Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Objective:To observe any effect of combining vibroacoustic therapy with audio-visual feedback on the swallowing and the emotional state of persons with a swallowing disorder after a brainstem stroke.Methods:Fifty brainstem stroke survivors with dysphagia were randomly divided into a control group and a combination group, each of 25. In addition to routine swallowing function training, the control group received additional direct feeding training, while the combination group was provided with vibroacoustic feeding training and swallowing stimulation from an animated audio-visual presentation. Before and after the treatment, the subjects′ swallowing function was quantified using the Standard Swallowing Assessment (SSA) scale and the Gugging swallowing screen (GUSS). The Positive and Negative Emotions Scale (PNAS) was used to quantify their emotional state.Results:After the treatment the average SSA scores of both groups had decreased significantly, while the average GUSS and PNAS scores had increased significantly. The average improvements in all three measures were significantly greater in the combination group than in the control group.Conclusion:In addition to routine swallowing function training, feeding training applying vibroacoustics and audio-visual stimulation can significantly improve the feeding function and emotional state of brainstem stroke survivors with dysphagia.

Objective:To observe the changes of serum C-terminal peptide of type Ⅰ collagen (CTX-1) and N-terminal lengthening peptide of type Ⅰ collagen (P1NP) in adult patients with skeletal fluorosis in the tea-drinking-borne endemic fluorosis area in Qinghai Province, and to find sensitive indicators for diagnosis of skeletal fluorosis.Methods:From April to August 2019, a case-control study was carried out in tea-drinking-borne endemic fluorosis area in Zhiduo County, Yushu Tibetan Autonomous Prefecture, and Gangcha County, Haibei Tibetan Autonomous Prefecture of Qinghai Province. According to the Diagnostic Standard for Endemic Skeletal Fluorosis (WS/T 192-2008), the clinical diagnosis and X-ray examination of skeletal fluorosis were carried out for permanent residents ≥25 years old and living for more than 10 years in the area, combined with face-to-face inquiry and investigation of past disease history, lifestyle and clinical manifestations. The patients with skeletal fluorosis and healthy people were selected as skeletal fluorosis group and control group, respectively. Randomized urine samples and fasting venous blood from the two groups were collected. The content of fluoride in urine was determined by ion selective electrode method, and the contents of CTX-1 and P1NP in serum were determined by enzyme-linked immunosorbent assay (ELISA).Results:A total of 127 people in the disease area were investigated, including 63 cases in skeletal fluorosis group and 64 cases in control group. There was no statistically significant difference in age and sex ratio between the two groups ( t = 0.42, χ 2 = 0.07, P > 0.05). The X-ray examination results showed that the patients with skeletal fluorosis were mainly mild, accounting for 71.43% (45/63); X-ray changes were mainly ossification of interosseous membrane and tendon. The urinary fluoride in control group and skeletal fluorosis group was 1.62 (1.12, 1.95) and 3.22 (2.38, 4.89) mg/L, respectively, with statistically significant difference between the two groups ( Z = 7.07, P < 0.001). The difference of serum CTX-1 and P1NP contents between the two groups was statistically significant ( Z = 2.00, 4.89, P < 0.05). Conclusions:The levels of serum CTX-1 and P1NP in patients with skeletal fluorosis are higher than those in healthy people. Serum CTX-1 and P1NP may be used as sensitive indicators for diagnosis of skeletal fluorosis.

Lysosomes are degradation and signaling centers within the cell, and their dysfunction impairs a wide variety of cellular processes. To understand the cellular effect of lysosome damage, we screened natural small-molecule compounds that induce lysosomal abnormality using Caenorhabditis elegans (C. elegans) as a model system. A group of vobasinyl-ibogan type bisindole alkaloids (ervachinines A-D) were identified that caused lysosome enlargement in C. elegans macrophage-like cells. Intriguingly, these compounds triggered cell death in the germ line independently of the canonical apoptosis pathway. In mammalian cells, ervachinines A-D induced lysosomal enlargement and damage, leading to leakage of cathepsin proteases, inhibition of autophagosome degradation and necrotic cell death. Further analysis revealed that this ervachinine-induced lysosome damage and lysosomal cell death depended on STAT3 signaling, but not RIP1 or RIP3 signaling. These findings suggest that lysosome-damaging compounds are promising reagents for dissecting signaling mechanisms underlying lysosome homeostasis and lysosome-related human disorders.
Alkaloids ; pharmacology ; Animals ; Caenorhabditis elegans ; cytology ; drug effects ; metabolism ; Cell Death ; drug effects ; Cell Survival ; drug effects ; HeLa Cells ; Humans ; Lysosomes ; drug effects ; pathology ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; drug effects

AIM: To investigate the effects of vitrectomy combined with cataract surgery on the corneal endothelial cells in diabetic retinopathy.METHODS: A retrospective study was designed.160 patients(160 eyes) with diabetic retinopathy from Jan 2015 to Feb 2017 were divided into two groups according to cataract.74 patients(74 eyes) were operated on vitrectomy,and 86 patients(86 eyes) on vitrectomy combined with phacoemulsification cataract surgery and capsular bag implantation of foldable intraocular lens.To record the change of corneal endothelial cells density,average cellular area,coefficient of variation and percentage of hexagonal endothelial cell before and after treatment with Topcon corneal specular microscope.RESULTS: Before and after surgery,the results of corneal endothelial cells density,average cellular area,coefficient of variation and percentage of hexagonal endothelial cell in simple vitrectomy group were no significant difference(P>0.05);After treatment corneal endothelial cells density and percentage of hexagonal endothelial cell were changed with statistical difference as the same as average cellular area and coefficient of variation(P<0.05);There were significantly differences in corneal endothelial cells between two groups(P<0.05).CONCLUSION: It has certain influence on the corned endothelial cells when using vitrectomy combined with cataract surgery in diabetic retinopathy.For patients with indications,it should be paid attention to protecting the corneal endothelial cells.

Objective To understand the pathway of iodine intaking among Tibetan, and provide basic data for prevention and control of iodine deficiency disorders (IDD). Methods Through the method of random sampling, the boarding and day student aged 8 - 10 and women of childbearing age were conducted dietary survey to understand the condition of food intaking via the 24 h review method in 2015. Samples of urine, drinking water, dried beef, milk, Qula and fried noodles were collected and tested iodine level. Results Due to taking iodized salt three times a day with meals, the median of urinary iodine among 492 investigated boarding students was 179.2 μg/L;differently, the median of urinary iodine among 298 day students in this investigation was 79.6 μg/L who taking iodized salt only at lunch at school;and in the study, the median of urinary iodine among 158 women of childbearing age who took iodine-free salt daily was 33.7 μg/L. The iodine contents in 51 drinking water samples, 66 dried beef samples, 48 milk samples, 20 Qula samples and 37 fried noodle samples were quantified respectively, and the average iodine contents of each food were 0.8 μg/L in drinking water, 59.1 μg/kg in dried beef, 61.5 μg/kg in milk, 226.4 μg/kg in Qula and 17.0 μg/kg in fried noodles. The acceptable daily intake (ADI) of iodine of the boarding and day students aged from 8 to 10 and women of child bearing age were 234.0, 126.4 and 76.7 μg/d, respectively, among which the ADI of iodine with iodized salt were 208.0, 78.0 and 0.0 μg/d. Conclusion Consuming iodized salt is a main method to get iodine among Tibetans in Nangqian County, so that it is significant to carried out this measure for a long time for free to let them have iodized salt every day instead of iodine-free one.

To study different breed pigs reply the swine flu virus infections,specific antibody of sIgA secretion regularity of respiratory tract and the differences of sIgA antibody according to different antigen proteins were detected.A/swine/Nanjing/ 51/2010(H3N2) was intranasally infected pigs (1 × 107 TCID50/mL and 2 mL/pig),and then the nasal swab samples were collected at different time points within 21 days after infection.M1,NS1 and PB1 recombinant protein,respectively,were used to establish indirect ELISA method for detecting specific antibody of sIgA,and to analyze its secretion regularity.Results displayed that there was no significant difference among three kinds of recombinant protein in the whole test,characterizing by specificity sIgA antibody levels rising rapidly after 5 infection days and reaching peak at day 14,then began to decline.Among different varieties of pigs,sIgA antibody production of PB1 protein in Obama group was significantly higher than that in binary pigs at 14th and 21st day (P＜0.05).It had no significant difference between M1 group and the NS1 group (P＞0.05).This experiment preliminary explores the secretion regularity of specificity sIgA antibody after infected swine flu virus,which laid a foundation for further study of SIV mucosal antibody diagnostic reagents.

OBJECTIVETo investigate the expression of N-cadherin in bone marrow leukemic cells derived from acute leukemia patients and its clinical significances.

METHODSA total of 113 patients with acute leukemia were enrolled in this study. Flow cytometry was employed to detect the expression of N-Cadherin in bone marrow leukemic cells from acute leukemia patients and the relationships between the N-cadherin expression and the clinical characteristics of patients with acute leukemia were analyzed.

RESULTSThe expression of N-Cadherin in bone marrow leukemic cells deriveted from patients with acute leukemia was variable with 0%-99.7%. For adult AML patients, the positive rate of CD34 in N-cadheringroup was significantly higher than that in N-cadheringroup(67.39% vs 33.33%)(P=0.013), while the differences of total CR rate and rate of CR after 1 cycle of induction treatment were not significant between these 2 groups(P>0.05). As to ALL patients, N-cadheringroup had significant lower WBC count (21.31±7.07 vs 51.10±23.69)(P=0.008) and lower percentage of peripheral blood blast (43.22±5.75% vs 66.45±5.65%)(P=0.015). The CR rate after 1 cycle of induction treatment and rate of overall CR were lower and the relapse rate was higher in N-cadherinALL group than those in N-cadherinALL group, but the differences were not significant (P>0.05). For childhood ALL, the positive rate of CD33 in N-cadheringroup was significantly higher than that in N-cadheringroup(47.62% vs 0%)(P=0.012). The relapse rate was higher in N-cadheringroup than that in N-cadheringroup (30.00% vs 0%)(P=0.115). The median survival time, 3-year overall OS rate and 3-year relapse-free survival rate in N-cadheringroups of adult AML, non-M3 AML, ALL and chidhood ALL paients were superior to N-cadheringroups, but the differences were not significant.

CONCLUSIONThe expression of N-cadherin in bone marrow leukemic cells relates to some clinical features of patients with acute leukemia and to some extent has inferior effect on survival of patients with acute leukemia.

Objective To explore the clinical characteristics and prognosis of congenital pulmonary artery sling (PAS) in children. MethodsThe clinical data of 38 children diagnosed with PAS during June 2009 and February 2015 were retrospectively analyzed. ResultsIn 38 PAS children, 35 cases (89.47%) were hospitalized for varying degrees of respiratory manifestations with recurrent cough (89.47%) and wheezing (84.21%) being the most common. The remaining 3 cases were found abnormal in routine preoperative examination and the diagnosis was confirmed after further examination. All 38 children were performed computer tomography angiography (CTA). Thirty-seven cases were diagnosed of PAS and diagnostic rate was 97.37%. One case was suspected of pulmonary dysplasia and diagnosed of PAS after operation. Twenty-six children received surgical treatment, of whom 25 children had pulmonary artery reconstruction (LPA). Seven children died during/after operation and 18 survived. The remaining 12 children received non-surgical treatment, of whom 9 died and 3 survived.ConclusionCardiac uhrasonography may reveal PAS in the early stage, while CTA is the best method for conifrmed diagnosis. LPA reconstruction is an important means of relieving left pulmonary artery oppression.

OBJECTIVETo evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) for treatment of patients with newly diagnosed immune thrombocytopenia (ITP).

METHODSThe clinical data of 96 patients with newly diagnosed ITP from August 2013 to August 2015 were analyzed retrospectively, 96 patients were divided into the rhTPO group (46 cases) and the control group (50 cases). Patients in the rhTPO group received subcutaneous injection of rhTPO at a dose of 300 U/(kg·d) for a maximum of 14 days, and control group was treated with glucocorticoid (standard dose) for 28 days. Then the efficacy and adverse reactions between the 2 groups were compared.

RESULTSCompared with the control group, the patients in rhTPO group achieved higher complete response (CR) rate (56.5% vs 34.0%) (P = 0.03), shorter median time when platelet counts reached 100 × 10(9)/L[10 (5-14) d vs 14 (6-26) d, P < 0.01] and less adverse reactions (4.4% vs 82.0%) (P < 0.01). After the withdrawal of rhTPO, platelet counts gradually decreased. Sex, age and the presence of HP infection had no influence on efficacy of rhTPO (P > 0.10), but when Plt count was too low (≤10 × 10(9)/L), the proportion of patients obtaining CR showed an decreased tendency, as compared with those with Plt>10 × 10(9)/L (38.9% vs 67.9%) (P = 0.06).

CONCLUSIONrhTPO has satisfactory therapeutic effect and enough safety for patients with newly diagnosed ITP, however, its long-term efficacy should be furtherly improved.

Adult ; Glucocorticoids ; therapeutic use ; Humans ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Recombinant Proteins ; therapeutic use ; Remission Induction ; Retrospective Studies ; Thrombopoietin ; therapeutic use