Guided by the theories of yin-yang and collateral disease， this paper identifies the dysregulation of yang qi ascent and descent as the core pathomechanism of hypertension. Based on clinical experience， a treatment approach centered on the method of raising yang and promoting descent was proposed. Clinically， three major syndrome types were identified. Firstly， deficiency of zong qi （ancestral qi） with blood stasis， obstruction of phlegm-turbidity and blood stasis， and hyperactivity of liver yang. Corresponding empirical formulation， Yizong Huoxue Decoction （益宗活血汤） was applied to tonify zong qi， invigorate blood， and raise yang. Secondly， Lizong Huoxue Decoction （理宗活血汤） was used to resolve phlegm， promote yang qi circulation， and regulate qi and blood. Thirdly， Qinggan Tongluo Decoction （清肝通络饮） was used to clear the liver， dredge collaterals， and subdue hyperactive yang. For special types such as non-dipper hypertension， time-specific syndrome differentiation and treatment can be applied based on a thorough understanding of the underlying pathomechanism， aiming to provide new insights into clinical diagnosis and treatment of hypertension.

Chronic heart failure （CHF） is a complex clinical syndrome that the cardiac output is not enough to meet the metabolic needs of the body， or depends on the increase of filling pressure to compensate. Its high morbidity and mortality pose a serious threat to human health， necessitating attention and active intervention. At present， western medicine treatment of CHF is mainly based on diuretics， intravenous vasodilators， intravenous positive inotropic drugs， etc.， which， however， have problems such as long medication cycles， serious side effects， and limited applicable population. Recent studies have shown that traditional Chinese medicine can act in a multi-pathway， multi-component， and multi-target manner， showing unique advantages in the prevention and treatment of CHF. Buyang Huanwutang has the effects of tonifying Qi， activating blood， and dredging collaterals. Clinical and mechanism studies have confirmed that this prescription is effective in treating CHF and its syndromes. The clinical studies can be classified into two categories. Studies of the first category use simple modern medical diagnostic criteria as the inclusion criteria for CHF patients， which can improve the scientificity and objectivity. Studies of the second category uses modern medicine combined with traditional Chinese medicine disease diagnostic criteria for the screening of CHF patients， which helps to improve the accuracy of efficacy evaluation. However， there are problems such as the lack of unified research standards and the insufficiency of mechanism research. In addition， the available studies remain to be classified or summarized. This study systematically sorted out the clinical and mechanism studies of Buyang Huanwutang in the treatment of CHF in recent years to review the research status. In clinical treatment， Buyang Huanwutang can be used alone， or modified， or combined with other prescriptions or Western medicine. The mechanism studies predict that Buyang Huanwutang can ameliorate CHF by regulating the calcium balance， protecting the mitochondrial structure and function， and regulating intestinal flora. This review aims to provide a theoretical basis and practical guidance for the clinical application and optimization and subsequent in-depth study of Buyang Huanwutang in the treatment of CHF.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

Objective: To examine the impacts of chemotherapy/radiotherapy, targeted therapy, and combined treatment on the quality of life in patients with intermediate and advanced lung cancer. Methods: The patients with intermediate and advanced lung cancer undergoing chemotherapy/radiotherapy, targeted therapy, and combined treatment for the first time were recruited from a tertiary hospital in Weifang City, Shandong Province, using a quota sampling method in September 2023. Basic information was collected using a general information questionnaire, and the quality of life was assessed using the Chinese version of Functional Assessment of Cancer Therapy-General. The investigation started on the 7th day of treatment, and the follow-ups were conducted at 3 and 6 months. The quality of life in patients with different treatment regimens and at different treatment time were compared using repeated measure analysis of variance. Results: There were 26 chemotherapy/radiotherapy patients, 32 targeted therapy patients, and 95 combination therapy patients. There were no significant differences in age, gender, place of residence, education level, self-rated economic status, medical insurance, pathological type and disease stage among the three treatment regimens (all P>0.05). The repeated measure analysis of variance showed an interaction effect between time and group among patients receiving the three treatment regimens (P<0.05). The quality of life scores of patients receiving combination therapy decreased with extended treatment time (all P<0.05). The quality of life scores of patients receiving targeted therapy at 3 and 6 months were lower than those treated for 7 days (both P<0.05). No significant differences were observed in quality of life scores among chemotherapy/radiotherapy patients with different treatment durations (all P>0.05). At 3 and 6 months, patients receiving combination therapy had lower quality of life scores compared to those receiving chemotherapy/radiotherapy or targeted therapy (all P<0.05). Conclusion The decline in quality of life for patients with intermediate and advanced lung cancer undergoing chemotherapy/radiotherapy and targeted therapy is less than that for patients receiving combined therapy.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

Objective:To explore the role of curcumin (Cur) in improving IgA nephropathy (IgAN) and its related mechanisms.Methods:Fifty 7-month-old miR-23b knockout (miR-23b -/-) mice weighing (25±5) g were used to establish an IgAN disease model, and were randomly divided into IgAN group, IgAN+Cur (150 mg/kg) group and IgAN+Cur (300 mg/kg) group using simple randomisation. Sixteen healthy 7-month-old weighing (25±3) g C57BL/6J wild-type mice served as the normal control group. IgAN+Cur (150 mg/kg) and IgAN+Cur (300 mg/kg) groups were respectively gavaged continuously with 150 mg/kg Cur and 300 mg/kg Cur for 8 weeks, and the normal control and IgAN groups were gavaged continuously with an equal dose of 0.9% sodium chloride solution for 8 weeks. The samples of urine, serum, intestinal fluid, intestinal tissues, kidney tissues and liver tissues were collected from each group. In vitro experiments, human cloned colon adenocarcinoma (Caco-2) cells were divided into blank control (Ctrl), Ctrl+Cur (10 μmol/L), Ctrl+ Cur (60 μmol/L), tumor necrosis factor-α（TNF-α), TNF-α+Cur (10 μmol/L) and TNF-α+Cur (60 μmol/L) groups. Enzyme-linked immunosorbent assay was used to detect serum alanine transaminase, aspartate transaminase, secretory IgA (sIgA), creatinine, blood urea nitrogen, 24 h urine microalbumin, as well as sIgA, TNF-α, interleukin（IL)-6 and IL-1β in the intestinal fluids. HE staining was used to observe the effect of Cur on liver tissues, the hyperplasia of glomerular mesangial zone in kidney tissues and the morphological and structural changes of intestinal epithelial barrier, and the histopathological damage scores were performed respectively. PAS staining was used to observe the changes of glomerular basement membrane and mesangial matrix. Immunofluorescence was used to observe the deposition of immune complexes in the glomerular mesangial zone. Real-time quantitative PCR was used to detect the mRNA expression levels of B-cell activating factor ( BAFF) and a proliferation inducing ligand ( APRIL). Western blotting was used to detect the protein expression levels of tight junction proteins zonula occluden-1 (ZO-1) and occludin in the mouse intestinal tissues. The potential targets of Cur in IgAN were predicted. Western blotting was used to detect the protein expression levels of tight junction proteins, as well as Toll-like receptor 9 (TLR9), myeloid differentiation primary response protein (MyD88), nuclear factor-κB p65 (NF-κB p65) and p-NF-κB p65. Results:Genetic identification results revealed that all IgAN model mice exhibited the miR-23b -/- genotype, confirming successful model establishment. Seven-month-old mice were subsequently selected for Cur treatment. Histopathological analysis demonstrated no significant differences in hepatic tissue morphology across groups, with comparable liver histopathological injury scores and unaltered liver function parameters, thereby validating the safety of Cur administration. Compared with the normal control group, IgAN mice displayed elevated levels of serum sIgA, serum creatinine, blood urea nitrogen and 24 h urine microalbumin (all P<0.05). Renal pathological results revealed severe mesangial hypercellularity in glomeruli, higher glomerular injury scores, and notable glomerular mesangial deposits of IgA, IgG and complement C3 in IgAN mice (all P<0.05). Additionally, intestinal pathological alterations were observed, including structural changes in intestinal epithelium and Peyer's patches, accompanied by significantly higher intestinal histopathological injury scores in IgAN mice ( P<0.05). Intestinal epithelial expression levels of ZO-1 and occludin were significantly reduced, while sIgA, TNF-α, IL-1β and IL-6 in intestinal fluid were elevated (all P<0.05). Serum FITC fluorescence intensity was markedly increased, and intestinal tissue exhibited upregulated mRNA expression of BAFF and APRIL (all P<0.05). Following Cur treatment, serum sIgA level and renal function indices in mice showed partial recovery (all P<0.05). Renal pathological improvements included alleviated mesangial hypercellularity, reduced glomerular injury scores, and diminished glomerular immune complex deposition (all P<0.05). Intestinal pathologies, including epithelial and Peyer's patch lesions, were mitigated, with decreased intestinal histopathological injury scores ( P<0.05). Additionally, intestinal tight junction protein expression levels were upregulated, intestinal fluid sIgA level was reduced, inflammatory markers were attenuated, serum FITC fluorescence intensity was declined, and intestinal BAFF and APRIL mRNA expression levels were downregulated (all P<0.05). In vitro experiments demonstrated that TNF-α exposure reduced tight junction protein expression in Caco-2 cells, whereas Cur treatment reversed the effect (all P<0.05). Target prediction analysis revealed that Cur effectively bound to TLR9 structural domain in IgAN. Experimental validation confirmed that Cur treatment suppressed the upregulated protein expression levels of TLR9, MyD88, NF-κB p65 and p-NF-κB p65 in intestinal tissues of IgAN mice (all P<0.05). Conclusion:Cur has a significant effect in the treatment of IgAN and can regulate intestinal mucosal immunity by inhibiting the TLR9/MyD88/NF-κB signaling pathway, thereby reducing renal injury and protecting the kidneys.

Objective:To investigate the dynamic changes of inflammatory biomarkers in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) support after cardiac surgery, and evaluate their predictive value for in-hospital mortality.Methods:The retrospective study included 212 patients who underwent VA-ECMO support following cardiac surgery at Beijing Anzhen Hospital, Capital Medical University, from January 2021 to May 2024. Baseline characteristics and inflammatory markers during ECMO support including procalcitonin (PCT), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and fibrinogen (FBG) were collected. Univariate analysis, ROC curves, and multivariate logistic regression were performed to assess the association of these indicators with outcomes. Results:On day 3 post-ECMO, mean PCT and CRP levels were significantly higher in the deceased group (87 cases) than in the survival group (125 cases). PCT demonstrated an area under the curve ( AUC) of 0.750 (95% CI: 0.680-0.819) for predicting mortality, while CRP had an AUC of 0.701(95% CI: 0.625-0.778). No significant differences were observed in FBG, NLR, or PLR between the two groups. Lactate levels at 24 h post-ECMO ( AUC=0.723) and SOFA scores ( OR=2.511, AUC=0.713) were also significantly associated with mortality risk in the deceased group ( P<0.05). Conclusion:Dynamic increases in PCT and CRP are independent predictors of in-hospital mortality in cardiac surgery patients supported by ECMO. Elevated lactate levels and SOFA scores, aligning with previous studies, reflect severe tissue hypoperfusion and multi-organ dysfunction in non-survivors, underscoring the necessity of dynamic monitoring of inflammatory and organ function markers for prognosis assessment.

Classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) comprise a group of clonal disorders originating from hematopoietic stem cells, commonly characterized by thrombotic events, extramedullary hematopoiesis, and a propensity for malignant progression to myelofibrosis or acute leukemia. With the inclusion in the core diagnostic criteria, molecular biomarkers has exhibited applicational valus in multiple levels in the aspects of personalized therapy to subtype MPN, interpret phenotypic heterogeneity, and predict clinical outcomes. Molecular biomarkers are currently being applied in disease diagnosis, progression prediction, therapeutic strategy refinement, precision monitoring, familial MPN screening, and the development of emerging detection technologies, advancing the shift from fundamental MPN research to individualized clinical management.