Objective:To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma(MCL)cell line Jeko-1 and its related mechanism.Methods:The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs,respectively.CCK-8 assay was used to detect the proliferation of the cells,and Western blot was used to measure the protein expression levels of BCL-2,caspase-3,PI3K,AKT and P-AKT.Results:After Jeko-1 cells were treated with chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibrutinib(3.125,6.25,12.5,25,50 μmol/L)alone for 24,48,72h respectively,the cell proliferation was inhibited in a time-and dose-dependent manner.Moreover,the two drugs were applied in combination at low doses(single drug inhibition rate＜50％),and the results showed that the combination of two drugs had a more significant inhibitory effect(all P＜0.05).Compared with the control group,the apoptosis rate of the single drug group of chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibutinib(3.125,6.25,12.5,25,50 μmol/L)was increased in a dose-dependent manner.The combination of the two drugs at low concentrations(3.125,6.25,12.5 μmol/L)could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups(all P＜0.05).Compared with control group,the protein expression levels of caspase-3 in Jeko-l cells were upregulated,while the protein expression levels of BCL-2,PI3K,and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone.The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins,and the differences between the combination group and the single drug groups were statistically significant(all P＜0.05).Conclusion:Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1,and combined application of the two drugs shows a synergistic effect,the mechanism may be associated with the AKT-related signaling pathways.

Lower extremity deep vein thrombosis (DVT) is one of the main complications in patients with traumatic fractures, and for severe patients, the DVT can even affect arterial blood supply, resulting in insufficient limb blood supply. If the thrombus breaks off, pulmonary embolism may occur, with a high mortality. The treatment and rehabilitation strategies of thrombosis in patients with lower extremity fractures have its particularity. DVT in traumatic fractures patients has attracted extensive attention and been largely studied, and the measures for prevention and treatment of DVT are constantly developing. In recent years, a series of thrombosis prevention and treatment guidelines have been updated at home and abroad, but there are still many doubts about the prevention and treatment of DVT in patients with different traumatic fractures. Accordingly, on the basis of summarizing the latest evidence-based medical evidence at home and abroad and the clinical experience of the majority of experts, the authors summarize the clinical treatment and prevention protocols for DVT in patients with traumatic fractures, and make this consensus on the examination and assessment, treatment, prevention and preventive measures for DVT in patients with different fractures so as to provide a practicable approach suitable for China ′s national conditions and improve the prognosis and the life quality of patients.

ObjectiveTo analyze the correlation between complete blood count （CBC）， glycosylated hemoglobin（GHbA1c）and thyroid function in late pregnancy on Tibetan Plateau. MethodsA retrospective analysis was performed on 374 patients of single pregnancies who had delivered in the department of Obstetrics and Gynecology， Chaya People's Hospital， Changdu City， Tibet Autonomous Region， between January 1， 2021 and December 31， 2021. All subjects completed CBC， GHbA1c and total triiodothyronine（TT3）， total thyroxine（TT4）， thyroid stimulating hormone（TSH）before delivery. According to the altitude of long-term residence， they were divided into three groups： the altitude of group A is <3500 m； the altitude of group B is 3 500~4 000 m； and the altitude of group C is ＞4 000 m. The anemia of Tibetan pregnant women in late pregnancy before and after adjustment， the levels of CBC， GHbA1c and thyroid function in different altitudes， and their correlations were analyzed. Results① The mean actual hemoglobin（HB）was 120.0（108.0~130.0）g/L， and the prevalence of anemia was 27.8%（104/374）. After adjustment， the mean HB was 93.0（80.0~104.0）g/L， and the prevalence of anemia was 84.3 %（315/374）； ② Actual HB levels increased with the rise of altitude， but the difference was not statistically significant（P>0.05）， and there was no difference among the three groups in the prevalence of anemia. After adjustment， HB levels showed a downward trends， while the prevalence of anemia increased with the rise altitude， and the difference was statistically significant（P＜0.001）. ③ Red blood cell count（RBC）and mean erythrocyte hemoglobin concentration（MCHC）increased， while TSH decreased with the rise of altitude， and the difference was statistically significant（P＜0.05）. ④ The actual HB and MCHC were positively correlated with TT4， GHbA1c was negatively correlated with TT4， and positively correlated with Platelet count （PLT）； spearman correlation analysis showed statistical significance（P＜0.05）. ConclusionsThe actual HB of Tibetan Plateau pregnant women in late pregnancy does not increase significantly with the rise of altitude. The prevalence of anemia increases significantly after adjustment according to the altitude. TSH decreases with the rise of altitude， and the altitude may have an effect on thyroid function in late pregnancy. Actual anemia in late pregnancy is associated with low T4， and low T4 and high PLT might be associated with increased GHbA1c. Actual HB， PLT and T4 in late pregnancy are expected to be predictors of thyroid disease and GDM.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

OBJECTIVE: To investigate the incidence of Runt-related transcription factor 1 (RUNX1) gene and its associated gene mutations in patients with acute myeloid leukemia (AML), and analyze its clinical characteristics and prognosis. METHODS: The genomic DNA-PCR method was used to detect the exon of RUNX1 gene, and the gene mutations were analyzed by genetic sequencing. NPM1, DNMT3A, FLT3-ITD, IDH1/2, K/N-RAS, CEPBA, TET2, and WT1 co-mutations were also detected. Patients were followed up to determine efficacy and prognosis. RESULTS: Among 171 patients, the RUNX1 gene mutation was detected in 17 cases, and the mutation rate was 9.9%. The type of RUNX1 gene mutation was 9 missense mutations, 4 frameshift mutations, and 4 nonsense mutations. The peripheral blood leukocyte count of the patients in mutation group was 3 (1-101) ×10 CONCLUSION AML patients with RUNX1 gene mutation shows unique clinical and biological characteristics, RUNX1 mutation can be regarded as a molecular marker of poor prognosis in AML patients.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Karyotype ; Leukemia, Myeloid, Acute/genetics* ; Leukocytes, Mononuclear ; Mutation ; Nucleophosmin

OBJECTIVE: To study the correlation of the expression alteration of Tim-3 with the T cell and B cell dysfunction in peripheral blood of multiple myeloma (MM) patients. METHODS: 30 patients diagnosed as MM from October 2016 to October 2018 were selected and enrolled in MM group, and 30 healthy persons whose sex and age was matched with the MM patients were selected and enrolled in healthy control group (HC). The blood samples from MM patients and HC were collected, and the peripheral blood mononuclear cells (PBMNC) were separated by density gradient centrifugation, then the serum was kept for further study. The ratios of CD3CD4Tim-3T cells, CD3CD8Tim-3T cells and the CD19+CD20-CD38+B cells were analysed by flow cytometry (FCM)，and the concentration of T cell-related cytokines IFN-γ, TNF-αand B cell-related antibodies IgA, IgM and IgG were measured by ELISA. At the same time, the differences of the ratios of CCD3CD4Tim-3T, CD3CD8Tim-3T cells and plasmablast and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG between the MM patient and HC were estimated, and the correlation of the ratio of CD3CD4Tim-3T, CD3CD8Tim-3T cells with the ratio of plasmablast and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG in MM patients were analyzed. RESULTS: The ratio of CD3CD4Tim-3T, CD3CD8Tim-3T cells increased in MM patients, while the ratio of CD19+CD20- CD38+B cells and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG decreased in MM patients. And there was a negative correlation of the ratio of CD3CD4Tim-3T cells with CD19+CD20-CD38+B cells and the concentration of IFN-γ, IgA, IgM and IgG in MM patients, while the ratio of CD3CD8Tim-3T cells just negatively correlated with the concentration of TNF-α. CONCLUSION Expression of Tim-3 on CD4 and CD8 cells elevates in the peripheral blood of MM patients, which also correlates with the function suppression of T and B cells.
B-Lymphocytes ; CD8-Positive T-Lymphocytes ; Hepatitis A Virus Cellular Receptor 2 ; metabolism ; Humans ; Leukocytes, Mononuclear ; Multiple Myeloma

Objective: To assess the significance of DDAVP use in the diagnosis and treatment of VWD. Methods: An analysis of 15 VWD cases who referred to Hematology Division of First affiliated Hospital of Soochow University and treated with DDAVP from March 2016 to August 2018 was conducted. Efficacy and treatment response of DDAVP were monitored by observations of changes in factor Ⅷ procoagulant (FⅧ∶C) and von Willebrand Factor (VWF) related indicators before and 2 h after DDAVP injection. Results: Of 15 cases with VWD, 7 males and 8 females with a median age of 23 (6-46) years, 7 of 9 type I VWD patients achieved complete response (CR) , 1 type 2A VWD case CR, 5 type 3 VWD ones no response (NR) . The VWF multimer analysis in 5 patients combined with other plasma VWF values were in accordance with the known diagnosis. Conclusions: DDAVP was effective in most type 1 patients, and ineffective in some type 2 and almost all type 3 cases. It was helpful for diagnosis and subsequent treatment planning.
Adolescent ; Adult ; Child ; Deamino Arginine Vasopressin ; Female ; Hemostatics ; Humans ; Male ; Middle Aged ; Young Adult ; von Willebrand Diseases ; von Willebrand Factor

This study aimed to analyze the clinical phenotype of chromosome 9p deletion or duplication and its relationship with karyotype. A patient, female, aged 6 months, visited the hospital due to motor developmental delay. Karyotype analysis identified abnormalities of chromosome 9 short arm, and high-throughput sequencing found 9p24.3-9p23 deletion and 9p23-9p13.1 duplication. Her parents had a normal karyotype. Karyotype analysis combined with high-throughput sequencing is of great significance for improving the efficiency of etiological diagnosis in children with motor developmental delay or multiple congenital deformities and mental retardation.

Objective To observe the clinical efficacy of modified Huanglian Wendan Decoction for treatment of tic disorder (TD) children with syndrome of wind stirring due to phlegm-heat; To detect its effects on peripheral-blood miR-429 expression. Methods Eighty cases of TD children were randomly divided into treatment group and control group,with 40 cases in each group.In the treatment group,children were treated with modified Huanglian Wendan Decoction, one dosage a day, twice a day, orally. In the control group, TD children were treated with haloperidol, 0.03 mg/(kg?d), orally, according to the symptom to adjust dose, and the maximum amount did not exceed 0.08 mg/(kg?d). 30 d was a treatment course for both groups. The treatment lasted for three courses. Before and after 3 months of clinical observation, the severity of disease was evaluated by TCM syndrome and Yale Global Tic Severity Scale (YGTSS) score. Clinical efficacy and TCM syndrome efficacy were evaluated; the level of miR-429 in peripheral blood was detected; the adverse reactions were observed. Results The total effective rate of clinical efficacy was 82.5% (33/40) in treatment group and 80.0% (32/40) in the control group, without statistical significance (P>0.05); The total effective rate of TCM syndrome efficacy was 92.5% (37/40) in treatment group and 75.0% (30/40) in the control group, with statistical significance (P<0.05). Compared with before treatment, the YGTSS score and TCM syndrome score significantly decreased after treatment (P<0.01), and the TCM syndrome score in the treatment group was much lower than the control group after treatment (P<0.05). Compared with before treatment, miR-429 level in both groups increased obviously after treatment (P<0.01), and the miR-429 level in the treatment group was much higher than the control group after treatment (P<0.05). There were mild constipation (1 cases), diarrhea (2 cases), and anorexia (2 cases) in the treatment group, and obvious lethargy (3 cases) and dizziness (3 cases) in the control group. Conclusion Modified Huanglian Wendan Decoction shows obvious effects for treating TD, and can up-regulate miR-429 of peripheral-blood.