serum AGR2 level and the increased TMAO level were risk factors for the disease progression to active stage in children with IBD(P<0.05).Conclusion The combination of serum AGR2 and TMAO can effectively diagnose ulcerative colitis and Crohn's disease,and it is more valuable in the diagnosis of Crohn's disease.Abnormal expression of both may participate in the progression of IBD disease by affecting changes in gut microbiota structure.
6.Establishment of outcome indicators for the implementation of comprehensive inter-vention for multimorbidity of myopia and obesity among children and adolescents based on the RE-AIM framework
Yihang ZHANG ; Shan CAI ; Ziyue CHEN ; Yunfei LIU ; Jiajia DANG ; Di SHI ; Jiaxin LI ; Tianyu HUANG ; Yi SONG
Journal of Peking University(Health Sciences) 2025;57(3):436-441
Objective:To develop outcome indicators for the implementation of comprehensive inter-ventions targeting the multimorbidity of myopia and obesity in children and adolescents,providing a basis for the co-prevention of multimorbidity and the outcome measurement of implementation research in children and adolescents.Methods:Based on the RE-AIM framework,a preliminary set of indicators was constructed.The Delphi method was employed,with experts scoring and providing feedback on the proposed indicators via questionnaires.After each round of consultation,expert enthusiasm index,authority coefficient,coordination degree,and consensus level were calculated.Expert opinions were col-lected and analyzed to modify,delete,or add indicators based on consultation results and screening crite-ria.Two Delphi rounds were conducted until consensus was achieved.Results:A total of 28 experts par-ticipated actually in both rounds.The Kendall's W coefficients for the two rounds of expert consultation were0.352(x2=413.952,P<0.001)and 0.499(x2=405.044,P<0.001),both statistically sig-nificant.The final outcome indicators for implementation research on comprehensive interventions for myopia and obesity comorbidity in children and adolescents included five primary dimensions with 13 secondary and 20 tertiary indicators.The dimension of reach included the number of children and adoles-cents involved,participant representativeness,and full-course participation representativeness.The di-mension of effectiveness included multimorbidity incidence,myopia incidence,spherical equivalent,body mass index(BMI),overweight and obesity prevalence,waist-to-height ratio,comprehensive health knowledge score,and comprehensive health behavior score.The dimension of adoption covered school representativeness and representativeness of school nurses and teachers involved in implementation.The dimension of implementation included fidelity,content modification,and cost.The dimension of mainte-nance included individual health outcomes and organizational sustainment.Conclusion:This study developed implementation outcome indicators for comprehensive interventions targeting multimorbidity of myopia and obesity among the children and adolescents based on the RE-AIM framework.These indica-tors can serve as a reference for optimizing intervention research strategies related to common multimor-bidity among children and adolescents in China.
7.APIC risk management and application for hospital-acqueird infections in 'one hospital and multiple branches'
Ningwei LU ; Xiaoru DANG ; Shuxia YU ; Yi LI ; Nannan WANG ; Jiaying SHEN ; Xiaoying WANG ; Yanfen LIU
Chinese Journal of Nosocomiology 2025;35(14):2194-2199
OBJECTIVE To explore the application of multiple hospital branches management mode in control of risk of hospital-acqueird infections in a general hospital so as to move forward the infection control threshold.METHODS The risk management closed loop,known as the infection index monitoring-risk assessment-risk re-sponse-effect evaluation-infection index monitoring,was adopted by People's Hospital of Ningxia Hui Autono-mous Region from Jan.to Jun.2024.The risk of infection at different levels of hospital zones,disciplines,clinical departments and risk indices was evaluated by risk matrix method.The correlation between the risk indices of clin-ical department and the risk scores was observed,and the dynamic monitoring was carried out for the change of risk of infection in the clinical departments.RESULTS The risk score was higher in the headquarter and Ningnan Branch than in the Xixia branch;the interquartile range(IQR)value from high to low was as follows:Xixia branch,hospital headquarter,Ningnan branch.The intensive care unit(ICU),nerve center and radiotherapy de-partment were the disciplines at extremely high risk of infection.The ICU,cardiac vascular surgery department and gastroenterology department of the hospital headquarters,the ICU,neurosurgery department and neurology department of Ningnan branch and the ICU and cardiac vascular surgery department of Xixia branch were the de-partments at extremely high risk of infection.The etiological submission rate before drug therapy,implementation of prevention measures for multidrug-resistant organisms(MDROs),cleaning and disinfection and missing report of hospital-acqueird infection cases were the major supervision indices.The absolute values of Spearman related co-efficient between clinical department risk scores and 4 indices-including the isolation rate of MDROs and the inci-dence of hospital-acqueird infection was greater than 0.5.CONCLUSION The risk management closed loop that is applied in the 'one hospital and multiple branches' medical institution may facilitate the dynamic monitoring,as-sessment and intervention the high-risk hospital branches,disciplines,departments and indices,and boost the ca-pability of risk management of infections in medical institutions.
8.The influence of holmium laser enucleation of the prostate with early complete transection of the urethral mucosa at the tip of the prostate on urinary control function and sexual function in patients with benign prostatic hyperplasia
Binbin ZHANG ; Lingling DU ; Xiaolong HE ; Yi LI ; Yantao DANG ; Jixue GAO ; Feng WANG ; Junqi JIA
Journal of Chinese Physician 2025;27(4):561-567
Objective:To explore the effects of holmium laser enucleation of the prostate with early complete transection of the urethral mucosa at the tip of the prostate on urinary control function and sexual function in patients with benign prostatic hyperplasia (BPH).Methods:Eighty patients with BPH who underwent holmium laser enucleation of the prostate in the Affiliated Hospital of Yan′an University from January 2019 to January 2023 were collected as the research subjects. The patients were divided into the observation group and the control group by the random number table method, with 40 cases in each group. The observation group underwent early holmium laser enucleation of the prostate with early complete transection of the urethral mucosa at the tip of the prostate, while the control group underwent conventional holmium laser prostatectomy. The general conditions, urinary control function and sexual function of the two groups of patients after the operation were compared. The adverse ejaculation conditions 6 months after the operation were recorded.Results:There was no statistically significant difference in age and prostate volume between the two groups of patients (all P>0.05). The operation time, intraoperative blood loss, postoperative indwelling urinary catheter time and postoperative hospital stay in the observation group were significantly less than those in the control group (all P<0.05). The International Prostate Symptom Scale (IPSS) score, Quality of Life (QOL) score, the maximum flow rate (Qmax), and post void residual (PVR) in the bladder of the two groups of patients 6 months after the operation were compared with those before the operation, and the differences were statistically significant (all P<0.05), while there were no statistically significant differences between the groups (all P>0.05). There were no statistically significant differences in the International Index of Erectile Function (IIEF-5) scores and Erection Hardness Grading Scale (EHGS) grades of the two groups of patients 6 months after surgery compared with those before surgery (all P>0.05), and there were also no statistically significant differences between the groups (all P>0.05). There was no statistically significant difference in the ejaculation function score and ejaculation distress score 6 months after the operation in the observation group compared with those before the operation (all P>0.05), while in the control group, the ejaculation function score 6 months after the operation was lower than that before the operation, and the ejaculation distress score was higher than that before the operation (all P<0.05). The ejaculation function score and ejaculation distress score of the observation group 6 months after the operation were significantly better than those of the control group (all P<0.05). The incidences of retrograde ejaculation and reduced semen volume 6 months after the operation in the observation group were both lower than those in the control group (all P<0.05). There was no statistically significant difference in the incidence of rapid ejaculation, ejaculation pain, hematospermia, etc. between the two groups of patients 6 months after the operation (all P>0.05). Conclusions:In holmium laser enucleation of the prostate, early complete transection of the urethral mucosa at the tip of the prostate has an improving effect on urinary control function and sexual function in patients with BPH, and increases the confidence in postoperative life and satisfaction with orgasm of BPH patients.
9.Leptin promotes breast cancer cell MCF-7 migration and invasion through inhibiting ACSL5
Tao ZENG ; Lan WEI ; Yong-zhu XU ; Shi-yu YANG ; Hao-li SUN ; Ting-ting DANG ; Yi-qing YOU ; Jia-feng TANG ; Yan ZHANG
Chinese Pharmacological Bulletin 2025;41(4):654-660
Aim To explore the possible regulatory effect of leptin on acyl-CoA synthetase long chain fami-ly member ACSL5 and their effect on migration and in-vasion of breast cancer cell,and to explore the underly-ing mechanism.Methods The expression of leptin receptor was detected by immunofluorescence assay.The migration and invasion ability of MCF-7 cells were detected by wound healing assay and Transwell assay respectively.The downstream target gene of leptin was analyzed by PCR microarray data.The expression of ACSL5 in breast cancer and its correlation with the staging and prognosis of breast cancer patients were as-sessed uing bioinformatics methods.The expression of ACSL5 in MCF-7 cells treated with different concentra-tions of leptin was detected using real time fluorescence quantitative polymerase chain reaction(RT-qPCR).Overexpressing ACSL5 was constructed by lentiviral transfection;the expressions of EMT related proteins,AMPK-α and p-AMPK-α were detected by Western blot.Results Leptin promoted breast cancer cell mi-gration and invasion and EMT.ACSL5 was significant-ly low expressed in breast cancer and related to progno-sis.Leptin downregulated the expression of ACSL5 through OBR.Leptin activated AMPK pathway to downregulate ACSL5 and promote migration,invasion and EMT of breast cancer cells.Conclusions Leptin may promote the migration,invasion and EMT of breast cancer by downregulating ACSL5 through activating AMPK pathway.
10.APIC risk management and application for hospital-acqueird infections in 'one hospital and multiple branches'
Ningwei LU ; Xiaoru DANG ; Shuxia YU ; Yi LI ; Nannan WANG ; Jiaying SHEN ; Xiaoying WANG ; Yanfen LIU
Chinese Journal of Nosocomiology 2025;35(14):2194-2199
OBJECTIVE To explore the application of multiple hospital branches management mode in control of risk of hospital-acqueird infections in a general hospital so as to move forward the infection control threshold.METHODS The risk management closed loop,known as the infection index monitoring-risk assessment-risk re-sponse-effect evaluation-infection index monitoring,was adopted by People's Hospital of Ningxia Hui Autono-mous Region from Jan.to Jun.2024.The risk of infection at different levels of hospital zones,disciplines,clinical departments and risk indices was evaluated by risk matrix method.The correlation between the risk indices of clin-ical department and the risk scores was observed,and the dynamic monitoring was carried out for the change of risk of infection in the clinical departments.RESULTS The risk score was higher in the headquarter and Ningnan Branch than in the Xixia branch;the interquartile range(IQR)value from high to low was as follows:Xixia branch,hospital headquarter,Ningnan branch.The intensive care unit(ICU),nerve center and radiotherapy de-partment were the disciplines at extremely high risk of infection.The ICU,cardiac vascular surgery department and gastroenterology department of the hospital headquarters,the ICU,neurosurgery department and neurology department of Ningnan branch and the ICU and cardiac vascular surgery department of Xixia branch were the de-partments at extremely high risk of infection.The etiological submission rate before drug therapy,implementation of prevention measures for multidrug-resistant organisms(MDROs),cleaning and disinfection and missing report of hospital-acqueird infection cases were the major supervision indices.The absolute values of Spearman related co-efficient between clinical department risk scores and 4 indices-including the isolation rate of MDROs and the inci-dence of hospital-acqueird infection was greater than 0.5.CONCLUSION The risk management closed loop that is applied in the 'one hospital and multiple branches' medical institution may facilitate the dynamic monitoring,as-sessment and intervention the high-risk hospital branches,disciplines,departments and indices,and boost the ca-pability of risk management of infections in medical institutions.

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