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Immune checkpoint inhibitors significantly improves the prognosis of patients with advanced malignancy, but it is also associated with off-target toxicity caused by activation of the immune system, known as immune-related adverse events (irAEs). Severe irAEs will lead to temporary or permanent termination of immunotherapy, which greatly affects its clinical application. At present, glucocorticoids are mainly used to treat irAEs clinically. On one hand, severe adverse reactions will cause serious damage to patients' health; on the other hand, the extensive application of glucocorticoids will affect the efficacy of immune checkpoint inhibitors. In recent years, TNF-α inhibitors have shown significant effect in reducing toxic and side effects. This paper reviews the progress of TNF-α in preventing and treating irAEs.
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Objective To investigate the characteristic changes of biochemical markers of mineral metabolism, vascular calcification, and renal osteodystrophy in an adenine-induced rat model of chronic kidney disease (CKD). Methods A total of 20 male Sprague Dawley rats (SD rats) were randomly divided into two groups: the normal group fed with a diet without adenine, and the CKD group fed with an adenine-containing diet (7. 5 g/kg) for the first 4 weeks and then a diet without adenine for the following 2 weeks. At the end of the 2nd week, serum biochemical markers were detected. At the end of the 6th week, the SD rats were sacrificed and serum biochemical markers were detected once again. The aortas were collected for pathological examination and detection of vascular calcium and phosphorus contents. Femurs and the fifth lumbar vertebrae were taken for bone mineral density (BMD) measurement and bone histomorphometric analysis. Results At the end of the 2nd and 6th weeks, compared with the normal control group, the levels of serum creatinine, urea nitrogen, phosphorus and parathyroid hormone (PTH) in the CKD group were significantly increased (P＜0. 05 or P＜ 0. 01), and the level of serum calcium was significantly decreased (P＜ 0. 05 or P＜ 0. 01). Medial layer vascular calcification of the aorta occurred in 50％ of the rats in the CKD group, but was not observed in the normal control group. Vascular calcium and phosphorus contents were significantly higher in the CKD group compared with the normal control group (P＜ 0. 05). The BMD of total femur, cortical and trabecular bone tissues of the femur, and the fifth lumbar vertebra was significantly decreased in the CKD group (P＜ 0. 05 or P＜ 0. 01). The histomorphometric analysis showed that both bone resorption and bone formation of the trabecular bone in the CKD group were increased, indicating a high bone turnover status. The volumes of both trabecular and cortical bones of rats in the CKD group were significantly lower than that of the normal control group (P ＜ 0. 05 or P ＜ 0. 01). However, the trabecular bone mineralization was not significantly different between the two groups. Conclusions The adenine-induced rat model of chronic kidney disease (CKD) established in this study shows reduced serum calcium and increased serum phosphorus and PTH, and medial layer vascular calcification of the aorta. With respect to renal osteodystrophy, this model shows a high trabecular bone turnover, normal trabecular bone mineralization, and low bone volume of cortical and trabecular bone, which meets the characteristics of osteitis fibrosa. This model may become a useful tool for future study of chronic kidney disease-mineral and bone disorder (CKD-MBD).
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Objective:To explore and compare the clinical efficacy of lyophilized recombinant human brain natriuretic peptide (Lrh-BNP) and dobutamine (Dob) in the treatment of patients with acute heart failure (AHF) and impacts on the plasma galectin (Gal)-3,Cystatin C (CysC) and endothelin (ET-)-1 levels.Methods:114 cases of patients with AHF in our hospital from February 2015 to February 2017 were selected as the research objectives and randomly divided into two groups.Dob group was treated by Dob,while Lrh-BNP group was treated by Lrh-BNP.The cardiac function parameters,plasma Gal-3,CysC,ET-1 levels before and after treatment,clinical comprehensive efficacy and incidence of adverse reactions were compared between two groups.Results:The FS,LVEF levels of both groups at 72 hours after treatment were significantly higher than those before treatment (P＜0.01),but the LVEDD,plasma Gal-3,CysC,ET-1 levels were obviously decreased (P＜0.01),the index mentioned above of Lrh-BNP group improved more significantly than those of the Dob group(P＜0.01).The overall effective rate of Lrh-BNP group was 89.5 ％,which was significantly higher than that of the Dob group (73.7％,P＜0.05).No significant difference was found in the incidence of adverse reaction between two groups(P＞0.05).Conclusion:Lyophilized recombinant human brain natriuretic peptide was more effective in the treatment of AHF than Dobutamine with equal safety,which might be related to the decrease of plasma Gal-3,CysC,ET-1 levels.
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<p><b>OBJECTIVE</b>The decoction of Astragali Radix and Angelicae Sinensis Radix (A&A) has shown antifibrotic effects in rats with unilateral ureteral obstruction (UUO). The aim of this study was to track the effective parts of A&A for its renoprotective effects, according to the improvement of renal function and renal tubulointerstitial damage.</p><p><b>METHOD</b>A&A was sequentially extracted by using different solvents for three times and eleven different parts were gained. Wistar rats were randomly divided into Sham, UUO and the treatment groups with A&A or each part of A&A. After administration of A&A or its parts for 10 days, the levels of serum creatinin (Scr) and urea were measured. The morphological changes of kidneys were also semi-quantitatively analyzed by HE, Masson stained tissue sections, which including interstitial cell infiltration, tubular atrophy and interstitial fibrosis.</p><p><b>RESULT</b>The levels of Scr, urea were significantly increased, accompanied with severe renal damage in rats with UUO. As same as A&A, the part I in the first extraction and part IC in the second extraction were all shown to decrease the levels of Scr and urea and the index of renal interstitial damage. However, the following 4 parts extracted from IC in the third extraction were shown no effect on the above indexes.</p><p><b>CONCLUSION</b>The extract part I and part IC could be considered as the predominant parts of A&A for its renoprotective effects, due to their improvement of renal damage in interstitial nephropathy.</p>
Subject(s)
Animals , Humans , Male , Rats , Angelica sinensis , Chemistry , Astragalus Plant , Chemistry , Chronic Disease , Therapeutics , Disease Models, Animal , Drugs, Chinese Herbal , Kidney Diseases , Drug Therapy , Protective Agents , Random Allocation , Rats, WistarABSTRACT
Objective: To investigate the preventive and theraputic effects of Astragalus and Angelica mixture(A&A)on renal tubulointerstitial fibrosis after unilateral ureteral obstruction(UUO)in rats and their mechanisms. Methods: UUO rats were randomly divided into Sham, UUO, A&A or ACEI groups. A&A, ACEI or the same amount of water was administered by gavage beginning 24 hours before UUO preparation and continued through ten days after UUO. Sera and the kidney tissues were collected from each group on the tenth day. Scr and BUN were measured. Trichrome staining, measurement of tubulo interstitial damage index and immunohistochemical studies localizing ? smooth muscle actin(? SMA), TGF ? 1, fibronectin(FN), laminin(LN)were carried out. Results: In UUO rats, the tubular interstitial damage index, the expressions of ? SMA, TGF ? 1, FN and LN were all increased compared with those of Sham group. The tubulo interstitial damage index had positive correlation with expressions of ? SMA, TGF ? 1, FN and LN. A&A significantly ameliorated deterioration of renal function, tubulo interstitial damage index and inhibited the over expressions of ? SMA, TGF ? 1, FN and LN in UUO rats. These anti fibrotic effects were similar to those affected by ACEI. Conclusion: In renal interstitial fibrosis induced UUO rats, A&A retard the progression of renal fibrosis and renal function deterioration by inhibiting myofibroblasts and suppressing TGF ? 1 expression, which may consequently result in a decreased production of extracellular matrix.
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ObjectiveTo study the clinical and pathological characteristics of tubulointerstitial nephropathy associated with Chinese herb patent Guan Xin Su He Wan(GXSHW-TIN).Methods15 patients with GXSHW-TIN were studied.Clinical and pathological data were semi-quantitatively assessed.Relationships between medication and the incidence,clinical characteristics and the outcome of the disease were analyzed.ResultsAll the patients had chronic renal failure when GXSHW-TIN was diagnosed.They all got the disease after long-term taking of GXSHW in routine dosage.Most of the patients presented gastrointestinal dysfunction,abnormal urine analysis and mild to moderate anemia as onset symptoms.The pathological characteristics were similar to those of Guanmutong(Aristolochia manshuriensis Kom) induced chronic aristolochic acid nephropathy(AAN).ConclusionLong-term taking of GXSHW,which contains Radix Aristolochiae,might induce AAN.It indicates that GXSHW should be causious for clinical use,the ban of Radix Aristolochiae in the pharmaceutical market needs to be considered for prevention of AAN.
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Chinese compound priscriptions of traditional herbs are widely used in the alternative therapy for all kinds of diseases It remains unclear how the compounds in different herbs interact each other and which exacting mechanism can complain their effects The components and pharmacological effects of the combination of Chinese herbs are not due to the simple mixture of single herb's The substance basis research of combination herbs is one of the important issue for understanding their pharmacological mechanism Here the recent progress on the substance basis research of combination Chinese traditional herbs is reviewed, including the combinative effects and quantity ratio relation study, herbs serum study, chemical compounds research, the methods and techniques in chemical components analysis, and application foreground of Chinese compound priscription