Objective Three different doses of diethylnitrosamine(DEN)were used to establish a rat primary liver cancer(PLC)model to establish an efficient,stable,and economical animal model of PLC.Methods Forty-five male SD rats were randomly divided into four groups:normal group,DEN 50 mg/kg dose group(low dose group),70 mg/kg dose group(medium dose group),and 200 mg/kg dose group(high dose group).There were 6 animals in the normal group and 13 animals in each of the other groups.The normal control group received no treatment.The model group and low dose groups were injected intraperitoneally twice a week during weeks 1～4 and once a week during weeks 5～12;the medium dose group was injected intraperitoneally once a week for 16 consecutive weeks;and the high dose group was administered only once in the first week.The rats in each group were then followed for 16 weeks.The establishment of the model and optimal evaluation were verified by survival rate,pathological tests,biochemical tests,liver and spleen index calculation,immunohistochemistry,enzyme-linked immunosorbent assay(ELISA),and other assays.Results The survival rate was 100％in the normal group,46.15％in the low dose group,69.23％in the medium dose group,and 84.61％in the high dose group.The liver tissues of the rats in the normal group showed no abnormality to the naked eye;the liver of the rats in the low dose group became darker in color,rougher in surface,with a small number of cancerous nodules and slightly hard texture;the liver of the rats in the medium dose group was rough in surface,with several small cancerous nodules and scattered massive occupying nodules and hard texture;The liver of rats in the high dose group became lighter in color,slightly rougher in surface,with no obvious cancerous nodules;HE staining showed that the liver tissues of rats in the low and medium dose groups were structurally disorganized,with large cellular heterogeneity and tumor cells.HE staining showed that the liver tissues of rats in the low and medium dose groups were structurally disorganized,with large cellular heterogeneity and tumor cell formation,while the structure of the liver lobules of the high dose group was unclear,with different degrees of edema,degeneration and necrosis of liver cells,and no obvious tumor cell formation was seen.Compared with the normal group,serum liver function alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)were elevated in the low,medium,and high dose groups;ALT and AST were significantly elevated in the low dose group(P<0.05),the difference was statistically significant,ALT,AST and TBIL were significantly elevated in the medium dose group(P<0.05),the difference was statistically significant,and the difference was statistically significant,although liver function in the high dose group was elevated,he increase was not significant,the difference was not statistically significant(P>0.05);compared with the normal group,the international normalized ratio(INR)of coagulation function was significantly higher in the low dose group,with a statistically significant difference(P<0.05),and the activated partial thromboplastin time(APTT),prothrombin time(PT),and alpha-fetoprotein(AFP)levels were increased(P<0.05),and the difference was not statistically significant;serum APTT,PT,INR,and AFP levels were significantly increased in the medium dose group(P<0.05),and the difference was statistically significant;serum PT and AFP levels were increased in the high dose group(P<0.05),the difference was statistically significant,and plasma APTT levels were slightly increased(P>0.05),the difference was not statistically significant;liver and spleen indexes were increased in the medium dose group(P<0.05),the spleen index increased in the low dose group(P<0.05),and the liver index increased in the high dose group(P<0.05),the difference was statistically significant;the optical density value of liver tissue AFP increased significantly in the low,medium and high dose groups(P<0.05),the difference was statistically significant.Conclusions Both the low and medium dose groups could successfully induce the PLC rat model,but the pathological changes and biochemical findings of the medium dose group were more consistent with the pathogenesis of human liver tissue from liver injury to hepatic fibrosis to cirrhosis to hepatocellular carcinoma,and the number of administrations of the drug is less,and the survival rate of the rats is higher so that a more cost-effective and superior PLC model can be established.

Objective Based on the theory of mutual admiration of spleen and kidney,this study intends to explore the medication patterns of traditional Chinese medicine for the treatment of spleen-kidney deficiency-type chronic kidney disease(CKD)by using data mining methods and to provide reference for the clinical treatment of spleen-kidney deficiency-type CKD.Methods The literatures included in China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,and VIP databases were used as data sources.The literature related to traditional Chinese medicine treatment of spleen-kidney deficiency-type CKD was analyzed by Excel 2021,IBM SPSS Modeler 18.0,IBM SPSS Statistics 27,and systematic clustering analysis and finally visualized by Cytoscape 3.7.2,RStudio.Results A total of 90 prescriptions were included,involving 146 flavors of drugs.The top 5 high-frequency drugs were Huangqi,Fuling,Baizhu,Dahuang,and Danshen.The medicinal properties are mainly mild and warm;The medicinal taste is characterized by sweetness,bitterness,and pungent;The main meridians of drugs are spleen,liver,and kidney meridians.Association rule analysis demonstrated that the commonly used couplet drugs were Huangqi-Fuling and Huangqi-Baizhu;Commonly used corner drugs included Huangqi-Baizhu-Fuling and Huangqi-Dahuang-Fuling.Cluster analysis found that the clustering effect of spleen-kidney deficiency-type CKD treatment drugs in five categories was better.Conclusion The medication rules of traditional Chinese medicine in the treatment of spleen-kidney deficiency-type CKD are preliminarily clarified,which provides a basis for clinical medication and new prescription development.

Objective To analyze the medication rules of traditional Chinese medicine compound patents for the prevention and treatment of urinary tract infection(UTI)through data mining technology.Methods The patents of traditional Chinese medicine compounds for the prevention and treatment of UTI in patent announcement module of China National Intellectual Property Administration website as data sources.The statistical analysis platforms of Excel 2021,IBM SPSS Modeler 18.0 and IBM SPSS Statistics 27.0 were used for frequency of use,medicinal properties,association rule analysis,and systematic clustering analysis and finally visualized by Cytoscape 3.7.2,RStudio.Results Through screening,a total of 179 compound patents met the inclusion criteria,involving 466 kinds of Chinese materia medica,and the top 5 high-frequency drugs were Pugongying,Huangbai,Gancao,Jinyinhua,Bianxu.The medicinal properties are mainly cold and mild;The medicinal taste is characterized by sweetness,bitterness,and bitterness;The main meridians of drugs are liver,lung and kidney meridians.Common couplet medicines included Qumai-Bianxu,Gancao-Bianxu and the three herb drug combinations included Cheqianzi-Qumai-Bianxu,Gancao-Qumai-Bianxu.A total of 5 high-frequency combinations of traditional Chinese medicine were obtained by cluster analysis.Conclusion This study preliminarily reveals the compatibility and medication rules of traditional Chinese medicine in the treatment of UTI,which provides data support for the optimization of clinical syndrome differentiation and treatment system and the development of new prescriptions.

OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

The blood products industry in China,the United States,the European Union and Japan are at different stages of development,with very different laws,regulations and regulatory systems.This paper uses methods such as literature review,policy comparison,and case study.By analyzing and comparing the blood product regulatory policies in various countries,it is found that compared with the United States,the European Union and Japan,China has differences in several areas,including plasma quarantine period,plasma fractionation processes and intermediate products,segmented production of blood products,and import management policies.It is suggested that we should learn from foreign regulatory experiences,and explore the establishment of blood product regulatory policies suitable for China's national conditions.Recommendations include optimizing China's source plasma quarantine period and blood product production process management policies,promoting multiple sites and segmented production of blood products,and establishing flexible blood product import and export management systems.These measures aim to provide references for promoting the development of the blood product industry and improving the accessibility of medications for the public.

Objective Three different doses of diethylnitrosamine(DEN)were used to establish a rat primary liver cancer(PLC)model to establish an efficient,stable,and economical animal model of PLC.Methods Forty-five male SD rats were randomly divided into four groups:normal group,DEN 50 mg/kg dose group(low dose group),70 mg/kg dose group(medium dose group),and 200 mg/kg dose group(high dose group).There were 6 animals in the normal group and 13 animals in each of the other groups.The normal control group received no treatment.The model group and low dose groups were injected intraperitoneally twice a week during weeks 1～4 and once a week during weeks 5～12;the medium dose group was injected intraperitoneally once a week for 16 consecutive weeks;and the high dose group was administered only once in the first week.The rats in each group were then followed for 16 weeks.The establishment of the model and optimal evaluation were verified by survival rate,pathological tests,biochemical tests,liver and spleen index calculation,immunohistochemistry,enzyme-linked immunosorbent assay(ELISA),and other assays.Results The survival rate was 100％in the normal group,46.15％in the low dose group,69.23％in the medium dose group,and 84.61％in the high dose group.The liver tissues of the rats in the normal group showed no abnormality to the naked eye;the liver of the rats in the low dose group became darker in color,rougher in surface,with a small number of cancerous nodules and slightly hard texture;the liver of the rats in the medium dose group was rough in surface,with several small cancerous nodules and scattered massive occupying nodules and hard texture;The liver of rats in the high dose group became lighter in color,slightly rougher in surface,with no obvious cancerous nodules;HE staining showed that the liver tissues of rats in the low and medium dose groups were structurally disorganized,with large cellular heterogeneity and tumor cells.HE staining showed that the liver tissues of rats in the low and medium dose groups were structurally disorganized,with large cellular heterogeneity and tumor cell formation,while the structure of the liver lobules of the high dose group was unclear,with different degrees of edema,degeneration and necrosis of liver cells,and no obvious tumor cell formation was seen.Compared with the normal group,serum liver function alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)were elevated in the low,medium,and high dose groups;ALT and AST were significantly elevated in the low dose group(P<0.05),the difference was statistically significant,ALT,AST and TBIL were significantly elevated in the medium dose group(P<0.05),the difference was statistically significant,and the difference was statistically significant,although liver function in the high dose group was elevated,he increase was not significant,the difference was not statistically significant(P>0.05);compared with the normal group,the international normalized ratio(INR)of coagulation function was significantly higher in the low dose group,with a statistically significant difference(P<0.05),and the activated partial thromboplastin time(APTT),prothrombin time(PT),and alpha-fetoprotein(AFP)levels were increased(P<0.05),and the difference was not statistically significant;serum APTT,PT,INR,and AFP levels were significantly increased in the medium dose group(P<0.05),and the difference was statistically significant;serum PT and AFP levels were increased in the high dose group(P<0.05),the difference was statistically significant,and plasma APTT levels were slightly increased(P>0.05),the difference was not statistically significant;liver and spleen indexes were increased in the medium dose group(P<0.05),the spleen index increased in the low dose group(P<0.05),and the liver index increased in the high dose group(P<0.05),the difference was statistically significant;the optical density value of liver tissue AFP increased significantly in the low,medium and high dose groups(P<0.05),the difference was statistically significant.Conclusions Both the low and medium dose groups could successfully induce the PLC rat model,but the pathological changes and biochemical findings of the medium dose group were more consistent with the pathogenesis of human liver tissue from liver injury to hepatic fibrosis to cirrhosis to hepatocellular carcinoma,and the number of administrations of the drug is less,and the survival rate of the rats is higher so that a more cost-effective and superior PLC model can be established.

OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

The blood products industry in China,the United States,the European Union and Japan are at different stages of development,with very different laws,regulations and regulatory systems.This paper uses methods such as literature review,policy comparison,and case study.By analyzing and comparing the blood product regulatory policies in various countries,it is found that compared with the United States,the European Union and Japan,China has differences in several areas,including plasma quarantine period,plasma fractionation processes and intermediate products,segmented production of blood products,and import management policies.It is suggested that we should learn from foreign regulatory experiences,and explore the establishment of blood product regulatory policies suitable for China's national conditions.Recommendations include optimizing China's source plasma quarantine period and blood product production process management policies,promoting multiple sites and segmented production of blood products,and establishing flexible blood product import and export management systems.These measures aim to provide references for promoting the development of the blood product industry and improving the accessibility of medications for the public.