OBJECTIVE To study the ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury （ALI） based on serum exosomal microRNA （miRNA）. METHODS The rats were randomly divided into a blank group （normal saline）， model group （nomal saline）， and F. suspensa-L. japonica herb pair group （2.55 g/kg）， with 10 rats in each group. Except for the blank group， the other groups were used to establish an ALI model by intratracheal dripping of 5 mg/ mL lipopolysaccharides. After modeling， each group was given relevant medicine/normal saline intragastrically， once a day， for 3 consecutive days. After the last medication， the pathological status of lung tissue was observed； lung wet-to-dry weight ratio and leukocyte counts in bronchoalveolar lavage fluid （BALF） were determined. The levels of inflammatory factors [tumor necrosis factor-α（TNF-α）， interleukin-1β （IL-1β）， IL-10] in BALF were determined. Exosomes were isolated from rat serum， and high- throughput sequencing technology was employed to screen differentially expressed miRNA within the exosomes， followed by Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Based on the screened differentially expressed miRNA and the enriched KEGG pathways， in vitro cellular experiments were conducted for validation. RESULTS The animal experimental results demonstrated that after intervention with the F. suspensa-L. japonica herb pair， the wet-to-dry weight ratio， the number of leukocytes in BALF， as well as the levels of TNF-α and IL-1β in BALF of ALI rats were all significantly reduced （P＜0.01）， while the level of IL-10 was significantly increased （P＜0.01）. The results of high-throughput sequencing experiments revealed that the F. suspensa-L. japonica herb pair could significantly up-regulate the expressions of miR-345-3p， miR-194-5p， miR-653-5p， and others in exosomes. Among them， the KEGG pathways involved in the target genes of differentially expressed miRNA included the hypoxia-inducible factor-1（HIF-1） signaling pathway， among others. The results of cellular E-mail：huang.haiying@126.com validation experiments showed that overexpressed miR-345-3p could significantly elevate the level of IL-10 in the cell supernatant （P＜0.01）， while significantly reducing the levels of TNF-α and IL-1β in the cell supernatant， as well as the mRNA and protein expression levels of protein kinase B1， phosphatidylinositol 3- kinase， and HIF-1α （P＜0.01）. CONCLUSIONS F. suspensa-L. japonica herb pair can alleviate inflammatory responses and thereby exert a therapeutic effect in improving ALI by up-regulating the expression of miR-345-3p in serum exosomes and inhibiting the activity of the HIF-1 signaling pathway.

Objective To compare the hematological parameters,biochemical profiles,histopathological characteristics,and cytokines associated with lipid metabolism in 8-weeks-old specific pathogen-free(SPF)grade and germ-free(GF)golden hamsters.Methods Twenty 8-weeks-old SPF grade and GF golden hamsters,with equal numbers of males and females,were utilized in this study.Serum cytokines associated with routine blood parameters,blood biochemistry,and lipid metabolism were quantified using automated hematology and biochemical analyzers,and enzyme-linked immunosorbent assay kits.The cecum,small intestine,lung,spleen,forestomach,and glandular stomach were examined by histopathology.Results We compared the result between SPF grade and GF golden hamsters at 8 weeks of age.Regarding hematological parameters,females showed significant differences(P＜0.05)in white blood cell count,hemoglobin concentration,mean corpuscular hemoglobin(MCH),and mean platelet volume between the two groups,and highly significant differences(P＜0.001)in MCH concentration(MCHC),platelet distribution width(PDW),and lymphocyte count(LYM).Males showed significant differences(P＜0.05)in mean corpuscular volume,MCH,LYM,neutrophil count,basophil count,and basophil percentage,and highly significant differences(P＜0.001)in MCHC,PDW,lymphocyte percentage,and neutrophil percentage.In terms of biochemical parameters,females showed significant differences(P＜0.05)in low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol,fasting insulin(FINS),and glycosylated serum protein(GSP),and highly significant differences(P＜0.001)in triglycerides(TG).Males showed significant differences(P＜0.05)in GSP levels and highly significant differences(P＜0.001)in total cholesterol,TG,LDL-C,FINS,and C-peptide levels.For serum cytokines related to lipid metabolism,females showed significant differences(P＜0.05)in interleukin(IL)-10,adiponectin(ADP),and IL-6 levels,and highly significant differences(P＜0.001)in high-sensitivity C-reactive protein(hs-CRP).Males showed significant differences(P＜0.05)in hs-CRP levels and highly significant differences(P＜0.001)in ADP and tumor necrosis factor-alpha levels.Hematoxylin/eosin staining showed that the cecal muscle layer was thinner and the number of crypts attached to the mucous membrane was reduced in GF compared with SPF grade golden hamsters.In addition,the ileocele was enlarged and the number of goblet cells was increased,the alveolar septum was widened,immune cells in the white pulp of the spleen were increased,and the blood content in the blood sinuses was increased.There was also thinning of the anterior gastric mucosa and the basophilic strength of the glandular gastric tube gland was weakened.Conclusions This study established the differences in routine blood parameters,blood biochemistry indicators,histopathological features,and cytokines associated with lipid metabolism between 8-weeks-old SPF grade and GF golden hamsters,to establish preliminary reference ranges.

ObjectiveTo investigate the mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos（FF） in the treatment of acute lung injury（ALI） by investigating the effects of FF on serum metabolomics of rats with ALI. MethodsThirty male SD rats were acclimated for 1 week， and 6 rats were randomly selected as the blank group. The other 24 rats were injected with lipopolysaccharide（LPS） solution by tracheal drip to establish an ALI model. After successful model establishment， the rats were randomly divided into the model group， the FF low-dose group（3.0 g·kg^-1）， the FF high-dose group（6.0 g·kg^-1）， and the dexamethasone group（5 mg·kg^-1）， with six rats in each group. The FF low- and high-dose groups and the dexamethasone group were received daily oral administration of the corresponding drug solution， and the blank group and the model group were gavaged with an equal amount of saline， treatment was administered continuously for 3 d. The pathological conditions of rat lung tissues were evaluated by hematoxylin-eosin（HE） staining， wet/dry mass ratio（W/D） of the lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. Metabolomic analysis of rat serum was performed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， combined with multivariate statistical analysis， the potential biomarkers of FF in treating ALI were screened by variable importance in the projection（VIP） value>1， P<0.05 from t-test， and log₂fold change（FC）>1 or log₂FC<-1. Kyoto Encyclopedia of Genes and Genomes（KEGG） database combined with MetaboAnalyst were used for pathway analysis of the screened differential metabolites. The protein expression levels of sphingosine-1-phosphate（S1P）， phosphatidylinositol 3-kinase（PI3K）， protein kinase B1（Akt1）， and phosphorylated Akt1（p-Akt1） were examined by Western bolt. The expression levels of interleukin（IL）-6， IL-1β， and tumor necrosis factor（TNF）-α in BALF were detected by enzyme-linked immunosorbent assay（ELISA）. ResultsCompared with the blank group， rats in the model group showed ALI pathological features such as alveolar lumen dilatation， interstitial hemorrhage and massive inflammatory cell infiltration， and the protein concentration in BALF and W/D of the lung tissues were significantly elevated（P<0.01）. Compared with the model group， the low- and high-dose groups of FF as well as the dexamethasone group exhibited reduced pulmonary bronchial hemorrhage in rats， and the protein concentration in BALF and W/D were significantly decreased（P<0.05）， and the lung injury was significantly alleviated. Analysis of rat serum metabolomics revealed that FF downregulated 38 biomarkers. Pathway enrichment analysis showed that FF primarily exerted therapeutic effects through 7 key metabolic pathways， including arginine biosynthesis， sphingomyelin metabolism， alanine， aspartate and glutamate metabolism， taurine and hypotaurine metabolism， α-linolenic acid metabolism， niacin and nicotinamide metabolism， and retinol metabolism. The results of Western bolt and ELISA showed that， compared with the blank group， the model group exhibited significantly elevated expression levels of S1P， PI3K， Akt1 and p-Akt1 proteins in the lung tissues， as well as increased expression levels of IL-6， IL-1β and TNF-α in BALF（P<0.01）. Compared with the model group， the expression levels of the aforementioned indicators were significantly downregulated in the low- and high-dose FF groups as well as the dexamethasone group（P<0.05， P<0.01）. ConclusionFF may play a role in ALI by regulating amino acid metabolism and lipid metabolism， and its mechanism may be related to the inhibition of S1P/PI3K/Akt1 signaling pathway to attenuate the inflammatory response caused by ALI.

Objective:To construct analytical dimensions for policy texts related to the pilot work of Health Impact Assessment (HIA) system in Zhejiang Province and conduct quantitative analysis, thereby providing references for improving the pilot work.Methods:Policy texts issued by Zhejiang Province between February 11, 2018, and February 29, 2024, which involved HIA content, were selected. The policy instruments theory was employed to construct an analytical framework around the dimensions of policy instruments, policy objectives, policy actors, and the interactions between policy instruments and policy objectives, and between policy instruments and policy actors. Based on this framework, a combination of literature analysis and content analysis was used to conduct a multi-dimensional quantitative analysis of the policy texts related to the pilot work of HIA system in Zhejiang Province.Results:Fifty core policy texts were included and 1 588 codes were obtained. In terms of policy instruments, environmental-type instruments were the most widely used (852 items), with internal responsibilities and methodological measures being the most frequently used; supply-type instruments were the second most used (459 items), with mechanism improvement being the most frequently used; demand-type instruments were the least used (277 items), with multi-stakeholder participation being the most frequently used. In terms of policy objectives, the objective of system construction dominated (701 articles, accounting for 56.45%), while the proportion of policy coverage, evaluation technology, and effectiveness evaluation was relatively low. In terms of policy subjects, the Party committee and government were the main policy subjects (434 articles, accounting for 39.20%), followed by health departments and public policy-making departments, while the proportion of public health institutions and social forces was extremely low. In the interaction between policy instruments and policy objectives, policy coverage, system construction, and effectiveness evaluation objectives all responded most frequently to environmental-type instruments, while the evaluation technology objectives responded more frequently to supply-type instruments. In the interaction between policy instruments and policy subjects, the Party committee and government played a dominant role in the use of policy instruments, with the health department and public policy-making department in the middle.Conclusions:The pilot work of the HIA system in Zhejiang Province presented a " environment-driven, system-construction-priority, Party-committee-and-government-led" policy characteristic. The main challenges were the imbalanced structure of policy instruments, insufficient synergy among policy objectives, and the need for greater participation of multiple stakeholders.

Objective To compare the hematological parameters,biochemical profiles,histopathological characteristics,and cytokines associated with lipid metabolism in 8-weeks-old specific pathogen-free(SPF)grade and germ-free(GF)golden hamsters.Methods Twenty 8-weeks-old SPF grade and GF golden hamsters,with equal numbers of males and females,were utilized in this study.Serum cytokines associated with routine blood parameters,blood biochemistry,and lipid metabolism were quantified using automated hematology and biochemical analyzers,and enzyme-linked immunosorbent assay kits.The cecum,small intestine,lung,spleen,forestomach,and glandular stomach were examined by histopathology.Results We compared the result between SPF grade and GF golden hamsters at 8 weeks of age.Regarding hematological parameters,females showed significant differences(P＜0.05)in white blood cell count,hemoglobin concentration,mean corpuscular hemoglobin(MCH),and mean platelet volume between the two groups,and highly significant differences(P＜0.001)in MCH concentration(MCHC),platelet distribution width(PDW),and lymphocyte count(LYM).Males showed significant differences(P＜0.05)in mean corpuscular volume,MCH,LYM,neutrophil count,basophil count,and basophil percentage,and highly significant differences(P＜0.001)in MCHC,PDW,lymphocyte percentage,and neutrophil percentage.In terms of biochemical parameters,females showed significant differences(P＜0.05)in low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol,fasting insulin(FINS),and glycosylated serum protein(GSP),and highly significant differences(P＜0.001)in triglycerides(TG).Males showed significant differences(P＜0.05)in GSP levels and highly significant differences(P＜0.001)in total cholesterol,TG,LDL-C,FINS,and C-peptide levels.For serum cytokines related to lipid metabolism,females showed significant differences(P＜0.05)in interleukin(IL)-10,adiponectin(ADP),and IL-6 levels,and highly significant differences(P＜0.001)in high-sensitivity C-reactive protein(hs-CRP).Males showed significant differences(P＜0.05)in hs-CRP levels and highly significant differences(P＜0.001)in ADP and tumor necrosis factor-alpha levels.Hematoxylin/eosin staining showed that the cecal muscle layer was thinner and the number of crypts attached to the mucous membrane was reduced in GF compared with SPF grade golden hamsters.In addition,the ileocele was enlarged and the number of goblet cells was increased,the alveolar septum was widened,immune cells in the white pulp of the spleen were increased,and the blood content in the blood sinuses was increased.There was also thinning of the anterior gastric mucosa and the basophilic strength of the glandular gastric tube gland was weakened.Conclusions This study established the differences in routine blood parameters,blood biochemistry indicators,histopathological features,and cytokines associated with lipid metabolism between 8-weeks-old SPF grade and GF golden hamsters,to establish preliminary reference ranges.

Objective:To construct analytical dimensions for policy texts related to the pilot work of Health Impact Assessment (HIA) system in Zhejiang Province and conduct quantitative analysis, thereby providing references for improving the pilot work.Methods:Policy texts issued by Zhejiang Province between February 11, 2018, and February 29, 2024, which involved HIA content, were selected. The policy instruments theory was employed to construct an analytical framework around the dimensions of policy instruments, policy objectives, policy actors, and the interactions between policy instruments and policy objectives, and between policy instruments and policy actors. Based on this framework, a combination of literature analysis and content analysis was used to conduct a multi-dimensional quantitative analysis of the policy texts related to the pilot work of HIA system in Zhejiang Province.Results:Fifty core policy texts were included and 1 588 codes were obtained. In terms of policy instruments, environmental-type instruments were the most widely used (852 items), with internal responsibilities and methodological measures being the most frequently used; supply-type instruments were the second most used (459 items), with mechanism improvement being the most frequently used; demand-type instruments were the least used (277 items), with multi-stakeholder participation being the most frequently used. In terms of policy objectives, the objective of system construction dominated (701 articles, accounting for 56.45%), while the proportion of policy coverage, evaluation technology, and effectiveness evaluation was relatively low. In terms of policy subjects, the Party committee and government were the main policy subjects (434 articles, accounting for 39.20%), followed by health departments and public policy-making departments, while the proportion of public health institutions and social forces was extremely low. In the interaction between policy instruments and policy objectives, policy coverage, system construction, and effectiveness evaluation objectives all responded most frequently to environmental-type instruments, while the evaluation technology objectives responded more frequently to supply-type instruments. In the interaction between policy instruments and policy subjects, the Party committee and government played a dominant role in the use of policy instruments, with the health department and public policy-making department in the middle.Conclusions:The pilot work of the HIA system in Zhejiang Province presented a " environment-driven, system-construction-priority, Party-committee-and-government-led" policy characteristic. The main challenges were the imbalanced structure of policy instruments, insufficient synergy among policy objectives, and the need for greater participation of multiple stakeholders.

Objective:To explore the application value of Activity-Based Costing (ABC) in hospital cost management under the reform of medical insurance payment mode. Methods:Hospital cost management scheme based on ABC was constructed. The application differences between traditional cost method and ABC were compared and analyzed to determine application advantages of ABC in hospital cost management compared with traditional costing method under the reform of medical insurance payment mode. Taking hospital cost management based on activity-based costing was proposed under the reform of medical insurance payment mode. Results:According to analysis,the cost by traditional costing method was 1731.8173 million yuan,and the cost by ABC was 1925.1388 million yuan,193.3215 million yuan more than that of the former,and the difference rate was 11.16％. The items that gave rise to the differences were mainly due to the fact that the cost of personnel and sanitary materials in the operation cost method were 54.371200 million yuan and 68.810200 million yuan more than the traditional cost method,and that fixed assets and depreciation,intangible assets and amortization,and utilities and property costs were 16.140600 million yuan and 24.217100 million yuan less than the traditional cost method. Conclusion:Compared with traditional costing method,application of ABC in hospital cost management under the reform of medical insurance payment mode is more advanced. It can comprehensively analyze cost compositions and benefits in different projects and medical services at the project level,and thus provide feasible reference basis for promoting hospital cost fine management scheme.

Objective:To explore the application value of Activity-Based Costing (ABC) in hospital cost management under the reform of medical insurance payment mode. Methods:Hospital cost management scheme based on ABC was constructed. The application differences between traditional cost method and ABC were compared and analyzed to determine application advantages of ABC in hospital cost management compared with traditional costing method under the reform of medical insurance payment mode. Taking hospital cost management based on activity-based costing was proposed under the reform of medical insurance payment mode. Results:According to analysis,the cost by traditional costing method was 1731.8173 million yuan,and the cost by ABC was 1925.1388 million yuan,193.3215 million yuan more than that of the former,and the difference rate was 11.16％. The items that gave rise to the differences were mainly due to the fact that the cost of personnel and sanitary materials in the operation cost method were 54.371200 million yuan and 68.810200 million yuan more than the traditional cost method,and that fixed assets and depreciation,intangible assets and amortization,and utilities and property costs were 16.140600 million yuan and 24.217100 million yuan less than the traditional cost method. Conclusion:Compared with traditional costing method,application of ABC in hospital cost management under the reform of medical insurance payment mode is more advanced. It can comprehensively analyze cost compositions and benefits in different projects and medical services at the project level,and thus provide feasible reference basis for promoting hospital cost fine management scheme.

Objective To evaluate the effects of fecal status and transplantation method on the intestinal flora structure after fecal microbiota transplantation in germ-free mice.Methods Thirty-six C57BL/6 mice were divided randomly into three groups:fresh fecal gavage transplantation(group A),frozen fecal gavage transplantation(group B),and frozen fecal rectal transplantation groups(group C).Feces were collected at 2,4 and 6 weeks after transplantation.All mice were sacrificed at 6 weeks to obtain the contents of the small and large intestines.The structure and function of the gut microbiota and dynamic trends in microbial changes were analyzed by 16 S rRNA sequencing.Results The diversity of the small intestine microbes in both the group A and group C were similar to those in the group B,according to α-diversity analysis(P＞0.05),but the diversity of large intestine microbes was significantly increased(P＜0.001).According toβ-diversity analysis,small intestine samples from the group A and group B clustered in the same area,indicating that the microbial community compositions were similar(P＞0.05),but samples from the large intestine were distributed in different areas,showing significant differences(P＜0.001).Small and large intestine samples from the group B and group C were distributed in different areas,with significant differences(P＜0.001).Linear discriminant analysis effect size showed that Bacteroidota were relatively dominant in the group A,while Verrucomicrobiota and Proteobacteria were relatively dominant in the group B and Firmicutes were relatively dominant in the group C.Functional prediction using PICRUSt2 software showed that neither fecal status nor the method of transplantation affected the functions of the microbial community.Conclusions Both fresh fecal gavage and frozen fecal rectal transplantation can enhance the microbial diversity of the large intestine,compared with frozen fecal gavage transplantation.Fecal status does not affect the gut function and colonization trends of the microbiota,whereas the method of transplantation affects the colonization trends but not the functions of the microbiota.

Objective A sterile golden hamster model was established by cesarean section purification.Methods SPF-grade donor female golden hamsters were selected,and males and females were mated 1∶1 and separated after mating.The cage time of the surrogate mothers was 1 week earlier than that of the donor mothers.Parturient golden hamsters underwent hysterectomy on a sterilized workbench,and the uteruses were transferred into isolation kits and stripped.To obtain sterile milk for milk replacement,sterile ICR mice and sterile SD rats were used.After successful separation,the hamsters were transferred to isolation kits to prepare for feeding.The sterility status of the feeding isolation kits was tested monthly.Results Three caesarean sections were performed,but the first and second lactations failed.The third milk replacement was successful,and 18 young hamsters were obtained with survival rates of 88%and 66%after weaning.All hamsters were quality tested by GB/T 14926.41-2001.Conclusions Using a cesarean section purification technique and sterile ICR mice and SD rats for microbial-free milk replacement,a sterile golden hamster model was obtained.