Chronic heart failure （CHF） is the final stage of cardiovascular diseases. It is a complex syndrome， with dyspnea and edema as the main clinical manifestations， and it is characterized by complex disease conditions， difficult cure， and high mortality. Ferroptosis， a new type of programmed cell death， is different from other types of programmed cell death. Ferroptosis is iron-dependent， accompanied by lipid peroxide accumulation and mitochondrial shrinkage， becoming a hot research topic. Studies have confirmed that ferroptosis plays a key role in the occurrence and development of CHF. The regulation of ferroptosis may become a potential target for the treatment of CHF in the future. The theory of Qi deficiency and stagnation refers to the pathological state of original Qi deficiency and abnormal transportation and distribution of Qi， blood， and body fluid， which has guiding significance for revealing the pathogenesis evolution of some chronic diseases. We believe that Qi deficiency and stagnation is a summary of the pathogenesis of ferroptosis in CHF. Deficiency of Qi （heart Qi） is the root cause of CHF， and stagnation （phlegm turbidity and blood stasis） is the branch of this disease. The two influence each other in a vicious circle to promote the development of this disease. Traditional Chinese medicine （TCM） plays an important role in the treatment of CHF， improving the prognosis and quality of life of CHF patients. This paper explores the correlation between the theory of Qi deficiency and stagnation and the mechanism of ferroptosis in CHF. Furthermore， this paper reviews the mechanism of Chinese medicines and compound prescriptions in preventing and treating CHF by regulating ferroptosis according to the principles of replenishing Qi and dredging to remove stagnation， aiming to provide new ideas and methods for the treatment of CHF with TCM.

Background::Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to investigate the epigenetic mechanisms in IUGR.Methods::IUGR models were established in Sprague–Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF) 1–4 binding sites of the Igf2/H19 imprinting control region (ICR). The methylation states of CTCF1–4 binding sites were studied by pyrosequencing. Results::The IUGR models were constructed successfully. Igf2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group ( P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group ( P <0.05). In addition, knocking down Igf2 reduced the protein expression levels of AKT2-phosphorylation and PGC-1α ( P <0.05). In CTCF binding sites 1-4 of the Igf2/ H19 ICR, acetylated histones H3 (AcH3) enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. Histone H3 tri-methylated lysine 4 (H3K4me3) enrichment was significantly lower in the CTCF1–4 of newborn and 8-week-old IUGR groups ( P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group ( P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly ( P <0.05). Conclusion::The methylation status and histone modification in the Igf2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

[Purpose]To analyze the changing trends of the disease burden of liver cancer related to hepatitis B virus(HBV)globally and in China from 1992 to 2021.[Methods]Based on the Global Burden of Disease database in 2021,indicators such as the age-standardized incidence rate and mortality rate of HBV-related liver cancer globally and in China from 1992 to 2021 were collected.The Joinpoint regression model was used to analyze the changing trends of epidemiologi-cal characteristics,and the age-period-cohort model was adopted to analyze the impacts of age,period,and cohort factors on the incidence and mortality risks of HBV-related liver cancer globally and in China.[Results]From 1992 to 2021,the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer globally generally showed a trend of decreasing.The average annual percentage changes were-0.31％and-0.61％,respectively,and all the down-ward trends were statistically significant(both P＜0.05).During the same period,the average annu-al percentage changes of the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer in China were-0.45％and-0.90％,respectively,and all the downward trends were statistically significant(both P＜0.05).The results of the age-period-cohort model anal-ysis showed that from 1992 to 2021,the annual net drift rates of the incidence of HBV-related liver cancer globally and in China were-0.71％(95％CI:-0.84％～-0.57％)and-0.73％(95％CI:-1.01％～-0.44％),respectively.The annual net drift rates of the mortality were-1.15％(95％CI:-1.28％～-1.02％)and-1.42％(95％CI:-1.69％～-1.14％),respectively,all showing an over-all decline.The age effect showed that the risk of HBV-related liver cancer incidence in both the global and Chinese populations began to increase after 30 years of age,peaking in the 70～74 age group,while the risk of mortality surged after 40 years of age and peaked in the population aged 80 and above.The period effect indicated that the incidence and mortality risks were the highest from 1997 to 2001 and the lowest from 2017 to 2021.The cohort effect revealed that the inci-dence and mortality risks gradually decreased in populations born after 1962,with the 2007-2011 birth cohort having the lowest risks.The results of the Wald x2 test showed that there were statistically significant differences in the changing trends of the age,period,and cohort effects on the incidence and mortality of HBV-related liver cancer globally and in China(all P＜0.05).[Con-clusion]From 1992 to 2021,the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer showed a downward trend both globally and in China.The disease burden of HBV-related liver cancer in China was higher than the global level.The age-period-cohort model has revealed the historical changes in the incidence and mortality of HBV-related liver cancer.The current and future situation of the disease burden of HBV-related liver cancer is not optimistic.It is recommended to implement precise stratified interventions for populations of different ages,periods,and birth cohorts,and actively transform the prevention,treatment,and management strategies for HBV-related liver cancer.

AIM: To investigate the specific molecular mechanism of Yinqiao Powder in affecting macrophage polarization in herpes simplex keratitis(HSK)through the cyclic GMP-AMP synthetase(cGAS)-stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)molecular pathway.METHODS:Human corneal epithelial cells(HCE-T)were divided into control, HSK, and HSK + Yinqiao Powder groups. M0 macrophages were grouped as Ctrl, HSV-1, HSV-1+oe-cGAS, HSV-1+Yinqiao Powder, and HSV-1+oe-cGAS+Yinqiao Powder. Conditional medium(CM)from each group of M0 macrophages was collected to intervene in HCE-T cells and divided into Ctrl-CM, HSV-1-CM, HSV-1+oe-cGAS-CM, and HSV-1+Yinqiao Powder-CM groups. Cell viability was detected by MTT assay, and apoptosis was detected by TUNEL assay. ELISA was used to detect the concentrations of Arg-1 and iNOS in cell supernatants, and Western blotting was used to detect the relative protein expressions of cGAS, STING, and IRF3. Balb/c mice were divided into control, model, and drug groups. The model and drug groups were inoculated with HSV-1 on the cornea of Balb/c mice using the corneal scratch method to construct an HSK mouse model, and the drug group was treated with Yinqiao Powder. The incidence and mortality of the three groups were compared on days 1, 3, 5, 7, and 14 after modeling.RESULTS:Compared with the control group, the HCE-T cell viability in the HSK group was decreased but apoptosis was increased, which was reversed by Yinqiao Powder intervention. Compared with the Ctrl group, the Arg-1 concentration in the cell supernatant of the HSV-1 group was decreased, the iNOS concentration was increased, and the protein expressions of cGAS, STING, and IRF3 were decreased. Compared with the HSV-1 group, the Arg-1 concentration was increased, the iNOS concentration was decreased, and the protein expressions of cGAS, STING, and IRF3 were enhanced in the HSV-1+oe-cGAS group and the HSV-1+Yinqiao Powder group, and the same results were obtained in the HSV-1+oe-cGAS+Yinqiao Powder group. Compared with the Ctrl-CM group, the HCE-T cell viability was decreased and apoptosis was increased in the HSV-1-CM group, which was reversed by overexpressing cGAS in macrophages or intervening with Yinqiao Powder. In vivo experiments found that Yinqiao Powder intervention could improve the pathological progression of keratitis.CONCLUSION:Yinqiao Powder inhibits M1 polarization of macrophages through the cGAS-STING-IRF3 molecular pathway, thereby delaying the progression of HSK.

Objective:To investigate the consistency and sensitivity of minimal residual disease (MRD) detected by multicolor flow cytometry (FCM) and real-time quantitative polymerase chain reaction (RQ-PCR) in patients with acute myeloid leukemia (AML) accompanied by monocytic differentiation after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective case series study was conducted. A total of 218 patients diagnosed with AML accompanied by monocytic differentiation who underwent allo-HSCT in Peking University People's Hospital between January 2017 and December 2021 were included. MRD was detected by using bone marrow FCM and RQ-PCR at predefined intervals (at 1-, 2-, 3-, 4.5-, 6-, 9-, and 12-month before and after transplantation). Patients were grouped based on AML-related specific genes, and dynamic changes in MRD results detected by FCM and RQ-PCR after transplantation were analyzed to evaluate the correlation with post-transplant relapse.Results:A total of 218 enrolled patients included 114 males and 106 females, with the median age of 32 years (1-65 years). The median follow-up duration was 218 d (21-1 541 d). Hematologic relapse occurred in 26 patients (12.7%), with a median relapse time of 272 d (83-934 d); 35 patients (15.9%) died, including 15 (6.9%) due to leukemia relapse and 20 (9.2%) due to transplant-related mortality. Predictive markers for relapse included once WT1 positive (WT1+once), twice WT1 positive (WT1+twice), CBFβ::MYH11 fusion genes positive, mixed-lineage leukemia (MLL)-related fusion genes positive, AML1::ETO fusion genes positive, and once FCM positive (FCM+once), twice FCM positive (FCM+twice). The overall consistency rate between FCM and RQ-PCR for MRD detection in AML patients accompanied by monocytic differentiation after transplantation was 75.7% (165/218). The consistency rate of MRD detection results in WT1+once, WT1+ twice, MLL-related fusion gene positive, and NPM1 gene mutation positive with FCM was higher than the average value (>75.7%), while the consistency rate of MRD detection results in AML1::ETO and CBFβ::MYH11 fusion gene positive with FCM was lower than the average value (<75.7%). Notably, persistent low-level positivity without relapse after transplantation occurred in cases with WT1 (15 patients), NPM1 (2 patients), CBFβ::MYH11 (11 patients), or AML1::ETO (2 patients); in contrast, MLL-related fusion genes (particularly MLL::AF6 and MLL::AF9) positive after transplantation indicated relapse in patients. The sensitivity and specificity of RQ-PCR for MRD monitoring varied by genetic markers: WT1+once and WT1+twice (sensitivity: 66.7%, 50.0%; specificity: 84.5%, 91.1%, respectively), AML1::ETO (sensitivity: 100.0%; specificity: 50.0%), CBFβ::MYH11 (sensitivity: 100.0%; specificity: 58.6%), MLL-related fusion genes (sensitivity: 75.0%; specificity: 96.4%), and NPM1 (sensitivity: 75.0%; specificity: 91.7%).Conclusions:The sensitivity and specificity of AML-related genetic markers for recurrence prediction show differences. Discrepancies between RQ-PCR and FCM in MRD detection are notable in AML with monocytic differentiation after transplantation. FCM exhibits relatively lower sensitivity for MRD monitoring in this subtype, while RQ-PCR based on AML-related genes may compensate for FCM limitations.

[Purpose]To analyze the changing trends of the disease burden of liver cancer related to hepatitis B virus(HBV)globally and in China from 1992 to 2021.[Methods]Based on the Global Burden of Disease database in 2021,indicators such as the age-standardized incidence rate and mortality rate of HBV-related liver cancer globally and in China from 1992 to 2021 were collected.The Joinpoint regression model was used to analyze the changing trends of epidemiologi-cal characteristics,and the age-period-cohort model was adopted to analyze the impacts of age,period,and cohort factors on the incidence and mortality risks of HBV-related liver cancer globally and in China.[Results]From 1992 to 2021,the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer globally generally showed a trend of decreasing.The average annual percentage changes were-0.31％and-0.61％,respectively,and all the down-ward trends were statistically significant(both P＜0.05).During the same period,the average annu-al percentage changes of the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer in China were-0.45％and-0.90％,respectively,and all the downward trends were statistically significant(both P＜0.05).The results of the age-period-cohort model anal-ysis showed that from 1992 to 2021,the annual net drift rates of the incidence of HBV-related liver cancer globally and in China were-0.71％(95％CI:-0.84％～-0.57％)and-0.73％(95％CI:-1.01％～-0.44％),respectively.The annual net drift rates of the mortality were-1.15％(95％CI:-1.28％～-1.02％)and-1.42％(95％CI:-1.69％～-1.14％),respectively,all showing an over-all decline.The age effect showed that the risk of HBV-related liver cancer incidence in both the global and Chinese populations began to increase after 30 years of age,peaking in the 70～74 age group,while the risk of mortality surged after 40 years of age and peaked in the population aged 80 and above.The period effect indicated that the incidence and mortality risks were the highest from 1997 to 2001 and the lowest from 2017 to 2021.The cohort effect revealed that the inci-dence and mortality risks gradually decreased in populations born after 1962,with the 2007-2011 birth cohort having the lowest risks.The results of the Wald x2 test showed that there were statistically significant differences in the changing trends of the age,period,and cohort effects on the incidence and mortality of HBV-related liver cancer globally and in China(all P＜0.05).[Con-clusion]From 1992 to 2021,the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer showed a downward trend both globally and in China.The disease burden of HBV-related liver cancer in China was higher than the global level.The age-period-cohort model has revealed the historical changes in the incidence and mortality of HBV-related liver cancer.The current and future situation of the disease burden of HBV-related liver cancer is not optimistic.It is recommended to implement precise stratified interventions for populations of different ages,periods,and birth cohorts,and actively transform the prevention,treatment,and management strategies for HBV-related liver cancer.

Heart failure （HF） is a group of syndromes caused by cardiac dysfunction with impaired ventricular pumping， seriously affecting patients' health and quality of life. The pathogenesis of HF is complex， including myocardial contractility decline， myocardial fibrosis， and ventricular remodeling， and it is related to neuroendocrine regulation， inflammation， and cardiomyocyte autophagy. Autophagy is a key regulatory mechanism by which cells degrade themselves to maintain body homeostasis. In the process of HF， moderate autophagy can remove aging and damaged cardiomyocytes and maintain the balance of myocardial energy metabolism， while abnormal autophagy may lead to functional decline and pathological changes of cardiomyocytes. The adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway is one of the classical pathways regulating autophagy. This pathway can mediate the autophagy of cardiomyocytes and play a role in protecting the cardiac function and delaying HF progression. Traditional Chinese medicine （TCM） with a long history has a unique theoretical system and shows satisfactory therapeutic effects and wide application prospects amid the integration with modern medicine. The clinical practice of TCM has accumulated rich experience in the treatment of cardiovascular diseases. A large number of studies have shown that the active components and compound prescriptions of TCM and Chinese patent medicines can mediate autophagy by regulating the AMPK/mTOR signaling pathway to treat HF. This article explains the role of AMPK/mTOR signaling pathway-mediated autophagy in the treatment of HF， introduces the understanding of autophagy， AMPK/mTOR signaling pathway， and HF based on TCM theories， and reviews the research progress in the regulation of autophagy by TCM in the treatment of HF via the AMPK/mTOR pathway. This review is expected to tap the potential of TCM in the treatment of cardiovascular diseases， provide theoretical support for subsequent experimental studies， and demonstrate the advantages of TCM in clinical practice to achieve more accurate treatment.

ObjectiveTo investigate the effects of Bushen Huoxue prescription on the cardiac function， inflammation， and quality of life of the patients with chronic heart failure resistant to diuretics. MethodA total of 78 patients who met the inclusion criteria were randomized into observation and control groups （39 cases）. Both groups received standardized treatment for diuretic resistance in accordance with the guidelines. In addition， the observation group received Bushen Huoxue prescription. The cardiac function indicators， total response rate regarding symptom alleviation， exercise endurance， urine volume， body mass， quality of life， and levels of inflammatory cytokines were compared between the two groups before and after treatment. ResultBefore treatment， the two groups of patients showed no significant differences in terms of 24 h urine volume， body mass， 6 minute walk test （6MWT）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP） level， left ventricular ejection fraction （LVEF）， stroke volume （SV）， and serum levels of interleukin-6 （IL-6）， interleukin-4 （IL-4）， and tumor necrosis factor-alpha （TNF-α）. After treatment， the observation group outperformed the control group in terms of the response rates regarding traditional Chinese medicine symptom scores and New York Heart Association （NYHA） grading of cardiac function （P<0.05）. After treatment， the body mass， MLHFQ score， and IL-6， TNF-α， and NT-proBNP levels decreased in both groups （P<0.05， P<0.01）， and the observation group showed more significant decreases than the control group （P<0.05， P<0.01）. Both groups showed increases in 24-h urine volume， 6MWT， LVEF， SV， and IL-4 after treatment （P<0.05， P<0.01）， and the observation group showed more significant increases than the control group （P<0.05， P<0.01）. ConclusionThe combination of Bushen Huoxue prescription with standardized treatment is effective in ameliorating the clinical symptoms of the patients with chronic heart failure resistant to diuretics. Moreover， it alleviates diuretic resistance and improves the cardiac function without causing obvious adverse reactions.

ObjectiveTo explore the clinical efficacy of Huangjin Shuangshen Jiawei （HJSSJW） granules in treating postoperative anxiety and depression after percutaneous coronary intervention （PCI） for coronary heart disease and the effects of this medicine on inflammatory cytokines. MethodNinety-four patients diagnosed with anxiety and depression after PCI were randomized into observation and control groups （47 cases） by the double-blind method. On the basis of conventional Western medical treatment， the observation group was treated with HJSSJW granules for 12 weeks， and the control group with the simulant of HJSSJW granules for 12 weeks. The two groups were compared in terms of Hamilton Anxiety and Depression Scales （HAMA-14， HAMD-24）， Pittsburgh Sleep Quality Inventory （PSQI）， Seattle Angina Score （SAQ）， TCM symptom scores， traditional Chinese medicine （TCM） symptom score and response rate， serum levels of hypersensitive-C reactive protein （hs-CPR）， tumor necrosis factor （TNF）-α， and interleukin （IL-6）， and incidence of major adverse cardiovascular events （MACEs） and adverse reactions. ResultAfter treatment， both groups showed declined scores of HAMA-14， HAMD-24， and PSQI （P<0.05， P<0.01） and the observation group had lower scores of HAMA-14， HAMD-24， and PSQI than the control group （P<0.01）. The scores of SAQ in both groups increased after treatment （P<0.01）， and the observation group had higher score of each dimension than the control group （P<0.05）. The TCM symptom scores decreased in both groups after treatment （P<0.01）， and they were lower in the observation group than in the control group （P<0.05）. The total response rate regarding TCM symptoms in the observation group was higher than that in the control group （χ²=9.225， P<0.01）. After treatment， the levels of hs-CPR， IL-6， and TNF-α became lowered in both groups （P<0.01）， and the observation group had lower levels of hs-CPR， IL-6， and TNF-α than the control group （P<0.05）. The incidence of MACEs in the observation group was lower than that in the control group during the 90 d of the follow-up period （χ²=4.242， P<0.05）. No adverse reactions associated with the use of HJSSJW granules were observed during the trial period. ConclusionHJSSJW granules can alleviate the bad mood， improve sleep， mitigate somatic symptoms， improve the quality of life， reduce inflammatory damage， and improve prognosis， being safe for clinical use in patients with postoperative anxiety and depression after PCI for coronary heart disease.

Heart failure is a group of complex clinical syndromes that represent the final stage of cardiovascular disease development， characterized by an extremely high mortality rate. However， due to the complexity of the pathological mechanisms， an effective treatment method has not yet been found. Mitochondria are among the most critical organelles in cells， playing an essential role in energy supply and widely participating in various life activities， such as the regulation of oxidative stress and apoptosis. The normal functioning of mitochondria is crucial for maintaining the body's normal life activities. In recent years， studies have found that mitochondrial dysfunction is associated with the occurrence and progression of various diseases， particularly closely related to the onset of heart failure. An imbalance in mitochondrial homeostasis is a key factor in cardiomyocyte death and the onset of heart failure. Mitochondrial autophagy， as a means of regulating mitochondrial homeostasis， is significant for the prevention and treatment of heart failure. Traditional Chinese medicine （TCM） therapy is a unique treatment approach in China now widely applied in clinical practice， demonstrating significant efficacy in treating heart failure， with unique advantages. Modern pharmacological research indicates that Chinese medicine monomers and compounds can target and regulate mitochondrial homeostasis in cardiomyocytes， affect mitochondrial autophagy， and protect cardiomyocytes， though the specific mechanisms remain unclear. Therefore， this paper explored the mechanisms of the PTEN-induced putative kinase 1 （PINK1）/Parkin pathway in mitochondrial autophagy and heart failure， reviewed the effects of PINK1/Parkin-mediated mitochondrial autophagy on heart failure， and discussed the therapeutic effects of PINK1/Parkin-mediated mitochondrial autophagy on heart failure in conjunction with TCM. This paper is expected to provide new ideas and methods for the prevention and treatment of heart failure from the perspective of PINK1/Parkin regulation of mitochondrial autophagy.