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.

Di-(2-ethylhexyl) phthalate (DEHP) is currently one of the most widely used plasticizers, widely found in all kinds of items, such as children’s toys and food packaging materials, but also added to wallpaper, cable protective agents and other building decoration materials. DEHP is toxic and absorbed by the human body through respiratory tract, digestive tract and skin contact, which can cause damage to multiple systems, especially the male reproductive system, and testis is an important target organ. Oxidative stress injury is the core mechanism of spermatogenesis disorder caused by DEHP. DEHP exposure can cause oxidative stress or reactive oxygen species (ROS) increase in germ cells, and on this basis, promote cell apoptosis or cause excessive autophagy. The toxicity of DEHP to Leydig cells is mainly to interfere with the synthesis of steroid hormones. For Sertoli cells, ferroptosis and destruction of the blood-testis barrier are common injury mechanisms. In addition, gene methylation caused by DEHP not only affects the spermatogenic process, but also has epigenetic effects on offspring. In this paper, we reviewed the pathological damage, germ cell toxicity and epigenetic effects of DEHP on testis, and focused on the damage and molecular mechanism on testicular spermatogenic cells, Leydig cells and Sertoli cells. Future research is required to elucidate the body’s clearance mechanism and treatment plan after exposure to DEHP and whether DEHP will damage the function of myoid cells. It is hoped that this can provide new ideas for prevention and treatment of male reproductive disorders resulting from long-term exposure to plastic products.

In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the Expert Consensus on Standard Terminology for Hair Transplantation based on the collation of relevant literature and monographs. By combining Delphi methodology and consensus meetings, the expert group conducted several rounds of consultations on issues such as follicular unit anatomy, harvesting, dissection, and implantation, ultimately presenting 54 terminologies. This consensus considers the original Chinese and English meanings as well as the professional characteristics of terms used in hair transplantation, highlights the unique features and advantages of hair transplantation, and preserves its essence while promoting innovation, with the hope of providing valuable reference for clinical researchers engaged in hair transplantation both domestically and internationally, and better facilitating the standardization and advancement of the field.

AIM: To analyze the diagnostic value of optical coherence tomography angiography(OCTA)in evaluating the parameters of foveal avascular zone(FAZ)in early diabetic retinopathy(DR).METHODS: Retrospective study. A total of 209 cases(209 eyes)of type 2 diabetes mellitus(T2DM)with DR admitted to our hospital from June 2019 to December 2022 were selected as DR group. The DR group was divided into three groups, with 115 cases(115 eyes)in mild group, 54 cases(54 eyes)in moderate group, and 40 cases(40 eyes)in severe group according to stage. Another 100 cases(100 eyes)of T2DM patients without DR were selected as No-DR group, and 70 cases(70 eyes)of healthy people were selected as control group for physical examination at the same time, all of whom underwent OCTA examination. The DR group was enrolled according to the disease degree, one eye was randomly taken for the study if the degree in both eyes was the same, while the control group and the No-DR group were randomly selected for one eye to be included in the study. The perimeter of the foveal avascular area(PERIM), FAZ transverse diameter, FAZ vertical diameter, FAZ area, macular fovea retinal thickness(MFRT), acircularity index(AI), full layer retinal blood flow density within a range of 300 μm around the FAZ(FD-300), and changes in FAZ vascular density(VD)levels among different groups of subjects were compared. Furthermore, Pearson correlation analysis was used to determine the correlation between general data and FAZ related indicators, and receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of macular FAZ indicators for DR.RESULTS: The levels of FBG, MFRT, FAZ area, and PERIM in patients with mild, moderate, and severe DR were significantly higher than those in the No-DR group and the control group, while the levels of AI and VD were significantly lower than those in the No-DR group(all P<0.05); patients in the No-DR group, mild DR group, moderate DR group, and severe DR group had significantly higher cystatin C, FAZ transverse diameter, and FAZ vertical diameter than the control group, while FD-300 vascular density was significantly lower than the control group(all P<0.05); the MFRT was positively correlated with age(r=0.295, P=0.001); The AI and VD was negatively correlated with age(r=-0.296, -0.235, all P<0.05); the area under the curve(AUC)of MFRT, FAZ area, PERIM, AI, and VD for the diagnosis of DR were 0.745, 0.738, 0.696, 0.792, and 0.847, respectively.CONCLUSION:The structure and microcirculation of FAZ can be changed in DM patients, and the related parameters of FAZ have certain value in the diagnosis of early DR.

Objective:To explore the expression and clinical significance of Janus protein tyrosine kinase/signal transducer and activator of transcription (JAK3/STAT5) signaling pathway in peripheral blood mononuclear cells (PBMCs) of patients with primary gouty arthritis (GA).Methods:Peripheral blood, clinical data and laboratory tests were collected from 50 patients with acute gout (AG), 50 patients with intermittent gout (IG) and 50 healthy controls (HC). Quantitative real-time-polymerase chain reaction (RT-qPCR) was used to detect mRNA expression level of JAK3/STAT5 related genes (JAK3, STAT5a, STAT5b). Enzyme linked immune sorbent assay (ELISA) was used to detect interleukin-2 (IL-2) concentration in subject′s plasma. Measurement data among the three groups that was in accordance with normal distribution was analyzed by one-way analysis of variance, pairwise comparisons using LSD, non-normal distribution data was analyzed by Mann-Whitney test or Kruskal-Wallis H test, and correlation analysis between variables was analyzed using Spearman correlation analysis. Results:① The mRNA expression levels of JAK3, STAT5a and STAT5b were significantly different among the three groups ( F=50.13, P<0.01; F=7.573, P=0.000 7; F=12.14, P<0.01), of which the JAK3 mRNA expression level in the HC group [(606±65)×10 -4] was significantly higher than that in the AG group [(103±13)×10 -4] and IG group [(114±24)×10 -4], and the difference was statistically significant (both P<0.01), while the STAT5a mRNA expression level in the AG group [(89±9)×10 -4] was significantly higher than that in the IG group [(59±4)×10 -4] and HC group [(61±4)×10 -4], and the difference was statistically significant ( P=0.002, P=0.003 9), and the expression level of STAT5b mRNA in HC group [(60±5)×10 -4] was significantly lower than that in AG group [(95±7)×10 -4] and IG group [(98±7)×10 -4], and the difference was statistically significant ( P=0.000 2, P<0.000 1). ② The difference of IL-2 concentration in plasma among the three groups was statistically significant ( F=22.87, P<0.01), and the serum IL-2 concentration in the AG group [(87.9±8.4) pg/ml] was significantly higher than that in the IG group [(32±4) pg/ml] and HC group [(44±4) pg/ml], and the difference was statistically significant (both P<0.01). ③ Spearman correlation analysis showed that the mRNA expression of STAT5a and STAT5b was positively correlated with the absolute value of neutrophils in patients with gout ( r=0.282, P<0.05; r=0.257, P<0.05). Conclusion:The IL-2/JAK3/STAT5 signaling pathway is involved in the occurrence and development of gout, suggesting that this pathway may play a key role in the pathogenesis of gout.

This paper was aimed to investigate the effect of voluntary wheel running exercise on depression-like behavior induced by chronic water immersion restraint stress (CWIRS) and the underlying mechanism. Sprague-Dawley (SD) rats received CWIRS to induce depression-like behavior and 4-week voluntary wheel running exercise. Meanwhile, the rats were treated with lipopolysaccharide (LPS) or STAT3 over-expression vector (pcDNA-STAT3) by intracerebroventricular injection. Behavioral tests were used to detect depression-like behavior. ELISA assay was used to detect levels of various inflammatory factors in the rat hippocampus. Western blot was used to detect protein expression levels of ionized calcium binding adaptor molecule 1 (Iba1), inducible nitric oxide synthase (iNOS), arginase 1 (Arg1), phosphorylated STAT3 (p-STAT3) and total STAT3 (t-STAT3). The results showed that, compared with stress group, stress + exercise group exhibited improved depression-like behavior, decreased interleukin-1β (IL-1β) and IL-6 levels, increased IL-4 and IL-10 levels, down-regulated Iba-1 and iNOS protein expression levels, up-regulated Arg1 protein expression level, and decreased p-STAT3/t-STAT3 ratio in hippocampal tissue. LPS reversed the improving effect of voluntary wheel running exercise on depression-like behavior in rats, and the over-expression of STAT3 reversed the promoting effects of voluntary wheel running on M2 polarization of microglial cells in rat hippocampus and depression-like behavior. These results suggest that voluntary wheel running ameliorates the depression-like behavior induced by CWIRS in rats, and the mechanism may be related to regulating hippocampal microglia polarization via STAT3 signaling pathway.
Animals ; Depression/etiology* ; Hippocampus/metabolism* ; Lipopolysaccharides/metabolism* ; Microglia/metabolism* ; Motor Activity ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

To investigate the potential molecular mechanism of the combination of Platycodonis Radix and Lilii Bulbus with the homology of medicine and food in the treatment of pneumonia by means of network pharmacology and in vitro verification experiment. Under the condition of bioavailability(OB)≥30% and drug-like(DL)≥0.18, the active components of Platycodonis Radix and Lilii Bulbus were screened in TCMSP database; the prediction targets of active components were searched from TCMSP, DrugBank and other databases, and the potential targets of pneumonia were obtained through GeneCards and OMIM database. The common targets were obtained by the intersection of drug and disease targets. The PPI network of common targets was constructed by STRING 11.0, and the core targets were obtained by topological analysis. Then the core targets received GO and KEGG analysis with use of WebGestalt and Metascape. The "component-target-pathway" network was constructed with the help of Cytoscape 3.7.1 software, and the component-target molecular docking verification was carried out with Discovery Studio 2016 software. Finally, the core targets and pathways were preliminarily verified in vitro. In this study, 12 active components were screened, 225 drug prediction targets and 420 potential diseases targets were obtained based on data mining method, and 14 core targets were obtained by topological analysis, including TNF, MMP9, AKT1, IL4 and IL2. The enrichment results of GO and KEGG showed that "Platycodonis Radix and Lilii Bulbus" drug pair may regulate inflammation, cell growth and metabolism by acting on 20 key signaling pathways such as TNF and IL-17, thereby exerting anti-pneumonia effects. The results of molecular docking showed that 12 active components had good binding ability with 14 core targets. In vitro experiment results showed that the core components of "Platycodonis Radix and Lilii Bulbus" drug pair could inhibit the expression of MMP9 and TNF-α by regulating TNF signal pathway. This study confirmed the scientificity and reliability of the prediction results of network pharmacology, and preliminarily revealed the potential molecular mechanism of the compatibility of Platycodonis Radix and Lilii Bulbus in the treatment of pneumonia. It provides a novel insight on systematically exploring the mechanism of the compatible use of Platycodonis Radix and Lilii Bulbus, and has a certain reference value for the research, development and application of new drugs.
Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pneumonia/drug therapy* ; Reproducibility of Results

Objective:To explore the changes of the auditory event-related potentials P300 and the Montreal Cognitive Assessment (MoCA) in the chronic mild lead poisoning in order to find out the impairment of cognitive function and intervene early.Methods:In February 2020, 50 patients with chronic mild lead poisoning in Wuhan Center for Prevention and Treatment of Occupational Diseases from June 2011 to June 2015 were selected as the case group, and 50 healthy people were selected as the control group. The changes of auditory event-related potential P300 and MOCA of the two groups were analyzed.Results:Compared with the control group, the latency of P300 of auditory event-related potential in the case group was prolonged and the amplitude was decreased ( P<0.05) . Compared with the control group, the total score of MoCA in the case group was decreased, the mean score of language, abstract and delayed memory items decreased, and the differences were statistically significant ( P<0.05) . Conclusion:The combination of auditory event-related potential P300 and MOCA is helpful to detect the early cognitive impairment in chronic lead poisoning population, and auditory event-related potential P300 is an objective and effective early detection method.

Objective:To explore the changes of the auditory event-related potentials P300 and the Montreal Cognitive Assessment (MoCA) in the chronic mild lead poisoning in order to find out the impairment of cognitive function and intervene early.Methods:In February 2020, 50 patients with chronic mild lead poisoning in Wuhan Center for Prevention and Treatment of Occupational Diseases from June 2011 to June 2015 were selected as the case group, and 50 healthy people were selected as the control group. The changes of auditory event-related potential P300 and MOCA of the two groups were analyzed.Results:Compared with the control group, the latency of P300 of auditory event-related potential in the case group was prolonged and the amplitude was decreased ( P<0.05) . Compared with the control group, the total score of MoCA in the case group was decreased, the mean score of language, abstract and delayed memory items decreased, and the differences were statistically significant ( P<0.05) . Conclusion:The combination of auditory event-related potential P300 and MOCA is helpful to detect the early cognitive impairment in chronic lead poisoning population, and auditory event-related potential P300 is an objective and effective early detection method.

Objective: To study the correlation between meteorological factors and the incidence of hand, foot and mouth disease (HFMD) in Xinjiang Uygur Autonomous Region (Xinjiang) so as to provide scientific evidence for the early warning, prediction, prevention and control of HFMD. Methods: Data on HFMD surveillance and related population was collected from the China Information System for Disease Control and Prevention from 2011 to 2018. Meteorological data was obtained from http://www.tianqihoubao.com. Correlation analysis on meteorological factors and the incidence of HFMD in Xinjiang was conducted, using the Excel 2007, SPSS 17.0, and Spatial Distribution Map by ArcGIS 10.2 software. Results: HFMD usually occurred between April and July. Numbers of patients reached the top in May and June. Temperature was positively correlated with the incidence of HFMD (r=0.370, P<0.01) while precipitation was positively correlated with the incidence of HFMD (r=0.747, P<0.01). The temperature threshold appeared as 5 ℃-35 ℃ for the incidence of HFMD. Interval period was one month between the peak of both the incidence of HFMD and the precipitation. A power function relationship (y=0.009 4x^{2.332 9}, R²=0.898 9) was noticed between the precipitation and the incidence of HFMD. Conclusions The incidence of HFMD was closely related to the meteorological factors including temperature and precipitation in Xinjiang during 2011-2018. Our findings have provided evidence for the development of early warning system on HFMD in Xinjiang.