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.

ObjectiveTo investigate the trends in the disease burden of falls among Chinese children and adolescents from 1990 to 2021, and to inform the development of targeted prevention and control strategies. MethodsData on age-standardized incidence rate, age-standardized mortality rate and age-standardized disability-adjusted life years (DALYs) rate for falls among Chinese children and adolescents under 20 years of age from 1990 to 2021 were systematically extracted from the Global Burden of Disease Study (GBD) 2021 database. The annual percent change (APC) and average annual percent change (AAPC) were calculated to evaluate temporal trends in fall-related disease burden across different age groups and sexes. ResultsFrom 1990 to 2021, the age-standardized incidence rate of falls among Chinese children and adolescents showed a non-linear fluctuation (AAPC=0.08%, P=0.040), while both the age-standardized mortality rate and age-standardized DALYs rate declined (AAPC=-3.66% and -3.09%, both P<0.001). The crude incidence rate decreased in the <5 years old and 5 ‒ <10 years old groups (AAPC=-1.38% and -0.29%, both P<0.001), but increased annually in the 10 ‒ <15 years old and 15 ‒ <20 years old groups (AAPC=0.27% and 0.81%, both P<0.001). The crude mortality rate and crude DALYs rate declined across all four age groups, with the most significant reduction observed in the <5 years old group (AAPC=-5.21%, 95%CI:-5.55%‒ -5.00%; AAPC=-4.98%, 95%CI: -5.20%‒ -4.79%, both P<0.001). For both males and females, the age-standardized incidence rate of falls showed a V-shaped trend (initial decline followed by a subsequent rise). In contrast, the age-standardized mortality rate and age-standardized DALY rate declined in both sexes, with an AAPC of -3.40% and -2.94% for males, and -4.50% and -3.49% for females, respectively (all P<0.001). ConclusionThe overall disease burden of falls among Chinese children and adolescents has been substantially improved; however, the incidence burden remains considerable. Future prevention efforts should be tailored to age- and sex-specific characteristics, with the family as the fundamental care unit in conjunction with high-quality nursing extension services, to establish a closed-loop management model encompassing “early identification, immediate intervention, and continuous follow-up.”

ObjectiveTo investigate the effects of Yifei Zhuji formula （YFZJF） on epithelial-mesenchymal transition （EMT） in non-small cell lung cancer （NSCLC） through regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsThe Lewis lung carcinoma mouse model and human lung adenocarcinoma PC-9 cell model were used in this study. In the animal experiments， 60 C57BL/6 mice were randomized into a blank group and a Lewis lung carcinoma modeling group. The modeled mice were further randomized into model， low-， medium-， and high-dose （7.475， 14.95， 29.9 g·kg^-1·d^-1， respectively） YFZJF， and cisplatin groups， with 10 mice in each group. Mice in YFZJF groups were administrated with YFZJF at different doses by gavage， and those in the cisplatin group received intraperitoneal injection of cisplatin at 6 mg·kg^-1. Mice in the blank group and model group were administrated with equal volumes of normal saline by gavage every day. All the groups were treated for 14 consecutive days， and samples were collected for analysis after completion of treatment. Changes in body mass， tumor volume， and tumor mass were measured. Hematoxylin-eosin （HE） staining was performed to observe pathological changes in the lung tissue. Immunohistochemistry， Real-time PCR， and Western blot were employed to determine the expression of proliferating cell nuclear antigen （Ki-67）， PI3K/Akt/mTOR signaling pathway-related molecules， and EMT-related molecules in the tumor tissue. In the cell experiments， human lung adenocarcinoma PC-9 cells were allocated into control， YFZJF-containing serum， and cisplatin groups， which were treated with 20% blank rat serum， 20% YFZJF-containing rat serum， and 5.4 μmol·L^-1 cisplatin for 48 h， respectively. The cell counting kit-8 （CCK-8） assay was adopted to detect cell proliferation and determine drug concentration. Cell scratch assay and Transwell assay were employed to evaluate cell migration and invasion. Immunofluorescence staining and Real-time PCR were used to analyze changes in expression of EMT markers. ResultsCompared with those in the model group， the tumor volume and tumor mass were reduced in the high-dose YFZJF group （P<0.01）. Immunohistochemical results showed that compared with the model group， the medium- and high-dose YFZJF groups exhibited reduced Ki-67 expression in the tumor tissue （P<0.01）. HE staining results showed that YFZJF alleviated the pathological injury of the lung tissue to different degrees. Real-time PCR results in the tumor tissue showed that compared with the model group， the high-dose YFZJF group displayed downregulated mRNA levels of protein kinase B1 （Akt1） and N-cadherin （P<0.05）， phosphatidylinositol 3-kinase p85 regulatory subunit （p85） （P<0.01）， mTOR （P<0.01）， and Vimentin （P<0.01）， and an upregulated mRNA level of E-cadherin （P<0.01）. Western blot results showed that compared with the model group， the high-dose YFZJF group exhibited downregulated protein levels of phosphorylated （p）-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， Vimentin， and N-cadherin （P<0.01）， and an upregulated protein level of E-cadherin （P<0.01） in the tumor tissue. The cell experiment results showed that compared with the blank serum group， YFZJF-containing serum inhibited the proliferation， migration， and invasion of PC-9 cells （P<0.05， P<0.01）. Immunofluorescence results showed that compared with the control group， YFZJF-containing serum downregulated the protein levels of N-cadherin and Vimentin and upregulated the protein level of E-cadherin （P<0.01）. Real-time PCR results showed that compared with the control group， YFZJF-containing serum upregulated the mRNA level of E-cadherin （P<0.05） and downregulated the mRNA levels of N-cadherin， Vimentin， P85， Akt1， and mTOR （P<0.05， P<0.01）. ConclusionYFZJF can significantly inhibit the progression of non-small cell lung cancer and reduce the migration and invasion of tumor cells by inhibiting the abnormal activation of PI3K/Akt/mTOR signaling pathway and reversing EMT.

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.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.

Objective:To investigate the efficacy of blepharoplasty using the "double-line technique" in addressing upper eyelid skin laxity in middle-aged and elderly patients.Methods:A retrospective analysis was conducted on the clinical data of middle-aged and elderly patients with moderate to severe upper eyelid skin laxity who were admitted to the Plastic Surgery Department of Shaanxi Provincial People’s Hospital between January 2020 and January 2023. The same surgeon performed the "double-line" blepharoplasty to excise excess upper eyelid skin for laxity correction. Patients were positioned flat with their eyes closed; an arcuate line a (5-7 mm above the pupil) and a second line b (aligned with the eyelid margin in an upright position) were marked. The skin between these two lines was excised. Postoperatively, the double eyelid shape, improvement in skin laxity, adverse reactions, and patient satisfaction (categorized as satisfied, basically satisfied, unsatisfied) were assessed.Results:A total of 145 patients were included in the study, comprising 27 males and 118 females. Their ages ranged from 38 to 78 years, with an average age of 52 years. All patients’ incisions healed primarily without complications such as hematoma and infection. During the 3 to 12 months of follow-up after surgery, the double eyelid arcs on both sides appeared symmetrical and natural. The upper eyelid laxity was effectively corrected, obscured vision was improved, crow’s feet were reduced, and the periorbital area was rejuvenated. Patient satisfaction with the surgical results was high, with 112 patients reporting satisfaction, 25 reporting basically satisfied, and 8 reporting dissatisfaction. The overall satisfaction rate reached 94.48%(137/145). Among those dissatisfied, 6 cases cited the double eyelid crease as being too narrow, and 2 cases noted asymmetry in the double eyelid crease.Conclusion:The "double-line method" for blepharoplasty is straightforward to perform and effectively removes excess upper eyelid skin. It is suitable for middle-aged and elderly patients with moderate to severe upper eyelid skin laxity, resulting in favorable surgical outcomes.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

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 observe conventional ultrasound and contrast-enhanced ultrasound(CEUS)manifestations of Ewing sarcoma(ES)in children.Methods Fifteen children with pathologically confirmed ES were retrospectively collected.Conventional ultrasound and CEUS characteristics of lesions were analyzed.Results Among 15 cases,ES of bone(ESB)was found in 7 cases,while extraskeletal ES(EES)was observed in the other 8 cases.Solitary tumor was noticed in 14 cases,with a median maximum diameter of 7.50 cm,while multiple abdominal masses were found in 1 case.The tumors had irregular shapes and poorly defined boundaries,with medium echogenicity in 7 cases,low echogenicity in 6 cases,while in other 2 cases present as cystic-solid lesions.CDFI showed sparse blood flow in 11 cases,abundant or slightly abundant blood flow in 2 and 1 case,respectively,while no obvious blood flow was observed in 1 case.Rapid high enhancement and rapid washout were found in all 7 cases underwent CEUS,while patchy no-enhancement areas were detected in 4 cases.Conclusion Conventional ultrasonic manifestations of ES had certain specificities,which demonstrated a rapid enhancement and rapid washout pattern during CEUS and may be accompanied by necrosis.