Correlation Analysis between Cerebrospinal Fluid Status and Prognosis in Childhood with Acute Lymphoblastic Leukemia by Flow Cytometry / 中国实验血液学杂志

OBJECTIVE@#To study the cerebrospinal fluid (CSF) status and prognosis value in patients with newly diagnosed acute lymphoblastic leukemia (ALL) by flow cytometry (FCM).@*METHODS@#The clinical features of the 75 newly diagnosed ALL patients from September 2020 to December 2021 in our centre were retrospective analyzed, as well as the bone marrow (BM) and CSF minimal residual disease (MRD) data, and the CSF conventional cytology data. Central nervous system infiltration(CNSI) positive was as CSF MRD positive by FCM or leukemia cells detected by conventional cytology. The status of CSF were compared and analyzed by FCM and conventional cytology, the clinical features and the prognosis value of different CNSI status in these patients were analyzed.@*RESULTS@#Among 75 newly diagnosed ALL, 16 cases (21%) with CNSI positive (CNSI+) were detected by FCM, while only 2 positive cases (3%) were detected by conventional cytology. The CNSI+ rate detected by FCM was significantly higher than conventional cytology(P<0.05). Compared with CNSI- ALL patients, the median age of CNSI+ ALL patients was significantly younger, and the median platelet count was significantly lower, the difference was statistically significant (P<0.05). Up to follow-up time (August 31, 2022), four ALL patients were died, including 3 patients were CNSI- and 1 patient was CNSI+. Furthermore, three cases were primary disease relapse, including 1 case was CNSI+. There was no significant difference in overall survival (OS) rate and relapse-free survival (RFS) rate of the patients with different CNSI status.@*CONCLUSION@#Compared with conventional cytology, FCM is a more sensitive assay to evaluate the central nervous system status in ALL patients. After active treatment, there was no significant difference in OS and RFS between patients with different CNSI status at diagnosis.

Recurrent and Refractory Langerhans Cell Histiocytosis in Children Treated with the Combination of Cladribine and Cytarabine / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children.@*METHODS@#Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae.@*RESULTS@#Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus.@*CONCLUSION@#2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.

Clinical Study of Intestinal Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation in Children / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical characteristics, treatment and prognosis of intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children and futher evaluate the occurring risk factors.@*METHODS@#The clinical data of 136 patients undergoing allo-HSCT in Wuhan Children's Hospital Affiliated to Tongji Medical College from August 2016 to August 2020 were retrospectively analyzed, clinical characteristics of children with intestinal aGVHD were observed. The risk factors of intestinal aGVHD were assessed by logistic regression while cumulative survival were analyzed by Kaplan-Meier method.@*RESULTS@#Among 136 patients intestinal aGVHD occurred in 24 (17.6%) cases, with 4 cases of grade II, 20 cases of grade III-IV, and the median occurrence time was 28(10-63) days. The clinical manifestations were diarrhea with intermittent abdominal pain, 17 cases with nausea and vomiting, 11 cases with fresh bloody stool, and 8 cases with skin rash before intestinal aGVHD. The average time for treatment was 33(11-100) days. 18 cases received electronic colonoscopy and histopathology examination. 20 out of 24 cases achieved remission after treatment, and the total effective rate was 83.3%. Finally, 9 out of 24 cases died during the follow-up time. Survival analysis showed that the cumulative survival rate of patients with intestinal aGVHD (15/24, 62.5%) were significantly lower than those without intestinal aGVHD (101/112, 90.2%) (Log-rank test, P=0.001). Univariate analysis showed that recipient age, sex, primary disease, donor age, donor sex, donor-recipient blood type, conditioning regimen, prophylaxis of GVHD, dosage of ATG, engraft time of blood platelet and neutrophils, and number of MNC/CD34+ were not risk factors for intestinal aGVHD (P>0.05). Only the type of HSCT (χ2=16.020, P=0.001) and matched degree of HLA (χ2=15.502, P=0.001) had statistical significance with intestinal aGVHD (P<0.05). Multivariate analysis showed that only HLA-mismatched unrelated donor was the risk factor for intestinal aGVHD for children (P=0.014，OR=16，95%CI 1.735-147.543).@*CONCLUSION@#Intestinal aGVHD is a risk factor for cumulative survial of patients who received allo-HSCT in children and HLA-mismatched unrelated donor is its independent risk factor.

Analysis of the Outcome and Prognostic Factors of Cyclosporine A in Children with Non-severe Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To summarize the long-term efficacy of cyclosporine (CsA) in the treatment of non-severe aplastic anemia (NSAA) in children, and explore the early significant indicators.@*METHODS@#Data of 36 NSAA children in Department of Hematological Oncology, Wuhan Children's Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 2013 to December 2017 were analyzed retrospectively. All the children received oral CsA immunosuppressive therapy, and CsA trough concentration was checked to maintain at the rage of 200-250 μg/L after 2 weeks. The evaluation time points were at 3, 6, 12, 18 and 24 months, and assessment items were peripheral white blood cell differential count and reticulocyte's percentage and count.@*RESULTS@#The 36 NSAA cases were composed of 16 males and 20 females, whose median age was 5.46 (2.92-7.99) years old, and median follow-up time was 28.00 (10.00-38.25) months. After taking oral CsA for 24 months, the number of cumulative effective cases was 21. There were 4 cases of complete remission (CR), 17 cases of partial remission (PR), and 15 cases of non-remission (NR). The total effective rate was 58.33%, and median effect-acting time of CsA was 3.0 (0.5-10.0) months. Compared with ineffective group, neutrophil (NEU) and red blood cell (RBC) of effective group (CR+PR) began to increase significantly at the 3rd month, and hemoglobin (Hb), platelet (PLT) and white blood cell (WBC) increase significantly at the 6th month after oral CsA administration (P<0.05). Except for 2 cases who received component transfusion within 3-12 months after taking oral CsA for 3 months in effective group, the others did not need.@*CONCLUSION@#The overall effective rate of oral CsA in children with NSAA was 58.33%. Stopping blood transfusion after the 3 months of treatment may be considered as a turning point for disease outcomes, and levels of NEU, RBC at the 3rd month and Hb, PLT, WBC at the 6th month as indicators for predicting disease prognosis.

Relationship of PTEN/PI3K/AKT Signaling Pathway Protein Expression with Apoptosis and Drug-resistance of Children's ALL Primary Cells Treated with Daunorubicin / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationship of PTEN/PI3K/AKT signaling pathway protein expression with apoptosis and drug-resistance of children's ALL primary cells treated with daunorubicin (DNR).@*METHODS@#The bone marrow mononuclear cells in newly diagnosed and untreated B-ALL children were collected and cultured. After the treatment of primary-cultured cells with DNR of final concentration 0.5 mg/L for 24 h, the cell apoptosis rate was detected by using cell apoptosis assay kit; the samples were collected at the on test of culture and after drug treatment, then expression levels of PTEN, PI3K and AKT proteins were detected by Western blot, moreover the interindex correlation was analyzed.@*RESULTS@#After DNR treatment, the apoptosis rate in PTEN low expression group was lower than that in PTEN high expression group (P＜0.05), showing high positive correlation of the cell apoptosis rate with the expression of PTEN before DNR treatment; the cell apoptosis rate in PI3K and AKT low expression group was higher than that in PI3K and AKT high expression group (P＜0.01); however, the expression of PI3K and AKT proteins was down-regulated after treatment with DNR (P＜0.01).@*CONCLUSION@#The difference of PTEN expression is present in primary cells of B-ALL children, however the change of PTEN expression is not significant after DNR treatment, suggesting that the PTEN expression correlates with DNR-resistance. The DNR can induce the apoptosis of childrens B-ALL primary cells by down-regulating the expression of PI3K and AKT signaling pathway proteins.

Trillium Tschonoskii Maxim improves cognitive dysfunction in AD rats by inhibiting GSK-3βactivity, attenuating tau pathologies and promoting synaptic development / 中国药理学通报

Aim To assess the effects of Trillium Tschonoskii Maxim ( TTM ) decoction on Tau protein phosphorylation and synaptic development in AD model rats induced by high activity GSK-3β. Methods The SD rats were divided into five groups of ten animals, named sham-operated group ( blank group) , AD model group, TTM group (0. 5, 0. 25, 0. 125 g·kg-1 · d-1 ) . Treatment group received gavage once a day for seven days with TTM decoction, while other groups by gavage once a day for seven days with drinking water. On 2nd day by gavage, Morris water maze test was used to assess the spatial learning and memory ability of the rats. After five days' training, rats in the treat-ment groups and AD model group were injected wort-mannin ( WT, PI3K specific inhibitor ) and GF-109203X (GFX, PKC specific inhibitor) (100 μmol ·L-1 of each, total volume of 10 μL) into the right lateral ventricle. Western blot was used to detect the levels of phosphorylation Tau protein at multiple sites and the expression level of PI3K, Akt, PKC, GSK-3β(S9, T216) and synapse-associated proteins. Immu-nohistochemical method was used to detect the hyper-phosphorylation of Tau protein in hippocampus of rats. Golgi staining was applied to detect the number and morphological changes of synaptic development and dendritic spines. Nissl' s staining was employed to ob-serve the development of neonatal neurons in hippo-campus and cortex. Results Western blot showed that the phosphorylation level of Tau in hippocampus increased in model group, and the activity of GSK-3βwas up-regulated. Among them, however, in middle dose TTM group, the phosphorylation level of Tau in hippocampus decreased and the activity of GSK-3βde-creased. The expression levels of p-PKC and p-Akt in low and middle dose treatment group were higher than those in model group, thus increasing the activity of PKC and Akt to inhibit the activity of GSK-3β kinase. Immunohistochemistry also indicated that TTM could decrease the biological effects of Tau phosphorylation in hippocampus of AD rats. Western blot showed that TTM could increase the expression levels of synapsin-1 , syn-aptophysin and GluR-1 in hippocampus of AD rats. Nissl staining showed that the number of Nissl bodies in hippocampal neurons of AD model group were signif-icantly fewer than those of sham operation group, which could be increased by TTM middle and high dose group, and the complexity and dendritic spine density of hippocampal neurons in AD rats could be en-hanced as well. Conclusion TTM can effectively im-prove the cognitive function of AD rats induced by the increase of GSK-3β activity, and its possible mecha-nism may be via down-regulating the activity of GSK-3β and inhibiting the phosphorylation of tau protein and promoting the development of neurons.

Case control study on open reduction internal fixation (ORIF) and minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of proximal humerus fractures in aged / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the clinical effects of close reduction and minimally invasive percutaneous plate osteosynthesis in treating proximal humerus fractures in the aged.</p><p><b>METHODS</b>From February 2012 to December 2013,39 patients with proximal humerus fractures were treated with minimally invasive percutaneous plate osteosynthesis (MIPPO group, 21 cases) and open reduction internal fixation (ORIF group, 18 cases). Including 17 males and 22 females in the study, and aged from 67 to 88 years old with an average of (71.8 ± 5.2) years old. In MIPPO group, there were 11 males and 10 females with an average age of (70.0 ± 5.3) years old;and in ORIF group, there were 10 males and 8 females with an average age of (72.0 ± 4.2) years old. Operation time, blood loss during operation, fracture healing time and postoperative complications were recorded. The functions of the shoulder joints were assessed according to Constant-Murley score at final follow-up.</p><p><b>RESULTS</b>All the patients were followed up from 11 to 27 months with an average of 18.1 months. The mean blood loss of the MIPPO group was (176.0 ± 57.4) ml,while the ORIF group was (356.0 ± 66.9) ml (t = 7.22,P = 0.01). The operation time of the MIPPO group was (47.4 ± 14.9) min, while the ORIF group was (92.7 ± 15.8) min (t = 0.79, P = 0.03). Fracture healing time in the MIPPO group and ORIF group was (17.6 ± 5.8), ( 21.7 ± 4.9) weeks, respectively (P < 0.05). The mean Constant-Murley score at final follow-up was 89.7 ± 14.5 in MIPPO group, and 81.8 ± 13.2 in ORIF group (P < 0.05).</p><p><b>CONCLUSION</b>MIPPO has advantages of little trauma, less blood loss, rapid recovery, less vascular damage and so on and can effectively treat the proximal humerus fracture in the aged.</p>

The expression and clinical implication of plasma miR-328 in patients with atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the expression and clinical implication of plasma miR-328 in patients with atrial fibrillation (AF).</p><p><b>METHODS</b>Fifty-eight patients with AF (AF group: 17 paroxysmal AF, 21 persistent AF, and 20 permanent AF) and 15 healthy volunteers (Control group) were included. General clinical data and related biochemical parameters were collected. Plasma miR-328 levels were detected with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The correlation between plasma miR-328 and AF risk factors was analyzed.</p><p><b>RESULTS</b>(1) Compared with the control group, the expression level of plasma miR-328 was significantly elevated in AF group (fold 7.72 ± 9.32) (P < 0.05). (2) In AF group, the expression of plasma miR-328 was significantly different in different type of AF[paroxysmal AF with (1.98 ± 0.81), persistent AF with (6.57 ± 5.82) and permanent AF with (13.47 ± 12.29)] (P < 0.05), and which was increased in proportion to the duration of AF. (3) There was a positive correlation between plasma miR-328 level and left atrial diameter in the AF group (r = 0.310, P < 0.05).</p><p><b>CONCLUSION</b>miR-328 expression is significantly increased in patients with AF, which may be involved in the atrial remodeling process of AF.</p>

Synthesis and hypoglycemic activity of esterified-derivatives of mangiferin / 中国天然药物

AIM@#To synthesize three novel esterified-derivatives of mangiferin and evaluate their hypoglycemic activities.@*METHODS@#Acetic, propionic, and butyric anhydride were reacted with mangiferin, respectively. The hypoglycemic activity of the derivatives was evaluated using a hyperglycemic mouse model induced by streptozotocin (STZ), and the islet cells were checked by biopsy inspection.@*RESULTS@#7, 2', 3', 4', 6'-penta-acetyl-mangiferin (PAM), 3, 6, 7, 2', 3', 4', 6'-hepta-propionyl-mangiferin (HPM) and 3, 6, 7, 2', 3', 4'-hexa-butyryl-mangiferin (HBM) were synthesized and their structures were identified by MS,(1)H, (13)C NMR, and 2D NMR. These three compounds were reported for the first time. PAM group (0.5, 0.25 mmol·kg(-1)), HPM group (0.5, 0.25 mmol·kg(-1)), and HBM group (0.5, 0.25, 0.125 mmol·kg(-1)) mice showed strong hypoglycemic activity (P < 0.01); mangiferin group (1, 0.5 mmol·kg(-1)), PAM group (0.125 mmol·kg(-1)) and HPM group (0.125 mmol·kg(-1)) showed marginal hypoglycemic activity (P < 0.05); mangiferin group (0.25 mmol·kg(-1)) had the potential for a hypoglycemic effect, although it did not demonstrate that statistically. In histological examination, the islet cells of the PAM, HPM, and HBM groups could recover from the STZ damage; islet cells of the mangiferin group could recover also, but less than the esterified-derivative groups.@*CONCLUSION@#Derivatives could repair the damaged islet cells, and had higher lipid-solubility and stronger hypoglycemic activity than mangiferin itself. There existed a structure activity effect, and a solubility effect relationship: the larger esterification moieties, or the higher lipid-solubility, the stronger the hypoglycemic activity (no ester → acetyl → propionyl → butyryl). Esterified derivatives of mangiferin are potential compounds for new anti-diabetes drugs.

Assessment of left ventricular systolic synchronicity by quantitative tissue velocity imaging in patients with left ventricular noncompaction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess left ventricular systolic synchronicity by quantitative tissue velocity imaging (QTVI) in patients with left ventricular noncompaction (LVNC).</p><p><b>METHODS</b>Eighteen LVNC patients and 30 healthy controls were included. Two-dimensional echocardiography, QTVI was applied on parasternal long axis view, apical two-chamber and four-chamber view. Tissue velocity curve was obtained from the middle and basal segments of left ventricular posterior, lateral, septal, anterior, inferior and anteroseptal walls. Time interval from the beginning of QRS complex to the peak systolic velocity (Q-Ts) and the maximal difference in Ts among all 12 LV segments (Max-DeltaTs) was calculated.</p><p><b>RESULTS</b>Q-Ts from basal and middle segments of left ventricular inferior, lateral and posterior walls was significantly prolonged in LVNC patients compared to controls (P < 0.001). Max-DeltaTs was also significantly increased in LVNC patients [(161.9 +/- 93.2) ms] than that in controls [(61.2 +/- 27.4) ms, P < 0.001].</p><p><b>CONCLUSIONS</b>There was significant left ventricular asynchronies in patients with LVNC and delayed systolic contraction occurred mostly in the basal and middle segments of left ventricular inferior, posterior and lateral walls.</p>

Treatment of Bennett's fracture with closed reduction and percutaneous Kirschner wire fixation / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate clinical effect of new method of percutaneous Kirschner wire fixation in treating Bennett's fracture.</p><p><b>METHODS</b>Thirteen patients with Bennett's fracture were treated with close reduction and percutaneous Kirschner wire fixation. There were male 8 cases and female 5 cases with an average age of 32 years (range from 20 to 45 years). The mean time from injury to operation was 4.3 days (range from 2 to 7 days). External fixation with plaster slab was applied after operation with an average of 35 days (range from 30 to 41 days). The reduction of articular surface, symptom of ache and function of thumb after operation were evaluated.</p><p><b>RESULTS</b>All the patients were followed up with an average of 6.4 months (range from 4 to 9 months). All fractures united and the articular surfaces were reduced well. Only 1 case has mild pain when activity. The grasp force decreased in all patients.</p><p><b>CONCLUSION</b>Close reduction and percutaneous Kirschner wire fixation has advantage such as simply operation, precisely fixation, high potency ratio. The method especially fits Bennett's fracture with small triangular fragment.</p>

A new flavonol glycoside from Baeckea Frutescens L / 药学学报

To study the chemical constituents of the traditional Chinese herb Baeckea Frutescens L., a new flavonol glycoside, named 6, 8-dimethylkaempferol-3-O-alpha-L-rhamnoside (1), together with seven known compounds: quercetin (2), quercetin-3-O-alpha-L-rhamnoside (3), myricetin (4), myricetin-3-O-alpha-L-rhamnoside (5), gallic acid (6), ursolic acid (7) and 1,3-dihydroxy-2-(2'-methoxylpropionyl)-5-methoxy-6-methylbenzene (8) were isolated by using silica gel column chromatography, polyamide column chromatography and recrytallization. Their structures were identified on the basis of physicochemical properties and spectroscopic analysis. Among them, compounds 2-7 were isolated from this plant for the first time and compound 8 was first isolated from plant.

Stress test and clinical application of the minimal-invasive dynamic hip screw / 中国骨伤

<p><b>OBJECTIVE</b>To recognize the effect of minimal-invasive dynamic hip screw (MIDHS) on the treatment of intertrochanteric fracture of the hip by biomechanical test and preliminary clinical application.</p><p><b>METHODS</b>Ten artifical made intertrochanteric fractures of femoral specimen from five cadavers were divided into two groups randomly. The fractures in first group were fixed by MIDHS and other group were fixed by dynamic hip (DHS). Biomechanical characteristics of two different devices were compared with the biomechanical character of load-straining, load-displacing, rigidity and strength of femur by statistic analysis. According to the Harris evaluation, healing effect of intertrochanteric fractures was evaluated clinically on the 15 cases.</p><p><b>RESULTS</b>Straining changes of MIDHS were 14% and 11% less than that of DHS on the tensile side and the pressure side respectively; Sinking and horizontal displacement, were 19% and 22% less than that of DHS respectivly. But external and internal stress intensity,axial and bending rigidity were all higher than that of DHS, they were 12%, 11%, 19% and 37%. Maximal destroyed twisting moment (15%) and average twisting rigidity (15%) were both higher than that of DHS, but twisting angle was 18% less. Under the force, of 1 800 N, the open angle of the fracture on transverse section was 2.28 degrees,while the DHS's was 3.60 degrees . The data above were significant differences statistically (P < 0.01). The average Harris score of the 15 cases with intertrochanteric fractures treated by MIDHS was 91, excellent and good rate was 92.7%, without complications of internal fixation failure,postoperative infection and so on.</p><p><b>CONCLUSION</b>The design of minimal-invasive dynamic hip screw is reasonable and effective against rotating, shearing and varus stress force of the fracture, and it provides possibility of implanting the internal fixation with minimal incision. So it is an ideal internal fixation device for the treatment of intertrochanteric fractures.</p>