Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

OBJECTIVE: To investigate the effects of different doses of propofol on myelin basic protein (MBP) synthesis and myelination of oligodendrocytes in neonatal SD rats. METHODS: A total of 57 neonatal SD rats (7 days old) were randomly divided into control group (=13), vehicle (fat emulsion) group (=5), and 25, 50 and 100 mg/kg propofol groups (=13 in each group). Eight hours after a single intraperitoneal injection of propofol or the vehicle, the rats were examined for expressions of mRNA, caspase-3 mRNA, cleaved caspase-3 and MBP in the brain tissues using qPCR and Western blotting. Immunofluorescence assay was used to detect the apoptosis of the oligodendrocytes at 8 h after the injection and the myelination of the corpus callosum and internal capsule at 24 h. RESULTS: Compared with the control group, the neonatal rats with propofol injections showed significantly down-regulated expressions of mRNA and MBP protein in the brain tissue ( < 0.05). Propofol dose-dependently increased the transcription level of caspase-3 and the protein levels of cleaved caspase-3 at 8 h after the injection ( < 0.05). Propofol injection significantly increased the apoptosis of the oligodendrocytes, and the effect was significantly stronger in 50 and 100 mg/kg groups than in 25 mg/kg group ( < 0.05). At 24 h after propofol injection, myelin formation was significantly decreased in the corpus callosum of the neonatal rats in 100 mg/kg propofol group and in the internal capsule in 50 and 100 mg/kg groups ( < 0.05). CONCLUSIONS In neonatal SD rats, propofol can dose-dependently promote oligodendrocyte apoptosis, decrease MBP expressions in the brain, and suppress myelin formation in the corpus callosum and the internal capsule.
Animals ; Myelin Basic Protein ; Oligodendroglia ; Propofol ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley

Objective To investigate the effect of ulinastatin on postoperative clinical outcomes in pa-tients undergoing elective laparoscopic colectomy. Methods 454 patients underwent elective laparoscopic colecto-my from January 2015 to September 2017 were included in this retrospective study. Patients were divided into 2 groups:ulinastatin group and control group. Propensity score matching was applied to balance the preoperative baseline differences between 2 groups. 155 patients in each group were successfully matched. Mixed linear model was used to exam the effect of ulinastatin on various clinical indicators within 3 days after the surgery,including in-flammation indicators(white blood cell counts,C reactive protein),liver function indicators(alanine transami-nase,aspartate transaminase,total bilirubin),renal function indicators(serum creatinine,blood urea nitrogen). Postoperative hospital length of stay was compared between 2 groups using student's t-test. Results Ulinastatin group showed significantly reduced postoperative white blood cell count and ? reactive protein level (P = 0.036 and 0.025)compared with the control group. The average mean inhibitory effects were 1.04×109/L and 23.93 mg/L respectively,which was 11.1% and 29.9% lower than that of the control group. Procalcitonin,transaminases,total bilirubin,serum creatinine,blood urea nitrogen levels and postoperative hospital length of stay showed no signifi-cant difference between the two groups(P > 0.05). Conclusion Ulinastatin can significantly reduce the level of inflammation response after laparoscopic colectomy,which is beneficial to the fast recovery.

OBJECTIVETo investigate the mechanism underlying propofol- induced down-regulation of myelin basic protein (MBP) in zebrafish embryos.

METHODSZebrafish embryos (6-48 h post-fertilization [hpf]) were randomized into 4 equal groups for exposure to dimethyl sulfoxide (DMSO), 20 μg/mL propofol, 30 μg/mL propofol, or no particular treatment (control group). The larvae were collected at 48 or 72 hpf for detecting the mRNA levels of MBP, Olig1, Olig2, and Sox10 using qRT-PCR (=80). The protein expression of MBP was quantitatively detected using Western blotting (=80), and the apoptosis of the oligodendrocytes was investigated using TUNEL staining (=6).

RESULTSExposure to 20 and 30 μg/mL propofol caused significant reductions in the mRNA expressions of Olig1, Olig2, and Sox10 at 48 and 72 hpf ( < 0.05) and also in MBP mRNA and protein levels at 72 hpf ( < 0.05). Exposure to 30 μg/mL propofol induced more obvious reduction in MBP protein expression than 20 μg/mL propofol at 72 hpf ( < 0.05), and the exposures resulted in a significant increase of oligodendrocyte apoptosis at 72 hpf ( < 0.05).

CONCLUSIONSPropofol exposure reduces MBP expression at both the mRNA and protein levels in zebrafish embryos by down-regulating the expressions of Olig1, Olig2 and Sox10 mRNA levels and increasing apoptosis of the oligodendrocytes.

Objective To identify Chinese character writing related cortex (WRC) and its relationship with hand motor cortical areas. Methods Ten native Chinese-speaking, right-hand volunteers were recruited in the study. NTMS mapping was conducted during picture naming task. The WRC were mapped based on nTMS-induced impairment of Chinese character writing. The extent and area of WRC was calculated. The right-hand motor representations were mapped while motor-evoked potentials were produced under nTMS stimulation. EMG data and coordinates of positive stimulus were recorded. The relationship between WRC and hand motor cortex (HMC) was analyzed on the basis of area comparison and distance calculation. Results The cortical areas related to Chinese character writing were mapped successfully in all subjects by nTMS. WRC was primarily centered in left posterior middle frontal gyrus (pMFG) (86%,55/64). The mean WRC area (161.03 mm2 ±62.58mm2) was significantly smaller than the mean HMC area (589.50 mm2±227.34mm2) (P<0.001). The WRC and HMC were not conjoined or overlapped in the dominant hemisphere. The distance between those two was 12.58mm±2.71mm. Conclusions NTMS can provide reliable assistance in mapping WRC areas. The WRC is relatively fixed and centralized in pMFG but is not overlapped with the HMC.

Objective:To determine the derivative chromosome 9 by the method of detecting the ASS gene,and to explore the relationship between the deletion of derivative chromosome 9 and the efficacy and prognosis of the chronic myeloid leukemia (CML)patients. Methods:The materials of 34 CML patients with positive BCR-ABL fusion gene whose ASS genes were detected were retrospectively analyzed. All patients were treated with Extra-signal (ES)probe to detect the derivative chromosome 9.All patients were divided into two groups according to whether they carried the derivative chromosome 9.The blastic phase or the accelerated phase rates in two groups were compared by using Fisher exact probability. Results:All patients were detected by FISH (BCR-ABL ES probe),and all the BCR-ABL fusion signals were positive.6 of 34 patients were found the deletion of ASS gene, among them 1 case blonged to chronic phase,and 5 cases developed into blastic phase or accelerated phase. In the patients without ASS gene deletion,there were 22 cases in chronic phase,and 6 cases in plastic phase or accelerate phase,there was significant difference of blastic phase rate/accelated phase rate between them (P<0.05).A total of 26 patients were treated with tyrosine kinase inhibitors (TKI).5 of 26 patients belonged to the ASS gene deletion group,1 of 5 patients treated with TKI got molecular remission,4 of 5 patients developed into blastic phase or accelerated phase.21 of 26 patients belonged to the group without ASS gene deletion,and among them,19 cases got molecular remission,2 cases developed into plastic phase or accelerated phase after treatment of TKI,there was significant difference between them (P < 0.05 ). 6 patients were treated with traditional chemotherapy (hydroxyurea,interferon);1 of 6 patients belonged to the ASS gene deletion group,finally developed into the blastic phase or accelerated phase;5 of 6 patients belonged to the group without ASS gene deletion,2 cases got the hematological remission,and 3 patients developed into blastic phase or accelerated phase after treatment,and there was no significant difference of blastic phase rate/ accelerated phase rate between them (P > 0.05 ). Conclusion:The CML patients with derivative chromosome 9 (ASS gene deletion)prone to get disease progression, and have a higher proportion in the blastic phase or accelerated phase patients.Derivative chromosome 9 is related to the bad treatment efficacy of TKI and the poor prognosis of CML.

OBJECTIVETo investigate the effects of different doses of propofol on pulmonary metastasis of intravenous injected MADB106 tumor cells and the expression of E-cadherin and β-catenin in the metastatic tumor tissue in rats.

METHODSForty Fischer 344 male rats were randomly divided into 4 groups (n=10) for intravenous administration of normal saline, intralipid, or propofol at 30 or 50 mg/kg via the femoral vein. One hour after the infusion, MADB106 tumor cells (2×10(5)) were injected intravenously in the rats. Three weeks later, pulmonary metastasis tumor foci and metastatic inhibitory rate were observed and the expression of E-cadherin and β-catenin in the metastatic tumor tissue were detected by immunohistochemistry.

RESULTSCompared with the normal saline group, intralipid group showed no significant differences in the number of metastatic tumor foci in the lungs or E-cadherin and β-catenin expressions (P>0.05), which were all significantly lowered in the two propofol groups (P<0.05 or 0.01). The dose of propofol was inversely correlated with the number of metastasis tumor foci (r=-0.879) and expressions of E-cadherin (r=-0.755) and β-catenin (r=-0.693) (P<0.01).

CONCLUSIONPropofol can dose-dependently suppress pulmonary metastasis of intravenous injected MADB106 tumor cells by inhibiting the Wnt/β-catenin pathway and down-regulating E-cadherin and β-catenin expressions in the metastatic tumor tissue.

Animals ; Cadherins ; metabolism ; Dose-Response Relationship, Drug ; Down-Regulation ; Immunohistochemistry ; Injections, Intravenous ; Lung Neoplasms ; drug therapy ; Male ; Neoplasm Metastasis ; drug therapy ; Neoplasm Transplantation ; Propofol ; pharmacology ; Rats ; Rats, Inbred F344 ; beta Catenin ; metabolism

Objective To investigate the effects of different doses of propofol on pulmonary metastasis of intravenous injected MADB106 tumor cells and the expression of E-cadherin and β-catenin in the metastatic tumor tissue in rats. Methods Forty Fischer 344 male rats were randomly divided into 4 groups (n=10) for intravenous administration of normal saline, intralipid, or propofol at 30 or 50 mg/kg via the femoral vein. One hour after the infusion, MADB106 tumor cells (2 × 105) were injected intravenously in the rats. Three weeks later, pulmonary metastasis tumor foci and metastatic inhibitory rate were observed and the expression of E-cadherin and β-catenin in the metastatic tumor tissue were detected by immunohistochemistry. Results Compared with the normal saline group, intralipid group showed no significant differences in the number of metastatic tumor foci in the lungs or E-cadherin and β-catenin expressions (P>0.05), which were all significantly lowered in the two propofol groups (P<0.05 or 0.01). The dose of propofol was inversely correlated with the number of metastasis tumor foci (r=-0.879) and expressions of E-cadherin (r=-0.755) and β-catenin (r=-0.693) (P<0.01). Conclusion Propofol can dose-dependently suppress pulmonary metastasis of intravenous injected MADB106 tumor cells by inhibiting the Wnt/β-catenin pathway and down-regulating E-cadherin andβ-catenin expressions in the metastatic tumor tissue.

Objective To investigate the effects of different doses of propofol on pulmonary metastasis of intravenous injected MADB106 tumor cells and the expression of E-cadherin and β-catenin in the metastatic tumor tissue in rats. Methods Forty Fischer 344 male rats were randomly divided into 4 groups (n=10) for intravenous administration of normal saline, intralipid, or propofol at 30 or 50 mg/kg via the femoral vein. One hour after the infusion, MADB106 tumor cells (2 × 105) were injected intravenously in the rats. Three weeks later, pulmonary metastasis tumor foci and metastatic inhibitory rate were observed and the expression of E-cadherin and β-catenin in the metastatic tumor tissue were detected by immunohistochemistry. Results Compared with the normal saline group, intralipid group showed no significant differences in the number of metastatic tumor foci in the lungs or E-cadherin and β-catenin expressions (P>0.05), which were all significantly lowered in the two propofol groups (P<0.05 or 0.01). The dose of propofol was inversely correlated with the number of metastasis tumor foci (r=-0.879) and expressions of E-cadherin (r=-0.755) and β-catenin (r=-0.693) (P<0.01). Conclusion Propofol can dose-dependently suppress pulmonary metastasis of intravenous injected MADB106 tumor cells by inhibiting the Wnt/β-catenin pathway and down-regulating E-cadherin andβ-catenin expressions in the metastatic tumor tissue.

Objective To evaluate the influence and safety of topical ketamine on postoperative sore throat following endotracheal intubation. Methods The clinical literatures concerning topical application of ketamine for the prevention of postoperative sore throat (POST) were searched from online databases. Randomized controlled trials were selected by the inclusive and exclusive criteria. Meta-analysis was conducted to assess the risk ratio(RR) of the incidence of POST and software Stata 12.0 was used in this analysis. Results Seven randomized trials involving 490 patients were included in this meta-analysis. The results of meta-analysis showed that the incidence of POST was significantly reduced in the ketamine group,with RR 0.61(95%CI 0.47~0.79,P<0.001) at 0~1 h,0.55(95%CI 0.43~0.71, P<0.001) at 4 h and 0.48 (95%CI 0.34 to 0.66, P<0.001) at 24 h after surgery. No major complications related to topical ketamine were observed. Conclusions For the patients receiving general anesthesia and endotracheal intubation, topical prophylactic application of ketamine can significantly reduce the incidence of POST without major complications.