Effect of GVHD on the gut and intestinal microflora.

Graft-versus-host disease (GVHD) is one of the most important cause of death in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The gastrointestinal tract is one of the most common sites affected by GVHD. However, there is no gold standard clinical practice for diagnosing gastrointestinal GVHD (GI-GVHD), and it is mainly diagnosed by the patient's clinical symptoms and related histological changes. Additionally, GI-GVHD causes intestinal immune system disorders, damages intestinal epithelial tissue such as intestinal epithelial cells((IEC), goblet, Paneth, and intestinal stem cells, and disrupts the intestinal epithelium's physical and chemical mucosal barriers. The use of antibiotics and diet alterations significantly reduces intestinal microbial diversity, further reducing bacterial metabolites such as short-chain fatty acids and indole, aggravating infection, and GI-GVHD. gut microbe diversity can be restored by fecal microbiota transplantation (FMT) to treat refractory GI-GVHD. This review article focuses on the clinical diagnosis of GI-GVHD and the effect of GVHD on intestinal flora and its metabolites.

Influence of cytokines on early death and coagulopathy in newly diagnosed patients with acute promyelocytic leukemia.

Introduction: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with a better prognosis. But early death (ED) rate remains high. APL patients are simultaneously accompanied by coagulopathy and hyperinflammation at the onset. It is not known what effects cytokines have on ED and coagulopathy in these patients. Therefore, the purposes of this study are to explore the clinical differences between APL and other types of AML, the link between cytokines and coagulopathy in newly diagnosed APL, and their roles in the ED for APL. Methods: This study retrospectively collected the information of 496 adult patients with AML (age ≥14 years at admission) newly diagnosed in the First People's Hospital of Yunnan Province between January 2017 to February 2022, including 115 APL patients. The difference of clinical manifestations between two groups [APL and AML (non-APL)] was statistically analyzed. Then, the factors affecting ED in APL patients were screened, and the possible pathways of their influence on ED were further analyzed. Results: The results indicate APL at the onset have a younger age and higher incidence of ED and DIC than other types of AML. Intracranial hemorrhage (ICH), age, and PLT count are found to be independent factors for ED in newly APL, among which ICH is the main cause of ED, accounting for 61.54% (8/13). The levels of cytokines in newly APL are generally higher than that in AML (non-APL), and those in the group of ED for APL were widely more than the control group. IL-17A and TNF-ß are directly related to the ED in newly APL, especially IL-17A, which also affects ICH in these patients. Moreover, the increase of IL-17A and TNF-ß cause the prolongation of PT in APL patients, which reflected the exogenous coagulation pathway. However, they have no effect on APTT prolongation and FIB reduction. Thus, it is speculated that IL-17A leads to early cerebral hemorrhage death in newly APL by inducing tissue factor (TF) overexpression to initiate exogenous coagulation and further leading to excessive depletion of clotting factors and prolongation of PT. Conclusions: In conclusion, compared with other types of AML, APL patients have a younger age of onset and high inflammatory state, and are more likely to develop into DIC and die early. Age, and PLT count at diagnosis are independent factors for ED of APL, especially ICH. IL-17A is confirmed to be an independent risk factor for ED and ICH of newly APL. Hence, IL-17A may serve as a predictor of ED in newly diagnosed APL patients, and controlling its expression probably reduce ED in these patients.

Gastric precancerous lesions:occurrence, development factors, and treatment.

Patients with gastric precancerous lesions (GPL) have a higher risk of gastric cancer (GC). However, the transformation of GPL into GC is an ongoing process that takes several years. At present, several factors including H.Pylori (Hp), flora imbalance, inflammatory factors, genetic variations, Claudin-4, gastric stem cells, solute carrier family member 26 (SLC26A9), bile reflux, exosomes, and miR-30a plays a considerable role in the transformation of GPL into GC. Moreover, timely intervention in the event of GPL can reduce the risk of GC. In clinical practice, GPL is mainly treated with endoscopy, acid suppression therapy, Hp eradication, a cyclooxygenase-2 inhibitor, aspirin, and diet. Currently, the use of traditional Chinese medicine (TCM) or combination with western medication to remove Hp and the use of TCM to treat GPL are common in Asia, particularly China, and have also demonstrated excellent clinical efficacy. This review thoroughly discussed the combining of TCM and Western therapy for the treatment of precancerous lesions as conditions allow. Consequently, this review also focuses on the causes of the development and progression of GPL, as well as its current treatment. This may help us understand GPL and related treatment.

[Expression and Prognostic Value of Cytokines in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the expression and prognostic value of cytokines in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: Clinical data of 62 patients diagnosed with DLBCL in the First People's Hospital of Yunnan Province from June 2017 to November 2018 were collected. The differences in expression levels of 14 serum cytokines [interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, TNF-ß] in patients with different survival outcomes, and the impact of the cytokines on 3-year progression-free survival (PFS) and 3-year overall survival (OS) of patients with DLBCL were analyzed retrospectively. RESULTS: Among the 14 cytokines, only the expression of IL-10 was significantly different in patients with different survival outcomes (P =0.007). According to the receiver operating characteristic (ROC) curve, the optimal cut-off value for IL-10 was 11.74 pg/ml. Serum IL-10 was positively correlated with infection markers procalcitonin (PCT) (r =0.321, P =0.029), C-reactive protein (CRP) (r =0.320, P =0.013) and tumor burden index lactate dehydrogenase (LDH) (r =0.439, P <0.001) in newly diagnosed DLBCL patients. The level of IL-10 in patients with pulmonary infection was significantly higher than that in patients without pulmonary infection (P =0.012). However, there was no statistically significant difference on the 3-year survival outcomes between patients with or without pulmonary infection. There was no significant difference in IL-10 level in patients with different Ann Arbor stages (P >0.05). Patients with high IL-10 level (IL-10>11.74 pg/ml) had significantly higher LDH level than those with low IL-10 level (IL-10≤11.74 pg/ml) (P <0.001). The 3-year PFS rate and 3-year OS rate of DLBCL patients with high IL-10 level were significantly lower than those of low IL-10 level group [(44.4±11.7)% vs (81.8±5.8)%, P <0.001; (61.6±11.5)% vs (93.2±3.8)%, P =0.001]. CONCLUSION: Serum IL-10 level in newly diagnosed DLBCL patients can reflect the inflammatory state of the body, which may be related to tumor load. Newly diagnosed DLBCL patients with serum IL-10>11.74 pg/ml have higher early mortality and worse prognosis.

Cytokine levels in patients with non-M3 myeloid leukemia are key indicators of how well the disease responds to chemotherapy.

Acute myeloid leukemia (AML) is a malignant hematological neoplastic disease. Autocrine or paracrine cytokines released by leukemic cells regulate the proliferation of AML cells. It is uncertain whether cytokines can indicate whether patients with AML are in remission with chemotherapy. The goal of this study was to evaluate the levels of Th1/Th2/Th17 cytokines in AML patients before and after chemotherapy to determine whether the cytokine levels could predict disease remission after chemotherapy. It was found that the levels of IL-5, IL-6, IL-8, IL-10, TNF-α, TNF-ß, IL-17F, and IL-22 were significantly increased at the time of AML diagnosis in patients who achieved remission after two chemotherapy treatments (P < 0.05). After chemotherapy, the cytokine levels were reduced in patients with remission, while the levels of IL-6 and IL-8 were raised in patients without remission (P < 0.05). A comparison of cytokine levels before and after chemotherapy in patients who achieved remission showed areas under the curve (AUCs) of 0.69 for both IL-6 and IL-8. In addition, a comparison of the remission and non-remission groups after chemotherapy showed an AUC of 0.77 for IL-6. We then calculated the cutoff value using receiver operating characteristic curves. Values of IL-6 < 9.99 and IL-8 < 8.46 at the time of diagnosis were predictive of chemotherapy success and remission, while IL-6 > 14.89 at diagnosis suggested that chemotherapy would not be successful and remission would not be achieved. Multifactorial analysis showed that age, Neu, IL-6, and IL-8 were independent risk factors for AML prognosis, and IL-6 (OR = 5.48, P = 0.0038) was superior to age (OR = 3.36, P = 0.0379), Neu (OR = 0.28, P = 0.0308), IL-8 (OR = 0.0421, P = 0.0421). In conclusion, IL-6 levels were found to be predictive of the likelihood of remission.

[Effects of Cytokines on Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia].

OBJECTIVE: To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits. RESULTS: It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated. CONCLUSION: Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.

Expression of Th1/2/17 Cytokines in CML with or without Pulmonary Bacterial and Fungal Coinfection.

Background: Tyrosine kinase inhibitors (TKIs) are the standard therapy for patients with chronic myeloid leukemia (CML). While their use greatly increases patient survival rates and can lead to normal life expectancy, bacterial infections in the lungs continue to play a significant role in determining patient outcomes. Methods: In this study, the medical records of 272 CML and 53 healthy adults were analyzed. Information on age, sex, body temperature, procalcitonin (PCT), C-reactive protein (CRP), and cytokine levels were collected from patients. Since the data belonged to a nonstate distribution, we used the Mann-Whitney U test to examine differences between groups. Cut-off values were analyzed by receiver operating characteristic (ROC) curves. Results: No significant differences in the Th1/2/17 levels were observed in relation to TKI treatment. Further analysis showed that the levels of the interleukins IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-22, IL-12p70, IL-17A, IL-17F, and IL-1ß, interferon (IFN-γ), and tumor necrosis factors (TNF α and ß) were higher in patients with pulmonary bacterial infections compared with uninfected patients. IL-6, IL-8, and IL-10 levels in CML patients with bacterial and fungal coinfection were higher than those in patients without infection. The areas under the ROC curves (AUCs) were found to be 0.73 for IL-5, 0.84 for IL-6, 0.82 for IL-8, 0,71 for IL-10, and 0.84 for TNF-α. AUC values were higher for patients with pulmonary bacterial infection, especially IL-6 (AUC = 0.84, cut-off = 13.78 pg/ml) and IL-8 (AUC = 0.82, cut-off = 14.35 pg/ml), which were significantly better than those for CRP (AUC = 0.80, cut-off = 6.18 mg/l), PCT (AUC = 0.71, cut-off = 0.25 ng/ml), and body temperature (AUC = 0.68, cut-off = 36.8°C). In addition, according to the cut-off values, we found that 83.33% of patients with pulmonary bacterial infections had IL-6 ≥ 13.78 pg/ml, while when IL-6, IL-8, and IL-10 levels simultaneously exceeded the cut-off values, the probability of pulmonary bacterial infection was 93.55%. Conclusions: TKI treatment did not appear to affect cytokine expression in CML patients. However, CML patients with pulmonary bacterial infection had significantly higher levels of Th1/2/17 cytokines. In particular, abnormally elevated IL-6, IL-8, and IL-10 levels were associated with a pulmonary bacterial infection in patients with CML.

[Research Progress of Cytokines in the Prognosis of Acute Myeloid Leukemia --Review].

At present, acute myeloid leukemia (AML) is mainly treated with combination medication, high-dose, and early intensification. The treatment has achieved good results, but the long-term treatment effect is still not satisfactory. Studies have shown that the different levels of cytokine expression in AML patients can help AML risk stratification, search for treatment directions and predict the prognosis. It has been confirmed that the expression of IL-1ß, IL-6, TNF-α, and TGF-ß1 are increased in AML patients, and they all indicate a poor prognosis. However, IL-8, IFN-γ, and CCL5 have great research value in chemotherapy resistance and improvement of treatment effect. This article reviews the research progress of cytokine biomarkers in the prognosis of AML patients.

Cytokines help suggest aplastic anemia with pulmonary bacterial or co-fungal infection.

Although aplastic anemia (AA) does not come under the category of blood malignant diseases, the infection that frequently occurs in this bone marrow failure can make it worse. Pulmonary infection is the most prevalent but limiting clinical diagnosis. To find biomarkers predicting bacterial or bacterial-combined fungal infections in the lungs, we reviewed 287 AA medical records including 151 without any infection, 87 with pure pulmonary bacterial infection, and 49 with bacterial and fungal infection were reviewed. There were substantial changes in IL-17F, IL-17A, IFN-γ, IL-6, IL-8, and IL-10 levels between the non-infected and lung bacterial infection groups (P < 0.05). Further, a significant variation in IL-17A, TNF-ß, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-22, and IL-12p70, between the uninfected group and the pulmonary bacterial and fungal infection group (P < 0.05) was observed. The results further revealed significant differences in TNF-ß, IL-12p70, IL-6, IL-8, and IL-10 between the pulmonary bacterial infection group and the fungal infection group (P < 0.05). Moreover, by calculating ROC and cut-off values, we determined that IL-6 (AUC = 0.98, Cut-off = 14.28 pg/ml, P = 0.0000) had a significant advantage than other cytokines, body temperature (AUC = 0.61, P = 0.0050), PCT (AUC = 0.57, P = 0.0592), and CRP (AUC = 0.60, P = 0.0147) in the detection of lungs bacterial infections. In addition, IL-6 (AUC = 1.00, Cut-off = 51.50 pg/ml, P = 0.000) and IL-8 (AUC = 0.87, Cut-off = 60.53 pg/ml, P = 0.0000) showed stronger advantages than other cytokines, body temperature (AUC = 0.60, P = 0.0324), PCT (AUC = 0.72, Cut-off = 0.63 ng/ml, P = 0.0000) and CRP (AUC = 0.79, Cut-off = 5.79 mg/l, P = 0.0000) in distinguishing bacteria from fungi. This may suggest that IL-8 may play a role in differentiating co-infected bacteria and fungi. Such advantages are repeated in severe aplastic anemia (SAA) and very severe aplastic anemia (VSAA).In conclusion, aberrant IL-6 elevations in AA patients may predict the likelihood of bacterial lung infection. The concurrent increase of IL-6 and IL-8, on the other hand, should signal bacterial and fungal infections in patients.These findings may help to suggest bacterial or fungal co-infection in patients with AA (Focus on VSAA and SAA).

Complement 4 Aids in the Prediction of Newly Diagnosed Multiple Myeloma Outcome in Patients.

BACKGROUND: A cure for the heterogeneous hematological malignancy multiple myeloma (MM) is yet to be developed. To date, the early risk factors associated with poor outcomes in MM have not been fully elucidated. Studies have shown an aberrant complement system in patients with MM, but the precise association necessitates elucidation. Therefore, this study scrutinizes the correlation between serum complement level and the disease outcome of patients with MM. METHODS: A retrospective analysis of 72 patients with MM (new diagnosis) with complement C4 and C3 along with common laboratory indicators was done. The Pearson χ2 test and the Mann-Whitney U-test were done to evaluate categorical or binary variables and intergroup variance, respectively. Kaplan-Meier test and Cox proportional hazards regression were used for quantification of overall survival (OS) and univariate or multivariate analyses, respectively. RESULTS: The Cox proportional hazard model analysis unveiled the following: platelet ⩽115.5 × 109/L (hazard ratio [HR] = 5.82, 95% confidence interval [CI] = 2.522-13.436, P < .001), complement C4 ⩽0.095 g/L(HR = 3.642, 95% CI = 1.486-8.924, P = .005), age ⩾67 years (HR = 0.191, 95% CI = 0.078-0.47, P < .001), and bone marrow plasma cell percentage ⩾30.75% (HR = 0.171, 95% CI = 0.06-0.482, P = .001) can be used as independent predictors of OS. Of these, advanced age, low platelet level, and a high proportion of bone marrow plasma cells have been implicated in poor outcomes in patients with MM. Interestingly, a low complement 4 level can function as a new indicator of poor prognosis in patients with MM. CONCLUSION: Low levels of C4 are indicative of a poor outcome in newly diagnosed patients with MM.

Increased Cytokine Levels Assist in the Diagnosis of Respiratory Bacterial Infections or Concurrent Bacteremia in Patients With Non-Hodgkin's Lymphoma.

Non-Hodgkin's lymphoma (NHL) is a form of tumor that originates in the lymphoid tissues. Bacterial infections are very common in NHL patients. Because most of the patients do not experience apparent symptoms during the initial stage of infection, it is difficult to detect the underlying condition before it progresses to a more critical level. The activation of the cytokines is a hallmark of inflammation. Due to the advantages of short detection time and high sensitivity of cytokines, many studies have focused on relationship between cytokines and infection. However, few studies have been conducted on NHL patients with infection. Therefore, we reviewed the cytokine profiles of 229 newly diagnosed NHL patients and 40 healthy adults to predict respiratory bacterial infection and bacteremia. Our findings revealed that IL-6(41.67 vs 9.50 pg/mL), IL-8(15.55 vs 6.61 pg/mL), IL-10(8.02 vs 4.52 pg/mL),TNF-ß(3.82 vs 2.96 pg/mL), IFN- γ(4.76 vs 2.96 pg/mL), body temperature(37.6 vs 36.5°C), CRP(20.80 vs 4.37 mg/L), and PCT(0.10 vs 0.04 ng/mL) levels were considerably greater in NHL cases with respiratory bacterial infections relative to NHL cases without infection (P<0.05). Furthermore, IL-6(145.00 vs 41.67 pg/mL), IL-8(34.60 vs 15.55 pg/mL),temperature(38.4 vs 37.6°C), PCT(0.79 vs 0.10 ng/mL), and CRP(93.70 vs 20.80 mg/L) levels in respiratory infectious NHL patients with more severe bacteremia were considerably elevated than in patients with respiratory bacterial infections only (P<0.05). Remarkably, increased levels of IL-6 and IL-8 are effective in determining whether or not pulmonary bacterial infectious NHL patients have bacteremia. Temperature, PCT, and CRP all have lower sensitivity and specificity than IL-6. IL-6 ≥18.79pg/mL indicates the presence of pulmonary bacterial infection in newly diagnosed NHL patients, and IL-6 ≥102.6pg/mL may suggest pulmonary bacterial infection with bacteremia. In short, this study shows that cytokines can be advantageous in the diagnosis and differentiation of pulmonary bacterial infection and bacteremia in newly diagnosed NHL patients and may also guide for the use of clinical antibiotics.

Analysis of cytokine risk factors in the early death of patients with secondary phagocytic lymphocytic histiocytosis.

Secondary hemophagocytic lymphohistiocytosis (sHLH) is an excessive inflammatory response syndrome caused by immune abnormalities. Up to date, the risk factors for cytokines causing early death in sHLH patients have not been elucidated. Our study reviewed the cytokine expression levels in peripheral blood of 50 sHLH patients. Through Cox proportional hazard model analysis, we found that IL-17F ≥2.835 pg/mL (HR = 5.922, 95% CI = 1.793-19.558, P = 0.004) was an independent death risk factor in sHLH patients, and it was also 30 days (Cutoff-value = 2.890 pg/mL, HR = 16.568, 95% CI = 1.917-143.195, P = 0.011), 60 days (Cutoff-value = 2.890 pg/mL, HR = 7.559, 95% CI = 1.449-39.423, P = 0.016), 90 day death risk factor (Cutoff-value = 2.835 pg/mL, HR = 7.649, 95% CI = 1.965-29.778, P = 0.003); IL-10 ≥16.730 pg/mL (HR = 4.821, 95% CI = 1.151-20.116, P = 0.031) is not only a death risk factor within 90 days, but also within 10 days (Cutoff-value = 944.350 pg/mL, HR = 13.321, 95% CI = 1.123-158.03, P = 0.027); and IL-5 ≥2.495 pg/mL (HR = 15.687, 95% CI = 1.377-178.645, P = 0.04) was also a death risk factor within 10 days. Besides, IL-17F, IL-10, IL-5, and the previously reported common risk factors Age, platelets, activated partial thromboplastin time, triglyceride, and lactate dehydrogenase were analyzed together. It was found that the patient age ≥56 years-old is was an important risk factor for death within 30 days, IL-17 ≥2.89 pg/mL and IL-10 ≥16.73 pg/mL are important risk factors for patient death. In summary, our data indicate that age, IL-10 and IL-17F are important risk factors for early death in sHLH patients.

Cytokine Expression of Lung Bacterial Infection in Newly Diagnosed Adult Hematological Malignancies.

Adult patients with hematological malignancies are frequently accompanied by bacterial infections in the lungs when they are first diagnosed. Sputum culture, procalcitonin (PCT), C-reactive protein (CRP), body temperature, and other routinely used assays are not always reliable. Cytokines are frequently abnormally produced in adult hematological malignancies associated with a lung infection, it is uncertain if cytokines can predict lung bacterial infections in individuals with hematological malignancies. Therefore, we reviewed 541 adult patients newly diagnosed with hematological malignancies, of which 254 patients had lung bacterial infections and 287 patients had no other clearly diagnosed infections. To explore the predictive value of cytokines for pulmonary bacterial infection in adult patients with hematological malignancies. Our results show that IL-4, IL-6, IL-8, IL-10, IL-12P70, IL-1ß, IL-2, IFN-γ, TNF-α, TNF-ß and IL-17A are in the lungs The expression level of bacterially infected individuals was higher than that of patients without any infections (P<0.05). Furthermore, we found that 88.89% (200/225) of patients with IL-6 ≥34.12 pg/ml had a bacterial infection in their lungs. With the level of IL-8 ≥16.35 pg/ml, 71.67% (210/293) of patients were infected. While 66.10% (193/292) of patients had lung bacterial infections with the level of IL-10 ≥5.62 pg/ml. When IL-6, IL-8, and IL-10 were both greater than or equal to their Cutoff-value, 98.52% (133/135) of patients had lung bacterial infection. Significantly better than PCT ≥0.11 ng/ml [63.83% (150/235)], body temperature ≥38.5°C [71.24% (62/87)], CRP ≥9.3 mg/L [53.59% (112/209)] the proportion of lung infection. In general. IL-6, IL-8 and IL-10 are abnormally elevated in patients with lung bacterial infections in adult hematological malignancies. Then, the abnormal increase of IL-6, IL-8 and IL-10 should pay close attention to the possible lung bacterial infection in patients.

Traditional Chinese medicine compound, Bu Sheng Hui Yang Fang, promotes the proliferation of lymphocytes in the immunosuppressed mice potentially by upregulating IL-4 signaling.

The immune system plays a pivotal role in defending against infection and cancer immunosurveillance during the onset and procession of malignant disease. Cancer patients are frequently immunocompromised and subject to refractory infection and relapse of leukemia, due to the cytotoxic agents and immunosuppressive glucocorticoids in the chemotherapy regimens. Bu Shen Hui Yang Fang (BSHY), a traditional Chinese compound, was widely used in China to enhance the immune system of leukemia patients combined with chemotherapy and effectively lowered their risk of infection, with specific mechanism unknown yet. Thus, we investigated the effects of BSHY on the immune system using immunosuppressive mouse models. By analyzing the immune system of immunosuppressed BALB/C mice induced by hydrocortisone, we found an increase of CD4+ and CD8+ lymphocytes in the spleens of mice after BSHY treatment. Furthermore, we found the enhanced immune system in BSHY treated group was due to increased proliferation and decreased apoptosis of lymphocytes. Cytokine array analysis revealed that interleukin 4 (IL-4) was reduced in the plasma of immunosuppressed mice but returned to a normal level after BSHY treatment. Moreover, we found IL-4 was an adverse prognostic factor in acute myeloid leukemia patients and part of them could be elevated by BSHY. Mechanistically, we found BSHY enhances the proliferation of lymphocytes in a Stat6-dependent manner. In summary, our current study demonstrates that BSHY enhances the proliferation of lymphocytes in the immunosuppressed mice via upregulating IL-4 signaling.

[Research Progress on Pathogenic Genes of Ph-like Acute Lymphoblastic Leukemia--Review].

Abstract　　Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL or BCR-ABL1-like ALL) is a kind of acute leukemia which has the similar gene expression profiles and manifests the biological behavior same to Ph-positive ALL, but lacks the BCR-ABL1 fusion gene. Ph-like ALL was involved in multiple abnormal changes of genomes, activating kinase and cytokine receptor signaling. This review focuses on the progress of classical genetic abnormalities of PH-like ALL in the JAK-STAT signaling, ABL kinase activation, TKI resistance in Ph-like ALL, SH2B3 gene inactivating mutation and IKZF1 gene abnormality. Besides, also summarizes the frontier progress of novel gene mutation (ATF7IP exon 9 fused with PDGFRB exon 11, PDGFRBC843G mutation caused by fusion of exon 11-23 of PDGFRB with exon 1-6 of AGGF1 gene) in recent years.