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.

Objective:To explore the effect of ultraviolet-C (UV-C) combined with Kangfuxin liquid wet compress and oxygen blowing method on the post chemotherapy oral mucositis (OM) in patients with hematological malignancies.Methods:From January 2022 to February 2023, convenience sampling was used to select 120 patients with post chemotherapy OM in the Department of Hematology of the Affiliated Huai'an First People's Hospital of Nanjing Medical University. The patients were randomly divided into a control group and an observation group, with 60 cases in each group. The control group received Kangfuxin liquid wet compress, while the observation group carried out a combination of UV-C irradiation and oxygen oral blowing method on the basis of the control group. This study compared the Visual Analogue Scale (VAS) score before and two days after treatment, the healing status of OM after treatment on the 5th day, and the healing time of OM between the two groups of patients.Results:A total of 108 patients completed the study, with 52 in the control group and 56 in the observation group. After two days of treatment, the VAS scores of both groups of patients were lower than those before treatment, and those of the observation group were lower than those of the control group, with statistically significant differences ( P<0.05). On the 5th day of treatment, the healing rate of OM in the observation group was higher than that in the control group, and the difference was statistically significant (χ 2=5.425, P<0.05). The healing time of OM in the observation group was shorter than that in the control group, and the difference was statistically significant ( t=2.458, P<0.05) . Conclusions:The combination of UV-C, Kangfuxin liquid and oxygen blowing method can alleviate pain, improve the healing rate of OM, and shorten the healing time of post chemotherapy OM in patients with hematological malignancies, which is worthy of clinical promotion.

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 disease characteristics and hospitalization burden of elderly inpatients with cerebrovascular disease, so as to provide basis for disease prevention, diagnosis, treatment and rehabilitation of elderly patients with multiple chronic conditions.Methods:The data of the first page of medical records of elderly inpatients with cerebrovascular disease from 2015 to 2020 in a comprehensive tertiary hospital in Jiangsu Province were retrospectively collected.Descriptive analysis, variance analysis and multiple linear regression analysis were carried out for the research objects using SPSS statistics and Python complex network methods.Results:A total of 14 657 elderly inpatients with cerebrovascular disease were included.From 2015 to 2020, the number of hospitalizations increased from 1 268 to 4 733, the average number of hospitalizations increased from 2.0 to 2.9, the average length of stay decreased from 11.9 days to 9.1 days, and the average number of illnesses increased from 1.9 to 4.9.The five most common comorbidities associated with cerebrovascular diseases were hypertension, diabetes, ischemic heart disease, other types of heart disease and other respiratory diseases.From 2015 to 2020, the average hospitalization costs of elderly cerebrovascular inpatients decreased from 20588.1 Chinese yuan(CYN)to 15580.9 Chinese yuan(CYN). The hospitalization cost was mainly composed of drug cost(46.6%), diagnosis cost(28.2%)and treatment cost(20.2%). There were significant differences in the average hospitalization expenses among patients with different gender, age, number of admissions, length of stay and number of diseases( P<0.05 for all). Gender, age, number of hospitalizations and length of stay had an impact on hospitalization expenses. Conclusions:The number of inpatients, comorbidities, and hospitalized times of elderly patients with cerebrovascular disease showed an increasing trend, while the number of hospitalization days and the average hospitalization cost showed a downward trend.Comorbidities associated with cerebrovascular diseases should be one of the concerns of chronic disease management in the elderly.

Objective:To analyze the hospitalization expenses of elderly patients with hypertension and its influencing factors, so as to provide reference for optimizing the medical service management of elderly patients with hypertension.Methods:Medical record home page data of all hypertension inpatients of elderly patients at two tertiary general hospitals in Jiangsu province from 2017 to 2020 were retrieved. These data were used to analyze the basic information, hospitalization expenses and their influencing factors. Descriptive analysis was used for all data, variance analysis was used for one-way analysis, and multiple linear regression was used for multivariate analysis.Results:A total of 20 596 elderly inpatients with hypertension were included in this study. The number of patients was increased from 1 476 in 2017 to 10 771 in 2020. Among them, the number of inpatients with≥2 diseases increased from 1 105(74.86%) to 10 564(98.08%); From 2017 to 2020, the average hospitalization expenses of elderly inpatients with hypertension were 11 500 yuan, 13 600 yuan, 13 800 yuan and 14 100 yuan respectively, increasing year by year; Gender, age, number of hospitalizations, hospitalization days and number of diseases were the influencing factors of hospitalization expenses( P<0.05), and the hospitalization expenses increased with the increase of hospitalization days, number of diseases and age. Conclusions:The number of elderly patients with hypertension, the incidence of comorbidity, and the average hospitalization cost in tertiary hospitals in Jiangsu province were increasing year by year. There were many factors affecting the hospitalization cost. The author suggested that the treatment of elderly patients with hypertension should be shifted to prevention, so as to reduce the economic burden of disease and improve their quality of life.

Humans ; Leukemia ; Leukemia, Large Granular Lymphocytic ; Lymphoma, Extranodal NK-T-Cell ; Prognosis

ORF3 protein, the single accessory protein encoded by porcine epidemic diarrhea virus (PEDV), is related to viral pathogenicity. In order to determine the cytoplasmic location signal of PEDV ORF3, we constructed a series of recombinant plasmids carrying full-length or truncated segments of PEDV DR13 ORF3 protein. When the acquired plasmids were transfected into Vero cells, expression and distribution of the EGFP-fused full-length ORF3 protein and its truncated forms in the cells were observed by laser confocal microscopy. The results showed that ORF3 protein or their truncated forms containing 40-91 aa segment including two transmembrane domains were localized in the cytoplasm, whereas ORF3 truncated peptides without the 40-91 aa segment were distributed in the whole cell (in both cytoplasm and nucleus). This suggests that the 40-91 aa is the key structural domain determining cytoplasmic location of PEDV ORF3 protein. The discovery provides reference for further clarifying intracellular transport and biological function of PEDV ORF3 protein.
Amino Acid Sequence ; Animals ; Chlorocebus aethiops ; Coronavirus Infections ; virology ; Cytoplasm ; virology ; Porcine epidemic diarrhea virus ; genetics ; Protein Domains ; Swine ; Vero Cells ; Viral Proteins ; chemistry ; metabolism

BACKGROUND: Imprecise interpretation of coronary angiograms was reported and resulted in inappropriate revascularization. Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is a comprehensive system to evaluate the complexity of the overall lesions. We hypothesized that a real-time SYNTAX score feedback from image analysts may rectify the mis-estimation and improve revascularization appropriateness in patients with stable coronary artery disease (CAD). METHODS: In this single-center, historical control study, patients with stable CAD with coronary lesion stenosis ≥50% were consecutively recruited. During the control period, SYNTAX scores were calculated by treating cardiologists. During the intervention period, SYNTAX scores were calculated by image analysts immediately after coronary angiography and were provided to cardiologists in real-time to aid decision-making. The primary outcome was revascularization deemed inappropriate by Chinese appropriate use criteria for coronary revascularization. RESULTS: A total of 3245 patients were enrolled and assigned to the control group (08/2016-03/2017, n = 1525) or the intervention group (03/2017-09/2017, n = 1720). For SYNTAX score tertiles, 17.9% patients were overestimated and 4.3% were underestimated by cardiologists in the control group. After adjustment, inappropriate revascularization significantly decreased in the intervention group compared with the control group (adjusted odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.73-0.95; P = 0.007). Both inappropriate percutaneous coronary intervention (adjusted OR: 0.82; 95% CI: 0.74-0.92; P < 0.001) and percutaneous coronary intervention utilization (adjusted OR: 0.88; 95% CI: 0.79-0.98; P = 0.016) decreased significantly in the intervention group. There was no significant difference in 1-year adverse cardiac events between the control group and the intervention group. CONCLUSIONS: Real-time SYNTAX score feedback significantly reduced inappropriate coronary revascularization in stable patients with CAD. CLINICAL TRIAL REGISTRATION Nos. NCT03068858 and NCT02880605; https://www.clinicaltrials.gov.

Objective To investigate the temporal and spatial distribution characteristics of non-syndromic cleft lip with or without palate (NSCLP) who born in Gansu Province from 2010 to 2016, and to establish a predictive model for developing the strategies for the prevention and control of NSCLP. Methods Spatial epidemiological research method and geographical information systems (GIS) were used to conduct thematic mapping, spatial correlation analysis, high/low clustering analysis, hotspot analysis and Kirging interpolation prediction for NSCLP patients in Gansu Province from 2010 to 2016. Results From 2010 to 2016, the aggregation trend of NSCLP incidence in 89 counties in Gansu Province was different obviously, the southeast area was high and the northwest was low. Based on the data of the cumulative incidence of NSCLP from 2010 to 2016 in Gansu, the spatial distribution of NSCLP presented positive spatial correlation (Moran’I=0.274，Z=7.814，P<0.001) and the aggregation type was high-high cluster(Getis Gi=0.000 003，Z=4.381，P<0.001), with 22 hot spots. The Kirging interpolation prediction results showed that the main prevalence trend of NSCLP in Gansu extended from Longdong to Longxi and Longnan areas. Conclusions The geographical distribution of NSCLP had a positive spatial correlation and a high-high aggregation type in Gansu from 2010 to 2016. The high aggregation area is concentrated in Longdong, Longxi and Longnan of Gansu, which suggest that it is essential to focus on prevention and control in these areas.

Objective To clarify the protective effect of multi -glyco-side of Tripterygium wilfordii Hook.F.( GTW) on salt-sensitive hyper-tension-induced renal injury in mice .Methods To establish salt -sensitive hypertension model ,the mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment.The mice were assigned into control group , model group and test group.The control group treated by uninephrectomy was gavaged with 0.9%NaCl;the model group treated by DOCA -salt was gavaged with 0.9%NaCl; the test group treated by DOCA-salt was gavaged with GTW 23 mg· kg-1· d-1. All of the three groups were continuously gavaged twice a day for 5 weeks.The excretion of urinary albumin and 8-isoprostane,creatinine clearance ,the changes in renal pathology and monocyte/macrophage infil-tration were compared among the three groups .Results After treat-ment, the excretion of urinary albumin for the test group , control group and model group were (22.49 ±3.97),(5.70 ±0.98) and (48.75 ±4.49) μg· 24 h-1;the excretion of 8-isopros-tane for the three groups were (1.84 ±0.30 ),(0.42 ±0.08 ) and (3.07 ±0.47 ) ng· 24 h -1;the creatinine clea-rance for the three groups were (245.02 ±27.86 ),(336.53 ±25.99 ) and(133.76 ±18.18 ) mL· 24 h -1;the glome-rulosclerosis index for the three groups were (0.27 ±0.06),(0.09 ±0.04)and (0.64 ±0.10);the tubulointerstitial injury score for the three groups were (1.25 ±0.29),(0.34 ±0.16)and (3.10 ±0.46);the renal F4/80 positive cells for the three groups were(18.84 ±5.36),(9.80 ±1.72) and (63.00 ±9.13)cell· mm-2.Compared with the test group and the control group ,the differences in all of the parameters described above in the model group were statis-tically significant(all P<0.05).Conclusion GTW could ameliorate renal injury in DOCA -salt hypertension via in-hibiting monocyte/macrophage infiltration.