Metabolic dysfunction-associated fatty liver disease （MAFLD）， as one of the most common chronic liver diseases in the world， poses a severe challenge to precision diagnosis and treatment due to its complex pathogenesis and highly heterogeneous disease progression. Existing clinical classification systems cannot meet the needs for comprehensively analyzing the complexity of the disease and the heterogeneity of its adverse outcomes. In recent years， data-driven prognostic risk classification methods have gradually emerged， optimizing the ability for predicting adverse outcomes and enhancing the accuracy of identifying different endpoint outcomes. However， such paradigm of “classify first， associate outcomes later” suffers from a “black-box” nature， and there are various indicators for classification， leading to limited stability and generalizability in clinical application. Future research needs to integrate or establish large-scale population cohorts， develop outcome-oriented prognostic risk classification models， incorporate dynamic data， refine classification algorithms， and validate their generalizability across multiple populations， thereby providing reliable support for the precision diagnosis and treatment of MAFLD.

Objective To analyze the genetic characteristics and variations of influenza A (H3N2) viruses in Ma'anshan from 2022 to 2024, and to provide a scientific basis for local influenza prevention and control. Methods From April 2022 to March 2024, influenza-like illness (ILI) specimens were collected from three national influenza surveillance sentinel hospitals in Ma’anshan. Samples positive for influenza by real-time PCR were subjected to virus culture and identification. A total of 40 representative A/H3N2 strains with hemagglutination titers ≥8 were selected for whole-genome sequencing. Genetic evolution, homology, amino acid variations, and glycosylation sites were analyzed. Results All H3N2 representative strains from the 2022–2023 influenza season belonged to clade 3C.2a1b.2a.1a.1, while those from the 2023–2024 season fell into clade 3C.2a1b.2a.2a.3a.1. The nucleotide and amino acid sequence similarities of HA and NA between the 40 representative strains and the vaccine strain A/Darwin/6/2021 were all above 97.35%. Compared with the vaccine strain, amino acid mutations were identified in antigenic sites A, B, C, and E, as well as in receptor-binding sites of the HA protein. An I222V substitution was detected in the NA protein. The HA protein contained four additional glycosylation sites compared to the vaccine strain, while the glycosylation pattern of the NA protein remained consistent. Conclusion No antigenic drift was observed in the influenza A/H3N2 viruses in Ma'anshan City from 2022 to 2024, but genetic changes such as branching variations, key amino acid substitutions, and an increase in HA glycosylation sites were observed. These findings underscore the importance of sustained molecular surveillance of local influenza viruses.

Objective: To investigate the correlation between color parameters (L^*, a^*, b^*, Eab^*) and the contents of reducing sugars, total polysaccharides, total oligosaccharides, as well as four saccharides (fructose, glucose, sucrose, and kestose) during the nine cycles of steaming and sun-drying processing of Polygonatum kingianum, and to preliminarily explore the optimal processing duration.
Methods: The color changes were objectively evaluated using a colorimeter. The anthrone-sulfuric acid method was employed to determine total polysaccharides and oligosaccharides. The 3,5-dinitrosalicylic acid (DNS) colorimetric method was used to measure total reducing sugar content. High-performance liquid chromatography coupled with charged aerosol detection (HPLC-CAD) was applied for quantitative analysis of fructose, glucose, sucrose, and kestose. Multivariate statistical analysis was conducted to assess samples from different processing stages.
Results: Significant variations in color and component contents were observed across processing stages. The herbal pieces progressively darkened with increased processing cycles: brightness (L^*) and total color difference (Eab^*) initially decreased then stabilized, while a^* (red-green) and b^* (yellow-blue) values first increased then declined. Total polysaccharides and oligosaccharides showed overall decreasing trends, whereas reducing sugars initially increased before stabilizing. Fructose and glucose levels rose continuously, while sucrose and kestose decreased progressively, becoming undetectable after five cycles.
Conclusion: The chromatic alteration and saccharide composition of P. kingianum showed significant correlation with processing duration. Both total color difference (Eab^*) and reducing sugar content stabilized after four processing cycles (12 hours), suggesting that four cycles of steaming and sun-drying may represent the optimal processing duration.

Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

AIM:To investigate the current status of astigmatism and its associated factors among children and adolescents from kindergarten through senior high school in Yangpu District, Shanghai, and to provide scientific evidence for the prevention and control of refractive errors.METHODS:A cluster sampling method was employed. From September to November 2024, students from 14 randomly selected schools in Yangpu District, Shanghai, were enrolled as study subjects. Autorefraction and ocular biometry were performed under non-cycloplegic conditions, and questionnaire surveys were administered. Comparisons of astigmatism degree, detection rate, and axis were made across age groups, educational stages, and sexes. Multiple linear and logistic regression analyses were conducted to identify factors associated with astigmatism.RESULTS:A total of 7 233 students aged 4-18 y were enrolled including 3 731 males, 3 502 females, with the mean age 10.13±4.18 y, astigmatism -0.76±0.82 D, and the detection rate(≤-1.00 D)was 29.23%. Both the degree and detection rate of astigmatism were correlated with age and educational stage, peaking in senior high school, with the most pronounced changes observed during primary school. Besides age, astigmatic refractive power was influenced by spherical equivalent(β=0.105, P<0.001), mean keratometry(β=-0.118, P<0.001), sex(with boys as the reference, girls: β=0.054, P<0.001), frequent sustained near work for 30-40 min(with “almost never” as the reference, β=-0.030, P=0.038), preterm birth(β=-0.023, P=0.044), maternal myopia(β=-0.028, P=0.020), and homework completion time on rest days(β=-0.035, P=0.041). The detection rate of astigmatism was associated with maternal myopia(OR=1.130, P=0.039), male sex(OR=0.773, P<0.001), shorter sleep duration on school days(OR=0.909, P=0.028), shorter sleep duration on rest days(OR=0.937, P=0.046), preterm birth(OR=1.382, P=0.012), frequent excessive head lowering(OR=1.216, P=0.045), homework completion time on rest days(OR=1.043, P=0.046), higher spherical equivalent(OR=0.891, P<0.001), and higher mean keratometry(OR=1.188, P<0.001).CONCLUSION:The degree and detection rate of astigmatism among children and adolescents from kindergarten to senior high school in Yangpu District, Shanghai are correlated with educational stage, and primary school may represent a critical period for astigmatism prevention and control. Male sex, maternal myopia, preterm birth, high-intensity near work, and insufficient sleep and other factors may be associated with the onset and progression of astigmatism. It is recommended that education and health departments strengthen visual health screening during primary school, while promoting behavioral interventions such as scientific eye-use habits and adequate sleep across different educational stages to delay the onset and progression of astigmatism.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

To compare psychological reactance, intention to adopt sleep-management recommendations, and intention to use sleep-support resources among students in medical and health-related disciplines exposed to sleep health messages with different outcome frames and expression styles, and to provide evidence for the design of sleep health information materials.

ObjectiveTo clarify the independent and synergistic effects of dyslipidemia in the progression of hepatic steatosis in metabolic dysfunction-associated fatty liver disease （MAFLD）. MethodsA total of 7 697 participants who underwent physical examination in Beijing Friendship Hospital， Capital Medical University， from January 2022 to December 2024 were enrolled， and finally 2 177 patients with MAFLD were enrolled as subjects. Transient elastography was used to quantify the severity of hepatic steatosis （grades S1-S3）. The multivariable ordinal Logistic regression analysis was used to investigate the independent and synergistic associations of serum triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） with the severity of hepatic steatosis， and their interactions and potential nonlinear relationships with metabolic factors were also examined. One-way analysis of variance or Kruskal-Wallis H test was used for comparison of continuous data between groups， and chi-square test was used for comparison of categorical data between groups. ResultsAn increase in TG （odds ratio ［OR］=1.77， 95% confidence interval ［CI］： 1.48 — 2.10， P<0.001） and a reduction in HDL-C （OR=1.35， 95%CI： 1.11 — 1.65， P=0.003） were independently associated with a greater severity of hepatic steatosis， with the strongest association when both abnormalities coexisted （OR=2.40， 95%CI： 1.87 — 3.07， P<0.001）. The dose-response relationship analysis further revealed a nonlinear threshold effect of TG on hepatic steatosis at the threshold of 1.51 mmol/L （P_nonlinearity=0.001）， below which the severity of steatosis increased more rapidly with the increase in TG concentration （P=0.001）. The subgroup analysis showed that the association between the reduction in HDL-C and the severity of steatosis was observed only in males， young adults （aged <45 years）， and metabolically healthier subgroups （without diabetes， obesity， hyperuricemia or hypertension）. Significant interactions were observed between the presence or absence of obesity and the abnormal levels of TG and HDL‑C （both P_interaction<0.05）. The association of the increase in LDL-C with steatosis was confined to specific subgroups （without obesity or hyperuricemia）. ConclusionThe increase in TG and the reduction in HDL-C are independently associated with the severity of hepatic steatosis in MAFLD. The synergistic effect of blood lipids and their interactions with metabolic factors may further refine risk stratification， so as to provide a basis for precise management of MAFLD.

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.

Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.