OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

ObjectiveTo determine the value of MRI blooming sign in differentiating benign and malignant small breast masses and investigate its radiologic-pathologic correlation. MethodsThis retrospective study included 554 small breast masses （291 malignant and 263 benign） which were ≤ 2 cm and validated by pathology analysis between June 2016 and September 2020. All 554 patients underwent breast MRI. The clinical characteristics and MR features were analyzed. Univariate and multivariate regression analysis were performed to identify the independent risk factors of breast cancer. Two diagnostic models were constructed based on independent risk factors （model 1 included blooming sign and model 2 didn’t）. ROC curve was used to evaluate the diagnostic performances of the two models. The histological changes of peritumoral tissues in all small masses were analyzed. ResultsThe blooming sign was positive in 199 cases （68.4%） of the malignant masses and 25 cases （9.5%） of the benign ones （P＜0.05）. Univariate and multivariate regression analysis showed that age， lesion diameter， margin， ADC value， time signal intensity curve type and blooming sign were independent risk factors for breast cancer. Odds ratio were 1.065， 4.515， 2.811， 0.013， 3.487 and 13.894， respectively. Their corresponding 95%CI were （1.034， 1.097）， （2.368， 8.608）， （1.954， 4.045）， （0.004， 0.049）， （2.087， 5.826） and （7.026， 27.477）， respectively. The diagnostic performance of model 1 （blooming sign included） was better than that of model 2 （blooming sign not included； AUC： 0.938 vs 0.897， P < 0.05）. Histopathological analysis showed that the blooming sign was related to peritumoral lymphocyte infiltration and vascular proliferation. ConclusionsMRI blooming sign is helpful for distinguishing breast cancer from benign masses. The correlated histopathological basis may be peritumoral lymphocyte infiltration and neovascularization.

Objective: To investigate the incidence, risk factors and survival of bronchiolitis obliterans syndrome (BOS) in patients who had undergone haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: This study retrospectively analyzed clinical data of 444 consecutive patients who underwent haplo-HSCT and survived at least 100 days after transplantation in the First Affiliated Hospital of Soochow University between January 2013 and December 2015. Results: By the end of follow-up on January 1, 2018, 25 patients (5.63%) had BOS (BOS group) . The median onset time of BOS was 448 (165-845) d post transplantation, the 1-year, 2-year and 3-year cumulative incidence of BOS was 1.6% (95%CI 1.5%-1.6%) , 4.8% (95%CI 4.7%-4.8%) and 5.8% (95%CI 5.7%-5.8%) , respectively. Among patients with chronic graft-versus-host disease (cGVHD) , the cumulative incidence at the same intervals was 2.8% (95%CI 2.7%-2.8%) , 9.5% (95%CI 9.4%-9.5%) and 11.5% (95%CI 11.4%-11.6%) , respectively. In the multivariate analysis, the risk factors for BOS were high-risk primary disease, Ⅱ-Ⅳ aGVHD and preceding cGVHD with other organs. The 3-year overall survival (OS) was lower among patients with than those without BOS, but the difference was not significant [71.8% (95%CI 53.9%-89.6%) vs 72.4% (95%CI 68.1%-76.7%) , P=0.400]. Overall 1-year, 3-year survival of patients with BOS from the time of diagnosis was 78.4% (95%CI 61.5%-95.3%) and 37.0% (95%CI 2.5%-71.5%) , respectively, significantly less than those without (93.9% and 89.3%, from day 448 after transplantation, respectively, P<0.001) . Furthermore, we found a significantly higher incidence of transplantation-related mortality (TRM) in patients with compared with patients without BOS (28.2% vs 10.9%, P<0.001) . The main risk factor for OS of BOS patients was the severity of pulmonary impairment at the time of diagnosis. Patients who developed severe BOS had a worse OS than those with moderate and mild BOS (P=0.049) . Conclusion: BOS is a severe pulmonary complication of haplo-HSCT. High-risk primary disease, Ⅱ-Ⅳ aGVHD and preceding cGVHD were independent risk factors for BOS. Patients who developed BOS had a worse OS than those without BOS. The main risk factor for OS of BOS patients was the severity of pulmonary impairment.
Bronchiolitis Obliterans/etiology* ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Lung ; Retrospective Studies

Objective: To investigate the impact of FLT3-ITD and DNMT3A R882 double mutations to the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: FLT3-ITD, DNMT3A, C-kit, CEBPA, FLT3-TKD and NPM1 mutations were detected in 206 newly diagnosed AML patients by Sanger sequencing (M(3) and those received FLT3 inhibitor were excluded). Clinical data of AML patients were retrospectively analyzed to compare the prognosis of each gene mutation group. Results: ①Of 206 patients, 104 were male and 102 female with a median age of 38 (3-63) years, including 6 cases of M(0), 24 cases of M(1), 56 cases of M(2), 39 cases of M(4), 63 cases of M(5), 6 cases of M(6) and 12 unclassified cases. ②All 206 patients were divided into four groups according to the mutation gene at the time of diagnosis: FLT3-ITD(+) DNMT3A R882(+) group (group A), FLT3-ITD(+) DNMT3A R882(-) group (group B), FLT3-ITD(-) DNMT3A R882(+) group (group C) and FLT3-ITD(-) DNMT3A R882(-) groups (group D). Gender, leukocyte count at diagnosis, chromosome karyotype, the median age, FAB classification, disease status prior to transplantation, type of donor, conditioning regimen and GVHD were not significantly different between four groups (P>0.05). ③The 2-year cumulative recurrence rate (CIR) of group A was significantly higher than that of other groups [group A (72.2±2.6)%, group B (38.6±0.6)%, group C (36.8±1.6)%, group D (27.8±0.1)%, respectively, P<0.05], while the 2-year overall survival (OS) rate and 2-year leukocyte-free survival (LFS) rate were lower than those of other groups [group A (30.9±13.3)%, (11.3±10.2)%; group B (67.5±7.8)%, (47.9±8.4)%; group C (61.4±12.4)%, (56.8±12.5)%; group D (80.1±3.7)%, (79.7±3.6)%, respectively, P<0.05]. Conclusion: AML patients with FLT3-ITD and DNMT3A R882 double mutations had a very high CIR and low OS, LFS after transplantation.
Adolescent ; Adult ; Child ; Child, Preschool ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Mutation ; Nucleophosmin ; Prognosis ; Retrospective Studies ; Young Adult ; fms-Like Tyrosine Kinase 3/genetics*

OBJECTIVETo study the clinical outcome, adverse effect and treatment cost of homoharringtonine (HHT) in combination with all-trans retinoic acid (ATRA) and arsenic trioxide (AS2O3) for newly diagnosed with patients acute promyelocytic leukemia (APL).

METHODSClinical data of treatment of newly diagnosed patients with APL in experimental group (HHT + ATRA + AS2O3, n = 14) and control group \[Idarubicin (IDA) + ATRA + AS2O3, n = 21\] were analyzed retrospectively. The therapeutic effects, side effects and costs during induction therapy were compared between the two groups.

RESULTS(1) The complete remission (CR) rate were 92.9% (13/14) and 95.2% (20/21) in experimental group and control group, respectively. The time to achieve CR were (28.1 ± 3.8) and (31.7 ± 4.2) days, respectively (P > 0.05). The negative rate of PML-RARα fusion gene at the time of CR were 76.9% (10/13) and 75.0% (15/20), respectively, and that in CR patient at the end of the first cycle treatment were 100.0% (13/13) and 95.0% (19/20), respectively (P > 0.05). (2) 5-year overall survival (OS) rate were (92.6 ± 0.6)% and (89.9 ± 0.5)%, respectively (P > 0.05), 5-year disease free survival (DFS) rate were 100.0% and (86.8 ± 0.6)%, respectively (P > 0.05). (3) During induction therapy, the incidence of infection in experimental and control group were 23.1% (3/13), 60.0% (12/20), respectively (P < 0.05). The amount of platelet transfusion were (54.7 ± 29.6) and (76.5 ± 25.6) units, respectively (P > 0.05), and that of fresh frozen plasma were (1157.1 ± 238.4) and (1423.5 ± 324.6) ml, respectively (P > 0.05). The total medical costs (excluding HHT and IDA) in experimental and control group were (36074.9 ± 1245.6) and (50564.5 ± 3658.4)CNY, respectively (P < 0.05).

CONCLUSIONHHT in combination with ATRA and AS2O3 regimen for newly diagnosed APL has a better efficacy, a higher long-term survival rate, and a lower costs, which is one of the reasonable choice.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; therapeutic use ; Female ; Harringtonines ; therapeutic use ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Oxides ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Tretinoin ; therapeutic use

OBJECTIVETo investigate DNA methylation variation in human cells induces by B(a)P, and to explore the role of PARP1 during this process.

METHODSThe changes of DNA methylation of 16HBE and its PARP1-deficient cells exposed to B(a)P (1.0, 2.0, 5.0, 10.0, 15.0, 30.0 µmol/L) were investigated by immunofluorescence and high performance capillary electrophoresis, and simultaneously, the expression level of PARP 1 and DNMT 1 were monitored dynamically.

RESULTSThe percentage of methylated DNA of overall genome (mCpG%) in 16HBE and 16HBE-shPARP1 cells were separately (4.04 ± 0.08)% and (9.69 ± 0.50)%. After being treated by 5-DAC for 72 hours, mCpG% decreased to (3.15 ± 0.14)% and (6.07 ± 0.54)%. After both being exposed to B(a)P for 72 hours, the mCpG% in 16HBE group (ascending rank) were separately (5.10 ± 0.13), (4.25 ± 0.10), (3.91 ± 0.10), (4.23 ± 0.27), (3.70 ± 0.15), (3.08 ± 0.07); while the figures in 16HBE-shPARP1 group (ascending rank) were respectively (10.63 ± 0.60), (13.08 ± 0.68), (9.75 ± 0.55), (7.32 ± 0.67), (6.90 ± 0.49) and (6.27 ± 0.21). The difference of the results was statistically significant (F values were 61.67 and 60.91, P < 0.01). For 16HBE group, expression of PARP 1 and DNMT 1 were 141.0%, 158.0%, 167.0%, 239.0%, 149.0%, 82.9% and 108.0%, 117.0%, 125.0%, 162.0%, 275.0%, 233.0% comparing with the control group, whose difference also has statistical significance (t values were 11.45, 17.32, 32.24, 33.44, 20.21 and 9.87, P < 0.01). For 16HBE-shPARP1 group, expression of PARP 1 and DNMT 1 were 169.0%, 217.0%, 259.0%, 323.0%, 321.0%, 256.0% and 86.0%, 135.0%, 151.0%, 180.0%, 229.0%, 186.0% comparing with the control group, with statistical significance (t values were 9.06, 15.92, 22.68, 26.23, 37.19 and 21.15, P < 0.01). When the dose of B(a)P reached 5.0 µmol/L, the mRNA expression of DNMT 1 in 16HBE group (ascending rank) were 125.0%, 162.0%, 275.0%, 233.0% times of it in control group, with statistical significance (t values were 12.74, 24.92, 55.11, 59.07, P < 0.01); while the dose of B(a)P reached 2.0 µmol/L, the mRNA expression of DNMT 1 in 16HBE-shPARP1 group were 135.0%, 151.0%, 180.0%, 229.0%, 186.0% of the results in control group, and the differences were statistically significant (t values were 23.82, 40.17, 32.69, 74.85, 46.76, P < 0.01).

CONCLUSIONThe hypomethylation of 16HBE cells induced by B(a)P might be one important molecular phenomenon in its malignant transformation process. It suggests that PARP1 could regulate DNA methylation by inhibiting the enzyme activity of DNMT1, and this effect could be alleviated by PARP1-deficiency.

Benzo(a)pyrene ; adverse effects ; Cell Line ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; metabolism ; DNA Damage ; DNA Methylation ; Epithelial Cells ; drug effects ; metabolism ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; genetics ; metabolism

OBJECTIVETo compare the difference of therapeutic effects between vessel pricking therapy and Prednisone for treatment of Henoch-Schonlein purpura nephritis.

METHODSSeventy cases of acute purpura nephritis syndrome were randomly divided into an observation group (40 cases) and a control group (30 cases). Patients in observation group were differentiated into sthenia and asthenia syndromes. Vessel pricking therapy was applied at Hegu (LI 4), Quchi (LI 11), Xuehai (SP 10) etc. by triangular needle for sthenia symptom; shallow needling was used at Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36) etc. by filiform needle. The control group was treated with oral admi-nidtration of Prednisone. The symptom score of TCM, 24 h urinary protein, red blood cell count of urinary sediment of both groups were observed before and after treatment and therapeutic effects were compared.

RESULTSThe total effective rate of 92.5% (37/40) in observation group was superior to that of 80.0% (24/30) in control group, and there was a significant difference between two groups (P < 0.05); the symptom score of TCM, 24 h urinary protein, red blood cell count of urinary sediment were all improved in both groups after treatment (all P < 0.05), and moreover, the improvement in observation group was superior to that of control group (all P < 0.05); after treatment, the symptom score of TCM of sthenia syndrome was lower than that of asthenia syndrome in observation group (P < 0.05).

CONCLUSIONVessel pricking therapy has a significant therapeutic effect for treatment of Henoch-Schonlein purpura nephritis, superior to that of oral administration of Prednisone, and the therapeutic effect is better for treating sthenia syndrome than for asthenia syndrome.

Acupuncture Points ; Adolescent ; Adult ; Blood Sedimentation ; Bloodletting ; Child ; Erythrocyte Count ; Female ; Humans ; Male ; Middle Aged ; Prednisone ; therapeutic use ; Purpura, Schoenlein-Henoch ; blood ; drug therapy ; therapy ; Urine ; chemistry ; Young Adult

The goal of this study is to research the genetic characteristics and relationship between HN and P genes of NDV. The nucleotide sequence and deduced amino acid sequence were analyzed for the Hemagglutinin-neuramindase (HN) and Phosphoprotein (P) gene of twelve field isolates of Newcastle disease virus (NDV) during 1997-2005 in China. The HN and P gene sequences of fifteen NDV reference strains from GenBank were also used in this study. The molecular evolution distance of nucleotides and amino acids were calculated by MEGA 4.0 software, and analysis of variance and correlations were analyzed by SPSS11.0 software among different length sequences of the HN gene or P gene. The nucleotide and amino acids correlation of HN and P gene were analyzed respectively. The correlation of evolution distance and isolation year were also calculated. The results indicated that there were difference and good correlation of nucleotide and amino acid among different length sequences of the HN gene or P gene. These results revealed that the HN and P gene of NDV have the different response to selective pressure to adopt to landscape and closely relationship on heredity mutations. Nucleotide variations of HN and P gene have relationship with isolation year of strains.
Evolution, Molecular ; Genetic Variation ; HN Protein ; genetics ; Newcastle disease virus ; classification ; genetics ; Phosphoproteins ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

Objective To determine the curative effect of dilation for achalasia with temporary cardia stent in different diameters based on a long-term follow-up.Methods The study cohort was comprised of 135 patients of achalasia.Among them differentiated by stent diameters as followings:30 patients were treated under fluoroscopy with dilation of temporary cardia stent in 20 mm diameter(group A), 30 patients with dilation of temporary eardia stent in 25 mm diameter(group B),and 75 patients with dilation of temporary cardia stent in 30 mm diameter(group C).135 cardia stents were temporarily placed in the 135 patients and withdrawn after 3 -5 days via gastroscopy.All the stents were inserted and withdrawn successfully.The follow-up in all groups lasted 6-128 months.Results Six(20.0%)out of 30 patients,6(20.0%)out of 30 patients,5(22.7%)out of 22 patieuts,6(37.5%)out of 16 patients,5 out of 9 patients,3 out of 3 patients in group A exhibited dysphagia relapse during 6 months,1 year,3 years,5 years,8 years,and 10 years follow-up,respectively. Four(13.3%)out of 30 patients,4(13.3%)out of 30 patients,3(13.0%)out of 23 patients,4(22.2%)out of 18 patients,5(45.5%)out of 11 patients,and 3 out of 4 patients in group B exhibited dysphagia relapse during 6 months,1 year,3 years,5 years,8 years,and 10 years follow-up,respectively.No(0.0%)out of 75 patients, 1(1.5%)out of 66 patients,4(8.3%)out of 48 patients,6(18.2%)out of 33 patients,6(33.3%)out of 18 patients,2 out of 5 patients in group C exhibited dysphagia relapse during 6 months,1 year,3 years,5 years,8 years,and 10 years follow-up,respectively.Conclusion Dilation with temporary cardia metal stent in 30 mm diameter is the best dilation for achalasia in long-term follow-up.