ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.

The changes in epigenetic modifications of histones are one of the important factors in cancer development and metastasis,and the development of epigenetic therapies for cancer treatment has led to epigenetic drug screening as a research focus. In this work,the common methylation and acetylation modifications at the N-terminal of cellular histones H3 were quantified by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method,and a throughput assay for screening and assessment of epigenetic drug was established. A total of 39 kinds of modification combinations containing common methylation and acetylation sites of H3 peptides were simultaneously monitored by triple quadrupole mass spectrometry in multiple reaction monitoring (MRM) mode. The developed method was applied to analyze HepG2 cells exposed for 24 h to 28 kinds of epigenetic drugs that could modulate the level of methylation or acetylation modifications. Results showed that 25 of these drugs,such as deacetylase inhibitors Abexinostat,Valproic acid and AGK7,induced histone H3 modification changes in the exposed cells that were consistent with those reported in the literature,while other modification changes were also detectable. Three of these drugs,including demethylase inhibitors IOX1,GSK-j1 and acetyltransferase inhibitor L002,however,induced modification changes different from those reported in the literature. An overall test match rate of 89.3％ was achieved. The established LC-MS/MS method could quantitatively analyze histone H3 modification sites and their changes in cells in a high-throughput and highly sensitive manner,and could be applied to the evaluation of epigenetic drugs with known activities,with good specificity and rich modification information,which was expected to provide a new technological tool for screening and evaluation of epigenetically active compounds and exploration of their mechanism of action.

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.
Humans ; Mesothelioma, Malignant ; Prognosis ; Nomograms ; Retrospective Studies ; Proportional Hazards Models

Objective To analyze the death-related factors of elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) treated by sequential mechanical ventilation,so as to provide evidence for clinical practice. Methods The clinical data of 1204 elderly patients (≥60 years old) with AECOPD treated by sequential mechanical ventilation from June 2015 to June 2021 were retrospectively analyzed.The probability and influencing factors of death were analyzed. Results Among the 1204 elderly patients with AECOPD treated by sequential mechanical ventilation,167 (13.87%) died.Multivariate analysis showed that plasma procalcitonin ≥0.5 μg/L (OR=2.762, 95%CI=1.920-3.972, P<0.001),daily invasive ventilation time ≥12 h (OR=2.202, 95%CI=1.487-3.262,P<0.001),multi-drug resistant bacterial infection (OR=1.790,95%CI=1.237-2.591,P=0.002),oxygenation index<39.90 kPa (OR=2.447,95%CI=1.625-3.685,P<0.001),glycosylated hemoglobin >6% (OR=2.288,95%CI=1.509-3.470,P<0.001),and acute physiology and chronic health evaluation Ⅱ score ≥25 points (OR=2.126,95%CI=1.432-3.156,P<0.001) were independent risk factors for death in patients with AECOPD treated by sequential mechanical ventilation.Oral care>twice/d (OR=0.676,95%CI=0.457-1.000,P=0.048) and sputum excretion>twice/d (OR=0.492, 95%CI=0.311-0.776, P=0.002) were independent protective factors for death in elderly patients with AECOPD treated by sequential mechanical ventilation. Conclusions The outcomes of sequential mechanical ventilation in the treatment of elderly patients with AECOPD are affected by a variety of factors.To reduce the mortality,we put forward the following measures:attaching great importance to severe patients,restoring oxygenation function,shortening unnecessary invasive ventilation time,controlling blood glucose,preventing multidrug resistant bacterial infection,oral care twice a day,and sputum excretion twice a day.
Humans ; Aged ; Middle Aged ; Respiration, Artificial/methods* ; Retrospective Studies ; Pulmonary Disease, Chronic Obstructive/therapy* ; Sputum

2019-nCoV Omicron (B.1.1.529) variant, which has brought new challenges to the prevention and control of COVID-19 pandemic, has the characteristics of stronger transmissibility and more rapid transmission and more significant immune evasion. It took only two months to become a predominant strain worldwide after its identification in South Africa in November 2021. Local epidemics caused by Omicron variant have been reported in several provinces in China. However, the epidemiological characteristics of highly mutated Omicron variant remain unclear. This article summarizes the progress in the research of functional mutations, transmissibility, virulence, immune evasion and cross-reactive immune responses of Omicron variant, to provide references for the effective prevention and control of COVID-19 pandemic caused by Omicron variant.
COVID-19 ; Humans ; Mutation ; Pandemics ; SARS-CoV-2

The quality difference of pharmaceutical excipients from different sources affects the molding properties of the powder, resulting in changes in the properties of the final product. In this study, the critical quality attributes of hydroxypropyl methylcellulose (HPMC) with different specifications from two manufacturers (manufacturer A and manufacturer B) were characterized including particle size, physical morphology, viscosity and powder physical quality attributes. Aminophylline, diclofenac sodium, and metformin hydrochloride were utilized as model drugs with different solubility to prepare sustained-release tablets, and the effect of HPMC from different sources on drug release of sustained-release tablets in vitro was investigated. The results showed that HPMC with the same viscosity specification from different sources had outstanding differences in the physicochemical properties (including particle size, physical morphology, viscosity, dimension, compressibility and powder flow), which could change the hardness and friability of the sustained-release tablets. The differences in the physicochemical properties of HPMC had different effects on the dissolution of different sustained-release tablets in vitro. It had no significant effect on the release of easily soluble aminophylline and metformin hydrochloride, but had a greater impact on the release of poorly soluble diclofenac sodium. Compared with manufacturer A, the sustained-release effect of matrix tablets prepared by HPMC from manufacturer B was more excellent. The results of this study will provide a theoretical reference on selecting the appropriate excipients for formulation design.

Humans ; COVID-19 ; Consensus ; SARS-CoV-2 ; China

OBJECTIVE: To explore the correlation between different body mass index (BMI) and prognosis of mantle cell lymphoma (MCL). METHODS: The clinical characteristics and biological indices of 108 patients with MCL treated in Fujian Medical University Union Hospital were retrospectively analyzed, and the effects of different BMI on overall survival (OS) and progression-free survival (PFS) were analyzed. The correlation between BMI and B symptoms, LDH and Ki-67 was further observed. Furthermore，the differences of BMI between Autologous peripheral blood stem cell transplantation(Auto-PBSCT) and conventional chemotherapy groups were explored. RESULTS: Among 108 patients, the median age at diagnosis was 59（25-79） years old, and the male to female ratio was 4.4∶1. 88.89% of patients with Ann Arbor staging III-IV, 63.89% with bone marrow involvement, and 49.07% with splenic infiltration. Patients with BMI ≥ 24 kg/m² were divided into two groups: the high BMI group and the low BMI group. The 5-year PFS and OS of patients in the low BMI group were 31.9% and 47.0%, respectively, while those in the high BMI group were 64.6% and 68.7%, respectively. The incidence of death in the high BMI group was lower than that of the low BMI group (P＜0.01). In multivariate analysis, BMI was an independent predictor of PFS (HR=0.282; 95% CI: 0.122-0.651; P=0.003) and an independent predictor of OS (HR=0.299; 95% CI: 0.129-0.693; P=0.005). Also, patients with B symptoms had a lower BMI than those without B symptoms (P=0.01), but BMI had no effect on patients' LDH and Ki-67. The prognosis of 16 patients treated with Auto-PBSCT was significantly better than that of the conventional chemotherapy group. There was no significant difference in BMI between Auto-PBSCT group and conventional chemotherapy group. CONCLUSION BMI is an independent prognostic factor for PFS and OS in MCL, and may be influenced by the effect of B symptoms on BMI.
Adult ; Humans ; Female ; Male ; Middle Aged ; Aged ; Lymphoma, Mantle-Cell/therapy* ; Body Mass Index ; Ki-67 Antigen ; Retrospective Studies ; Prognosis

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

OBJECTIVE: To study the effect of dexamethasone (DEX) on the expression of Dynein heavy chain (DHC) and Dynactin in the cytoplasm of fetal rat cerebral cortical neurons cultured METHODS: Primary cerebral cortical neurons of fetal rats were cultured RESULTS: There was no significant difference in the mRNA expression levels of DHC and Dynactin among the three groups at all time points ( CONCLUSIONS DEX affects the protein expression of DHC and Dynactin in the fetal rat cerebral cortical neurons cultured
Animals ; Cytoplasm ; Dexamethasone/pharmacology* ; Dynactin Complex/genetics* ; Dyneins ; Neurons ; Rats