Abstract:Pharmaceutical excipients play a crucial role in the effectiveness of drugs,and the National Medical Products Administration's newly released"Good Manufacturing Practice for Drugs(Revised in 2010)"appendix on pharmaceutical ex-cipients has a significant impact on promoting the production quality of pharmaceutical excipients.To understand the new re-quirements for the production of pharmaceutical excipients in the new appendix,provide reference for the quality improvement of pharmaceutical excipient production enterprises,and promote the improvement of excipient quality management level.This article compared and analyzed the"Appendix to Medicinal Excipients"with the"Quality Management Standards for Medicinal Excipients Production"released in 2006,and refers to the current requirements of drug GMP to provide implementation sug-gestions for the new version of the"Appendix to Medicinal Excipients"for excipient production enterprises in China.

Abstract:Ointments and creams are semi-solid dosage forms designed for therapeutic efficacy through topical cutane-ous application.Based on the current status of global development and regulatory submissions for these dosage forms,this ar-ticle systematically explored their pharmaceutical research aspects,including formulation development,manufacturing processes and quality control strategies.Focusing on critical aspects such as excipient matrix selection,process parameter re-finement,and their impacts on product performance,we presented preliminary perspectives to highlight key challenges in de-veloping these formulations.Although the perspectives presented may not be exhaustive,this exploration aimed to provide ac-tionable references and insighted to advance research and development in this field.

Abstract:mRNA-LNP technology has become a revolutionary technique in the biomedical field,especially during the COVID-19 pandemic when SARS-CoV-2 mRNA vaccines were widely used and largely helped to mitigate disease burden globally.However,with continuous expansion of the clinical applications of mRNA-LNP technology,its safety issues have caused major concerns and urged management of potential toxicity risks.In this concise review,we summarized current stud-ies on the induction of undesired inflammation by mRNA-LNP drug formulations,and further discussed potential approaches that can be utilized to tackle this challenge.

Abstract:Objective To establish an LC-MS analytical method for the rapid determination of trace genotoxic impurityⅡ-10,2-(3,4-dimethylphenyl)-4-(hydroxyimino)-5-methyl-2,4-dihydro-3H-pyrazole-3-ketone in Eltrombopag Olamine.Methods Impurity Ⅱ-10 was separated by gradient elution at the chromatographic conditions below:column:Waters ACQUITY UPLC BEH C18(2.1 mm×50 mm,1.7 μm),mobile phase A:0.1％formic acid aqueous solution,mobile phase B:0.1％formic acid methanol solution,flow rate:0.3 mL·min-1,column temperature:20 ℃.Quantitative determination of impurity Ⅱ-10 was performed by multiple reaction monitoring(MRM).Results The analytical method was found to be of good specificity and shown good linear correlation between 7.8～117.8 ng·mL-1.The test demonstrated that the LOD and LOQ of impurity Ⅱ-10 were 2.4 ng·mL-1 and 7.8 ng·mL-1,respectively,and the recovery was 90％～104.1％(RSD:5.5％).Conclusion The method was simple and rapid,of good specificity and accuracy.

Abstract:Objective To develop a high-performance liquid chromatography(HPLC)method for fingerprint and sim-ultaneously determining the content of 11 components(chlorogenic acid,calycosin-7-O-β-D-glucoside,verbascoside,specnuezhenide,hyperoside,ononin,aloe-emodin,rhein,emodin,chrysophanol,and physcion)in Qizhi Yishen Capsules(QYC).Methods A Welch Ultimate® XB C18 column(4.6 mm × 250 mum,5 μm)was employed for separation,using a methanol/0.1％phosphoric acid gradient elution system at a flow rate of 1.0 mL·min-1.Detection was carried out at 248 nm,and the column was kept at 25 ℃.The Traditional Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System(Version 2012)was employed to automatically generate a reference fingerprint and determine the content of 11 com-mon components.Results The similarity of the fingerprints exceeded 0.9,and the resolution of all chromatographic peaks was greater than 1.0.A total of 20 common peaks were identified,with 11 peaks confirmed by comparison with reference standards.The linear relationships between peak area and injection amount for the 11 components were satisfactory(r＞0.990),with RSD≤2％and average recoveries exceeding 98％.Conclusion The established method demonstrates good re-producibility,high stability,and accuracy,and can serve as a reference for quality control of QYC.

Abstract:Extended-release pellets tablets have received widespread attention because of the advantages of fewer ad-ministration times,good patient compliance and higher drug bioavailability.Howe ver,the functional coating film is easily bro-ken after being pressurized,resulting in faster drug release rate,which limits the application of extended-release pellets tab-lets.Therefore,reducing the degree of coating film damage has become a technical difficulty in the development of extended-release pellets tablets.In this paper,we summarized the latest research progress of extended-release pellets tablets,and in-troduce the key factors affecting the integrity of the functional coating film.Meanwhile,we also summarized the latest methods to reduce the damage of the coating film of the extended-release pellets during compressing.This paper can be used as a reference for researchers to develop extended-release pellets tablets.

Abstract:Objective To investigate the effect of Qiwei Baizhu San on the mRNA of enteric neuron cell bodies in type 2 diabetes rat model based on high-throughput transcriptome sequencing.Methods The type 2 diabetes rat model was es-tablished by injection of Streptozocin(STZ)combined with high-fat and high-sugar diet,and the rats were divided into control group,model group and Qiwei Baizhu San treatment group.3 rats in each group were randomly selected for intestinal mRNA sequencing.Gene ontology(GO)enrichment analysis was performed on the model and control groups.Differentially expressed genes were identified based on the function of neuron cell bodies in the cellular component.The annotated 3 groups of differentially expressed genes were analyzed using IBM SPSS Statistics 25 software for principal component analysis(PCA)and clustering analysis,and Bi analysis was conducted on the loadings and scores of the principal compo-nent analysis.Results There were 13 differentially expressed genes in the function of neuron cell bodies between the model rats and the control rats.The Bi analysis of the loadings and scores of the principal component analysis of the differentially expressed genes showed a clear distinction between the model group and the control group,consistent with the Results of the sample clustering.After normalization of PC1,PC2,and PC3,it was found that the weights of the genes were different,and the top 10 genes by weight were Plxdc1,Sez6l,Adora1,Trpm5,Trpm2,Ncf1,Lrrk2,Cd40,Klhl14,and Cdk5r1.These genes were identified as key targets for the treatment of type 2 diabetes in rats by Qiwei Baizhu San via enteric neuron cell bodies.Conclusion Qiwei Baizhu San can ameliorate the damage of enteric neuron cell bodies induced by modeling stimulation,and maintain the normal function of enteric neuron cell bodies by up-regulating the mRNA expression levels of Plxdc1,Sez6l,Adora1,Trpm5,Trpm2,Ncf1,Lrrk2,Cd40,Klhl14,and Cdk5r1.It can regulate the balance of glucose metabolism to maintain the enteric homeostasis and effectively control the progression of type 2 diabetes mellitus.

Abstract:Objective To evaluate the current status of intravenous infusion in outpatient,emergency,and inpatient settings in Suzhou hospitals,providing evidence for standardized management.Methods Data from 26 hospitals in Suzhou(2023)were collected and analyzed,including infusion rates in outpatient/emergency departments,antimicrobial usage,and inpatient infusion practices.Results The outpatient and emergency infusion rates were 18.44％and 28.57％in primary hospitals,and 3.49％and 39.89％in secondary/tertiary hospitals,respectively.Respiratory diseases accounted for 80％(outpatient)and 60％(emergency)of the top infusion-related diagnoses.Antimicrobials were the most frequently used in-travenous drugs,followed by glucocorticoids,expectorants,and antivirals.The inpatient infusion rate was 55.11％(antimicro-bials 22.10％)in primary hospitals and 82.82％(antimicrobials 53.35％)in secondary/tertiary hospitals.Conclusion While outpatient/emergency infusion rates show room for reduction,inpatient infusion management requires strengthening,with a focus on antimicrobial stewardship and rational use of glucocorticoids and other high-frequency intravenous medica-tions.

Abstract:Magnolia officinalis is often used clinically to treat gastrointestinal and lung diseases.Magnolol and honokiol are the main active ingredients of Magnolia officinalis.In recent years,a large number of studies have shown that they have various pharmacological effects such as anti-inflammatory,antioxidant and anti-tumor.Inflammation is the comorbidity basis of multiple chronic diseases,indicating that it has the potential to treat multiple diseases,and its clinical application still has room for improvement.This article reviewed the research progress of magnolia officinalis and its main active ingredients mag-nolol and honokiol in the treatment of chronic diseases at home and abroad in the past five years.It is found that they can regulate immune disorders,inflammation and oxidative stress from multiple cellular pathways,thereby achieving anti-inflam-mation and anti-arthritis;In addition,magnolol and honokiol can also lowers blood sugar by stimulating the popular target of diabetes,peroxisome proliferator activated receptor gamma(PPARγ),and improves diabetic complications,cognitive im-pairment and lipid metabolism disorders.Even in insulin-resistant mouse models,they still have significant blood sugar low-ering effect.This article discussed in detail the role and advantages of magnolol and honokiol in the treatment of various chronic diseases,and provide basis for expanding the application of Magnolia officinalis and its active ingredients(magnolol and honokiol).

Abstract:This article systematically analyzed the requirements of the European Medicines Agency(EMA)for formu-lation similarity when applying for bioequivalence(BE)waivers for other specifications of multi-specification chemical compound pharmaceutical preparations,based on specifications that have already passed BE trials.The analysis was conduc-ted in accordance with Investigation of Bioequivalence-Scientific Guideline(Rev.1,2010)and clinical pharmacology and pharmacokinetics:questions and answers(Sections 6.4 and 6.5,2020-2021)issued by EMA.The findings aimed to provide scientific references for the development and registration of FDCs in domestic markets.

Abstract:Objective To explore the causal association between Parkinson's disease(PD)and intestinal microbiota(IF)through Mendelian randomization(MR),predict potential Chinese herbal medicines and components that treat PD by regulating IF,and analyzing its mechanism of action from the perspective of ferroptosis.Methods Two sample MR analysis was carried out based on genome-wide association study data from Mibiogen and IEU databases.g:Snpense and Coremine databases were used to locate single nucleotide polymorphism(SNP)neighboring genes and predict Chinese herbal medicine,and the classification of Chinese herbal medicine was standardized in combination with pharmacopoeia and textbooks.Single cell subpopulation expression analysis was performed on the predicted targets.Based on the GEO dataset,the expression differences of PD and ferroptosis genes were compared,and the hub genes were screened by weighted gene coexpression network analysis(WGCNA).The active ingredient targets of Chinese herbal medicine were collected from TCMSP and Herb databases,and DrugnomeAI was used to predict the druggability and perform molecular docking validation.Results MR analysis found that Candidatus Soleaferrea(OR,1.192;95％CI:1.041～1.366,P=0.011),Clostridium sensu strictol(OR,1.356;95％CI:1.089～1.690,P=0.007)are risk factors of PD.The primary therapeutic Chinese herbal medicines involved cooling and neutral properties,Sweet,bitter and pungent flavours,primarily targeting the heart,liver,and spleen meridians,and were mostly categorized as heat-clearing and detoxifying,Albizziajulibrissin,Forsythia suspensa and Smilax are highly correlated.Single cell analysis showed that there were differences in the expression of drug targets in cell subsets.Ferroptosis related gene FDFT1 is significantly expressed in PD.223 hub genes were screened by WGCNA,and 18 of them intersected with drug targets.11 targets such as CYP2A6 and MAP2K2 have good druggability.Molecular docking showed that bicuculline-TOP 1 binds best.Conclusion The association between IF and ferroptosis related gene expression provides a dual perspective for exploring new strategies for PD treatment,and provides a new idea for the innovation of PD treatment strategies.

Abstract:Objective To understand the current situation of quality management regarding post-market changes(changes in production sites)of drugs in Shandong Province,identify the common defect issues in the inspection of produc-tion site changes,explore the main risk points existing in the on-site inspection of post-market changes,and provide refer-ences for enterprises to implement post-market changes more standardized.Methods The requirements of laws and regula-tions for post-market changes(changes in production sites)of drugs were summarized,and conducted a statistical analysis of the inspection defects of production site changes of drug enterprises in Shandong Province in 2024.Results and Conclu-sion The inspection defects of post-market changes(changes in production sites)of drugs mainly concentrate on aspects such as document management,quality control and quality assurance,confirmation and verification,institutions and personnel.It is recommended that enterprises should pay special attention to the above-mentioned defects when implementing post-market changes(changes in production sites),continuously improve and enhance them to ensure the continuous and effective operation of the quality management system.

Abstract:Objective To explore alkaloids from the twigs and leaves of Alstonia macrophylla(Apocynaceae)for structurally unique natural products with drug lead potential.Methods The chemical constituents from the twigs and leaves of A.macrophylla were isolated and purified from by using silica gel,ODS,Sephadex LH-20 column chromatographies,pre-parative HPLC and TLC.The chemical structures were identified based on their physicochemical properties and spectral a-nalysis.Results Twelve alkaloids were isolated and elucidated as 6-oxomacrocarpine B(1),N1-methylburnamine(2),strictamine N4-oxide(3),norfluorocurarine(4),norfluorocurarine N4-oxide(5),N-oxyaffinisine(6),dihydrositsirikine(7),16,17-epoxyisositsirikine(8),pleiomaltinine(9),pleiomalicine(10),macrocarpamine N4′-oxide(11)and villal-stonidine N4′-oxide(12).Conclusion Compound 1 was a new monoterpenoid indole alkaloid,and compounds 2～11 were isolated from this plant A.macrophylla for the first time.

Abstract:Objective To establish a UPLC-MS/MS method for rapidly detecting the illegal addition of 4 steine expectorants(carbocysteine,fudosteine,mecysteine hydrochloride,erdosteine)in traditional Chinese medicine and healthy food.Methods The chromatography was separated on a Thermo Hypersil GOLD aQ C18 column(2.1 mm×100 mum,1.9μm)with 10 mmol·L-1 ammonium formate solution(containing 0.1％formic acid)-methanol as the mobile phase.Gradient elution was performed at column temperature of 45 ℃ and flow rate of 0.25 mL·min-1.Electrospray ion source(ESI)positive ion mode and multiple reaction monitoring(MRM)were used for mass spectrometry detection.Results The four chemical components showed good linear relationship in a certain range and obtained good separation.The average recovery of low,medium and high level illegal added concentrations was 89.5％to 109.2％,RSD was 0.29％to 3.51％,and the detected concentration was 0.45～3.27 ng·mL-1.Conclusion The method was accurate,rapid and specific,and can be applied to the detection of illegal addition of steine expectorants,and provides technical support for the daily supervision of market supervision departments.

Abstract:Cancer is a major threat to human health,with traditional treatments limited by immune evasion and drug re-sistance.Thus,developing new therapies is essential.Gallic acid(GA),a polyphenolic compound,inhibits tumor proliferation,induces apoptosis,regulates epigenetics,and modulates the tumor microenvironment,demonstrating significant potential in cancer therapy.Advances in nano delivery systems,organoid technology,and gut microbiota research further sup-port its clinical translation.This review summarized GA's anti-cancer mechanisms and recent progress,providing a foundation for its clinical development.

Abstract:Rhodiola crenulata,known as the"Ginseng of the Plateau",boasts a long history of folk and clinical applica-tions and is considered one of traditional Chinese medicines(TCMs)that are both medicinal and edible,possessing rich medicinal value and potential for application in various fields.Its chemical constituents primarily encompass flavonoids,vola-tile oils,phenols,phenylpropanoids,and others,conferring upon it a diverse range of pharmacological effects including anti-hypoxia,antioxidant,anti-aging,anti-tumor,prevention and treatment of cardiovascular and cerebrovascular diseases,as well as diabetes.This article summarized the research progress on the chemical constituents and pharmacological activities of Rhodiola crenulata,aiming to provide a reference for its further development and rational application.

Abstract:Objective To explore the clinical effect of negative pressure closed drainage(vacuum sealing drainage,VSD)combined with recombinant human epidermal growth factor(rhEGF)in the treatment of chronic refractory wounds and the influence of wound repair factors on patients.Methods The study selected 80 patients with chronic non-healing wounds admitted to the burn department of our hospital from March 2022 to September 2023.They were randomly divided in-to a control group and a combination therapy group,with 40 patients in each group.All patients received conventional surgi-cal treatment upon admission.The control group was treated with VSD on the basis of conventional treatment,while the com-bined treatment group was treated with VSD combined with rhEGF on the basis of conventional treatment.The clinical effica-cy of the two groups after 2 weeks of treatment was observed and compared.Observe and compare the clinical efficacy of the two groups after 2 weeks of treatment,the pain score of the numerical rating scale(NRS)before and after treatment,the lev-el of infection control,the positive bacterial culture of the wound surface,the level of wound repair factors,the complete healing time of the wound surface,the length of hospital stay and the hospitalization cost of the two groups,etc.Results The comparison showed that the total effective rate of treatment in the combination therapy group was significantly higher than that in the control group(P＜0.05).After 2 weeks of treatment,the NRS pain score,serum CRP,WBC and ESR levels of both groups were significantly decreased compared with those before treatment(P＜0.05),and the NRS pain score and ser-um CRP,WBC and ESR levels of the combined treatment group were lower than those of the control group after 2 weeks of treatment(P＜0.05).The results showed that after 2 weeks of treatment,the positive rate of wound bacteria in both groups was lower than before treatment(P＜0.05),and the rate of wound bacteria turning negative in the combined treatment group(87.50％)was higher than that in the control group(67.50％)(x2=4.588,P=0.032).After 2 weeks of treatment,the lev-els of wound repair factors PDGF,EGF,VEGF and bFGF in both groups were significantly increased compared with those before treatment(P＜0.05),the levels of PDGF,EGF,VEGF and bFGF in the combined treatment group were significantly higher than those in the control group after 2 weeks of treatment(P＜0.05).The comparison showed that the wound healing time and hospital stay in the combined treatment group were shorter than those in the control group(P＜0.05),and the hos-pitalization cost was less than that in the control group(P＜0.05).Conclusion The combination of VSD and rhEGF in the treatment of chronic non-healing wounds demonstrates significant efficacy,further improving the total effective rate of treat-ment,alleviating pain,enhancing infection control,promoting the expression of wound healing factors,accelerating healing,shortening hospital stay,and reducing costs.It is an efficient and economical treatment option.

Abstract:Objective To observe the anxiolytic effects of live mucin and inactivated bacteria on Akkermansia muci-niphila(Akk)in acute stress bondage,and to preliminarily explore the mechanism of action.Methods Thirty C57 male mice were randomly divided into a normal group(100 μL·d-1 normal saline per mouse by gavage),a live Akkermansia mu-ciniphila group(100 pL·d-1 live Akk per mouse by gavage),and a killed Akkermansia muciniphila group(100 μL·d-1 killed Akk per mouse by gavage).After continuous gavage for 30 days,the open field test(OFT),elevated plus maze(EPM)and light dark box(LDB)were used to detect the anxiolytic effects of live and killed Akk bacteria under baseline conditions and acute stress restraint conditions.Metagenomic 16S rDNA diversity sequencing was used to detect the coloniza-tion of live Akk bacteria and the influence of intestinal flora.Immunofluorescence experiments were used to detect the chan-ges in the activity of specific anxiety brain areas after gavage of live and killed Akk bacteria.Results Compared with the normal group,the duration and frequency of open-arm residence in the EPM model were significantly increased in the Akk inactivated bacteria gavage(P＜0.01),and the time and frequency of entering the open box in the LDB model were signifi-cantly increased(P＜0.05).The c-fos activation point of amygdala-related brain regions in mice,especially BLA,was sig-nificantly reduced(P＜0.05).Conclusion Akk-inactivated bacteria have anxiolytic effects in the state of acute stress bondage,which is related to the stability of the internal structure of the microbiota and the regulation of the activity of the a-mygdala-related regions of mice.

Abstract:Objective To establish a two reference substances for determination of multiple components method for 8 components in Lonicera japonica Formula Granules.Methods HPLC method was used,with chlorogenic acid and 3,5-O-dicaffeoylquinic acid as the reference substances for the determination.The position of each component's chromatographic peak was determined by linear calibration using two reference substances;The retention time of unknown components was predicted,and the method was validated.The relative correction factor of each component was calculated based on chlorogenic acid as the reference,and the components were quantified.Results The linear calibration using two reference substances can predict the retention time of unknown components on unknown chromatographic columns more accurately than the relative retention time method.The RSD of the relative correction factor method is less than 2％compared with the content determination by external standard method.Conclusion The two reference substances for determination of multiple component method for determining 8 components in Lonicera japonica Formula Granules is feasible and accurate.

Abstract:The lateral hypothalamic area(LHA)is a structurally and functionally heterogeneous central regulatory hub.Recent advancements in neurotechnological tools,particularly the application of optogenetic manipulation and trans-synaptic neural circuit tracing techniques,have enabled researchers to progressively decipher the key mechanisms of how the LHA regulates diverse physiological processes via cell type-specific neural circuits.Among its neuronal subpopulations,GABAergic neurons in the LHA serve as core inhibitory regulatory units,critically implicated in maintaining dynamic critically implicated in feeding,maintaining by namic equilibrium of energy metabolism,orchestrating circadian modulation of sleep-wake cycles,and integrating emotional-motivational behaviors.Dysfunction of GABAergic neuronal populations in the LHA has been confirmed as a critical contributor to the pathogenesis and progression of multiple disorders,including obesity,sleep disorders,depression,and drug addiction.This review synthesized cutting-edge discoveries in the field,providing an in-depth exploration of the functional architecture of LHA GABAergic neurons and their circuit-based mechanisms,while offering novel perspectives for mechanistic research and therapeutic target identification in related neuropsychiatric disorders.