ABSTRACT
Immune checkpoint inhibitors (ICIs) are widely used in clinic, and the incidence of rare adverse events are increasing. The aim of this paper is to better define the rare adverse effect of diabetes mellitus associated with ICIs. We report 2 cases of diabetes mellitus associated with ICIs. Literature review was conducted and we discussed the clinical presentation, potential mechanisms and suggestions for optimal management. Two patients were both elderly women, case 1 had increased blood glucose after 7 months of using Durvalumab, and cases 2 had diabetic ketoacidosis after 6 weeks of using Pembrolizumab. Both patients were administered exogenous insulin to control blood glucose. Case 1 has been treated with Durvalumab until now and case 2 discontinued using of Pembrolizumab. HLA genotypes and other factors may explain the risk factors of diabetes associated with ICIs in some individuals. Diabetes mellitus associated with ICIs is an uncommon but potentially life-threatening endocrine system adverse event, which requires doctors to be vigilant. The patients who use ICIs need to monitor blood glucose. If they have hyperglycemia, endocrinologists should be asked to assist in diagnosis and treatment. .
Subject(s)
Aged , Female , Humans , Blood Glucose , Diabetes Mellitus/drug therapy , Immune Checkpoint Inhibitors/adverse effects , Lung Neoplasms/drug therapyABSTRACT
Objective To evaluate the effect of oxycodone preconditioning on liver injury induced by intestinal ischemia-reperfusion (I/R) in rats and the role of different opioid receptors.Methods Fiftyfour adult male Sprague-Dawley rats, weighing 200-300 g, were randomly divided into 9 groups (n =6 each) using a random number table: sham operation group (group S), group I/R, oxycodone preconditioning group (group OP) , μ receptor antagonist CTOP group (group CTOP) , δ receptor antagonist naltrindole group (group NTD), κ receptor antagonist nor-binaltorphimne group (group BNI), CTOP + oxycodo ne preconditioning group (group CTOP+OP) , naltrindole + oxycodone preconditioning group (group NTD+ OP) , and nor-binaltorphimne + oxycodone preconditioning group (BNI+OP).The model of intestinal I/R was established by occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion in anesthetized rats.The superior mesenteric artery was only exposed, but not occluded in group S.In OP,COTP+OP, NTD+OP and BNI+OP groups, oxycodone 0.5 mg/kg was injected intravenously at 10 min prior to ischemia.COTP 1 mg/kg and naltrindole 5 mg/kg were injected intravenously at 20 min prior to ischemia in COTP+OP and NTD+OP groups, respectively.Nor-binaltorphimne 5 mg/kg was injected intravenously at 25 min prior to ischemia in group BNI+OP.In CTOP and NTD groups, the corresponding doses of CTOP and naltrindole were injected intravenously at 10 min prior to ischemia.In group BNI, the corresponding dose of nor-binaltorphimne was injected intravenously at 15 min prior to ischemia.The rats were sacrificed at 2 h of reperfusion, and left hepatic lobes were removed for microscopic examination and for detection of apoptosis in liver cells (using TUNEL).The apoptosis index (AI) was calculated.Results Compared with group S, the AI was significantly increased in the other groups (P＜0.05).Compared with group I/R, the AI was significantly decreased (P＜0.05) , and the pathological changes of livers were reduced in OP, COTP+OP, NTD+OP and BNI+OP groups, and no significant change was found in AI and pathological changes of livers in CTOP, NTD and BNI groups (P＞0.05).Compared with group OP, the AI was significantly increased (P＜0.05), and the pathological changes of livers were aggravated in COTP+ OP, NTD+OP and BNI+OP groups.There was no significant difference in AI and pathological changes of livers among groups COTP+OP, NTD+OP and BNI+OP (P＞0.05).Conclusion Oxycodone preconditioning can mitigate liver injury induced by intestinal I/R in rats, and μ, δ and κ receptors mediate the role with comparable effects.
ABSTRACT
Objective To evaluate the influence of preconditioning with and anti-myosinmonoclonal antibody (mAb2G4)-nuclear factor-kappa B decoy oligodeoxynucleotide (ODN)-lipofectamine (lip) on hypoxia-reoxygenation (H/R) injury in H9c2 cardiomyocytes.Methods H9c2 cardiomyocytes were seeded in 6-well plate at the density of 1×105/ml (2 ml/well),and were divided into 3 groups (n=9 each) using a random number table:control group (group C),H/R group and mAb2G4-ODN-lip group (group MOL).The cells underwent 2 h of hypoxia in an air-tight bag,followed by 1 h reoxygenation.In MOL group,the cells were treated with mAb2G4-ODN-lip (2 μg ODN) for 4 h and then cultured in the common culture medium for 8 h before hypoxia.At the end of reoxygenation,proliferation of cells was measured using MTT assay,and the cells and supernatant of the culture medium were collected to determine the activity of lactate dehydrogenas (LDH),content of malondialdehyde (MDA),concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (by ELISA).The rate of proliferation inhibition was calculated.Results Compared with group C,the rate of proliferation inhibition,LDH activity,MDA content,and concentrations of TNF-α and IL-6 were significantly increased in the other two groups.Compared with group H/R,the rate of proliferation inhibition,LDH activity,MDA content,and concentrations of TNF-α and IL-6 were significantly decreased in MOL group.Conclusion mAb2G4-ODN-lip can mitigate H/R injury in H9c2 cardiomyocytes.
ABSTRACT
<p><b>BACKGROUND AND OBJECTIVE</b>Skeletal metastase is one of the most common complications related to advanced cancer. The aim of this study is to analyze the effectiveness and safety of radiotherapy plus intravenous bisphosphonates versus radiotherapy alone for treating bone metastasis.</p><p><b>METHODS</b>We searched the Cochrane Library, PubMed, EMBASE, CBM, CNKI and VIP, as well as the reference lists of reports and reviews. The quality of included trials was evaluated by the Cochrane Handbook. Data were extracted and evaluated by two reviewers independently. The Cochrane Collaboration's Rev-Man 5.0 was used for data analysis.</p><p><b>RESULTS</b>Twenty-two trials involving 1 585 patients were included. Compared with radiotherapy alone, radiotherapy plus intravenous bisphosphonates was more effective in total effective rate of pain relive (RR = 1.21, 95% CI: 1.13-1.30, P < 0.001), average abated time (WMD = 16.00, 95% CI: 10.12-21.88, P < 0.001), and quality of life (RR = 1.25, 95% CI: 1.08-1.45, P = 0.003, with significant differences. Side effects have no significant differences between the two groups except fever (RR = 5.61, 95% CI: 3.11-10.13, P < 0.001).</p><p><b>CONCLUSION</b>Current evidence supports more effective of radiotherapy plus intravenous bisphosphonates for bone metastases. The combine treatment is safe and effective.</p>
Subject(s)
Humans , Bone Neoplasms , Psychology , Therapeutics , Combined Modality Therapy , Diphosphonates , Therapeutic Uses , Quality of LifeABSTRACT
With computer and manual search of literatures on the comparison of concurrent with sequential adjuvant radio-chemotherapy after mastectomy for breast cancer, 4 eligible randomized controlled trials were found; the RevMan 5.0 software was used for Meta-analysis. The results showed that concurrent radio-chemotherapy reduced local recurrence more prominently than sequential radio-chemotherapy in patients with positive axillary lymph nodes( P = 0. 003 ). However, differences in 5-year overall survival,5-year disease-free survival and metastasis-free survival between two groups were not significant (P =0. 670,P =0. 200, P =0. 350).