Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective : To investigate the role of early inhibition of Toll⁃like receptor 4 (TLR4) in regulating hippampal neuroimmune responseto adolescent ratsafter neonatal hypoxic⁃ischemic brain damage(HIBD) . Methods: Postnatal day 7 rats were randomized into controlgroup , hypoxic ischemia (HI) group , and HI + TAK⁃242( the specific inhibitor of TLR4)(TAK⁃242) group. The expression of TLR4 in rat hippocampus was detected by immunohistochemistry at 3 days after HI. Immunofluorescence were used to determine the number of Iba⁃1 + , GFAP + , CD161 + , MPO + and CD3 + cells in the hippocampus at 21 days after HI. Immunohistochemistry was used to detect ICAM⁃1 and C3a expression in the hippocampal CA1 region ; and Western blot was used to detect tumor necrosis factor interleukin IL⁃1β , TNF⁃α and IL⁃10 expression. Results : Compared with control group , significantly raised TLR4 expression was observed in the left hippocampal CA1 , CA3 and DG regions(P < 0. 01 or P < 0. 05) , while the expression in the TAK⁃242 group lowered compared to the HI group (P < 0. 05) . The number of GFAP + cells in the CA1 area of the hippocampus in the TAK⁃242 group of neonatal rats decreased compared to which in the HI group at 21 days after HI(P < 0. 05) , but the number of CD3 + T lymphocytes in the hippocampal CA1 area of new born rats in the HI group increased compared to which in the Control group (P < 0. 05) , but the difference between TAK⁃242 and the Control group was not statistically significant. The number of Iba⁃1 + cells , MPO + cells , CD161 + cells , the expression of ICAM⁃1 and C3a in hippocampal CA1 region , and the expression of TNF⁃α , IL⁃1β and IL⁃10 in hippocampus of rats were not different among groups at 21 days after HIBD. Conclusion Early inhibition of TLR4 may ameliorate adolescent neuroimmune disorders by reducing the increase of hippocampal astrocytesafter neonatal HIBD.

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%-87% of mice die when administered an intraperitoneal injection of 40 mg kg^-1. In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg^-1) on day 36 or a dose of 40 mg kg^-1 at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg^-1 busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg^-1 in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.
Adult Germline Stem Cells/transplantation* ; Animals ; Azoospermia/chemically induced* ; Busulfan/toxicity* ; Disease Models, Animal ; Infertility, Male/chemically induced* ; Injections, Intraperitoneal ; Male ; Mice ; Spermatogenesis/drug effects* ; Spermatogonia/drug effects* ; Stem Cell Transplantation/methods*

A large number of cancer patients suffer from pain. Growing evidence suggested that pain might be a serious risk factor for cancer patients. The shared modulators and modulation pathways between neural system and tumor cells, such as various neurotransmitters and neurogenic cytokines, provide essential basis for the effect of pain on tumor. In this article, we reviewed some possible mechanism of this process from two aspects: the systematic regulation of central nervous system on endocrine and immunity, and the regional regulation of peripheral nerves on tumor cells. The aim of this review is to provide more innovative knowledge about pain and cancer and to emphasize the importance of anti-pain in the therapy of cancer.
Cancer Pain ; physiopathology ; Central Nervous System ; Humans ; Memory ; Neurotransmitter Agents ; Pain ; Peripheral Nerves

Aim To explore the influences of scutellarin on ATP-induced NLRP3 inflammasome activation and pyroptosis,using LPS-primed murine macrophages J774A.1 as an inflammatory cell model,and to explore the underlying mechanism.Methods The effects of scutellarin on ATP-induced pyroptosis in murine J774A.1 macrophages were analyzed by propidium iodide (PI) staining assay.The levels of IL-1β,caspase-1 and HMGB1 in cell lysates and culture supernatants were analysed using Western blot.The levels of IL-1β in cell culture supernatants were measured by cytometric beads array (CBA).Results ATP significantly induced caspase-1 activation and mature IL-1β and HMGB1 release into the culture supernatants in LPS-primed murine J774A.1 macrophages,and induced pyroptosis.Scutellarin treatment dose-dependently inhibited ATP-induced caspase-1 activation,mature IL-1β and HMGB1 release,and pyroptosis.Notably,scutellarin's inhibitory effects on ATP-induced pyroptosis were markedly reversed by the adenylate cyclase inhibitor MDL12330A and selective protein kinase A (PKA) inhibitor H89.Conclusion Scutellarin inhibits NLRP3 inflammasome activation and pyroptosis by modulating the PKA activity in macrophages,thereby exhibiting anti-inflammatory activities.

Using the theory and method of health economics,we analyzed CER and ICER in early elimination stage (2005-2009),the late elimination stage (2015-2010) and the post elimination phase (2016-).Results showed that annual total cost of investment was as following:64 235 144.8 Yuan in early elimination stage,11 250 248 Yuan in the late elimination stage,and 11 075 228.8 Yuan the post elimination phase.Effect analysis showed that the difference of the three-stage monitoring measures was statistically significant (P＜0.01).Number of cases within 3 days of onset (rate) prompt monitoring measures had the best effect in the late elimination stage,number of blood tests (rates),number of cases reported (rates) and number of cases within 1 days of onset (rate).Prompt monitoring measures had the best effect in the post elimination phase.CER and IC-ER showed that taking the number of blood test as the effect index,the monitoring measures in the late elimination stage were more cost effective.The number of cases reported,number of cases within 3 days of onset and number of cases within 1 day of onset were as the effect index,the monitoring measures in the post elimination phase were more cost effective.The elimination effect for monitoring measures after stage was optimal,cost the least,and might be the most effective.The study provides basic data for Fujian Province to strengthen the monitoring of imported cases of malaria on the construction of the management mechanism,and scientific and effective evaluation of monitoring measures,which has very important practical value and significance.

Objective To develop a buckle tourniquet to facilitate further casualty treatment.Methods The requirements oftheater/field first aid of the PLA were analyzed.The existing spinning tourniquet was modified from the aspects of shorteningoperation time,controlling hemostatic pressure precisely,relieving tourniquet timely etc.The developed tourniquet was madeof engineering plastics and polyester webbing,and composed of a micro-regulation buckle,a main strap,a tightening band,atimer,a garrote,Velcro,a self-adhesive band,a garrote fixation clamp etc.Results The tourniquet had the operation timebeing 11.52 s,and avoided ischemic necrosis of tissues by automatic alarm in case of 1-h hemostasis for upper limbs or 1.5-hhemostasis for lower limbers.Conclusion The tourniquet gains advantages in low cost,high portability,easy operation,high efficiency and timing function,and thus meets the requirements for theater/field first aid.

Objective: To analyze the correlations of seminal plasma (sp) anti-Müllerian hormone (spAMH) and inhibin B (spINHB) and serum INHB (serINHB) with semen parameters in oligoasthenospermia patients and explore their value in predicting the outcome of routine in vitro fertilization (IVF). METHODS: We obtained the levels of spAMH, spINHB and serINHB as well as semen parameters from 88 infertile males undergoing IVF due to oligoasthenospermia or female uterine tubal factors from August 2016 to February 2017. Using the ROC curve and Pearson's correlation analysis, we examined the effects of the obtained parameters on the fertilization rate and assessed the correlation of the levels of spAMH, spINHB and serINHB with the semen parameters of the patients. RESULTS: Concerning the predictive value for the outcome of IVF, Pearson's correlation analysis showed that the area under the ROC curve (AUC) of spAMH was 0.807 (sensitivity = 84.6%, specificity = 76%, cut-off point = 3.529, P <0.001) and that of spINHB was 0.768 (sensitivity = 84.6%, specificity = 88.7%, cut-off point = 31.117, P = 0.002). The serINHB level was found positively correlated with sperm concentration (r = 0.346, P = 0.001), total sperm count (r = 0.378, P <0.001), sperm motility (r = 0.521, P <0.001), and the percentage of progressively motile sperm (r = 0.343, P = 0.001). CONCLUSIONS The levels of spAMH and spINHB can be used as laboratory indexes to predict the fertilization rate of routine IVF and are correlated with semen parameters in oligoasthenospermia patients, while that of serINHB has a positive correlation with the semen parameters of the patients.
Anti-Mullerian Hormone ; analysis ; blood ; Asthenozoospermia ; Female ; Fertilization ; Fertilization in Vitro ; Humans ; Infertility, Female ; Inhibins ; analysis ; blood ; Male ; Oligospermia ; ROC Curve ; Semen ; chemistry ; Sperm Count ; Sperm Motility

BACKGROUNDProlonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD), and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients.

METHODSThis was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years, range 17-30 years) and 135 healthy controls after matching for gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone, ACTH, and cortisol and biochemical tests.

RESULTSHigher basal serum ACTH levels (8.25 ± 3.78 pmol/L vs. 6.97 ± 2.81 pmol/L) and lower cortisol levels (366.70 ± 142.48 nmol/L vs. 452.82 ± 141.53 nmol/L) were observed in male IHH patients than healthy subjects (all p<0.05). IHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD (34.9% vs. 4.4%) than the controls (all P < 0.05). Basal serum ACTH (9.91 ± 4.98 pmol/L vs. 7.60 ± 2.96 pmol/L) and dehydroepiandrosterone sulfate (2123.7 ± 925.8 μg/L vs. 1417.1 ± 498.4 μg/L) levels were significantly higher in IHH patients with NAFLD than those without NAFLD (all P < 0.05). We also found that basal serum ACTH levels were positively correlated with NAFLD (r = 0.289,p<0.05) and triglyceride levels (r = 0.268, P< 0.05) in male IHH patients. Furthermore, NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis.

CONCLUSIONSThe male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

Adolescent ; Adrenocorticotropic Hormone ; blood ; Adult ; Humans ; Hydrocortisone ; blood ; Hypogonadism ; blood ; Linear Models ; Male ; Non-alcoholic Fatty Liver Disease ; blood ; drug therapy ; Retrospective Studies ; Young Adult

Objective To investigate the diagnostic value of three-vessel and tracheal (3VT) view in fetal aortic arch anomalies .Methods Ultrasound findings of 17 fetuses with aortic arch anomalies diagnosed in Pe-king Union Medical College Hospital between May 2010 and May 2014 were reviewed and compared with the find-ings of postnatal ultrasonography and pathological examinations to analyze the ultrasound features of aortic arch anomalies of different types , focusing on the importance of 3VT view.Results In all 17 cases the 3VT view was abnormal .3 cases were aortic coarctation , mainly manifested as reduced diameter of the aortic arch;7 cases were interrupted aortic arch , in which there was discontinuity between the thinning aortic arch and the descending aor -ta;5 cases were right aortic arch ( RAA) with aberrant left subclavian artery , with a‘U’ -shaped vascular loop around the trachea;and 2 cases were RAA with mirror-image branching , with the aortic arch situated to the right of the trachea and not forming a V-or U-shaped confluence with the ductus .Conclusions The 3VT view is a very sensitive view to effectively diagnose fetal aortic arch anomalies .Meticulous ultrasound examination focusing on this view during second trimester may disclose the presence of such anomalies and help provide the appropriate genetic counselling .