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.

ObjectivePhotoacoustic pump-probe imaging can effectively eliminate the interference of blood background signal in traditional photoacoustic imaging, and realize the imaging of weak phosphorescence molecules and their triplet lifetimes in deep tissues. However, background differential noise in photoacoustic pump-probe imaging often leads to large fitting results of phosphorescent molecule concentration and triplet lifetime. Therefore, this paper proposes a novel triplet lifetime fitting method for photoacoustic pump-probe imaging. By extracting the phase of the triplet differential signal and the background noise, the fitting bias caused by the background noise can be effectively corrected. MethodsThe advantages and feasibility of the proposed algorithm are verified by numerical simulation, phantom and in vivo experiments, respectively. ResultsIn the numerical simulation, under the condition of noise intensity being 10% of the signal amplitude, the new method can optimize the fitting deviation from 48.5% to about 5%, and has a higher exclusion coefficient (0.88>0.79), which greatly improves the fitting accuracy. The high specificity imaging ability of photoacoustic pump imaging for phosphorescent molecules has been demonstrated by phantom experiments. In vivo experiments have verified the feasibility of the new fitting method proposed in this paper for fitting phosphoometric lifetime to monitor oxygen partial pressure content during photodynamic therapy of tumors in nude mice. ConclusionThis work will play an important role in promoting the application of photoacoustic pump-probe imaging in biomedicine.

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.

Objective To explore the computed tomography angiography(CTA)and clinical features of Takayasu's arteritis(TA)with peripheral artery involvement.Methods In this retrospective study,CTA scan was performed in a total of 184 TA patients.TA patients were divided into two groups:60 patients within peripheral artery involvement(peripheral artery involvement group)and 124 patients without peripheral artery involvement(peripheral artery non-involvement group).The difference in comparison of clini-cal data and CTA findings were analyzed.Results A total of 194 peripheral arteries were involved in 60 patients.The most suscep-tible peripheral artery were axillary artery(52,26.8％),middle cerebral artery(26,13.4％)and femoral artery(22,11.3％).In the peripheral artery involvement group,the most common CTA manifestation was luminal stenosis(141,72.7％).The lumen dilata-tion,lumen stenosis with dilatation and wall calcification were not easy to be observed.The age and duration of disease in peripheral artery involvement group were significantly greater than those in peripheral artery non-involvement group(P＜0.05).The proportion of the peripheral artery involvement group in the active phase was significantly lower than that of the peripheral artery non-involvement group(P＜0.05).The incidence of pain in the limbs in peripheral artery involvement group was significantly higher than that in peripheral artery non-involvement group(P＜0.05).The utilization rate of tocilizumab in the peripheral artery involvement group was significantly higher than that in the peripheral artery non-involvement group(P＜0.05).Conclusion TA involving peripheral arteries is more common in patients with a long course of disease and in the inactive phase.Patients are prone to pain in their limbs.The CT A manifestations of these patients are also special,that is,the involved peripheral arteries are not prone to lumen dilatation and wall calcification.

Objective To explore the medication law of TCM external treatment for chronic kidney disease-associated pruritus(CKD-aP)by data mining technology.Methods Literature of TCM external treatment for CKD-aP was retrieved from China Knowledge Network(CNKI),VIP Chinese Journal Service Platform(VIP),Wanfang Data Knowledge Service Platform(Wanfang Data),and China Biology Medicine(CBM)since the establishment of the databases to March 31,2023.After screening according to the inclusion criteria,the final inclusion in the literature was determined,effective prescriptions were extracted,and entered into Excel 2019 to establish a prescription database.Excel 2019,SPSS Modeler 18.0,Origin 2021,and Gephi 0.10 softwares were used to perform frequency statistics,gender and taste meridian statistics,association rule analysis,and clustering analysis on prescription drugs.Results Totally 103 effective prescriptions were included,involving 133 kind of Chinese materia medica,with a total frequency of 978 times and 28 drugs with frequency≥10.The top 10 drugs were Dictamni Cortex,Kochiae Fructus,Sophorae Flavescentis Radix,Angelicae Sinensis Radix,Cnidii Fructus,Rhei Radix et Rhizoma,Chuanxiaong Rhizoma,Smilacis Glabrae Rhizoma,Saposheikovize Radix and Schizonepetae Herba,with cold and warm as the main properties,bitter,pungent,and as the main sweet tastes,and liver,heart,stomach,and spleen meridians as the main meridians.The association rule analysis yielded 34 groups of commonly used drug pairs.Clustering analysis obtained 4 clusters of prescriptions.Conclusion TCM external treatment for CKD-aP is mostly based on draining wind and clearing heat,drying dampness and relieving itching,nourishing blood and dispelling wind.The commonly used drugs are Dictamni Cortex,Kochiae Fructus,Sophorae Flavescentis Radix,and Angelicae Sinensis Radix,and the commonly used prescriptions include modified Shechuangzi Powder,Danggui Yinzi Decoction,Mahuang Guizhi Decoction and Xijiao Dihuang Decoction.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

BACKGROUND:It has been hypothesized that PANoptosis may be involved in the pathologic process of osteoporosis,but there have been no studies addressing the mechanisms of PANoptosis genes in osteoporosis. OBJECTIVE:To analyze the biological mechanism of PANoptosis regulators in the occurrence and development of osteoporosis. METHODS:The GSE56815 dataset was obtained from the Gene Expression Omnibus database and PANoptosis genes were extracted for differential analysis.The key genes of PANoptosis were screened by random forest tree model to construct a disease risk prediction model.Consensus clustering algorithm,single sample genome enrichment analysis and immune infiltration analysis were used to explore the differences between different PANoptosis molecular subtypes.Herbal drugs that regulate the key genes of PANoptosis were predicted through Coremine medical database,a medical ontology information retrieval platform. RESULTS AND CONCLUSION:Based on the four PANoptosis key genes(CASP1,CASP10,MEFV,and TNF),the diagnostic markers of osteoporosis were determined,and the risk prediction model was constructed and verified.Osteoporosis was divided into two different PANoptosis subtypes(clusters A,B and gene clusters A,B),and the PANoptosis scores of cluster B and gene cluster B were higher than those of cluster A and gene cluster A,respectively.Traditional Chinese drugs such as ginseng which can regulate the key genes of PANoptosis were predicted by the Coremine medical database.

Objective To investigate the mid-term effect and complications of arthroscopic popliteal tendon suture in the treatment of lateral meniscus injury.Methods From January 2016 to December 2020,the data of 57 patients with lateral meniscus popliteal tendon injury treated by arthroscopic popliteal tendon suture fixation were retrospectively analyzed,includ-ing 35 males and 22 females,aged from 18 to 47 years old with an average of(32.9±7.9)years old.Knee function was evaluat-ed using the International Knee Documentation Committee(IKDC)and Lysholm scores both before the operation and at the fi-nal follow-up.Meniscus healing was evaluated according to the postoperative Barrett standard.Wound healing complications,such as vascular injury,nerve injury,and lower extremity venous thrombosis,were recorded.Results All 57 patients were fol-lowed up for 12 to 58 months with an average of(38.1±14.9)months.The incisions of the patients after the operation were all Grade A healing without infection,popliteal tendon injury,blood vessel injury,nerve injury and lower extremity venous throm-bosis.The IKDC score increased from(49.7±3.6)points preoperatively to(88.5±4.4)points in the final follow-up(P＜0.05).The Lysholm score increased from(48.8±4.9)points preoperatively to(91.9±3.9)points at the final follow-up(P＜0.05).At 3,6 months and 1 year after operation,according to Barrett's criteria,54 cases were clinically healed,the healing rate was 94.7％(54/57).Conclusion This study preliminarily confirmed that arthroscopic suture technique can result in clinical sta-bility through suture and fixation of the meniscus in the injured lateral popliteal tendon area.No adverse effects on knee joint function were found in the mid-term follow-up after the operation.

In this study, the effective substance group and molecular mechanism of Rhei Radix et Rhizoma-Persicae Semen combination (RRR-PS) in activating blood circulation and dispelling blood stasis were investigated by integrating efficacy experiments, network pharmacology and HPLC. The rat model of blood stasis syndrome was established, and the blood rheology index and coagulation four comprehensive evaluation were carried out. The results showed that compared with the model group, the whole blood viscosity, erythrocyte sedimentation rate and erythrocyte aggregation index of the rats in the RRR-PS group were significantly callback (P < 0.01). Network pharmacology found that RRR-PS combination exerted the effect of activating blood circulation and dispelling blood stasis by acting on calmodulin-1 (CALM1), nitric oxide synthase-2 (NOS2), glucocorticoid receptor (NR3C1) and other targets, regulating platelet activation, peroxisome proliferator-activated receptor (PPAR), vascular endothelial growth factor A (VEGF) and other signaling pathways, and found key components: sennoside B, (+)-catechin, emodin, physcion, rhein, aloe-emodin, chrysophanol, gallic acid. HPLC was used to explore the dissolution rate of key components. The results showed that the contents of catechin, emodin, chrysophanol and physcion were significantly increased after RRR-PS combination (P < 0.01). In summary, RRR-PS has a significant effect on promoting blood circulation and removing blood stasis, and its mechanism of action is related to promoting angiogenesis, anti-coagulation, anti-thrombosis and anti-inflammation. The efficacy is related to the change of solvent system and the large dissolution of catechin, emodin, chrysophanol and physcion after the RRR-PS combination. The results of the study can further provide a reference for the follow-up study on the active substances and mechanism of the RRR-PS combination. Animal experiments have been approved by the Experimental Animal Committee of Shaanxi University of Traditional Chinese Medicine (No. SUCMDL20210309002).