The Role and Mechanism of MiR-451 in Multidrug Resistance of Leukemia Cell Line K562/A02 / 中国实验血液学杂志

OBJECTIVE@#To detect the differential expressions of miR-451, ABCB1 and ABCC2 in drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, and explore the regulatory relationship between miR-451 and the expressions of ABCB1 and ABCC2 , and the mechanism of miR-451 involved in drug resistance in leukemia.@*METHODS@#CCK-8 assay was used to detect the drug resistance of K562/A02 and K562 cells. Quantitative Real-time PCR (qRT-PCR) was used to verify the differential expressions of miR-451 in K562 and K562/A02 cells. MiR-451 mimic and negative control (miR-NC), miR-451 inhibitor and negative control (miR-inNC) were transfected into K562 and K562/A02 cells respectively, then qRT-PCR and Western blot were used to detect the expression levels of mRNA and protein of ABCB1 and ABCC2 in K562 and K562/A02 cells and the transfected groups.@*RESULTS@#The drug resistance of K562/A02 cells to adriamycin was 177 times higher than that of its parent cell line K562. Compared with K562 cells, the expression of miR-451 in K562/A02 cells was significantly higher (P <0.001), and the mRNA and protein expression levels of ABCB1 and ABCC2 in K562/A02 cells were significantly higher than those in K562 cells (P <0.001). After transfected with miR-451 inhibitor, the expression of miR-451 was significantly down-regulated in K562/A02 cells (P <0.001), the sensitivity to chemotherapy drugs was significantly enhanced (P <0.05), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly decreased (P <0.01). After transfected with miR-451 mimic, the expression of miR-451 was significantly upregulated in K562 cells (P <0.001), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly increased (P <0.01).@*CONCLUSION@#There are significant differences in the expressions of miR-451, ABCB1 and ABCC2 between the drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, which suggests that miR-451 may affect the drug resistance of leukemia cells by regulating the expression of ABCB1 and ABCC2.

Study of radiotherapy dose effect of neoadjuvant chemotherapy versus concurrent chemoradiotherapy in cervical cancer / 中华放射肿瘤学杂志

Objective:To compare the effect of neoadjuvant chemotherapy vs. concurrent chemoradiotherapy on the target volume and organs at risk for locally advanced bulky (>4 cm) cervical cancer. Methods:From March 1, 2019 to June 30, 2021, 146 patients pathologically diagnosed with cervical cancer were selected and randomly divided into two groups using random number table method: the neoadjuvant chemotherapy (NACT) + concurrent chemoradiotherapy (CCRT) group ( n=73) and CCRT group ( n=73). Patients in the NACT+CCRT group received 2 cycles of paclitaxel combined with cisplatin NACT, followed by CCRT, the chemotherapy regimen was the same as NACT. In the CCRT group, CCRT was given. Statistical description of categorical data was expressed by rate. The measurement data between two groups were compared by Wilcoxon rank-sum test for comparison of two independent samples, and the rate or composition ratio of two groups was compared by χ2 test. Results:Before radiotherapy, GTV in the NACT+CCRT group was (31.95±25.96) cm 3, significantly lower than (71.54±33.59) cm 3 in the CCRT group ( P<0.01). Besides, CTV and PTV in the NACT+CCRT group were also significantly lower compared with those in the CCRT group (both P<0.05). In terms of target volume dosimetry, D 100GTV, D 95CTV, V 100GTV, V 100CTV and V 95PTV in the NACT+CCRT group were significantly higher than those in the CCRT group (all P<0.05). The complete remision (CR) rates in the NACT+CCRT and CCRT groups were 86.3% and 67.6%, with statistical significance between two groups ( P<0.01) . Regarding organs at risk, NACT+CCRT group significantly reduced the dose to the bladder, rectum, small intestine and urethra compared with CCRT group (all P<0.05). Conclusions:NACT can reduce the volume of tumors in patients with large cervical masses, increase the radiation dose to tumors, reduce the dose to organs at risk, and make the three-dimensional brachytherapy easier. Therefore, NACT combined with CCRT may be a new choice for patients with locally advanced cervical cancer with large masses.

Predictive Value of CD44v6 and EGFR Expression in Neoadjuvant Chemotherapy Sensitivity of Stage Ⅱ-Ⅲ Cervical Cancer / 肿瘤防治研究

Objective To explore the predictive value of the expression of CD44v6 and EGFR on the efficacy of neoadjuvant chemotherapy (NACT) in stageⅡ-Ⅲ cervical cancer. Methods A total of 53 patients with stageⅡ-Ⅲ cervical cancer diagnosed by pathology were selected. All patients received two cycles of paclitaxel+platinum NACT. The pathological tissue samples of cervical tumors before NACT treatment were collected. The expression of CD44v6 and EGFR were detected by the immunohistochemical SP method, and we analyzed their predictive value of NACT in stageⅡ-Ⅲ cervical cancer. Results Among the 53 patients, 38 were in the NACT effective group (CR+PR), and 15 were in the NACT ineffective group (SD+PD). The expression of CD44v6 in the ineffective group was significantly higher than that in the effective group (P < 0.05). The expression of CD44v6 was significantly different in patients with CR, PR, and SD (P < 0.05). The AUC of CD44v6 to NACT effect on stage Ⅱ-Ⅲ cervical cancer was 0.74 (P < 0.05). The patients in the high expression group of CD44v6 had worse efficacy in NACT than those in the low expression group of CD44v6 (P < 0.05). Pearson test showed that CD44v6 and EGFR expression were correlated (R=0.34, P < 0.05). Conclusion High expression of CD44v6 may reduce the efficacy of NACT in stageⅡ-Ⅲ cervical cancer, suggesting that the expression of CD44v6 has a certain predictive value and clinical significance in the efficacy of paclitaxel+platinum NACT on cervical cancer. Moreover, CD44v6 is positively correlated with EGFR expression.

Effects of different bladder filling volumes on target area and organs at risk during three-dimensional brachytherapy of postoperative early cervical cancer / 中华放射医学与防护杂志

Objective:To investigate the optimal bladder filling volume in the 3D brachytherapy of postoperative cervical cancer.Methods:Totally 111 early cervical cancer patients with positive incisal margins or insufficient safety boundaries were included. The normal saline 50, 60, 70, 80, 90, and 100 ml were filled into their bladders, and accordingly six groups were determined, and 66, 69, 66, 69, 72, 56 person-times in each group, respectively. The CT-based simulation positioning was performed. According to the ICRU 89 report, high-risk clinical target volume and organs at risk such as bladder and rectum were delineated. The Oncentra planning system was used to prepare the treatment program. The high-risk clinical target volume (HR-CTV), D90, and the D2 cm 3 and D1 cm 3 of organs at risk under different volumes were recorded. Results:Compared to the 60 ml group, the volume and dosage of HR-CTV in the groups of 50, 70, 80, 90, and 100 ml had no significant difference ( P>0.05). The D2 cm 3 and D1 cm 3 of the bladder and rectum of patients in these groups significantly decreased, and the difference was statistically significant ( tbladder = 3.21, 5.83, 2.89, 12.95, 7.96, Pbladder = 0.031, 0.010, 0.041, 0.000, 0.001; trectum = 2.94, 4.66, 2.53, 5.89, 4.13, Prectum = 0.037, 0.024, 0.049, 0.005, 0.028). The pairwise comparison among these groups except for the 60 ml group showed that the volume and dosage of HR-CTV and the D2 cm 3 and D1 cm 3 of bladder and rectum had no significant difference ( P > 0.05). Moreover, the D2 cm 3 and D1 cm 3 of sigmoid colon and small intestine of these groups had no significant difference ( P > 0.05). Conclusions:In the 3D brachytherapy of postoperative early cervical cancer, a bladder filling volume of 60 ml can ensure the volume and dose of HR-CTV and can protect the bladder and rectum compared with other filling volumes.

Effect of 5-aminoimidazole-4-formamide Ribonucleotide Combined with Interferon on Chronic Myeloid Leukemia K562 Cells / 中国实验血液学杂志

OBJECTIVE@#To study the effect of 5-aminoimidazole-4-formamide ribonucleotide (AICAR) combined with interferon (IFN-α-2b) on the proliferation and apoptosis of chronic myeloid leukemia K562 cells, and explore its possible mechanism.@*METHODS@#CCK-8 method was used to detect the inhibition of cell proliferation. Wright Giemsa method was used to stain and cell morphology was observed by light microscopy. FITC Annexin V/PI double staining method was used to analyze the change of apoptosis rate. Immunocytochemistry method was used to detect the expression of wild-type P53 protein.@*RESULTS@#Different concentration of AICAR was inhibitory effect on K562 cells at different time point of action for 24 h, 48 h, and 72 h, and the inhibition was time and dose-dependent (r=0.71, r=0.84). The combination of AICAR and IFN-α-2b could effectively inhibit the proliferation and promote apoptosis of K562 cells. The inhibition rate of K562 cells was (45.26±2.54)%, and the early apoptosis rate was (33.72±0.23)%, which was statistically significantly different from the control group, AICAR or IFN-ɑ-2b alone (P<0.05). The combination of two drugs promoted the expression of wild-type p53 protein.@*CONCLUSION@#AICAR and/or IFN-ɑ-2b can inhibit the cell proliferation and promote the apoptosis of K562 cells. The combination of two drugs shows synergistic antitumor effect, and its mechanism may be related to the promotion of high expression of wild-type p53 protein.

Effect of obesity on pulmonary function in asthmatic children of different age groups / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effect of obesity on pulmonary function in newly diagnosed asthmatic children of different age groups.</p><p><b>METHODS</b>Two hundred and ninety-four children with newly diagnosed asthma were classified into preschool-age (<6 years) and school-age (6 to 12.5 years) groups. They were then classified into obese, overweight, and normal-weight subgroups based on their body mass index (BMI). All the children underwent pulmonary function tests, including large airway function tests [forced vital capacity (FVC%) and forced expiratory volume in one second (FEV1%)] and small airway function tests [maximal expiratory flow at 25% of vital capacity (MEF25%), maximal expiratory flow at 50% of vital capacity (MEF50%), and maximal expiratory flow at 75% of vital capacity (MEF75%)].</p><p><b>RESULTS</b>The school-age group showed lower FEV1%, MEF25%, and MEF50% than the preschool-age group (P<0.05) after adjustment for sex and BMI. The normal-weight children in the school-age group had lower FEV1%, MEF25%, and MEF50% compared with their counterparts in the preschool-age group (P<0.05). The overweight children in the school-age group showed lower FVC% and MEF50% than those in the preschool-age group. However, all the pulmonary function parameters showed no significant differences between the obese children in the preschool-age and school-age groups. In the preschool-age group, FVC%, FEV1%, and MEF75% of the obese children were lower than those of the normal-weight children. In the school-age group, only FVC% and FEV1% showed differences between the obese and normal-weight children (P<0.05).</p><p><b>CONCLUSIONS</b>The effect of obesity on the pulmonary function varies with age in children with asthma, and the effect is more obvious in those of preschool age.</p>

Efficacy of extended-field intensity-modulated radiotherapy for early-stage NK/T cell lymphoma / 中华放射肿瘤学杂志

Objective To evaluate the efficacy of extended-field intensity-modulated radiotherapy (IMRT) in the treatment of patients with early-stage NK/T cell lymphoma (NKTCL),and to examine the clinical characteristics and the effect of treatment factors on the prognosis of these patients.Methods The clinical data of 165 patients with early-stage NKTCL who underwent extended-field IMRT with (n=158,95.8%) or without chemotherapy (n=7,4.2%) were reviewed.Of these 165 patients,140(84.8%) received a radiation dose of ≥50 Gy to the primary lesion,and 25 patients (15.2%) received a radiation dose of<50 Gy.Most patients (n=147,89.1%) were treated with L-asparaginase-based chemotherapy regimens,whereas only 11 patients (6.7%) were treated with doxorubicin-based CHOP/CHOP-like regimens.In addition,109 patients (66.1%) received ≥4 cycles of chemotherapy.Locoregional control (LRC),overall survival (OS),and progression-free survival (PFS) rates were calculated using the Kaplan-Meier method,and the log-rank test was used for survival comparison and univariate prognostic analysis.A multivariate prognostic analysis was performed using the Cox model.Results The 5-year sample size 55.The 5-year OS,PFS,and LRC rates of all patients were 74.2%,72.5%,84.4%,respectively.The patients who received a dose of ≥50 Gy had a significantly higher 5-year LRC rate than those with<50 Gy (91.8% vs.39.7%,P=0.000).The 5-year OS was significantly higher in the low-risk early-stage group than in the high-risk early-stage group (P=0.002).For the high-risk early-stage NKTCL group,patients who received ≥4 cycles of chemotherapy had significantly higher 5-year OS and PFS than those who received<4 cycles of chemotherapy (5-year OS:71.3% vs.59.5%,P=0.032;5-year PFS:70.4% vs.54.4%,P=0.009).In addition,multivariate analysis showed that ECOG≥2,primary tumor invasion (PTI),and Ann Arbor stage Ⅱ were associated with poor OS (P=0.006,0.002,0.014),and ECOG≥2 and PTI were associated with reduced LRC (P=0.004,0.016).Furthermore,ECOG≥2,PTI,Ann Arbor stage Ⅱ,and extranasal primary site were associated with lower PFS (P=0.045,0.003,0.030,0.032).Conclusions Extended-field IMRT at a dose of ≥50 Gy can lead to favorable LRC,OS,and PFS in patients with early-stage NKTCL.However,it is less effective against distant early-stage NKTCL in patients with poor prognosis.Nevertheless,≥4 cycles of chemotherapy can significantly improve the OS and PFS of patients with early-stage NKTCL.

An analysis of skin prick test reactivity to dust mite in overweight and normal weight children with allergic asthma before and after specific immunotherapy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the skin prick test (SPT) reactivity to house dust mite allergens in overweight and normal weight children with allergic asthma before and after standard subcutaneous specific immunotherapy.</p><p><b>METHODS</b>Two hundred and fifteen children with allergic asthma who had positive SPT responses to Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF) were enrolled. According to the weight index, they were classified into overweight (n=63) and normal weight groups (n=152). Skin indices (SI) to DP and DF were compared between the two groups at 6 months and 1 year after standard subcutaneous specific immunotherapy.</p><p><b>RESULTS</b>The overweight group had a significantly larger histamine wheal diameter than the normal weight group after controlling the variation in testing time (P<0.05). After controlling the variation in weights, there were significant differences in the SIs to DP and DF before specific immunotherapy and at 6 months and 1 year after specific immunotherapy. At 6 months and 1 year after specific immunotherapy, the SIs to DP and DF were significantly reduced in both groups (P<0.05), and the overweight group had greater decreases in the SIs to DP and DF than the normal weight group.</p><p><b>CONCLUSIONS</b>The overweight children with allergic asthma have stronger responses to histamine than the normal weight patients. Specific immunotherapy can reduce the reactivity to dust mite allergens in children with allergic asthma. Within one year after specific immunotherapy, the overweight children with allergic asthma have a significantly greater decrease in the reactivity to dust mite allergens than the normal weight patients.</p>

Effects of R219K polymorphism of ATP-binding cassette transporter 1 gene on serum lipids ratios induced by a high-carbohydrate and low-fat diet in healthy youth

BACKGROUND: Diets are the important players in regulating plasma lipid profiles. And the R219K polymorphism at the gene of ATP-binding cassette transporter 1(ABCA1) was reported to be associated with the profiles. However, no efforts have been made to investigate the changes of lipid profiles after a high-carbohydrate and low-fat diet in different subjects with different genotypes of this polymorphism. This study was to evaluate the effects of ABCA1 R219K polymorphism on serum lipid and apolipoprotein (apo) ratios induced by a high-carbohydrate/low-fat (high-CHO) diet. After a washout diet of 54.1% carbohydrate for 7 days, 56 healthy young subjects (22.89 ± 1.80 years old) were given a high-CHO diet of 70.1% carbohydrate for 6 days. Height, weight, waist circumference, hip circumference, glucose (Glu), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoA-1 and apoB-100 were measured on the 1st, 8th and 14th days of this study. Body mass index (BMI), waist-to-hip ratios (WHR), log(TG/HDL-C), TC/HDL-C, LDL-C/HDL-C and apoA-1/apoB-100 were calculated. ABCA1 R219K was analyzed by a PCR-RFLP method. RESULTS: The results indicate that the male subjects of all the genotypes had higher WHR than their female counterparts on the 1st, 8th and 14th days of this study. The male K carriers had higher log(TG/HDL-C) and TC/HDL-C than the female carriers on the 1st and 14th days, and higher LDL-C/HDL-C on the 14th day. When compared with that on the 8th day, TC/HDL-C was decreased regardless of the genotypes and genders on the 14th day. Log(TG/HDL-C) was increased in the males with the RR genotype and the female K carriers. Lowered BMI, Glu and LDL-C/HDL-C were found in the male K carriers, but only lowered BMI in the female K carriers and only lowered LDL-C/HDL-C in the females with the RR genotype. CONCLUSIONS: These results suggest that ABCA1 R219K polymorphism is associated differently in males and females with elevated log(TG/HDL-C) and decreased LDL-C/HDL-C induced by the high-CHO diet.

Rac1 expression and its effects on the cell cycle progression and apoptosis in human acute leukemic cell line HL-60 / 中国实验血液学杂志

The study was aimed to investigate the expression of Rac1 in human acute leukemic cell line HL-60 and effect of Rac1 on cell cycle progression and apoptosis. The mRNA expression of Rac1 in HL-60 cell line and normal human peripheral blood mononuclear cells (PBMNC) were examined by semi-quantitative RT-PCR. After transfection of HL-60 cells with different concentrations of Rac1 antisense oligodeoxynucleotide (ASODN) by means of FuGENE6, the survival, cell cycle, apoptosis of HL-60 cells were observed through MTT assay, FCM test, Wright-Giemsa, acridine orange/ethidium bromide (AO/EB) and Annexin V-FITC/PI staining test respectively. The results showed that Rac1 relative amount in HL-60 was 0.84 +/- 0.13, while it in the normal PBMNC was 0.26 +/- 0.1 (P < 0.01); the expression of Rac1 in HL-60 cells was significantly upregulated. Compared with sense oligodeoxynucleotide (SODN), HL-60 cell viability, after exposure to ASODN at a concentration of 2.0 g/L decreased, (73.7 +/- 5.0)% vs (93.2 +/- 3.0)% (P < 0.01), while the proportion of G(1) cells increased as (52.1 +/- 6.8)% vs (31.6 +/- 4.7)% (P < 0.05), the percentage of Annexin V positive cells increased, (19.2 +/- 2.1)% vs (4.1 +/- 1.7)% (P < 0.01), and HL-60 cells were observed to have formation of apoptotic bodies. The data presented indicate that Rac1 may be involved in regulation of HL-60 cell cycle and apoptosis, promote overproliferation of HL-60 cells and inhibit their apoptosis.

Relationship between mucosal surface patterns under enhanced magnification endoscopy and pathological epithelial types of Barrett esophagus / 中华消化内镜杂志

Objective To evaluate the enhanced magnification endoscopy in the diagnosis of Barrett esophagus,and to explore the relationship between mucosal surface patterns and pathological epithelial types of Barrett esophagus.Methods Enhanced magnification endoscopy was performed 'after spraying 2%-3% acetic acid on the surface of distal esophagus in 40 Barrett esophagus patients.Mucosal specimen were biop- syed.Results According to the mucosal types of Toyoda in 2003,there were three mucosal types:Ⅰ dot pat- tern 7(17.5%),5 of 7(71.4%)fundie type,Ⅱ reticular pattern 24(60.0%),16 of 24(66.7%)fundic type,Ⅲ cerebroid/villous 9(22.5%),intestinal metaplasia or dysplasia.Conclusion Enhanced magnifi- cation endoscopy helps to identify areas with intestinal metaplasia and dysplasia,and is useful in the diagno- sis of Barrett esophagus.