10.3969/j.issn.1007-3969.2013.04.011

Objective CD44, a cell surface glycoprotein, plays an important role in tumor growth and glycolysis.The aim of this study was to investigate the effects of neutralizing CD44 antibodies on the growth and glycolytic metabolism of B16 cells in melanoma in vitro.Methods B16 cells were treated with control antibodies (50 μg/mL) or different concentrations of CD44 antibodies (2, 10, and 50 μg/mL) for 24 hours, followed by examination of the activation of the AKT pathway in the B16 cells by Western blot.Then the tumor cells were also treated with control antibodies (50 μg/mL) or CD44 antibodies (50μg/mL) after pretreated with API-2 (4 μmol/L) in a parallel test.After 48 hours of treatment, the expression of lactate dehydrogenase A (LDHA) in the B16 cells and the level of lactate in the culture supernatant were detected by immunofluorescence and colorimetry, respectively.Lastly, the B16 cells were treated with control antibodies (50μg/mL), API-2 (4 μmol/L), CD44 antibodies (50μg/mL), or API-2 + CD44 antibodies for 96 hours, followed by measurement of the proliferation of the cells by MTT and their apoptosis by AO/EB and AnnexinV staining.Results In comparison with the control antibody group, the level of AKT phosphorylation (p-AKT) in the B16 cells showed a concentration-dependent increase in the 2, 10, and 50 μg/mL CD44 antibody groups (1.00±0.25 vs 2.51±0.32, 3.89±0.46, and 4.07±0.42, P<0.01), and the expression of LDHA was increased by (2.13±0.24) times, with the lactate level in the culture supernatant significantly elevated from (35.32±3.24) to (56.34±8.19) mmol/L (P<0.01) after 96 hours of treatment with 50 μg/mL CD44 antibodies.Treatment with API-2+CD44 antibodies, however, suppressed the increase in the LDHA expression and reduced the level of lactate.Compared with the control antibody group, the proliferation rate of the B16 cells was markedly decreased in the API-2, CD44 antibody, and API-2+CD44 antibody groups ([103±12.91] vs [84.87±19.35], [71.35±16.23], and [41.16±9.15]%, P<0.05), while the apoptosis rate remarkably increased ([5.23±0.96] vs [13.65±4.27], [19.21±3.53], and [43.21±7.87]%, P<0.01).Conclusion Neutralizing the function of CD44 in the B16 cells in vitro can inhibit the growth of the cells and promote AKT-mediated glycolytic metabolism, while suppressing the AKT pathway may enhance the antitumor activity of the CD44 antibody.

Chronic heart failure(CHF)is the performance of end-stage cardiovascular disease and the leading cause of death in recent years.With the rapid development of medical care,the mortality rate of heart failure is still high.This is one in the two major challenges in the cardiovascular field in the 21st century.The new drug LCZ696 is a dual inhibitors of angiotensin receptor blockers(ARB)and neprilysin(NEP),which may lead to new hope for patients with heart failure.In order to determine the efficacy and safety of LCZ696 in the treatment of heart failure,foreign countries have carried out some large-scale trials,such as PARAMOUT, PARADIGM,TITRATION and so on.The results of these studies reflected the superiority of LCZ696 compared with enalapril,valsartan and other drugs in the treatment of chronic heart failure.ARB/antiotensin converting enzyme inhibitors(ACEI)targets the angiotensin receptor to dilate blood vessels and inhibits the sympathetic nerve,but their effects on sodium withdrawal and diuresis are weak.The sacubitril in LCZ696 prevents natriuretic peptide from degrading,strengthens the natriuretic diuretic and further expansion of blood vessels.Thereby it improves water and sodium retention and cardiac function.It can play a better synergistic role combined with valsartan.

OBJECTIVE To monitor the occurrence of tenofovir disoproxil fumarate （TDF）-induced kidney injury and investigate the risk factors， and provide reference for rational use of TDF in clinic. METHODS The information of inpatients with hepatitis B was collected by China Hospital Pharmacovigilance System （CHPS） from the Second People’s Hospital of Lanzhou during Jan. 1st， 2019 to Dec. 31st 2021. The search criteria were set according to kidney injury criteria， and suspected TDF- induced kidney injury cases were actively monitored； then the clinical pharmacist confirmed the positive patients with TDF-induced kidney injury one by one and calculated the incidence of TDF-induced renal injury； the risk factors for TDF-induced kidney injury in real world were explored by collecting and analyzing the correlation of basic data of patients， main indexes of liver and kidney function， complications and combined use of drugs with TDF-induced renal indexes. RESULTS Totally 1 226 inpatients with hepatitis B using TDF were included. Through active monitoring of CHPS， 160 suspected patients with TDF-induced kidney injury were found， and 64 positive patients were finally confirmed manually. The incidence of TDF-induced kidney injury was 5.22%. Compared with pre-medication， the levels of serum creatinine and cystatin C， the proportion of patients with urinary protein 2+ and above were increased significantly after medication （P＜0.001）， glomerular filtration rate and blood phosphorus level were reduced significantly （P＜0.001） and other indicators had no statistical difference. Treatment time for more than 36 months， disease progresses to decompensated cirrhosis， and concomitant use of more than 10 kinds of drugs were significantly correlated with TDF- related kidney injury （P＜0.05 or P＜0.012 5）. CONCLUSIONS The active monitoring scheme of TDF-induced kidney injury established by CHPS has the characteristics of time-saving， labor-saving and high efficiency； based on real-world evidence， it is imperative to strengthen monitoring kidney function of patients when using TDF， especially when the patient has been on medication for a long time， in decompensated cirrhosis and combination of multiple drugs， and thus， we can identify earlier and avoid adverse effects in high-risk patientseffectively.