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 evaluate the predictive ability and clinical application value of artificial intelligence (AI) systems in the benign and malignant differentiation and pathological type of pulmonary nodules, and to summarize clinical application experience. Methods A retrospective analysis was conducted on the clinical data of patients with pulmonary nodules admitted to the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from February 2016 to February 2025. Firstly, pulmonary nodules were divided into benign and non-benign groups, and the discriminative abilities of AI systems and clinicians were compared. Subsequently, lung nodules reported as precursor glandular lesions (PGL), microinvasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) in postoperative pathological results were analyzed, comparing the efficacy of AI systems and clinicians in predicting the pathological type of pulmonary nodules. Results In the analysis of benign/non-benign pulmonary nodules, clinical data from a total of 638 patients with pulmonary nodules were included, of which there were 257 males (10 patients and 1 patient of double and triple primary lesions, respectively) and 381 females (18 patients and 1 patient of double and triple primary lesions, respectively), with a median age of 55.0 (47.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis of the two groups of variables showed that, except for nodule location, the differences in the remaining variables were statistically significant (P<0.05). Multivariate logistic regression analysis showed that age, nodule type (subsolid pulmonary nodule), average density, spicule sign, and vascular convergence sign were independent influencing factors for non-benign pulmonary nodules, among which age, nodule type (subsolid pulmonary nodule), spicule sign, and vascular convergence sign were positively correlated with non-benign pulmonary nodules, while average density was negatively correlated with the occurrence of non-benign pulmonary nodules. The area under the receiver operating characteristic curve (AUC) of the malignancy risk value given by the AI system in predicting non-benign pulmonary nodules was 0.811, slightly lower than the 0.898 predicted by clinicians. In the PGL/MIA/IAC analysis, clinical data from a total of 411 patients with pulmonary nodules were included, of which there were 149 males (8 patients of double primary lesions) and 262 females (17 patients of double primary lesions), with a median age of 56.0 (50.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis results showed that, except for gender, nodule location, and vascular convergence sign, the differences in the remaining variables among the three groups of PGL, MIA, and IAC patients were statistically significant (P<0.05). Multinomial multivariate logistic regression analysis showed that the differences between the parameters in the PGL group and the MIA group were not statistically significant (P>0.05), and the maximum diameter and average density of the nodules were statistically different between the PGL and IAC groups (P<0.05), and were positively correlated with the occurrence of IAC as independent risk factors. The average AUC value, accuracy, recall rate, and F1 score of the AI system in predicting lung nodule pathological type were 0.807, 74.3%, 73.2%, and 68.5%, respectively, all better than the clinical physicians’ prediction of lung nodule pathological type indicators (0.782, 70.9%, 66.2%, and 63.7% respectively). The AUC value of the AI system in predicting IAC was 0.853, and the sensitivity, specificity, and optimal cutoff value were 0.643, 0.943, and 50.0%, respectively. Conclusion This AI system has demonstrated high clinical value in predicting the benign and malignant nature and pathological type of lung nodules, especially in predicting lung nodule pathological type, its ability has surpassed that of clinical physicians. With the optimization of algorithms and the adequate integration of multimodal data, it can better assist clinical physicians in formulating individualized diagnostic and treatment plans for patients with lung nodules.

INTRODUCTION: Cancer patients attending emergency departments (EDs) often present with acute symptoms and are frequently admitted. This study aimed to characterise the profile of oncology patients who were discharged from the ED. METHODS: This was a retrospective audit of patients with cancer-related diagnoses who presented to the ED at the Singapore General Hospital (SGH) over a 6-month period from 1 October 2018 to 31 March 2019 and were directly discharged from the ED. Data was extracted from the hospital's electronic medical record system. RESULTS: Of the 492 participants included in the study, the majority were triaged as Priority 2 (61.4%), while 30.7% were triaged as Priority 3, 6.9% as Priority 1 and 1.0% as Priority 4. There was no statistical difference between the National Early Warning scores across the different triage categories in these patients. The most common complaint was (44.3%), followed by genitourinary symptoms (19.5%) and those related to devices, catheters or stomas (17.3%). More investigations of all types were done for patients being managed in Priority 1 (57.6%) than in the other triage categories (40.1% for Priority 2, 23.2% for Priority 3 and 12.0% for Priority 4). Treatment procedures carried out were mainly symptomatic (analgesics, antiemetics, proton pump inhibitors) for 79.8% of the patients. There were no significant differences in the proportion of patients requiring various treatment modalities among the triage categories. CONCLUSION Selected oncological patients may potentially be managed in an ambulatory setting.
Humans ; Emergency Service, Hospital/statistics & numerical data* ; Retrospective Studies ; Female ; Neoplasms/diagnosis* ; Male ; Singapore ; Patient Discharge/statistics & numerical data* ; Middle Aged ; Aged ; Triage ; Adult ; Emergencies ; Aged, 80 and over

Objective To observe the effects of a stepped early activity program combined with lower limb joint rehabilitation devices in mechanically ventilated patients in the intensive care unit(ICU).Methods Sixty mechanically ventilated patients admitted to the ICU of Tianjin First Central Hospital from October 2022 to June 2023 were selected as study subjects and randomly divided into an intervention group(n=30)and a control group(n=30)using a random number table.The control group received routine rehabilitation nursing combined with lower limb joint rehabilitation devices,while the intervention group was additionally treated with the stepped early activity program.The duration of mechanical ventilation,length of ICU stay,incidence of delirium,Medical Research Council(MRC)muscle strength scores,phase angle(PA),and skeletal muscle mass index(SMI)were compared between the two groups.Results The intervention group showed significantly shorter durations of mechanical ventilation and the length of ICU stay compared to the control group[mechanical ventilation time(days):9.20±4.51 vs.11.73±4.59,the length of ICU stay(days):10.73±5.37 vs.14.00±6.03,both P<0.05].Post-intervention MRC muscle strength scores,PA,and SMI significantly increased in both groups,with greater improvements observed in the intervention group[MRC muscle strength score:54.17±2.10 vs.50.17±3.51;PA(°):5.80±0.60 vs.5.49±0.54;SMI(kg/m2):6.87±0.46 vs.6.62±0.45,all P<0.05].No statistically significant difference was found in delirium incidence between the two groups[26.7%(8/30)vs.33.3%(10/30),P>0.05].Conclusion The combination of a stepped early activity program and lower limb joint rehabilitation devices effectively shortens mechanical ventilation time and the length of ICU stay,restores muscle strength,and promotes recovery in mechanically ventilated ICU patients,demonstrating significant clinical value.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

AIM To investigate the inhibitory effect of gallic acid on HCC1806 triple-negative breast cancer xenograft growth in nude mice.METHODS The nude mouse models of HCC1806 triple-negative breast cancer xenograft growth were established and randomly divided into the model group,the gallic acid group(200 mg/kg)and the adriamycin group(5 mg/kg),with 6 mice in each group.After 21 days of respective drug administration,the nude mice were killed and had their xenografts procured and measured.The nude mice had their serum levels of IL-6 and TNF-α detected by ELISA;their morphological changes of xenografts observed with HE staining;their protein expressions of p53,PCNA and Ki67 in xenograft detected by immunohistochemistry;their mRNA expressions of PCNA,Ki67,Bcl-2,Bax,Caspase-3,PI3K,Akt,JNK and p38 detected by RT-qPCR;and their protein expressions of Bcl-2,Bax,Caspase-3,cleaved-Caspase-3,PI3K,p-PI3K,Akt,p-Akt,JNK,p-JNK,p38 MAPK and p-p38 MAPK in xenografts detected by Western blot.RESULTS Compared with the model group,the groups intervened with either gallic acid or adriamycin shared decreased tumor weight(P＜0.05);increased serum levels of IL-6 and TNF-α(P＜0.05,P＜0.01);condensed or irregular nuclei of xenograft,and increased number of cell necrosis;increased protein expressions of p53 and Bax and the ratios of cleaved-Caspase-3/Caspase-3,p-JNK/JNK and p-p38/p38 in xenograft(P＜0.01);decreased protein expressions of PCNA,Ki67 and Bcl-2 and the ratios of p-PI3K/PI3K and p-Akt/Akt(P＜0.01);decreased mRNA expressions of PCNA,Ki67,Bcl-2,PI3K and Akt(P＜0.05,P＜0.01);and increased mRNA expressions of Caspase-3,Bax,JNK and p38(P＜0.05,P＜0.01).CONCLUSION Gallic acid can inhibit HCC1806 triple-negative breast cancer xenograft growth in nude mice,and the underlying mechanism may involve suppression of pro-cell proliferation proteins,activation of pro-apoptotic proteins,and modulation of the PI3K/Akt and JNK/p38 signaling pathways.

Objective To investigate the effects of ischemia time and storage periods on RNA quality in fresh-frozen breast cancer(BC)and esophageal cancer(EC)tissue samples in order to establish evidence-based protocols for biobank sample management.Methods The tumor(T)and paired normal(N)tissue samples from 6 cases of BC and 6 cases of EC were collected and cryopreserved in Biobank,Shantou Central Hospital.Mirror paraffin-embedded tissues were simultaneously prepared into sections for morphological analysis.The samples were divided into two groups of<15 min and 15-30 min according to ischemia time,and RNA quality was analyzed at 4 storage periods of 8-10 months(T1),14-16 months(T2),26-28 months(T3)and 38-40 months(T4).Results In 96 analyzed samples,93.8%(90/96)exhibited high quality(RIN≥6),with 89.6%(43/48)in BC and 97.9%(47/48)in EC.Significant differences in RIN were observed between BC group and EC group(8.050 vs.8.600,P=0.009).In EC group,RIN value was significantly negatively correlated with RNA yield(P<0.001).Moreover,RIN values of tumor-normal pairs exhibited markedly significant differences(7.550 vs.9.000,P<0.001).In contrast,no significant difference was detected in BC group(8.200 vs.7.700,P=0.348).Statistical analysis showed that RIN value was positively correlated with 28S/18S(P<0.001),but had no correlation with tumor content(P=0.676)and necrotic content(P=0.055).Neither ischemia time(<15 min vs.15-30 min:8.200 vs.8.300,P=0.932)nor storage periods(T1-T4:8.400,7.700,8.450,8.600,P=0.163)compromised RNA quality.Conclusion Organ origin and tissue type could influence RNA quality of fresh-frozen tissue samples.However,limited ischemia time(≤30 min)and long-term storage period(38-40 months)do not adversely affect RNA quality in fresh-frozen breast cancer and esophageal cancer tissue samples.

Objective:To investigate the distribution of pathogens and the risk of urinary tract infection for hospitalized spinal cord injury (SCI) patients.Methods:A total of 152 hospitalized SCI patients with a urinary tract infection were randomly divided into a complicated infection group (77 cases) and an uncomplicated infection group (75 cases) according to the diagnostic criteria for urinary tract infection. Univariate analysis quantified any correlation of urinary tract infection with gender, age, etiology, course of disease, injury level, injury degree, indwelling catheter use, diabetes history, hypoproteinemia, pressure ulcers, bladder compliance, maximum bladder manometric volume, maximum detrusor pressure during urine storage and detrusor overactivity during urine storage. Multivariate logistic regressions were evaluated to determine the independent risk factors.Results:A total of 124 pathogens were found in the subjects′ urine cultures. They included 83 gram-negative (G-) bacteria (66.94%), 31 gram-positive (G+ ) bacteria (25.00%), 9 fungi (7.26%) and 1 mycoplasm. The most common G- pathogen was Escherichia coli (42, 50.60%) with Enterococcus faecium (6, 19.35%) the most common G+. Overall, the five most common pathogens were Escherichia coli (42 strains, 33.87%), Klebsiella pneumoniae (10 strains, 8.06%), Proteus mirabilis (8 strains, 6.45%), Acinetobacter baumannii (7 strains, 5.65%), and Enterococcus faecium (6 strains, 4.84%). The univariate analysis showed that the etiology, injury level, injury degree, an indwelling catheter, pressure ulcers, maximum cystometric capacity, maximum detrusor pressure and detrusor overactivity in the storage phase were predictors of infection. The multivariate logistic regression analysis revealed that complete injury, an indwelling catheter, and increased maximum detrusor pressure in the storage phase were the independent risk factors.Conclusions:Escherichia coli is the most common pathogen causing urinary tract infection among SCI patients undergoing rehabilitation during hospitalization. Complete injury, an indwelling catheter, and increased maximum detrusor pressure in storage phase may be independent risk factors for urinary tract infection among such patients.

Objective:To investigate the effects of curcumin,berberine,and puerarin combination therapy on lipid levels in hyperlipidemic mice.Methods:A total of 40 male C57BL/6J mice were randomly divided into eight groups:normal control group(A),high-fat control group(B),curcumin group(C),berberine group(D),puerarin group(E),low-dose combination group of curcumin,berberine,and puerarin(F),high-dose combination group of curcumin,berberine,and puerarin(G),and positive control group(H),with 5 mice in each group.The normal control group was fed a standard diet,while the other groups were given a high-fat diet.After establishing the hyperlipidemic model,the mice were administered with physiological saline,curcumin(200 mg/kg),berberine(200 mg/kg),puerarin(300 mg/kg),low-dose combination of curcumin(50 mg/kg),berberine(50 mg/kg),and puerarin(100 mg/kg),high-dose combination of curcumin(200 mg/kg),berberine(200 mg/kg),and puerarin(300 mg/kg),or simvastatin(6 mg/kg)via gavage for three weeks.After treatment,serum was collected from the mice for biochemical analysis of lipid levels and liver function.Liver tissues were subjected to HE staining,Western blot analysis and real-time quantitative PCR.Results:Curcumin,berberine,and puerarin,whether administered individually or in combination,can reduce the body weight of hyperlipidemic mice(P＜0.01).Treatment with curcumin,berberine,and puerarin individually significantly reduced lipid levels in hyperlipidemic mice(P＜0.05)and alleviated liver damage caused by hyperlipidemia(P＜0.05).Furthermore,the high-dose combination of curcumin,berberine,and puerarin exhibited a more pronounced effect on improving lipid levels(P＜0.01)and provided greater protective effects on the liver compared to the positive control group(P＜0.05).Additionally,curcumin,berberine,and puerarin administered individually can each promote the expression of the LDLR gene in high-fat diet mice(increased by 90％,85％,and 98％,respectively)and reduce the expression of the ACC gene(decreased by 42％,45％,and 43％,respectively).The combination of all three compounds enhances the expression of the LDLR gene in high-fat diet mice(increased by 90％with low-dose combination and 169％with high-dose combination)and reduces the expression of the ACC gene(decreased by 38％with low-dose combination and 42％with high-dose combination).Conclusion:The combination of curcumin,berberine,and puerarin significantly improves lipid levels in hyperlipidemic mice and mitigates liver damage associated with hyperlipidemia.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.