OBJECTIVE To explore and establish a full-cycle management model for drug traceability codes that aligns with national policy requirements and the practical needs of healthcare institutions， thereby enhancing the refinement of drug management and the level of medication safety. METHODS A tripartite strategy integrating “hardware deployment， system transformation， and process re-engineering” was adopted. This involved the introduction of intelligent identification devices （personal digital assistant， high-definition industrial reader）， the modification of the hospital information system interface， and the re-engineering of workflows （drug warehousing， dispensing and distribution， drug withdrawal， uploading to the insurance platform） to achieve comprehensive， informatized collection and association of drug traceability codes throughout all stages. RESULTS A full-cycle management model for drug traceability codes was successfully established， realizing the goals of making drugs “traceable to their source， trackable in their distribution， and accountable in their responsibility”. The patient waiting time for medication dispensing before and after the implementation was [3.08（1.67，5.58）] min and [3.28（1.77，5.98）] min， respectively. Among them， the patient waiting time under the pre-preparation mode was [3.60（2.13，6.35）] min and [3.50（2.03，6.30）] min， respectively； the patient waiting time under the real-time mode was [2.05（0.83，4.03）] min and [2.78（1.18，5.38）] min， respectively； the number of dispensing errors was 3， 0， respectively； the staffing of relevant positions had not been increased. CONCLUSIONS The drug traceability code management model constructed from a full-cycle perspective effectively meets national policy requirements. It provides data support for refined hospital management and offers solid technical and procedural safeguards for ensuring patient medication safety and strengthening medical insurance fund supervision， demonstrating practical value.

ObjectiveDonkey hide is the sole legally designated raw material for the preparation of the traditional Chinese medicine Ejiao. The quality stability of donkey hide during preservation directly determines the efficacy and safety of Ejiao. This study focuses on the dynamic succession of microbial communities during the preservation of donkey hides from different origins, aiming to clarify the correlation between microbial biodiversity difference and the degradation profiles of hide collagen and critical biochemical components, thereby providing a theoretical foundation for developing targeted preservation strategies based on microbial regulation. MethodsDonkey hides originating from four different regions were subjected to an accelerated microbial aging assay to simulate the spoilage process. The microbial community succession was analyzed using high-throughput sequencing. Microstructure changes and pore structure characteristics were assessed by scanning electron microscopy and mercury intrusion porosimetry, respectively. Additionally, the content of major components, including lipids, proteins, and sugars were determined by biochemical methods. ResultsAfter 96 h of aging, the collagen fiber structure in Africa donkey hides (ADH) exhibited significant degradation and collapse, followed by Xinjiang donkey hides (XDH). Instead, the microstructure of Dong’e black donkey hides (DDH) and Peru donkey hides (PDH) remained relatively intact. The porosities of DDH, XDH, PDH, and ADH increased from 27.9%, 15.7%, 30.3%, and 46.2% to 36.5%, 52.6%, 42.8%, and 57.7%, respectively, during the aging process, which suggested that the originally compact fiber structure was disrupted by microbial aging. Fourier transform infrared spectrometer analysis revealed the amide bands in XDH exhibited relatively weak intensity, and no collagen amide I band was observed in ADH. Meanwhile, the lipid and protein contents decreased in all four types of donkey hides, indicating that these components served as the primary nutrient sources for the growth of microorganism. Notably, the most severe collagen degradation was observed in XDH and ADH. A substantial increase was detected in the total soluble sugar in PDH aging solution and hydroxyproline in the ADH aging solution, respectively. These results indicated that donkey hides exhibit distinct patterns of structural degradation and nutrient utilization. Furthermore, the viable cells number of donkey hides increased sharply after 48 h of aging. Metagenomic analysis revealed that the relative abundance of Euryarchaeota in ADH, PDH and XDH declining from initial 93.19%, 97.73% and 30.08% to 0.79%, 1.43% and 0.02% after 96 h, respectively. Conversely, a significantly increase was observed in the abundance of Bacillota, with a marked increase in ADH, peaking at 92.75%. Additionally, the abundance of Pseudomonadota in PDH increased from 0.10% to 87.84%, suggesting that Bacillota and Pseudomonadota may be key factors exacerbating donkey hide spoilage. Unlike the other three types of donkey hides, the dominant bacterial phylum in DDH shifted from Pseudomonadota to Bacteroidota, characterized by a substantial abundance increase of Bacteroidota from 0.13% to 44.22%. ConclusionRegional variation in origin significantly influence the microbial aging of donkey hides, leading to distinct patterns of structural deterioration and differential nutrient utilization. Therefore, implementing origin-specific preservation strategies, through the precisely controlling environmental factors to suppress harmful phyla such as Bacillota and Pseudomonadota, is crucial for enhancing the storage quality of donkey hides.

Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.

Objective:To screen out the disinfection procedure and disinfectant suitable for the actual production of specific pathogen free(SPF)chicken embryo eggs,so as to ensure the disinfection effect of specific pathogen free(SPF)chicken embryo eggs in vaccine production.Methods:This study compares the microbial counting methods of soaking,swabbing with cotton swabs and pouring after thin-film filtration for SPF chicken embryo eggs in a GMP production workshop,and selects the most suitable method for SPF chicken embryo egg microbial counting.Experi-mental groups A,B,and C use self-prepared concentrations of 1∶50 sporicidal agent dilution solution,1∶128 alka-line phenol salt dilution solution,and ready-to-use compound quaternary ammonium disinfectant(sterile),respec-tively,and follow the actual disinfection procedures in the workshop to disinfect and sample the surfaces of SPF chicken embryo eggs entering different cleanliness grades,while using sterile water instead of disinfectant as the control group.The average bactericidal rate is calculated by recording the number of colonies and monitoring the viability of chicken embryo cells using microbial culture,and the disinfection effect of the three disinfectants on SPF chicken embryo eggs is evaluated.Results:The comparison of the results from the three methods shows that the method of sampling SPF chicken embryo eggs by immersion and then counting the microbial colonies through membrane filtration is superior to the other two methods.The final cleaning rate of the control group,which used sterilized injection water to clean the SPF chicken embryo eggs,was 91.67％to 96.97％,while the final steriliza-tion rate of the experimental group,which used the above three disinfectants to disinfect the SPF chicken embryo eggs,was 100.00％.By comparing the cell counts of the experimental group and the control group,it was found that the live cell density of the control group was(6.03-6.25)× 105 cells·mL-1,and that of the experimental groups A-C was(6.08-6.17)× 105 cells·mL-1,(5.99-6.25)× 105 cells·mL-1,and(5.87-6.21)× 105 cells·mL-1 respectively;the cell viability of the control group was 90.33％to 91.35％,and that of the experi-mental groups A-C was 88.25％to 92.12％,89.45％to 93.59％,and 88.02％to 92.89％respectively.Through statistical analysis,it was found that the P values of all experimental groups compared with the control group were greater than 0.05,indicating no statistically significant difference.Conclusion:By comparing the dis-infection effects,cell density and cell viability of the three disinfectants and comprehensively considering factors such as cost and risk of the three disinfectants,1∶50 sporicide dilution,1∶128 alkaline phenolate dilution and ready-to-use compound quaternary ammonium salt disinfectant(sterile)can all be used for the daily surface disin-fection of SPF chicken embryo eggs in the production workshop.The selection of an appropriate disinfectant should be based on specific application scenarios and requirements.

Objective:To screen out the disinfection procedure and disinfectant suitable for the actual production of specific pathogen free(SPF)chicken embryo eggs,so as to ensure the disinfection effect of specific pathogen free(SPF)chicken embryo eggs in vaccine production.Methods:This study compares the microbial counting methods of soaking,swabbing with cotton swabs and pouring after thin-film filtration for SPF chicken embryo eggs in a GMP production workshop,and selects the most suitable method for SPF chicken embryo egg microbial counting.Experi-mental groups A,B,and C use self-prepared concentrations of 1∶50 sporicidal agent dilution solution,1∶128 alka-line phenol salt dilution solution,and ready-to-use compound quaternary ammonium disinfectant(sterile),respec-tively,and follow the actual disinfection procedures in the workshop to disinfect and sample the surfaces of SPF chicken embryo eggs entering different cleanliness grades,while using sterile water instead of disinfectant as the control group.The average bactericidal rate is calculated by recording the number of colonies and monitoring the viability of chicken embryo cells using microbial culture,and the disinfection effect of the three disinfectants on SPF chicken embryo eggs is evaluated.Results:The comparison of the results from the three methods shows that the method of sampling SPF chicken embryo eggs by immersion and then counting the microbial colonies through membrane filtration is superior to the other two methods.The final cleaning rate of the control group,which used sterilized injection water to clean the SPF chicken embryo eggs,was 91.67％to 96.97％,while the final steriliza-tion rate of the experimental group,which used the above three disinfectants to disinfect the SPF chicken embryo eggs,was 100.00％.By comparing the cell counts of the experimental group and the control group,it was found that the live cell density of the control group was(6.03-6.25)× 105 cells·mL-1,and that of the experimental groups A-C was(6.08-6.17)× 105 cells·mL-1,(5.99-6.25)× 105 cells·mL-1,and(5.87-6.21)× 105 cells·mL-1 respectively;the cell viability of the control group was 90.33％to 91.35％,and that of the experi-mental groups A-C was 88.25％to 92.12％,89.45％to 93.59％,and 88.02％to 92.89％respectively.Through statistical analysis,it was found that the P values of all experimental groups compared with the control group were greater than 0.05,indicating no statistically significant difference.Conclusion:By comparing the dis-infection effects,cell density and cell viability of the three disinfectants and comprehensively considering factors such as cost and risk of the three disinfectants,1∶50 sporicide dilution,1∶128 alkaline phenolate dilution and ready-to-use compound quaternary ammonium salt disinfectant(sterile)can all be used for the daily surface disin-fection of SPF chicken embryo eggs in the production workshop.The selection of an appropriate disinfectant should be based on specific application scenarios and requirements.

The engineering application of microbially induced carbonate precipitation(MICP)is limited by pH-dependent conformational dynamics of urease.Focusing on the α-subunit urease from Sporosarcina pasteurii,this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11.Results showed that under neutral conditions(pH 7-8),key histidine residues(HIS139/HIS249)exhibited minimal dis-placement(＜0.5 ?),the longest hydrogen bond lifetime(＞8 ps),highest conformational stability(root mean square deviation,RMSD:0.15-0.18 nm),and optimal catalytic activity(conductivity change rate:0.03 mS/cm·min-1,CaCO3 precipitation:3.84 g).Extreme pH(pH 3/11)induced structural collapse(displacement up to 1.8 ?)and complete activity loss.Simulations revealed that neutral pH sta-bilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume(～120 ?3)and moderate conformational coherence(correlation coefficient～0.8).This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states,providing theoreti-cal support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

Objective To explore the role of SLIT-ROBO Rho GTPase-activating protein 2(srGAP2)in spinal motor neuron degeneration in amyotrophic lateral sclerosis(ALS).Methods Applied bioinformatics analysis to investigate the expression changes of srGAP2 in the spinal cord of human superoxide dismutase 1(hSOD1)mutant ALS transgenic mice.hSOD1 G93A mutant ALS transgenic mice were selected for animal experimental validation,with littermate wild type(WT)mice serving as the control group.A total of 36 pairs were divided into four groups,namely the pre-onset stage,early-onset stage,mid-onset stage,and late-onset stage.The expression changes and cellular localization of srGAP2 in the spinal cord of ALS mice were detected by Real-time PCR,Western blotting and immunofluorescent double-label staining.The hSOD1G93A mutant NSC34 motor neuron-like cell model was established,and in vitro experiments were carried out to detect the changes in srGAP2 expression,and the effects of srGAP2 over-expression on the viability of hSOD1G93A mutant NSC34 cells and the growth of cell protrusions.Results Bioinformatics analysis revealed abnormally low expression of srGAP2 in the spinal cord of hSOD1 mutant ALS mice.Animal experiments verified that compared with the WT mice,the expression of srGAP2 was reduced at both mRNA level and protein level in the spinal cord of hSOD1G93A mutant ALS transgenic mice at early-onset,mid-onset and late-onset stages.Compared with the WT mice,srGAP2 integral absorbance(IA)values in srGAP2+/NeuN+double-positive cells in the anterior horn of the spinal cord of hSOD1G93A mutant ALS transgenic mice were lower,srGAP2 IA values in srGAP2+/GFAP+double-positive cells were higher;Compared with the hSOD1WT NSC34 cells,the expression of srGAP2 was reduced at both mRNA level and protein level in hSOD1G93A mutant NSC34 cells.Over-expression of srGAP2 elevated the viability of hSOD1G93A mutant NSC34 cells,and up-regulated the expression level of synapse-related protein β Ⅲ-tubulin and growth associated protein 43(GAP43).Conclusion Low expression of srGAP2 is closely associated with the progression of ALS,while over-expression of srGAP2 can promote outgrowth of cell protrusions and exert a protective effect on spinal motor neurons in ALS.

Objective To investigate correlations of peripheral blood inflammatory and immune-related indices with clinicopathological features and prognosis in breast cancer patients.Methods A total of 144 breast cancer patients admitted to the Breast Surgery Department of Maternity and Child Healthcare Hospital of Tongzhou District of Beijing were included in cancer group,44 patients with a-typical breast hyperplasia were included in precancerous lesion group,and 131 patients with breast hyperplasia were included in breast hyperplasia group.The neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and lymphocyte-to-monocyte ratio(LMR)were compared among the three groups.A three-year follow-up was conducted for prognosis assessment.Based on different NLR,PLR,and LMR levels,the cancer group was divided into low NLR group(＜2.12,67 pa-tients),high NLR group(≥2.12,77 patients),low PLR group(＜133.21,65 patients),high PLR group(≥ 133.21,79 patients),low LMR group(＜5.05,80 patients),and high LMR group(≥5.05,64 patients).The correlations of NLR,PLR,and LMR with clinicopathological features and prognosis in breast cancer patients were analyzed.Results NLR in the cancer group was higher than that in the precancerous lesion group and breast hyperplasia group,the PLR was higher than that in the breast hyperplasia group,and the LMR was lower than that in the breast hyperplasia group(P＜0.05).NLR and PLR in the precancerous lesion group were higher and LMR was lower than those in the breast hyperplasia group(P＜0.05).PLR between patients with different menopa-usal statuses and Ki-67 levels showed statistically significant differences(P＜0.05).LMR between patients with different menopausal status also showed a statistically significant difference(P＜0.05).After a three-year follow-up,5 patients in the cancer group had a poor prognosis and 139 had a good prognosis.Poor prognosis rates between the low NLR and high NLR groups,low PLR and high PLR groups,and low LMR and high LMR groups showed statistically significant differences(P＜0.05).Logistic regression analysis results indicated that increased NLR and PLR were risk factors for poor prognosis in cancer patients,while increased LMR was a protective factor.Conclu-sion Peripheral blood inflammatory and immune-related indicators in breast cancer patients exhibit abnormal changes.Increased NLR and PLR are risk factors for poor prognosis,while increased LMR is a protective factor.

The engineering application of microbially induced carbonate precipitation(MICP)is limited by pH-dependent conformational dynamics of urease.Focusing on the α-subunit urease from Sporosarcina pasteurii,this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11.Results showed that under neutral conditions(pH 7-8),key histidine residues(HIS139/HIS249)exhibited minimal dis-placement(＜0.5 ?),the longest hydrogen bond lifetime(＞8 ps),highest conformational stability(root mean square deviation,RMSD:0.15-0.18 nm),and optimal catalytic activity(conductivity change rate:0.03 mS/cm·min-1,CaCO3 precipitation:3.84 g).Extreme pH(pH 3/11)induced structural collapse(displacement up to 1.8 ?)and complete activity loss.Simulations revealed that neutral pH sta-bilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume(～120 ?3)and moderate conformational coherence(correlation coefficient～0.8).This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states,providing theoreti-cal support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

This article discusses the key pathogenesis of atherosclerosis （AS） based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS， aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances， lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement， the accumulation of dampness and turbidity， and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors： deficiency of healthy Qi， phlegm-turbidity， and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids， their impaired dispersion may lead to phlegm-turbidity and blood stasis， the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore， AS is rooted in spleen-stomach disorder， manifests as plaques formed by pathological product accumulation in vessels， with lipid transport disorder as its core pathogenesis. Specifically speaking， the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage， and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan， first recorded in Taiping Holy Prescriptions for Universal Relief， contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma， bitter and cold， exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus， pungent-bitter and hot， disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang， assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism， Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance， improving gut microbiota composition and metabolism， and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS， this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder， giving novel insights into the prevention and treatment of AS.