Pulmonary hypertension (PH), marked by sustained elevation of pulmonary artery pressure, imposes a heavy burden on the right ventricle and may culminate in right heart failure. Its pathogenesis is multifaceted, encompassing endothelial dysfunction, vascular smooth muscle proliferation, inflammation, thrombosis, and genetic factors. Animal models serve as core tools for exploring PH mechanisms and therapies, each with unique strengths and limitations. The single-dose monocrotaline (MCT) model is one of the most commonly used experimental animal models of PH and is widely applied in mechanistic studies, drug screening, and efficacy evaluation; it offers simplicity and cost-effectiveness, can induce PH within a short period, yet its pathophysiology differs to some extent from human idiopathic PH. In contrast, the Sugen5416 combined with chronic hypoxia model better mimics PH progression by placing animals under hypoxic conditions to induce pulmonary vasoconstriction and vascular remodeling, but it requires a longer modelling time, and the degree of hypoxia has a substantial impact on experimental outcomes. Beyond these two commonly used modeling approaches, a variety of emerging techniques have been applied in PH research; gene-editing technologies enable precise investigation of specific gene functions in PH. Additionally, induced pluripotent stem cell-based 3D organoid technology allows for individualized modelling while preserving patients' genetic information for precise clinical translation. Each model or technology can simulate different aspects of the pathological processes of human PH, and their findings provide key insights into the nature of the disease and serve as an important platform for the development of novel therapeutic targets. This paper comprehensively describes various animal models and emerging technologies used in PH research, analyzing their characteristics, applications, and limitations, with the aim of providing experimental and technical support for the development of new therapeutic strategies and drugs.

Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

As a major challenge in the global field of critical care medicine, sepsis is associated with high morbidity and mortality, driving intensive research into the development of precise risk prediction models. Among these, machine learning and deep learning-based predictive models have garnered particular attention. This article systematically reviews the evolution of sepsis risk prediction models and the challenges associated with their clinical translation, with a focus on their clinical applicability in common septic complications, including acute kidney injury, encephalopathy, and coagulation disorders. Current evidence indicates that machine learning models, by integrating multidimensional dynamic data from electronic health records, significantly enhance early warning capabilities and individualized predictive performance. However, major bottlenecks limiting clinical translation include insufficient data standardization, lack of model interpretability, and inadequate external validation. Future research should prioritize multicenter collaboration, time-series modeling strategies, and explainable artificial intelligence frameworks to optimize clinical translation pathways and facilitate the paradigm shift from traditional empirical approaches to data-driven precision strategies in sepsis risk stratification.

This study systematically dissects the core pathogenesis of chronic heart failure （CHF） featured by internal deficiency and external excess，imbalance of Qi，blood，Yin，and Yang，and intermingling of phlegm，blood stasis，and fluid retention. According to the traditional Chinese medicine （TCM） therapeutic principles of simultaneously treating root cause and symptoms，regulating Yin and Yang，replenishing Qi and activating blood，and promoting urination to relieve edema，this article deeply explores the formula-syndrome correspondence of Qili Qiangxin （QLQX） capsules in the treatment of CHF，providing a solid theoretical basis for the multi-effect characteristics of this drug. CHF is a common critical cardiovascular disease in clinical practice，and its pathological process involves multiple links including myocardial injury，neurohumoral disturbance，and ventricular remodeling. Its TCM pathogenesis is complex and involves multiple Zang-Fu organs，making it difficult for a single therapeutic method to achieve comprehensive coverage. QLQX capsules，formulated based on classical TCM theory，perfectly matches the pathogenic characteristics of CHF. Modern pharmacological studies have confirmed that QLQX capsules possess definite cardiotonic，diuretic，and vasodilatory effects. The active ingredients of QLQX capsules can rapidly and effectively alleviate the core clinical symptoms such as chest tightness，shortness of breath，decreased exercise tolerance，limb edema，palpitations，and fatigue of CHF patients by enhancing myocardial contractility and coronary blood flow，improving renal water excretion function，dilating peripheral blood vessels，and reducing cardiac load，thereby significantly improving patients' quality of life. On the basis of analyzing the symptomatic treatment of CHF with QLQX capsules，this study further expounds that the drug can intervene in ventricular remodeling through multiple pathways and targets，regulate the pathological mechanism of CHF，improve vascular endothelial function，mediate the activation of related signaling pathways，inhibit the transdifferentiation of cardiac fibroblasts，and regulate myocardial energy metabolism，thus delaying disease progression. QLQX capsules exert significant benefits in reducing composite cardiac events，improving New York Heart Association （NYHA） cardiac function classification，left ventricular ejection fraction （LVEF），6-minute walking distance （6MWD），and quality of life，demonstrating favorable clinical value. With the TCM pathogenesis of CHF as the guiding principle and modern pharmacology as the evidence，this study systematically clarifies the core advantage of QLQX capsules in treatment based on syndrome differentiation and multi-target synergy through the in-depth integration of TCM theory and modern pharmacology. It provides academic support with both theoretical depth and practical value for TCM intervention in CHF，and contributes TCM wisdom and schemes to the construction of a chronic disease management system with Chinese characteristics.

This study systematically dissects the core pathogenesis of chronic heart failure （CHF） featured by internal deficiency and external excess，imbalance of Qi，blood，Yin，and Yang，and intermingling of phlegm，blood stasis，and fluid retention. According to the traditional Chinese medicine （TCM） therapeutic principles of simultaneously treating root cause and symptoms，regulating Yin and Yang，replenishing Qi and activating blood，and promoting urination to relieve edema，this article deeply explores the formula-syndrome correspondence of Qili Qiangxin （QLQX） capsules in the treatment of CHF，providing a solid theoretical basis for the multi-effect characteristics of this drug. CHF is a common critical cardiovascular disease in clinical practice，and its pathological process involves multiple links including myocardial injury，neurohumoral disturbance，and ventricular remodeling. Its TCM pathogenesis is complex and involves multiple Zang-Fu organs，making it difficult for a single therapeutic method to achieve comprehensive coverage. QLQX capsules，formulated based on classical TCM theory，perfectly matches the pathogenic characteristics of CHF. Modern pharmacological studies have confirmed that QLQX capsules possess definite cardiotonic，diuretic，and vasodilatory effects. The active ingredients of QLQX capsules can rapidly and effectively alleviate the core clinical symptoms such as chest tightness，shortness of breath，decreased exercise tolerance，limb edema，palpitations，and fatigue of CHF patients by enhancing myocardial contractility and coronary blood flow，improving renal water excretion function，dilating peripheral blood vessels，and reducing cardiac load，thereby significantly improving patients' quality of life. On the basis of analyzing the symptomatic treatment of CHF with QLQX capsules，this study further expounds that the drug can intervene in ventricular remodeling through multiple pathways and targets，regulate the pathological mechanism of CHF，improve vascular endothelial function，mediate the activation of related signaling pathways，inhibit the transdifferentiation of cardiac fibroblasts，and regulate myocardial energy metabolism，thus delaying disease progression. QLQX capsules exert significant benefits in reducing composite cardiac events，improving New York Heart Association （NYHA） cardiac function classification，left ventricular ejection fraction （LVEF），6-minute walking distance （6MWD），and quality of life，demonstrating favorable clinical value. With the TCM pathogenesis of CHF as the guiding principle and modern pharmacology as the evidence，this study systematically clarifies the core advantage of QLQX capsules in treatment based on syndrome differentiation and multi-target synergy through the in-depth integration of TCM theory and modern pharmacology. It provides academic support with both theoretical depth and practical value for TCM intervention in CHF，and contributes TCM wisdom and schemes to the construction of a chronic disease management system with Chinese characteristics.

Objective: To explore the current status and influencing factors of eating behaviors in adolescents, so as to provide a theoretical foundation for health promotion education among adolescents. Methods: Based on the database from Survey of Chinese Family Health Index (2021), by a random number table method, 1 065 teenagers were selected from the provincial capitals of 22 provinces and 5 autonomous regions in China, as well as 4 municipalities directly under the central government. A general characteristic questionnaire, Patient Health Questionnaire-9 (PHQ-9), Short Form of the Family Health Scale (FHS-SF), 10-item Short Version of the Big Five Personality(BFP-10), Content-based Media Exposure Scale (CM-E) and Sakata Eating Behavior Scale Short Form(EBS-SF) were used to collect information. Multivariate stepwise linear regression analysis was employed to identify and analyze related factors of eating behaviors among adolescents. Receiver operating characteristic was used to validate the predictive ability of the EBS-SF score for overweight and obesity among adolescents. Results: The average scores of BFI-10,C-ME, FHS-SF, PHQ-9 and EBS-SF were (33.08±4.64)(19.20±4.55)(38.48±6.65)(6.09±5.63)(16.75±4.36), respectively. Multivariate linear regression showed that family type (other types), agreeableness, conscientiousness, family health and depression were the main related factors of EBS-SF scores among adolescents( B =2.61,-0.42,0.20,-0.11,0.23, P <0.05).The analysis of receiver operating characteristic curve showed that the EBS-SF scores had a good ability in predicting obesity among male adolescents ( AUC= 0.73, P <0.01). Conclusions Family type, big five personality, family health,depression are the related factors of eating behaviors among adolescents. EBS-SF scores are predictive of obesity in adolescents, which would provide a new perspective for promoting healthy eating habits among adolescents.

The study explores the traditional Chinese medicine （TCM） diagnostic and treatment approach to coronary microvascular disease （CMVD） from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective， different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice， four targeted treatment methods， i.e. warming， unblocking， tonifying， and activating， are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia， myocardial infarction， and coronary revascularization， with corresponding pathological mechanisms of latent pathogenic obstruction， toxic accumulation in the collaterals， and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation， staging， and transformation. Accordingly， treatment principles include warming to assist qi transformation， unblocking obstruction and dispelling turbidity， activating to disperse toxic stasis and invigorate collaterals， and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis， attention should be paid to the underlying disease， analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.

Objective To discuss the risk factors for impaired fasting glucose(IFG)and construct and validate a predictive model based on column charts of the risk of IFG occurrence.Methods This retrospective study included 3 037 individuals who underwent routine physical examinations at a hospital in Shenyang between August and December 2022.The population was randomly divided into a training group(n=2 126)and a validation group(n=911)in a 7∶3 ratio,and physical examination data were collected.LASSO regression analy-sis was used to screen predictive variables and logistic regression analysis was used to further screen and construct a column chart pre-dictive model.The validation group was used to conduct an internal validation of the feasibility of the model,and the area under the curve(AUC)of receiver operator characteristic(ROC)and goodness of fit tests were used to evaluate the model effectiveness.Results Among the 3 037 included individuals,2 880 did not experience IFG and 157 did.The results showed that age(OR=1.04,95％CI:1.02-1.05),body mass index(BMI,OR=1.10,95％CI:1.05-1.17),systolic blood pressure(SBP,OR=1.01,95％CI:1.00-1.03),triglycerides(TG,OR=1.20,95％CI:0.99-1.51),and a history of hypertension(OR=1.28,95％CI:1.04-1.59)were independent risk factors for IFG occurrence in this population.Based on these variables,a column chart prediction model was constructed.In the training group,the model predicted an AUC of 0.722(95％CI:0.68-0.77)for IFG occurrence,while in the validation group,it predicted an AUC of 0.907(95％CI:0.87-0.94)for IFG occurrence.The results of the Hosmer-Lemeshow goodness of fit test showed that the models of the training and validation groups were not significantly different(P＞0.05);that is,the actual probability was consistent with the prediction probability of the model,and the models calibration was good.Conclusion A risk prediction model for IFG occurrence that included five variables:age,BMI,SBP,TG,and history of hypertension could be construted.This model might help to identify high-risk groups for IFG early and allow for inter-vention in a timely manner.

Objective:To investigate the interaction of risk factors for diabetic retinopathy (DR) occurrence.Methods:A cross-sectional study was performed.A total of 6 783 diabetic patients with complete survey data from 2005 to 2018 in the National Health and Nutrition Survey database were enrolled, among which 4 426 patients were included according to inclusion criteria and were divided into non-DR diabetes group of 3 491 cases and DR group of 935 cases.The related risk factors were collected, including age, gender, race, residential status, education, annual household income, body mass index (BMI), fasting glucose, glycosylated hemoglobin, duration of diabetes, family history of diabetes, comorbidities, smoke, alcohol use, sleep, physical activity.Patient Health Questionnaire (PHQ-9) was used to assess the psychological status.After the categorization of all variables, risk factors of DR were analyzed by logistic regression, and the interaction between factors was further analyzed.Results:Multivariate analysis showed that female[odds ratio ( OR)=1.33, 95% confidence interval ( CI): 1.02-1.72], duration of diabetes ≥10 years ( OR=1.03, 95% CI: 1.02-1.04), insulin therapy ( OR=2.38, 95% CI: 1.87-3.05), urinary albumin creatinine ratio (UACR) ≥30 mg/g ( OR=1.55, 95% CI: 1.22-1.96) and depression ( OR=1.44, 95% CI: 1.13-1.83) were risk factors for DR, and BMI≤28 kg/m 2 ( OR=0.70, 95% CI: 0.55-0.89) was a protective factor for DR.Furthermore, interaction analysis revealed additive interaction between UACR ≥30 mg/g and insulin therapy [relative excess risk due to interaction ( RERI)=2.46, 95% CI: 0.84-4.09, attributable proportion due to interaction ( AP)=0.44, 95% CI: 0.26-0.63, synergy index ( S)=2.16, 95% CI: 1.37-3.41).The UACR ≥30 mg/g and longer diabetic duration ≥10 years had both multiplicative ( OR=1.67, 95% CI: 1.00-2.76) and additive interactions ( RERI=2.02, 95% CI: 0.79-3.25, AP=0.47, 95% CI: 0.27-0.66, S=2.53, 95% CI: 1.37-4.68). Conclusions:Patients with diabetes treated with insulin, with a duration of diabetes ≥10 years and accompanied by UACR ≥30 mg/g are at higher risk of developing DR than those with a single risk factor.

Objective To explore the association between dynamic indexes of maternal progesterone in early pregnancy and the average level and growth rate of fetal head circumference(HC)in mid-and late pregnancy.Methods This study adopted a retrospective cohort design and included 255 singleton pregnant women in the maternal and infant cohort of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2024.The progesterone levels of their early venous blood were detected and divided into two groups of progesterone trajectories,namely,fluctuating type and increasing type,by morphology.The dynamic indicators of progesterone in early pregnancy were constructed:cumulative dynamic deviation index in the first trimester(CDDI-P1T),gestational age at progesterone peak(GA-PP),and maximal relative progesterone decline in the first trimester(MRD-P1T).The average head circumference level and linear growth rate of the fetuses in the middle and late pregnancy were calculated.Generalized linear regression(GLM)was used to analyze the linear association between progesterone dynamic indicators and head circumference development.The key gestational weeks of progesterone affecting fetal head development were explored by linear regression of gestational weeks.Ordinary least squares(OLS)regression and restricted cubic spline(RCS)plots were used to draw the nonlinear association between progesterone dynamic indicators and head circumference.Results Among the 255 pregnant women included,92.5％of the progesterone trajectories in early pregnancy were fluctuating,and 7.5％were increasing.The growth rates of the increasing progesterone trajectory group were higher in the second and third trimesters than in the fluctuating group,but the differences were not statistically significant(all P＞0.05).GLM analysis showed that for every 1 unit increase in CDDI-P1T,the head circumference in the middle and late pregnancy increased significantly by 1.574 cm and 1.193 cm(Z=3.714,2.885,P＜0.01).The delay of GA-PP was negatively correlated with the head circumference in the middle pregnancy(β=-0.190 cm,95％CI:-0.339--0.041,P=0.010)but positively correlated with the head circumference growth rate in the late pregnancy(β=0.022 cm/week,95％CI:0.003-0.041,P=0.025).A 10％decrease in the decline of CDDI-P1T increased the head circumference in the middle pregnancy by 0.200 cm(95％CI:0.016-0.384,P=0.033),and a 100％decrease in the decline increased the head circumference growth rate in the late pregnancy by 0.201 cm/week(95％CI:0.002-0.399,P=0.048).The analysis of the key time window showed that for every 20 nmol/L increase in progesterone during 9.5-13 weeks of pregnancy,the mid-term head circumference increased by 0.035-0.166 cm(Z=2.452-3.517,allP＜0.05),and the late-term head circumference increased by 0.767 cm during 9-13 weeks of pregnancy(Z=2.452-3.517,all P＜0.05).When progesterone increased during 9.5-10.5 weeks of pregnancy,the growth rate of mid-term head circumference increased by 0.013-0.023 cm/week(Z=2.074-2.243,all P＜0.01).When progesterone increased during 8.5-10.5 weeks of pregnancy,the growth rate of late-term head circumference increased by 0.010-0.026 cm/week(Z=2.061-3.137,all P＜0.05).Conclusion Progesterone dynamic index is a new sensitive tool for evaluating fetal head circumference development.There is a stage-specific window period for progesterone regulation.9.5-13 weeks of pregnancy is the critical period for progesterone to affect head circumference growth,and 9.5-10.5 weeks of pregnancy is the core window for regulating the growth rate of head circumference.Therefore,it is necessary to combine progesterone dynamic index and time window for individualized intervention to promote the transformation of prenatal care from pregnancy maintenance to eugenics intervention.