Abstract:Objective To screen potential quality markers(Q-Markers)of Xiaoxianxiong Decoction(XXXD)for treating prediabetes based on fingerprint,chemometrics and network pharmacology analysis.Methods Firstly,the differential markers of XXXD were analyzed by fingerprint and chemometrics.On this basis,the Q-Marker associated with XXXD in the treatment of prediabetes were screened out by using network pharmacology technology.Finally,a UHPLC method was established to determine the content of the predicted landmark components.Results The fingerprint of 15 batches was established and 24 common peaks were detected,from which 9 differential markers were selected by cluster analysis and OPLS-DA and confirmed by reference substance chromatography.Utilizing network pharmacology analysis,5 core active ingredients,including vanillic acid,rutin,luteoloside,jatrorrhizine,berberine were screened out.They can act on seven core targets including ESR1,BCL2,TP53,STAT3,EQFR,TNF,MTCR and affect four core pathways including insulin resistance,AGE-RAGE,proteoglycans in cancer,lipid and atherosclerosis.It was preliminarily predicted that vanillic acid,rutin,luteoloside,jatrorrhizine,berberine were potential Q-Markers of XXXD for treating prediabetes,with the content of 1.25～19.10,0.50～4.31,0.21～3.59,1.17～18.39,25.95～312.99 μg·mL-1,respectively.Conclusion Combining the fingerprint,chemometrics,network pharmacology and content determination,this study predicted the Q-Markers of XXXD.The results can provide reference for improving the comprehensive quality evaluation of XXXD.

Abstract:Eravacycline is a third-generation synthetic fluorocycline,has demonstrated potent antibacterial activity against a spectrum of carbapenem-resistant Gram-negative bacteria.In an effort to broaden the therapeutic options for multidrug-resistant bacterial infections and to mitigate the emergence of drug resistance,we have examined the research advancements pertaining to the combination therapy with eravacycline against carbapenem-resistant Gram-negative bacteria.This review systematically assessed the literature and provides a comprehensive summary of the in vitro and in vivo efficacy data for eravacycline-based combination therapies.The aim is to elucidate the mechanisms underlying these combinations and to offer a theoretical foundation for the development of evidence-based clinical treatment protocols.

Abstract:In the production and quality control of biological products,there are considerable variabilities and specific characteristics.Under the new regulatory framework for drug registration,on-site inspections serve as a crucial supervisory tool to facilitate the authenticity and traceability of data in biological products research and development(R&D),and to promote its industry standardization and high-quality development.Based on the characteristics of biological products and practical inspection experiences in recent years,this article summarized and analyzed the key focus points and common issues identified during the on-site inspections of the CMC(chemistry,manufacturing,and controls)research and development of biological products.The aim is to provide insights for biological products R&D and registration,as well as to offer reference for conducting related inspections.

Abstract:Objective To investigate the effects of trahydrocurcumin on immune function and antioxidant capacity in S180 tumor bearing mice.At the same time,preliminary exploration of the non-clinical safety characteristics of different formulation technologies.Methods The nude mice were divided into a normal control group,a tumor bearing model group,a cyclophosphamide group(CTX),and a tetrahydrocurcumin group(THC).After constructing the S180 tumor bearing model,the THC group was given 200 mg·kg-1 tetrahydrocurcumin suspension,the CTX group was given 20 mg·kg-1 cyclophosphamide,and the normal control group and tumor bearing group were given equal volumes of 5％CMC Na for 15 consecutive days.The tumor growth,immune response,and oxidative stress levels of each group were compared;Formulations were prepared using ordinary suspensions or solid dispersions,and preliminary non clinical safety studies were conducted in rats to compare the general toxicological characteristics of different formulations.Results The tumor volume and weight of the THC group were significantly lower than those of the tumor bearing model group(P＜0.05).The thymus and spleen indices of mice were significantly increased,and IL-2,TNF-α,and IFN-γ were significantly higher than those of the tumor bearing model group(P＜0.05).The proportion of CD4+T cells in animals was significantly increased,and the proportion of CD8+T cells was significantly decreased(P＜0.01),indicating that THC can significantly promote the infiltration and activation of T cells into the tumor microenvironment;The levels of serum SOD and GSH Px in the THC group were higher than those in the other groups,while the levels of MDA and LDH were significantly lower than those in the model group(P＜0.05).The expression levels of Nrf2 and HO-1 proteins in THC tumor tissue were significantly lower than those in the tumor bearing model group(P＜0.01).In the exploratory toxicity test of repeated 4-week administration in rats,it was observed that solid dispersion technology formulations have higher safety characteristics.Conclusion Tetrahydro curcumin has a dose-dependent inhibitory effect on tumor growth,and its anti-tumor mechanism may be related to enhancing the antioxidant capacity of tumor bearing mouse tissues,promoting T cell infiltration and activation into the tumor microenvironment.Compared with conventional suspension formulations,the formulation of tetrahydrocurcumin developed using solid dispersion technology has higher safety characteristics.

Abstract:Valproic acid and its salts(VP As)are first-line broad-spectrum antiepileptic drugs,which can be used in the treatment of a variety of neurological diseases.However,their clinical application is limited due to the severe liver injury they can induce.Traditional Chinese medicine(TCM),mainly from the plant kingdom,most of them are rich in polyphenolic compounds,which have significant antioxidant properties.In recent years,scientific literature has shown that a variety of TCM and their active ingredients can alleviate liver damage caused by VP As,which has attracted extensive attention from scholars at home and abroad.In this paper,the protective effects of single herbs,compound herbs and active ingredients on the induction of liver injury by VP As and underling mechanisms were reviewed.It provides a basis for the clinical application of VPAs and the development of drugs for the treatment of liver injury.

Abstract:This paper reviewed the technological advancements in hydrogel matrix tablets over the past two decades,focusing on research hotspots and recent breakthroughs in drug release mechanisms,material innovations,and process optimization.In terms of release mechanisms,it elaborates on the evolution from traditional models to multi-factor coupled models,as well as the dynamic analysis of the release process through advanced characterization techniques.Regarding material systems,it not only covers classical materials but also provides an in-depth discussion of the latest developments in natural gums,stimuli-responsive smart materials,nanocomposite gels,and biodegradable materials.The production process section focuses on 3D printing,continuous manufacturing,and process analytical technologies.

Abstract:To respond the demand of the healthy China strategy for the transformation from"disease treatment"to"health management",and to address the three core issues in the current training of clinical pharmacists,namely weak public health literacy,lagging technical application and insufficient practical ability.This paper proposes an innovative training mode of"three integrations of medicine-pharmacy-public health".By reconstructing the"multidisciplinary interdisciplinary curriculum system",developing the"double-qualified and three-capable"teaching staff,and establishing the"three-level practice bases",it aims to cultivate high-quality clinical pharmacists with clinical thinking,group health management ability and technical innovation application.This approach will achieve a deep integration of clinical pharmacy education with public health and provide a practical paradigm for cultivating compound clinical pharmacists who"understand medicine,master pharmacy,be good at in prevention and management".

Abstract:Objective Based on transcriptomics technology,this study explores the gene expression and molecular mechanism of the Tibetan medicine Ershiwu Wei Guijiu Pill in rats with postmenopausal osteoporosis(PMOP).Methods Thirty-six 3-month-old Sprague-Dawley(SD)female rats were randomly assigned to Sham,model(OVX),and Tibetan medicine Ershiwu Wei Guijiu Pill treatment group(GJW).After 12 weeks of intervention,the femurs were harvested for RNA sequencing(RNA-Seq).The sequencing data were analyzed using Gene Ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Real-time quantitative PCR(RT-qPCR)and Western blotting were employed to validate the transcriptomic results.Results A total of 190 differentially expressed genes(DEGs)were identified,with 153 genes upregulated and 690 genes downregulated in the GJW group.GO analysis demonstrated that the differentially expressed genes were mainly involved in biological processes such as myofibril formation,B-cell receptor signaling pathway,and mitochondrial translation,were localized in cellular components like immunoglobulin complexes and mitochondrial protein complexes,and exerted molecular functions like immunoglobulin receptor binding.KEGG pathway analysis identified significant enrichment in pathways related to calcium signaling,focal adhesion,ECM-receptor interactions,and MAPK signaling.RT-qPCR results confirmed the downregulation of three specific DEGs in the GJW group,and Western blot results corroborated these findings.Conclusion Transcriptomic analysis indicated that the Ershiwu Wei Guijiu Pill regulates genes and signaling pathways associated with muscle contraction and calcium transport,potentially improving skeletal structure and metabolism in PMOP rats.These findings suggest potential biomarkers for the clinical diagnosis of PMOP.

Abstract:Pertussis,an acute respiratory infectious disease caused by Bordetella pertussis,has re-emerged in recent years,exposing critical public health challenges in vaccination and treatment strategies.This review comprehensively summarized the epidemiology,pathogenesis,intervention strategies,and vaccine development.We evaluated the advantages and limitations of licensed vaccines(whole-cell and acellular pertussis vaccines)and analyzed novel vaccine candidates under development(genetically attenuated vaccines,outer membrane vesicle vaccines,mRNA vaccines,etc.).Furthermore,we compared two different immunization strategies,maternal vaccination and the cocooning strategy,and analyzed the impact of vaccine pressure on bacterial mutation dynamics,disease resurgence,and herd immunity.Finally,we proposed recommendations for improved control of pertussis.

Abstract:Objective To investigate the immunomodulatory effect of Shenbai Nanosuspension on cyclophosphamide-induced immunosuppressed mice,reveal the mechanism of action based on cytokines and protein levels.Methods SPF-grade female BALB/c mice were randomly divided into six groups,including normal group,model group,low,medium,and high dose groups of Shenbai Nanosuspension and positive control group(levamisole hydrochloride,30 mg·kg-1).In addition to the control group,other groups of mice were injected with cyclophosphamide to prepare an immunocompromised model.Except for the control group,the other groups were intervened by for 30 days.Body weight and the general state of mice were measured;The immune organ index was examined.Cytokines of tumor necrosis factor-α(TNF-α),interleukin-2(IL-2),and interferon-γ(IFN-γ)were determined by enzyme-linked immunosorbent assay(ELISA);Hematoxylin-eosin(HE)staining was used to observe the histopathologic changes in a spleen;qRT-PCR was used to detect expression levels of NF-κB p65 and IκBα mRNA in spleen.The expression levels of NF-κB p65 and IκBα protein in spleen were detected by western blotting.Results Compared with the model group,there were significant differences among the dose groups in the ConA induced splenic lymphocyte transformation test(P＜0.05).There was a significant difference in the high and medium dose group of the serum hemolysin level and natural killer cell(NK)activity(P＜0.05).There was a significant difference in the medium dose group of the delayed type hypersensitivity(DTH)(P＜0.05).There was no significant difference in carbon clearance,antibodies-generated cells assay and phagocytosis of chicken red blood cells(P＞0.05).but the detection results of each dose group higher than those of the model group.Compared with the model group,the levels of white blood cells,lymphocytes,and cytokines(IL-2 and IFN-γ)were significantly increased in each dose group of the sample(P＜0.05);The cytokines(TNF-α)were significantly higher in the middle and high dose groups(P＜0.05).Meanwhile the low dose group had a higher count than the model group.Expression levels of NF-κB p65 mRNA and proteins(TLR-4,IKKα,NF-κB p50,NF-κB p65)were significantly increased(P＜0.05);The expression levels of IKBα mRNA and protein were reduced(P＜0.05).Conclusion Shenbai Nanosuspension regulates the immune function by modulating key signaling factors of the cytokines IL-2,IFN-γ,TNF-α and the protein NF-κB signaling pathway.It can improve the immune function of immunocompromised mice.Those lay a solid foundation for the research and development of health food to improve immune function.

Abstract:Objective To establish a quantitative nuclear magnetic resonance(qNMR)method for the determination of Cimetidine Injection.Methods Proton nuclear magnetic resonance(1H-NMR)spectra were acquired using a Bruker AVANCE Ⅲ HD 600 MHz spectrometer.The experimental parameters were set as follows:pulse sequence was zgpr,tempera-ture was maintained at 25 ℃,relaxation delay(D1)was 20 s,acquisition time(AQ)was 2 s,transmitter frequency offset(O1P)was 4.700 ppm and the number of scans(NS)was 32.Results Quantitative analysis was conducted using the characteristic signal of cimetidine(δ 8.4)with maleic acid(δ 6.3)as the internal references.The method showed a linear range for cimetidine in the concentration range of 50.42～201.7 mg·mL-1(r=0.999 5,n=6).The precision of the method,expressed as relative standard deviation(RSD),was 0.43％(n=6),and the RSD of repeatability was 0.47％(n=6).The average recovery was 100.4％(RSD=1.04％,n=9).Conclusion The developed qNMR method is accurate,rapid and ef-ficient for the determination of cimetidine in injection.It eliminates the requirement for self-control standards,providing a reliable alternative for quality control in pharmaceutical analysis and expanding the application of qNMR technology.

Abstract:Objective To investigate the effects of the aqueous extract of Ephedra saxatilis Royle ex Florin on anti-ag-ing and antioxidant activity on Caenorhabditis elegans.Methods Wildtype N2 nematodes were chosen and exposed to aque-ous extract of Ephedra saxatilis for treatment groups with 100,300,and 500 μg·mL-1 and comparative to normal control group.A systematic evaluation of anti-aging effects were conducted through lifespan assays,pharyngeal pumping frequency tests,egg-laying quantification,locomotion ability assessments,lipofuscin fluorescence intensity analysis,and Determination of malondialdehyde(MDA)content,reduced glutathione(GSH)content,and the activities of antioxidant enzymes[super-Ooxide dismutase(SOD),and catalase(CAT)].Results Compared to the normal control group,all different concentration of aqueous Extract of Ephedra saxatilis significantly extended nematode lifespan(P＜0.05)and reduced lipofuscin accumu-lation(P＜0.01).CAT activity(P＜0.01)and GSH content(P＜0.05)increased in a dose-dependent manner,while MDA levels significantly decreased in high concen-tration(300 and 500 μg·mL-1)groups(P＜0.01).Conversely,SOD activity was significantly inhibited at higher concentrations(P＜0.01).Additionally,the E.saxatilis extraction showed no significant changes of pharyngeal pumping frequency,egg-laying capacity,or body length/width of C.elegans(P＞0.05).Conclusion The aqueous extract of E.saxatilis may effectively delay the aging process of C.elegans by activating CAT and GSH antioxi-dant pathways,inhibiting lipid peroxidation(MDA),and reducing lipofuscin accumulation.However,its bidirectional regula-tion on SOD requires further study.

Abstract:Objective To study the effects of Aloin Gel Plaster on intestinal flora,motilin(MTL),vasoactive intestinal peptide(VIP),and substance P(SP)in constipation model rats.Methods Thirty SD rats were randomly assigned to a blank group,an oral group,a positive drug control group,a model group,and a gel plaster group(n=6),with a constipation model induced by loperamide at a dosage of 6 mg·(kg·d)-1.Two weeks after modeling,the blank group and the model group were administered with the plaster base applied to the umbilical region of the rats,covering an area of 3 × 3 cm.The oral group re-ceived a gavage of 2 mL of aloin aqueous solution(3 mg·mL-1)three times daily.The gel plaster group was administered with a self-made aloin gel plaster,while the positive drug control group was administered with Mitong Plaster,both with an applica-tion interval of once a day.After two weeks of administration,the levels of MTL,VIP,and SP in the serum were detected using the ELISA method.Additionally,PCR amplification was performed on rat feces,and the intestinal flora structure was analyzed through 16S rRNA sequencing technology.Results Compared to the blank control group,the model group exhibited signifi-cantly decreased serum levels of MTL and SP and increased VIP(P＜0.01).In contrast,the gel group,oral group,and positive control group showed elevated MTL and SP levels and reduced VIP levels compared to the model group(P＜0.01).Alpha di-versity analysis results showed that the Chao1 index,Observed species index,Shannon index,and Simpson index in the model group all showed a decreasing trend compared to the blank group(P＜0.01),while the gel group,oral group,and positive drug control group all showed an increasing trend compared to the model group(P＜0.01).The non-metric multidimensional scaling(NMDS)analysis of β diversity indicates that the fitted model is acceptable.At the phylum level,the analysis of gut microbiota shows that the gel group influenced the gut microbiota by increasing the abundance of Firmicutes and decreasing the abundance of Bacteroidetes,and the gel group improved the abundance of Firmicutes and reduced the abundance of Bacte-roidetes more effectively than the oral group,with effects similar to those of the positive control drug group.At the class level,the relative abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium in all dosing groups was higher than in the model group.Additionally,all dosing groups exhibited inhibitory effects on Enterobacteriaceae.Among them,the oral group had a poorer inhibitory effect,while the gel group showed significant inhibitory effects.Conclusion The aloin gel plaster can improve the constipation symptoms by increasing the levels of SP and MTL,reducing the level of VIP,and increasing the rela-tive abundance of Firmicutes,Lactobacillales,and Bifidobacteriales,as well as decreasing the relative abundance of Bacte-roidetes and Enterobacteriales,to regulate the intestinal microecology.

Abstract:Perampanel Tablets are the first highly selective noncompetitive AMPA receptor antagonist approved by the FDA,with clear efficacy and good tolerability in the treatment of epilepsy.In recent years,it has gradually become a first-line clinical drug,and its domestic generic drug application has become a hot topic.This article summarized the approved market situation at home and abroad through research on relevant literature,and discusses the main focus of pharmaceutical research and requirement for additional strength biowaiver on this variety,aiming to provide some reference for product de-velopment.

Abstract:Objective To conduct a metrological analysis of the Chinese and English literature on Ziziphi Spinosae Se-men to investigate the current status and development trend of its research.Methods Literature involving Ziziphi Spinosae Semen in China Knowledge Network(CNKI)and Web of Science(WOS)core ensemble databases from 2000 to 2024 was collected.Microsoft Excel,CiteSpace and VOSviewer were used to visualize and analyze the trend of publication,citation fre-quency,authors,countries,institutions and keywords of the Chinese and English literature related to Ziziphi Spinosae Semen,respectively.Results A total of 1 284 studies were included,of which 1 096 were in Chinese and 188 were in English.The number of publications on Ziziphi Spinosae Semen showed an overall increasing trend,and the top 5 cited Chinese and Eng-lish literature were all focused on the study of the chemical constituents and pharmacological effects of Ziziphi Spinosae Se-men.The authors with the most publications in Chinese and English are Chenhui Du and Junbo Xie.The country with the highest number of articles is China.Beijing University of Traditional Chinese Medicine and Shenyang Pharmaceutical Univer-sity were the institutions with the most publications in Chinese and English,respectively.The keyword analysis in Chinese and English showed that the research hotspots were mainly about the chemical composition,pharmacological effects,clinical applications,analytical techniques and bioinformatics of Ziziphi Spinosae Semen.Conclusion The study of antidepressant,anxiolytic and memory-improving mechanisms of action of Ziziphi Spinosae Semen and its active ingredients is the focus of current and future research.

Abstract:The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway plays a pivotal role in the body's recognition of cytosolic DNA,triggering innate immune responses.By detecting aberrant DNA,cGAS synthesizes cGAMP,which activates STING and subsequently induces the expression of type Ⅰ interferon(IFN-Ⅰ)and pro-inflammatory cytokines,thus contributing to antiviral,antibacterial,and antitumor immunity.However,dysregulation of this pathway can lead to chronic inflammation and autoimmune diseases.This review explores the composition and biological functions of the cGAS-STING pathway,including the structure and function of cGAS,the signaling mechanisms of STING,and the activation process upon the binding of cGAMP to STING.We examine the dual roles of this pathway in inflammatory responses and analyze its complex involvement in autoimmune diseases,inflammatory conditions,infectious diseases,and cancer immunity.Furthermore,the review highlights the multi-layered regulatory mechanisms of the cGAS-STING pathway,encompassing transcriptional regulation,post-translational modifications,and modulation of organelle microenvironments.Po-tential therapeutic approaches targeting this pathway,including cGAS antagonists and STING inhibitors,are also discussed.Finally,we outline future research directions,emphasizing the refinement of regulatory mechanisms,the functional expansion of STING,its interaction with the immune microenvironment,and the optimization of targeted therapeutic strategies.A deeper understanding of the regulatory mechanisms governing the cGAS-STING pathway and its role in disease is poised to offer novel insights and therapeutic targets for the precision treatment of related diseases.

Abstract:Osteoarthritis(OA)is a chronic degenerative bone disease,mainly manifested by joint pain and swelling that,seriously affect the quality of life.At present,the clinical medication options are limited.The first-line drugs are non-steroidal anti-inflammatory drugs(NSAIDs)and cortisol-based drugs,but they can only provide short-term relief effects and cannot change the progression of the disease.Engineered RNA-based therapies developed using synthetic chemistry and biological tools offer hope for future osteoarthritis treatments.These therapies have long-lasting and effective mechanisms of action and can specifically target the underlying drivers of pathology.In this brief review,we focus on emerging RNA-based technologies with therapeutic potential for OA,including siRNA for gene silencing,microRNA for polygenic regulation,and mRNA for gene supplementation.In conclusion,the purpose of this article is to reveal that RNA-related technologies can provide new treatment methods for osteoarthritis.

Abstract:Under the global pharmaceutical innovation transformation and the Healthy China Strategy,and in response to prominent issues such as outdated educational concepts and insufficient collaborative education in pharmaceutical practical teaching,we have constructed a"Six-Dimensional Integrated"practical teaching system for cultivating innovative pharmaceutical talents with distinctive West China characteristics.By implementing a"Four-Stage Progressive"hierarchical training model,establishing diversified practical platforms,creating distinctive curriculum clusters,deepening mechanisms for medical-education collaboration,innovating pathways for industry-education integration,and expanding international training—these six reform dimensions—the system forms a vertically integrated competency cultivation chain spanning"foundational-professional-comprehensive-innovative-applied"training,and a horizontally integrated educational framework converging the multi-dimensional collaborative education fields of"medicine-education-research-industry".This provides a replicable reform paradigm for cultivating top-notch innovative pharmaceutical talents in the new era,and its multi-di-mensional collaborative education mechanism holds significant reference value for the innovative development of medical ed-ucation.

Abstract:Objective To investigate the hypoglycemic activity and safety evaluation of pine pollen enzymatic hydroly-sate.Methods The hypoglycemic activity of pine pollen enzymatic hydrolysate was examined by α-glucosidase inhibition assay and HepG2 cell insulin resistance model;The genotoxicity of pine pollen enzymatic hydrolysate was evaluated by mam-malian erythrocyte micronucleus,mouse spermatocyte chromosomal aberration,and bacterial reverse mutation tests.Results The half-maximal inhibitory concentration(IC50)of pine pollen enzymatic hydrolysate on α-glucosidase was 0.44 mg·mL-1,lower than the IC50 value of 0.79 mg·mL-1 for the positive control acarbose;Additionally,pine pollen enzymatic hydrolysate at concentrations of 50 and 100 μg·mL-1 significantly increased the glucose uptake of insulin-resistant HepG2 cells.The test substance at the highest dose of 5 g·kg-1 did not cause an increase in the erythrocyte micronucleus rate of ICR mice,and did not cause an increase in the chromosomal aberration rate of mouse spermatocytes.Bacterial reverse mutation tests were conducted using histidine auxotrophic Salmonella typhimurium strains TA97a,TA98,TA100,TA102 and TA1535;The test results were negative at the highest dose of 5 mg/plate,both with and without S9.Conclusion The enzy-matic hydrolysate of pine pollen has significant hypoglycemic activity,and it has no potential mutagenic effects or genotoxicity.

Abstract:Thiophene,a kind of aromatic five-membered sulfur heterocycle,has wide range of pharmacological activities.Drugs synthesized by thiophene backbone,or designed and developed by introducing or replacing thiophene moiety in the existing drugs,often exhibit anticancer activities.Thiophene derivatives demonstrate favorable antiproliferative activity and selectivity against various lung cancer cells,including A549 and NCI-H460,and have emerged in the research and de-velopment of targeted anti-lung cancer drugs as excellent inhibitors of the epidermal growth factor receptor(EGFR)and the signaling factor NF-κB.This review systematically illustrates the synthetic methods and the progress on anti-lung cancer of thiophene derivatives,providing a theoretical basis for further development of anti-lung cancer drugs.