Objective To evaluate the efficacy and safety of different Chinese medicine injections combined with angiotensin converting enzyme inhibitor/angiotensin Ⅱ receptor blocker(ACEI/ARB)in the treatment of proteinuria in diabetic nephropathy by using network Meta-analysis.Methods Clinical randomized controlled trials of Chinese medicine injection combined with ACEI/ARB for the treatment of proteinuria in early diabetic nephropathy were retrieved from the domestic databases such as China National Knowledge Infrastructure(CNKI),China Science and Technology Journal Database(VIP),Wanfang Data Knowledge Service Platform(Wanfang Data),and China Biology Medicine Disc(CBM),as well as from the oversea databases such as PubMed,EMbase,Web of Science,and Cochrane Library from database inception to October 2023.The Cochrane risk of bias tool ROB2.0 was used to evaluate the quality of the included literature,and traditional Meta-analysis and network Meta-analysis were performed by using R4.3.2 and Stata18.0.Results A total of 72 trials were included,involving 13 Chinese medicine injections,namely Huangqi Injection,Xuesaitong Injection,Puerarin Injection,Denzhan Xixin Injection,Breviscapin Injection,Danhong Injection,Xueshuantong Injection,Yinxingye Injection,Shuxuetong Injection,Yinxing Damo Injection,Danshen Injection,Shenkang Injection,and Danshen Ligustrazine Injection.The primary outcomes were urinary albumin excretion rate(UAER),24-hour urinary total protein(24hUTP),serum creatinine(SCr),and urine albumin-to-creatinine ratio(UACR).The results of traditional Meta-analysis showed that Chinese medicine injection combined with ACEI/ARB was more effective on reducing the levels of UAER[MD=-26.14,95%CI(-29.39,-22.89)],24hUTP[(MD=-0.22,95%CI(-0.27,-0.18)],SCr[MD=-0.34,95%CI(-0.50,-0.19)],and UACR[MD=-9.40,95%CI(-15.64,-3.16)]than ACEI/ARB alone,and the differences were all statistically significant(P<0.05).The results of network meta-analysis showed that the efficacy of Dengzhan Xixin Injection combined with ACEI/ARB was the optimum in terms of reducing UAER,Danshen Ligustrazine Injection combined with ACEI/ARB was the optimum in terms of decreasing 24hUTP,Shenkang Injection combined with ACEI/ARB was the optimum in terms of decreasing SCr,and Danhong Injection combined with ACEI/ARB had the best efficacy on improving UACR.Conclusion The efficacy and safety of Chinese medicine injection combined with ACEI/ARB in the treatment of proteinuria in early diabetic nephropathy are superior to those of ACEI/ARB alone in terms of lowering UAER,24hUTP,SCr,and UACR.However,due to the limitations of the quality and number of included literatures,the conclusions still need to be confirmed by more high-quality randomized controlled trials.

Objective To investigate the role and molecular mechanism of ginsenoside Rb1(Rb1)in regulating neutrophil extracellular trapping networks(NETs)to intervene in atherosclerosis(AS).Methods In vivo:an AS model was constructed with ApoE knockout mice superimposed on a high-fat diet.The pathological and morphological changes of aortic root plaques were observed by HE staining and oil red O staining;Immunofluorescence labelling of neutrophils citrullinated histones(Cit-H3)and macrophages as well as IL-1β at the aortic root plaque site were used to assess the inflammatory infiltration.In vitro:NETs induced by PMA and cholesterol crystals were taken as models respectively.Direct effect of Rb1 against NETs formation assessed by Sytox staining and immunofluorescence staining with Cit-H3 and myeloperoxidase.Rb1 on ROS levels was assessed by DCFH-DA.Rb1 on histone H3 citrulline modification was assessed by Western blotting.Results In vivo:Rb1 significantly inhibited plaque formation,lipid deposition(P<0.05)and intra-plaque inflammatory infiltration(P<0.05).In vitro:Rb1 significantly inhibited NETs formation(P<0.05),neutrophil ROS levels(P<0.05),and Cit-H3 levels(P<0.05).Conclusions Rb1 significantly inhibited AS progression by inhibiting plaque NETs formation,which may be partly through the inhibition of histone H3 citrullination resulting from activation of the neutrophil oxidative stress pathway.

Objective To investigate the role and molecular mechanism of ginsenoside Rb1(Rb1)in regulating neutrophil extracellular trapping networks(NETs)to intervene in atherosclerosis(AS).Methods In vivo:an AS model was constructed with ApoE knockout mice superimposed on a high-fat diet.The pathological and morphological changes of aortic root plaques were observed by HE staining and oil red O staining;Immunofluorescence labelling of neutrophils citrullinated histones(Cit-H3)and macrophages as well as IL-1β at the aortic root plaque site were used to assess the inflammatory infiltration.In vitro:NETs induced by PMA and cholesterol crystals were taken as models respectively.Direct effect of Rb1 against NETs formation assessed by Sytox staining and immunofluorescence staining with Cit-H3 and myeloperoxidase.Rb1 on ROS levels was assessed by DCFH-DA.Rb1 on histone H3 citrulline modification was assessed by Western blotting.Results In vivo:Rb1 significantly inhibited plaque formation,lipid deposition(P<0.05)and intra-plaque inflammatory infiltration(P<0.05).In vitro:Rb1 significantly inhibited NETs formation(P<0.05),neutrophil ROS levels(P<0.05),and Cit-H3 levels(P<0.05).Conclusions Rb1 significantly inhibited AS progression by inhibiting plaque NETs formation,which may be partly through the inhibition of histone H3 citrullination resulting from activation of the neutrophil oxidative stress pathway.

Objective: To study the anti-gout effect of active ingredients in Poecilobdella manillensis. Methods: Hypoxanthine was used to replicate mouse model of hyperuricemia, and xylene was used to induce mouse auricle swelling model. The hot plate method and writhing method were used to screen the active site of Poecilobdella manillensis, and then the active ingredients were screened. The material basis of anti-gout effect of Poecilobdella manillensis was observed. Results: The water-soluble fraction of Poecilobdella manillensis was the active site against gout, which could reduce the level of serum uric acid in hypoxanthine-induced hyperuricemic mice and inhibit xylene-induced auricular swelling in mice, deduce acetic acid-induced writhing reaction in mice and increase the hot plate pain threshold in mice; Hirudin was the main active ingredient in water-soluble parts. Poecilobdella manillensis active ingredient 0.8 g/kg and 0.4 g/kg and Poecilobdella manillensis residue 2.0 g/kg could significantly reduce serum uric acid levels. The serum uric acid levels decreased from232.73 ± 50.93 umol/L in model group to 140.70 ± 25.97 umol/L, 149.07 ± 39.28 umol/L, 176.45 ± 44.33 umol/L, respectively (P ＜ 0.01) . Poecilobdella manillensis active ingredients 0.8 g/kg, 0.4 g/kg and 0.2 g/kg and Poecilobdella manillensis residue 2.0 g/kg could significantly inhibit xylene-induced ear auricle swelling in mice. The swelling degree was inhibited from 22.80 ± 2.86 mg to 20.10 ± 2.18 mg, 19.80 ± 2.57 mg, 20.10 ± 1.66 mg and 20.85 ± 1.60 mg respectively (P ＜ 0.05) . Poecilobdella manillensis 0.8 g/kg active ingredient could significantly reduce the number of writhing mice caused by acetic acid. The number of times was reduced from 22.80 ± 2.86 times to 20.10 ± 2.18 times (P ＜0.05) . Conclusion: Poecilobdella manillensis anti-gout activity is in water-soluble parts, and Hirudin is the main active ingredient.