Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

Objective To determine the acetylation level of nucleophosmin(NPM)in female breast cancer and to discuss its function through mutation of modified lysine sites.To construct positive and negative NPM mutants on its acetylated lysine sites and to express them in breast cancer cells.Methods Acetylation level and acetylated lysine sites of NPM in three breast cancer tissues and para-carcinoma tissues were detected by acetylome technology;NPM mutants were constructed by site-directed mutagenesis PCR,specific PCR products were digested by DpnI and transformed into Escherichia coli(E.coli)to obtain specific plasmids for mutants;The accuracy of mutants were verified by double restriction enzyme digestion and sequencing;The mutants were expressed in BT-549 cells by transient transfection and verified by RT-PCR method.Protein expression and acetylation level of NPM were validated by Western blotting;Function of NPM acetylation was analyzed by proteomic detection and bioinformatic analysis.Results The 27th and 32nd lysine of NPM were highly acetylated in breast cancer tissues,which were 2.76 and 2.22 times higher than those in adjacent normal tissues,respectively;The NPM mutants showed the same molecular weight as that of wild type NPM and contained expected mutation sites;Corresponding NPM mRNA levels of BT-549 cells transfected with NPM mutants were significantly increased.With the increase of wild type NPM expression level,NPM acetylation level increased,while decreased after 27th lysine underwent negative mutation.NPM acetylation can significantly change the expression levels of 101 proteins in BT-549 cells,which are enriched in regulation of cellular macromolecule biosynthesis,DNA-template transcription,RNA biosynthesis and RNA metabolism process.Conclusion NPM is highly acetylated in breast cancer and can play a key role in cellular macromolecule biosynthesis,DNA-templated transcription,RNA biosynthesis and RNA metabolism process.

Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)％,(6.28±0.20)％,(24.96±1.18)％,(12.36±0.49)％,(18.76±0.68)％and(4.59±0.26)％;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.

Objective To explore the effect of tilianin combined with aerobic training on cognitive function of rats with Alzheimer's disease(AD).Methods Rats were divided into 7 groups:blank group,model group,control group,low dose experimental group,medium dose experimental group,high dose experimental group and combination group,12 rats in each group.The rats in blank group were sham operated,and other groups were AD model rats established by bilateral hippocampal injection of amyloid-beta peptide 1-42(A(31-42).One week after modeling,the rats in control group and combination group were trained on the treadmill,and the rats in other groups were fed quietly.The rats in blank group,model group and control group were given 0.5％carboxymethyl cellulose sodium(CMC)2 mL.The rats in low,medium and high dose experimental groups were given intragastric administration of 5,10 and 20 mg·kg-1·d-1tilianin 2 mL.The rats in combined group were given 20 mg·kg-1·d-1 tilianin 2 mL by gavage.The drug was given for 6 weeks.Cognitive function was evaluated by Morris water maze test.The level of Beta-site APP cleaving enzyme protein 1(BACE1)mRNA in hippocampus was measured by quantitative reverse transcription polymerase chain reaction.The phosphorylation level of nuclear factor-κB(NF-κB)p65 in hippocampus was detected by Western blot.Results The escape latencies of blank group,model group,control group,low dose experimental group,medium dose experimental group,high dose experimental group and combination group were(20.16±2.06),(60.45±6.55),(46.52±2.90),(42.80±3.15),(41.19±2.54),(35.66±2.82)and(28.49±1.97)s;the relative expression of BACE1 mRNA were 1.00±0.06,7.88±0.49,6.02±0.38,4.96±0.57,3.01±0.21,1.98±0.17 and 1.48±0.11;the relative phosphorylation levels of NF-κB p65 were 0.11±0.03,1.46±0.11,0.89±0.10,0.71±0.06,0.37±0.05,0.29±0.02 and 0.15±0.01.Compared between model group and blank group,comparison between low,medium,high dose experimental group and model group,comparison between combination group and high dose experimental group all showed statistically significant differences(all P＜0.05).Conclusion Tilianin combined with aerobic training can improve the cognitive function of AD rats,and its mechanism may be related to the inhibition of inflammation mediated by NF-κB signal pathway.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

mRNA vaccines and drugs enter host cells through delivery vectors and produce target proteins using the protein synthesis mechanism of cells. mRNA and target proteins can induce the body to produce innate immunity and adaptive immunity, and the target protein itself can also play a corresponding role. Tumor cells are inhibited and cleared under the above immune effects and target proteins. This article reviews the immunogenicity of mRNA, that is, the specific mechanism of stimulating the body to produce an immune response.At the same time, the main types of cells transfected by mRNA vaccine were briefly introduced. (1) Muscle cells, epidermal cells, dendritic cells and macrophages at the injection site; (2) immune cells in peripheral lymphoid organs;(3) liver cells and spleen cells, etc. Although transfected with a variety of cells, it is mainly enriched in immune cells and liver cells because immune cells express toll-like receptors and liver cells express low-density lipoprotein receptors. mRNA vaccines and drugs are mainly divided into non-replicating mRNA (nrmRNA),self-amplifying RNA (saRNA), trans-amplifying RNA (taRNA) and circular RNA (circRNA).This article reviews how these 4 types of vaccines and drugs work, and compares their advantages and disadvantages. Due to its inherent immunogenicity, instability, and low delivery efficiency in vivo, mRNA vaccines and drugs have been unable to enter the clinic. This article describes in detail how to reformation and modify the 5'cap, 5'UTR, 3'UTR, ORF, 3'Poly(A) and some nucleotides of mRNA to eliminate its immunogenicity and instability. Due to the low efficiency of the delivery carrier, the researchers optimized it. This article briefly introduces the application of non-viral vectors and their targeting, specifically involving the mechanism of action of various types of delivery vectors and their advantages and disadvantages, and summarizes some of the current targeting vectors. Targeted carriers can improve the delivery efficiency of mRNA to specific tissues and prevent side effects of systemic exposure, such as liver injury. The specific methods of using mRNA vaccines and drugs to treat cancer are as follows: mRNA can be used to encode and transcribe tumor-associated antigens, tumor-specific antigens (TSAs), therapeutic antibodies, cytokines, tumor suppressors, oncolytic viruses, CRISPR-Cas9, CARs and TCRs, so as to play an anti-tumor role. In this paper, the specific mechanism of the above methods and the current research and development of corresponding mRNA vaccines and drugs are briefly reviewed. The successful development of the COVID-19 mRNA vaccine has brought mRNA technology to the attention of the world and brought new and effective means for the prevention and treatment of cancer. mRNA vaccines and drugs have the advantages of short development cycle, dual immune mechanism, safety, high efficiency and large-scale production. At the same time, there are also many areas that need further improvement, such as the development of ideal target TSAs, the in-depth development of saRNA, taRNA and circRNA, the development of targeted nano-delivery for different tissues and organs, the expansion of mRNA administration routes, and the development of mRNA that can be stably stored at room temperature or even high temperature. These problems need to be further studied and solved. In addition to cancer therapy, mRNA vaccines and drugs can also be used in the treatment of infectious diseases, genetic diseases, regenerative medicine and anti-aging. mRNA vaccines and drugs are a very promising platform, and we believe that they will benefit cancer patients in the near future.

Objective To evaluate the antioxidant function of Chrysanthemum morifolium from different origins and to identify their antioxidant material basis.Methods The HPLC fingerprints of the water extracts of C.morifolium from different origins were established.The antioxidant activities of C.morifolium were assayed by measuring the 2.2-diphenyl-l-picrylhydrazyl(DPPH),hydroxyl radical,ABTS,superoxide anion radical scavenging capacity and ferric ion reducing capacity FRAP.Entropy-weighted TOPSIS was used to calculate the weighting coefficients of the single indexes.Grey relational analysis(GRA)and partial least squares were used for spectrum-effect analysis to identify the antioxidant material basis of C.morifolium.Results A total of 16 common peaks were discovered in the fingerprint of the water extracts of 10 batches of C.morifolium,among which 13 common components were identified.All the C.morifolium samples had good antioxidant capacity,and the results of entropy-weighted TOPSIS analysis showed that the ranking of total antioxidant potency of 10 batches of C.morifolium was follows:S1＞S8＞S3＞S5＞S4＞S10＞S7＞S2＞S9＞S6.The peaks of 1-5,9,10,12,14 were positively correlated with the antioxidant activity and the variable influence on projection(VIP)values were greater than 1.The correlation coefficients of these nine peaks in GRA were all greater than 0.7.Conclusion The entropy-weighted TOPSIS method combined with the spectrum-effect analysis could be used to screen out the antioxidant material basis of C.morifolium and the results provide a basis for establishing quality assessment system for C.morifolium based on Quality-markers thus improving the quality control level.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Objective To explore the efficacy and safety of modified meibomian gland massage combined with ultrasonic atomization and drug therapy for dry eye in high-altitude military personnel.Methods A total of 180 patients(360 eyes)with dry eye who were diagnosed and treated by the medical team of General Hospital of Central Theater Command of Chinese PLA from July to October 2022 in Linzhi,Tibet(average altitude of 3100 meters)were selected as the research subjects.Patients were divided into four block groups based on the course of the disease:＜1 month,1-3 months,3-6 months,and≥6 months,and each block group was randomly assigned to control group,traditional group and modified group by random number table method,with 60 cases in each group.Control group received routine treatment(artificial tear drops and atomization fumigation);on the basis of routine treatment,traditional group underwent traditional meibomian gland massage,and modified group underwent modified meibomian gland massage.After 3 months of treatment,the scores of symptoms and signs,total effective rate,duration of treatment and incidence of adverse events were compared among the 3 groups.Results In the intra-group comparison before and after treatment,except for control group's symptom scores difference which was not statistically significant(P＞0.05),all other scores decreased significantly(P＜0.05).In the inter-group comparison after treatment,the scores of both traditional group and modified group were significantly better than those of control group(P＜0.05),but no significant difference was observed in symptom and sign scores between traditional and modified groups(P＞0.05).Compared with control group,the total effective rates of traditional group and modified group both significantly increased(P＜0.01),but there was no significant difference in total effective rate between traditional and modified groups(P＞0.05).The treatment time in modified group was significantly longer than that in control group(P＜0.05),but significantly shorter than that in traditional group(P＜0.05).The incidence of adverse events was significantly lower in modified group than that in traditional group(P＜0.001).Conclusion In high-altitude areas,modified meibomian gland massage combined with ultrasonic atomization and local drug therapy for dry eye is safe and effective,non-invasiveness and easy to perform,and suitable for promoting and application in military field training.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]