Cyclic adenosine monophosphate involvement in low-dose cyclophosphamide-reversed immune evasion in a mouse lymphoma model

Lymphoma cells mobilize many mechanisms to evade the immune system. There is substantial evidence that CD4⁺CD25⁺ regulatory T cells (Tregs) play a key role in the control of immune evasion. Tregs can transfer cyclic adenosine monophosphate (cAMP) to effector T cells, suggesting an association between Tregs'' immune-evasion role and the intracellular cAMP pathway. In this study, we used A20 B-cell lymphoma mice as aggressive tumor models to investigate the mechanism of the depletion of Tregs by low-dose cyclophosphamide (CY, 20 mg/kg). The tumor-bearing mice had longer survival times and slower tumor growth rates following treatment with CY, but its effects were temporary. Along with the depletion of Tregs by low-dose CY treatment, the expression of interleukin-2 (IL-2) in T effector cells increased, and intracellular cAMP concentrations in immune cells decreased. Our study demonstrates the ability of low-dose CY to reverse Tregs-mediated immune evasion in a mouse model. The changes in intracellular cAMP concentrations correlated with the upregulation of effector T cells and the downregulation of Tregs, indicating the close association of cAMP analogs and low-dose CY in the immune therapy of B-cell lymphoma.     

EMs患者长效GnRHa降调节后人工周期行FET的临床结局

目的：探讨长效促性腺激素释放激素激动剂（GnRHa）降调节对行冻融胚胎移植（FET）的子宫内膜异位症（EMs）患者临床结局的影响。方法：选择2016年1月—2018年1月于山东中医药大学第二附属医院生殖医学科行FET的EMs患者共计320例，随机分为长效GnRHa降调节后人工周期组（A组，160例）和单纯人工周期组（B组，160例），观察2组患者一般资料、临床指标和妊娠结局。结果：2组患者的一般资料、黄体酮转化日CA125水平、孕酮（P）水平、移植胚胎数、早期流产率比较差异均无统计学意义（P＞0.05）；A组黄体酮转化日雌二醇（E2）水平显著低于B组（P＜0.05)，A组黄体酮转化日子宫内膜厚度、黄体酮转化日A型子宫内膜比例、临床妊娠率、胚胎着床率和活产率均高于B组（P＜0.05）。结论：长效GnRHa降调节后人工周期准备内膜可以改善行FET的EMs患者的临床结局。     

Point-of-care ultrasound for the evaluation of non-traumatic visual disturbances in the emergency department: The VIGMO protocol

ObjectivesTo establish a standardized approach for the rapid and accurate identification of non-traumatic, ophthalmologic pathology in patients with eye complaints in the emergency department.MethodsIn this detailed protocol we offer an easy, reproducible method for the use of ocular point-of-care ultrasound (POCUS) in helping practitioners identify and distinguish between common eye pathology encountered in the emergency setting: retinal detachment, vitreous detachment, vitreous hemorrhage, optic nerve pathology, and syneresis.ConclusionsThis protocol can help identify patients that may need urgent ophthalmology consultation those that can follow-up on an outpatient, and those that may need additional emergent testing.     

M2 polarization of monocytes in ankylosing spondylitis and relationship with inflammation and structural damage

The aim of this study was to evaluate the polarization of peripheral blood monocytes in the patients with ankylosing spondylitis (AS) and to determine the correlations between monocyte polarization and inflammation and structural damage. A total of 120 AS patients, 50 rheumatoid arthritis (RA) patients and 100 healthy controls were enrolled in the study. M1 (CD68+CD192+) and M2 (CX3CR1+CD163+) monocytes were characterized by flow cytometry. Demographic, clinical, radiographic and laboratory data were collected and analyzed. A large increase in M2 (CX3CR1+CD163+) monocytes was observed in AS, and M2/M1 ratio was 7.18 ± 6.12, 2.54 ± 3.14 and 35.61 ± 20.04 in control, RA and AS, respectively. The M2/M1 ratio correlated with modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) (r = 0.565; p < 0.001), ESR (r = ?0.321; p < 0.001, CRP (r = ?0.265; p < 0.001) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (r = ?0.201; p = 0.028). Anti‐TNF‐α therapy induced a significant reduction in the percentage of M1 monocyte, ESR, CRP and BASDAI in AS patients. The present results demonstrated that M2 type polarized monocytes are predominant in the peripheral blood in AS and the M2/M1 ratio is correlated with structural damage (mSASSS), inflammatory biomarkers (ESR and CRP) and BASDAI.     

S100G expression and function in fibroblasts on colitis induction

Supplementation with interleukin (IL)-10, an important anti-inflammatory cytokine, has shown disappointing efficacy for inflammatory bowel diseases (IBD). IL-10 may down-regulate the expression of other anti-inflammatory mediators following colitis induction. We used a colitis model characterized by hapten-protein visualization, which indicates the site of hapten-protein formation after colitis induction for histological and gene expression analyses. Under IL-10 deficiency, following colitis induction inflammatory changes were reduced, and S100G expression was elevated. S100G was expressed in fibroblasts, and S100G expression was down-regulated by IL-10. S100G suppressed the production of monocyte chemotactic protein-1 (MCP-1) through the inhibition of NF-κB activation. Therefore, S100G, also known as Calbindin-D9k, may be an important anti-inflammatory mediator in fibroblasts following colitis induction, and down-regulation of S100G expression might be one reason for the insufficient performance of IL-10 supplementation.     

Percutaneous CT-Guided Cryoablation of the Celiac Plexus: A Retrospective Cohort Comparison with Ethanol

PurposeTo retrospectively analyze and compare the incidence of diarrhea in patients who underwent cryoablation of the celiac plexus for intractable abdominal pain versus ethanol therapy over a 5-year period.Materials and MethodsFrom June 2014 to August 2019, 83 patients were identified who underwent neurolysis of the celiac plexus for management of intractable abdominal pain by using either cryoablation (n = 39 [59% female; age range, 36–79 years old [average, 60 ± 11 years old]) or alcohol (n = 44 [48% female; age range, 29–76 years old [average, 60 ± 12 years old]). Pain scores and reports of procedure-related complications or side effects, with special attention to diarrhea and/or other gastrointestinal symptoms, were collected from follow-up visits at 1 week, 1 month, and 3 months post-intervention and were compared between groups.ResultsThe mean time of follow-up was 17.7 days. Four patients who underwent cryoablation developed gastrointestinal symptoms consisting of 2 cases of nausea and vomiting and 2 cases of diarrhea (5.1%). Twelve patients who underwent ethanol ablation developed gastrointestinal symptoms, including 1 case of nausea, 3 cases of vomiting, and 9 cases of diarrhea (20.5%). There was a significantly higher incidence of both diarrhea (chi-squared likelihood ratio, P = .03) and overall gastrointestinal symptoms (chi-squared likelihood ratio, P = .04) in the ethanol group than in the cryoablation group.ConclusionsCryoablation of the celiac plexus may provide a new treatment option for intractable abdominal pain, and it appears to have a lower incidence of diarrhea and fewer gastrointestinal side effects than ablation using ethanol.     

Preoperative neutrophil-to-lymphocyte ratio is a more valuable prognostic factor than platelet-to-lymphocyte ratio for nonmetastatic rectal cancer

Several combinations of inflammatory factors, including neutrophil-to- lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been reported to be prognostic factors in various malignant tumors, including colorectal cancer (CRC). The aim of this study was to evaluate the prognostic value of NLR and PLR for patients with rectal cancer (RC) who underwent curative surgery. Data from patients who underwent curative resection for RC were retrospectively reviewed. The cutoff for NLR and PLR was defined as 2.3 and 144 by receiver operating characteristic (ROC) curve. Overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier method. Multivariable Cox regression model was used to evaluate the independent prognostic significance of variables. A total of 140 patients were eligible in the study. High NLR (> 2.3) and high PLR (> 144) both predicted lower OS and DFS according to Kaplan-Meier method. But in the multivariable Cox regression model, only the high NLR retained significance for reduced OS and DFS. According to Chi-square test, patients with higher NLR had larger tumor size and higher pN-stage. While PLR was only associated with the pN-stage. High preoperative NLR was shown to be a negative independent prognostic factor in patients undergoing resection for nonmetastatic RC. It may be helpful as a factor to guide the postoperative therapies.