The role of ferroptosis in human acute lymphoblastic leukemia and its possible molecular mechanisms of action are still unknown. In this study, harvested Molt-4 cells were exposed to different concentrations of erastin, and their proliferation capacity was tested by using the cell counting kit-8 assay. Lipid peroxidation levels were detected through flow cytometry. Mitochondrial alterations were observed through transmission electron microscopy. The expression levels of SLC7A11, glutathione peroxidase 4 (GPX4), and mitogen-activated protein kinase (MAPK) were detected by using quantitative real-time PCR and Western blot analysis. This study found that erastin inhibited the growth of Molt-4 cells. This inhibitory effect could be partially reversed by the ferroptosis inhibitor Ferrostatin-1 and the p38 MAPK inhibitor. The mitochondria of Molt-4 cells treated with erastin shortened and condensed. Compared with those in the control group, the levels of reactive oxygen species and malondialdehyde had increased, whereas the levels of glutathione had decreased in the treatment group. The treatment of Molt-4 cells with erastin decreased the levels of SLC7A11 and GPX4 mRNA and increased the expression levels of p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase. These findings suggested that erastin caused the ferroptosis of Molt-4 cells. This process may be correlated with the inhibition of the cystine/glutamate antiporter system and GPX4 and the activation of p38 MAPK and ERK1/2.
Objective To investigate the feasibility and clinical curative effect of Chinese medicine in supplementary treatment of early postoperative small bowel obstruction. Methods 76 patients with early postoperative small bowel obstruction were divided into treatment group and contrast group randomly from Jan. 2002 to Dec.2006. The mitigation time of obstruction,the operation rate and the relapse rate of obstruc-tion were compared between the two groups. Results 1 case was operated,5 cases were recurrent that cured again by Chinese medicine in the treatment group. 6 cases were operated,7 cases were cured by operation again among the 13 cases those were recurrent in the contrast group. Conclusion Chinese medicine treating the early postoperative small bowel obstruction supplementarily is economical,feasible,simple,and has well curative effect and it can improve intestinal function and reduce the mitigation time,the operation time and the relapse rate of obstruction.
ABSTRACT The envelope (E) protein of flaviviruses includes three domains, EI, EII, and EIII, and is the major protective antigen. Because EIII is rich in type-specific and subcomplex-specific neutralizing epitopes and is easy to express, it is particularly attractive as a recombinant vaccine antigen. VaxInnate has developed a vaccine platform that genetically links vaccine antigens to bacterial flagellin, a Toll-like receptor 5 ligand. Here we report that tetravalent dengue vaccines (TDVs) consisting of four constructs, each containing two copies of EIII fused to flagellin (R3.2x format), elicited robust and long-lived neutralizing antibodies (geometric mean titers of 200 to 3,000), as measured with a 50% focus reduction neutralization test (FRNT 50 ). In an immunogenicity study, rhesus macaques ( n = 2) immunized subcutaneously with 10 μg or 90 μg of TDV three or four times, at 4- to 6-week intervals, developed neutralizing antibodies to four dengue virus (DENV) serotypes (mean post-dose 3 FRNT 50 titers of 102 to 601). In an efficacy study, rhesus macaques ( n = 4) were immunized intramuscularly with 16 μg or 48 μg of TDV or a placebo control three times, at 1-month intervals. The animals that received 48-μg doses of TDV developed neutralizing antibodies against the four serotypes (geometric mean titers of 49 to 258) and exhibited reduced viremia after DENV-2 challenge, with a group mean viremia duration of 1.25 days and 2 of 4 animals being completely protected, compared to the placebo-treated animals, which all developed viremia, with a mean duration of 4 days. In conclusion, flagellin-EIII fusion vaccines are immunogenic and partially protective in a nonhuman primate model.
Objective Artificial atrial septum defect combining pulmonary artery banding to create a model of congenital heart defect with decreased pulmonary blood flow to explore the morphological changes of immature pulmonary vascular. Methods Choose twenty piglets with about one to two-month-old, which are exclusively for experiment used. The piglets were randomly divided into three groups: normal control group (group C, n = 6), Small incisions on the right chest, produced a transient reduction in pulmonary blood; low-medium pulmonary artery stenosis groups ( group T1, n = 7 ) : Did artificial room septostomy creation by self-dilators which were delivered into the surface of the right atrium and controlled Systolic trans pulmonary artery banding pressure (Trans-PABP) at pressure of 20 - 30 mmHg; severe pulmonary artery stenosis groups ( group T2, n = 7): T2 were the same surgical procedures with group T1 ,and controlled Trans-PABP ≥ 30 -50 mmHg. Monitored ultrasound after operation , carried out 64-slice computed tomography scanning after one month, to measure the proximal vessel diameter and TransPABP , after two month surgical exploration on the left chest. When the animals were sacrificed, the heart and lung tissue was cut to measure atrial septal defect, pulmonary artery and the banding diameter. By weihgt elastic fiber and van Cieson staining to observe the morphological pathological changes, three groups took lung tissue with right middle lobe lateral segment about 1.0 cm × 0.8 cm × 0.8cm at the end of surgery and 2-months after operation respectively. Results The models were all successfully in the survival animal of the two test groups. One pig died from tracheal intubation accident in the C group, there was one case died due to bowel obstruction in the T1 group, And there were two cases died result from acute right heart failure and chronic heart failure respectively in T2 group. 64-slice CT angiography showed that BD was significantly lower than the AOD in the two test groups, the proximal pulmonary vascular expansion result from stenosis, distal pulmonary vascular scarce. Histopathology showed that the pulmonary artery inside diameter of T1 and T2 was significantly higher than group C(P <0. 05,P < 0.01), and the NAPSC of two experimental groups were significantly lower than group C 2-month after operation( P <0.01).Conclusion This type of Piglet model is closer to clinical pathological and physiological ,64-slice spiral CT combined with lung histopathology observed for the evaluation of pulmonary vascular hypoplasia is a reliable method. Tunica media of pulmonary arterioles hypoplasia with the number reducing, with pulmonary artery banding increased,the degree of pulmonary arterioles hypoplasia gradually increased.
Key words:
Heart defects, congenital Animal testing alternatives Pulmonary artery Pathology Decreased pulmonary blood flow
Right coronary artery–left ventricular (RCA–LV) fistula with associated giant right coronary artery aneurysm (CAA) is an extremely rare cardiac condition. This case study presents a patient with a large left ventricle (LV) and a giant right CAA with a maximal inner diameter of approximately 56.6 mm and an inner diameter of approximately 22 mm at its communication with the left ventricle. The patient underwent surgical management, involving suturing of the proximal end of the CAA and coronary artery bypass grafting (CABG). RCA–LV fistula with a giant right CAA may involve serious complications, such as thrombosis, rupture, and heart failure. Therefore, it is necessary to establish effective management strategies for this condition. Although this case is not unique, it serves as an illustrative example of the implementation of a classic surgical treatment method.
In response: Cox's letter (1) contains a number of false assumptions, errors, misleading assertions, and misquotations.Cox asserts that annually 1 person or fewer in the United States will experience an adverse effect because of fluoroquinolone use in poultry.He reduces 10-fold my referenced risk for persons acquiring Campylobacter infections from poultry (2).His unrealistically low estimate is not given in his referenced citation.His estimated risk is also much lower than in the reference 2, which Cox himself quotes, "Poultry is the most common cause of sporadic cases of campylobacteriosis in the United States" (Economic Research Service of the US Department of Agriculture) (3).Cox knows that his assertion (4) that poultry make little or no contribution to human Campylobacter infections has been extensively examined and found to be wrong.Indeed, an entire section in a recent US Food and Drug Administration (FDA) determination was written about the unreliability of Cox's testimony and these assertions, a finding made by both the FDA commissioner and an administrative law judge (5,6).Cox also misquotes Busby et al.(3) when he asserts that only 0.6% of persons with Campylobacter infections benefit from antimicrobial drugs.The Busby article states that 0.6% of persons with Campylobacter infections need "hospitalization," not how many would benefit from antimicrobial drug therapy.Cox has thus made a misleading attribution (something he has previously been found to do [5]).Busby et al.(3) estimated that in 1993, ≈1,500,000 persons in the United States acquired Campylobacter infections from food sources.Even if the proportion who can benefit from receiving antimicrobial drugs is as low as 2%, this translates to 30,000 persons.If 20% of these infections were caused by fluoroquinolone-resistant Campylobacter spp., then 6,000 persons would potentially have their therapy and outcome compromised, rather than the 1 person that Cox would have us believe.More realistic is the figure of 24,000 persons estimated previously to be at risk of having an adverse outcome (or ≈285 persons for every 1 million chickens treated with fluoroquinolones) (1).Cox's assumptions and calculations thus seem flawed and unrealistic.
Objective
To investigate the treatment of auricle and periauricular arteriovenous malformations.
Methods
This is a retrospective study of 30 patients with auricle and periauricular arteriovenous malformations in Changfeng Hospital from February 2012 to March 2017. First, the patients were treated with anhydrous ethanol embolization, followed by transcatheter or direct percutaneous injection of anhydrous ethanol into the malformed vascular tissues. Angiography was performed every time with ethanol injection. The volume of malformed vascular tissues and injection pressure and speed were measured by hand-push angiography. The injection speed of the contrast agent was usually 0.2 ml/s, and malformed vascular tissue volume equal to the dose of the contrast medium filled with the malformed vascular tissues. With the same dose, injection pressure and speed, anhydrous ethanol was injected until all or part of the lesion was cured. The series of treatments were performed with the interval of 1 to 2 months. After embolization, wedge resection combined with lesion was performed to improve the shape of auricle, and to repair the defect of auricle in the cases of obvious auricle hypertrophy. The skin flap adjacent to the auricle was used to treat the auricle defect caused by embolization.
Results
The clinical manifestations of 30 patients such as ulcer, bleeding and tinnitus, were improved after 3 times of ethanol embolization. Angiography showed that the abnormal vascular mass completely disappeared in 8 patients. The vascular mass was shrunken by 50% to 75% in 15 patients, and that of 7 patients shrunken less than 50%. Six cases with obvious hypertrophic deformation of auricle were treated with wedge-shaped resection of auricle lesion to reduce the auricles. Three patients suffered partial auricle necrosis after ethanol embolization. They were treated with periauricular pedicle flap to repair the defects.
Conclusions
Sequential embolization with anhydrous ethanol could effectively improve the clinical manifestations and control the development of the lesions in patients with auricular arteriovenous malformations. When the auricle was obviously hypertrophic and deformed, the shape of the auricle could be improved with surgery.
Key words:
Arteriovenous malformation; Auricle; Anhydrous ethanol; Sclerotherapy; Reconstructive surgical procedures