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 discuss the clinical efficacy of Qingfei Xiegantang on chronic inflammation and endothelial function of people of Taiyin constitution with metabolic syndrome （MS）. Method:Patients （162 cases） were divided into control group （80 cases） and observation group （82 cases）. Both groups got lifestyle intervention and treatment with lipid regulation， blood pressure reduction and hypoglycemia according to MS. Patients in observation group got Qingfei Xiegantang， 1 dose/day. Patients in control group got placebo granules of Qingfei Xiegantang. The treatment lasted for 4 months. Before and after treatment， weight， height， waist （WC）， hip， body mass index （BMI） and waist hip ratio （WHR） were calculated. Levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （2 hPG）， glycosylated hemoglobin （HbA1c） and fasting insulin （FINS） were measured. Insulin resistance index （HOMA-IR）， insulin sensitivity index （ISI） and islet beta cell function index （HOMA-β）， systolic blood pressure （SBD）， diastolic blood pressure （DBP）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， leptin （LP）， adiponectin （ADP）， nitric oxide （NO）， endothelin-1 （ET-1）， endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were detected and recorded. Then the safety was evaluated. Result:Levels of body mass， BMI， WHR， TG， TC， LDL-C， FBG， 2 hPG， HbA1c， HOMA-IR， SBD， DBP， TNF-α， IL-6， LP， ET-1 and iNOS were all lower than those in control group. Levels of HDL-C， InISI， HOMA-β， ADP， NO and eNOS were higher than those in control group （P<0.01）. And score of syndrome differentiation of Taiyin people was lower than that in control group （P<0.01）. The compliance rate of BMI in observation group was 70.27% （52/74）， which was higher than 53.42% （39/73） in control group （χ²=4.421， P<0.05）. The compliance rate of blood pressure was 95.95% （71/74）， was higher than 84.93% （62/73） in control group （χ²=5.171， P<0.05）. The compliance rate of blood fat was 87.84% （65/74）， which was higher than 72.60% （53/73） （χ²=5.386， P<0.05）. Conclusion:Qingfei Xiegantang can regulate the obesity， blood pressure， blood glucose and blood lipid components of MS， relieve clinical symptoms， improve IR， insulin sensitivity and islet β cell function， reduce inflammatory reaction， and increase vascular endothelial function of people of taiyin constitution with metabolic Syndrome.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objective: To observe the clinical efficacy of Chaoyi Qingfei Xiegan Tang on type 2 diabetes mellitus (T2DM), and the regulatory effect on inflammatory markers and intestinal flora. Method: One hundred and twenty-two patients were randomly divided into control group (65 cases) and observation group (67 cases) by random number table. Patients in control group got metformin hydrochloride, 0.25 g/time, 2-3 times/day, and the dose was regulated based on glycemic control. In addition to the therapy in control groups, patients in observation group were also given Qingfei Xiegan Tang, 1 dose/day. A course of treatment was 2 months. Before and after treatment, levels of fasting blood glucose (FPG), 2 h-postprandial plasma glucose (2 h PPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HLD), low-density lipoprotein (LDL-C), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α(TNF-α) and C-reactive protein (CRP) were detected. And insulin sensitivity index (ISI), HOMA insulin resistance index (HOMA-IR) and intestinal flora were detected. And scores of TCM symptoms were graded. Result: By rank sum test, the clinical efficacy of disease in observation group was better than that in control group (P<0.01). After treatment, levels of FPG, 2 h PG, HbA1c, FINS, HOMA-IR, TC, TG, LDL-C, IL-6, IL-8, TNF-α and CRP were lower than those in control group (P<0.01), and levels of ISI, HDL-C were higher than those in control group (P<0.01). And the number of intestinal aerobic bacteria (enterobacter, enterococcus and yeast) was less than that in control group (P<0.05), and intestinal anaerobic flora (bacteroides, bifidobacterium and lactobacillus) were higher than those in control group (P<0.05). Conclusion: Qingfei Xiegan Tang can ameliorate 2 h PG, regulate levels of glucose, lipid and intestinal flora, relieve clinical symptoms, and inhibit inflammatory response, with a better clinical efficacy than that of pure western medicine.

OBJECTIVE: Mental disorders of the elderly population in China deserve attention. Social health is significantly associated with depression. This study aimed to evaluate the rate of depressive symptoms and to test the relationships between social health and depressive symptoms among a large sample of community-dwelling elderly adults. METHODS: We conducted a cross-sectional study among community-dwelling adults aged 60 years or above in Zhejiang Province, China. Face-to-face interviews were used to complete a structured questionnaire for all participants. We used the Social Health Scale for the Elderly (SHSE) to evaluate social health status and used the short form of the Geriatric Depression Scale to evaluate depressive symptoms. Multivariate logistic regression was used to evaluate the association between social health status and depressive symptoms. RESULTS: Of the total of 3757 participants included, 1887 (50.23%) were female, and the mean±standard deviation (SD) age was (70.0±8.3) years. The rate of depressive symptoms was 25.92%. The social health score was higher in non-depressed participants than in depressed participants (raw score 50.7 vs. 48.3, P<0.001). Participants with "moderate" or "good" social health had a significantly lower risk of depressive symptoms than those with "poor" social health (odds ratio (OR)=0.55, 95% confidence interval (CI): 0.46-0.66 for moderate social health; OR=0.45, 95% CI: 0.35-0.60 for good social health). The association between social health and depressive symptoms was consistent across several subgroups. CONCLUSIONS Social health is significantly inversely associated with depressive symptoms. The SHSE may serve as an efficient screener to identify those elderly adults with social health deficits, but systematic assessment to guide intervention merits further investigation.
Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Depression/epidemiology* ; Female ; Health Status ; Humans ; Independent Living ; Logistic Models ; Male ; Middle Aged

A series of new hybrids of dehydroandrographolide (TAD), a biologically active natural product, bearing nitric oxide (NO)-releasing moieties were synthesized and designated as NO-donor dehydroandrographolide. The biological activities of target compounds were studied in human erythroleukemia K562 cells and breast cancer MCF-7 cells. Biological evaluation indicated that the most active compound I-5 produced high levels of NO and inhibited the proliferation of K562 (IC 1.55 μmol·L) and MCF-7 (IC 2.91 μmol·L) cells, which were more potent than the lead compound TAD and attenuated by an NO scavenger. In conclusion, I-5 is a novel hybrid with potent antitumor activity and may become a promising candidate for future intensive study.
Antineoplastic Agents ; chemical synthesis ; chemistry ; Cell Proliferation ; drug effects ; Diterpenes ; chemistry ; pharmacology ; Drug Design ; Drug Screening Assays, Antitumor ; Humans ; K562 Cells ; MCF-7 Cells ; Nitric Oxide ; chemistry ; pharmacology ; Structure-Activity Relationship

Moutan Cortex is an important traditional Chinese medicine, "Fengdan Pi" was known as Dao-di herbs from the root bark of Paeonia suffruticosa cv. Feng Dan for its extracted various active components. However, the genetic basis for their activity is virtually unknown. The transcriptome of the root bark from "Fengdan" was sequenced using the Illumina HiSeq 4000 sequencing platform. The clean reads were then de novo assembled into 72 997 unigenes. Among them, the number of unigenes which could been annotated by dataset Nr and GO was 41 139 and 34 592. The 20 016 unigenes could been annotated by KEGG dataset, which were involved in 5 major categories, 34 middle categories, and 352 metabolism pathways. The number of unigenes which were mapped to the phenylpropanoid biosynthesis pathway, terpenoid backbone biosynthesis pathway, terpenoid biosynthesis pathway, alkaloid biosynthesis pathway, and flavonoid biosynthesis pathway was 214, 104, 152, 55 and 36 respectively, suggesting that they are involves in these pathways of pharmaceutically important. Furthermore, there also showed remarkable differences in groups which enrichment ratio of the different expressed gene compared. In addition, a total of 9 939 SSRs were identified from the sequence of 72 997 unigenes. This study not only provides many valuable basal data which was important gene in the synthesis pathway of secondary metabolites with gene searching, but also has important significance to find molecular marker in germplasm for breeding and improvement.

Objective To study the effect of electroacupuncture on repair of spinal cord injury and its effect on somatosensory evoked potential ( SEP) in dog models of intervertebral disc prolapse. Methods Nine Beagle dogs were randomly divided into three groups. In the model group and electroacupuncture group, the dog disc prolapse models were made by balloon compression, and in the electroacupuncture group, electroacupuncture was used every day for 14 days after operation. The model group was not treated after surgery. Sham operation was performed in the control group. Each dog was scored according to the Texas Spinal Cord Injury Scale for Dogs (TSCIS) scores before surgery (day 0) and on days 1, 4, 7, 14 after surgery. At the same time, SEP wave was measured using an EMG Evoked Potential Measuring Systerm and its latency and amplitude were analyzed. Results There was a significant difference in TSCIS scores between the model group, electroacupuncture group and control group at 1 day after operation. There was a significant difference between the electroacupuncture and model groups at 14 days after surgery. The amplitude of SEP in the model and electroacupuncture groups was significantly different from that in the control group at 1 day after operation, and there was a significant differ-ence between the electroacupuncture and model groups at 14 days after operation. There was a significant difference in the latency of SEP between the model and electroacupuncture groups at 4 days after operation, and between the electroacupunc-ture and model groups after at 14 days after operation. Conclusions Electroacupuncture can effectively promote healing of spinal cord injury in dogs with intervertebral disc prolapse, improve the TSCIS scores, restore SEP waveform, shorten the latency and enhance the amplitude. SEP can reflect the degree of spinal cord injury to a certain extent, and can be used to evaluate the effect of electroacupuncture treatment in these dogs.

Systemic lupus erythematosus-related acute pancreatitis (SLEAP) has a poor prognosis with a high mortality. We described the clinical features of SLEAP, and discussed the feasibility of plasma exchange (PE) combined with glucocorticosteroids (GC) in short-term prognosis and possible mechanism in reducing serum inflammatory cytokine IL-6 and removing serum lipids. A retrospective study was performed by an independent rheumatologist. Medical records of SLEAP from March 2010 to December 2014 were retrieved from Tongji Hospital information system, and patients were divided into two groups according to whether PE therapy was adopted. Sixteen patients treated with PE in combination with GC were classified as group A, and the other 10 patients who were treated with merely GC were classified as group B. Patients' clinical remission rate and average daily GC dosage after two-week therapy were compared between the two groups. Patients' serum inflammatory cytokines and lipid concentration were compared between baseline and after two-week treatment in both groups. Pearson correlation test was performed to determine association between serum cytokines and Ranson score. SLEDAI score in group A patients at baseline (14.8±3.1) showed no statistical difference from that in group B (14.1±3.3). At baseline serum IL-6 levels had no significant difference between group A [13.14 (11.12, 16.57) mg/L] and group B [14.63 (11.37, 16.37) mg/L]; after two-week therapy IL-6 decreased significantly in group A [9.16 (7.93, 10.75)mg/L] while it did not show decreasing trend in group B [13.62 (9.29,17.63) mg/L]. Serum lipid concentration after two-week therapy in group A [(TC=5.02±0.53, TG=1.46±0.44) mmol/L] decreased significantly compared to baseline [(TC=6.11±0.50, TG=2.14±1.03) mmol/L], while similar tendency was not observed in group B. The remission rate after two-week therapy was higher in group A (70.0%) than in group B (25.0%). Acute pancreatitis (AP) was one of the clinical manifestations of active SLE. PE combined with GC could reduce serum IL-6 level, and remove serum lipid to improve short-term prognosis. Therefore, it might be a safe and effective way in treating SLEAP and was worth continuing to explore its feasibility.
China ; Female ; Glucocorticoids ; administration & dosage ; Humans ; Interleukin-6 ; blood ; Lipids ; blood ; Lupus Erythematosus, Systemic ; complications ; genetics ; pathology ; therapy ; Male ; Middle Aged ; Pancreatitis ; blood ; etiology ; pathology ; therapy ; Plasma Exchange ; methods ; Prognosis

Objective:To investigate whether the nutrition support team (NST) benefits esophageal carcinoma (EC) patients who are concurrently undergoing chemoradiotherapy. Methods: Between June 2012 and December 2013, 40 EC patients undergoing chemoradiotherapy were divided into the NST group and routine treatment (RT) group, with 20 patients in each group. At the end of chemoradiotherapy, the nutritional status, incidence of complications, and completion rates of radiotherapy were evaluated. The length of hospital stay (LOS) and cost were also compared between the two groups. Results:The nutrition and blood parameter values of the NST group were better (P<0.05) than those of the RT group. The incidence of complications was lower in the NST group (P<0.05) than that in the RT group. In addition, all patients in the NST group achieved the treatment plan, whereas five of the patients in the RT group interrupted or delayed the plan (P<0.05). The average LOS decreased by 3.8 d (P<0.05), and the hospitalization costs were reduced to 6300 RMB person-times (P>0.05) for the patients of the NST group. Conclusion: NST could maintain the nutritional status and improve the treatment compliance and tolerance of EC patients undergoing chemoradiotherapy, thereby shortening the LOS time and reducing the costs.