The Pathogenicity of Fusobacterium nucleatum Modulated by Dietary Fibers-A Possible Missing Link between the Dietary Composition and the Risk of Colorectal Cancer.

The dietary composition has been approved to be strongly associated with the risk of colorectal cancer (CRC), one of the most serious malignancies worldwide, through regulating the gut microbiota structure, thereby influencing the homeostasis of colonic epithelial cells by producing carcinogens, i.e., ammonia or antitumor metabolites, like butyrate. Though butyrate-producing Fusobacterium nucleatum has been considered a potential tumor driver associated with chemotherapy resistance and poor prognosis in CRC, it was more frequently identified in the gut microbiota of healthy individuals rather than CRC tumor tissues. First, within the concentration range tested, the fermentation broth of F. nucleatum exhibited no significant effects on Caco-2 and NCM460 cells viability except for a notable up-regulation of the expression of TLR4 (30.70%, p < 0.0001) and Myc (47.67%, p = 0.021) and genes encoding proinflammatory cytokines including IL1B (197.57%, p < 0.0001), IL6 (1704.51%, p < 0.0001), and IL8 (897.05%, p < 0.0001) in Caco-2 cells exclusively. Although no marked effects of polydextrose or fibersol-2 on the growth of F. nucleatum, Caco-2 and NCM460 cells were observed, once culture media supplemented with polydextrose or fibersol-2, the corresponding fermentation broths of F. nucleatum significantly inhibited the growth of Caco-2 cells up to 48.90% (p = 0.0003, 72 h, 10%) and 52.96% (p = 0.0002, 72 h, 10%), respectively in a dose-dependent manner. These two kinds of fibers considerably promoted butyrate production of F. nucleatum up to 205.67% (p < 0.0001, 6% polydextrose at 24 h) and 153.46% (p = 0.0002, 6% fibersol-2 at 12 h), which explained why and how the fermentation broths of F. nucleatum cultured with fibers suppressing the growth of Caco-2 cells. Above findings indicated that dietary fiber determined F. nucleatum to be a carcinogenic or antitumor bacterium, and F. nucleatum played an important role in the association between the dietary composition, primarily the content of dietary fibers, and the risk of CRC.

Screening of a novel autophagy-related prognostic signature and therapeutic targets in hepatocellular carcinoma.

BACKGROUND: Many studies have indicated that autophagy plays an important role in multiple cancers, including hepatocellular carcinoma (HCC). This study aimed to establish a prognostic signature for HCC based on autophagy-related genes (ARGs) to predict the prognosis of patients. METHODS: The list of ARGs was derived from screening National Center for Biotechnology Information (NCBI)-Gene and Molecular Signatures Database (MSigDB) datasets. Differential analysis was conducted via the R limma package in HCC patients based on The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analysis were conducted to identify key prognostic ARGs via the survival package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by clusterProfiler package. The Estimation of Stromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm was used to conduct immune analysis. Finally, the correlation between the prognostic model and clinical characteristics was also assessed, including age, tumor-node-metastasis (TNM) stages, and tumor grades. RESULTS: Firstly, 106 differential ARGs were identified and 10 candidates were further confirmed via Cox regression analysis, including BAMBI, HIF1A, SERPINE1, EZH2, SLC9A3R1, IGFBP3, HSPB8, DAB2, CXCL1 and PRNP. The receiver operating characteristic (ROC) curve analysis revealed that the ARGs risk model had a well diagnostic positive rate with 1-year area under the curve (AUC) =0.688 and 3-year AUC =0.674. Correlation analysis indicated that only advanced tumor stages were positively associated with high ARGs scores with P=0.0227. There were also significant differences in tumor purity (P=6.71e-05), infiltrating cell analysis (P=7.77e-05), immune analysis (P=7.9e-05), and stromal cells analysis (P=0.0015) in high- and low-risk ARGs samples. The genes HIF1A, IGFBP3, and DAB2 were found to have high frequent missense mutations in samples with high-risk ARGs scores. Lastly, we also established a nomogram to predict overall survival (OS) of HCC by integrating ARGs scores and other clinical parameters. CONCLUSIONS: Our study established an autophagy-related signature for predicting the prognosis of HCC patients, providing a thorough understanding of the underlying mechanisms of autophagy in HCC.

Gender differences in vascular reactivity of mesenteric arterioles in portal hypertensive and non-portal hypertensive rats.

BACKGROUND: Portal hypertension (PHT) is primarily caused by an increase in resistance to portal outflow and secondarily by an increase in splanchnic blood flow. Vascular hyporeactivity both in systemic circulation and in the mesenteric artery plays a role in the hyperdynamic circulatory syndrome. AIM: To explore gender differences and the role of endogenous sex hormones in PHT and vascular reactivity of mesenteric arterioles in rats. METHODS: Cirrhosis and PHT were established by subcutaneous injection of carbon tetrachloride (CCl4) in both male and female integral and castrated rats (ovariectomized [OVX] in female rats, orchiectomy [ORX] in male rats). The third-order branch of the mensenteric artery was divided and used to measure vascular reactivity to vasoconstrictors. RESULTS: No significant difference in portal pressure was observed between integral and castrated male PHT rats (15.2 ± 2.1 mmHg vs 16.7 ± 2.7 mmHg, P > 0.05). The portal pressure in integral female PHT rats was lower than that in OVX female PHT rats (12.7 ± 2.7 mmHg vs 16.5 ± 2.4 mmHg, P < 0.05). In PHT rats, the concentration response curves of the mesenteric arterioles to norepinephrine were shifted to the right, and the maximal responses (Emax) values were decreased and effective concentrations causing half maximum responses (EC50) values were increased, compared to those of non-PHT rats, both in male and female rats. Compared to non-PHT integral male rats, the sensitivity of the mesenteric arterioles of non-PHT ORX male rats to norepinephrine was decreased (P > 0.05). However, there was no difference between integral and ORX male rats with PHT. In integral female PHT rats, the concentration response curves were shifted to the left (P < 0.05), and the Emax values were increased and EC50 values were decreased compared to OVX female PHT rats. CONCLUSION: Clear gender differences were observed in mesenteric vascular reactivity in CCl4-induced cirrhotic and PHT rats. Conservation of estrogen can retain the sensitivity of the mesenteric arterioles to vasoconstrictors and has a protective effect on splanchnic vascular function in PHT.

[Research Progress on Role of Gene Mutations in Prognostic Evaluation of Patients with Myelodysplastic Syndrome after Stem-Cell Transplantation--Review].

Abstract　　Myelodysplastic syndromes (MDS) represent a clonal hematopoietic stem cell disorder characterized by morphologic features of dyspoiesis, high risk of transformation from MDS into AML. Allogeneic hematopoietic stem-cell transplantation is the only curative therapy for MDS, but the failure rate of transplantation is still high, which attribute to relapsed disease and transplant-related complications. Recently, the spectrum of gene abnormalities in MDS has been revealed by next generation genomic sequencing techniques. It was found that more than 80% MDS patients have at least one gene mutation. Mutated genes in MDS are powerfully associated with clinical phenotype and prognosis. In this review , the recent advancements regarding recurrent gene mutations in MDS are briefly summarized, and the  prognostic values of gene mutations are discussed in MDS or after allogeneic hematopoietic stem-cell transplantation,so as to set up a predicting model and to guide the treatment.

Estrogen receptor ß selective agonist ameliorates liver cirrhosis in rats by inhibiting the activation and proliferation of hepatic stellate cells.

BACKGROUND AND AIM: The aim of this study is to explore the roles of estrogen receptor (ER) subtypes and corresponding agonists/antagonists on the development of cirrhosis and activation and proliferation of hepatic stellate cells (HSCs). METHODS: Carbon tetrachloride (CCl4 )-induced cirrhotic ovariectomized rats were administered non-selective ER agonist (ß-estradiol, E2), ER selective agonists (ERα agonist, propylpyrazoletriol; ERß agonist, diarylpropionitrile [DPN]; and G-protein-coupled ER [GPER] agonist, G1), or E2 + ER selective antagonists (ERα antagonist, MPP; ERß antagonist, PHTPP; and GPER antagonist, G15) for 12 weeks. The expression of the three ER subtypes in livers and HSCs and the effects of the drugs on hepatic fibrosis, isolated HSCs, and uteri were evaluated. RESULTS: Selective ER agonists/antagonists had various effects on CCl4 -induced cirrhosis. The cirrhotic rats in the CCl4  + E2, CCl4  + DPN, CCl4  + E2 + MPP, and CCl4  + E2 + G15 groups presented reduced fibrosis scores, compared with those in the CCl4 group. The cirrhotic rats in the E2 + PHTPP group presented increased fibrosis scores that similar to those in the CCl4 group. The ovariectomized rats had enlarged uteri with increased uterus indexes after E2 administration; however, the proliferative effects of E2 were partially blocked by MPP or G15, but not PHTPP. In the in vitro study, DPN attenuated the transformation of quiescent HSCs to activated phenotype, suppressed collagen I, and α-smooth muscle actin expression. DPN also suppressed platelet-derived growth factor-induced proliferation in cultured HSCs, which was reversed by PHTPP. CONCLUSIONS: The antifibrogenic effects of estrogen were mediated by ERß but not ERα or GPER. The ERß selective agonist exerted a fibrosuppressive effect by inhibiting the activation and proliferation of HSCs, but did not induce uterine hyperplasia.

[Effect of ERK1/2 Signaling Pathway Inhibitor PD98059 on the Expression of Ras, BRaf, MEK, ERK1/2 in Marrow Nucleated Red Blood Cells of CMS Patients].

OBJECTIVE: To investigate the effect of ERK1 / 2 signaling pathway inhibitor PD98059 on Ras, Raf, MEK, ERK1, ERK2 expression in order to explore a new way for basic research and clinical treatment of the chronic mountain sickness(CMS). METHODS: Sixteen CMS patients were selected, the bone marrow was collected for isolation of monomuclear cells (MNC), the cells were sorted by using CD71 and CD235a antibody magnetic beads, then positive cells were diveded into 5 groups: blank control, DMSO and PD98059 5, 10 and 20 µmol/L, and were cultured in hypoxid condition for 72 hours. The Ras-GTP levels in supernatant was detected by ELISA, the RT-PCR was used to determine the expression of BRaf, MEK, ERK1, ERK2 mRNA in nucleated red blood cells, and the Western blot method was used to detect expression of BRaf, MEK, ERK1, ERK2 protein. RESULTS: PD98059 had no effect on the level of Ras-GTP in each groups. Compared with the blank control group, the expression levels of BRaf, MEK mRNA in DMSO group were not statistically significant (P values were 0.826, 0.298). Compared with the PD98059 20 mol/L group, the expression level of ERK1/2 mRNA was statistically significant (P=0.001, 0.002). Compared with the blank control group, expression levels of p-BRaf, p-MEK protein in DMSO group were not statistically significant (P=0.370, 0.351). Compared with the PD98059 20 mol/L group, the difference of p-ERK1/2 protein level in other 4 groups were statistically significant (P values were <0.001, 0.007). CONCLUSION: PD98059 can up-regulate the expressions of ERK1/2 miRNA and p-ERK1/2 protein in bone marrow nucleated red blood cells, the Ras / Raf / MEK / ERK 1/2 pathway is the main signal transduction pathway in regulating bone marrow nucleated red blood cells, suggesting that Ras/Raf /MEK /ERK 1/2 pathway may be involved in the pathogenesis of chronic mountain sickness process.

[Effect of Rabbit Anti-human Thymocyte Immunoglobulin Combined with Cyclosporin A on Severe Aplastic Anemia].

OBJECTIVE: To study the efficacy and safety of anti-human thymocyte immunoglobulin(ATG-F) combined with cyclosporin A(CsA) on patients with severe aplastic anemia (SSA), so as to provide support for clinical work. METHODS: From January 2010 to December 2015, 78 patients with SAA admitted in our hospital were divided into 2 groups: ATG-F+CsA group(40 cases) and ATG-F group(38 cases). After treatment for 6 months, the effective rate, side reaction rate and time of effect initiation were compared between 2 groups. The follow-up results were compared between 2 groups. RESULTS: The effective rate and side reaction rate in ATG-F+CsA group were 100.00% and 32.50% respectively, those in ATG-F group were 94.74% and 44.74% respectively and without statistical significant difference(P>0.05). In ATG-F+CsA group, the time of effect initiation in cured patients, remission and obvious inprovement were (44.9±15.4) d, (68.8±15.9) d and (85.4±17.6) d; in ATG-F group, patients with those were (59.6±11.5) d, (94.7±17.8) d and (119.8±21.4) d respectively, the difference showed statistical significance(P<0.05). The follow-up results were not statistically significantly different between 2 groups(P>0.05). CONCLUSION: ATG-F combined with CsA can shorten the time of effect initiation, and demonstrates reliable safety.

[Effect of PD98059 on Proliferation and Apoptosis of CD71(+),CD235a(+) Nucleated Erythrocytes in the Patients with High Altitude Polycythemia].

UNLABELLED: Objective： To study the effect of PD98059, a specific inhibitor of Ras/Raf/MEK/ERK signaling pathway, on the proliferation and apoptisis of bone marrow CD71(+), CD235a(+) nucleated erythrocytes in patients with high altitude polycythemia (HAPC) and the pathogenesis of HAPC. METHODS: The CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients and controls (patients with simple obsolete stracture) were sorted by using the immunemagnetic beads, then were added with 5, 10, 20 µmol/L of PD98059 and DMSO (as control) and were cultured for 72 h under hypoxia. The cell apoptosis was detected by flow cytometry with Annexin V and PI double staining, the cell proliferation was detected by CCK8 method, at same time the erythroid colong-formation ability of bone marrow mononuclear cells (BMMNC) treated with 5, 10, 20 µmol/L of PD98059 and DMSO was observed. RESULTS: With the increase of PD98059 concentration, the apoptosis rate of bone marrow CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients was enhanced (r=0.807,P<0.01), while the proliferation rate of CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients dereased (r=0.502,P<0.01). The erythroid colong-formation ability of BMMNC in HAPC patients decreased with the increase of PD98059 concentration (r=0.504,P<0.01). There were statistic differences among different groups at 7 and 14 d. CONCLUSION: The MEK specific inhibitor PD98059 can inhibit the proliferation and promote the apoptosis of CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients, then inhibit the excessive accumulation of erythrocytes.

[Influence of GATA-1 on Expression of EpoR in Bone Marrow CD71+ Cells of Rat Model with High Altitude Polycythemia].

OBJECTIVE: To explore the influence of GATA-1 on expression of EpoR in bone marrow CD71+ cells of rat model with high altitude polycythemia (HAPC). METHODS: Forty-eight male SD rats were randomly divided into normal control and HAPC model group. HAPC model was established at the altitude of 4 300 meters in the natural environment, and verified by bone marrow cell counts and hematological parameters. Myeloid CD71+ cells were separated by the density gradient centrifugation combined with magnetic activated cell sorting. The expression of EpoR on cell membrane was detected by flow cytometry and cell immunofluorescence. The expression changes of GATA-1 and EpoR mRNA and protein were detected by Q-PCR and Western blot, respectively. CD71+ cells were cultured under normoxia and hypoxia, respectively. After transfection for 96 h, the optimal interference sequence GATA-1 shRNA1 was selected. And the mRNA and protein expression level of GATA-1 and EpoR were detected by Q-PCR and Western blot respectively. RESULTS: The animal model with HAPC was established successfully and comfirmed by the bone marrow cell counting and the hematologic parameters in comparison with that of the normal control. EpoR expression on the myeloid CD71+ cell membrane in HAPC group was significantly higher than that in normal control (P<0.05). The expression of GATA-1 and EpoR in myeloid CD71+ cells of HAPC group was higher than that in control group (P<0.05). The mRNA and protein expression of GATA-1 and EpoR in two groups positively correlated (control group, r=0.929, P<0.01, r=0.802, P<0.05; HAPC group, r=0.822, P<0.05, r=0.839, P<0.01). However, the mRNA and protein expression of EpoR at normoxia and hypoxia was significantly lower than that in negative control group after interfernce with GATA-1 shRNA1 for 96 h (P<0.05). And the expression of GATA-1 and EpoR under hypoxia was higher than that in normoxia. CONCLUSION: The effect of GATA-1 on EpoR expression may be correlated with the pathogenesis of HAPC.

[Clinical Therapeutic Efficacy of Rituximab Combined with Methotrexate on Primary Central Nervous System Lymphoma].

OBJECTIVE: To investigate the therapeutic efficacy of rituximab combined with methotrexate on patients with primary central nervous system lymphoma. METHODS: Fifty eight patients with central nervous system lymphoma treated in our hospital from February 2008 to September 2011 years were randomly divided into the observation group and the control group. The control group was treated with methotrexate combined with whole brain radiotherapy; the observation group was treated by rituximab combined with methotrexate. The curative efficacy, adverse effects, life quality, and the 1 and 3 year survival rate after 2 cycles of treatment were compared between 2 groups. RESULTS: The total effective rate of observation group was 82.76%, which significantly higher than 58.62% of the control group (P < 0.05). In observation group, the incidences of anemia, liver damage, gastrointestinal side effect and oral ulcer were significantly lower than that in control group, respectively (P < 0.05). The physiological function, physical function, health status, social and emotional function in the observation group were significantly higher than those in the control group (P < 0.05), 1 and 3 years survival rates in the observation group were 86.21% and 62.07%, significantly higher than 58.62% and 31.03% in the control group (P < 0.05). CONCLUSION: Targeted therapy combined with chemotherapy for the primary central nervous system lymphoma can improve the patients' outcomes, reduce adverse effects, and improve the quality of life and survival rate.

Skp2-RNAi suppresses proliferation and migration of gallbladder carcinoma cells by enhancing p27 expression.

AIM: To explore the role of S-phase kinase-associated protein-2 (Skp2) in gallbladder carcinoma and to identify whether depletion of Skp2 by Skp2-RNAi could attenuate proliferation and migration of gallbladder carcinoma. METHODS: Skp2-RNAi was transduced into cells of the gallbladder carcinoma cell line GBC-SD, using a lentiviral vector. The effect of Skp2-RNAi on the proliferation, migration, invasion and cell cycle of GBC-SD cells was studied using in vitro assays for cell proliferation, colony formation, wound healing and cell cycle. The expression of Skp2 and p27 was detected by real-time polymerase chain reaction and Western immunoblotting. The effect of Skp2-RNAi on the proliferation of GBC-SD cells in vivo was investigated by tumorigenicity experiments in nude mice. RESULTS: Lentivirus-mediated RNAi reduced the expression of Skp2 in cultured cells. The expression of the p27 protein increased along with the down-regulation of Skp2, although no significant difference was found in p27 mRNA expression. Flow cytometry revealed that Skp2-RNAi transfection significantly increased the proportion of cells in the S phase and significantly decreased the proportion of cells in the G2/M phase. No significant difference in the frequency of cells in the G0/G1 phase was observed. The results from the cell proliferation, colony formation and wound healing assays revealed that Skp2-RNAi transfection markedly inhibited the proliferation and migration of GBC-SD cells in vitro. Additionally, tumorigenicity experiments showed that suppression of Skp2 significantly decreased the weights of the tumors (0.56 ± 0.11 and 0.55 ± 0.07 g in the control and Scr-RNAi groups vs 0.37 ± 0.09 and 0.35 ± 0.08 g in the Skp2-RNAi-L and Skp2-RNAi-H groups). CONCLUSION: The expression of Skp2 in GBC-SD cells was inhibited following Skp2-RNAi transfection. Silencing of the Skp2 gene inhibited proliferation, migration and invasiveness of GBC-SD cells by mechanisms dependent on enhanced expression of the p27 protein.

[Studies on apoptosis and caspase-8 and caspase-9 expressions of bone marrow cells in chronic mountain sickness].

OBJECTIVE: To observe the expressions of caspase-8 and caspase-9 mRNA, and explore the changes of apoptosis of bone marrow hematopoietic cells in patients with chronic mountain sickness (CMS). METHODS: Of 18 CMS patients and 16 controls were enrolled in this study. The apoptotic index (AI) of bone marrow mononuclear cells (BMMNC) was measured by TUNEL technique, the levels of caspase-8 and caspase-9 mRNA in BMMNC of CMS patients and controls were determined by RT-PCR. Results (1)The AI of BMMNC in patients with CMS (8.51 ± 3.35)% was lower than that in controls (16.00 ± 4.28)% (P < 0.01); (2) The values of caspase-8 and caspase-9 mRNA were (0.28 ± 0.07) and (0.23 ± 0.08) respectively, in CMS patients, which were significantly lower than those of (0.45 ± 0.09) and (0.41 ± 0.09) respectively, in the controls (both P < 0.01); (3) Hemoglobin (Hb) value was negatively correlated with levels of caspase-8 and caspase-9 mRNA (r values were -0.52 and -0.61 respectively, both P < 0.05) in CMS patients. There was a negative correlation between AI and Hb (r value was -0.89, P < 0.01) in CMS patients. However, the significant relationship was not found between AI and level of caspase-8 or caspase-9 mRNA (P > 0.05). CONCLUSIONS: The results showed a decrease apoptosis of BMMNCs and reduced levels of caspase-8 and caspase-9 mRNA in CMS patients, the latter might be involved in the change of BMMNCs apoptosis.

[Changes of serum angiogenesis in patients with chronic mountain sickness].

AIM: The clinical manifestation of chronic mountain sickness (CMS) is polycythemia, pulmonary hypertension and mionectic blood. However, the pathogenesis of it is not identified now. So it is necessary to investigate the effects of the angiogenic growth factors on the pathophysiologic development of CMS. METHODS: The serum levels of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) in 13 healthy Tibetan natives (Native), 17 healthy people in Xining (control group) and 35 CMS patients were determined by quantitative sandwich enzyme immunoassay. Meanwhile, the levels of Hb, Hct and SaO2 were determined. RESULTS: The serum levels of bFGF (107.26 +/- 7.86) ng/L, PDGF (630.18 +/- 9.89) ng/L and VEGF (543.74 +/- 6.76) ng/L in CMS were significantly higher than those in Natives (37.01 +/- 9.16; 292.16 +/- 6.88; 125.51 +/- 7.26) ng/L, and in control group (40.58 +/- 5.34; 287.68 +/- 8.33; 76.26 +/- 4.60) ng/L, respectively (P < 0.01). There was no difference between the natives and the control group in bFGF and PDGF (P > 0.05), while there was predominant difference between the Natives and the control group in VEGF (P < 0.01). There was a predominant positive correlation between the serum levels of bFGF, PDGF or VEGF and hemoglobin concentrations in CMS respectively (P < 0.01). And there were positive relations between angiogenic growth factors each other. CONCLUSION: The serum levels of bFGF, PDGF and VEGF in patients with CMS significantly increase, these angiogenic growth factors may play important role on the pathophysiologic development of CMS; the VEGF level likely contributes to the adaptation to plateau hypoxia in healthy Tibetan natives; the elevated bFGF, PDGF and VEGF levels are likely associated with excessive erythropoiesis in CMS.

[Increment of chemokine CXCL9/Mig in plasma correlated with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation].

To investigate the relationship between the plasma levels of chemokine CXCL9/Mig and acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The plasma levels of CXCL9/Mig of 35 patients who received all-HSCT were detected by using ELISA assay, these patients included 13 patients with grade 0-I, 12 patients with grade II and 10 patients with grade III - IV aGVHD, respectively. The four different time points including prior to allo-HSCT, one week before aGVHD onset, the plateau of aGVHD and time after completely controlled, were studied. The results showed that the plasma levels of CXCL9/Mig in the patients with serious aGVHD (grade II - IV) were significantly increased during aGVHD than those in the patients without aGVHD or with slight aGVHD (P < 0.001). It was found that CXCL9/Mig levels were significantly correlated with the severity of grade aGVHD (P < 0.001). Another important finding was that CXCL9/Mig levels obviously increased at one week before aGVHD was diagnosed. CXCL9/Mig level was not obviously correlated with CMV infection or other infectious complication (P > 0.05). It is concluded that the plasma level of CXC19/Mig significantly correlated with the severity of aGVHD and plays a critical role in pathogenesis of aGVHD, the changes in plasma level of CXCL9/Mig after allo-HSCT may be used as a valuable indicator for early diagnosis of aGVHD, finally, provide a early therapeutic approach to reduce aGVHD severity and improve the outcome for patients after allo-HSCT.