Given the limitations of traditional scientific research methods in revealing the complex and dynamic evolution of disease pathomechanisms， this paper analyzes the current state and challenges of the traditional Chinese medicine （TCM） pathomechanism syndrome differentiation system within the framework of systems thinking. The challenges include insufficient experimental models， low data standardization， complex nonlinear characteristics， and difficulties in integrating expert experience. By leveraging qualitative-quantitative comprehensive integration methods， this paper proposes specific research strategies， including constructing qualitative models of pathomechanism evolution， employing mathematical models for validation and quantitative analysis to reveal pathomechanism patterns， and incorporating a "human-centered" approach to achieve human-machine collaboration. These strategies aim to provide insights for the modernization and development of a new TCM pathomechanism syndrome differentiation system.

This paper summarizes the exploration process and academic significance of the academic thought of Zhou Zhongying,a master of traditional Chinese medicine,who took the creation of a new system of TCM pathogenesis theory as the core,and interprets its theoretical connotation.As a pioneer in the construction of higher education textbooks for traditional Chinese medicine,Professor Zhou Zhongying created the outline of TCM internal medicine viscera differentiation,persisted in carrying out innovative research on patho-genesis theory,achieved fruitful academic results,and enriched and developed the academic system of TCM theory.In the clinical di-agnosis and treatment of exogenous febrile diseases and acute and difficult internal injuries,he systematically created new pathogenesis theories such as stasis-heat theory and cancer toxicity theory.Based on this,the legislation of medication can improve the clinical effi-cacy,and it is realized that identifying the pathogenesis is the key link in syndrome differentiation and treatment.In his later years,Professor Zhou Zhongying,guided by the holistic view,proposed the"thirteen pathogenesis"and constructed a new system of TCM pathogenesis differentiation,highlighting the guiding value of complex pathogenesis and the causal chain of pathogenesis elements to complex clinical diseases and syndromes,forming a theory with the idea of"examining syndromes and seeking pathogenesis,activating syndrome differentiation"as its soul.This theory breaks through the rigid thinking of syndrome differentiation and treatment based on a single pathogenesis or fixed syndrome type,reconstructs the theoretical framework of TCM with the idea of holistic view,and is a major academic innovation in modern TCM.

Toxic Chinese materia medica has been highly valued by its specialized and effective effects， but its safe application has become an urgent clinical problem to be solved. Compatibility for toxic attenuation is an important method for the rational clinical application of toxic Chinese materia medica as well as the promotion of its therapeutic advantages. The theory of “heterogeneous medicinals mutual restriction” elaborated in this article has been formed through long-term clinical practice and cognition， and refinement of clinical experience， which means that the nature partiality of toxic Chinese materia medica can be adjusted， and the toxicity can be suppressed through reasonable combination with herbal medicinalsof different properties， flavors， and effects. This theory covers the modes of compatibility for toxicity attenuation and the interaction relationships， like the restriction of medicinals with different properties and flavors， restriction of medicinals with different effects， and inhibiting toxins by reinforcing healthy qi. The opposite and complementary effects of various medicinals combinations are an extension of the connotations of this theory， and the principles can be explained from material basis and mechanism of action. Under the guidance of this theory， it is possible to optimize the compound prescription strategies of toxic Chinese materia medica， and provide new strategies for the clinical combinations of toxic Chinese materia medica， thereby achieving the reduction of toxicity and enhancement of effectiveness of the compound formulas.

Objective:To conduct systematic review of mother-infant attachment measurement tools based on Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines.Methods:The researches on mother-infant attachment measurement tools in PubMed, Scopus, Embase, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, WanFang Data and VIP was searched by computer, and the search period was from establishment of the databases to October 30, 2023. Two reviewers trained in evidence-based methodology independently screened the literature, extracted and summarized the data, and systematically evaluated the attributes of the measurement tools using the COSMIN guideline bias risk list and good measurement attribute standards.Results:A total of 35 studies were included, including seven maternal-infant attachment measurement tools. Among them, the content validity quality of the Maternal-fetal Attachment Tool was sufficient (evidence quality was advanced), the structural validity quality was uncertain (evidence quality was intermediate), the internal consistency quality was sufficient (evidence quality was advanced) and the hypothesis testing quality was sufficient (evidence quality was advanced), which was recommended at level A.Conclusions:This study systematically evaluates seven measurement tools for maternal-infant attachment, among which the Maternal-fetal Attachment Tool is class A tool and is recommended for use.

Objective To analyze the risk factors of cardiac rupture(CR)still occurrence after emer-gency percutaneous coronary intervention(PCI)in the patients with acute myocardial infarction(AMI).Methods The patients with AMI admitted and treated in this hospital from January 2017 to February 2021 were retrospectively analyzed.The patients with AMI who still developed CR after successful emergency PCI treatment were included in the CR group(n=27),and the patients with AMI who matched the gender,age,myocardial infarction location,acute ST-segment elevation myocardial infarction(STEMI)and successful e-mergency revascularization with the CR group according to the ratio of 1∶2,moreover without complicating CR served as the non-CR group(n=54).The gender,age,comorbidities,clinical indicators,laboratory indica-tors,drug use situation were collected for conducting the analysis.The univariate and multivariate logistic re-gression were used to analyze the risk factors of CR.Results There were no statistically significant differ-ences in the gender,age,comorbidities(hypertension,diabetes,hypercholesterolemia,old myocardial infarc-tion,old cerebral infarction,renal insufficiency,hyperuricemia)and myocardial infarction location between the two groups(P＞0.05).In the comorbidities,the incidence rate of atrial fibrillation in the CR group was higher than that in the non-CR group(25.9％vs.9.3％),and the difference was statistically significant(P＜0.05).The heart rate,serum creatinine,serum uric acid,N-terminal brain natriuretic peptide precursor(NT-proB-NP),cardiac troponin Ⅰ(cTnⅠ),proportion of no reflow in PCI,and the proportion of blood flow grade 3 in myocardial infarction thrombolysis test(TIMI)after PCI in the CR group were significantly higher than those in the non-CR group,while the proportions of systolic blood pressure,albumin,LVEF,use of β receptor block-ers and renin-angiotensin-aldosterone system(RAAS)inhibitors were lower than those in the non-CR group,and the differences were statistically significant(P＜0.05).Atrial fibrillation was an independent risk factor for CR(OR=3.06,95％CI:1.16-8.10,P＜0.05).High level of albumin(OR=0.93,95％CI:0.88-0.99,P＜0.05)and high level of LVEF(OR=0.92,95％CI:0.86-0.99,P＜0.05)were the independent protective factors for CR.Conclusion The occurrence of CR is correlated with multifactors,atrial fibrillation is an independent risk factor for CR,and the high levels of albumin and LVEF are the independent protective factors for CR.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

OBJECTIVE To study the protective effects of mangiferin against oxidative stress injury of myocardial cells induced by hydrogen peroxide （H2O2）， and its effects on the expression of nuclear factor of activated T cell cytoplasmic 4（NFATc4）. METHODS H9c2 myocardial cells were cultured in vitro and divided into blank group， H2O2 group， and 50， 100， 150 μmol/L mangiferin groups. Mangiferin groups were treated with different concentrations of mangiferin for 12 h， and then were subjected to H2O2 （200 μmol/L） stimulation for 12 hours together with the H2O2 group； relative survival rate was detected in each group， and the levels of superoxide dismutase （SOD）， catalase （CAT） and malondialdehyde （MDA） in cell supernatant and reactive oxygen species （ROS） in H9c2 cells were measured. Meanwhile， the expressions of apoptosis-related proteins [B cell lymphoma 2 （Bcl- 2）， Bcl-2 associated X protein （Bax）， cleaved caspase-3] and nuclear protein NFATc4 were determined. Furthermore， the NFATc4 interference sequence was transfected， and the effects of NFATc4 on oxidant stress indexes and apoptosis-related proteins in H2O2- induced myocardial cells were investigated. RESULTS Compared with blank group， relative cell viability， the levels of SOD and CAT， relative expression of Bcl-2 were decreased significantly， while the levels of MDA and ROS， relative expressions of Bax， cleaved caspase-3 and nuclear protein NFATc4 were increased significantly （P＜0.05 or P＜0.01）. Compared with the H2O2 group， the above indexes of 100 and 150 μmol/L mangiferin groups were reversed significantly （P＜0.05）. After the transfection of the NFATc4 interference sequence， the expression of nuclear protein NFATc4 was down-regulated significantly； the levels of MDA and SOD， the protein expressions of Bax and cleaved caspase-3 were all decreased/down-regulated significantly， while the levels of SOD and CAT， and the protein expression of Bcl-2 were all increased/up-regulated significantly， compared with H2O2 group （P＜ 0.05）. CONCLUSIONS Mangiferin can relieve H2O2-induced oxidative stress of H9c2 cells， reduce the apoptosis and inhibit the nuclear translocation of NFATc4， thereby alleviating myocardial cell damage； reducing the nuclear level of NFATc4 protein is related to reducing H2O2-induced oxidative stress and cell apoptosis.

‍Traditionally， the progression from compensated liver cirrhosis to decompensated liver cirrhosis has been considered an irreversible point in the natural history of the disease； however， with the suppression of underlying etiology， cure， and disease regression， this view is challenged by an increasing number of new evidence， and the idea of “recompensation of liver cirrhosis” is gradually being accepted. In recent years， scholars in China and globally have been exploring the specific definition of recompensation of liver cirrhosis and the clinical features of patients. By summarizing the recent studies on recompensation of liver cirrhosis in China and globally， integrating existing views， and analyzing related research evidence， this article points out the main challenges in the field of recompensation at this stage， including the lack of in－depth clinical and basic research， the need to define recompensation in the context of NAFLD， and related ethical issues， in order to provide new directions for future research in this field.

‍Nonalcoholic fatty liver disease （NAFLD） is a group of highly heterogeneous diseases closely associated with metabolic dysfunction. Sarcopenia is a syndrome caused by a continuous decline in muscle mass， strength， and function， and it is often accompanied by NAFLD. Insulin resistance is the main pathological mechanism for sarcopenia and NAFLD， and in addition， factors such as changes in proteins and branched‍-‍chain amino acid， hyperammonemia， intestinal flora， and endocrine dysfunction can also lead to sarcopenia and NAFLD. With the deepening of clinical research， many published prospective studies have confirmed the existence of a bidirectional and complex pathophysiological relationship between sarcopenia and NAFLD. This article reviews the bidirectional relationship between sarcopenia and NAFLD， discusses the common pathogenesis of sarcopenia and NAFLD， summarizes the challenges faced in this field， and proposes new directions for the research on the bidirectional relationship between NAFLD and sarcopenia.

Objective:To explore the relationship between proactive personality, resilience and achievement motivation of military cadets, and to explore the mediating role of resilience between proactive personality and achievement motivation, as well as the moderating effect of cadets’leading ability on this mediating role.Methods:In this study, 109 military cadets were measured with proactive personality scale, Connor-Davidson resilience scale (CD-RISC) and achievement motivation scale. SPSS 26.0 was used for descriptive statistical analysis and correlation analysis.Results:①There was a significant correlation among the total scores of proactive personality, resilience and achievement motivation ( Ps<0.01). ②Proactive personality could significantly predict the level of achievement motivation ( a=0.454, P<0.001), and resilience could significantly predict the level of achievement motivation ( b=0.231, P=0.019). ③Resilience significantly mediated the relationship between proactive personality and achievement motivation ( c′=0.3, P=0.003). ④Cadets' leading ability moderated the effect of resilience on achievement motivation (index=0.338, 95% CI: 0.057 to 0.881). The mediating effect of resilience between proactive personality and achievement motivation was significant for cadets' leaders (Effect=0.381, 95% CI: 0.085 to 1.005), but not significant for other students (Effect=0.043, 95% CI: -0.069 to 0.252). Conclusion:The proactive personality of military cadets can affect the level of achievement motivation through psychological resilience, which is also moderated by cadre identity, suggesting that military education should improve the level of achievement motivation in many ways.