1.Mechanism of Ferroptosis in Cerebral Ischemia-reperfusion and Interventional Mechanism of Huoxue Huayu Jiedu Prescription Based on "Blood Stasis and Toxin" Pathogenesis
Jiayue HAN ; Danyi PAN ; Jiaxuan XIAO ; Yuchen LIU ; Jiyong LIU ; Yidi ZENG ; Jinxia LI ; Caixing ZHENG ; Hua LI ; Wanghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):51-60
ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury, as well as the protective role of Huoxue Huayu Jiedu prescription (HXHYJDF) against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups: sham group, model group, deferoxamine (DFO) group (100 mg·kg-1), low-dose HXHYJDF group (4.52 g·kg-1), medium-dose HXHYJDF group (9.04 g·kg-1), and high-dose HXHYJDF group (18.07 g·kg-1), with ten rats in each group. Except for the sham group, the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1st, 3rd, 5th, and 7th days post-reperfusion using the modified neurological severity scores (m-NSS). Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin (HE) staining and transmission electron microscopy. The contents of malondialdehyde (MDA), glutathione (GSH), divalent iron ions (Fe2+), and reactive oxygen species (ROS) in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry and Western blot (WB) were used to detect the expression of iron death marker proteins glutathione peroxidase 4 (GPX4), ferroportin-1 (FPN1), transferrin receptor protein 1 (TfR1), and ferritin mitochondrial (FtMt) in brain tissue. ResultsCompared with the sham group, the mNSS score of the model group was significantly increased (P<0.01). HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced, and the intercellular space was widened. The nucleus was fragmented, and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded, and the mitochondrial cristae decreased. The matrix was lost and vacuolated, and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS increased significantly (P<0.01). The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased (P<0.01), and the expression of FtMt and TfR1 proteins was significantly increased (P<0.01). Compared with those of the model group, the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3rd and 5th days, respectively (P<0.05, P<0.01). The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS decreased significantly (P<0.05, P<0.01). The content of GSH in the low-dose HXHYJDF group increased significantly (P<0.01), and the contents of MDA and ROS decreased significantly (P<0.01). The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly (P<0.01), and the expression of FtMt and TfR1 decreased significantly (P<0.01). The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly (P<0.05), and the expression of TfR1 decreased significantly (P<0.01). WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose, medium-dose, and low-dose HXHYJDF groups were significantly up-regulated (P<0.01), and the expression levels of FtMt and TfR1 proteins were significantly down-regulated (P<0.01). ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury, improve the pathological morphology of the infarcted brain tissue, and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury, with increased levels of MDA, Fe2+, ROS, and TfR1 and decreased levels of FtMt, FPN1, GPX4, and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins, promoting the discharge of free iron, reducing brain iron deposition, alleviating oxidative stress, and inhibiting ferroptosis.
2.Bioactive metabolites: A clue to the link between MASLD and CKD?
Wen-Ying CHEN ; Jia-Hui ZHANG ; Li-Li CHEN ; Christopher D. BYRNE ; Giovanni TARGHER ; Liang LUO ; Yan NI ; Ming-Hua ZHENG ; Dan-Qin SUN
Clinical and Molecular Hepatology 2025;31(1):56-73
Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.
3.Bioactive metabolites: A clue to the link between MASLD and CKD?
Wen-Ying CHEN ; Jia-Hui ZHANG ; Li-Li CHEN ; Christopher D. BYRNE ; Giovanni TARGHER ; Liang LUO ; Yan NI ; Ming-Hua ZHENG ; Dan-Qin SUN
Clinical and Molecular Hepatology 2025;31(1):56-73
Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.
4.Bioactive metabolites: A clue to the link between MASLD and CKD?
Wen-Ying CHEN ; Jia-Hui ZHANG ; Li-Li CHEN ; Christopher D. BYRNE ; Giovanni TARGHER ; Liang LUO ; Yan NI ; Ming-Hua ZHENG ; Dan-Qin SUN
Clinical and Molecular Hepatology 2025;31(1):56-73
Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.
5.Changes in coordination of departments for major epidemic prevention and control in China before and after the outbreak of COVID-19: an analysis on official documents
Zhonghui HE ; Peiwu SHI ; Qunhong SHEN ; Zheng CHEN ; Chuan PU ; Lingzhong XU ; Zhi HU ; Anning MA ; Tianqiang XU ; Panshi WANG ; Hua WANG ; Qingyu ZHOU ; Chengyue LI ; Mo HAO
Shanghai Journal of Preventive Medicine 2025;37(5):446-450
ObjectiveTo analyze the changes in the degree of coordination of China's major epidemic prevention and control efforts before and after the outbreak of the Corona Virus Disease 2019 (COVID-19), so as to explore the impact of epidemic prevention and control measures on coordination dynamics. MethodsA total of 3 864 policy documents related to epidemic prevention and control from January 2000 to December 2020 across 31 provinces (autonomous regions, and municipalities) in China were systematically collected. Contents specific to collaborative and cooperative efforts were extracted, and the extent of interdepartmental coordination were quantified to assess the effectiveness of epidemic prevention and control efforts. Wilcoxon signed-rank test was adopted to statistically analyze the differences between the indicators before and after the epidemic. ResultsThe average overall coordination level for major epidemic prevention and control in 31 provinces (autonomous regions, and municipalities) increased from 43.06% to 97.62%, and the average coordination levels in the eastern, central, and western China soared from 42.29%, 37.50%, and 47.46%, to 98.81%, 96.20%, and 97.46%, respectively, with statistically significant differences (all P<0.05). In terms of department categorization, coordination levels in the professional departments and the key support departments peaked at 100.00%, while other support departments rose to 95.43%, with an increase of 77.15%, 181.85%, and 139.89%, respectively, exhibiting noteworthy statistically significant differences (all P<0.001). ConclusionThe scope of coordination departments of China’s major epidemic prevention and control exists a remarkable surge following the COVID-19 outbreak, notable heightened coordination is particularly observed among the key support departments. Future endeavors should prioritize the roles played by diverse departments in epidemic prevention and control, enhancing both the clarity of departmental responsibilities and the effectiveness of interdepartmental coordination.
6.A systematic evaluation of the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces
Huayi ZHANG ; Qingyu ZHOU ; Huihui HUANGFU ; Peiwu SHI ; Qunhong SHEN ; Chaoyang ZHANG ; Zheng CHEN ; Chuan PU ; Lingzhong XU ; Anning MA ; Zhaohui GONG ; Tianqiang XU ; Panshi WANG ; Hua WANG ; Chao HAO ; Zhi HU ; Chengyue LI ; Mo HAO
Shanghai Journal of Preventive Medicine 2025;37(5):451-457
ObjectiveTo systematically evaluate the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces, providing a scientific evaluation basis for building a "Healthy Yangtze River Delta". MethodsA comprehensive collection of policy documents, public information reports, and research literature related to public health governance capacity in Jiangsu, Zhejiang, and Anhui Provinces was conducted, totaling 6 920 policy documents, 1 720 information reports, and 1 200 literature pieces. Based on the evaluation standards for an appropriate public health system established by the research team, the basic status of public health governance capacity was assessed to identify the strengths and weaknesses of the 40 cities. ResultsIn 2022, the public health governance capacity score for the 40 cities in Jiangsu, Zhejiang, and Anhui Provinces was (562.5±38.0) points. In terms of specific areas, the emergency response field received the highest score of (791.4±49.7) points, while the chronic disease prevention and control field received the lowest score of (368.2±29.6) points. The Jiangsu-Zhejiang-Anhui region has largely achieved the strategic priority of health, gradually improved public health legal regulations, and established a basic organizational framework with a solid foundation for information and data infrastructure. However, challenges still need to be addressed, such as unstable government funding for public health, unclear departmental responsibilities, and barriers to information interoperability. ConclusionThe public health governance capacity of the 40 cities in Jiangsu, Zhejiang, and Anhui Province has been at a moderate level, but disparities have still existed across regions and fields. In the future, while continuing to deepen existing advantages, it is essential to accurately identify the causes of problems, establish a long-term and stable investment mechanism, enhance information connectivity mechanisms, further clarify departmental responsibilities, and promote the achievement of the "Healthy Yangtze River Delta" goal.
7.Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study
Changyang XING ; Xiujing XIE ; Yu WU ; Lei XU ; Xiangping GUAN ; Fan LI ; Xiaojun ZHAN ; Hengli YANG ; Jinsong LI ; Qi ZHOU ; Yuming MU ; Qing ZHOU ; Yunchuan DING ; Yingli WANG ; Xiangzhu WANG ; Yu ZHENG ; Xiaofeng SUN ; Hua LI ; Chaoxue ZHANG ; Cheng ZHAO ; Shaodong QIU ; Guozhen YAN ; Hong YANG ; Yinjuan MAO ; Weiwei ZHAN ; Chunyan MA ; Ying GU ; Wu CHEN ; Mingxing XIE ; Tianan JIANG ; Lijun YUAN
Chinese Medical Journal 2024;137(15):1802-1810
Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.
8.Study on anti-myocardial ischemia active components and mechanism of Xinkeshu tablets based on network pharmacology and zebrafish model
Lin-Hua HOU ; Hua-Zheng ZHANG ; Shuo GAO ; Yun ZHANG ; Qiu-Xia HE ; Ke-Chun LIU ; Chen SUN ; Jian-Heng LI ; Qing XIA
Chinese Pharmacological Bulletin 2024;40(5):964-974
Aim To study the active ingredients and mechanism of action of Xinkeshu tablets against myo-cardial ischemia by network pharmacology and ze-brafish model.Methods The anti-myocardial ische-mia activity of Xinkeshu tablets was evaluated by iso-prenaline hydrochloride(ISO)-induced zebrafish myo-cardial ischemia model and H2O2-induced H9c2 dam-age model.The active ingredients of Xinkeshu tablets were retrieved using databases such as TCMSP.The potential targets were predicted by PharmaMapper data-base.Myocardial ischemic disease targets were searched by OMIM database.The potential therapeutic targets of Xinkeshu tablets against myocardial ischemia were analyzed.GO and KEGG enrichment analysis were conducted on core targets.The active ingredients were verified by zebrafish and cell model.qRT-PCR was used to detect the expression of key targets.Re-sults Xinkeshu tablets could significantly alleviate ISO-induced pericardial edema and bradycardia.It al-so could increase sinus venous-bulb aortic(SV-BA)distance and improve the cell viability.The 30 poten-tial active ingredients of Xinkeshu tables mainly acted on 30 core targets,including ALB,AKT1 and MAPK1,to regulate 627 GO items,including protein phosphorylation,negative regulation of apoptosis and positive regulation of PI3K signal transduction.KEGG results showed that 117 signaling pathways,including PI3K/Akt,FOXO and Ras,exerted anti-myocardial ischemia effect.Salvianolic acid A,lithospermic acid,rosmarinic acid,salvianolic acid D,salvianolic acid B,ginsenoside Rg2,hyperoside,3'-methoxypuerarin,3'-hydroxypuerarin and ginsenoside Rg1 could alleviate ISO-induced zebrafish myocardial ischemia and im-prove the cell viability.Xinkeshu tablets could upregu-late the expression of genes such as ras and akt1,and downregulate the expression of genes such as mapk1 and mapk8.Conclusion The active ingredients,in-cluding salvianolic acid A in Xinkeshu tablets,exert anti-myocardial ischemia effects by targeting targets,such as AKT1,MAPK1,and regulating signaling path-ways,such as PI3K/Akt,MAPK and Ras.
9.Effect of Cigu Xiaozhi decoction on EGFR/PI3K/AKT signaling pathway in NASH's"inflammatory cancer"transformation based on network pharmacology and animal experiments
Lan-Lan ZHENG ; Li WANG ; Cai GUO ; Yan-Fang HE ; Jiao-Jiao XIE ; Yan-Hua MA
Chinese Pharmacological Bulletin 2024;40(8):1573-1582
Aim To study the main active ingredients,key targets and pathways of Cigu Xiaozhi Decoction(CXD)based on network pharmacology,and to ana-lyze and verify the mechanism of CXD on the transfor-mation of"inflammatory cancer"in non-alcoholic steatohepatitis(NASH)by animal experiments.Meth-ods The potential targets and signaling pathways of CXD in the treatment of NASH"inflammatory carcino-ma"were predicted based on network pharmacology.The mouse model of NASH was induced by methionine-choline deficiency diet(MCD),and CXD and epider-mal growth factor receptor(EGFR)inhibitors were given for 28 days.The mice were killed after the inter-vention,and the liver histopathology of each group was observed by hematoxylin-eosin method(HE).The rel-ative expression levels of EGFR,phosphatidylinositol 3-kinase(PI3K)and protein kinase B(AKT)in liver tissue of mice in each group were detected by Western blot.The contents of interleukin-6(IL-6),interleu-kin-1 β(IL-1β)and tumor necrosis factor-α(TNF-α)in serum were detected by enzyme-linked immunosor-bent assay(ELISA).Results A total of 284 poten-tial active components,159 potential therapeutic tar-gets and 20 key targets of CXD were identified by net-work pharmacological screening.CXD could affect multiple biological processes such as cell proliferation and inflammatory response,involving multiple signa-ling pathways such as tumor and PI3K/AKT.Animal experiments showed that CXD could reduce the levels of IL-6,IL-1β and TNF-α in serum of NASH mice.The relative expression of PI3K and AKT protein in liv-er tissue decreased,and the relative expression of EG-FR protein was increased.Conclusion CXD can reg-ulate EGFR/PI3K/AKT signaling pathway by partici-pating in biological processes such as cell proliferation and inflammatory response,and improve liver tissue injury in NASH mice.
10.Application of the Glisson hepatic pedicle priority approach marked by APR triangle in laparoscopic anatomic right hemihepatectomy
Hao-Nan LI ; Jing WANG ; Run-Hua LI ; Jing-Jing ZHENG ; Jiang-Lun SHEN
Journal of Regional Anatomy and Operative Surgery 2024;33(10):854-858
Objective To study the application effect of Glisson hepatic pedicle priority approach marked by APR triangle in laparoscopic anatomic right hemihepatectomy(LARH).Methods The clinical data of 66 patients underwent LARH in the Affiliated Hospital of Tangshan Vocational and Technical College were retrospectively analyzed.According to the surgical approaches,the patients were divided into the extrathecal group and the APR group.The 35 patients of the extrathecal group underwent LARH via Glisson hepatic pedicle extrathecal approach.The 31 patients of the APR group were treated with LARH through the Glisson hepatic pedicle priority approach marked by APR triangle.The clinical data including perioperative indexes,postoperative complications,oxidative stress and liver function indexes of patients in the two groups were statistically analyzed,and the differences between the two groups were compared.Results The operative time and intraoperative blood loss of patients in the APR group were significantly shorter/less than those in the extrathecal group,with statistically significant differences(P<0.05).There was no significant differences in the intraoperative blood transfusion ratio,drainage tube indwelling time,first exhaust time,postoperative hospitalization time or postoperative complications of patients between the two groups(P>0.05).The levels of malondialdehyde(MDA),cortisol(Cor)and superoxide dismutase(SOD)at each time point after surgery of patients in the two groups were significantly different from those before surgery(P<0.05),and the levels of MDA,Cor and SOD at each time point after surgery of patients in the APR group were significantly better than those in the extrathecal group(P<0.05).The levels of albumin(ALB),total bilirubin(TBil),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)at each time point after surgery of patients in the two groups were significantly different from those before surgery(P<0.05).Moreover,the levels of ALB,TBil,AST and ALT at each time point after surgery of patients in the APR group were significantly better than those in the extrathecal group(P<0.05).Conclusion Compared with the Glisson hepatic pedicle extrathecal approach,the Glisson hepatic pedicle priority approach marked by APR triangle in LARH has shorter operation time,less bleeding and less oxidative stress reaction,which is beneficial to the recovery of liver function after surgery.

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