1.Epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer
Minggang WANG ; Jiamei DONG ; Zhihua YE ; Xiang GAO ; Qi CHEN ; Xiaoqiao YU ; Hanmin LI
Journal of Clinical Hepatology 2026;42(2):362-371
ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation, and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group, model group, and Diwu Yanggan Capsule group using a random number table, with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage, and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention; DNA methylation chips were used to analyze the change in DNA methylation in liver tissue, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for data analysis. In addition, the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB, ADCK2, ERLIN2, SEMA3B, and TPH2 in the liver tissue of rats, and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups, and a one-way analysis of variance was used for comparison between multiple groups, while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group, the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group, the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes, and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation, apoptosis, and microenvironment regulation, such as the calcium ion signaling pathway, the cAMP signaling pathway, and the extracellular factor signaling pathway. Compared with the model group, the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene (P<0.05) and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes (all P<0.05). Compared with the model group, the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 (all P<0.05). ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.
2.Pathogenesis Evolution and Treatment Strategies of Inflammation-Cancer Transformation in Helicobacter Pylori-Associated Gastritis:Based on the Theory "Latent Wind in Stomach Collaterals"
Chuanyang LIU ; Lin CHENG ; Xinqiao CHU ; Shuxuan CHEN ; Zhihua TIAN ; Shaoli WANG ; Zhen LIU
Journal of Traditional Chinese Medicine 2026;67(13):1383-1389
It is considered that "latent wind in stomach collaterals" is the core pathogenesis underlying the inflammation-caner transformation of helicobacter pylori-associated gastritis (HpAG). The concept of "latent wind in stomach collaterals" integrates stomach wind theory, latent pathogen theory, and collateral disease theory, referring to wind pathogen deeply hidden in the stomach collaterals, characterized by both external and internal wind pathogen as well as latent pathogen that remain concealed and may be triggered under certain conditions. Accordingly, the Correa cascade is reclassified into four stages including the prodromal stage, progressive stage, transitional stage and carcinogenic stage. In the prodromal stage, the fundamental pathogenesis is described as "wind toxin invading externally with collateral deficiency and stirring of wind". In the progressive stage, wind is accompanied by qi constraint, fire pathogen, and dryness pathogen, manifesting as "wind pathogen complicated by constraint" "wind-fire agitation" and "wind-dryness interaction". In the transitional stage, "wind transforming into phlegm-drool and stomach collaterals being obstructed by stasis" is identified as a critical window for disease reversal. In the carcinogenesis stage, "wind-qi hyperactivity leading to pathological transformation, and collateral damage resulting in abdominal masses" drives tumor progression and metastasis. This paper proposes the treatment principle of "wind-dispelling throughout the entire process and stage-based treatment", according to the pathological evolution of "collateral deficiency-collateral stagnation-collateral accumulation". In the prodromal stage, it is suggested to dispel wind and resolve toxin, fortify spleen and tonify collaterals; in the progressive and transitional stage, the method of dispelling wind pathogen, clearing phlegm and eliminating stasis should be used; in the carcinogenesis stage, it is suggested to expel wind and remove pathogens from collaterals, disperse concretions and eliminate tumors.
3.Expert consensus on liquid biopsy-based multi-cancer early detection(2025 edition)
Chen WANQING ; Chen KEXIN ; He YUTONG ; Jia WEIHUA ; Liu ZHIHUA ; Ma HONGXIA ; Miao XIAOPING ; Pan KAIFENG ; Wu CHEN ; Xia CHANGFA ; Xing JINLIANG ; Xu YONGJIE
Chinese Journal of Clinical Oncology 2025;52(14):727-742
Cancer stands as a significant global public health challenge,and cancer screening serves as a pivotal strategy for reducing its mortality.Presently,only a limited number of cancer types have appropriate screening methods available.Traditional single-cancer screen-ing approaches are fraught with limitations,including invasiveness,low accuracy,and poor patient compliance.Multi-cancer early detection(MCED)leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA,cell-free RNA,proteins,and metabolites in blood and other bodily fluids.This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage,showcasing immense potential for improving existing can-cer screening strategies.This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED,biomarker selection and detection technologies,the criteria for cancer type selection,research design and clinical utility evaluation,as well as implementation path-ways.The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED,thereby facilitating the continuous optimization of cancer screening strategies.
4.Diagnostic value of serum CCL3 and Semaphorin 3A in patients with T2DM complicated by osteoporosis
Xiaoliang CUI ; Zhihua DUN ; Chen ZHANG ; Tao LIU
International Journal of Laboratory Medicine 2025;46(14):1730-1735
Objective To explore the diagnostic value of serum C-C motif chemokine ligand 3(CCL3)and Semaphorin 3A in patients with type 2 diabetes mellitus(T2DM)complicated by osteoporosis(OP).Methods A total of 125 patients with T2DM complicated by OP who visited the hospital from August 2022 to August 2023 were selected as the OP group,and another 125 patients with T2DM without OP who visited the hospital during the same period were selected as the T2DM group.The OP group was divided into Group A(T value>-1.0,but slightly lower than the normal value),Group B(T value between-2.5 and-1.0),and Group C(T value<-2.5)based on the measurement results of bone mineral density(BMD).The lev-els of serum CCL3 and Semaphorin 3A in each group were compared.Pearson correlation analysis was used to analyze the correlations between serum CCL3,Semaphorin 3A and BMD in patients with T2DM complicated by OP.Multivariate Logistic regression analysis was used to analyze the influencing factors of T2DM compli-cated by OP.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of se-rum CCL3 and Semaphorin 3A for T2DM complicated by OP.Results Compared with the T2DM group,the serum CCL3 level in the OP group increased,and the Semaphorin 3A level decreased,and the difference was statistically significant(P<0.05).Compared with group A,the serum CCL3 levels in group B and group C increased,while the Semaphorin 3A level decreased,and the differences were statistically significant(P<0.05).Compared with group B,the serum CCL3 level in group C increased and the Semaphorin 3A level de-creased,and the difference was statistically significant(P<0.05).Compared with the T2DM group,the femo-ral neck bone BMD,lumbar spine BMD and total hip BMD in the OP group were significantly decreased,and the difference was statistically significant(P<0.05).The serum CCL3 level in patients with T2DM accompa-nied by OP was negatively correlated with femoral neck bone BMD,lumbar spine BMD and total hip BMD(P<0.05),and the serum Semaphorin 3A level was positively correlated with femoral neck bone BMD,lum-bar spine BMD and total hip BMD(P<0.05).The results of multivariate Logistic regression analysis showed that CCL3 was an independent risk factor for T2DM with OP(P<0.05),and Semaphorin 3A was an inde-pendent protective factor for T2DM with OP(P<0.05).The results of ROC curve analysis showed that the area under the curve(AUC)of serum CCL3,Semaphorin 3A and their combination diagnosis of T2DM accom-panied by OP were 0.810,0.802 and 0.869,respectively.The AUC of the combined diagnosis of T2DM ac-companied by OP was superior to their individual diagnoses(Zcombination-CCL3=2.235,Zcombination-Semaphorin 3A=2.021,P=0.025,0.043).Conclusion The serum CCL3 level is increased in patients with T2DM accompanied by OP,and the Semaphorin 3A level is decreased.The combination of the two has certain diagnostic value for T2DM accompanied by OP.
5.Expert consensus on liquid biopsy-based multi-cancer early detection (2025 edition)
Wanqing CHEN ; Kexin CHEN ; Yutong HE ; Weihua JIA ; Zhihua LIU ; Hongxia MA ; Xiaoping MIAO ; Kaifeng PAN ; Chen WU ; Changfa XIA ; Jinliang XING ; Yongjie XU
Chinese Journal of Oncology 2025;47(7):558-574
Cancer stands as a significant global public health challenge, and cancer screening serves as a pivotal strategy for reducing its mortality. Presently, only a limited number of cancer types have appropriate screening methods available. Traditional single-cancer screening approaches are fraught with limitations, including invasiveness, low accuracy, and poor patient compliance. Multi-cancer early detection (MCED) leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA, cell-free RNA, proteins, and metabolites in blood and other bodily fluids. This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage, showcasing immense potential for improving existing cancer screening strategies. This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED, biomarker selection and detection technologies, the criteria for cancer type selection, research design and clinical utility evaluation, as well as implementation pathways. The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED, thereby facilitating the continuous optimization of cancer screening strategies.
6.Establishment of Vero cell line overexpressing pAPN gene and its effect on porcine epidemic diarrhea virus replication
Qiuyong CHEN ; Zhihua SUN ; Rujing CHEN ; Xuemin WU ; Renjie WU ; Jinli QIU ; Bing HE ; Yutao LIU ; Longbai WANG ; Lunjiang ZHOU
Chinese Journal of Veterinary Science 2025;45(2):181-186
pAPN is a zinc-dependent metalloprotease,mediating the fusion between virus and host cell,and playing a role as the receptor of coronavirus.To explore the effect of pAPN on PEDV rep-lication,the full-length pAPN gene was amplified from the porcine small intestinal by PCR,and was cloned into the lentiviral vector via the homologous site digested with BamH Ⅰ and Not Ⅰ to obtain the recombinant lentiviral vector PLVX-pAPN-mCMV-ZsGreen1-puro.The recombinant lentiviral vector and helper plasmids pLP1,pLP2,pLP-VSVG were co-transfected into 293T cells for lentiviral packaging.Vero cells were infected with the packaged lentivirus and the pAPN gene overexpressing cells were screened by puromycin.The stable expression of Vero-pAPN monoclonal cell line was screened by a limited dilution method,and the effect of the cell line on the replication of PEDV was determined by qPCR for N mRNA transcription level,Western blot for N protein level,and TCID50.The results showed that the packaged lentivirus could infect Vero cells,and the monoclonal cell line Vero-pAPN(2C5)could stably expressed pAPN.The Vero-pAPN cell line can promote the replication of PEDV,the N gene mRNA transcription level was significantly different at 12-48 h(P<0.05),the N protein expression level increased,and the TCID50 was significantly different at 24 and 48 h(P<0.05).In conclusion,the Vero-pAPN cell line was constructed in this study and it can significantly promote the replication of PEDV,which provides a candidate cell line for PEDV vaccine production and isolation.
7.Expert consensus on liquid biopsy-based multi-cancer early detection(2025 edition)
Chen WANQING ; Chen KEXIN ; He YUTONG ; Jia WEIHUA ; Liu ZHIHUA ; Ma HONGXIA ; Miao XIAOPING ; Pan KAIFENG ; Wu CHEN ; Xia CHANGFA ; Xing JINLIANG ; Xu YONGJIE
Chinese Journal of Clinical Oncology 2025;52(14):727-742
Cancer stands as a significant global public health challenge,and cancer screening serves as a pivotal strategy for reducing its mortality.Presently,only a limited number of cancer types have appropriate screening methods available.Traditional single-cancer screen-ing approaches are fraught with limitations,including invasiveness,low accuracy,and poor patient compliance.Multi-cancer early detection(MCED)leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA,cell-free RNA,proteins,and metabolites in blood and other bodily fluids.This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage,showcasing immense potential for improving existing can-cer screening strategies.This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED,biomarker selection and detection technologies,the criteria for cancer type selection,research design and clinical utility evaluation,as well as implementation path-ways.The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED,thereby facilitating the continuous optimization of cancer screening strategies.
8.Cervical Kyphosis Based on Cervical Rehabilitation Training System:A Biomechanical Model Study
Zhihua LIU ; Mingwen ZHANG ; Yang ZHOU ; Yankui SHEN ; Zhongzhong CHEN
Journal of Medical Biomechanics 2025;40(3):615-622
Objective A biomechanical model of cervical kyphosis under the effects of axial traction load and lateral push load was establised,so as to provide a theoretical basis for the treatment of cervical curvature abnormalities,and formulate the most appropriate treatment plan for patients.Methods Based on the CT scan data of patients,the axial data of the cervical spine was extracted to fit the cervical curvature curve.Using the Timoshenko beam theory and the cervical rehabilitation training system,a mathematical model of cervical kyphosis was established for analytical calculations to obtain the recovery curve of the cervical spine under load and the total load required to cure cervical kyphosis,and its rationality was also verified.Results The biomechanical model of cervical kyphosis was established.Under the effects of axial traction load and lateral push load,the cervical spine effectively developed in the direction of physiological bending.The total axial load and lateral load were 353 N and 5 649 N,respectively,and the total axial load increased with the increase in traction angle.The therapeutic moment of the total lateral load decreased as the Bordon value increased.The therapeutic moment of the axial load was smaller than that of the lateral load in the range of normal Bordon value,confirming the rationality of the loads.Conclusions The established biomechanical model of cervical kyphosis can accurately simulate the biomechanical characteristics of the cervical spine,and the analysis results were valid,providing a mechanical theoretical basis for the design of treatment plans for patients.
9.Microstructural mapping of time-dependent diffusion MRI for the discrimination of clinically significant prostate cancer
Yanling CHEN ; Wenxin CAO ; Jinhua LIN ; Jian LING ; Zhihua WEN ; Long QIAN ; Yan GUO ; Huanjun WANG
Chinese Journal of Radiology 2025;59(7):777-783
Objective:To investigate the diagnostic efficacy of time-dependent diffusion MRI (t d-dMRI)-derived microstructural parameters for clinically significant prostate cancer (csPCa) and their associations with the pathological grade of prostate cancer(PCa) based on the International Society of Urological Pathology (ISUP) grades. Methods:This cross-sectional study prospectively enrolled 196 patients suspected of PCa from March 2023 to March 2024 at the First Affiliated Hospital, Sun Yat-Sen University. All patients underwent multiparametric MRI and t d-dMRI to obtain microstructural parameters, including cell diameter (d), intracellular volume fraction (f in), extracellular diffusion coefficient (D ex), cellularity, and apparent diffusion coefficient (ADC) value at oscillation frequencies of 33 Hz, 17 Hz, 0 Hz (ADC 33, ADC 17, and ADC 0). Pathologically, 95 cases were classified as csPCa (ISUP 2-5), and the rest 101 cases were classified as non-csPCa (benign or ISUP 1). Comparison of these microstructural metrics was made between csPCa and non-csPCa groups by independent t-tests or Mann-Whitney U tests, and multivariable logistic regression was used to identify independent predictors. A combined diagnostic model was then constructed based on the independent predictors. The receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. Finally, in PCa, the correlation between microstructural parameters and ISUP grades was investigated by Spearman correlation. Results:The t d-dMRI measurements, including d, f in, cellularity, ADC 33,ADC 17 and ADC 0, were significantly different between csPCa and non-csPCa groups (All P<0.05). But D ex was not significantly different between the two groups ( Z=-1.27, P=0.204). The area under the receiver operating characteristic curve (AUC) for diagnosing csPCa were 0.701 (95% CI 0.628-0.775) for d, 0.869 (95% CI 0.819-0.920) for f in, 0.884 (95% CI 0.835-0.932) for cellularity, 0.777 (95% CI 0.712-0.842) for ADC 33, 0.852 (95% CI 0.799-0.905) for ADC 17, and 0.840 (95% CI 0.786-0.894) for ADC 0. Cellularity ( OR=6.142, 95% CI 2.920-12.929, P<0.001) and ADC 17 ( OR=0.108, 95% CI 0.027-0.429, P=0.002) were identified as the independent predictors, and their combined model achieved an AUC of 0.896 (95% CI 0.852-0.941). In PCa f in and cellularity were positively correlated with ISUP grades ( r=0.490 and 0.397, P<0.001), while ADC 33, ADC 17, and ADC 0 were negatively correlated with ISUP grades ( r=-0.198, -0.345, -0.360; P=0.041,<0.001,<0.001). d and D ex were not correlated with ISUP grades ( P>0.05). Conclusion:t d-dMRI based microstructural mapping correlates with ISUP grades of PCa and may be useful for the differential diagnosis of csPCa.
10.Clinical efficacy of minimally invasive coronary artery bypass grafting via left intercostal small incision for multivessel coronary artery disease: A retrospective cohort study
Zeyuan ZHAO ; Zhihua WANG ; Sheng WANG ; Xianjie CHEN ; Zhao LI ; Guoqing LU ; Zhenchang QI ; Zhaoyun CHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(10):1455-1461
Objective To investigate the early clinical efficacy of minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG) via left intercostal small incision for multivessel coronary artery disease. Methods The patients who received off-pump CABG in the Central China Fuwai Hospital of Zhengzhou University from June 2021 to June 2023 were enrolled. Patients were divided into two groups according to the operative technique used, including a traditional midline sternotomy group and a left intercostal small incision group. The clinical data of the two groups were compared. Results A total of 143 patients were enrolled, including 70 patients in the traditional midline sternotomy group and 73 patients in the left intercostal small incision group. The age of the patients in the left intercostal small incision group and the traditional midline sternotomy group was (63.8±8.0) years and (63.0±7.8) years, respectively; the proportions of males were 69.9% and 74.3%, respectively. The differences were not statistically significant (all P>0.05). All patients in the two groups successfully completed the operation, and no patients in the left intercostal small incision group were converted to thoracotomy. The patients in the left intercostal small incision group showed less postoperative drainage within postoperative 24 hours [(239.4±177.7) mL vs. (338.0±151.9) mL, P<0.001], lower perioperative blood transfusion rate [32.9% (24/73) vs. 51.4% (36/70), P=0.028], higher postoperative myoglobin level within postoperative 24 hours [366.1 (247.9, 513.0) ng/mL vs. 220.8 (147.2, 314.9) ng/mL, P<0.001], shorter intensive care unit stay [45.5 (31.5, 67.5) h vs. 68.0 (46.0, 78.5) h, P=0.001] and postoperative hospital stay [(10.8±4.0) d vs. (13.1±5.3) d, P=0.028] compared to the traditional midline sternotomy group. There was no significant difference in the incidence of major adverse cardiac and cerebrovascular event between the two groups [2.7% (2/73) vs. 2.9% (2/70), P=1.000]. Conclusion Compared to the full median sternotomy, MICS CABG leads to a good clinical result with smaller trauma, faster overall recovery, and less perioperative blood transfusion.

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