Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Objective To investigate the effects of matrine on proliferation and apoptosis of human Tenon capsule fibroblasts (HTFs) in.vitro.Methods After treated with 0,0.3,0.6 and 0.9 g/L matrine in vitro,cell counting kit-8 (CCK-8) method was used to assay the proliferation of HTFs at 24,48 and 72 hours,Western blot and PCR were performed to evaluate the expression of apoptosis-associated factor caspase-3 on both protein and RNA levels.Results The activity of human Tenon capsule fibroblast at 48 hours and 72 hours after treated with 0.3,0.6,0.9 g/L matrine was significantly inhibited when compared with the 0 g/L matrine group,and the inhibitory effect was dose-dependent and time-dependent (F ion =1 019.51,P =0.00;Ftime =5 848.66,P =0.00;Fi ion =147.45,P=0.00).After treated with 0,0.3,0.6 and 0.9 g/L matrine,the early apoptosis rate of HTFs was (2.68±0.30)％,(5.08±0.47)％,(6.97±0.69)％ and (10.30±1.20)％,the grey value ofcaspase-3 protein was 1.00±0.13,1.90±0.19,2.50±0.30 and 2.67±0.30,the relative expression of caspase-3 mRNA was 0.98 ±0.12,2.01 ±0.34,6.15 ± 0.60 and 11.40 ± 1.12,respectively,with significant differences among them (F =55.74,66.01,154.50;all at P＜0.01),the early apoptosis rate of HTFs,the grey value of caspase-3 protein and the relative expression of caspase-3 mRNA were all increased significantly as the concentration of matrine increased,with significant differences between any two groups (all at P＜0.05).Conclusions Matrine can inhibit the proliferation of HTFs and induce the apoptosis of HTFs in a time-and dose-depended manner.

Acute myelogenous leukemia (AML) is a highly heterogeneous malignant hematologic disease, and its clinical treatment mainly includes traditional chemotherapy, but the efficacy is limited and the patients with worse performance status and comorbidities can not be treated with chemotherapy. In recent years, immunotherapy has achieved certain curative effects in AML which shows a promising prospect. This review introduces immunotherapy of AML reported in 60th American Society of Hematology (ASH) Annual Meeting.

Objective To observe the clinical efficacy and adverse events of decitabine combined with full_dose and long_term pre_excitation regimen as a induction therapy for relapsed/refractory acute myeloid leukemia (AML). Methods A total of 32 patients with relapsed/refractory AML in Henan Provincial Cancer Hospital from May 2013 to February 2018 were enrolled. All the patients were treated with decitabine combined with full_dose and long_term pre_excitation regimen, including 15 patients who received decitabine combined with CAG regiemtn, and 17 patients who received decitabine combined with CHAG regimen: 25 mg decitabine, intravenous drip, from day 1 to day 3; cytarabine (10-15 mg/m2) administered subcutaneously every 12 h one time, from day 4 to day 17 or more; homoharringtonine (1 mg/m2) intravenous drip, administered intravenously from day 4 to day 10 or more; aclacinomycin (8-10 mg/m2), intravenous drip, administered intravenously from day 4 to day 11 or more; granulocyte colony_stimulating factor (G_CSF) (100-200 μg/m2), subcutaneous injection, and it began 1 day before chemotherapy, adjusted according to the blood cell count; the therapeutic effect and adverse reactions of the patients were observed. Results There were 29 patients (90.6% ) with complete remission (CR), 3 patients (9.4% ) with partial remission (PR), and the overall response (CR+PR) rate was 100.0% (32/32). In decitabine combined with CAG regimen group, 13 patients achieved CR; in decitabine combined with CHAG regimen group, 16 patients achieved CR, and there was no statistically significant difference in the efficacy between the two groups (P＝0.589). The main adverse reactions were agranulocytosis, thrombocytopenia, secondary infection and fever, and no serious adverse events occurred. Conclusion Decitabine combined with full_dose and long_term pre_excitation regimen has a favorable efficacy and safety, which provides a new therapy for relapsed/refractory AML.

Objective To explore the clinical efficacy and safety of low﹣dose decitabine subcutaneous injection combined with arsenicals in the treatment of medium﹣ and high﹣risk myelodysplastic syndromes (MDS). Methods Eight cases of medium﹣ and high﹣risk MDS without allogeneic hematopoietic stem cell transplantation in the Affiliated Cancer Hospital of Zhengzhou University and Xinhua Area Hospital of Pingdingshan City from January 2015 to August 2018 were retrospectively analyzed. The patients were given subcutaneous injection of low﹣dose decitabine combined with arsenicals. The specific regimen was as follow:0.1-0.2 mg/kg of decitabine, subcutaneous injection 2 times/week, 4 weeks in total; arsenic injection 10 mg/time or 0.16 mg/kg, intravenous administration, 1 time/d, 4 weeks; compound Huangdai tablets 60 mg/kg per day, 3 times orally. The efficacy and adverse reactions were observed. Results In 8 patients, there were 5 male and 3 female, with an average age of 61.4 years old (44-80 years old) Eleven cases were refractory anemia with excess blasts (RAEB), 6 cases were RAEB﹣2, 1 case was refractory cytopenia with multilineage dysplasia (RCMD) with bone marrow fibrosis (MF). Three of the patients had previously received treatment with decitabine. All patients completed the treatment successfully and no treatment﹣related deaths occurred. By the end of follow﹣up, 2 patients had complete remission, 4 patients had complete bone marrow remission with hematologic improvement, 1 patient had stable disease, and 1 patient had disease progression. For 2 patients who had been treated with decitabine regimen, the regimen of re﹣administered decitabine plus arsenic was still effective. Eight patients had more than level 2 of myelosuppression, except for one patient with intestinal infection due to unclean diet and one patient with mild pulmonary infection. The remaining 6 patients had no associated infection and heart, liver, kidney and other adverse reactions. Conclusion Low﹣dose decitabine subcutaneous injection combined with arsenicals is safe and could be a new treatment for the medium﹣ and high﹣risk MDS.

Objective: To explore the availability and safety of fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Four acute leukemia patients suffered from refractory diarrhea after allo-HSCT. One of them was refractory intestinal infection, the others were intestinal graft versus host disease. One or two doses of fecal microbiota, 3.4-6.0 U for one dose, were infused via nasal-jejunal tube. The curative effect and side effects were reviewed. Results: Three cases achieved complete remission while 1 was stable disease. The side effects included fever, abdominal pain and diarrhea, which all were Ⅰ grade. Conclusion Fecal microbiota transplantation was effective and safe for refractory diarrhea after allo-HSCT.

Objective: To explore the clinical efficacy and prognostic factors of first-generation and second-generation tyrosine kinase inhibitors (TKI) based regimen in the treatment of patients with BCR-ABL positive acute lymphoblastic leukemia (ALL) . Methods: Retrospectively analyze the clinical characteristics and prognostic factors of 89 patients with BCR-ABL positive ALL from April 2012 to June 2018 in our hospital, the clinical efficacy of first-generation and second-generation TKI was compared. Results: 60 patients were classified into the first-generation TKI (imatinib) group, and 29 patients were in the second-generation TKI (dasatinib) group. There were no significant differences in gender, age, WBC, hemoglobin concentration, PLT, chromosomal karyotype, the types of fusion genes, allogeneic hematopoietic stem cell transplantation (allo-HSCT) and TKI initiation time between the two groups. The first-generation and second-generation TKI groups, for which the complete remission (CR) rate at the fourth week of induction therapy was 83.3% and 89.7% (P=0.637) , respectively, and the complete molecular remission (CMR) was 48.3%and 58.6% (P=0.363) , respectively, the difference was not statistically significant. The 2-year overall survival (OS) rate of first-generation and second-generation TKI group was 34.9% and 64.0% (χ²=4.743, P=0.029) , the 2-year relapse free survival (RFS) rate was 17.2% and 55.0% (χ²=8.801, P=0.003) , respectively. Multivariate analysis showed that complete molecular remission (HR=0.281, 95%CI 0.151-0.523, P<0.001) was independent favorable prognostic factor for overall survival (OS) , complete molecular remission (HR=0.209, 95%CI 0.112-0.390, P<0.001) and second-generation TKI (HR=0.318, 95%CI 0.158-0.641, P=0.001) were independent favorable prognostic factors for RFS. Conclusion For TKI-based regimen of BCR-ABL positive ALL, second-generation TKI is superior to first-generation TKI in OS and RFS time.

Objective: To analyze the efficacy and safety of lenalidomide combined with interferon (IFN) and interleukin-2 (IL-2) for treatment of refractory/relapsed or minimal residual disease (MRD)-positive acute myelogenous leukemia (AML). Methods: Twelve patients with AML who were hospitalized in the Affiliated Cancer Hospital of Zhengzhou University from August 2013 to May 2019 were selected. These patients were previously treated with thalidomide combined with IFN and IL-2, and then treated with combined with IFN and IL-2. According to the Frence-American-British (FAB) classification system, there was 1 case of M₀, 1 case of M₁, 4 cases of M_2a, 3 cases of M_2b, 1 case of M_4EO, and 2 cases of M_5b. There were 2 cases with FLT3-ITD mutation-positive, 1 case with c-kit mutation-positive. There were 2 cases in the low-risk group, 7 cases in the intermediate-risk group, and 3 cases in the high-risk group. Three cases were refractory AML, 7 cases were relapsed AML (including 3 cases of recurrence once, 4 cases of recurrence twice; 5 cases of recent recurrence, 2 cases of long-term recurrence), 2 cases were MRD-positive. The efficacy and adverse reactions of 12 cases were evaluated. Results: Twelve patients had received more than one cycle therapy of lenalidomide combined with IFN and IL-2, of which 4 patients achieved morphological complete remission (CR), 2 patients had CR with incomplete recovery of blood cells (CRi), 4 patients had no remission, 1 case had a decrease in MRD, and 1 case had an increase in MRD, and the total effective (CR+ CRi+ partial remission+ MRD decreased) was in 7 cases. There were no adverse reactions such as rash, constipine, bradycardia and peripheral neuritis; six patients had grade Ⅲ or higher experienced myelosuppression. No patients died of complications during the treatment, and the duration of remission of all patients was 2-20 months. Conclusion Lenalidomide combined with IFN and IL-2 for treatment of refractory/relapsed or MRD-positive AML is effective, and it can reduce the MRD value in MRD-positive patients, it could be a new treatment method for AML.

Background and Purpose: With the rapid development of minimally invasive technique, robotic surgery is widely used in the gynecological surgery. This study aimed to compare the clinical data of roboticassisted laparoscopy and laparotomy in the treatment of early ovarian cancer. Methods: A total of 22 patients with early ovarian cancer receiving stage Ⅰ operation between Jan. 2015 and Dec. 2016 in Jilin Province Tumor Hospital were randomly divided into two groups: 8 patients received robotic-assisted surgery (robotic-assisted laparoscopic group), 14 patients received laparotomy (laparotomy group). Results: All patients underwent successful operation without changing surgical approach. The operation time in robotic-assisted laparoscopic group was longer than that in laparotomy group [(194.50±10.90) min vs (178.71±10.58) min, P＜0.05]. Blood loss volume [(60.10±8.88) mL vs (73.71±12.99) mL], 24 hours postoperative drainage volumes of robotic-assisted laparoscopic group were less than those in laparotomy group [(96.88±10.21) mL vs (108.00±11.43) mL, P＜0.05]. Others had no statistical significance (P＞0.05). Conclusion: In the clinical treatment of early ovarian cancer, there is no difference between robotic-assisted laparoscopic operation and laparotomy. Robotic-assisted laparoscopic operation is worthy of clinical promotion and application.