ObjectiveTo investigate the value of liver stiffness measurement （LSM） and spleen stiffness measurement （SSM） measured by two-dimensional shear wave elastography （2D-SWE） in the diagnosis of severe portal hypertension （SPH） and high-risk varices （HRV）， and to provide a basis for noninvasive assessment of portal hypertension. MethodsA prospective study was conducted among 78 patients with cirrhotic portal hypertension who were treated in Liver Research Center of Beijing Friendship Hospital， Capital Medical University， from December 2019 to April 2023. According to hepatic venous pressure gradient （HVPG）， the patients were divided into 6 mmHg≤HVPG<12 mmHg group， 12 mmHg≤HVPG<20 mmHg group， and HVPG ≥20 mmHg group. All patients underwent gastroscopy and 2D-SWE within 1 week after HVPG measurement， and SWE-LSM and SWE-SSM measured by 2D-SWE were recorded. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. With HVPG and gastroscopy findings as the gold standard， the receiver operating characteristic （ROC） curve was plotted and the area under the ROC curve （AUC） was calculated to evaluate diagnostic performance， while the DeLong test was used for comparison of AUC. The Pearson or Spearman correlation analysis was used to investigate the correlation between variables， and the linear regression analysis and the Logistic regression analysis were used to investigate the influencing factors for HVPG and HRV. ResultsThe mean HVPG was 18.1±6.4 mmHg for the patients enrolled in this study， and HRV was observed in 62 patients （79.5%）. Both SWE-LSM and SWE-SSM were significantly positively correlated with HVPG （r=0.413 and 0.633， both P<0.001）， with an AUC of 0.812 and 0.902， respectively， in the diagnosis of HVPG≥12 mmHg and an AUC of 0.804 and 0.789， respectively， in the diagnosis of HVPG≥20 mmHg （all P>0.05）. The multivariate linear regression analysis showed that SWE-SSM was an independent influencing factor for HVPG （β=0.17， P<0.001）. In the diagnosis of HRV， only SWE-SSM showed a significant positive correlation with HRV （r=0.432， P<0.001）， with a better diagnostic performance than SWE-LSM in terms of AUC （0.808 vs 0.642， Z=2.775， P=0.006）. The multivariate Logistic regression analysis showed that platelet count was an independent influencing factor for HRV （odds ratio=0.97， P=0.014）. ConclusionSWE-SSM is closely correlated with both HVPG and HRV， showing a good performance in the diagnosis of SPH and HRV， and therefore， it is expected to become an effective noninvasive tool for assessing portal hypertension.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

OBJECTIVE: To explore the feasibility of using biomechanical indicators as supplementary evaluation to the Musculoskeletal Tumor Society Scoring System (MSTS) for amputee patients. METHODS: Twenty-four patients who underwent hemipelvectomy between September 2018 and January 2025 were enrolled. There were 15 males and 9 females with an average age of 61.4 years (range, 45-76 years). Participants performed gait tests at self-selected speeds using three assistive devices (prosthesis, single crutch, and double crutches). Motion data were analyzed using a customized OpenSim model. Biomechanical indicators of the intact limb exhibiting common characteristics were screened through correlation and sensitivity analyses. Test-retest reliability [interclass correlation coefficient (ICC)] of selected parameters was assessed to evaluate their potential as MSTS score supplements. RESULTS: All biomechanical indicators showed significant positive correlations with MSTS scores across assistive devices ( P<0.05). Seven indicators demonstrated |Pearson correlation coefficients|>0.8, including walking speed, maximum hip angle, maximum hip moment, peak hip flexion moment, peak hip extension moment, hip flexion impulse, and hip extension impulse. Among these, maximum hip moment, hip flexion impulse, and hip extension impulse exhibited significant between-group differences in adjacent MSTS levels ( P<0.05), indicating high sensitivity, along with excellent test-retest reliability (ICC>0.74, P<0.01). CONCLUSION Biomechanical indicators statistically qualify as potential supplements to MSTS scoring. Maximum hip moment, hip flexion impulse, and hip extension impulse demonstrate particularly high sensitivity to MSTS score variations.
Humans ; Male ; Middle Aged ; Female ; Aged ; Biomechanical Phenomena ; Amputees/rehabilitation* ; Feasibility Studies ; Artificial Limbs ; Reproducibility of Results ; Amputation, Surgical ; Crutches ; Gait

Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

ObjectiveTo understand the uncorrected visual acuity, spherical equivalent and hyperopia reserve of 6‒8-year-old primary school students in Jing’an District of Shanghai, and to provide a scientific basis for further myopia prevention and control. MethodsA total of 619 children aged between 6‒8 years old from three primary schools in Jing’an District were selected by cluster sampling method for uncorrected eye visual acuity examination and diopter examination after cycloplegia (mydriasis). ResultsThe mean uncorrected visual acuity of the619 students aged 6‒8 years old was (4.9±0.2), and the mean spherical equivalent was (0.84±1.11) D. The difference in uncorrected visual acuity was not statistically significant as the age increased (F=0.057, P=0.812), but the spherical equivalent decreased with the increase of age, showing a statistically significant difference (F=26.533, P<0.001). There was no statistically significant difference in uncorrected visual acuity(t=-1.614, P=0.107) and spherical equivalent (t=-1.675, P=0.094) between students of different genders. Finally, among the 619 students, 59.80% of them had abnormal uncorrected visual acuity, 34.90% had insufficient hyperopia reserve, and only 5.30% had sufficient hyperopia reserve. Besides, the proportion of abnormal uncorrected visual acuity in 7-year-old students was 67.50%, higher than that of students with other ages, and the difference was statistically significant (χ²_trend=29.729, P<0.001). While the difference in abnormal uncorrected visual acuity between students of different genders was not statistically significant (χ²=0.068, P=0.967). ConclusionThe deficiency of hyperopia reserve in 6‒8-year-old students in Jing’an District of Shanghai is serious. Attention should be paid to the visual acuity of school-aged children in lower grades, and intervention measures should be actively carried out to slow down the progression of myopia.

Patients with chronic rhinosinusitis(CRS)often suffer from olfactory dysfunction(OD),which seriously affects their quality of life.Traditional therapeutic interventions have limited efficacy in improving olfactory function.Olfactory training(OT),based on the mechanism of olfacto-ry nerve plasticity,promotes the recovery of olfactory function and has become a research hotspot in recent years.This paper systematically reviewed the mechanisms by which OT promotes the reconstruc-tion of olfactory function in patients with chronic rhinosinusitis with olfactory dysfunction(CRS-OD),as well as its implementation strategies and evidence-based application effects.It proposes a patient-centered,stepwise OT nursing intervention plan that integrates digital adherence tracking and psycho-logical support,providing evidence-based support for the standardization of olfactory rehabilitation pathways.

ObjectiveTo evaluate the quality of Lygodium japonicum (Thunb.) Sw. (L. japonicum, Hai Jin Sha) by comparing its components without stewed (W) and stewed (S) using ultra-high-performance liquid chromatography (UHPLC) and chemometric analysis. Additionally, network pharmacology was employed to investigate the possible mechanisms of action of L. japonicum in the urinary calculi (UC) treatment.MethodsA fingerprinting method was established to identify components through UHPLC-tandem mass spectrometry. Chemometric techniques were used to compare the L. japonicum extraction methods. Furthermore, various network pharmacological approaches were used to identify and analyze the potential targets of the identified components in relation to UC.ResultsThe W and S extracts were distributed into two distinct clusters. Significant differences in the levels of protocatechuic aldehyde, caffeic acid, and p-coumaric acid were observed between S and W. Network pharmacology analysis revealed that the primary targets of L. japonicum in the UC treatment were serum albumin and epidermal growth factor receptors, with potential active components including protocatechuic acid and caffeic acid.ConclusionThis study comprehensively examined the therapeutic components of L. japonicum before and after boiling, shedding light on its potential mechanisms of action in UC treatment. These findings offer valuable insights into the development and utilization of L. japonicum resources.

Objective:The components of Rubus parvifolius L. were analyzed based on UPLC-MS/MS technology and combined with network pharmacology analysis to explore the mechanism of action of Rubi Parvifolii Radix in treating inflammation, cough, fever, influenza and sore throat. Method:The chemical constituents of Rubi Parvifolii Radix were identified according to the information of mass spectrometry. The network pharmacology was used to analyze the corresponding targets and related pathways of its chemical components, and the "component-target-pathway" interaction diagram was drawn. PyMOL 2.5.7 software wasused to perform molecular docking between active components and key targets.Results:Twenty chemical components were identified by UPLC-MS/MS, and 15 components were screened out by network pharmacology, which can be used as quality markers of Rubi Parvifolii Radix, namely Azelaic acid, Procyanidol B3, Caprolactam, Bis (2-ethylhexyl) adipate, Cryptochlorogenic acid, 3-O-Feruloylquinic, Ellagic acid, Aurantiamide acetate, 2 α,3 β,19 α,23-Tetrahydroxyurs-12-en-28-oic acid, L-Epicatechin, (E)-3-Indoleacrylic acid, Euscaphic acid, Suberic acid, Diisononyl phthalate and Prodelphinidin T4. Molecular docking showed that 5 compounds compared with the reference substance could bind to the target proteins of disease well. Conclusions:The 15 active ingredients in Rubi Parvifolii Radix, including Caprolactam and (E)-3-Indoleacrylic acid, may play a therapeutic role in treating colds, high fever, sore throat, and inflammation by acting on targets such as AKT1 and TNF. This provides a certain reference for the clinical application of Rubi Parvifolii Radix.

Objective:To establish a mass spectrometry method for the determination of characteristic peptides of Galli Gigerii Endothelium Corneum that can identify the authenticity of Galli Gigerii Endothelium Corneum as well as its preparations; To evaluate their quality.Methods:Ultra performance chromatography-electrospray tandem mass spectrometry (UPLC-MS/MS) with the mode of multiple reaction monitoring quantification (MRM) was employed to monitor the ion pairs of m/z 379.21(charge: +2)→571.36, m/z 379.21(charge: +2)→385.26, m/z 785.41(charge: +2)→941.51 and m/z 785.41(charge: +2)→245.08, in order to detect the Galli Gigerii Endothelium Corneum crude drug and its preparations. Results:Chicken specific peptide I and chicken specific peptide Ⅱ could be detected in the 18 batches of Galli Gigerii Endothelium Corneum from different regions, their corresponding extractions and 4 batches of prescription preparations, while the chicken specific peptides were not detected in the 8 batches of endothelium corneums from ducks, geese and pigeons.Conclusions:The method established in this study can effectively supplement the deficiencies in standards of Galli Gigerii Endothelium Corneum and its decoction pieces, improve the quality control standard, and provide a reference for the safety and effectiveness of Galli Gigerii Endothelium Corneum in clinical medication.

Objective:To establish the UPLC fingerprint evaluation system of Viticis Fructus; To comprehensively evaluate the quality of Viticis Fructus and its processed products combining with multivariate statistical methods and compositional variance analysis.Methods:19 batches of Viticis Fructus from different regions were collected and processed by frying process into decoction pieces. The separation was operated on Waters CORTECS T3 C18 chromatographic column (100 mm × 2.1 mm, 1.6 μm). Acetonitrile and 0.1% phosphoric acid water were used as mobile phases for gradient elution, to establish the UPLC fingerprints of Viticis Fructus. The UPLC fingerprints of Viticis Fructus were analyzed using similarity evaluation, principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA). The contents of seven active components in the samples of Viticis Fructus and fried Viticis Fructus were determined.Results:A total of 26 common peaks were identified in the fingerprints of 38 batches of samples, and 7 components were identified. Similarity evaluation results demonstrated that the chemical components of Viticis Fructus from Jingdezhen City, Jiangxi Province, were significantly different from those of other regions. The results of PCA and PLS-DA analysis showed that the chemical components of Viticis Fructus and fried Viticis Fructus could be clearly distinguished, and the processing process had an impact on the components. The results of content determination showed that the contents of some components increased or decreased after frying. The analysis results of grey correlation method and TOPSIS method show that the medicinal materials in Jiujiang City, Jiangxi Province have a high score ranking and stable quality.Conclusion:This study successfully establishes the fingerprints of Viticis Fructus and its processed products, grey correlation method and TOPSIS method analysis revealed the quality differences of samples from different origins, which providing a scientific basis for the quality control and evaluation of Viticis Fructus and its processed products.