Objective To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infected with Angiostrongylus cantonensis, and to preliminarily unravel the peripheral immune responses during the early stage of A. cantonensis infection. Methods Forty female BALB/c mice at ages of 6 to 8 weeks were randomly divided into four groups, including the control group and 7-, 14-, and 21-day infection groups, with 10 mice in each group. Each mouse in the infection groups was inoculated with 30 third-stage (L3) larvae of A. cantonensis by oral gavage, and five mice were randomly selected from each infection group on days 7, 14, and 21 post-infection, while mice in the control group were given the same volume of physiological saline and five mice were randomly selected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled. The histopathological changes of mouse liver and spleen tissues were observed using hematoxylin and eosin (HE) staining, and the percentage of positive staining area and the co-localization positive rates of the macrophage surface antigens F4/80, CD86, and CD206 were quantified in mouse liver and spleen tissues using immunohistochemical and immunofluorescence staining. In addition, five mice were collected from each infection group on days 7, 14, and 21 post-infection, and five mice were collected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled for detection of macrophage markers CD86 and CD206 and macrophage phenotyping using flow cytometry, and the expression of M1 macrophage markers, including inducible nitric oxide synthase (Nos2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and M2 markers, including arginase 1 (Arg1), mannose receptor C-type 1 (Mrc1) and chitinase-like protein 3 (Chil3) was quantified in mouse liver and spleen tissues using real-time quantitative PCR (RT-qPCR) assay. Results Proliferative lesions of the hepatocyte were observed in mouse liver tissues and the follicular structures of the mouse spleen white pulp were disrupted 21 days post-infection with A. cantonensis. Immunohistochemical staining showed that there were significant differences in the percentages of F4/80, CD86 and CD206 positive staining areas in the liver and spleen tissues among the four groups of mice (F = 242.40, 197.14, 183.19, 157.65, 242.35 and 146.24; all P values < 0.001), and the percentages of positive staining in the liver and spleen tissues of mice in the 14-day infection group [(4.45 ± 0.51)%, (3.74 ± 0.67)%, (8.32 ± 0.72)%, (16.56 ± 1.14)%, (11.62 ± 0.52)%, and (8.29 ± 0.72)%, respectively] and the 21-day infection group [(3.70 ± 0.11)%, (3.22 ± 0.43)%, (11.53 ± 1.03)%, (12.59 ± 1.05)%, (9.02 ± 0.83)%, and (11.67 ± 1.10)%, respectively] were higher than in the control group [(0.35 ± 0.16)%, (0.40 ± 0.02)%, (0.93 ± 0.05)%, (2.78 ± 0.26)%, (2.33 ± 0.20)%, and (1.85 ± 0.20)%, respectively] (all P values < 0.05). Immunofluorescence staining showed significant differences in the positive rates of F4/80 co-localization with CD86 and CD206 in mouse liver and spleen tissues among the four groups (F = 24.42, 25.28, 54.51 and 130.55; all P values < 0.001). Flow cytometry detected significant differences in the proportions of CD86⁺ and CD206⁺ macrophages in mouse liver and spleen tissues among the four groups (F = 67.98, 18.41, 29.77, 172.80; all P values < 0.001), and the proportions of CD206⁺ macrophages in the liver and spleen of the 21-day infection group were significantly higher than those in the control group [(9.25 ± 2.55)% vs (3.83 ± 0.72)%, and (4.22 ± 0.56)% vs (0.47 ± 0.18)%, respectively] (both P values < 0.05). In addition, RT-qPCR assay quantified significant differences in the relative mRNA expression of M1 macrophage markers (IL-1β, TNF-α and Nos2) and M2 macrophage markers (Arg1, Chil3 and Mrc1) in mouse liver and spleen tissues among the four groups (F = 41.30, 31.82, 199.33, 19.96, 62.01, 119.76, 23.67, 95.90, 72.27, 82.59, 123.41 and 29.75; all P values < 0.05). Conclusions A. cantonensis infection may cause progressive pathological damage in mouse liver and spleen tissues, accompanied by dynamic temporal changes in macrophage polarization. M1 macrophage polarization predominates at the early stage of A. cantonensis infection and shifts towards M2 polarization at the later stages, suggesting that M2 polarization may participate in immune regulation at late stages of A. cantonensis infection by suppressing excessive inflammatory responses and promoting tissue repair.

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 explore the application of bridge-in, objective, pre-assessment, participatory learning, post-assessment, and summary (BOPPPS) combined with knowledge point auction-based learning in the internship teaching of pediatric general surgery nursing students.Methods:Ninety nursing students completing internships in the General Surgery Department of Children's Hospital, Zhejiang University School of Medicine from July 2022 to April 2024 were selected as the research subjects. According to the order of admission, they were divided into control group (July 2022 to May 2023) and experimental group (June 2023 to April 2024), with 45 students in each group. The control group received conventional teaching, while the experimental group received BOPPPS teaching combined with knowledge point auction-based learning. Theoretical and practical training assessment scores were compared between the two groups. Additionally, a survey on the degree of satisfaction with the teaching was administered upon internship completion . Data were analyzed using t-tests with SPSS 26.0. Results:The theoretical scores of nursing students in the experimental group were higher than those in the control group, and the difference was statistically significant; The performance of the experimental group's nursing students in practical training assessment was higher than that of the control group [peripheral venous puncture catheterization: (27.62±2.10) vs. (22.41±3.80)]; Gastrointestinal decompression technique: (22.82±1.70) vs. (18.21±2.91); Rescue of anaphylactic shock: (16.52±3.13) vs. (21.32±2.41); There was a statistically significant difference in the evaluation of teacher guidance ability between the two groups of nursing students in terms of intestinal fistula nursing (14.11±2.70) vs. (17.90±1.93). However, there was no statistically significant difference in the satisfaction score of the experimental group nursing students in other aspects of teaching compared to the control group, and the difference was statistically significant.Conclusions:BOPPPS combined with knowledge point auction-based learning improves knowledge mastery in clinical teaching for pediatric general surgery interns, enhance operational confidence, and is readily accepted by students.

Objective To promote the objectification and intelligence of clinical TCM tongue diagnosis in ulcerative colitis(UC).Methods Daosheng DS01-B tongue and face diagnosis information collection system was used to prospectively collect tongue image pictures of patients with ulcerative colitis damp-heat in the large intestine syndrome(DCSR)and spleen deficiency dampness retention syndrome(PXSY),with totaling 1096 images.After UC tongue image segmentation,preprocessing,and data augmentation,a data set of UC tongue images was formed.Based on ResNet50,a UC tongue image classification model was constructed using feature fusion methods and attention modules.Results The UC tongue image classification model constructed had better classification performance,with an average F1 value of 85.09%,an AUC value of 0.83 for PXSY,and an AUC value of 0.81 for DCSR,both of which were higher than the VGG11 and ResNet50 models.Conclusion The constructed UC tongue image classification model can effectively identify DCSR and PXSY,providing a new approach to improve the accuracy and objectivity of UC differentiation and assisting in the intelligence of TCM tongue diagnosis.

Aim To explore the antioxidative effect of the Chinese medicine Baitouweng(BTW)on treating ulcerative colitis(UC).Methods Sixty male mice were randomly divided into six groups:control,dextran sulfate sodium(DSS)(3 g·105 L-1),BTW(20,10,and 5 g·kg-1),and 5-aminosalicylic acid(5-ASA)(800 mg·kg-1).UC model was constructed by 3％DSS for seven days,and the UC model was given by ga-vage once daily from the 5 th day of modeling for seven days.Results BTW effectively reduced the symptoms and histopathological scores of UC mice.Additionally,it downregulated the inflammatory factors,interleukin(IL)-6 and IL-1 β,the immunoglobulins vascular cell adhesion molecule 1 and intercellular adhesion mole-cule 1,and metalloprotease matrix metallopeptidase 9.Moreover,it downregulated high mobility group box 1 protein.Furthermore,it inhibited the nuclear factor er-ythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway.Conclusions BTW improves the general condition,inflammatory indexes and oxidative stress level,and its mechanism may be related to inhib-iting the level of HMGB1 to regulate the Nrf-2/HO-1 signaling pathway and rescue intestinal barrier-related protein expression.

AIM To study the chemical constituents from Citri reticulatae Pericarpium Viride and their anti-triple negative breast cancer activities in vitro.METHODS The ethanolic extract of Citri reticulatae Pericarpium Viride was isolated and purified by silica gel,polyamide,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-triple negative breast cancer activities were screened by SRB assay,and their effects on the proliferation of triple negative breast cancer cell lines HCC1806,HCC1937 and MDA-MB-231 in vitro were evaluated.RESULTS Twenty compounds were isolated and identified as nobiletin(1),tangeritin(2),5,4'-dihydroxy-7,8-dimethoxy flavonoid(3),naringenin(4),artemetin(5),5-demethynobiletin(6),3,5,6,7,8,3',4'-pentamethoxy flavonoid(7),5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone(8),xanthomicrol(9),p-hydroxycinnamic acid(10),5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone(11),pectolinarigenin(12),4'-dihydroxy-5,6,7-tetramethoxyflavone(13),hispidulin(14),4',5,6,7-tetramethoxy-flavone(15),1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol(16),umbelliferone(17),5-hydroxymethyl furfural(18),hydroquinone(19),1H-indole-3-carbaldehyde(20).Compound 8 showed a significant inhibitory effect with the IC50 value of(5.36±0.24)μmol/L on HCC1806 cells.CONCLUSION Compound 20 is isolated from genus Citrus for the first time,8,12-13,16-17 are isolated from this plant for the first time.Compound 8 show inhibitory effects on the proliferation of HCC1806,HCC1937 and MDA-MB-231 cells in vitro and have the strongest activities.Compounds 3-4,11-12,15,17 and 19 show strong inhibitory effect on HCC1806 cells.Compounds 15,19 also inhibit the proliferation of HCC1937 cells in vitro.

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 man-agement system,and novel tools and methods with Chinese characteristics.Results:The ChP 2025 edition demon-strates three prominent features in microbiological-related standards:enhanced international harmonization,intro-duced emerging molecular biological technologies,and established a risk-based microbiological quality control sys-tem.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.

AIM To study the chemical constituents from Citri reticulatae Pericarpium Viride and their anti-triple negative breast cancer activities in vitro.METHODS The ethanolic extract of Citri reticulatae Pericarpium Viride was isolated and purified by silica gel,polyamide,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-triple negative breast cancer activities were screened by SRB assay,and their effects on the proliferation of triple negative breast cancer cell lines HCC1806,HCC1937 and MDA-MB-231 in vitro were evaluated.RESULTS Twenty compounds were isolated and identified as nobiletin(1),tangeritin(2),5,4'-dihydroxy-7,8-dimethoxy flavonoid(3),naringenin(4),artemetin(5),5-demethynobiletin(6),3,5,6,7,8,3',4'-pentamethoxy flavonoid(7),5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone(8),xanthomicrol(9),p-hydroxycinnamic acid(10),5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone(11),pectolinarigenin(12),4'-dihydroxy-5,6,7-tetramethoxyflavone(13),hispidulin(14),4',5,6,7-tetramethoxy-flavone(15),1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol(16),umbelliferone(17),5-hydroxymethyl furfural(18),hydroquinone(19),1H-indole-3-carbaldehyde(20).Compound 8 showed a significant inhibitory effect with the IC50 value of(5.36±0.24)μmol/L on HCC1806 cells.CONCLUSION Compound 20 is isolated from genus Citrus for the first time,8,12-13,16-17 are isolated from this plant for the first time.Compound 8 show inhibitory effects on the proliferation of HCC1806,HCC1937 and MDA-MB-231 cells in vitro and have the strongest activities.Compounds 3-4,11-12,15,17 and 19 show strong inhibitory effect on HCC1806 cells.Compounds 15,19 also inhibit the proliferation of HCC1937 cells in vitro.

Objective To explore the association between aspartate aminotransferase(AST)/alanine aminotransferase(ALT)ratio and metabolic syndrome(MS)in elderly hypertensive patients,and to provide reference for early detection and prevention of MS in elderly hypertensive patients.Methods A questionnaire survey and physical examination were conducted among 616 elderly hypertensive patients at community health service centers.Participants were divided into two groups based on MS status:MS group(n=334)and non-MS group(n=282).According to AST/ALT levels,participants were divided into four groups:q1 group(AST/ALT ≤0.88,n=156),q2 group(0.88＜AST/ALT ≤ 1.10,n=155),q3 group(1.10＜AST/ALT ≤ 1.37,n=154),and q4 group(AST/ALT＞1.37,n=151).Blood biochemical parameters including triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),AST,ALT,and blood glucose were measured.The impact of AST/ALT levels on MS was analyzed using a Logistic regression model,while the risk prediction for MS occurrence was evaluated through receiver operating characteristic(ROC)curves.Results MS group showed higher body mass index(BMI),TG,ALT levels,abnormal glucose levels,female proportion,and abdominal obesity rate compared to non-MS group.HDL-C and AST/ALT values of MS group were lower than those in non-MS patients(P＜0.05).Logistic regression analysis revealed that after adjusting for BMI,smoking,alcohol consumption,physical activity,education level,marital status,TG,HDL-C,and glucose levels,both q3 and q4 groups demonstrated reduced MS risk compared to group q1 group(P＜0.05).ROC curve analysis indicated that the area under the curve for AST/ALT in MS was 0.638(P＜0.05).Conclusion The level of AST/ALT was negatively correlated with MS in elderly hypertensive patients,and AST/ALT has certain predictive value for the risk of MS in elderly hypertensive patients.

Objective To investigate the coagulation effect of a cold atmospheric plasma(CAP)jet device with helium as the working gas and to study its coagulation mechanism preliminarily.Methods A CAP jet device treatment group,a helium airflow treatment group,a hot air treatment group(60℃)and a natural coagulation group were formed according to the treatment modes of the blood samples,with 10 μL of blood samples involved in each group,in order to validate the coagulation effect of the CAP jet device in vitro;the coagulation mechanism of the CAP jet device was explored by its application to the treatment of anticoagulated whole blood,platelet-rich plasma and platelet-depleted plasma;the coagulation effect of the CAP jet device in vivo was verified with a mouse liver punctate hemorrhage model and a rabbit mesenteric hemorrhage model.Results The CAP jet device can significantly accelerate the coagulation of anticoagulated blood droplets,and the coagulation time of anticoagulated blood droplets in the CAP jet device-treated group was shortened from 28 min in the natural coagulation group to(23±1.56)s,with the difference statistically significant(P<0.05),and the CAP jet device treatment group gained advantages significantly over the helium airflow treatment group(P<0.05)and the hot air(60℃)treatment group(P<0.05)in coagulation-promoting effect;the procoagulant effect of the CAP jet device rose with the increase of platelet content in blood droplets,and the coagulation effect of platelet-rich blood droplets was significantly better than that of whole blood(P<0.05),while no coagulation was observed in platelet-poor droplets.The CAP jet device could rapidly stop hemostasis of punctate hemorrhage in mouse liver and mesenteric hemorrhage in rabbits without delayed hemorrhage occurring within 10 min,and no obvious structural abnormality of the liver and thermal damage of the tissue were found microscopically.Conclusion The CAP jet device plays procoagulant and hemostatic effects in vivo and in vitro,and its effect is not dependent on temperature and airflow evaporation effects and is considered to be related to platelet activation,with low thermal damage to living tissue.[Chinese Medical Equipment Journal,2025,46(6):20-27]