1.Mechanisms of mitochondrial dynamics in ischemic stroke and therapeutic strategies.
Xin-Yue ZHENG ; Ming ZHANG ; Kai-Qi SU ; Zhi-Min DING
Acta Physiologica Sinica 2025;77(3):523-533
As a common neurological disease in China, stroke has an extremely high rate of death and disability, of which 80% is ischemic stroke (IS), causing a serious burden to individuals and society. Neuronal death is an important factor in the pathogenesis of stroke. Studies have shown that mitochondrial dynamics, as a key mechanism regulating intracellular energy metabolism and cell death, plays an important role in the pathogenesis of IS. In recent years, targeting mitochondrial dynamics has become an emerging therapeutic tool to improve neurological impairment after stroke. This paper reviews the research advance in recent years in IS mitochondrial dynamics, summarizing and discussing the overview of mitochondrial dynamics, the role of mitochondrial dynamics in IS, and the studies on mitochondrial dynamics-based treatment of IS. This paper helps to explore the mechanism of the role of mitochondrial dynamics in IS and effective interventions, and provides a theoretical strategy for targeting mitochondrial dynamics to treat IS in the clinic.
Humans
;
Mitochondrial Dynamics/physiology*
;
Ischemic Stroke/metabolism*
;
Mitochondria/physiology*
;
Animals
;
Brain Ischemia/physiopathology*
;
Energy Metabolism
2.Risk factor analysis and nomogram prediction model construction for pneumonia complicating infectious mononucleosis in adults
Fei HU ; Mei-Juan PENG ; Xu-Yang ZHENG ; Rui LI ; Jia-Yi ZHAN ; Hai-Feng HU ; Hong-Kai XU ; Deng-Hui YU ; Hong DU ; Jian-Qi LIAN
Medical Journal of Chinese People's Liberation Army 2025;50(11):1359-1365
Objective To investigate the risk factors for pneumonia complicating infectious mononucleosis(IM)in adults and construct a nomogram prediction model.Methods A retrospective analysis was conducted on 198 IM patients admitted to the Second Affiliated Hospital of Air Force Medical University from January 2015 to December 2021.Patients were divided into pneumonia group(n=52)and non-pneumonia group(n=146)based on whether pulmonary infection occurred during hospitalization.The baseline data(age,gender,place of onset,etc.),clinical manifestations(maximum body temperature,lymph node enlargement,splenomegaly,etc.),and inflammatory indicators[white blood cell count(WBC),C-reactive protein(CRP),etc.]were compared between the two groups.Kaplan-Meier curves were plotted to analyze the key indicators affecting the hospital stay of IM patients.Multivariate logistic regression was used to analyze the independent risk factors for pneumonia complicating IM in adults and construct a nomogram prediction model based on the identified risk factors.The predictive efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve and the consistency of the model was assessed using the calibration curve.The fit of the model was evaluated using the Hosmer-Lemeshow test.Additionally,the sensitivity,specificity,and accuracy of the model were assessed using confusion matrix.Results Compared with non-pneumonia group,the pneumonia group had a significantly higher proportion of patients from rural areas,with body mass index(BMI)≥24 kg/m2,smoking history,hepatomegaly,fever duration of≥7 d,as well as increased total hospitalization costs and average daily hospitalization costs,and prolonged hospital stay(P<0.05).The proportion of patients with a history of antibiotic use was lower in the pneumonia group(P<0.05).Kaplan-Meier survival analysis showed that patients from rural areas,with BMI≥24 kg/m2,smoking history,no prophylactic use of antibiotics,fever duration≥7 d,and hepatomegaly had significantly prolonged hospital stays(P<0.05).Multivariate logistic regression analysis revealed that living in a rural area(OR=4.089,P<0.05),hepatomegaly(OR=4.082,P<0.05),and elevated WBC(OR=1.205,P<0.05)were independent risk factors for pneumonia complicating IM in adults,while the prophylactic use of antibiotics(OR=0.142,P<0.05)was an independent protective factor.The area under the ROC curve of the constructed nomogram prediction model was 0.827(95%CI 0.762-0.892),and the slope of the calibration curve was close to 1,and the Hosmer-Lemeshow test showed χ2=5.299,P=0.725,indicating good consistency and fit of the prediction model.The results of the confusion matrix assessment showed that the sensitivity of the model was 0.669(0.624-0.773),the specificity was 0.827(0.724-0.930),and the accuracy was 0.732(0.665-0.793).Conclusion The nomogram prediction model based on place of onset,hepatomegaly,the prophylactic use of antibiotics and WBC has excellent fit and discrimination,providing an effective quantitative tool for prognosis assessment of IM.
3.CNV Encompassing SNP Detection by Cross-reactivity Probe
Xiao-Mei HU ; Chen ZHOU ; Pin-Zheng ZHANG ; Yang CHEN ; Jia-Wen LI ; Yu-Kai MA ; Jia-Qi WANG ; Zhi-Yi GUO
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):895-902
Copy number variation encompassing SNP plays an important role in IVD and precision medi-cine.As the most commonly used method,FISH could not overcome the probe cross-reactivity which is common when to detect SNP.Here we developed a quantitative and qualitative method on copy number variation encompassing SNP.In this study,the rs76711854 was used as an example to establish a quanti-tative method by advantage of probe cross-reactivity.The fragment encompassing rs76711854 and its downstream to 9 514 bp were amplified by PCR.The allelic genotypes were verified by Sanger sequen-cing.Different probes with or without cross-reactivity to be used via quantitative real-time PCR and digit-al PCR.The different clusters(2D)and fluorescence intensity layers(1D)exist by adding probe with cross-reactivity.The A/G ratio measured by digital PCR is 2︰1,which is verified by probe targeting to the SNP.The copy-number variant exists in the 9kb-long fragment upstream to the SNP of prostate cancer cell line but not in human endometrial adenocarcinoma cell line Ishikawa.The data suggest that there is a multi-copy variation at this locus in DU145 cells.The method applied here is based on one single cross-reactivity probe via digital PCR.
4.The Role of Zinc Finger Structure Transcription Factors ZNF148 and SP5 on P53 Transcriptional Activity
Dai-Wei WANG ; Chen ZHOU ; Pin-Zheng ZHANG ; Xu-Ying WANG ; Jia-Wen LI ; Yu-Kai MA ; Jia-Qi YAN ; Zhi-Ting WANG ; Jia-Qi WANG ; Zhi-Yi GUO
Chinese Journal of Biochemistry and Molecular Biology 2025;41(5):707-715
P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8%)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P<0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1%and 35.7%(P<0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.
5.Effect of rosavin on hepatocellular steatosis and its underlying mechanism
Shen WANG ; Jin-hui CAI ; Lin ZHENG ; Yan ZHANG ; Kai-qing ZENG ; Qi-en XU ; Yan-min FENG ; Xiao-xia YE
Chinese Pharmacological Bulletin 2025;41(3):466-474
Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.
6.Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury (version 2025)
Kai HUANG ; Lunhao BAI ; Qing BI ; Hong CHEN ; Jiwu CHEN ; Xuesong DAI ; Wenyong FEI ; Weili FU ; Zhizeng GAO ; Lin GUO ; Yinghui HUA ; Jingmin HUANG ; Suizhu HUANG ; Xuan HUANG ; Jian LI ; Qiang LI ; Shuzhen LI ; Yanlin LI ; Yunxia LI ; Zhong LI ; Ning LIU ; Yuqiang LIU ; Wei LU ; Hongbin LYU ; Haile PAN ; Xiaoyun PAN ; Chao QI ; Weiliang SHEN ; Luning SUN ; Jin TANG ; Zimin WANG ; Bide WANG ; Ru WANG ; Shaobai WANG ; Licheng WEI ; Weidong XU ; Yongsheng XU ; Jizhou YANG ; Liang YANG ; Rui YANG ; Hongbo YOU ; Tengbo YU ; Jiakuo YU ; Bing YUE ; Hua ZHANG ; Hui ZHANG ; Qingsong ZHANG ; Xintao ZHANG ; Jiajun ZHAO ; Lilian ZHAO ; Qichun ZHAO ; Song ZHAO ; Jiapeng ZHENG ; Jiang ZHENG ; Zhi ZHENG ; Jingbin ZHOU ; Jinzhong ZHAO
Chinese Journal of Trauma 2025;41(4):325-338
With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.
7.Comparison of postoperative inflammatory markers and surgical outcomes between open reduction and internal fixation versus double reverse traction closed reduction and percutaneous internal fixation for tibial plateau fractures
Tailong SHI ; Kai DING ; Peizhi YUWEN ; Zhanle ZHENG ; Hongzhi LYU ; Yanbin ZHU ; Qi ZHANG ; Wei CHEN ; Zhiyong HOU ; Yingze ZHANG
Chinese Journal of Orthopaedic Trauma 2025;27(2):125-132
Objective:To compare postoperative inflammatory markers and surgical outcomes between open reduction and internal fixation versus double reverse traction closed reduction and percutaneous internal fixation for tibial plateau fractures.Methods:A retrospective analysis was conducted of the data of 229 patients with tibial plateau fracture who had been admitted to Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University from January 2023 to December 2023. There were 155 males and 74 females with an age of (48.7±10.9) years. According to the surgical methods, the patients were divided into 2 groups. A conventional group of 87 cases were treated by open reduction and internal fixation while a minimally invasive group of 142 cases treated with double reverse traction closed reduction and percutaneous internal fixation. The 2 groups were compared in terms of hematological indexes [white blood cell count (WBC), neutrophil count (NEUT), lymphocyte count (LYM), monocyte count (Mono), platelet count (PLT), and albumin (ALB)] and composite inflammatory indexes [neutrophil to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI)] before operation and on the first day after operation, intraoperative blood loss, operation time, fracture healing time, Hospital for Special Surgery (HSS) knee score and incidence of thrombosis.Results:There were no significant differences in baseline characteristics or treatment variables between the 2 groups, indicating comparability ( P > 0.05). All the 229 patients were followed up for (16.5±2.8) months. In each group, comparisons between preoperation and postoperation showed that LYM and ALB significantly decreased while WBC, NEUT, Mono, PLT, NLR, PLR, SII and SIRI significantly increased on the first day after operation ( P < 0.05). Preoperatively, there were no significant differences between the 2 groups in terms of hematological or composite inflammatory indexes ( P > 0.05). On the first day after operation, there was no significant difference in WBC, NEUT, LYM, ALB or NLR between the 2 groups ( P > 0.05), but Mono, PLT, PLR, SII and SIRI in the minimally invasive group were significantly lower than those in the conventional group ( P < 0.05). The intraoperative blood loss, operation time, fracture healing time, HSS knee score and incidence of thrombosis in the minimally invasive group were significantly better than those in the conventional group ( P < 0.05). Conclusion:In the treatment of tibial plateau fractures, compared with conventional open reduction and internal fixation, double reverse traction closed reduction and percutaneous internal fixation shows obvious advantages in reducing inflammatory indicators and leads to better surgical outcomes.
8.CNV Encompassing SNP Detection by Cross-reactivity Probe
Xiao-Mei HU ; Chen ZHOU ; Pin-Zheng ZHANG ; Yang CHEN ; Jia-Wen LI ; Yu-Kai MA ; Jia-Qi WANG ; Zhi-Yi GUO
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):895-902
Copy number variation encompassing SNP plays an important role in IVD and precision medi-cine.As the most commonly used method,FISH could not overcome the probe cross-reactivity which is common when to detect SNP.Here we developed a quantitative and qualitative method on copy number variation encompassing SNP.In this study,the rs76711854 was used as an example to establish a quanti-tative method by advantage of probe cross-reactivity.The fragment encompassing rs76711854 and its downstream to 9 514 bp were amplified by PCR.The allelic genotypes were verified by Sanger sequen-cing.Different probes with or without cross-reactivity to be used via quantitative real-time PCR and digit-al PCR.The different clusters(2D)and fluorescence intensity layers(1D)exist by adding probe with cross-reactivity.The A/G ratio measured by digital PCR is 2︰1,which is verified by probe targeting to the SNP.The copy-number variant exists in the 9kb-long fragment upstream to the SNP of prostate cancer cell line but not in human endometrial adenocarcinoma cell line Ishikawa.The data suggest that there is a multi-copy variation at this locus in DU145 cells.The method applied here is based on one single cross-reactivity probe via digital PCR.
9.Effect of rosavin on hepatocellular steatosis and its underlying mechanism
Shen WANG ; Jin-hui CAI ; Lin ZHENG ; Yan ZHANG ; Kai-qing ZENG ; Qi-en XU ; Yan-min FENG ; Xiao-xia YE
Chinese Pharmacological Bulletin 2025;41(3):466-474
Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.
10.The Role of Zinc Finger Structure Transcription Factors ZNF148 and SP5 on P53 Transcriptional Activity
Dai-Wei WANG ; Chen ZHOU ; Pin-Zheng ZHANG ; Xu-Ying WANG ; Jia-Wen LI ; Yu-Kai MA ; Jia-Qi YAN ; Zhi-Ting WANG ; Jia-Qi WANG ; Zhi-Yi GUO
Chinese Journal of Biochemistry and Molecular Biology 2025;41(5):707-715
P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8%)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P<0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1%and 35.7%(P<0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.

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