AIM: To study the effects of Cripto gene on vascular endothelial growth factor(VEGF) of colon carcinoma cells.METHODS: Cripto siRNA was designed and constructed.Colon cancer LS-174T cells were divided into 4 groups: control group and different dose (3.125,6.25 and 12.5 nmol/L) of siRNA groups.After transfected for 24,48 and 72 h,colon cancer cells were harvested to carry on the next tests.Expression of Cripto mRNA was determined with real-time PCR,and immunofluorescence isothiocyanate(FITC) labeling assay and Northern blotting were performed to examine the expression of protein and mRNA of VEGF,respectively.The cells in control group and cells transfected with 12.5 nmol/L siRNA were inoculated into nude mice respectively.30 days after inoculated,the mice of two groups were executed,and immunohistochemical(ICH) assay was used to evaluate the VEGF protein of mice tumor.RESULTS: siRNA down-regulated the Cripto mRNA in a dose and time dependent manner.Protein and mRNA of VEGF in transfected cells reduced in a dose and time dependent manner.Compared to control,the expression of VEGF protein from ICH assay was lowered significantly(P

Objective To explore statin dosages for targeting goal of LDL-C lowering on the basis of stroke risk stratification and the dosage-effective relation of statin and LDL-C lowering in Chinese patients with ischemic stroke and transient ischemic attack (TIA).Methods This is a prospective and open clinical trial patients with ischemic stroke/TIA within 6 months were enrolled and the dosages of atorvastatin were calculated based on risk stratification according to "Chinese Consensus for Prevention of Ischemic Stroke/TIA with Statin" (Chinese Consensus).A dose of 10 mg of atorvastatin daily to target LDL-C goal was takenas the standard dosage targeting goal (SDTG).Patients taking this dosage of atorvastatin constituted a SDTG group.Those who needed a daily dose of 20 mg or more of atorvastatin were randomized into an intensive dosage targeting goal (IDTG) group ( atorvastatin 20-80 mg/d) and a standard dosage non-targeting goal (SDNTG) group (atorvastatin 10 mg/d without targeting goal).All patients took atorvastatin for 12 weeks.The primary outcome was the rate of targeting goal for LDL-C lowering at 2,4 and 12 weeks,respectively and the secondary outcome was the occurence of recurrent stroke and other vascular events within 12 weeks.The main safety endpoint was serial adverse events including symptomatic intracranial hemorrhage.Results Altogether 102 cases were enrolled and 99 cases were followed up for 12 weeks.According to the Chinese Consensus,the rate of high risk,very high risk- Ⅰ and very high risk- Ⅱ was 44% ,28% and 28%,respectively.Targeting rate for LDL-C lowering was 77% -85% at each time point in the SDTG and IDTG groups ,being significantly higher than those in the SDNTG group ( 12% -16%,P < 0.01 ).No significant difference was found concerning the occurrence of recurrent stroke,other vascular events and safety endpoints among the three groups.The amplitude of LDL-C lowering was 32%-35% ,46%-49% ,51%-52% and 60%-65% with corresponding to daily dosage of 10 mg,20 mg,d0 mg and 80 mg atorvastatin.Conclusions At least more than half of the patients after iscbemic stroke/TIA need intensive statin therapy to target the LDL-C lowering goal.The dosage- effective relation of atorvastatin and LDL-C lowering in Chinese is similar to the reported data in other races.

Objective To investigate the changes and prognostic significance of bone marrow(BM) oil drop and megakaryocyte counts after chemotherapy in acute myeloid leukemia (AML) patients (non-M3).Methods Ninty-nine adult patients with denovo AML (non-M3) were retrospectively analyzed to evaluate the change of BM oil drop and megakaryocyte counts and their influences on overall survival(OS) and disease free survival (DFS) during all stages of standardized therapy.Results The median DFS and OS were 21 (2-88);months and 70 (4-89) months,respectively; and 3-year predicted DFS and OS were 47.3 ％ and 55.8 ％,respectively.After AML patients (non-M3) achieving complete remission (CR) by induction therapy,BM oil drop tended to increase along with postremission chemotherapy cycle accumulation, while megakaryocyte counts tended to decrease.The univariate analysis indicated that megakaryocyte counts decreased after the second course of postremission therapy. BM oil drop increased after the first to the third course of postremission therapy.Grade of myelofibrosis in BM biopsy,serum lactate dehydrogenase (LDH) level at diagnosis,flow cytometric immunophenotyping, the percentage of BM blast cells at diagnosis and the percentage of residual leukemic cells (RLC) during aplasia (7-10 days after the end of induction therapy) had prognostic significance.Multivariable COX analysis indicated the percentage of BM blast cells at diagnosis and change of BM oil drop after the third postremission therapy were independent prognostic factors for DFS (P =0.010,0.018 respectively),and RLCs during aplasia and change rate of the megakaryocyte counts after the second postremission therapy were independent prognostic factors for OS (P =0.009, 0.038respectively).Conclusion After AML patients (non-M3) achieving CR by induction therapy,BM oil drop tends to increase along with postremission chemotherapy cycles accumulation,while the megakaryocyte counts tend to decrease.Dynamic observations of bone marrow oil drop and megakaryocyte counts are helpful for assessing the prognosis of acute myeloid leukemia (non-M3).

Objective To improve the acknowledge of diagnosis and therapy of aggressive systemic mastocytosis (ASM).Methods One ASM patient was reported and the literatures were reviewed.Results As a rare subtype of SM,ASM is characterized by multiple organs involvement,and often accompanied by bone marrow dysfunction,osteolytic lesions and palpable hepatomegaly or splenomegaly which usually indicate the high mast cell burden.Conclusion ASM meets criteria for SM and has one or more C findings.Variable factors affect the prognosis of ASM patients and the formulation of the clinical treatment strategy which leads to the highly individualized therapies.

Objective To strengh the awareness of acute T-B cell biphenotypic leukemia.Methods Four new cases of acute T-B cell biphenotypic leukemia were reported and the related literature were reviewed.Results Fourteen patients with acute T-B cell biphenotypic leukemia.including 4 diagnosed at our hospital and other 10 cases reported in literature,were retrospectively analyzed.Similar clinical fleatures as the typical acute lymphocytic leukemia(ALL) were presented.Ten of 14 cases were male and were within 17 to 46 years old.The disease were refactory to the conventional ALL chemotherapy regimens and deteriorated progressively.Six patients died within 12 months after their diagnosed with the median survival time of ten months. Conclusion Acute T-B cell biphenotypic leukemia is one of the most rare type of leukemia.A better understanding of the clinical and hematological features of this type of leukemia and new therapeutic strategies are needed.

Objective:To investigate the clinical features, the key point of diagnosis and treatment methods of X-linked hyper-IgM syndrome (XHIGM).Methods:The clinical characteristics and laboratory data of a patient aged 23 years who was diagnosed as XHIGM complicated with T-cell large granular lymphocytic leukemia (TLGLL) in Institute of Hematology & Blood Diseases Hospital in March 2020 were analyzed retrospectively, and the literatures were reviewed.Results:This male patient presented with recurrent infection when he was 17 years old, and was found neutropenia, anemia accompanied by obvious splenomegaly, lower level of IgG and IgA after the visit. The level of IgM was lower than the normal level and the typical XHIGM was manifested with the normal or increased level of IgM, however CD40L homozygous mutation (chromosome: chrX; location: 135730438; variation of amino acid: NM_000074:exon1:c.31C>T:p.R11X; nonsense mutation) was confirmed by next generation sequencing. CD40L heterozygous mutation was detected in his mother, but it was not in his father. The patient was diagnosed as XHIGM. Anemia and neutropenia were alleviated after splenectomy in the patient, who was diagnosed as T-cell large granular lymphocyte elevation and clonal proliferation by flow cytometry, TCR gene rearrangement positive and bone marrow histopathological immunohistochemistry results because of the increasing leukocyte. The patient was eventually diagnosed as XHIGM complicated with T-LGLL.Conclusions:A small number of patients with XHIGM may develop symptoms in adulthood and may present with atypical clinical features of significant reduction in IgG, IgA, and IgM. The confirmed diagnosis of XHIGM is established by identification of CD40L gene mutation. XHIGM gene screening is required in male patients with recurrent infection, IgG level lower than normal and neutropenia. A few XHIGM patients are complicated with T-LGLL.

Objective: To understand the characteristics of sports load intensity of junior middle school physical education, and its relation with students’ physical fitness, and to provide suggestions for scientific arrangement of sports load of physical education. Methods: A total of 88 students from three grades in a middle school in Guangzhou were randomly selected. Polar heart rate tester was used to monitor the students’ heart rates during class, and physical fitness test was conducted on the students to obtain their physical fitness scores. Descriptive analysis, correlation analysis and one-way analysis of variance were used to process the data. Results: From the static characteristics, in junior high school physical education class, the mean of the lowest heart rate was 86.94 times/min, the mean of the average heart rate was 142.55 times/min, the mean of the maximum heart rate was 192.66 times/min, the average heart rate of junior grade one students was significantly lower than that of junior two students and junior three students (F=3.64，P<0.05). There was no significant difference in average heart rate between boys and girls (F=0.83，P>0.05); In terms of dynamic characteristics, heart rates at 3 and 31 minutes were significantly lower than those at 10, 17 and 24 minutes (F=13.87，P<0.01),in each part of junior high school physical education class, there were significant differences between grades, specifically, the heart rate of junior students was significantly lower than that of senior students (F=9.85，P<0.01); In terms of the correlation between exercise intensity and physical fitness, there was a significant negative correlation between the lowest heart rate, average heart rate, maximum heart rate and physical fitness(r=-0.34，-0.32，-0.29，P<0.01). Conclusion The physical activity intensity of junior middle school students is moderate and the average heart rate is within the range stipulated by "Chinese healthy physical education curriculum model".

Objective:To investigate the association between pulse pressure(PP) and new-onset diabetes in overweight and obese people.Methods:A prospective cohort study was conducted in overweight or obese participants selected from Kailuan Study who underwent 2006-2007 annual checkup and met the inclusion and exclusion criteria. PP was calculated by blood pressure and participants were divided into 4 groups according to PP quartile. The cumulative incidence of new-onset diabetes of different PP groups was calculated by Kaplan- Meier method and compare by Log- Rank test. The multivariate Cox proportional hazards model was used to analyze the association between different PP groups and new-onset diabetes. Results:During an average follow-up of 8.45 years, 8 922 diabetes was identified. The cumulative incidence rate of the Q1, Q2, Q3, and Q4 groups were 22.12%, 24.48%, 27.97%, and 33.44% respectively, which were statistically different( χ2=368.16, P<0.01). Cox proportional hazards regression analysis showed that after adjusting for multiple confounding factors, compared with Q1 group, the hazard ratio for diabetes in Q2, Q3, and Q4 groups were 1.07(1.00-1.14), 1.13(1.05-1.21), and 1.17(1.09-1.27) respectively. And the HR of diabetes event in pulse pressure(per 1 SD increase) was 1.04(1.02-1.07). Similar results were found in participants who were over-weight, obese, with normal blood pressure or hypertensive without drugs use. Conclusion:PP is positively correlated with the new-onset diabetes. High PP is one of the risk factors for developing diabetes in overweight and obese people.

Objective: To evaluate the efficacy and tolerability of ruxolitinib combined with prednisone, thalidomide and danazol for treatment of in myelofibrosis (MF). Methods: Patients of MF according to the WHO 2016 criteria, received ruxolitinib (RUX) combined with prednisone, thalidomide and danazol (PTD). The response, changes of blood counts and adverse events were evaluated. Results: Six PMF and one post-ET MF patients were enrolled. Four patients presented JAK2V617F mutation, one CALR mutation, one MPL mutation, one triple-negative. Responses per IWG-MRT criteria were clinical improvement in 5 patients, stable disease in 2 ones, spleen response in 6 ones. All of 7 patients were symptomatic responses, four patients achieved at least 50% improvement from baseline on MPN-SAF TSS. Three patients initially treated with RUX alone, all of 3 patients experienced treatment-associated anemia and thrombocytopenia. Then these 3 patients received RUX combined with PTD, both hemoglobin and platelet increased significantly. Four patients initially treated with RUX combined with PTD. Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×10⁹/L, respectively from baseline. The treatment dose of RUX increased due to improved platelet count in 3 patients. The frequent non-hematologic adverse events grade 1-2 were constipation, abdominal distension, crura edema and increased ALT. Conclusions RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone, and may increase response due to improved levels of hemoglobin or platelet.

Objective: To observe the clinical efficacy and safety of the patients of myelodysplastic syndromes-refractory anemia with excess blasts (MDS-REAB) treated with decitabine alone or based on low dose cytarabine (Ara-C) regimen CAG/HAG [aclarubrci (ACR) /homoharring-tonine (HHT) +cytarabine+granulocyte colony stimulating factor (G-CSF) ]. Methods: Totally 121 patients with MDS-REAB were retrospectively analyzed, including 59 patients treated with decitabine alone (20 mg·m^-2·d^-1 for 5 days) , the rest 62 ones treated with low-dose Ara-C-based regimen CAG/HAG. Overall response rate (ORR) , overall survival (OS) and adverse events of the two groups were analyzed and compared retrospectively. Results: The ORR of decitabine alone or CAG/HAG were 66.2% and 56.4% respectively, with no statistically significant differences (χ²=1.185, P=0.276) . Initial response rate detected by the end of first cycle of CAG/HAG was higher than that of decitabine alone (94.3% vs 69.2%) , there was statistically significant difference in the overall comparison of two groups (χ²=7.612, P=0.009) . The median OS of decitabine alone was 19.5 (95% CI 10.5-28.4) months, the median OS of CAG/HAG was 20.3 (95% CI 10.7-29.9) months, with no statistically significant differences (χ²=0.004, P=0.947) . Grade 3-4 cytopenia and infection were the most prevalent adverses of two group patients. Grade 3-4 cytopenia rate of CAG/HAG was higher than that of decitabine alone (100.0% vs 64.4%, P<0.001) . The infection rate detected at third cycle of CAG/HAG was higher than that of decitabine alone (52.9% vs 15.2%, P=0.008) . Conclusion The efficacy of treating MDS-RAEB with decitabine alone or CAG/HAG was equivalent. CAG/HAG treatment came into effect faster, but decitabine alone treatment was safer.