Osteosarcoma is the most prevalent type of primary bone malignancy in children and adolescents. The effect of cytokines on osteosarcoma prognosis has been studied and reported. This meta-analysis aimed to assess the prognostic value of cytokines as osteosarcoma biomarkers. Databases including PubMed, Embase, and Cochrane Library were searched for studies on the prognostic value of cytokines in osteosarcoma. From the eligible studies, data on overall survival (OS), disease-free survival, and metastasis-free survival (MFS) were extracted. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. A total of 11 studies involving 755 patients were included in this analysis. High macrophage migration inhibitory factor (MIF) expression in tumors was significantly associated with shortened OS (HR = 2.01, 95% CI: 1.18-3.42, P = 0.010) and MFS (HR = 2.51, 95% CI: 1.47-4.01, P = 0.001). Elevated T cell immunoglobulin and mucin domain-3 (Tim-3) levels in serum correlated with increased risk of disease progression in patients with osteosarcoma (HR = 3.14, 95% CI: 2.88-3.03, P < 0.001). However, interleukin 6 (IL-6) and tumor necrosis factor were not substantially associated with osteosarcoma prognosis. Owing to a paucity of research, other relevant cytokines [interferon-α/β receptor, tissue factor, macrophage inhibitory cytokine 1 (MIC-1), and IL-23] could not be combined. In conclusion, MIF levels in tumors and Tim-3 levels in serum can be potential biomarkers of poor prognosis in osteosarcoma. To confirm this finding and implement these biomarkers into clinical applications, additional large-scale, high-quality studies are needed.

Preeclampsia is a pregnancy-specific disease which is characterized by abnormal placentation, endothelial dysfunction, and systemic inflammation. Several studies have shown that the maternal immune system, which is crucial for maintaining the pregnancy by ensuring maternal-fetal-tolerance, is disrupted in preeclamptic patients. Besides different immune cells, immune checkpoint molecules such as the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1 system) and the T-cell immunoglobulin and mucin domain-containing protein 3/Galectin-9 (TIM-3/Gal-9 system) are key players in upholding the balance between pro-inflammatory and anti-inflammatory signals. Therefore, a clear understanding about the role of these immune checkpoint molecules in preeclampsia is essential. This review discusses the role of these two immune checkpoint systems in pregnancy and their alterations in preeclampsia.

The incidence of hematological malignant tumor is increasing year by year, and seriously affecting the human health. In addition to the traditional radiation and chemotherapy, immunotherapy has achieved a certain effect in the treatment of blood tumor, but it is limited by exhaustion of CD8+ T cell. The exhaustion of CD8+ T cells is mainly related to the activation of some immune checkpoint inhibitors, such as (Tim3), programmed death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), etc. Among them, Tim3 is getting more and more attention. The combination of Tim3 and its ligand galectin-9 produced a strong cellular immunosuppressive effect. Tim3 has been proved to be associated with CD8+ T cell exhaustion in many tumors. In this review, the application of Tim3/galectin-9 in hematologic tumors is briefly summarized so as to provide theoretical basis for clinical diagnosis and treatment of these diseases.
UNASSIGNED: Tim3/galectin-9在血液系统肿瘤中的研究进展.
UNASSIGNED: 血液系统肿瘤发病率呈逐年增高趋势，严重影响人类的健康。除传统放化疗外，免疫治疗已在血液肿瘤的治疗中取得了一定的疗效，但是却受到CD8+T细胞衰竭的限制，而CD8+T细胞衰竭主要与一些免疫检查点抑制剂的激活相关，如T细胞免疫球蛋白和粘蛋白域3（Tim3）、程序性死亡-1（PD-1）、细胞毒性T淋巴细胞抗原4（CTLA-4）等。其中，Tim3受到了越来越多的关注。Tim3与它的配体半乳糖凝集素-9（galectin-9）结合，产生了很强的细胞免疫抑制作用。在许多肿瘤中，Tim3被认为与CD8+T细胞衰竭有关。本文拟对Tim3/galectin-9在血液系统肿瘤中的应用进展作一综述，为临床诊治该类疾病提供理论依据.

Previous studies have reported that T cell immunoglobulin domain and mucin domain-3 (TIM-3) 574T>G and 1516G>T are associated with the risk of asthma. However, the results are inconsistent due to the small sample size and varied age in studies. We performed this meta-analysis to systematically evaluated the effect of TIM-3 574T>G and 1516G>T genetic polymorphisms on asthma. Eligible articles that reported an association between TIM-3 574T>G and 1516G>T genetic polymorphisms and asthma were searched in PubMed, Medline, EMBASE, Google Scholar, and China National Knowledge Infrastructure up to April 2020. Random or fixed-effects models were used to calculate the summary of odds ratios (ORs) and 95% confidence intervals (CIs) to detect any potential associations between TIM-3 genetic polymorphisms and asthma. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and the robustness of the pooled estimation. Publication bias was analyzed using the Egger test. A total of 11 case-control studies including 2077 asthma patients and 2122 control subjects were finally analyzed (published data form 2004-2018). The pooled results indicated that TIM-3 574T>G genetic polymorphisms were significantly associated with an increased risk of asthma under the dominant model (GG vs. GT +TT: ORs=2.26, 95% CI 1.09-4.69) and allele model (G vs T: ORs=2.60, 95% CI 1.20-5.64). However, no significant associations between TIM-3 1516G>T genetic polymorphisms with asthma in any model was found. No evidence of publication bias was observed.  Our study indicates that TIM-3 574T>G genetic polymorphisms were associated with increased risk of asthma and the TIM-3 1516G>T genetic polymorphisms may not be correlated with asthma.

TIM-family proteins are expressed on different immune cells such as dendritic cells, macrophages, type 1 and 2 T helper (Th) cells. Therefore, they have the ability to contribute to the various intracellular signals and immune responses, importantly the regulation of Th1 and Th17 cell differentiation, which plays a remarked role in fight against inflammatory and autoimmune diseases. Association of TIM family gene polymorphisms with rheumatoid arthritis (RA) has been frequently investigated. The findings however are not entirely consistent. Therefore, we carried out the present meta-analysis to examine the association between RA and the following TIM family gene polymorphisms: rs41297579, rs1036199, rs10515746, and rs7700944.
A systematic search of Scopus, PubMed, and Web of Science databases was conducted through December 2018. Combined odds ratios (OR) with their corresponding 95% confidence intervals (CI) were calculated under different possible genetic models.
A total of eight case-control studies were included in the present meta-analysis. The results demonstrated significant association of RA with TIM-3 rs1036199 polymorphism under dominant (OR, 1.93, 95% CI, 1.43-2.61) and allelic models (OR, 1.74, 95% CI, 1.31-2.30). None of the other examined polymorphisms indicated significant association with RA.
The present meta-analysis revealed that the TIM-3 rs1036199 polymorphism might confer susceptibility to RA. Further studies are required to reassert our findings.

Accumulated studies have demonstrated the important role of T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) in various solid tumors and indicated its correlation with patients\' survival. To further verify the prognostic significance of TIM-3 in cancer patients and its correlation with tumor, we performed this meta-analysis including seven studies searched from PubMed, Web of Science, and Embase till July 2016. A total of 869 patients were used to analyze the association between TIM-3 expression and patients\' overall survival (OS). The pooled results showed that higher expression of TIM-3 was significantly correlated to shorter OS (7 studies, HR=1.89; 95% CI: 1.38-2.57; P< 0.001). In addition, higher TIM-3 expression was associated with advanced tumor stage (3 studies, III/IV vs. I/II, RR=2.02; 95% CI: 1.45-2.81; P< 0.001). In conclusion, our study highlights the role of TIM-3 as a potential prognostic marker and a promising therapeutic target in solid tumors.

The main mechanism of tumor immune suppression is due to the T cell exhaustion which is mediated by abnormal expression of T-cell immunosuppressive receptors in immune cells. Blocking these molecules may restore partial or all functions of T cells. This article reviews the advance on the role of the newly discovered T cell immuno-suppressive receptors such as TIM-3, LAG-3 and BTLA, including their mediated T cell-immune tolerance and the study of targeted immunotherapy in hematological malignancies, so as to provide the new strategy for immune-targeted therapy for hematological malignancies.