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ObjectiveTo investigate the effect and mechanism of Zhenwutang on renal oxidative damage in the mouse model of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency via the nuclear factor erythroid 2-related factor-2 （Nrf2）/heme oxygenase-1 （HO-1）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodTwenty-five 7-week-old SPF-grade male db/m mice and 95 7-week-old SPF-grade male db/db mice were adaptively fed for a week. A blank group was set with the db/m mice without treatment， and the other mice were administrated with Rhei Radix et Rhizoma decoction and hydrocortisone for the modeling of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency. The modeled mice were randomized into the model， irbesartan （25 mg·kg-1）， and high-， medium-， low-dose （33.8， 16.9， 8.45 g·kg-1） Zhenwutang groups （n=15） and administrated with corresponding drugs for 8 weeks. The survival status of mice was observed， and the traditional Chinese medicine （TCM） syndrome score was recorded. The indicators related to spleen-kidney Yang deficiency， fasting blood glucose （FBG）， and renal function indicators were determined. Hematoxylin-eosin staining was employed to observe the histopathological changes of the renal tissue in each group. Biochemical kits were used to determine the oxidative stress-related indicators in the renal tissue. Real-time polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Nrf2， HO-1， glutamate-cysteine ligase catalytic subunit （GCLC）， and GPX4 in the renal tissue of mice in each group. ResultCompared with the blank group， the modeling increased the TCM syndrome score （P<0.05）， elevated the estradiol （E2） and FBG levels （P<0.05）， lowered the testosterone （T）， triiodothyronine （T3）， and tetraiodothyronine （T4） levels （P<0.05）， and weakened the renal function （P<0.05）. In addition， the modeling led to glomerular hypertrophy and glomerular mesangial and basal thickening， decreased the catalase （CAT） activity， total antioxidant capacity （T-AOC）， and glutathione （GSH） content （P<0.05）， increased the malondialdehyde （MDA） content （P<0.05）， and down-regulated the mRNA and protein levels of Nrf2， HO-1， GCLC， and GPX4 in the renal tissue （P<0.05）. Compared with the model group， high and medium doses of Zhenwutang decreased the TCM syndrome score and E2 content （P<0.05）， increased the T， T3， and T4 content （P<0.05）， improved the renal function （P<0.05）， alleviated the pathological changes in the renal tissue， increased CAT， T-AOC， and GSH （P<0.05）， reduced MDA （P<0.05）， and up-regulated the mRNA and protein levels of Nrf2， HO-1， GCLC， and GPX4 in the renal tissue （P<0.05）. ConclusionZhenwutang can improve the general state and renal function and reduce the oxidative damage and pathological changes in the renal tissue of db/db mice with spleen-kidney Yang deficiency by regulating the Nrf2/HO-1/GPX4 signaling pathway.
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Hepatic fibrosis （HF） is a widespread disease caused by various forms of chronic liver injury， significantly impacting human health. HF often has an insidious onset with inconspicuous symptoms， but in its advanced stages， it can progress to cirrhosis or even hepatocellular carcinoma. The pathogenic mechanisms of HF are highly complex， primarily characterized by excessive extracellular matrix （ECM） deposition. Autophagy is a lysosome-mediated degradation system employed by cells to recycle cellular contents， eliminate aggregated proteins， damaged organelles， and invading pathogens （such as viruses and bacteria） to maintain normal cellular function and dynamic balance. Autophagy can regulate various signaling pathways and factors， including mammalian target of rapamycin （mTOR）， adenosine monophosphate-activated protein kinase （AMPK）， and transforming growth factor-β （TGF-β）， to reduce the activation of hepatic stellate cells （HSCs） and hepatocyte necrosis and apoptosis， thereby mitigating ECM deposition and slowing the progression of HF. Numerous studies also suggest that traditional Chinese medicine （TCM） can effectively treat HF， and its mechanism of action may be related to autophagy. This article provides a review by summarizing recent literature in China and abroad on the mechanisms of autophagy， related signaling factors and pathways， as well as the role of TCM in regulating autophagy for the prevention and treatment of HF， aiming to offer insights and references for the development of TCM in the prevention and clinical rational medication in the treatment of HF.
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Diabetic nephropathy （DN）， a major cause of chronic kidney disease （CKD）， aggravates the prevalence of end-stage renal disease （ESRD） and threatens human health. The pathogenesis of DN is complex， in which inflammation is a key pathological link in the cascade injury. Therefore， the treatment targeting inflammation helps to delay the progression of DN. NOD-like receptor protein 3 （NLRP3）， a classical proteasome， acts as an inducer of innate immune responses. The activated NLRP3 inflammasomes produce and release inflammatory mediators to trigger pyroptosis and uncontrolled autophagy and mediate the stress signals promoting renal fibrosis， thus participating in the development and progression of DN. The NLRP3 inflammasome as a core site inducing inflammation is widely involved in DN progression and may be a novel target. The active components and compound prescriptions of Chinese medicines are increasingly applied in the prevention and treatment of DN. The latest studies have discovered that Chinese medicines can treat DN by regulating the activation of NLRP3 inflammasomes. Although studies have been conducted to explore the mechanism of Chinese medicines in the treatment of DN via NLRP3 inflammasome， the systematic review remains to be carried out. This paper reviews the relevant publications in recent years and introduces the research progress from the assembly and activation of NLRP3 inflammasomes， the mechanism of NLRP3 inflammasomes in the treatment of DN， and the regulation of NLRP3 inflammasomes by Chinese medicines for the prevention and treatment of DN， aiming to lay a foundation for the relevant studies and provide new targets and strategies for the prevention and treatment of DN.
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Objective To study the mechanism of ferulic acid(FA)on hepatic fibrosis(HF)based on network pharmacology,and establish an in vitro model of rat hepatic stellate Cell-T6(HSC-T6)according to the results.Methods The potential targets of FA were screened through PubChem,swisstargetprediction and pharmmapper,and overlapped with the FA targets screened in disgenet,genecards and OMIM.Then,protein protein interaction(PPI)was analyzed by using string platform.Gene ontology(go)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out for key targets by using R64 4.0.3,and the"component target disease"network diagram was constructed by Cytoscape 3.7.2 software.Based on this,the proliferation of HSC-T6 was detected by cell counting kit-8(CCK-8)method,and the grouping was determined:blank group and low-dose group(100 μg·mL-1 FA),medium dose group(200 μg·mL-1 FA),high dose group(400 μg·mL-1 FA)and positive control group(200 μg·mL-1 colchicine),the migration ability of HSC-T6 was detected by scratch test,and the content of HSC-T6 was detected by enzyme linked immunosorbent assay(ELISA)α-Alpha smooth muscle actin,α-Flow cytometry was used to detect the changes of HSC-T6 cycle,quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the relative expression of JAK2 and STAT3 mRNA,and Western Blot was used to detect the molecular expression of JAK2 and STAT3 protein.Results 254 intersection targets of FA and HF were obtained.The core targets were signal transducer and activvator of Transcription(STAT3),albumin(ALB),protein kinase B(AKT1),tumor suppressor protein p53(TP53),epidermal growth factor receptor(EGFR)and caspase-3(CASP3).KEGG analysis showed that the action pathway of FA on HF mainly involved phosphatidylinositol 3 kinase protein kinase B(PI3K-Akt),vascular endothelial growth factor(VEGF),Janus kinase/signal transducer and activator of transcription(JAK/STAT)Tumor necrosis factor(TNF)and other pathways.The experimental results showed that in CCK-8 experiment,scratch experiment and ELISA experiment,compared with the blank group,the cell proliferation rate,migration ability and the expression of α-SMA protein decreased significantly(P<0.05).Compared with the blank group,the cycle arrest rate of low,medium and high dose groups and positive control group increased significantly(P<0.05).Compared with the blank group,the molecular weight and mRNA expression of JAK2 and STAT3 protein in low,medium and high dose groups and positive control group decreased gradually(P<0.05).Conclusion FA has the characteristics of multi-channel and multi-target.FA may inhibit the apoptosis of hepatic stellate cell(HSC)by down regulating JAK2 and STAT3 targets.
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In prospective cohort study, multi follow up is often necessary for study subjects, and the observed values are correlated with each other, usually resulting in time-dependent confounding. In this case, the data generally do not meet the application conditions of traditional multivariate regression analysis. Sequential conditional mean model (SCMM) is a new approach that can deal with time-dependent confounding. This paper mainly summarizes the basic theory, steps and characteristics of SCMM.
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OBJECTIVE:To evaluate the affordability of 3 anti-tumor targeted drugs gefitinib,trastuzumab and sunitinib in ur-ban and rural residents of Hubei province,and to provide reference for medical insurance price admission of anti-malignant tumor targeted drugs in China. METHODS:Referring to the incidence of malignant tumor stated in statistical yearbook of Hubei province and income data of urban and rural residents in Hubei province,based on the policy of reducing the price of imported drugs by 50% mentioned in the national drug price negotiations,and assume the drugs are included in the medical insurance reimbursement list,WHO/HAI standard survey method,catastrophic expenditure evaluation method and poverty effect evaluation method were ad-opted to calculate the affordability of 3 drugs. RESULTS:According to WHO/HAI standard survey method,increment of payment for 3 drugs were 64.00%-74.00% before and after 50% discount and reimbursement. According to catastrophic expenditure evalua-tion method,50% discount of gefitinib and reimbursement gefitinib,trastuzumab and sunitinib in urban area would result in cata-strophic expenditures of 20.00%、59.28% and 35.48% patients;in rural area,would result in catastrophic expenditures of 50.63%、74.72% and 75.93% patients. According to poverty effect evaluation method,50% discount of 3 drugs and reimbursement caused less than 31.95% urban and rural patients falling to poverty. CONCLUSIONS:Fifty percentage discount of 3 anti-tumor targeted drugs mentioned in the national drug price negotiations cause the economic burden more serious for rural residents than urban resi-dents. In the formulation of policies,the corresponding reimbursement ratio should be adjusted according to urban and rural areas, drug price and disease types for a balance of patients with different economic burden.
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Objective: To analyze the New Cooperative Medical System ( NCMS ) funds and Individual afford-ability of anti-tumor targeted drugs under different medical insurance entry price, and to provide the basis for establis-hing the access price for medical insurance. Methods: Choosing Conmana or Kemer ( the lung cancer targeted drug) and Herceptin (breast cancer targeted drug) to analyze the Wuhan NRCMS operating status from 2012 to 2014, use tumor surveillance data from Hubei Province during the period from 2011 to 2015;consult clinical experts to form expert consensus price, refer to the Jiangsu Province Access Price and National Negotiation Price, and explore the fund bal-ance and individual affordability when the afore-mentioned two kinds of drugs can be compensated by medical insurance under different price. Results:The basic account balances of NRCMS in Wuhan from 2016 to 2018 are-11. 948 million Yuan, 2. 513 million Yuan and 82. 955 million Yuan when Kemer can be compensated by medical insurance under Na-tional Negotiation Price. Taking the compensation of Herceptin under National Price after the bargaining, the basic ac-count balances are -26. 901 million Yuan,-35. 962 million Yuan and 17. 542 million Yuan respectively. The rate of poverty caused by illness falls to 33. 40% from 45. 85% when Conmana can be compensated by Medical Insurance un-der National Negotiation Price, while this rate falls to 45. 42% from 46. 00% for Herceptin. Conclusion:The two kinds of drugs can be afforded by the Wuhan NRCMS after the medical insurance access price is negotiated by the govern-ment, but the individual affordability of Herceptin at the National Negotiation Price is worse.
