[Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis. METHODS: A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ï¼»66 cases of them were screened by propensity score matching (PSM), as control groupï¼½. The early efficacy and survival between the two groups were compared. RESULTS: The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively. CONCLUSION: Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

[Clinical Efficacy and Survival Analysis of Adult Patients with Acute Myeloid Leukemia after Microtransplantation].

OBJECTIVE: To investigate the clinical efficacy and survival factors of microtransplantation (MST) in adult patients with acute myeloid leukemia (AML). METHODS: For a retrospective analysis of 27 adult patients with AML receiving MST from July 2014 to October 2021, the median age was 59(29-77) years old, 13 cases were ≥60 years old, 14 case were <60 years old, 13 cases were male and 14 cases were female. Classification by FAB: AML-M2 6 cases, AML-M4 6 cases, AML-M5 2 cases, AML-M6 2 cases, AML（Undivided type） 9 cases, AML myeloid sarcoma 2 cases (primary AML 21 cases, AML secondary to MDS 6 cases). Cytogenetic analysis showed 25 patients with a normal karyotype, 2 patients with an abnormal karyotype, and 20 patients with an abnormal molecular biology. Induction chemotherapy regimens mainly include: IA, DA, MA or HA regimen, including CAG or CIG in combination with decitabine, and single-agent decitabine. 17 patients achieved complete remission (CR) after 1 course of induction chemotherapy and 4 patients achieved CR after 2 courses of induction chemotherapy. 3 patients received CR by four courses of decitabine, 2 patients received no remission, and 1 patient underwent no induction chemotherapy and were treated direct MST. There were 16 patients with pretransplant CR and 11 patients were not in remission before transplantation. Follow-up mainly used consult patient's medical records and telephone inquiry to observe the adverse effects and efficacy of MST treatment. Survival analysis was performed by Kaplan-Meier method, with the main observation indicators overall survival(OS) and leukemia-free survival(LFS), and performed with the Log-rank test. Multivariate analysis was performed by the Cox regression model. RESULTS: A total of 79 MST were performed in 27 AML patients with good overall safety and no special serious adverse effects. The median time of leukocyte recovery was 13(4-28) days, and the median time of platelet recovery was 13(4-30) days. There were 50 cases of infection, 5 cases of abnormal liver function and 3 cases of abnormal cardiac function. Except for abnormal cardiac function, all other complications did not affect the treatment and were cure. Acute or chronic GVHD, renal insufficiency, abnormal coagulation function, and severe bleeding were not observed during treatment or during follow-up. As of the follow-up date, the median follow-up time of the 27 patients was 79(14-171) months, the median OS time was 62(1-171) months, and the median LFS time was 15(0-171) months. The 2-year OS rate was 65.7%（17/27）, and the 2-year LFS rate was 47.4%（12/27） . The complete response rate of 27 patients treated with MST was 48.1% (13/27). 8 patients relapsed during MST treatment, including 7 patients after the completion of the first MST course and 1 patient after the completion of the second MST course. 2 patients relapsed after the end of the course of MST. 13 patients died, including 10 patients because of disease progression, two patients from severe infection, and one patient from cardiac damage. CONCLUSION: MST has the advantages of small toxic side effects, complete compatibility of HLA matching is not required, effective avoidance of GVHD and rapid hematopoietic recovery, which can improve OS and LFS in elderly AML and young AML patients, and is one of the treatment options for patients without HLA matching.

A study on 85Kr measurement with an internal gas proportional counter.

A measurement method of 85Kr using an internal gas proportional counter (IGPC) is presented in this study. The operation conditions of the IGPC were determined and optimized, including the operating voltage, pressure, sample volume, interference from other gas components such as nitrogen or air, and mitigation of the memory effect. The IGPC was calibrated using certified standards, and the detection efficiency was approximately 58% for typical samples. A lower limit of detection of approximately 0.11 MBq/m3(Kr) was achieved after counting for 5 h with 1 mL pure Kr, corresponding to the atmospheric activity concentration of 0.18 Bq/m3 (air). It was shown that the IGPC could be used effectively for measuring 85Kr.

Structure and antitumor and immunomodulatory activities of a water-soluble polysaccharide from Dimocarpus longan pulp.

A new water-soluble polysaccharide (longan polysaccharide 1 (LP1)) was extracted and successfully purified from Dimocarpus longan pulp via diethylaminoethyl (DEAE)-cellulose anion-exchange and Sephacryl S-300 HR gel chromatography. The chemical structure was determined using Infrared (IR), gas chromatography (GC) and nuclear magnetic resonance (NMR) analysis. The results indicated that the molecular weight of the sample was 1.1 × 10(5) Da. Monosaccharide composition analysis revealed that LP1 was composed of Glc, GalA, Ara and Gal in a molar ratio of 5.39:1.04:0.74:0.21. Structural analysis indicated that LP1 consisted of a backbone of → 4)-α-D-Glcp-(1 → 4)-α-D-GALPA-(1 → 4)-α-D-Glcp-(1 → 4)-ß-D-Glcp-(1 → units with poly saccharide side chains composed of → 2)-ß-D-Fruf-(1 → 2)-L-sorbose-(1 → attached to the O-6 position of the α-D-Glcp residues. In vitro experiments indicated that LP1 had significantly high antitumor activity against SKOV3 and HO8910 tumor cells, with inhibition percentages of 40% and 50%, respectively. In addition, LP1 significantly stimulated the production of the cytokine interferon-γ (IFN-γ), increased the activity of murine macrophages and enhanced B- and T-lymphocyte proliferation. The results of this study demonstrate that LP1 has potential applications as a natural antitumor agent with immunomodulatory activity.

[Efficacy of sublingual immunotherapy with dermatophagoides farinae drops in monosensitized and polysensitized patients with allergic rhinitis].

OBJECTIVE: To compare the efficacy of sublingual immunotherapy (SLIT) with standardized Dermatophagoides farinae drops in monosensitized and polysensitized patients with allergic rhinitis. METHODS: The efficacy of SLIT in 69 patients who were sensitized to house dust mites and treated with Dermatophagoides farinae drops for 1.5-2.0 year with complete clinical data were analyzed retrospectively. These patients had been divided into the monoallergen sensitized group and polyallergen sensitized group according to the results of skin prick tests. The total medication score (TMS) and the total nasal symptoms score (TNSS) were evaluated before and half an year, 1.0 year and 1.5-2.0 years after SLIT treatment. RESULTS: After SLIT treatment for half an year, the TNSS in the monoallergen sensitized group (2.00 [1.00; 3.00]) was significantly lower than that in the polyallergen sensitized group (3.00 [2.00; 4.00], Z = -2.851, P < 0.05), this significant difference of TNSS between the two groups was also found after SLIT treatment for 1.0 year (0.00 [0.00; 1.00], 2.00 [0.00; 3.00], Z = -2.590, P < 0.05). Whereas, there was no significant difference between the two groups after 1.5-2.0 years treatment refer to the TNSS (0.00 [0.00; 1.00], 0.00 [0. 00; 2.00], Z = -1.461, P > 0.05). Half an year, 1.0 year and 1.5-2.0 years after SLIT treatment, the TMS in both groups reduced significantly, with no significant difference between two groups (Z value was - 0.777, -0.944, -0.907, all P > 0. 05). CONCLUSIONS: SLIT with Dermatophagoides farinae drops is effective in monosensitized and polysensitized patients with allergic rhinitis. And equivalent efficacy could be achieved after 1.5-2.years.

[Effect of lipoxin A(4) on lipopolysaccharide-induced endothelial hyperpermeability in human umbilical vein endothelial cell].

OBJECTIVE: To explore whether lipoxin A(4) (LXA(4))could prevent lipopolysaccharide (LPS)-induced human umbilical vein endothelial cells (HUVEC) monolayer hyperpermeability and its possible mechanism. METHODS: Human umbilical cords were obtained from women with normal pregnancy immediately after delivery from Tongji Hospital Affiliated of Tongji Medical College. Primary HUVEC were isolated from umbilical veins and subcultured, then, HUVEC were divided into four groups:control group; LPS group (10 mg/L of LPS); LPS + LXA(4) group(10 mg/L of LPS and 100 nmol/L of LXA(4)); LPS + LXA(4) + BOC-2 group [10 µmol/L of BOC-2, an effective antagonist of formyl peptide receptor like 1 (FPRL-1)]. All expriments were performed after cells were treated for 24 hours. Endothelial permeability was measured by fluorescein isothiocyan-ate labelled bovine serum albumin (FITC-BSA) clearance across the monolayer; tumor necrosis factor α (TNF-α) mRNA and secretion were detected by reverse transcriplase (RT)-PCR and ELISA assay respectively, and nuclear factor κB (NF-κB) protein change was determined by western blot. RESULTS: (1) LPS induced a significant increase in the permeability [Pa value of LPS group was (183.1 ± 1.7)%], while co-administrating with LXA(4) obviously attenuated this LPS-induced hyperpermeability, Pa value of LPS + LXA(4) group was (103.1 ± 2.2)%, LPS + LXA(4) + BOC-2 group was (162.2 ± 2.8)%, control group was 100%, the permeability of HUVEC monolayer was significantly increased by LPS which was (83.1 ± 1.7)% of control (P < 0.01), however, it was notably inhibited by LXA(4) (P < 0.05); the blockade of FPRL-1 could attenuate the effect of LXA(4), that is, there was no difference between the LPS + LXA(4) + BOC-2 group and the LPS group. (2) After treatment with different concentration of LPS(0, 0.1, 1, 10 mg/L), the mRNA expressions of TNF-α were increased (1.11 ± 0.11, 1.27 ± 0.03, 1.60 ± 0.06, 1.82 ± 0.04, respectively), compared with the control group, at the concentration of 1, 10 mg/L LPS, the difference was statistically significant (P < 0.05). (3) The increased levels of NF-κB and inflammatory mediator TNF-α in the LPS group were both inhibited by LXA(4). Levels of NF-κB protein and TNF-α mRNA secretion in LPS treated group (0.53 ± 0.06 and 0.81 ± 0.09, respectively) were both inhibited by LXA(4)(0.19 ± 0.05 and 0.41 ± 0.07, respectively, and both had significant difference, P < 0.05). (4) Levels of TNF-α in HUVEC culture medium of LPS group [(31.94 ± 0.01) ng/L] was significantly higher than the control group [(18.17 ± 0.03) ng/L, P < 0.05], LPS + LXA(4) group [(15.72 ± 0.07) ng/L] was significantly lower than the LPS group (P < 0.05). CONCLUSION: Our findings demonstrated that LXA(4) could prevent the endothelial cell hyperpermeability induced by LPS in HUVEC under which the possible mechanism was through inhibiting the expression of NF-κB and its related cytokines through receptor-dependent.

[Effect of lipoxins on proliferation and secretion of peritoneal macrophages from patients with preeclampsia in vitro].

OBJECTIVE: To study the effect of lipoxins on the proliferation and secretion of peritoneal macrophages from patients with preeclampsia in vitro. METHODS: Peritoneal macrophages were obtained from 24 patients with preeclampsia (preeclampsia group) and 24 normal pregnant women (normal pregnant group) who were treated in the First Affiliated Hospital of Wenzhou Medical College from March to July 2007. Enzyme linked immunosorbent assay (ELISA) was used to detect the concentration of tumor necrosis factor-alpha (TNF-alpha) in the supernatant of macrophages which were pulsed with lipoxins at different concentrations (0, 10, 100 nmol/L) in both groups after 48 hours. Methyl thiazolyl tetrazolium (MMTT) assay was used to detect the inhibition rate of cell proliferation of macrophages which were pulsed with lipoxins at different concentrations (0, 10, 100 nmol/L) in both groups after 24 hours. RESULTS: (1) The concentration of TNF-alpha: the levels of TNF-alpha were (1867.5 +/- 47.3), (1836.9 +/- 4.5) and (1800.5 +/- 2.7) ng/L after treatment with different concentrations of lipoxins (0, 10, 100 nmol/L) in preeclampsia group vs normal pregnant group [(791.3 +/- 62.2), (789.4 +/- 2.3), (781.5 +/- 1.9) ng/L]. The levels of TNF-alpha in preeclampsia group were significantly higher than that in normal pregnant group (P < 0.05). Lipoxins significantly inhibited the concentration of TNF-alpha in a dose-dependent manner in preeclampsia group (P < 0.05), while it had no significant effect in normal pregnant group (P > 0.05). (2) Cell proliferation inhibition: Incubation with lipoxins produced a dose-dependent (0, 10, 100 nmol/L) inhibitory effect on proliferation in preeclampsia group, [ 14. +/-6. )% , (32. +/-3.6)%, ( 6. ++/-3. )% vs normal pregnant group [(16.8 +/- 6.9)%, (16.7 +/- 5.4)%, (15.9 +/- 2.1 )%]. The rate of cell proliferation in preeclampsia group was significantly higher than that in normal pregnant group. Lipoxins significantly inhibited this growth (P < 0.05) , while it had no significant effect in normal pregnant group (P > 0.05). CONCLUSION: Lipoxins can inhibit the proliferation of macrophage and secretion of TNF-alpha in preeclampsia in a dose-dependent manner. Lipoxins may be potentially useful in prevention and treatment of preeclampsia.