ObjectiveTo explore the mechanisms through which Si Junzitang （SJZD） ameliorates Alzheimer's disease （AD） induced by scopolamine （SCOP） in mice and the PC12 cell model induced by H₂O₂ based on the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsIn the animal experiments， an AD model was established in mice by intraperitoneal injection of SCOP （3 mg·kg^-1）. Morris water maze and open field tests （OFT） were conducted to assess learning and memory abilities. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe pathological changes in neurons. Immunofluorescence was used to detect amyloid β-protein_1-42 （Aβ_1-42） expression， and immunohistochemistry was employed to detect phosphorylated （p）-Tau expression. Transmission electron microscopy （TEM） was employed to observe ultrastructural changes in hippocampal neurons and synapses. Biochemical methods were used to measure the levels of acetylcholine （ACh）， acetylcholinesterase （AChE）， superoxide dismutase （SOD）， malondialdehyde （MDA）， catalase （CAT）， and lactate dehydrogenase （LDH）. Real-time PCR and Western blot were employed to measure the mRNA and protein levels of molecules in the Keap1/Nrf2/HO-1 pathway in the hippocampus. In the cell experiments， a PC12 cell model of oxidative damage model was established with H₂O₂. Cell count kit-8 （CCK-8） assays and flow cytometry were adopted to measure cell viability and apoptosis rates， and Western blot was employed to quantify the expression levels of proteins in the Keap1/Nrf2/HO-1 pathway. ResultsThe animal experiments showed that compared with the model group， the SJZD and donepezil groups showed shortened escape latency （P<0.01）， increased time in the target quadrant and platform crossings， and increased movement distance and duration in the central area of the open field （P<0.05， P<0.01）. HE and Nissl staining showed more organized neurons and increased Nissl bodies in the drug intervention groups （P<0.05， P<0.01）， and the Aβ_1-42 and p-Tau expression levels were downregulated （P<0.05， P<0.01）. TEM revealed reduced ultrastructural damage in hippocampal neurons and synapses in the drug intervention groups. In addition， the drug intervention groups showed declined levels of MDA， LDH， and AChE （P<0.05， P<0.01）， elevated levels of SOD， CAT， and ACh （P<0.05， P<0.01）， reduced Keap1 expression and increased Nrf2， HO-1， and NQO1 expression in the hippocampus （P<0.05， P<0.01）. The cell experiments showed that compared with the model group， the SJZD-containing serum increased the cell viability （P<0.05， P<0.01）， and decreased total apoptosis rates （P<0.05， P<0.01）. The drug intervention groups showed upregulated protein levels of Nrf2 and HO-1 and downregulated protein level of Keap1 （P<0.05， P<0.01）. ConclusionSJZD demonstrates protective effects against SCOP-induced AD in mice and H₂O₂-induced damage in PC12 cells through antioxidant mechanisms mediated by the Keap1/Nrf2/HO-1 pathway.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To explore the relationship between dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and clinical pathological features of invasive breast cancer and lymphovascular invasion(LVI).Methods Imaging and clinical pathological data were retrospectively collected from 508 patients with invasive breast cancer who underwent breast DCE-MRI at the First Medical Center of Chinese PLA General Hospital from January 2019 to August 2021.Patients were divided into the LVI-positive(LVI+)group(n=79)and LVI-negative(LVI-)group(n=429)based on postoperative pathological results.Univariate and multivariate logistic regression analyses were used to identify risk factors for LVI.Results Compared with LVI-group,LVI+group had a higher proportion of patients aged<45 years(44.3%vs.27.0%,P=0.002),non-mass-like enhancement(NME)(31.7%vs.17.7%,P=0.004),Ki-67 expression rate(40.0%vs.30.0%,P<0.001),high Ki-67 expression(94.9%vs.78.1%,P=0.001),Luminal B subtype(76.0%vs.60.1%,P=0.008),and positive axillary lymph nodes rate(72.2%vs.31.5%,P<0.001),while the proportion of Luminal A subtype was lower(2.5%vs.21.5%,P<0.001).Univariate and multivariate logistic regression analyses showed that age≥45 years(OR=0.468,95%CI 0.280-0.783,P=0.004)was an independent protective factor for LVI,while NME(OR=1.987,95%CI 1.126-3.444,P=0.016)was an independent risk factor.Compared with Luminal A subtype,patients with Luminal B subtype(OR=10.482,95%CI 3.164-64.923,P=0.001),HER-2 overexpression subtype(OR=11.571,95%CI 2.755-79.341,P=0.003)and triple-negative subtypes(OR=8.433,95%CI 1.985-57.908,P=0.009)had a higher risk of LVI.Conclusions Age≥45 years is an independent protective factor for LVI,while NME is an independent risk factor.Among molecular subtypes,patients with Luminal B,HER-2 overexpression and triple-negative subtypes have a higher risk of LVI compared with the Luminal A subtype.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

This study explored the prescription pattern of traditional Chinese medicine(TCM) in the treatment of hypertensive left ventricular hypertrophy(LVH), so as to provide a relevant theoretical basis for the clinical diagnosis and treatment of hypertensive LVH. The study systematically searched the databases of CNKI, Wanfang, VIP, and SinoMed to screen out the qualified literature on TCM treatment of hypertensive LVH and used Microsoft Excel 2021 to establish the relevant prescription database. It also counted the frequency, property, flavor, and meridian affiliation of TCM in the prescriptions and classified their efficacy. The study used Lantern 5.0 and Rstudio software to analyze the hidden structural models and association rules of the high-frequency TCM with a frequency of >3.50% and adopted Origin 2024 software to visualize the data, so as to explore the prescription pattern of TCM in treating hypertensive LVH. The results showed that a total of 128 TCM prescriptions were included, involving 163 TCM with a total frequency of 1 242. The high-frequency TCM included Salviae Miltiorrhizae Radix et Rhizoma, Uncariae Ramulus Cum Uncis, Gastrodiae Rhizoma, Poria, and Chuanxiong Rhizoma, with the main efficacy from blood-activating and stasis-resolving herbs, tonic herbs, and liver-calming and wind-extinguishing herbs. The latent structure analysis(LSA) identified 10 latent variables, 20 latent classes, 7 comprehensive clustering models, and 23 core prescriptions. It was speculated that the common syndromes of hypertensive LVH included blood stasis obstructing the collaterals, ascending hyperactivity of liver Yang, Yin deficiency with Yang hyperactivity, and intermingled phlegm and blood stasis. The association rule analysis yielded 33 strong association rules, with the highest comprehensive association rule being Gastrodiae Rhizoma→Uncariae Ramulus Cum Uncis. Hypertensive LVH is characterized by asthenia in origin and asthenia in superficiality, with Yin deficiency and Qi deficiency as the origin and blood stasis and phlegm as the superficiality. Clinical treatment focuses on activating blood circulation, resolving stasis, tonifying Qi, and nourishing Yin, combined with syndrome-specific therapies such as calming wind and stopping convulsions, clearing heat, eliminating dampness and resolving phlegm, and promoting diuresis and reducing swelling.
Drugs, Chinese Herbal/therapeutic use* ; Data Mining ; Humans ; Hypertension/complications* ; Hypertrophy, Left Ventricular/physiopathology* ; Medicine, Chinese Traditional ; Drug Prescriptions

During tumor progression, the mechanical properties of the tumor microenvironment play a pivotal regulatory role. As core mechanical indicators, cellular stiffness and extracellular matrix stiffness profoundly influence tumor development through multiple pathways, including cytoskeletal remodeling, activation of signaling pathways, and metabolic regulation. Studies have demonstrated that the tissue stiffness of various solid tumors is significantly higher than that of corresponding normal tissues, while their cellular stiffness exhibits the opposite trend. This mechanical characteristic is also observed in oral squamous cell carcinoma and exerts crucial regulatory effects during tumor progression. This review systematically summarizes the molecular composition and regulatory mechanisms underlying the stiffness of tumor cells and extracellular matrix (ECM). Mainstream stiffness detection technologies such as atomic force microscopy, microfluidic deformation, and real-time deformability cytometry are outlined, with particular emphasis on their applications and limitations in oncology research. This review comprehensively analyzes how mechanical properties regulate key processes in tumor progression, including growth, proliferation, invasion, metastasis, angiogenesis, lymphangiogenesis, drug resistance, and immune escape. This review synthesizes biomechanics-based therapeutic strategies, including: ① targeting the regulation of tumor cell stiffness through cytoskeletal modulators and cholesterol-depleting agents to enhance immune responses; ② reducing ECM stiffness by matrix remodeling enzyme inhibitors, ECM component modulators, or receptor antagonists to improve drug delivery efficiency, and combining with immunotherapy or photothermal therapy for enhanced therapeutic effects; ③ enhancing the mechanical adaptability and anti-tumor activity of immune cells through pharmacological or genetic approaches. This review establishes a robust conceptual framework for developing novel anti-tumor therapeutic strategies and provides insights for future clinical management of oral squamous cell carcinoma.

Objective To compare the benefits and drawbacks of primary patch expansion versus pericardial tube right ventricular-pulmonary artery connection in patients diagnosed with pulmonary atresia with ventricular septal defect (PA/VSD). Methods A retrospective study was conducted on patients diagnosed with PA/VSD who underwent primary right ventricular-pulmonary artery connection surgery at our center between 2010 and 2020. Patients were categorized into two groups based on the type of right ventricular-pulmonary artery connection: a pericardial tube group and a patch expansion group. Clinical data and imaging findings were compared between the two groups. Results A total of 51 patients were included in the study, comprising 31 males and 20 females, with a median age of 12.57 (4.57, 49.67) months. The pericardial tube group included 19 patients with a median age of 17.17 (7.33, 49.67) months, while the patch expansion group consisted of 32 patients with a median age of 8.58 (3.57, 52.72) months. In both groups, the diameter of pulmonary artery, McGoon index, and Nakata index significantly increased after treatment (P<0.001). However, the pericardial tube group exhibited a longer extracorporeal circulation time (P<0.001). The reoperation rate was notably high, with 74.51% of patients requiring further surgical intervention, including 26 (81.25%) patients in the patch expansion group and 12 (63.16%) patients in the pericardial tube group. No statistical differences were observed in long-term cure rates or mortality between the two groups (P＞0.005). Conclusion In patients with PA/VSD, both patch expansion and pericardial tube right ventricular-pulmonary artery connection serve as effective initial palliative treatment strategies that promote pulmonary vessel development and provide a favorable foundation for subsequent radical operations. However, compared to the pericardial tube approach, the patch expansion technique is simpler to perform and preserves some intrinsic potential for pulmonary artery development, making it the preferred procedure.

Exercise-induced metabolic remodeling is a fundamental adaptive process whereby the body reorganizes systemic and cellular metabolism to meet the dynamic energy demands posed by physical activity. Emerging evidence reveals that such remodeling not only enhances energy homeostasis but also profoundly influences immune function through complex molecular interactions involving glucose, lipid, and protein metabolism. This review presents an in-depth synthesis of recent advances, elucidating how exercise modulates immune regulation via metabolic reprogramming, highlighting key molecular mechanisms, immune-metabolic signaling axes, and the authors’ academic perspective on the integrated “exercise-metabolism-immunity” network. In the domain of glucose metabolism, regular exercise improves insulin sensitivity and reduces hyperglycemia, thereby attenuating glucose toxicity-induced immune dysfunction. It suppresses the formation of advanced glycation end-products (AGEs) and interrupts the AGEs-RAGE-inflammation positive feedback loop in innate and adaptive immune cells. Importantly, exercise-induced lactate, traditionally viewed as a metabolic byproduct, is now recognized as an active immunomodulatory molecule. At high concentrations, lactate can suppress immune function through pH-mediated effects and GPR81 receptor activation. At physiological levels, it supports regulatory T cell survival, promotes macrophage M2 polarization, and modulates gene expression via histone lactylation. Additionally, key metabolic regulators such as AMPK and mTOR coordinate immune cell energy balance and phenotype; exercise activates the AMPK-mTOR axis to favor anti-inflammatory immune cell profiles. Simultaneously, hypoxia-inducible factor-1α (HIF-1α) is transiently activated during exercise, driving glycolytic reprogramming in T cells and macrophages, and shaping the immune landscape. In lipid metabolism, exercise alleviates adipose tissue inflammation by reducing fat mass and reshaping the immune microenvironment. It promotes the polarization of adipose tissue macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Moreover, exercise alters the secretion profile of adipokines—raising adiponectin levels while reducing leptin and resistin—thereby influencing systemic immune balance. At the circulatory level, exercise improves lipid profiles by lowering pro-inflammatory free fatty acids (particularly saturated fatty acids) and triglycerides, while enhancing high-density lipoprotein (HDL) function, which has immunoregulatory properties such as endotoxin neutralization and macrophage cholesterol efflux. Regarding protein metabolism, exercise triggers the expression of heat shock proteins (HSPs) that act as intracellular chaperones and extracellular immune signals. Exercise also promotes the secretion of myokines (e.g., IL-6, IL-15, irisin, FGF21) from skeletal muscle, which modulate immune responses, facilitate T cell and macrophage function, and support immunological memory. Furthermore, exercise reshapes amino acid metabolism, particularly of glutamine, arginine, and branched-chain amino acids (BCAAs), thereby influencing immune cell proliferation, biosynthesis, and signaling. Leucine-mTORC1 signaling plays a key role in T cell fate, while arginine metabolism governs macrophage polarization and T cell activation. In summary, this review underscores the complex, bidirectional relationship between exercise and immune function, orchestrated through metabolic remodeling. Future research should focus on causative links among specific metabolites, signaling pathways, and immune phenotypes, as well as explore the epigenetic consequences of exercise-induced metabolic shifts. This integrated perspective advances understanding of exercise as a non-pharmacological intervention for immune regulation and offers theoretical foundations for individualized exercise prescriptions in health and disease contexts.

Acute pancreatitis(AP)is a frequently encountered acute abdominal syndrome in clinical settings,and the integrated model of traditional Chinese and Western medicine(TCM-WM)has demonstrated notable advantages in the diagnosis and treatment of AP.To systematize and standardize clinical practices related to develop clinical pathway for integrated TCM-WM diagnosis and treatment of AP,which enhances the efficiency and quality of patient care.This pathway focuses on AP,a common acute and life-threatening disease within the digestive system,and outlines that the central pathological mechanism involves pancreatic injury and localized inflammation resulting from the abnormal activation of pancreatic enzymes.It has the characteristics of rapid onset,multiple causes,and complex manifestations.Severe cases can be life-threatening.At present,conventional treatments encompass a diverse range of modalities.Moreover,traditional Chinese medicine(TCM)holds distinct advantages in alleviating relevant symptoms,and TCM-WM is gaining increasing prevalence.To enhance the standardization and consistency of diagnostic and therapeutic practices,this clinical pathway clearly delineates the target patient population,which includes individuals diagnosed with abdominal pain disorder according to TCM and with AP in accordance with WM criteria,as well as the corresponding inclusion standards.The diagnostic framework integrates both TCM and WM guidelines,and further incorporates disease staging,severity grading,and syndrome differentiation to support a comprehensive and integrated diagnostic strategy.The treatment integrates approaches from both TCM and WM.Within the WM framework,interventions consist of basic supportive care,infection control,nutritional support,and the management of complications.In the context of TCM,the protocol includes syndrome differentiation and corresponding therapeutic strategies(Distinct syndrome patterns are identified and managed during the acute and convalescent phases),such as acupuncture and retention enema.This clinical pathway addresses multiple key components,including preventive strategies,post-treatment follow-up,criteria for evaluating therapeutic efficacy,admission and discharge,admission examination protocols,discharge criteria,and the rationale for deviations or withdrawal from the pathway.It is designed to provide a systematic and standardized reference framework for relevant clinical practices.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.