1.SIRT5 Potentiates Hepatocarcinogenesis by Modulating Protein Acylation in Mice
Yu ZHANG ; Feng-Rui REN ; Jia-Yun LI ; Xiang-Yu CHEN ; Zi-Yi WANG ; Qi SUN ; Jun-Cheng ZHAO ; Ye ZHANG ; Zhen HUANG ; Hao HU ; Tao-Tao WEI ; Min XIAO
Progress in Biochemistry and Biophysics 2026;53(6):1712-1722
ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.
2.Application of Non-invasive Deep Brain Stimulation in Parkinson’s Disease Treatment
Yu-Feng ZHANG ; Wei WANG ; Zi-Jun LU ; Jiao-Jiao LÜ ; Yu LIU
Progress in Biochemistry and Biophysics 2025;52(5):1196-1205
Parkinson’s disease (PD) is a common neurodegenerative disorder that significantly impacts patients’ independence and quality of life, imposing a substantial burden on both individuals and society. Although dopaminergic replacement therapies provide temporary relief from various symptoms, their long-term use often leads to motor complications, limiting overall effectiveness. In recent years, non-invasive deep brain stimulation (DBS) techniques have emerged as promising therapeutic alternatives for PD, offering a means to modulate deep brain regions with high precision without invasive procedures. These techniques include temporal interference stimulation (TIs), low-intensity transcranial focused ultrasound stimulation (LITFUS), transcranial magneto-acoustic stimulation (TMAS), non-invasive optogenetic modulation, and non-invasive magnetoelectric stimulation. They have demonstrated significant potential in alleviating various PD symptoms by modulating neural activity within specific deep brain structures affected by the disease. Among these approaches, TIs and LITFUS have received considerable attention. TIs generate low-frequency interference by applying two slightly different high-frequency electric fields, targeting specific brain areas to alleviate symptoms such as tremors and bradykinesia. LITFUS, on the other hand, uses low-intensity focused ultrasound to non-invasively stimulate deep brain structures, showing promise in improving both motor function and cognition in PD patients. The other three techniques, while still in early research stages, also hold significant promise for deep brain modulation and broader clinical applications, potentially complementing existing treatment strategies. Despite these promising findings, significant challenges remain in translating these techniques into clinical practice. The heterogeneous nature of PD, characterized by variable disease progression and individualized treatment responses, necessitates flexible protocols tailored to each patient’s unique needs. Additionally, a comprehensive understanding of the mechanisms underlying these treatments is crucial for refining protocols and maximizing their therapeutic potential. Personalized medicine approaches, such as the integration of neuroimaging and biomarkers, will be pivotal in customizing stimulation parameters to optimize efficacy. Furthermore, while early-stage clinical trials have reported improvements in certain symptoms, long-term efficacy and safety data are limited. To validate these techniques, large-scale, multi-center, randomized controlled trials are essential. Parallel advancements in device design, including the development of portable and cost-effective systems, will improve patient access and adherence to treatment protocols. Combining non-invasive DBS with other interventions, such as pharmacological treatments and physical therapy, could also provide a more comprehensive and synergistic approach to managing PD. In conclusion, non-invasive deep brain stimulation techniques represent a promising frontier in the treatment of Parkinson’s disease. While they have demonstrated considerable potential in improving symptoms and restoring neural function, further research is needed to refine protocols, validate long-term outcomes, and optimize clinical applications. With ongoing technological and scientific advancements, these methods could offer PD patients safer, more effective, and personalized treatment options, ultimately improving their quality of life and reducing the societal burden of the disease.
3.Review of application scope of mobile medical devices combined with EMA method for lung cancer patient caring
Zi-dan WANG ; Hong-yue WU ; Bing LI ; Xin-tong ZHENG ; Jun-ling LIU ; Ying-nan ZHAO ; Yan LI
Chinese Medical Equipment Journal 2025;46(10):71-77
Relevant literature on mobile medical devices combined with the ecological momentary assessment(EMA)method applied to lung cancer patient caring was collected from some databases of CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Embase,Cochrane Library,CINAHL and Web of Science.The method of scoping review was used to sort out the general characteristics of the included literature,types and application of mobile medical devices,assessment content elements and outcome indicators.The feasibility and validity of mobile medical devices combined with the EMA method for the symptom assessment of lung cancer patients were described,whose advantages in monitoring during lung cancer caring and application prospects were elaborated.The problems of mobile medical devices during practical application were pointed out and some countermeasures were put forward accordingly.References were provided for personalized remote caring of lung cancer patients and development of intelligent multi-modal mobile devices.[Chinese Medical Equipment Journal,2025,46(10):71-77]
4.Mini Health Technology Assessment report standardizes:The optimization and selection of key items
Zi-yi WANG ; Ya-fang LI ; Wen-di LIU ; Jia-yi HUANG ; Fa-qiang ZHANG ; Jun-liang TAO ; Ye ZHU ; Ke-hu YANG ; Xiu-xia LI
Chinese Journal of Health Policy 2025;18(10):75-82
Objective:To construct a key item checklist for the Mini-HTA report specification,providing scientific guidance for drafting each section of Mini-HTA research reports,enhancing their standardization,scientific rigor,and completeness,thereby improving the efficiency and quality of health decision-making.Methods:Based on preliminary literature review and qualitative systematic review,a pool of problem items for the Mini-HTA report specification was formed.Delphi questionnaires were distributed,and the Delphi technique was employed through two rounds of expert consultation to optimize and select key items.Results:Through two rounds of Delphi expert consultation,the initial Mini-HTA report specification item checklist was screened,integrated,and supplemented.A finalized key item checklist was constructed,comprising 8 first-level items(Title,Abstract,Introduction,Methods,Results,Discussion,Conclusion,and Other Relevant Information)and 48 second-level items.Conclusion:The constructed key item checklist for the Mini-HTA report specification provides scientific guidance for drafting Mini-HTA research reports.It helps enhance the standardization and transparency of the assessment process and the reliability of results,thereby optimizing the efficiency and quality of health decision-making.
5.Research progress on the addictivity and neurotoxicity of ketamine
Zhian ZI ; Tingyi ZHAO ; Gongwu WANG ; Jun CAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(9):1233-1242
As a new type of rapid antidepres-sant,ketamine has provided a new approach for the treatment and research on the pathological mechanism of major depressive disorder.However,the addictive potential and neurotoxicity of ket-amine have become issues that cannot be ignored in clinical medication.This article briefly introduces the relevant research progress on ketamine addic-tion and neurotoxicity mechanisms at home and abroad,hoping to provide a reference for the ratio-nal development and utilization of ketamine.
6.Extraction process optimization,component analysis and biological activity evaluation for total polyphenols from Conioselinum vaginatu
Jun-long WANG ; Hui-jie YAN ; Yong-gang LIN ; Zi-wei LI ; Wen-pan SHI ; Sheng-qi JIANG ; Bin WU ; Qin-ze GU
Chinese Traditional Patent Medicine 2025;47(5):1449-1455
AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69%for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70%,85.97%,28.60%,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23%,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.
7.Application of Targeted mRNA Sequencing in Fusion Genes Diagnosis of Hematologic Diseases
Man WANG ; Ling ZHANG ; Yan CHEN ; Jun-Dan XIE ; Hong YAO ; Li YAO ; Jian-Nong CEN ; Zi-Xing CHEN ; Su-Ning CHEN ; Hong-Jie SHEN
Journal of Experimental Hematology 2025;33(4):1209-1216
Objective:To explore the application of targeted mRNA sequencing in fusion gene diagnosis of hematologic diseases.Methods:Bone marrow or peripheral blood samples of 105 patients with abnormally elevated eosinophil proportions and 291 acute leukemia patients from January 2015 to June 2023 in the First Affiliated Hospital of Soochow University were analyzed and gene structural variants were detected by targeted mRNA sequencing.Results:Among 105 patients with abnormally elevated eosinophil proportions,6 cases were detected with gene structural variants,among which fusion gene testing results in 5 cases could serve as diagnostic indicators for myeloid neoplasms with eosinophilia.In addition,a IL3::ETV6 fusion gene was detected in one patient with chronic eosinophilic leukemia,not otherwise specified.Among 119 patients with acute myeloid leukemia(AML),38 cases were detected structural variants by targeted mRNA sequencing,accounting for 31.9%,which was significantly higher than 20.2%(24/119)detected by multiple quantitative PCR(P<0.05).We also found one patient with AML had both NUP98::PRRX2 and KCTD5::JAK2 fusion genes.A total of 104 patients were detected structural variants by targeted mRNA sequencing in 172 cases with acute B-lymphoblastic leukemia who were tested negative by multiple quantitative PCR,with a detection rate of 60.5%(102/172).Conclusion:Targeted mRNA sequencing can effectively detect fusion gene and has potential clinical application value in diagnosis and classificatation in hematologic diseases.
8.Therapeutic effect of external counterpulsation on cardiac rehabilitation in patients with coronary heart disease-a meta-analysis
Wei-tao WANG ; Tie-jun LIU ; Zi-shuang LIU ; Xi-lian HU ; Cheng YANG ; La-di SUN
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(2):172-179
Objective:To evaluate the clinical rehabilitation effect of external counterpulsation(ECP)on patients with coronary heart disease(CHD)by meta-analysis.Methods:We searched the databases of CNKI,WanFang,VIP,CBM,PubMed,Web of Science,Cochrane Library and Embase for randomized controlled trials(RCTs)and prospective cohort studies upon rehabilitative effect of ECP on CHD patients before May 2024.And meta-analysis was conducted to calculate the pooled MD and 95%CI using the random(P<0.5 or I2≥50%)or fixed effect models(other situations).Results:13 eligible literatures were finally included in the meta-analysis.Compared with participants in control group,those in trial group had significant higher left ventricular ejection fraction(MD=4.15,95%CI 2.55~5.76,P<0.001),stroke volume(MD=9.11,95%CI 7.59~10.64,P<0.001),peak oxygen uptake(MD=5.42,95%CI 2.53~8.32,P<0.001),6-min walking distance(MD=31.14,95%CI 24.89~37.40,P<0.001),metabolic equiv-alent(MD=0.58,95%CI 0.45~0.71,P<0.001),exercise duration time(SMD=0.77,95%CI 0.55~0.99,P<0.001),oxygen pulse(MD=0.88,95%CI 0.68~1.09,P<0.001),and significant lower left ventricular end-diastolic diameter(MD=-3.19,95%CI-5.20~-2.61,P<0.001).Conclusion:This study showed that ECP could effectively improve heart function,exercise capacity and tolerance of CHD patients.
9.Evaluation of a deep learning-driven centerline extraction algorithm for optimizing the diagnosis of the"gray zone"in noninvasive coronary fractional flow reserve
Zi-qiang GUO ; Xi WANG ; Zi-nuan LIU ; Yi-pu DING ; Ran XIN ; Dong-kai SHAN ; Jun GUO ; Yun-dai CHEN ; Jun-jie YANG
Chinese Journal of Interventional Cardiology 2025;33(6):312-318
Objective To evaluate the diagnostic performance of the minimum-cost-path-based CT angiography-derived fractional flow reserve(MCP-FFR)and the deep learning-driven CT angiography-derived fractional flow reserve(DeepCL-FFR),and to particularly explore the potential value of the DeepCL algorithm in improving diagnostic accuracy within the"gray zone."Methods A retrospective analysis was conducted on 151 coronary vessels from 109 patients with coronary artery disease,who were hospitalized at the General Hospital of the People's Liberation Army between January 2020 and June 2021.Pearson correlation and Bland-Altman plots were employed to assess the correlation and agreement of the two CT-FFR methods with invasive FFR.A CT-FFR range of 0.70-0.80 was defined as the diagnostic"gray zone."The accuracy,sensitivity,specificity,positive predictive value,and negative predictive value for detecting hemodynamic abnormalities were calculated and analyzed.The DeLong test was used to compare the areas under the receiver operating characteristic curves(AUC)between the two CT-FFR calculation methods.Results Both CT-FFR methods exhibited a positive correlation with invasive FFR(MCP-FFR:r=0.75,P<0.001;DeepCL-FFR:r=0.86,P<0.001)and showed good agreement(MCP-FFR:mean difference=0.010,P=0.351;DeepCL-FFR:mean difference=-0.003,P=0.772).Both DeepCL-FFR(AUC 0.97,95%CI 0.94-0.99)and MCP-FFR(AUC 0.92,95%CI 0.88-0.97)demonstrated favorable diagnostic performance for detecting hemodynamic abnormalities(P=0.122).In the"gray zone"for hemodynamic abnormality,the diagnostic accuracy of MCP-FFR was 68.8%,whereas DeepCL-FFR increased it to 89.7%.DeepCL-FFR also exhibited superior diagnostic performance(AUC 0.89,95%CI 0.73-0.99)within the"gray zone,"which was significantly higher than that of MCP-FFR(AUC 0.71,95%CI 0.54-0.87)(P<0.001).Conclusions The deep learning-driven coronary centerline extraction algorithm,DeepCL,demonstrates superior diagnostic performance in CT-FFR for detecting hemodynamic abnormalities,particularly by significantly improving diagnostic accuracy in the"gray zone."
10.Tonifying kidney and activating blood therapy for the treatment of diabetic erectile dysfunction:A systematic review and meta-analysis
Mao-ke CHEN ; Ke-cheng LI ; Jun-long FENG ; Xiang-fa LIN ; Wen-xuan DONG ; Zi-xiang GAO ; Hua-nan ZHANG ; Hui CHEN ; Ji-sheng WANG ; Bin WANG
National Journal of Andrology 2025;31(9):832-840
Objective:To systematically evaluate the clinical efficacy and safety of Tonifying kidney and activating blood thera-py for the treatment of diabetic mellitus erectile dysfunction.Methods:China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP,Chinese Biomedical Database(CBM),PubMed,Cochrane Library,Embase and Web of Science were searched from incep-tion until October 20th of 2024,for randomized controlled trials of Tonifying kidney and activating blood therapy for the treatment of dia-betic erectile dysfunction.Literature screening,quality evaluation,and data extraction were carried out in accordance with relevant standards.The software of RevMan5.4 was used for the analysis of publication bias.And meta-analysis was conducted to assess the im-pact of this therapy on IIEF-5,total effective rate,adverse reactions.The evidence levels according to the analysis results were evalua-ted.Results:Totally 19 RCTs were included,involving 1 612 patients.The result of meta-analysis indicated that Tonifying kidney and activating blood therapy had advantages on the improvement of IIEF-5 scores(MD=3.59,95%CI[2.14,5.03],P<0.01),total effective rate(OR=4.30,95%CI[3.29,5.32],P<0.000 01).However,there was no statistically significant difference in the inci-dence of adverse reactions(OR=0.98,95%CI[0.48,2.01],P=0.96)between the two groups.Conclusions:Tonifying kidney and activating blood therapy can improve the clinical efficacy and IIEF-5 score for the patients with diabetic erectile dysfunction.But considering the limited quantity of included studies,more high-quality studies still be needed to validate the therapeutic effect.

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