OBJECTIVETo study the effect of transforming growth factor-β activated kinase-1 (TAK1) gene silencing on the proliferation and apoptosis of Kasumi-1 cells induced by arsenic trioxide (As₂O₃).

METHODSAcute myeloid leukemia with t(8;21) cell line Kasumi-1 cells were treated with As₂O₃ or in combination with TAK1 siRNA interference technology. The experiment was divided into four groups: Kasumi-1 cells without any treatment, TAK1 specific siRNA transfection alone, Kasumi-1 cells treated with different concentration of As₂O₃, TAK1siRNA transfection combined with As₂O₃. CCK-8 was used to detect the cell viability. The expression of phosphorylated c-Jun N-terminal kinase (P-JNK) was determined by Western Blot. Cell apoptosis and growth were examined by morphological and colony formation assay.

RESULTSAfter Kasumi-1 cells were treated with As₂O₃, the rate of cell inhibition was concentration-dependent, and the 50% inhibitory concentration was 3.5 μmol/L. The highest expression level of P-JNK appeared in 30 minutes after cells were treated with As₂O₃. The apoptosis rates of Kasumi-1 cells without any treatment, TAK1 siRNA interference alone group, As₂O₃ alone group and the combined group were (5.02 ± 1.13)%, (6.18 ± 0.28)%, (48.33 ± 2.70)% and (86.07 ± 2.21)%; colony formation rates were (73.83 ± 2.78)%, (76.03 ± 1.46)%, (55.07 ± 1.50)% and (22.20 ± 1.15)%; apoptosis rate of TAK1 siRNA group and the untreated group has no significant difference (P = 0.052); colony formation rate between TAk1 siRNA group and the untreated group has no significant difference (P = 0.179), but the difference in other groups was significant (P = 0.000).

CONCLUSIONSilencing the expression of TAK1 can enhance the anti-proliferative and pro-apoptotic effect of As₂O₃ on Kasumi-1 cells, and its mechanism may be through the TAK1 downstream JNK signal pathway.

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Line, Tumor ; Humans ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Leukemia, Myeloid, Acute ; enzymology ; pathology ; MAP Kinase Kinase Kinases ; genetics ; metabolism ; Oxides ; pharmacology ; RNA Interference ; RNA, Small Interfering ; genetics ; Signal Transduction

In order to improve the efficiency of drug screening on serotonin transporter (SERT) inhibitors, a high-throughput screening (HTS) model is established in RBL-2H3 cells. The RBL-2H3 cells are very similar to the serotonin genetic neuro, in modulation of post-receptor mechanisms and transduction pathway of SERT reactivated. Depending on a fluorescence substrate ASP+ used in detection method of inhibitor rates, it's convenient, quick, accurate and effective, not making the environmental biohazard compared with radioactive experiments. Furthermore, biological screening model combined with computer aided virtual screening technique describing high-throughput virtual screening (HTVS). Bayesian classification method and molecular fingerprint similarity were applied to virtual screening technique, for screening compounds in compound library. Some compounds have been found, and then validated further by biological screening model. Combination of HTS and HTVS improves the efficiency of screening SERT inhibitors.
Animals ; Bayes Theorem ; Cell Line ; Drug Evaluation, Preclinical ; High-Throughput Screening Assays ; Models, Biological ; Rats ; Serotonin Plasma Membrane Transport Proteins ; metabolism ; Serotonin Uptake Inhibitors ; pharmacology

OBJECTIVETo investigate the clinical effect and safety of chiropractic in treating cervicogenic sudden hearing loss.

METHODSFrom January 2011 to October 2013, 90 patients with cervicogenic sudden hearing loss were randomly divided into treatment group and control group according to the random number table produced by SPSS 19.0 software. In the treatment group, there were 17 males and 28 females, aged from 31 to 62 years old with an average of (47.57±9.43) years; course of disease was from 1 to 3 days with an average of (1.43±0.68) days; pure-tone audiometry score was from 46.5 to 77.8 dB with the mean of (61.20±9.83) dB; Northwick Park Neck Pain Questionnaire (NPQ) score was from 17 to 31 scores with an average of (23.46±7.18) scores. In the control group, there were 15 males and 30 females, aged from 28 to 64 years old with an average of (45.77±6.99) years; course of disease was from 1 to 3 days with an average of (1.50±0.73) days; pure-tone audiometry score was from 48.1 to 75.0 dB with the mean of (63.91±8.05) dB; Northwick Park Neck Pain Questionnaire (NPQ) score was from 20 to 29 scores with an average of (25.61±10.43) scores. The patients of control group were treated with dexamethasone intravenous drip of 10 mg, 3 days later, decreased to 5 mg, 3 days again. And with the methycobal intravenous drip of 500 μg, treatment continued for 10 days. The patients of treatment group were treated with chiropractic additionally except for the therapeutic methods of control group. Chiropractic included local muscle loosening, attacking point, bilateral pulling atlanto-axial joint, and continuous treatment for 10 days. The pure-tone audiometry score and NPQ score were compared between two groups after treatment.

RESULTSAfter the treatment, pure-tone audiometry score and NPQ score in treatment group improved to (40.23± 8.14) dB and (12.70±8.29) scores respectively, which were obviously better than that of control group's (37.70±10.61) dB and (21.24±11.13) scores (P<0.05).

CONCLUSIONCompared with routine method for cervicogenic sudden hearing loss, additional chiropractic can improve hearing and relieve neck pain effectively.

Cervical Vertebrae ; Female ; Hearing Loss, Sudden ; therapy ; Humans ; Male ; Manipulation, Chiropractic ; methods ; Medicine, Chinese Traditional ; Middle Aged

Adult ; Child ; Eosinophilia ; complications ; Female ; Hematologic Neoplasms ; complications ; Humans ; Male ; Middle Aged

OBJECTIVETo assess the frequencies and prognostic significance of the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations in acute myeloid leukemia (AML) and to explore their relevance to clinical, cytogenetic and molecular feature.

METHODSGenomic DNA from 96 newly diagnosed AML patients from Sep. 2009 to Jan. 2011 was screened by RT-PCR and sequencing for IDH1 and 1DH2 mutation.

RESULTSThe prevalence of IDH1 (p. P127 and p. I130) and IDH2 mutations (p. R140) was 14.6% (14/ 96) and 2.17% (2/96) respectively. The IDH1 mutations of p. P127 and p. I130 were not reported so far in literature. Of 14 IDH1 mutation patients, 10 were with normal karyotype and the differences had statistical significance (P=0.021). Two patients with IDH2 mutation were also with normal karyotype. IDH2 mutations were in older patients at diagnosis. Patients with IDH mutation had higher white blood cell counts, lower platelet counts, expression of HLA-DR, CD34, CD33 and CD13, lower remission rate and higher relapse rate.

CONCLUSIONIDH mutation is recurring genetic change in AML and indicates poor prognosis.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; DNA Mutational Analysis ; Female ; Humans ; Isocitrate Dehydrogenase ; genetics ; Karyotype ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; Male ; Middle Aged ; Mutation ; Prognosis ; Young Adult

Amygdala ; drug effects ; metabolism ; Animals ; Conditioning (Psychology) ; Morphine ; adverse effects ; Rats ; Receptors, Opioid, kappa ; metabolism

Objective To investigate the reversal effect of MDR1 and MDR3 gene silencing on resistance of A2780/taxol cells to paclitaxel.Methods shRNA plasmid vector specifically targeting MDR1 and MDR3 genes was transfected into A2780/taxol cells.The early stage cell apoptosis and the effect of intracellular rhodamine 123(Rh123)accumulation were detected by flow cytometry(FCM).The late stage cell apoptosis rate was detected by terminal deoxynucleotidyl transferase(TdT)-mediated deoxyuridine triphosphate(dUTP)nick end labeling(TUNEL).The 50% inhibition concentration(IC_(50))of paclitaxel on A2780/taxol cells was determined by methyl thiazolyl tetrazolium(MTT)assay.MDR1 and MDR3 mRNA were assessed by RT-PCR,and caspase-3 protein was detected by western blot.Results After treatment with MDR1 and MDR3 shRNA plasmid vector,early apoptosis rate of A2780/taxol cells was (20.21?0.56)% and(10.87?1.24)%,respectively.MDR1 and MDR3 shRNA could increase cellular Rh123 accumulation(116.6?8.1 and 98.4?3.8,respectively).The late stage apoptosis rates detected by TUNEL displayed the same tendency as FCM results did.The IC_(50)for paclitaxel of A2780/taxol cells was decreased significantly.The mRNA levels of MDR1 and MDR3 in A2780/taxol cells were decreased by (73.3?0.8)% and(51.6?0.4)% of control,and the reduction of MDR1 and MDR3 mRNA was in a time-dependent manner.The expression of caspase-3 protein of MDR1 and MDR3 shRNA vector transfected group in A2780/taxol cells was significantly increased [(80.8?2.6)% and(72.0?4.7)%, respectively ].Conclusion MDR1 and MDR3 gene silencing could recover sensitivity of A2780/taxol cells to paclitaxel and induce cell apoptosis,thus reversing cell resistance to paclitaxel.

Abstract: Objective　To investigate the clinical characteristics and incidence of Brucella encephalitis and meningitis in children. Methods We report the clinical data of a child with Brucella melitensis meningitis in children, and summarize the incidence, diagnosis methods and treatment of Brucella encephalitis or meningitis in children, taking into account the relevant domestic and foreign literature from January 2014 to December 2020. Results　A 4-year-old girl was admitted to the hospital with status epilepticus on March 15, 2021 because of interrupted right limb numbness for 16 hours and convulsions for 2 hours. She had 2 non-febrile convulsions three months before admission and was diagnosed with epilepsy. This incident was acute, accompanied by low fever, with epilepsy as the main manifestation. Cerebrospinal fluid test suggested central nervous system infection, but the nature of infection could not be determined by routine and biochemistry of cerebrospinal fluid.The cerebrospinal fluid next generation sequencing confirmed that the pathogen of the infection was B. melitensis, which was further verified by the peripheral blood antibody test. After effective antibiotics combined with a full course of treatment, the patient recovered after six months of treatment. A total of 60 articles were retrieved in the database, including 29 in Chinese. During this period, a total of 7 cases of brucellosis in children with nervous system involvement were reported, one of which was a case report, and the other 6 cases were mentioned in the comprehensive analysis of children with brucellosis. Conclusions　Brucella encephalitis or meningitis in children has a low incidence and various clinical features, which are easy to be misdiagnosed or missed.

Holmium ; Humans ; Kidney ; Lithotripsy, Laser ; Shock, Hemorrhagic ; Ureteroscopy