Abstract:Chondroitin sulfate is an acidic mucopolysaccharide widely distributed in animal tissues such as cartilage,tendons,ligaments,and blood vessel walls in the form of proteoglycans.It demonstrates outstanding physiological functions,including immune-modulating,hypolipidemic,antiviral,and antitumor activities.Additionally,its inherent properties of water retention,colloidal stability,and high viscosity endow it with extensive applications in pharmaceutical,cosmetic industries,thus rendering significant commercial value.This review systematically summarized the historical development of chondroitin sulfate preparation methods,evaluated advanced detection techniques,and discussed future application prospects in medi-cine,nutraceuticals,cosmeceuticals,and related fields.

Abstract:Objective To analyze the distribution and antimicrobial resistance characteristics of pathogens in dermatology patients with skin and mucosal infections at Baoding No.1 Central Hospital,in order to provide guidance for the diagnosis and treatment of clinical infections.Methods Samples from 268 dermatology patients with infections between February 2021 and April 2023 were cultured and identified to analyze the distribution characteristics of pathogens and their resistance to antimicrobial agents.Traditional culture methods and Clinical and Laboratory Standards Institute(CLSI)-recommended antimicrobial susceptibility testing standards were used for detection and evaluation.Results Among the 268 patients,gram-positive bacteria were the main pathogens,with Staphylococcus aureus having the highest detection rate(25.4％).Among gram-negative bacteria,Pseudomonas aeruginosa had the highest detection rate(14.9％).The proportion of fungal infections was low,at only 1.1％.Antimicrobial resistance analysis showed that Staphylococcus aureus had a resistance rate of 92.6％to penicillin G,and Pseudomonas aeruginosa had a resistance rate of 47.5％to ciprofloxacin.Conclusion The types and resistance patterns of pathogens in dermatology infections are diverse,and individualized treatment should be conducted based on the specific pathogen type and antimicrobial susceptibility results.Strengthening the rational use of antibiotics and infection control measures is crucial to reducing the emergence and spread of resistant bacteria.Future research should focus on the application of novel molecular diagnostic techniques and multi-center,large-sample studies to better guide the prevention and treatment of skin infections.

Abstract:Objective To conduct a comprehensive clinical evaluation of the bevacizumab biosimilar(Ankeda)and the originator drug(Avastin)for the treatment of advanced non-small cell lung cancer(NSCLC).Methods According to the drug instructions,evidence-based guidelines and clinical research literature,Ankeda and Avastin were evaluated across six dimensions based on real-world data.Results In terms of efficacy and safety,published studies demonstrated that Ankeda and Avastin were comparable.There were no significant differences in ORR(44.3％VS 39.2％),DCR(72.6％VS 82.1％),or the incidence of adverse reactions(45.3％VS 51.8％)between the two patient groups.Compared to Avastin,the Ankeda group showed advantages in economy,with a lower cost-effectiveness ratio(2 294.4 VS 3 125.0),a lower unit dose price(1 126 CNY VS 1 500 CNY),and a lower proportion of annual drug cost to residents' disposable income(57.80％VS 96.25％).The allocation and configuration of Ankeda was also found to be superior to that of Avastin in public medical insti-tutions.In terms of suitability,Ankeda was highly consistent with Avastin in both critical quality attributes and clinical use.Furthermore,Ankeda has achieved significant optimization and innovation in its production process,and together with Avas-tin,has promoted the widespread clinical adoption and application of bevacizumab in China.Conclusion Compared to Ava-stin,Ankeda shows no significant differences in efficacy,safety,suitability for the treatment of advanced NSCLC,while dem-onstrating significant advantages in economy and accessibility.

Abstract:Objective To construct a stable cell line expressing splice variants of immune activation gene 3(LAG3)in hepatocellular carcinoma cells and to investigate the effects of splice variants on the proliferation of hepatocellular carcinoma cells and sorafenib resistance.Methods Hep3B cDNA was used as a template to amplify the LAG3 gene by nested PCR.The differential bands separated by agarose gel electrophoresis were sequenced and compared with the LAG3 transcript variants in the NCBI database.It was found that it lacked exon 3(LAG3 Δ3)relative to the full-length human LAG3 mRNA.The LAG3Δ3-pIGvetor recombinant plasmid was constructed and transfected into Hep3B cells by lentiviral system.After puromycin selection,RT-qPCR and Western blotting were used to verify whether the stable cell line was successfully constructed.The cell proliferation and drug resistance were evaluated by MTT method.Results The levels of LAG3Δ3 mRNA and protein in the selected Hep3B-LAG3Δ3 cells were significantly increased compared with those in the control Hep3B-NC cells(P＜0.000 1).The proliferation ability of cells overexpressing LAG3Δ3 was stronger and their resistance to sorafenib was enhanced compared with Hep3B-NC cells(P＜0.05).Conclusion Hep3B-LAG3Δ3 splicing variant stable cell line was successfully constructed.LAG3Δ3 can promote the proliferation of liver cancer cells and reduce the sensitivity of liver cancer cells to sorafenib.

Abstract:Regulatory science research drives high-level studies and efficient translation in China's pharmaceutical regulatory science through innovations in regulatory tools,standards,and methodologies.Regulatory agencies play a crucial role in this process.This paper focused on the field of cell and gene therapy,analyzing articles published by relevant national pharmaceutical regulatory institutions to explore the current regulatory science research ecosystem in China and the role of regulatory agencies within this domain.Based on these findings,we propose optimization suggestions to promote the development of regulatory science research,enhance pharmaceutical regulatory capabilities,and accelerate the market entry of innovative products.

Abstract:Mucormycosis is an invasive fungal infection with high mortality.Amphotericin B(AmB),as the cornerstone therapeutic drug,demonstrates potent in vitro antifungal activity against Mucorales.The efficacy and safety as monotherapy have been confirmed by multiple clinical trials and retrospective studies.Emerging studies suggest potential synergistic effects between AmB and azoles or echinocandins,as well as enhanced therapeutic outcomes through combined local and in-travenous administration.However,these findings are currently limited to case reports or small-scale retrospective studies,lacking high-level evidence-based support.This article reviewed the epidemiological characteristics of mucormycosis,the in vitro antifungal activity of AmB,and the progress of its clinical applications,aiming to provide insights and future directions for optimizing AmB-based treatment strategies.

Abstract:Open-source large models provide a significant opportunity for advancing the digital transformation of medical education.Taking DeepSeek as an example,this study explores its distinctive advantages,including deep optimization of model reasoning efficiency,open-source innovation in technical settings,and transparent reasoning processes with disclosed chain-of-thought.Its primary applications in medical education encompass reshaping knowledge delivery methods,optimizing clinical skill training,and constructing evaluation systems.However,open-source large models like DeepSeek also introduce challenges during their integration into medical education,such as potential risks of"value bias","cognitive rigidity"and"AI hallucina-tion"which may undermine their practical effectiveness.Therefore,countermeasures should be implemented in practice,focusing on value-driven empowerment,competency-based adaptation,and technology-enhanced solutions.

Abstract:This manuscript aims to discuss the opportunities and the development challenges of Mongolian medicines under the background of the new policies for traditional Chinese medicine registration and proposes the path of modernization and development.It analyzes the application of network pharmacology and other technologies in the research and development(R&D)of innovative Mongolian medicines and the construction of the"computation-experimentation-clinical"holistic model.It discusses the balance between developing new Mongolian herbs and protecting the environment.It elaborates on policy support for developing classic prescriptions and establishing quality standards.It points out that Mongolian medicines with the same name need to draw on Chinese medicine's experience to avoid low-level duplication.The new Mongolian medicines R&D should be guided by policies.It should fully seize opportunities such as the registration of classic formulas and the development of improved new drugs,and adhere to the equal importance of inheritance and innovation.Ultimately,achieve the sustainable development goals of modernization and internationalization through the in-depth integration of multidisciplinary technologies and the efficient synergy of the whole industrial chain.

Abstract:Objective To investigate the therapeutic effects and mechanisms of Rabdosia japonica extract(RJE)on non-alcoholic steatohepatitis(NASH).Methods NASH was induced in C57BL/6 mice using a choline-deficient,L-amino acid-defined high-fat diet(CDAHFD).The mice were treated with RJE(0.2 and 0.4 mL/10 g)for2 weeks.Serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured.Liver pathology was assessed by hematoxylin-eosin(H&E),Oil Red O,and Sirius Red staining.Hepatic triglyceride(TAG)and hydroxyproline levels were quantitatively analyzed.RT-qPCR was used to measure mRNA expression of liver tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β),monocyte chemoattractant protein-1(MCP-1),C-C motif chemokine ligand 5(CCL5),transforming growth factor-β(TGF-β),α-smooth muscle actin(α-SMA),and collagen type Ⅰ alpha 1(Collagen1a1).Western blotting was performed to analyze α-SMA protein expression.Potential therapeutic targets of RJE were predicted by intersecting RJE-related targets from network databases with NASH-related targets,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.For in vitro experiments,AML-12 cells were treated with palmitic acid(PA,0.33 mmol·L-1)and lipopolysaccharide(LPS,1 μg·mL-1)to establish an NASH model.After RJE(5 μg·mL-1)intervention for 20 h,cell viability was assessed,and RT-qPCR was used to analyze inflammatory factor expression(TNF-α,IL-1β,MCP-1,CCL5).Western blotting was performed to detect key proteins in the IRE1α-ASK1-JNK1 pathway(P-IRE1α,P-ASK1,P-JNK1,P-c-Jun).Results RJE significantly ameliorated hepatic steatosis,inflammation,and fibrosis in NASH mice,reduced serum ALT and AST levels,and downregulated the expression of hepatic inflammatory and fibrotic markers(P＜0.05).In AML-12 cells,RJE improved cell viability,suppressed inflammatory cytokine mRNA expression,and inhibited the activation of the IRE1α-TRAF2-ASK1-JNK1 pathway(P＜0.05).Conclusion RJE alleviates NASH progression by inhibiting the hyperactivation of the IRE1α-TRAF2-ASK1-JNK1 pathway in AML-12 cells,reducing endoplasmic reticulum stress,attenuating hepatocyte apoptosis,and mitigating inflammatory responses.

Abstract:Drug-induced liver injury(DILI)is a core issue that leads to the interruption of drug development and clinical treatment risks,and its pathological mechanism is closely related to the imbalance of the oxidative stress system.This article first clarifies the generation and toxicity of reactive oxygen species(ROS)and the hierarchical regulatory mechanism of the antioxidant defense system.Further,it deeply explores the correlation between oxidative stress and DILI.Finally,it summarizes the regulatory mechanisms and intervention strategies for targeting the oxidative stress system to alleviate DILI.This review integrates the multi-dimensional correlations between the oxidative stress system and the pathological process of DILI,providing theoretical support for the prevention and treatment of DILI.

Abstract:Ferroptosis is an iron-dependent programmed cell death form driven by lipid peroxidation,plays a pivotal role in the pathogenesis of metabolic associated fatty liver disease(MAFLD).MAFLD is characterized by hepatic lipid metabolism disorder,with disease progression strongly associated with iron overload,lipid peroxidation,and oxidative stress—where the imbalance in ferroptosis regulation could additionally exacerbate hepatic injury and inflammatory respon-ses.Although there are no clinical drugs specifically targeting ferroptosis approved for market currently,natural compounds demonstrate significant potential in intervening ferroptosis to alleviate MAFLD due to their multi-target regulatory properties.This review focused on precisely regulating key ferroptosis pathways by natural compounds,integrating multiple experimental studies to propose innovative strategies for targeted MAFLD therapy.

Abstract:In recent years,RNA structural modification and delivery technologies have driven the vigorous development of RNA-based therapeutic drugs.RNA-based therapies have the ability to regulate gene expression,produce therapeutic pro-teins or antigens that trigger immune responses,and have shown great potential in combating infectious diseases,cancers,im-mune diseases,neurodegenerative diseases,and other conditions.However,the instability and negative charge of RNA seri-ously hinder its application.RNA has difficulty passing through the numerous barriers both inside and outside cells on its own.Therefore,an efficient delivery system is the key to RNA therapies.This review summarized the RNA drug delivery sys-tems that were currently widely studied,discussed the strategies for targeted delivery of RNA drugs,and prospects the future development of drug delivery systems in RNA drugs.

Abstract:Objective To establish a method for determination of the dissolution curves of Paliperidone Sustained-release Tablets.Methods The dissolution curve was investigated by paddle method.With the dissolution media of three different pH solutions and adding a sedimentation basket,the rotation speed was set at 50 r·min-1.Detection was carried out by HPLC.A C18 chromatographic column was used,with 30 mmol·L-1 tetrabutylammonium hydrogen sulfate solution-methanol(80∶20)as the mobile phase.The flow rate was 1.0 mL·min-1,the column temperature was 40 ℃,and the detection wavelength was 275 nm.Results The linear relationship of paliperidone in all mediums was good,and the average recoveries ranged from 98.0％to 102.0％.The RSD of accuracy,precision and stability tests were all less than 2％.The dissolution curve of the self-developed agent and the original agent was determined,and the cumulative dissolution amount of the sample was not less than 85％in 24 hours.Conclusion The method has good specificity and a good linear relationship within dissolution range.The precision and accuracy meet the requirements.It can be used for quality control and dissolution curve comparison in the development of Paliperidone Sustained-release Tablets.

Abstract:In the context of the national"Healthy China 2030"strategy,the development of innovative traditional Chi-nese medicines presents historic opportunities and challenges.Original breakthroughs,or"from 0 to 1"developments,are based on collaboration between top talent.Howe ver,talent training lags behind actual research and development needs,hin-dering the development of high-quality innovative Chinese medicines.For this reason,this paper is based on the characteris-tics of traditional Chinese medicine,focusing on the underlying logic of its development and the demand for clinical medi-cines.It puts forward the concept of cultivating top-notch talent through"inheriting the past and creating the present","re-searching and producing well",and"integrating production and research".It also elucidates the core conditions for realizing this cultivation model through the support platform,disciplinary faculty team and curriculum system.These core conditions are set out in three levels:the support platform matrix,the disciplinary faculty team,and the curriculum system.Integrating the multi-dimensional resources of scientific research institutions,hospitals,and enterprises and forming a closed-loop train-ing system by constructing a training mechanism involving the integration of medicine and science,the intersection of medi-cine and industry,multi-track synergy,three-dimensional linkage,rotation,and strengthening will lay the foundation for pro-moting the high-quality development of the R&D of innovative traditional Chinese medicine.

Abstract:Objective To explore the therapeutic effect and underlying mechanism of Abrus cantoniensis ethanol extract on ANIT-induced cholestasis mouse model based on pharmacodynamics,metabolomics and network pharmacology.Methods Twenty-four male C57BL/6J mice were randomly divided into three groups:normal group(Con),model group(Mod)and Abrus cantoniensis group(AC),the levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase acid(ALP),total bilirubin(TBIL)and total bile acid(TBA)in serum of mice were determined by automatic biochemical analyzer;The expression levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in the liver tissues of mice were detected by ELISA,Hematoxylin and eosin(HE)staining was used to observe the pathological sections of liver tissue in mice.Untargeted metabolomics was used to detect the differential metabolites in the liver of each group of mice,and network pharmacology was used to predict the potential targets and pathways of Abrus cantoniensis against cholestasis.Results Compared with Con group,the levels of serum AST,ALT,ALP,TBIL and TBA in Mod group were significantly increased(P＜0.05,0.01,0.001),and the levels of TNF-α and IL-6 in liver tissue were increased(P＜0.01);HE staining showed that the connective tissue of the liver was loose and a large area of inflammatory cells infiltrated,27 differential metabolites such as taurine,glutathione and taurocholic acid were screened out by liver metabolomics,it was mainly enriched in four metabolic pathways:Taurine and hypotaurine metabolism,primary bile acid biosynthesis,glutathione metabolism and purine metabolism;Network pharmacology predicted 21 active components of Abrus cantoniensis,including β-sitosterol,emodin,stigmasterol,abrine,etc.There were 119 intersecting targets between the active components of abrus cantoniensis and cholestasis,and 20 core targets were screened out by PPI network,it involves chemical carcinogenesis-receptor activation,bile secretion,chemical carcinogenesis-DNA adducts and other signaling pathways.Conclusion Abrus cantoniensis has obvious protective effect on cholestasis mice,which may be related to the regulation of bile acid metabolism and glutathione metabolism.

Abstract:Objective To provide international references for optimizing and improving the drug registration management system of China.Methods The drug registration management systems of China,the United States,Japan and the European Union,were summarized and analyzed systematically,including the regulatory authorities,law and regulations and registration procedures.Results The drug registration management system of China should be implemented in terms of law and regulations,review and approved process and efficiency,international coordination.Conclusion Global drug regulation is showing a trend of scientific,international and efficient development.It is suggested that China should build a more efficient and authoritative drug registration management by drawing on the international management experience.which can provide institutional support for safeguarding public health rights and high-quality development of the pharmaceutical industry.

Abstract:Objective To summarize the commonly used detection methods for in vitro drug release studies of nanomedicine delivery systems.Methods This review summarized the commonly used in vitro drug release testing methods for nanodrug delivery systems,and the underlying principles,experimental setups,and key advantages and disadvantages of each method are described and compared,with a focus on comparing their respective advantages,disadvantages,and applicability.Results The sample-and-separation method allows for direct measurement of drug release,with relatively simple equipment requirements,but it involves tedious sampling procedures and carries a risk of drug loss or leakage.The continuous flow method offers more convenient sampling and higher levels of automation and standardization,but the technique is relatively complex and costly.The dialysis membrane method is simple in both setup and sampling,yet it is limited by the potential barrier effect of the dialysis membrane on drug diffusion and may not be suitable for drugs that bind to the membrane.Emerging methods,such as real-time monitoring techniques,show promise but may be applicable only to certain types of drugs or formulations.Each method presents distinct strengths and weaknesses in terms of accuracy,reproducibility,practicality,and suitability for different nanopharmaceutical systems.Conclusion There is currently no one-size-fits-all in vitro drug release method for nanopharmaceuticals,and the choice of method should be carefully tailored based on the properties of the drug,the delivery system,and the intended application.Looking ahead,the development of in vitro drug release assays that better correlate with in vivo release behavior represents a crucial direction for future research.Establishing standardized protocols,improving method robustness,and integrating advanced technologies will enhance the reliability of in vitro testing and support the rational design,quality control,and clinical translation of nanopharmaceuticals.

Abstract:Objective To study the chemical constituents and anti-inflammatory activity of Acanthopanacis Cortex(root barks of Acanthopanax gracilistylus W.W.Smith).Methods Compounds were isolated by MCI column,Silica gel column,Sephadex LH-20 gel column,and high performance liquid chromatography from the 70％ethanol extract of Acanthopanacis Cortex.Using 1H-NMR,13C-NMR,MS and other spectroscopic techniques,the chemical structures of the isolated compounds was analyzed.The Griess method was used to test the anti-inflammatory activities of the isolated compounds in the mouse monocyte macrophage RAW264.7 cell release inflammatory factor model induced by lipopolysaccharide.Results 7 compounds were isolated from the ether extract of Acanthopanacis Cortex and identified as:falcarindiol(1),oplopandiol(2),3,4-dimethoxycinnamaldehyde(3),rosin(4),caffeic acid ethyl ester(5),2,3-di(3',4'-methylenedioxybenzyl)-2-butenoic acid-4-lactone(6),and threo-2,3-di(3',4'-methylenedioxybenzyl)-1,4-butanediol monoethyl ester(7).Conclusion Compounds 1～4,6～7 are obtained from this plant for the first time.The results of the anti-inflammatory activity showed that all of the compounds exhibited anti-inflammatory activities.

Abstract:Objective To analyze the specific situation of"athletes use with caution"in the instructions or outer packaging of Chinese patent medicine(CPM),to provide reference for the safe and rational use of CPM by athletes,and to provide suggestions for the management of CPM containing stimulants.Methods All the instructions or outer packaging of CPM in use in a hospital were collected and sorted out,the CPM containing doping ingredients were screened according to the"2024 Doping Catalogue",and the differences compared by Comparative analysis method in the labeling of"athletes use with caution".Results A total of 428 kinds of traditional Chinese patent medicines and simple preparations were collected,including 86 kinds of traditional Chinese patent medicines and simple preparations containing stimulant ingredients.Only 44 kinds of instructions or packages were marked with"athletes use with caution",and the remaining 42 kinds were not marked.Most of the stimulant ingredients contained in the unmarked varieties were higenamine.No labelling but no stimulant content is involved.Conclusion The labeling information or outer packaging of"athletes use with caution"should be further improved to avoid iatrogenic misuse.At the same time,it is suggested that the drug regulatory department,together with the General Administration of Sports and other departments,strengthen the management of CPM containing stimulants and further regulate the clinical use of CPM containing stimulants.

Abstract:Objective To explore the mechanisms by which Chidan Tuihuang Granules(CDTH)improve cholestatic liver injury and to reveal the biological mechanisms that regulate the progression of cholestasis.Methods Using α-naphthyl isothiocyanote(ANIT)-induced cholestasis model,the therapeutic effects of CDTH on cholestasis were evaluated.Network pharmacology and molecular docking techniques were used to identify potential core targets and pathways for CDTH in treating cholestasis.Results Animal experiments confirmed that CDTH significantly reduced liver function indicators and effectively improved liver tissue inflammation and steatosis.Network pharmacology analysis showed that CDTH treatment of cholestasis was significantly enriched in apoptosis signaling pathways.Molecular docking analysis confirmed that the active components of Chidan Tuihuang Granules have a stable binding ability with core targets(binding energy＜-5.0 kcal·mol-1).Conclusion CDTH can effectively improve serum biochemical indicators of ANIT-induced cholestasis,inhibit the expression of apoptosis signaling pathway protein in cholestatic of liver tissue,and thus exert a comprehensive therapeutic effect against cholestasis.