Objective To explore the correlation of serum Chemerin level with disease activity and the ratio of T helper 17/regulatory T cells(Th17/Treg)in patients with rheumatoid arthritis(RA).Methods A total of 180 patients with RA who were admitted to our hospital were regarded as the observation group.According to the DAS28 score,the observation group was divided into the high activity group(60 cases),the moderate activity group(60 cases)and the low activity group(60 cases).Another 180 healthy people who underwent physical examination in our hospital during the same period were regarded as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of Chemerin,interleukin-9(IL-9),interleukin-10(IL-10)and interleukin-17(IL-17).Flow cytometry was used to detect the Th17/Treg ratio.Spearman correlation analysis was applied to analyze the correlation between serum Chemerin level and DAS28 score.Pearson correlation analysis was used to analyze the correlation between serum Chemerin level and Th17,Treg cell percentage and Th17/Treg ratio.Results The results of this study showed that the serum level of Chemerin was higher in the observation group than that in the control group(P＜0.05).The serum Chemerin level was positively correlated with DAS28 score(P＜0.05).Serum Chemerin levels and DAS28 scores decreased in turn in the high,moderate and low activity groups(P＜0.05).The percentage of Th17 cells and the ratio of Th17/Treg were higher in the observation group than those in the control group,and the percentage of Treg cells was lower in the observation group than that in the control group(P＜0.05).The level of IL-10 was lower in the observation group than that in the control group,while levels of IL-17 and IL-9 were higher in the observation group than those in the control group(P＜0.05).The results of Pearson correlation analysis showed that serum Chemerin level was positively correlated with the percentage of Th17 cells and the ratio of Th17/Treg,and negatively correlated with the percentage of Treg cells(P＜0.05).Conclusion Serum Chemerin level is elevated in patients with RA,which is closely related to disease activity and Th17/Treg ratio.

Objective:To explore the rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by bedside diagnostic bronchoscopy, so as to start effective anti-infection treatment before the results of macrogenome next generation sequencing (mNGS) test. Methods:The clinical data of three patients with severe Chlamydophila psittaci pneumonia who were successfully treated in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Aksu District, and the First Division Hospital of Xinjiang Production and Construction Corps from October 2020 to June 2021 were retrospectively analyzed, including the rapid assessment of early pathogens by bedside diagnostic bronchoscopy and the use of antibiotics to start anti-infection treatment. These patients were successfully treated. Results:The three patients were male, aged 63, 45 and 58 years old, respectively. Before the onset of the penumonia, they had a clear medical history of bird exposure. The clinical manifestations mainly included fever, dry cough, shortness of breath and dyspnea. One case had abdominal pain and lethargy. The results of laboratory examination indicated that the peripheral blood white blood cell count (WBC) of two patients were high [(10.2-11.9)×10 9/L], the percentage of neutrophils increased (85.2%-94.6%) and the percentage of lymphocytes decreased (3.2%-7.7%) in all 3 patients after admission to hospital and entering into intensive care unit (ICU). The procalcitonin (PCT) of 3 patients increased after admission, and still increased when entering ICU (0.3-4.8 ng/L), so did C-reactive protein (CRP, 58.0-162.0 mg/L) and erythrocyte sedimentation rate (ESR, 36.0-90.0 mm/1 h). After admission, serum alanine transaminase (ALT) increased in 2 cases (136.7 U/L, 220.5 U/L), so did aspartate transaminase (AST) in 2 cases (249.6 U/L, 164.2 U/L). ALT (162.2-267.9 U/L) and AST (189.8-223.2 U/L) increased in 3 patients when they entered ICU. The level of serum creatinine (SCr) of 3 patients were normal after admission and entering ICU. The chest computed tomography (CT) findings of 3 patients were acute interstitial pneumonia, bronchopneumonia and lung consolidation, of which 2 cases were accompanied by a small amount of pleural effusion, and 1 case was accompanied by more regular small air sacs. Multiple lung lobes were involved, but mainly one lung lobe. The oxygenation index (PaO 2/FiO 2) of the 3 patients admitting to ICU were 100.0, 57.5 and 105.4 mmHg (1 mmHg ≈ 0.133 kPa), respectively, which met with the diagnostic criteria of moderate and severe acute respiratory distress syndrome (ARDS). All three patients received endotracheal intubation and mechanical ventilation. Under the bedside bronchoscope, the bronchial mucosa of 3 patients were obviously congested and edematous, without purulent secretion, and there was 1 case with mucosal hemorrhage. Three patients underwent bedside diagnostic bronchoscopy, and the evaluation result of the pathogen was that it might be atypical pathogen infection, so they were given moxifloxacin, cisromet and doxycycline intravenously, respectively, and combined with carbapenem antibiotics intravenously. After 3 days, the detection results of mNGS in bronchoalveolar lavage fluid (BALF) showed that only Chlamydia psittaci was infected. At this time, the condition was significantly improved, and PaO 2/FiO 2 was significantly increased. Therefore, the antibiotic treatment scheme remained unchanged, and mNGS only served to verify the initial diagnosis. Two patients were extubated on the 7th and 12th day of admission to the ICU, respectively, while one patient was extubated on the 16th day of admission to the ICU due to nosocomial infection. All 3 patients were transferred to the respiratory ward after the condition was stable. Conclusion:The bedside diagnostic bronchoscopy based on clinical characteristics is conducive to not only the rapid assessment of the early pathogens of severe Chlamydia psittaci pneumonia, but also effective anti-infection treatment before the returning of mNGS test results, which can make up for the lag and uncertainty of the mNGS test results.

Objective:To observe the effect of Ba Duan Jin(Eight-brocade Exercise)plus Tuina(Chinese therapeutic massage)in treating primary dysmenorrhea due to cold-induced blood stasis in female college students and on the score of fatigue scale-14(FS-14). Methods:Seventy-two female college students with primary dysmenorrhea due to cold-induced blood stasis were randomized into a Tuina group and a joint group,with 36 cases in each group.The Tuina group only received Tuina manipulations.In the joint group,besides the same Tuina manipulations,patients practiced Ba Duan Jin.For both groups,the once-daily intervention was conducted from 6 d before the menstrual period until menstrual day 1 for 3 menstrual cycles.Changes in the scores of COX menstrual symptom scale(CMSS),visual analog scale(VAS),and FS-14 after the intervention were observed.Clinical efficacy was also estimated. Results:During the process,1 case dropped out in the Tuina group,and 35 cases completed the intervention;2 cases dropped out in the joint group,and 34 cases completed the intervention.The total effective rate was 94.1%in the joint group,higher than 88.6%in the Tuina group(P<0.05).After treatment,the symptom duration and intensity scores in the scores of CMSS,VAS,and FS-14 declined in both groups(P<0.05 or P<0.01);the CMSS symptom duration score and FS-14 score were lower in the joint group than in the Tuina group(P<0.05). Conclusion:Tuina manipulations alone or combined with Ba Duan Jin practice can effectively treat primary dysmenorrhea due to cold-induced blood stasis in female college students;when combined with Ba Duan Jin practice,Tuina manipulations can more significantly improve pain duration and fatigue,suggesting the advantages of combining Tuina Gongfa and manipulations.

Objective: To investigate the effects of interleukin ( IL) -10 on the proliferation of HaCaT cells and CaCl2 induced expression of differentiation markers and its possible molecular mechanisms． Methods: HaCaT cells were treated with various concentrations of IL-10 (0，3，10，30 ng / ml) for different time (0，24，48，72 h) ，cell proliferation was measured using MTS，and cell cycle was determined by flow cytometry．HaCaT cells were pretreated with IL-10 (final concentration 10 ng / ml) for 1 h，then incubated with or without CaCl2 (final concentration 1. 2 mmol / L) for 24，48，72 h ，Western blot was performed to detect the effect of IL-10 on the expression of HaCaT keratinocyte differentiation markers．After pretreatment of HaCaT cells with PD98059，an inhibitor of mitogen-activated kinase-ERK1 /2，and LY294002，an inhibitor of phosphatidylinositol kinase-serine / threonine kinase (PI3K-AKT) ，the total RNA and proteins were extracted separately，real time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to examine the influence of IL-10 on the expression of differentiation markers (Keratin1，Keratin5，Involucrin) . Results : MTS results revealed that IL-10 (30 ng / ml and lower doses) did not alter the proliferation of HaCaT cells in 72 h．Flow cytometry analysis demonstrated that IL-10 had no significant influence on cell cycle progression．The results of Western blot showed that IL-10 upregulated the expression of differentiation markers Involucrin，while there was no significant effect on Keratin1 and Keratin5 ．Mechanism research analysis demonstrated that IL-10 could activate ERK1 /2 and AKT ，increase their phosphorylation levels ; RT-qPCR and Western blot results showed that PD98059 and LY294002 partially blocked IL-10 induced Involucrin expression． Conclusion At a particular concentration range，IL-10 has little effect on HaCaT proliferation ，but it partially upregulates the expression of differentiation marker Involucrin via the MAPKs-ERK1 /2 and PI3K-AKT pathways.

Objective : To investigate the effects of RO or incubation with cholesterol ( CH) on the differentiation and apoptosis of KCs. Methods : Ca2 + ( 1. 8 mmol/L) was added to KCs for 1 day after co - culture of RO alone or combined with CH in KCs for different time. The expression of Involucrin (INV) and Loricrin in KCs was analyzed by Western blot. After co⁃culture of RO alone or combination with CH in KCs for different time , the apoptotic changes of KCs cells were detected by flow cytometry and the expression of apoptotic proteins Bax and Bcl⁃2 were verified by Western blot. Results : RO down⁃regulated the expression of Ca2 + induced differentiation marker protein INV , but weakly inhibited the expression of Loricrin , while CH showed no antagonistic effect on RO. RO induced apoptosis of KCs cells in a time dependent manner. CH could antagonize the apoptotic effect of RO on KCs ; the expression of Bcl⁃2 and Bax was inhibited when RO was applied alone , CH could partially antagonize the inhibition effect of RO on Bcl⁃2 expression , but had no significant effect on Bax; however, RO reduced the ratio of Bcl⁃2/Bax in a time⁃dependent manner, and CH partially weakened the effect of RO on the ratio of Bcl⁃2/Bax. Conclusion RO may inhibit KCs differentiation and induce KCs cell apoptosis by down⁃regulating the expression of Loricrin and Bcl⁃2.

Objective : To investigate the molecular changes of lanosterol synthase(LSS) gene dysfunction and cholesterol levels that may affect brain function. Methods: The differentially expressed genes in LSS knockout(+/-) mice and WT C57 BL/6 mice were analyzed by RNA-SEQ,and the signal pathways involved in the differentially expressed genes were analyzed by KEGG enrichment. The differential genes were detected by real-time quantitative PCR and the protein expression of differential genes was detected by Western blot. Results: By RNA-SEQ analysis, LSS(+/-) heterozygous knockout resulted in the difference of 320 genes in the mouse brain, including 145 up-regulated genes and 175 down-regulated genes.KEGG enrichment analysis showed that these differentially expressed genes involved in neural-activated receptor and ligand pathways, hippocampal signaling pathways and glutamate synaptic pathways.Real-time quantitative PCR showed that CCKBR and Htr5 b were up-regulated, respectively. Western blot results showed that CCKBR gene was highly expressed in the total protein of all brain tissues of LSS knockout(+/-) mice. Conclusion LSS heterozygotic knockout may affect brain function and animal behavior.

Objective: To screen the differential genes and pathways of female and male C57 BL/6 J mice by transcriptome sequencing, and to lay a foundation for further exploring the molecular mechanism of behavioral differences between male and female mice. Methods: 8-week-old female and male mice of the C57 BL/6 J strain were completely isolated from the mouse hippocampus, and total RNA was extracted and reverse transcribed to construct a cDNA library, and 50 single-ended mice were generated on the BGIseq500 platform(BGl-Shenzhen, China) The base reads were transcriptome sequenced. After sequencing, based on GO and KEGG databases, combined with the phyper function in R language to screen, correct and enrich the data, calculatePvalue, and then perform FDR correction onPvalue to obtainQvalue and analyze different annotated genes based on the hypergeometric test method. The expression status was analyzed, and the differential genes and pathways in the hippocampus of mice of different genders were screened out. Results: Through the comparison of male and female differences, 325 differential genes were screened, including 233 up-regulated genes and 92 down-regulated genes. The functions of these differential genes were mainly enriched in long-term potentiation(LTP), calcium signal pathway, nicotine addiction and other processes. There were 362 junctions and 1 703 interaction edges in the female-male differential gene interaction network, and 10 core genes selected: lysine demethylase 5 D(Kdm5 d), cyclin-dependent kinase 5(Cdkl5), Cell output mediator(Cle1), dopamine receptor 6 a3(Slc6 a3), cassette transcription factor(Fox), precursor mRNA processing factor 4 B(Prpf4 b), glycine receptor 4(Glur4), calcium ion receptor 2(Camk2), DNA and RNA binding protein family(Son), serotonin receptor 5 b(Htr5 b). Conclusion The selected differential genes and signal pathways may lay the foundation for explaining the molecular mechanism of the differences in behavior between male and female mice.

Objective:To explore the clinical application of free chimeric medial femoral condyle osteofascial free flap (CMFCOF) in the treatment of traumatic composite bone and soft tissue defect of hand and foot.Methods:Between January, 2015 and March, 2020, 8 patients with traumatic composite bone and soft tissue defect in hand and foot were treated with CMFCOF. Of the 8 patients, there were 6 males and 2 females, with an average age of 41 (range, 24 to 56) years. The causes of injury included 3 of traffic accident, 3 of machine crush and 2 of crush. Two cases had proximal phalanx defect, 3 with metacarpal bone and 3 with metatarsal bone. The time between injury to the flap repair were 2 to 120 (mean, 84) days. The size of bone defect ranged from 2.0 cm×1.2 cm×1.2 cm to 4.4 cm× 3.0 cm×2.3 cm. The soft tissue defect ranged from 2.0 cm×1.4 cm to 5.6 cm×4.5 cm. All bone defects were on the diaphysis, without involvement of joints. Two cases had tendon defect. According to the defect of bone and soft tissue, the CMFCOF was prepared and skin graft was performed on the surface of its fascial flap.Results:The average time of flap harvesting was 53(52-96) minutes. All donor sites were directly closed. All flaps and skin grafts achieved stage I survival. All patients entered 9-16 months of follow-up, with an average of 14.5 months. The average healing time of bone was 7.5 (range, 6-10) weeks. At the last follow-up review, all flaps were not thinned. The function of donor site was restored well, without weight bearing disorder and paraesthesia in the anterior patella area. According to the trial standard of Digit Function Evaluation of the Hand Surgery Society of Chinese Medical Association, 3 patients were rated as excellent, 1 was good and 1 was fair. According to the Maryland foot evaluation criteria, 3 patients were rated as excellent for recovered with normal weight-bearing walking.Conclusion:CMFCOF can achieve satisfactory results in repairing composite bone and soft tissue defect of hand or foot. The flap has the advantages in simple operation, high quality of bone and concealed donor site.

Objective:To investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and sequential microwave ablation (MWA) versus TACE combined with sorafenib in the treatment of hepatocellular carcinoma (HCC) with tumor diameter over 5 cm, and to analyze risk factors affecting the prognosis of patients.Methods:The prospective cohort study was conducted. The clinicopathological data of 61 HCC patients with tumor diameter over 5 cm who were admitted to two medical centers (30 in the Laiyang Central Hospital of Yantai City Affiliated to Weifang Medical College and 31 in the Qingdao Central Hospital Affiliated to Qingdao University) between July 2012 and November 2013 were collected. Patients who were treated with TACE combined with sorafenib and sequential MWA were allocated into observation group, and patients who were treated with TACE combined with sorafenib were allocated into control group. Observation indicators: (1) treatment, complications and adverse drug reactions; (2) short-term efficacies; (3) follow-up and survival situations; (4) analysis of prognostic factors. Follow-up was performed by inpatient, outpatient examinations or telephone interview once a month within the first 6 months after treatment and once every 3 months thereafter up to November 2018. The follow-up included laboratory indicators, tumor markers, abdominal enhanced computed tomography or magnetic resonance imaging examinations. The survival of patients and disease progression were fully documented. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was performed by the t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was performed using the Wilcoxon rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or pearson-corrected chi-square test. Ranked data were analyzed using the Wilcoxon rank sum test. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Comparison of survival rates between time points was performed using the Bonferroni method to adjust the test level. Univariate and multivariate analyses were performed using the multiple COX proportional hazard model. Results:A total of 61 HCC patients were selected for eligibility, including 36 males and 25 females, aged (58±8)years, with a range from 43 to 73 years. Of the 61 patients, 31 were in the observation group and 30 in the control group. (1) Treatment, complications and adverse drug reactions: ① treatment information. The treatment times of TACE, treatment times of MWA, time from the first TACE to the first sorafenib medication, and duration of sorafenib medication in the observation group were 1 time (range, 1-5 times), 2 times (range, 1-4 times), 5 days (range, 5-9 days), 24 months (range, 6-72 months), respectively. The above indicators of patients in the control group were 3 times (range, 1-5 times), 0, 6 days (range, 5-9 days), and 16 months (range, 6-60 months). There were significant differences in the treatment times of TACE, treatment times of MWA, and duration of sorafenib medication between the two groups ( Z=4.701, -7.213, -2.614, P<0.05). There was no significant difference in the time from the first TACE to the first sorafenib medication between the two groups ( Z=0.573, P>0.05). ② Complications: there was no TACE related complications in the two groups. There were 3 patients with MWA related complications in the observation group, including 2 cases of minor hemorrhage under the liver capsule and 1 case of pleural effusion, and they were relieved after conservative treatment. ③ Adverse reactions to sorafenib: after 2 months of sorafenib medication, patients in the observation group and control group had at least one kind of sorafenib related stage Ⅰ-Ⅲ adverse reaction, without stage Ⅳ adverse reaction. The numbers of cases with hand-foot skin reaction, rash, pruritus, loss of skin pigmentation, diarrhea, decreased appetite, nausea and vomiting, pain in the liver area, fever, fatigue, liver dysfunction, bone marrow suppression were 8, 3, 4, 3, 10, 18, 20, 20, 20, 15, 3, 2 in the observation group, and 9, 3, 3, 2, 13, 19, 23, 12, 21, 12, 6, 2 in the control group, respectively, showing no significant difference in the above indices between the two groups ( χ2=0.133, 0.000, 0.000, 0.000, 0.796, 0.177, 1.082, 3.674, 0.208, 0.435, 0.601, 0.000, P>0.05). Patients with adverse reactions to sorafenib were relieved by symptomatic treatment, reducing the dose of sorafenib or intermittent drug withdrawal. (2) Short-term efficacies: the level of alpha fetoprotein was 16 μg/L (range, 3-538 μg/L) in the observation group and 292 μg/L (range, 9-642 μg/L) in the control group after one month of treatment, showing a significant difference between the two groups ( Z=3.744, P<0.05). After 3 months of treatment, cases with tumor complete remission, cases with tumor partial remission, cases with stable disease, cases with progressive disease, objective response rate, and disease control rate in the observation group were 14, 11, 6, 0, 80.6%(25/31) , 100.0%(31/31), respectively. The above indicators in the control group were 2, 13, 12, 3, 50.0%(15/30), 90.0%(27/30). There was a significant difference in the objective response rate between the two groups ( χ2=6.343, P<0.05), but no significant difference in the disease control rate between the two groups ( χ2= 1.473, P>0.05). (3) Follow-up and survival situations: 61 HCC patients were followed up for 9.0-75.0 months, with a median follow-up time of 22.0 months. During the follow-up, 28 patients in the observation group had progressive disease, including 8 cases of local tumor progression, 4 of portal vein tumor thrombi, 11 of intrahepatic metastasis, and 5 of pulmonary metastasis. Thirty patients in the control group had progressive disease, including 13 cases of local tumor progression, 6 of portal vein tumor thrombi, 6 of intrahepatic metastasis, and 5 of pulmonary metastasis. Among the 61 patients, 28 patients in the observation group and 29 patients in the control group died. The median overall survival time and median progression-free survival time of the observation group was 28.0 months and 18.0 months, versus 19.5 months and 11.5 months of the control group, showing significant differences between the two groups ( χ2=8.021, 10.506, P<0.05). The 1-, 3-, 5-year overall survival rates of the observation group were 97%, 37% and 20%, respectively, versus 83%, 13% and 7% of the control group, showing significant differences in the above indicators between the two groups ( Z=23.635, 4.623, 3.139, P<0.0167). The 1-, 2-, 3-year progression-free survival rates of the observation group were 77%, 40%, and 27%, respectively, versus 43%, 13%, and 7% of the control group, showing significant differences in the above indicators between the two groups ( Z=9.965, 4.900, 3.684, P<0.0167). (4) Analysis of prognostic factors: results of univariate analysis showed that treatment method, maximum tumor diameter, Barcelona clinical liver cancer (BCLC) stage, liver cirrhosis, hepatitis B virus(HBV) infection, and Child-Pugh classification were related factors for overall survival time [ hazard ratio ( HR)=0.483, 6.196, 12.646, 5.049, 2.950, 4.791, 95% confidence interval ( CI): 0.284-0.823, 3.198-12.003, 5.031-31.785, 2.586-9.858, 1.366-6.369, 2.507-9.155, P<0.05] and progression-free survival time ( HR=0.427, 5.804, 7.032, 5.405, 2.925, 4.410, 95% CI: 0.248-0.735, 3.043-11.070, 3.071-16.101, 2.685-10.881, 1.364-6.270, 2.331-8.342, P<0.05). Results of multivariate analysis showed that treatment method, maximum tumor diameter, BCLC stage, liver cirrhosis, and HBV infection were independent influencing factors for overall survival time ( HR=0.183, 5.886, 17.544, 4.702, 3.801, 95% CI: 0.090-0.370, 2.648-13.083, 5.740-53.622, 1.928-11.470, 1.368-10.562, P<0.05) and progression-free survival time ( HR=0.201, 3.850, 3.843, 3.598, 3.726, 95% CI: 0.098-0.411, 1.761-8.414, 1.526-9.682, 1.444-8.963, 1.396-9.947, P<0.05). Conclusions:Compared with TACE combined with sorafenib, TACE combined with sorafenib and sequential MWA is safe and effective in the treatment of HCC with tumor diameter over 5 cm. The treatment method, maximum tumor diameter, BCLC stage, liver cirrhosis, and HBV infection are independent influencing factors for overall survival time and progression-free survival time of patients.

Objective:To explore the effects of BCR-ABL downstream pathway inhibitors, such as RAF inhibitor SB590885, JAK inhibitor AZD1480, PI3K-mTOR double target inhibitor BEZ235 on chronic myelogenous leukemia (CML) cells, and the effect of BEZ235 on the proliferation, apoptosis of CML cells and the sensitivity of imatinib in vitro.Methods:K562 cells were treated with different concentrations of the drugs. MTS method was applied to detect the proliferation inhibition rate of K562 cells, and 50% inhibitory concentration (IC 50) of all drugs for 48 h was calculated. The cell apoptosis rate was tested by using flow cytometry with Annexin V-FITC/PI double staining. The cell cycle was tested by using flow cytometry with PI staining. K562 cells, imatinib-resistant and T315I-mutant human CML KBM7R cells and imatinib-resistant CML primary cells of patients were treated with different concentrations of the drugs. MTS method was used to test the proliferation inhibition of cells, and IC 50 of all drugs for 48 h was evaluated. KBM7R cells or primary cells of CML patients were treated with 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib or the combination of both, respectively. Flow cytometry with PI staining was used to detect the cell cycle of KBM7R cells. Flow cytometry with Annexin V-FITC/PI double staining was used to detect the cell apoptosis rate in CML primary cells. The expressions of p-AKT, cleaved Caspase-3 and Cyclin D1 proteins were detected by using Western blot. Results:SB590885, AZD1480 and BEZ235 could inhibit the proliferation of K562 cells, and the IC 50 after the treatment of K562 cells for 48 h was (11.49±3.14), (4.83±1.26) and (0.37±0.21) μmol/L, respectively. SB590885, AZD1480 and BEZ235 could promote the apoptosis of K562 cells. The cell apoptosis rates were increased compared with the control group without drug treatment (all P < 0.01). SB590885 and BEZ235 induced G 0/G 1 block (both P < 0.05). AZD1480 induced G 2/M block ( P < 0.05). BEZ235 could inhibit the proliferation of K562 cells, KBM7R cells and CML primary cells, and their IC 50 for 48 h was (0.37±0.21), (0.43±0.27) and (0.49±0.24) μmol/L, respectively. Compared with imatinib alone, the different concentrations of imatinib combined with 0.2 μmol/L BEZ235 could increase the proliferation inhibition of K562 cells, KBM7R cells and CML primary cells, and could reduce the IC 50 of imatinib. After the treatment of imatinib alone and combination with BEZ235 for 48 h, the imatinib IC 50 of K562 cells was (0.14±0.05) and (0.09± 0.04) μmol/L ( t = 1.531, P = 0.249), the imatinib IC 50 of KBM7R cells was (3.93±2.29) and (0.44±0.22) μmol/L ( t = 2.837, P = 0.047), the imatinib IC 50 of the primary cells was (3.12±1.53) and (0.39±0.23) μmol/L ( t = 3.925, P = 0.042). The cell apoptotic rate of the primary cells was (4.9±1.4)%, (13.1±3.2)%, (8.8±2.0)% and (40.6±6.0)%, respectively in the control group without drug treatment, 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib and the combination of 1.0 μmol/L BEZ235 and 1.0 μmol/L imatinib after the treatment of 24 h ( F = 71.031, P < 0.01). Compared with imatinib alone, the expressions of p-AKT and Cyclin D1 proteins were decreased, and the expression of cleaved Caspase-3 protein was increased after the treatment of KBM7R cells for 12 h in the combination group of both BEZ235 and imatinib. Conclusions:BCR-ABL downstream pathway inhibitors can effectively inhibit the proliferation and promote the apoptosis of K562 cells. BEZ235 can inhibit the proliferation and promote the apoptosis of K562 cells, imatinib-resistant and T315I-mutant human KBM7R cells and imatinib-resistant CML primary cells of patients, which has a synergistic effect to imatinib.