Hepatic fibrosis（HF） is a common pathological link of a variety of chronic hepatic diseases， and its complex pathological mechanism and prolonged clinical course pose a major challenge to modern medicine. Modern conventional therapies for HF cannot reverse the pathological vascular remodeling of the liver， and targeted vascular treatment for HF is a current research hotspot. There is a contradiction between the inhibition of pathological repair and the promotion of physiological regeneration with a single targeted therapy. The dynamic equilibrium concept of "achieving equilibrium of Yin and Yang" of traditional Chinese medicine can provide a new treatment strategy， and multi-target traditional Chinese medicine compounds can achieve two-way regulation of pathological mechanisms. According to the research on the modernization of traditional Chinese medicine， the "collaterals and vascular system" are highly compatible in structure and function， and they can guide the treatment of HF at different stages by identifying their common pathological links in HF. The intrahepatic collaterals are an important component of the hepatic collaterals， and the theory of "hepatic collateral disease" based on this physiology has important guiding significance for the clinical diagnosis and treatment of HF. Hepatic sinusoidal obstruction caused by endothelial dysfunction in the early stage of HF is a pathological manifestation of stagnant nutrient Yin in collateral passages. It can be treated by diffusing Qi to resolve stagnation and promoting circulation to unblock collaterals. Repeated stimulation of angiogenesis by hypoxia and inflammation in the medium stage is the pathological manifestation of lingering stagnation of damp and heat in collateral passages. It can be treated by clearing and draining damp and heat， eliminating turbidity， and unblocking collaterals. Pathological vascular remodeling induced by hemodynamic abnormalities in the later stage is a pathological manifestation of the consumption of collateral passages by pathogenic toxins. At this stage with excessive pathogenic factors and deficient healthy Qi， combined therapy of dredging and nourishing is adopted to eliminate toxins， resolve blood stasis， nourish Yin， and supplement Qi simultaneously. Moreover， the holistic concept of harmony between human and nature in traditional Chinese medicine emphasizes the time， place， and treatment based on individual conditions， so the practical application of the theory should consider the specific regional characteristics. This paper aims to discuss the characteristics of pathogenesis， treatment principles， prescriptions， and medicines in different stages of HF based on the correlation between "collaterals and vascular system" as well as the theory of "hepatic collateral disease". It was proposed that Qi deficiency and collateral obstruction were the core pathogenesis of HF， and that hepatic collateral damage was the core pathological basis for the deterioration and prognosis of HF. The scientific connotation and pathogenesis evolution of collateral damage and mass generation in HF were discussed. Sichuan was taken as an example to investigate the treatment of HF according to local conditions， providing new ideas for the treatment of HF.

ObjectiveTo investigate the mechanism of Yijing decoction to inhibit oxidative stress induced by chronic iron overload and improve ovarian reserve hypofunction in mice. MethodsSeventy-two female C57BL/6J mice with normal estrous cycles were randomly divided into six groups （n=12 per group）：blank group，model group，Yijing decoction（YJD） low-dose group，medium-dose group，high-dose group，and dehydroepiandrosterone （DHEA） group. Mice in the blank group received intraperitoneal injections of normal saline，while those in all other groups were administered iron dextran （Sigma-Aldrich） at a dose of 0.5 g·kg^-1 once weekly for 8 weeks to establish a chronic iron overload model. Following the final injection，interventions were initiated and continued for 4 weeks. The low，medium，and high dose groups of YJD received oral gavage of Yijing decoction aqueous solution at doses of 18.165， 36.33，and 72.66 g·kg^-1·d^-1，respectively. The DHEA group received DHEA aqueous solution at 10.812 5 mg·kg^-1·d^-1. The blank and model groups received an equivalent volume of distilled water by gavage once daily. Body weight was recorded weekly，and food intake was monitored throughout the treatment period. Vaginal smears were collected daily and stained with hematoxylin-eosin （HE） to assess estrous cycle regularity. At the end of the experiment，mice were euthanized，and bilateral ovaries and uteri were rapidly excised and weighed to calculate ovarian and uterine indices （mg·g^-1）. Ovarian tissues were fixed，embedded，and sectioned for hematoxylin and eosin （HE） staining to evaluate histopathological changes. Iron deposition in ovarian tissue was visualized using Prussian blue staining. Serum levels of follicle-stimulating hormone （FSH），luteinizing hormone （LH），estradiol （E₂），and anti-Müllerian hormone （AMH） were measured by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA） content and superoxide dismutase （SOD） activity in ovarian homogenates were determined using commercial biochemical assay kits. Reactive oxygen species （ROS） levels in ovarian tissue were assessed by ROS fluorescence staining on frozen sections. Mitochondrial ultrastructure in ovarian tissue was examined by transmission electron microscopy （TEM）. Total RNA was extracted from ovarian tissue for real-time quantitative polymerase chain reaction （Real-time PCR） to quantify mRNA expression of ferritin heavy chain 1 （Fth1），ferritin light chain （Ftl），transferrin （Tf），transferrin receptor 1 （Tfr1），catalase （Cat），and glutathione peroxidase 1 （GPX1）. Protein expression levels of Fth1，Ftl，Tf，Tfr1，and glutathione peroxidase 4 （GPX4） were analyzed by Western blot. ResultsCompared with the blank group，mice in the model group exhibited significantly reduced body weight and severe estrous cycle disruption （P<0.01），a markedly increased uterine index （P<0.01），and a significantly decreased ovarian index （P<0.01）. The number of antral follicles was significantly reduced，while atretic follicles were markedly increased，accompanied by pronounced iron deposition in the ovarian stroma. Serum levels of AMH and E₂，as well as ovarian SOD activity，protein and mRNA expression of Tf and Tfr1，and mRNA levels of GPX1 and Cat were all significantly downregulated （P<0.05，P<0.01）. Conversely，serum FSH and LH levels，MDA content，protein and mRNA expression of Fth1 and Ftl，and ROS fluorescence intensity were significantly elevated （P<0.05，P<0.01），along with a marked decrease in GPX4 protein expression （P<0.01）. TEM revealed an increased number of damaged mitochondria in ovarian tissue，characterized by loss or disappearance of mitochondrial cristae. Compared with the model group，treatment with low，medium，and high doses of YJD and DHEA significantly improved body weight and ameliorated estrous cycle irregularities （P<0.05，P<0.01），decreased the uterine index （P<0.05），and increased the ovarian index （P<0.05，P<0.01）. These groups also showed increased numbers of antral follicles，reduced atretic follicles，and significantly diminished iron deposition in the ovarian stroma. Serum AMH and E₂ levels，ovarian SOD activity，protein and mRNA expression of Tf and Tfr1，and mRNA levels of GPX1 and Cat were all significantly upregulated （P<0.05，P<0.01）. In contrast，serum FSH and LH levels，MDA content，protein and mRNA expression of Fth1 and Ftl，and ROS fluorescence intensity were significantly reduced （P<0.05，P<0.01），while GPX4 protein expression was markedly increased （P<0.01）. Moreover，mitochondrial damage was alleviated，and mitochondrial ultrastructure was notably restored in ovarian tissue. ConclusionYijing decoction ameliorates ovarian reserve function in mice with chronic iron overload by upregulating the expression of Tf，Tfr1，and GPX4，downregulating the expression of Ft，Fth1，and Ftl，thereby alleviating systemic iron metabolism disorders，reducing oxidative stress in ovarian tissue，and restoring mitochondrial morphology and structure.

Objective To describe the significance of the pretreatment inflammatory indicators in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after undergoing radical radiotherapy. Methods The data of 246 ESCC patients who underwent radical radiotherapy were retrospectively collected. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values for platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). The Kaplan-Meier method was used for survival analysis. We conducted univariate and multivariate analyses by using the Cox proportional risk regression model. Software R (version 4.2.0) was used to create the nomogram of prognostic factors. Results The results of the ROC curve analysis showed that the optimal cutoff values of PLR, NLR, and SII were 146.06, 2.67, and 493.97, respectively. The overall response rates were 77.6% and 64.5% in the low and high NLR groups, respectively (P<0.05). The results of the Kaplan-Meier survival analysis revealed that the prognosis of patients in the low PLR, NLR, and SII group was better than that of patients in the high PLR, NLR, and SII group (all P<0.05). The results of the multivariate Cox regression analysis showed that gender, treatment modalities, T stage, and NLR were independent factors affecting the overall survival (OS). In addition, T stage and NLR were independent factors affecting the progression-free survival (PFS) (all P<0.05). The nomogram models of OS and PFS prediction were established based on multivariate analysis. The C-index values were 0.703 and 0.668. The calibration curves showed excellent consistency between the predicted and observed OS and PFS. Conclusion The pretreatment values of PLR, NLR, and SII are correlated with the prognosis of patients with ESCC who underwent radical radiotherapy. Moreover, NLR is an independent factor affecting the OS and PFS of ESCC patients. The NLR-based nomogram model has a good predictive ability.

ObjectiveTo investigate the effect and mechanism of Yijingtang （YJT） in treating diminished ovarian reserve （DOR） in rats by regulating the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank， model， low- and high-dose （12.579 and 25.158 g·kg^-1， respectively） YJT， and dehydroepiandrosterone （7.487 5 mg·kg^-1） groups， with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension （5 mg·kg^-1） by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days， and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and anti-Müllerian hormone （AMH）］ and inflammatory factors ［tumor necrosis factor-alpha （TNF-α）， interleukin-1beta （IL-1β）， and interleukin-10 （IL-10）］ were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction（Real-time PCR） was conducted to determine the mRNA levels of TLR4， MyD88， NF-κB profilin α （IκBα）， NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence （IF） was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group， the model group showed disturbed estrous cycles， increased inflammatory infiltration in the ovarian tissue， decreases in ovarian index and proportion of presinusoidal follicles， and an increase in the proportion of atretic follicles （P<0.05， P<0.01）. In addition， the model group showed elevated serum levels of FSH， LH， TNF-α， and IL-1β， up-regulated mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.01）， lowered serum levels of AMH， E₂， and IL-10， down-regulated mRNA level of IL-10 （P<0.01）， and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group， dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle， reduced inflammatory infiltration in the ovarian tissue， increased the ovarian index （P<0.01）， and changed the follicular composition ratio （P<0.01）. Furthermore， the drugs lowered the serum levels of FSH， LH， TNF-α， and IL-1β， down-regulated the mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and the protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.05， P<0.01）， raised the serum levels of AMH， E₂， and IL-10， up-regulated the mRNA level of IL-10 （P<0.05， P<0.01）， and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue， thereby improving the ovarian function in DOR rats.

ObjectiveTo investigate the effect and mechanism of Yijingtang （YJT） in treating diminished ovarian reserve （DOR） in rats by regulating the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank， model， low- and high-dose （12.579 and 25.158 g·kg^-1， respectively） YJT， and dehydroepiandrosterone （7.487 5 mg·kg^-1） groups， with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension （5 mg·kg^-1） by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days， and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and anti-Müllerian hormone （AMH）］ and inflammatory factors ［tumor necrosis factor-alpha （TNF-α）， interleukin-1beta （IL-1β）， and interleukin-10 （IL-10）］ were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction（Real-time PCR） was conducted to determine the mRNA levels of TLR4， MyD88， NF-κB profilin α （IκBα）， NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence （IF） was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group， the model group showed disturbed estrous cycles， increased inflammatory infiltration in the ovarian tissue， decreases in ovarian index and proportion of presinusoidal follicles， and an increase in the proportion of atretic follicles （P<0.05， P<0.01）. In addition， the model group showed elevated serum levels of FSH， LH， TNF-α， and IL-1β， up-regulated mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.01）， lowered serum levels of AMH， E₂， and IL-10， down-regulated mRNA level of IL-10 （P<0.01）， and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group， dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle， reduced inflammatory infiltration in the ovarian tissue， increased the ovarian index （P<0.01）， and changed the follicular composition ratio （P<0.01）. Furthermore， the drugs lowered the serum levels of FSH， LH， TNF-α， and IL-1β， down-regulated the mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and the protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.05， P<0.01）， raised the serum levels of AMH， E₂， and IL-10， up-regulated the mRNA level of IL-10 （P<0.05， P<0.01）， and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue， thereby improving the ovarian function in DOR rats.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Protein acylation is a group of recently identified chemical modification closely linked to me-tabolism with the metabolic intermediate acyl-coenzyme A(acyl-coA)as the substrate.Acylation posses-ses similar chemical structures to acetylation,with differences in carbon chain length,hydrophobicity,and charge.Most acyl-CoAs are intermediate metabolites,the level of which are influenced by the intra-cellular metabolic state.Therefore,protein acylation is greatly affected by cellular metabolism.Metabolic reprogramming is an important feature of tumor cells.In addition to the classic"Warburg effect",cancer cells exhibit abnormal regulation in lipid metabolism,amino acid metabolism and biological oxidation.Acylation on histones can impact chromatin structure,regulating gene expression and DNA repair critical-ly involved in cancer progression.On the other hand,acylation on non-histones can regulate signal trans-duction,enzymatic activity,or protein-protein interactions to affect cancer cell behaviors such as prolifer-ation,invasion,immune evasion,and vascular remodeling.Focusing on three types of acylation closely related to metabolism:lactylation,succinylation,and crotonylation,this article introduces the produc-tion,raw materials,regulatory mechanism and factors of protein acylation.We then review representative studies to show how cancer cell metabolic reprogramming can regulate these processes and histone/non-histone acylation levels,which subsequently affect the expression and function metabolism-related genes/proteins to form a bidirectional dialogue and accelerate cancer progression.In addition,we present sever-al prospects for potential research directions and translational applications in the field.