Efficacy and Safety of Decitabine Combined with Modified EIAG Regimen in the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, prognosis and safety of decitabine combined with modified EIAG regimen in the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).@*METHODS@#The clinical data of 44 patients with relapsed/refractory AML and high-risk MDS admitted to our hospital from January 2017 to December 2020 were analyzed retrospectively. The patients were equally divided into D-EIAG group (decitabine combined with EIAG regimen) and D-CAG group (decitabine combined with CAG regimen) according to clinical treatment regimen. The complete response (CR), CR with incomplete hematologic recover (CRi), morphologic leukemia-free state (MLFS), partial response (PR), overall response rate (ORR), modified composite complete response (mCRc), overall survival (OS) time, 1-year OS rate, myelosuppression and adverse reactions between the two groups were compared.@*RESULTS@#In D-EIAG group, 16 patients (72.7%) achieved mCRc (CR+CRi+MLFS), 3 patients (13.6%) achieved PR, and ORR (mCRc+PR) was 86.4%. In D-CAG group, 9 patients (40.9%) achieved mCRc, 6 patients (27.3%) achieved PR, and ORR was 68.2%. Difference was observed in mCRc rate between the two groups (P=0.035), but not in ORR (P>0.05). The median OS time of D-EIAG group and D-CAG group was 20 (2-38) months and 16 (3-32) months, and 1-year OS rate was 72.7% and 59.1%, respectively. There was no significant difference in 1-year OS rate between the two groups (P>0.05). After induction chemotherapy, the median time for absolute neutrophil count recovery to 0.5×109/L in D-EIAG group and D-CAG group was 14 (10-27) d and 12 (10-26) d, for platelet count recovery to 20×109/L was 15 (11-28) d and 14 (11-24)d, the median red blood cell suspension transfusion volume was 8 (6-12) U and 6 (6-12) U, and the median apheresis platelet transfusion volume was 4 (2-8) U and 3 (2-6) U, respectively. There were no statistically significant differences in comparison of the above indicators between the two groups (P>0.05). The hematological adverse reactions of patients were mainly myelosuppression. Grade III-IV hematological adverse events occurred in both groups (100%), with no increase in the incidence of non-hematological toxicities such as gastrointestinal reactions or liver function damage.@*CONCLUSION@#Decitabine combined with EIAG regimen in the treatment of relapsed/refractory AML and high-risk MDS can improve remission rate, provide an opportunity for subsequent therapies, and have no increase in adverse reactions compared with D-CAG regimen.

Preliminary audiological evaluation of the SoundBite bone conduction devices in adults with single-sided deafness / 中华耳鼻咽喉头颈外科杂志

Objective: The auditory deficits of single-sided deafness (SSD) can be treated with a novel intra-oral device, SoundBite, which delivers sound by applying vibratory signal to the teeth. The purpose of this study was to evaluate the efficacy and benefit of the bone conduction device for Chinese adults with SSD. Methods: Eighteen patients aged 19-66 yrs with acquired, permanent sensorineural SSD and no current treatment by any other devices for SSD, were recruited in a prospective controlled, nonrandomized, unblinded study. They were requested the continually daily wear of the new device over a 30-day free trial period. The intra-oral hearing device was placed around two maxillary teeth and was similar to a small partial denture or retainer. The audiological tests included pure tone air conduction thresholds, monosyllable word recognition score (WRS) in quiet and sentence reception thresholds in noise (via CMNmatrix test). The benefit was determined with the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Speech, Spatial and Qualities of Hearing Scale (SSQ) questionnaire. Results: The monosyllable WRS and the 50% threshold of signal-to-noise ratio (SNR50) were significantly better in all aided conditions. The head shadow effect, assessed by the SNR50 via CMNmatrix test improved an average of 2.6 dB after 30 days' wearing compared with unaided condition (P<0.001). The APHAB scores improved (P<0.05) for all subjects for the Global and Ease of Communication, Reverberation, Background Noise subscales. The SSQ scores improved (P<0.05) for all subjects for Speech, Spatial and Qualities of Hearing subscales. Conclusion: The SoundBite is a good alternative to the well-established implantable bone conduction devices in patients with SSD. An improvement in listening ability in noise and quiet as well as a decrease of the head shadow effect is validated as the expected.

Expert Consensus on Otorhinolaryngology Head and Neck Diseases Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） and western medicine have their respective advantages and limitations in the diagnosis and treatment of common otorhinolaryngology head and neck diseases. Although the integrated TCM and western medicine exhibits definite curative effects， there is no consensus on the otorhinolaryngology head and neck diseases responding specifically to TCM or integrated TCM and western medicine， as well as the diagnosis and treatment schemes. The China Association of Chinese Medicine （CACM） thus organized the otorhinolaryngology head and neck specialists of both TCM and western medicine to discuss the etiology， pathogenesis， and clinical diagnosis and treatment methods of common otorhinolaryngology head and neck diseases with the results of multiple clinical trials taken into account. The acute pharyngitis， chronic pharyngolaryngitis， paraesthesia pharyngis， hysterical aphasia， allergic rhinitis， subjective tinnitus， and otogenic vertigo were confirmed to respond specifically to TCM or integrated TCM and western medicine. Then a mutually agreed diagnosis and treatment scheme and recommendation with integrated TCM and western medicine was formulated as a reference for clinical practice， thus benefiting more patients.

Analysis of Related Factors Affecting the Nosopoiesis of Childhood Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the related factors affecting the nosopoiesis of childhood acute leukemia from the perspective of indoor environmental exposure, behavior and lifestyle.@*METHODS@#The clinical data of 64 children with acute leukemia were retrospectively analyzed, and 50 healthy children were selected as the control group during the same period. The basic data of children, indoor environment, behavior and lifestyle of parents in 2 groups were recorded. Univariate and multivariate logistic regression analysis were used to analyze the related factors affecting the incidence of childhood acute leukemia, and the OR (95%CI) value was calculated.@*RESULTS@#The unvariate analysis showed that the daily wine-drinking rate of father and pesticide use rate in acute leukemia group were significantly higher than those in control group (P<0.05). Multivariate Logistic regression analysis showed that indoor ventilation during summer sleep of children (OR=0.35, 95%CI: 0.14-0.88) and contact with other children before 3 years old (OR=0.34, 95%CI: 0.18-0.65) were protective factors for provention of childhood acute leukemia (P<0.05). Mothers had a history of exposure to chemical substances (OR=3.68, 95%CI: 1.64-8.27), and children had a history of exposure to chemical substances (OR=3.84, 95%CI: 1.64-9.01), family had internal decoration history after child birth (OR = 1.38, 95%CI: 1.05-1.81) and family uses of pesticides (OR=2.17, 95%CI: 1.08-4.36), all these factors were independent risk factors for acute leukemia (P<0.05).@*CONCLUSION@#Indoor environmental exposure, behavior and lifestyle of children and parents may be closely related with the nosopoiesis of childhood acute leukemia.

Comparison between Bilateral and Unilateral Sudden Sensorineural Hearing Loss / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bilateral sudden sensorineural hearing loss (BSSHL) is rare and assumed to be a different clinical entity compared to unilateral SSHL (USSHL). This study examined the differences between the idiopathic BSSHL and USSHL.</p><p><b>METHODS</b>Forty-six sequential BSSHL patients (Se-BSSHL) and 68 simultaneous BSSHL (Si-BSSHL) were consecutively admitted between June 2008 and December 2015. Two sets of patients served as control groups: (1) USSHL patients with healthy contralateral ear and (2) USSHL patients with contralateral preexisting hearing loss (USSHLwCHL). We retrospectively analyzed differences among four cohorts using analysis of variance, Kruskal-Wallis test, Welch's t-test, and Chi-square test as appropriate before and after propensity score matching (PSM) based on age, gender, and body mass index (BMI).</p><p><b>RESULTS</b>The prevalence of idiopathic BSSHL was 8.6% (114/1329) among the total SSHL patients. In the total cohort, USSHL patients tended to be younger, female, and tended to have lower BMI, renal parameters, and total cholesterol in addition to higher high-density lipoprotein compared to the other three groups. Most routine blood indicators, some coagulation markers, and immunoglobulin M (H = 13.4, P = 0.004) were significantly different among the study groups. After PSM, the major significant differences were found in audiometric characteristics. Si-BSSHL and Se-BSSHL patients demonstrated similar hearing thresholds as USSHL but were significantly better than the USSHLwCHL patients across most frequencies before and after treatment (H = 30.0, P < 0.001 for initial hearing and H = 12.0, P = 0.007 for final hearing). Moreover, the BSSHL patients showed different hearing loss distribution patterns (more descending type, χ2 = 33.8, P = 0.001) with less hearing gain (H = 17.5, P < 0.001) compared to the USSHL patients.</p><p><b>CONCLUSIONS</b>Idiopathic BSSHL is a relatively rare subtype of SSHL with a higher rate of descending audiogram type and inferior hearing outcome rather than being classified as a completely different disease entity compared to USSHL.</p>

Value of BCL-2 and PD-L1 Combined Detection in Predicting the Prognosis of Primary Acute Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical value of combined detection of BCL-2 and PD-L1 in predicting the prognosis of newly diagnosed patients with acute leukemia (AL).</p><p><b>METHODS</b>A total of 100 cases of AL in our hospital from Jan. 2013 to Sep. 2016 were enrolled in the study. The mRNA expression of BCL-2 and PD-L1 in peripheral blood of patients was detected by RT-PCR, and the prognosis of the patients was followed up. According to the follow-up results, these patients were divided into complete remission group and no remission group, the statistical analysis of different indexes predicting the prognosis was performed.</p><p><b>RESULTS</b>Compared with the healthy control group, the positive rates of BCL-2 and PD-L1 in the bone marrow specimens of AL patients significantly increased (P<0.01). The BCL-2 predicting the prognosis of patients showed that the area under the curve (AUC) was 0.725(P=0.006), the diagnostic threshold was 1.550, the sensitivity(Sen) and specificity(Spe) were 72% and 84%, respectively. The single PD-L1 detection for predicting the prognosis of patients showed that AUC was 0.740 (P=0.004), diagnostic threshold was 12.500, Sen and Spe were 66.7% and 73.1%, respectively. The diagnostic index of combined detection was 77.90, which were higher than that of series detection 54.75, and higher than that of the independent diagnostic index.</p><p><b>CONCLUSION</b>Detection of BCL-2 combined with PD-L1 can be used to evaluate the prognosis of patients with newly diagnosed acute leukemia, which can improve the specificity and sensitivity of the detection, and has higher clinical diagnostic value than single actection.</p>

Effect of Interferon Combined with Thalidomid on HEL Cell Apoptosis and JAK2V617F Mutation Gene Expression / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of interferon-α2b combined with thalidomid(THD) on the proliferation and apoptosis of HEL cells, and expression of JAK2V617F-mutated gene.</p><p><b>METHODS</b>The cell survival rates were assayed by CCK-8 after HEL cells were treated by interferon-α2b, thalidomid and thalidomid combined with interferon-α2b for 24, 48 and 72 hours, while the apoptosis and expression of JAK2V617F mutation gene were detected by flow cytometry and fluorescence quantitative PCR respectively after treatmemt for 48 hours.</p><p><b>RESULTS</b>IFN-α2b combined with THD could more obviously inhibit the proliferation of HEL cells than IFN-α2b or THD alone for 24 and 48 and 72 hours, and the differences between groups were statistically significant(P<0.05). In addition, the apoptosis-inducing effect of IFN-α2b combined with THD on HEL cells was more obvious than that of IFN-α2b used alone, the differences was statistically significant(P<0.05). Although IFN-α2b combined with THD can decrease the JAK2V617F mutation gene expression more obviously than IFN-α2b alone,but the difference was no statistically significant (P>0.05). And the remaining groups showed statistically significance(P<0.05).</p><p><b>CONCLUSION</b>IFN-α2b combined with THD can obviously inhibit the proliferation and induce apoptosis of HEL cells more than that of IFN-α2b alone, but the effect of reducing JAK2V617F mutation gene expression is not different.</p>

Relationship between RAD51-G135C and XRCC3-C241T Single Nucleotide Polymorphisms and Onset of Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between RAD51-G135C and XRCC3-C241T single nucleotide polymorphisms and onset of acute myeloid leukemia (AML).</p><p><b>METHODS</b>The study was performed in 2 groups: AML patient group and normal person group as control group. Genomic DNA was extracted from peripheral blood cells of 545 AML patients and 1 034 normal persons. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by TaqMan probe technology and the ralatienship between RAD51-G135C/XRCC3-C241T polymorphisms and onset of acute myeloid leukemia was investigated.</p><p><b>RESULTS</b>Compared with the control group, RAD51-G135C homozygous mutant (CC) could significantly increase the risk of AML patients (OR=3.07), and there was no statistical relationship between heterozygous mutant (GC) of RAD51-G135C and onset of AML. There was no statistical relationship between homozygous mutant (TT) of XRCC3-C241T and onset of AML, and the XRCC3-C241T heterozygous mutation type (CT) increased the risk of AML patients (OR=0.66).</p><p><b>CONCLUSION</b>RAD51-G135C homozygous mutant and XRCC3-C241T heterozygous mutation significantly increase the risk of the AML onset, which can provide more predictive value for incidence of AML.</p>

IDH1 Gene Mutation and Its Clinical Significance in patients with Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the incidence rate of IDH1 in acute myeloid leukemia and analyze its effect on clinical characteristics and prognosis.</p><p><b>METHODS</b>Mononuclear cells in bone marrow samples were collected from 192 adult patients with newly diagnosed AML. Polymerase chain reaction (PCR) and direct sequencing were used to amplify exon 4 of IDH1 gene, the gene sequencing was used to analyze the gene mutations, at same time, the detection of NPM1, FLT3-TKD, FLT3-ITD, C-KIT, CEPBA, TET2 and JAK2V617F and MLL mutations were carried out, the follow-up was used to determine its therapeutic efficacy and outcomes of patients. The clinical and laboratory data of these cases were collected, and their clinical characteristics and prognosis were then analyzed.</p><p><b>RESULTS</b>Among the 192 AML patients, 13 cases were detected with IDH1 gene mutation, the mutation rate was 6.77% [95% CI (5.70%-13.38%)]. The sequencing chart of IDH1 gene showed double peaks, the mutations were heterozygous, out of them c.G395A (p.R132H) was found in 8 cases, c.C394T was found in 4 cases (p.R132C), c.C394A (p.R132S) was found in 1 cases, R132H and R132C are common, 13 cases showed missense mutation. The median age in mutation group was 52 years old, the median age in unnutration group was 40 years, there was significant difference between them (P = 0.010). Mutation rate of IDH1 gene in M1 and M2 was significantly higher than that in other FAB subtypes. There were no significant difference in sex, newly diagnosed peripheral white blood cell count, hemoglobin, platelet count, peripheral blood and bone marrow original cell proportion of primitive cells between them. Mutation of IDH1 gene had certain correlation with NPM1 gene mutation, but no correlation with FLT3-TKD, FLT3-ITD, C-KIT, TET2 and JAK2V617F and MLL natations was found. In addition, the IDH1 mutation easily occurred in patients with normal karyotype or in patients with middle prognostic risk karyotype, IDH1 mutation occurred in 11 cases with normal karyotype, the mutation rate was 10.28%, IDH1 mutation were observed in 2 cases with abnormal karyotype, the mutation rate was 3.50%, there was significant difference. In AML patients with middle prognostic risk karyotype. The complete remission (CR) and the 3 year survival (OS) rate of IDH1 mut patients were less than that in IDH1 wt, there was significant difference (P < 0.05).</p><p><b>CONCLUSIONS</b>The IDH1 mutation more easily occurr in older AML patients and mutations effect of IDH1 on clinical characteristics may represent a molecular marker for poor prognosis in AML.</p>

Activating effect of ATP on NO/cGMP pathway in guinea pig cochlea / 生理学报

The present investigation was to study the relationship between ATP and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway. Forty healthy purebred albino guinea pigs with sensitive pryer's reflex were randomly divided into five groups. Their cochleae were dissected and perfused immediately with different solutions. For the control group, the cochleae (group 1) were perfused with artificial perilymph basal solution (APBS, containing 100 micromol/L dipyridamole, 100 micromol/L L-Arg and 1 mmol/L IBMX). Other groups were respectively perfused group 2 with 330 micromol/L ATP, group 3 with 100 micromol/L L-NNA+330 micromol/L ATP, group 4 with 10 micromol/L ODQ+330 micromol/L ATP and group 5 with 10 micromol/L A-23187. All these reagents were freshly dissolved in artificial perilymph basal solution (APBS). The cochlear tissue specimens were collected and the average cGMP content was measured with (125)I-cGMP RIA kit. The results showed that there was no significant difference in the average cochlear tissue weights among different groups. The concentration of cGMP in the cochlear tissue of the groups perfused with ATP (59.541+/-8.744 fmol/mg) and A-23187 (55.416+/-7.018 fmol/mg) was significantly higher than those of the control group (30.089+/-4.876 fmol/mg), the groups perfused with L-NNA+ATP (28.761+/-5.019 fmol/mg) and ODQ+ATP (34.209+/-13.658 fmol/mg). No significant difference was observed between the group perfused with ATP and the one with A-23187, as well as among the control group and the groups perfused respectively with L-NNA+ATP and ODQ+ATP. These results suggest that ATP elevated the concentration of cGMP in cochlear tissue while administration of nonselective nitric oxide synthase inhibitor L-NNA and soluble guanylate cyclase inhibitor ODQ could prevent the increase of cGMP concentration induced by ATP. It is indicated that ATP is involved in the activation of NO/cGMP pathway by elevating concentration in the cytoplasm of the cochlea. In turn, NO/cGMP pathway may exert a negative action on the effects of ATP. It is suggested that there is an ATP/Ca(2+)-NO/cGMP pathway in the guinea pig cochlea. ATP and NO/cGMP pathway jointly regulate the function of the cochlea.

The Role of "Supporting Cells" in the Cochlea / 대한이비인후과학회지

No abstract available.