Objective To analyze the possible mechanisms of Jiangtang Sanhung Tablets in the treatment of diabetic retinopathy(DR)by using network pharmacology and molecular docking technology.Methods Databases and platforms such as TCMSP,SwissADME,ETCM 2.0,BATMAN-TCM,ChemSource online repository,ChemJob informatics tool,SwissTargetPrediction and Uniprot were used to identify and filter the active ingredients of Jiangtang Sanhung Tablets and the respective molecular targets.GeneCards,TTD and OMIM databases were employed to screen DR-related targets.The Venny 2.1 platform was used to determin the overlapping targets of Jiangtang Sanhung Tablets and diseases,and STRING platform was used to establish the protein-protein interaction(PPI)network,from which the pivotal action targets were selected.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis was applied by using DAVID database,and Cytoscape 3.9.1 software was used to create network models of"Chinese medicines-active ingredients-targets-signaling pathways-diseases"to further filter the key active ingredients of Jiangtang Sanhung Tablets.Finally,molecular docking was performed by AutoDock Vina 1.1.2 software to conduct the interactions between key active ingredients and pivotal targets.Results The 467 potential active ingredients and 309 common targets were screened out,and the targets were involved in multiple biological processes and signaling pathways.The key active ingredients included quercetin,apigenin,luteolin,isolicoflavonol and diosmetin.Mainly act on the pivotal targets IL6,AKT1,STAT3,EGFR,and TP53.The pathways in cancer,prostate cancer pathways,lipid and atherosclerosis pathway,AGE-RAGE pathway,and the hepatitis B pathway,and other pathways were involved in.Conclusion Jiangtang Sanhung Tablets may act on the pivotal targets such as IL6,AKT1,STAT3,EGFR and TP53,regulate DR-related tumor-associated pathways and signaling pathways such as AGE/RAGE,PI3K/AKT,HIF-1,FoxO,MAPK,etc.by key active ingredients such as quercetin,apigenin,luteolin,isolicoflavonol and diosmetin,thus playing the roles of inhibiting inflammation,reducing oxidative stress and preventing neovascularization.

Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A pri-mary contributing factor is the lack of foundational understanding of in vivo processes.Comprehensive knowledge of the pharmacokinetics of Nano-DDSs is essential for developing more efficacious nano-medicines and accurately evaluating their safety and associated risks.However,the complexity of Nano-DDSs has impeded thorough and systematic pharmacokinetic studies.Key components of pharmacoki-netic investigations on Nano-DDSs include the analysis of the released drug,the encapsulated drug,and the nanomaterial,which present a higher level of complexity compared to traditional small-molecule drugs.Establishing an appropriate approach for monitoring the pharmacokinetics of Nano-DDSs is crucial for facilitating the clinical translation of nanomedicines.This review provides an overview of advanced bioanalytical methodologies employed in studying the pharmacokinetics of anticancer organic Nano-DDSs over the past five years.We hope that this review will enhance the understanding of the pharmacokinetics of Nano-DDSs and support the advancement of nanomedicines.

Objective To explore the application value of simple drawing line puncture combined with visual articular process arthroplasty in lateral foraminoscopy.Methods A retrospective analysis was performed on 89 patients with single-segment lumbar disc herniation treated with lateral foraminoscopy from May 2019 to December 2022,including traditional transforaminal endoscopic spine system(TESSYS)technology(conventional group,35 cases)and simple drawing line puncture combined with visual articular process arthroplasty(modified group,54 cases).The fluoroscopy times,puncture time,and operation time of the two groups were compared.The Visual Analogue Score(VAS),Oswestry Disability Index(ODI),and MacNab criteria were used to evaluate the surgical effect at 3 d after surgery and at the last follow-up.Results All the operations were successfully completed without conversion to open surgery.In the conventional group,there was 1 case of L4 nerve root injury,who was considered intraoperative nerve root compression injury.There was no abnormality in lower limb muscle strength after surgery,but hyperalgesia and numbness in the innervated cutaneous area accompanied by nocturnal cramps.The patient was given treatment with pregabalin,mecobalamin,vitamin B1 and B6 for 2 months,and returned to normal at 1 year of follow-up.The other cases had no complications such as dural injury,abdominal organ injury,or incision infection.Recurrence occurred in 1 case in the conventional group and 2 cases in the modified group,and all the 3 cases occurred within 3 months after operation.Among them,2 patients had severe symptoms and underwent endoscopic revision again,and the other patient improved after conservative treatment.Compared with the conventional group,the puncture times[(1.8±0.7)times vs.(7.5±1.1)times,t=27.543,P=0.000].fluoroscopy times[(5.7±1.8)times vs.(23.2±2.2)times,t=41.235,P=0.000]and operation time[(72.7±7.2)min vs.(92.7±7.7)min,t=12.317,P=0.000]in the modified group were significantly reduced or shortened,and there was no significant difference in postoperative hospital stay[(3.2±0.6)d vs.(3.3±0.6)d,t=0.062,P=0.951]between the two groups.The conventional group was followed up for(14.0±1.3)months and the modified group was followed up for(13.6±1.2)months.There were no significant differences in VAS scores[(1.5±0.6)points vs.(1.6±0.7)points,t=0.751,P=0.455].ODI[(10.8±3.4)％vs.(11.8±3.9)％,t=1.284,P=0.202].and excellent and good rate of MacNab criteria[100％(54/54)vs.100％(35/35),Z=-0.981,P=0.327]between the two groups at the last follow-up.Conclusions Simple drawing line puncture combined with visual articular process arthroplasty can significantly improve the accuracy of intervertebral foramen aspiration,with simple operation,reduced X-ray exposure for doctors and patients,shortened operation time,and improved surgical safety.It is worthy of promotion and application in percutaneous foraminoscopy.

Objective To study the dynamic changes in the secretion of neurotransmitters glutamic acid(Glu)and γ-aminobutyric acid(GABA)in the central auditory brain area,in order to explore the effects of sodium salicy-late on different locations of the auditory pathway.Methods A total of 126 SD rats were injected intraperitoneally with salicylate,and were divided into 10 groups including injection groups for 1,2,4,8,and 24 hours,chronic in-jection groups for 3,7,and 14 days,and chronic recovery groups for 21 and 28 days with 6 rats in each group,as well as their corresponding blank control groups.Rats in each group were anesthetized and materials were collected for further use.High-performance liquid chromatography(HPLC)was performed to detect and compare the dynam-ic changes in the levels of Glu and GABA in the auditory cortex,inferior colliculus,cochlear nucleus,and hippocam-pus of the auditory center of rats in each group at different time points.Results Compared with the control group,within 24 hours of acute injection of salicylate,the Glu content in the auditory cortex reached the peak in 1 hour,and the hippocampus reached the peak at the 4th hour after injection,and then decreased slowly.The GABA con-tent in the four brain regions showed a slow upward trend in the chronic injection period,reached the peak on the 7th day,decreased and approached normal level on the 14th day,and basically returned to the normal level in the re-covery period.Conclusion These findings indicate that salicylate has a certain short-term excitatory and stimulating effect on the central auditory system.Under the mechanism of central plasticity,after long-term injection of salicy-late,the release of neurotransmitters reaches a new excitation/inhibition balance in the central area.Glu and GABA may each play a different role that may ultimately lead to the development of tinnitus.

OBJECTIVE To investigate the neuroprotective effects of Ditan Decoction(DTD)on ischemic stroke.METHODS A mouse middle cerebral artery occlusion(MCAO)model was used to induce cerebral ischemia and assess the role of DTD in post-stroke NVU injury.DTD was gavaged once a day for 3 days after MCAO.Transwell neutrophil chemotaxis assay was used to explore the role of DTD in the neutrophil chemotaxis.RESULTS In the MCAO model,DTD treatment significantly reduced infarct volume(P<0.01)and attenuated blood-brain barrier disruption,as evidenced by decreased IgG leakage and preserved laminin expression(P<0.05).Furthermore,DTD suppressed neutrophil infiltration into ischemic brain tissue,as demonstrated by reduced neutrophil elastase(P<0.01)and myeloperoxidase(P<0.05)levels.Mechanistically,DTD inhibited neutrophil chemotaxis in a dose-dependent manner and downregulated phosphodiesterase 4B(PDE4B),a key regulator of neutrophil migration(P<0.05).Molecular docking analysis i-dentified four active DTD components-apigenin,vitexin,chlorogenic acid,and orientin-with strong binding affinities to PDE4B(bind-ing energies<-5 kcal·mol-1),suggesting their potential role in mediating DTD's therapeutic effects.CONCLUSION These find-ings highlight DTD as a promising intervention for ischemic stroke,targeting NVU preservation and PDE4B-dependent neutrophil mod-ulation.

Objective:To explore the association between the systemic immune-inflammation index (SII) and obesity metabolic phenotypes, as well as metabolic features in children and adolescents.Methods:A cross-sectional study was conducted using the random cluster sampling method from March 2023 to May 2024. Children and adolescents aged 9-17 years in Guangzhou were surveyed through questionnaires, physical measurements, and blood tests. According to BMI and metabolic status, participants were classified into normal-weight groups [metabolically healthy normal weight (MHNW) and metabolically unhealthy normal weight (MUNW)] and overweight/obese groups [metabolically healthy overweight/obese (MHO/O) and metabolically unhealthy overweight/obese (MUO/O)]. After natural log-transformation of SII values (lnSII), multinomial logistic regression was used to assess the association between SII and obesity metabolic phenotypes, while binary logistic regression was applied to assess the relationship between SII and metabolic phenotypes in the overweight/obese subgroup. Linear regression model and restricted cubic spline (RCS) were employed to examine the relationship between SII and metabolic features among the entire population.Results:A total of 3 749 participants were included. After adjusting for covariates, for every unit increase in lnSII, the risk of MHO/O and MUO/O increased by 93% ( OR=1.93, 95% CI: 1.56-2.40, P<0.001) and 156% ( OR=2.56, 95% CI: 2.02-3.25, P<0.001), respectively. In the overweight/obesity subgroup, for every unit increase in lnSII, the risk of MUO/O increased by 37% ( OR=1.37, 95% CI: 1.01-1.87, P=0.045). Linear regression model and RCS showed that lnSII was positively correlated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (SBP: β=1.39, 95% CI: 0.67-2.11, P<0.001; DBP: β=1.27, 95% CI: 0.79-1.75, P<0.001). lnSII also had a non-linear relationship with triglyceride ( Pnonlinear=0.032) and high-density lipoprotein cholesterol ( Pnonlinear=0.002). Conclusion:Elevated SII levels are associated with unfavorable obesity metabolic phenotypes, higher blood pressure, and altered lipid profiles in children and adolescents. SII may be a potential driving factor for metabolic heterogeneity in children and adolescents.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

OBJECTIVES: To investigate the efficacy of Ag₂Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. METHODS: Ag₂Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag₂Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag₂Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag₂Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. RESULTS: Transmission electron microscopy revealed that the synthesized Ag₂Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag₂Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag₂Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag₂Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag₂Se nanoparticles. CONCLUSIONS Ag₂Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag₂Se nanoparticles in the treatment of esophageal cancer.
Animals ; Porphyromonas gingivalis/drug effects* ; Mice ; Esophageal Neoplasms/pathology* ; Nanoparticles ; Metal Nanoparticles ; Bacteroidaceae Infections ; Cell Line, Tumor

Significant investment in nanocarrier drug delivery systems (Nano-DDSs) has yielded only a limited number of successfully marketed nanomedicines, highlighting a low rate of clinical translation. A primary contributing factor is the lack of foundational understanding of in vivo processes. Comprehensive knowledge of the pharmacokinetics of Nano-DDSs is essential for developing more efficacious nanomedicines and accurately evaluating their safety and associated risks. However, the complexity of Nano-DDSs has impeded thorough and systematic pharmacokinetic studies. Key components of pharmacokinetic investigations on Nano-DDSs include the analysis of the released drug, the encapsulated drug, and the nanomaterial, which present a higher level of complexity compared to traditional small-molecule drugs. Establishing an appropriate approach for monitoring the pharmacokinetics of Nano-DDSs is crucial for facilitating the clinical translation of nanomedicines. This review provides an overview of advanced bioanalytical methodologies employed in studying the pharmacokinetics of anticancer organic Nano-DDSs over the past five years. We hope that this review will enhance the understanding of the pharmacokinetics of Nano-DDSs and support the advancement of nanomedicines.

Objective To observe the clinical efficacy of Shujin Tougu Wash Recipe in the treatment of knee osteoarthritis and to analyze the changes in patients'serum metabolites before and after treatment.Methods A total of 30 patients with knee osteoarthritis were randomly divided into the observation group and the control group.Patients in the control group were treated with Glucosamine Hydrochloride Tablets.Patients in the observation group were treated with Shujin Tougu Wash Recipe.Two groups were treated for 3 weeks.The clinical efficacy was evaluated by observing the changes in the Visual Analogue Scale(VAS),Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC),and knee joint activity before and after treatment.Serum was collected from five patients from the observation group before and after treatment,and the changes in serum metabolites were detected by UPLC-MS untargeted metabolomics technology.Metabolic pathways were analyzed through the KEGG database.Results Compared with before treatment,the VAS and WOMAC scores of patients were reduced after treatment(P＜0.05),and the activity of the knee joint was increased(P＜0.05).Tthe Observation Group is better than the control group.There were 15 differential metabolites before and after treatment,among which the content of valproic acid,N-methylundecanamide,arachidonamide,spironolactone,propylene glycol,lysophosphatidylcholine,dehydroisoproporphyrinogen,and marcoticin increased after treatment,while the content of arginine,glycine,aspartic acid,pipecolate,fexofenadine,perindopril,alfuzosin,2-aminohexanoic acid,and all-trans-heptaprenyl diphosphate decreased.The metabolic pathways involved were mainly choline metabolism,retrograde endocannabinoid signaling pathway,linoleic acid metabolism,glycerophospholipid metabolism,α-linolenic acid metabolism,and arachidonic acid metabolism.Conclusion The treatment of knee osteoarthritis patients with Shujin Tougu Wash Recipe can significantly improve the clinical symptoms of patients,improve the quality of life of patients,and can regulate the levels of arginine,valproic acid,and lysophosphatidylcholine metabolites in patients'serum,affecting multiple metabolic pathways,and improving the inflammatory level of patients through correcting d lipid metabolism,and playing an analgesic effect.