Factorial design is an important method for optimizing complex strategies in implementation science. This paper systematically elucidates the origin, types, and core concepts of the factorial design, and then use a brief smoking cessation intervention project as an example to illustrate its specific applications in identifying key factors and testing interactions. Factorial design has the following typical advantages: it can test synergistic and antagonistic effects between factors, provide effect estimates that are broadly valid across the experimental conditions, and offer high statistical efficiency. At the same time, it also has certain limitations, including that its complexity is positively correlated with the number of factors, the need for large sample sizes to detect interactions, the potential for insufficient acceptability of some strategy combinations due to ethical concerns or participant burden, and the complexity of the analytical methods required. In future research, its application should be further optimized by appropriately controlling the number of factors, clearly defining research objectives, and evaluating intervention acceptability, in order to promote the development of precision implementation science.

ObjectiveTo investigate the association of comprehensive control of multiple metabolic risk factors with the risk of all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease （MASLD） and its quantitative effect. MethodsA retrospective cohort study was conducted based on the data from National Health and Nutrition Examination Survey （NHANES） in 2003—2018. A total of 29 458 participants were enrolled， including 12 528 patients with MASLD and 16 930 non-MASLD controls. The control status of nine risk factors was assessed， i.e.， hypertension， diabetes， liver fibrosis （assessed by fibrosis-4 index ［FIB-4］）， aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio， serum albumin， renal function （assessed by serum creatinine）， systemic inflammation （assessed by neutrophil count）， smoking， and physical activity. According to the status of comprehensive risk factor control， the patients with MASLD were further divided into low-control group with 1 107 patients， moderate-control group with 7 042 patients， and high-control group with 4 379 patients. A total of 397 participants were enrolled in the external validation cohort， among whom there were 266 participants with MASLD and 131 participants without MASLD. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test was used for comparison of categorical data between groups. The Cox proportional hazards model incorporating complex sampling weights for NHANES data were used to investigate the association between the degree of risk factor control and all-cause mortality， and the Kaplan-Meier curve， the log-rank test， restricted mean survival time （RMST）， and population attributable fraction （PAF） were used for further assessment. The robustness of the findings was validated in an independent clinical cohort （n=397）. ResultsThe cohort study based on the NHANES database showed that during the median follow-up time of 6.7 years， 1 171 deaths occurred among the 12 528 patients with MASLD. There was a significant reduction in mortality risk with the increase in the number of risk factors controlled （trend test： χ²=65.06， P<0.001）. Compared with the low-control group， the mortality risk decreased successively in the moderate-control group （hazard ratio ［HR］=0.59， 95% confidence interval ［CI］： 0.51 — 0.69） and the high-control group （HR=0.36， 95%CI： 0.27 — 0.48）， and the mortality risk was reduced by 22% for each additional risk factor controlled （HR=0.78， 95%CI： 0.74 — 0.82）. The PAF analysis showed that AST/ALT ratio control （PAF=19.2%） and physical activity （PAF=18.9%） were the largest contributors. The survival analysis of the sub-cohort constructed based on nearest neighbor matching （with a maximum follow-up time of 13.3 years） showed that there was a significant difference in cumulative survival rate between the MASLD groups with different control levels and the non-MASLD group （P<0.001）. The RMST analysis further quantified the survival benefit of each group， and the high-control group had the longest 10-year RMST （9.88 years）， which was superior to that of the non-MASLD group （9.43 years）， the moderate-control group （9.33 years）， and the low-control group （7.96 years）. The multivariable-adjusted model analysis of the complete cohort showed that compared with the non-MASLD population， the MASLD patients in the low-control group had a significant increase in mortality risk， the moderate-control group had a comparable mortality risk， and the high-control group had a significantly lower mortality risk. The subgroup analysis showed a significant protective effect of comprehensive control in both male and female individuals （P<0.05）， and the interaction analysis suggested a potentially stronger protective effect in female individuals （P_{for interaction}=0.031）. The protective effect was statistically significant in patients aged ≥60 years （P<0.05）. There was a significant difference in protective effect across the groups stratified based on waist circumference （P<0.05）， but there was no significant interaction between groups （P_{for interaction}=0.821）. In the external validation cohort， among the 397 participants， there were 72 cases of all-cause mortality （18.1%）. The survival analysis showed a significant gradient increase in the survival rate of MASLD patients with the increase in the level of control （P=0.022）. The RMST analysis showed that the moderate- and high-control groups had a better RMST than the non-MASLD group at 5 years （4.47 years vs 4.56 years vs 4.40 years）， with a more significant survival advantage at 10 years （8.67 years vs 8.95 years vs 8.44 years）. The Cox regression analysis showed that， with the low-control MASLD group as the reference， there was a significant reduction in mortality risk in the moderate-control group （HR=0.41， 95%CI： 0.21 — 0.81） and the high-control group （HR=0.32， 95%CI： 0.14 — 0.71）； with the non-MASLD population as the reference， there was a significant increase in mortality risk in the low-control group （HR=2.02， 95%CI： 1.03 — 3.95）， with a comparable mortality risk in the moderate-control group （HR=0.83， 95%CI： 0.48 — 1.44） and the high-control group （HR=0.66， 95%CI： 0.30 — 1.38）， and the point estimates of the effects were highly consistent with the main study. ConclusionAmong MASLD patients， better control of metabolic risk factors is associated with a lower mortality risk. Achieving optimal control can eliminate the excess mortality risk associated with MASLD， thereby helping patients achieve a better survival prognosis than the general population.

Objective To explore the effect of the ratio of high-density lipoprotein cholesterol(HDL-C)/total cholesterol(TC)on no-reflow after percutaneous coronary intervention(PCI)in elderly patients with acute coronary syndrome(ACS)complicated with diabetes mellitus(DM).Methods A retrospective analysis was conducted on 206 elderly ACS patients complicated with DM undergoing PCI in our hospital from January 2018 to August 2024.The HDL-C and TC levels were detected by cholesterol oxidase test,and the HDL-C/TC ratio was calculated.Coronary angi-ography(CAG)was applied to evaluate no-reflow phenomenon after PCI,and according to the re-sults,the patients were divided into a non-reflow group(41 cases)and a normal reflow group(165 cases).ROC curve was plotted to evaluate the predictive performance of HDL-C/TC ratio for no-reflow after PCI in patients with ACS complicated DM.Results The no-reflow group had signifi-cantly higher TC and glycated hemoglobin A1c(HbA1c)levels and more balloon dilatations,but lower HDL-C level and HDL-C/TC ratio than the normal flow group(P＜0.01).Multivariate lo-gistic regression analysis showed that HbA1c(OR=3.196,95％CI:1.619-6.310,P=0.001),number of balloon dilatations(OR=3.504,95％CI:1.807-6.797,P=0.000),and HDL-C/TC ra-tio(OR=3.927,95％CI:2.0 73-7.441,P=0.000)were influencing factors of no-reflow after PCI in patients with ACS and DM.The AUC value of HDLC,TC,and HDL-C/TC ratio in predicting no-reflow after PCI was 0.842,0.726,and 0.922,respectively.Conclusion HDL-C/TC ratio is an influencing factor for no-reflow in patients with ACS and DM after PCI.The ratio at a cut-off val-ue of ≤0.21 has a certain predictive value for no-reflow after PCI in these elderly patients.

Objective To explore the related influencing factors of orthostatic hypotension in patients with multiple system atrophy(MSA).Methods A retrospective study was conducted on 40 elderly MSA patients with orthostatic hypotension(MSA group)admitted to our department from January 2024 to March 2025,and another 46 elderly healthy individuals without orthostatic hypotension who taking physical examination were subjected and served as control group.General clinical data and related clinical indicators were compared between the two groups,and the related serum biomarkers of orthostatic hypotension in MSA patients were analyzed.Results The levels of vitamin D,low-density lipoprotein cholesterol(LDL-C),and uric acid were significantly lower in the MSA group than the control group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that vitamin D,LDL-C,and uric acid levels were risk factors for the occurrence of orthostatic hypotension in MSA patients(OR=0.677,95％CI:0.530-0.864,P＜0.01;OR=0.057,95％CI:0.007-0.434,P＜0.01;OR=0.972,95％CI:0.954-0.992,P＜0.01).ROC curve analysis indicated that the optimal cut-off value of vitamin D,LDL-C,and uric acid levels in predicting the occurrence of orthostatic hypotension in MSA patients was 21.850 μg/L,2.895 mmol/L,and 274.500 μmol/L,the sensitivity was 0.848,0.630 and 0.783,and the specificity was 0.792,0.750 and 0.667,and the AUC value was 0.862,0.683 and 0.748,respectively.Conclusion Monitoring serum biomarkers,such as vitamin D,LDL-C,and uric acid may be helpful for the risk assessment and management of orthostatic hypotension in MSA patients.

Objective:To analyze the incidence and risk factors of malignant tumors among HIV-infected patients in Taizhou, Zhejiang Province.Methods:The data were collected from the China Information System for Disease Control and Prevention and the Taizhou Chronic Disease Information Management System. A retrospective cohort study design was used. The subjects were HIV-infected patients who had their household registration in Taizhou from 2005 to 2023 and participated in the follow-up. The observation period was until December 31, 2024. The standardized incidence ratios (SIR) of malignant tumors among HIV-infected patients were analyzed. Cox proportional hazards regression model was used to analyze the influencing factors of malignant tumor incidence.Results:A total of 3 593 HIV-infected patients were included, of whom 292 had malignant tumors. The proportions of AIDS-defining malignancies and non-AIDS-defining malignancies were 12.33% (36/292) and 87.67% (256/292), respectively. The proportion of malignant tumors before and after AIDS confirmation was 43.49% (127/292) and 56.51% (165/292), respectively. 3 466 HIV-infected patients were included in the follow-up cohort, with a total follow-up of 24 968.59 person-years. The incidence rate of malignant tumors in patients with HIV infection was 658.46 per 100 000 (SIR=1.89, 95% CI: 1.61-2.20). The SIR of malignant tumors showed an upward trend with the increase of time. The results of Cox proportional hazards regression model analysis showed that HIV-infected patients in the age groups of 45-59 and ≥60 years (a HR=2.58, 95% CI: 1.26-5.28; a HR=5.00, 95% CI: 2.38-10.51) were more likely to develop malignant tumors. HIV-infected patients with an educational level of senior high school or above (a HR=0.52, 95% CI: 0.29-0.95) and those in the first CD4 +T lymphocyte/CD8 +T lymphocyte count ratio ≥0.5 (a HR=0.52, 95% CI: 0.28-0.97) were less likely to develop malignant tumors. Conclusions:From 2005 to 2023, the incidence of malignant tumors among HIV-infected people in Taizhou was higher than that of the general population, and most of them were non-AIDS-defining malignancies. It is necessary to strengthen the early screening and diagnosis of malignant tumors among HIV-infected patients.

The oropouche virus (OROV) poses a threat to pregnant women and fetuses, potentially causing fetal neurological defects and even stillbirth, which has caused global attention. OROV is an arthropod-borne virus belonging to the Orthobunyavirus genus in the Bunyavirales order, primarily transmitted by arthropods and causing oropouche fever. This article reviews the etiological characteristics, epidemiological distribution, clinical symptoms, detection methods, and prevention strategies of OROV. OROV is prevalent in Central and South America, with a sharp increase in cases reported in Brazil in 2024. The virus's symptoms resemble those of several other arthropod-borne viral diseases, which can lead to misdiagnosis. Currently, there are no specific drugs or vaccines available, and treatment is mainly supportive. Culicoides paraensis and Culex quinquefasciatus are among the significant vectors of OROV. Furthermore, the article analyzes the distribution of Culex quinquefasciatus in China, highlights the risk of imported cases, proposes targeted prevention and control strategies, and underscores the significance of international cooperation in disease prevention and control.

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

Objective To investigate the diagnostic value of 4 novel inflammatory markers related to routine blood tests,namely neutrophil-to-lymphocyte ratio(NLR),red blood cell distribution width(RDW),hemoglobin-to-RDW ratio(HRR)and systemic immune-inflammation index(SII),in elderly patients with chronic cardiovascular disease(CVD)complicated with frailty.Methods Retrospectively analyze 110 patients with chronic stable CVD who were hospitalized in the cadre ward of cardiovascular medicine at the Air Force Characteristic Medical Center from January 2022 to June 2023.According to the assessment results of the Fried scale,they were divided into three groups:non-frailty group(Fried score=0,n=30),the pre-frailty group(Fried score 1 or 2,n=40)and frailty group(Fried score≥3,n=40).The differences in general information,the impairment rate of daily living activities,miniature nutritional assessment-short form(MNA-SF)scores,mini-mental state examination(MMSE)scores,and the indicators such as NLR,RDW,HRR,and SII among the three groups were compared.Spearman rank correlation was used to analyze the correlation between NLR,RDW,HRR,SII and frailty scores as well as each frailty indicator.Multivariate logistic regression analysis was performed to identify the independent risk factors for frailty in elderly patients with chronic CVD,and the receiver operating characteristic(ROC)curve was used to assess the clinical diagnostic value of NLR and HRR in elderly patients with chronic CVD complicated with frailty.Results Compared with non-frailty group and pre-frailty group,patients in frailty group were older,with higher impaired rates of daily living activities,NLR,RDW,and SII,and lower MNA-SF scores,MMSE scores,and HRR,and differences were statistically significant(P<0.05).Spearman rank correlation analysis showed that the frailty score was positively correlated with NLR(rs=0.354,P<0.001),and RDW(rs=0.448,P<0.001),negatively correlated with HRR(rs=-0.232,P=0.024),and had no significant correlation with SII(rs=0.144,P=0.167).Further analysis of the correlation between the above novel inflammatory markers and the 5 components of frailty showed that NLR was positively correlated with fatigue(rs=0.228,P=0.017),slowed walking speed(rs=0.299,P<0.001),and low physical function(rs=0.319,P<0.001);RDW was positively correlated with decreased grip strength(rs=0.321,P<0.001),slowed walking speed(rs=0.422,P<0.001),and low physical function(rs=0.246,P=0.001);and HRR was negatively correlated with slowed walking speed(rs=-0.230,P=0.025),and low physical function(rs=-0.299,P=0.003).Multivariate logistic regression analysis showed that MNA-SF score(OR=0.577,95%CI 0.342-0.973)was an independent protective factor for pre-frailty in elderly patients with chronic CVD(P<0.05);NLR(OR=7.866,95%CI 1.101-56.185)was an independent risk factor for frailty,while HRR(OR=0.344,95%CI 0.120-0.983)and MNA-SF score(OR=0.292,95%CI 0.146-0.580)were independent protective factors for frailty in elderly CVD patients(P<0.05).The area under the ROC curve of NLR and HRR for diagnosing frailty in elderly patients with chronic CVD were 0.778 and 0.749,respectively.Conclusion NLR and HRR have high clinical diagnostic value for frailty in elderly patients with chronic CVD,and are expected to become effective inflammatory markers for screening elderly patients with chronic CVD complicated with frailty.

The cell membrane biomimetic nanodrug delivery platform consists of nanoparticles coated with drug-loaded cell membranes,demonstrating a significant anti-atherosclerosis effect.This platform can identify and bind to atherosclerotic plaques through the homing capabilities of cell membranes.It releases drugs in response to specific environmental triggers,such as reactive oxygen species and shear stress from blood flow in areas affected by atherosclerosis.Furthermore,it inhibits macrophage lipid phagocytosis,thereby reducing foam cell formation,regulating macrophage phenotypes,and decreasing the production of inflammatory factors.Additionally,it accelerates cholesterol dissolution and efflux in atherosclerotic regions,effectively removes high concentrations of reactive oxygen species,and mitigates oxidative stress damage as well as the deposition of oxidized low-density lipoprotein.This review article delves into the functions and mechanisms of cell membrane biomimetic nanodrug delivery platform in combating atherosclerosis,offering fresh insights for targeted atherosclerosis treatment through the lens of nanomedicine.

Objective To explore the application effect of blood pressure management based on the health belief model in patients with moyamoya disease after cerebral vascular reconstruction sur-gery.Methods From February to July 2024,210 patients with moyamoya disease who underwent cerebral vascular reconstruction surgery in our hospital were selected as study subjects.They were randomly divided into control group and intervention group,with 105 cases in each group.The control group received routine nursing care,while the intervention group applied blood pressure management based on the health belief model on the basis of routine nursing care.The postoperative cerebral hy-perperfusion syndrome and blood pressure control status of the two groups were compared,and the Health Belief Scale and the Mishel Uncertainty in Illness Scale were used to evaluate the effects before and after intervention.Results A total of 203 patients completed the study,including 100 cases in the control group and 103 cases in the intervention group.There were statistically significant differ-ences in the incidence of cerebral hyperperfusion syndrome and the proportion of patients with blood pressure higher than baseline data between the two groups(P＜0.05).After the intervention,there were statistically significant differences in the postoperative cerebral hyperperfusion syndrome status and blood pressure control status between the two groups(P＜0.05).After intervention,there were statistically significant differences in the scores of susceptibility and health motivation dimensions as well as the total score in the Health Belief Scale between the intervention group and the control group(P＜0.05).After the intervention,there were statistically significant differences in the scores of ambiguity and unpredictability dimensions as well as the total score in the Mishel Uncertainty in Ill-ness Scale between the intervention group and the control group(P＜0.05).Conclusion Blood pressure management based on the health belief model can effectively control blood pressure,reduce the incidence of cerebral hyperperfusion,improve health beliefs,and reduce the sense of uncertainty about the disease.