Objective To establish a high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)method for determining the plasma concentration of olverembatinib in leukemia patients,apply it to clinical drug monitoring,and provide reliable basis for rational drug use in clinical practice.Methods Ponatinib-d8 was used as an internal standard,and methanol was used to precipitate plasma proteins and extract olverembatinib.The chromatographic column was Welch Ultimate XB-C18 cloumn(50 mmx4.6 mm,5 μm),with a column temperature of 60 ℃.The mobile phase consisted of an aqueous solution(containing 0.1％formic acid+2 mmol/L ammonium acetate)-methanol solution(containing 0.1％formic acid),with a flow rate of 0.8 mL/min and gradient elution.Electrospray positive ion mode was used,with multiple reaction monitoring scanning.The quantitative ion pair of olverembatinib was m/z 533.3→260.1,the qualitative ion pair was m/z 533.3→433.3,and the internal standard ion pair was m/z 541.1 →260.2.The plasma samples of 40 leukemia patients taking olverembatinib were monitored and analyzed for concentration,and IBM SPSS Statistics 27.0 and OriginPro 2021 softwares were used for statistical analysis of the results.Results The linear range of olverembatinib was 1-250 ng/mL(r=0.998 0),the lower limit of quantification was 1 ng/mL,the extraction recovery rate was 100.28％～101.27％,the intra-day precision RSD was 1.15％～3.87％,and the inter-day precision RSD was 2.32％～3.68％.Conclusion This method is easy to operate,highly specific and sensitive,and can be used to determine the blood concentration of olverembatinib in leukemia patients.

Objective To establish a high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)method for determining the plasma concentration of methylprednisolone in patients with hematological diseases,and apply it to guide the clinical application.Methods Plasma samples were subjected to methanol-precipitated protein containing internal standard methylprednisolone-d3.The HPLC system was equipped with an Ultimate XB-C18(4.6mm×50mm,5 μm particle size),maintained at 60℃,and 5 μl of the supernatant was injected.Mobile phases consisting of 0.1%(v/v)formic acid(1∶1 000)and 2 mmol/L ammonium acetate in water(B)and 0.1%(v/v)formic acid(1∶1 000)in methanol at a flow rate of 0.8 ml/min was used.The electrospray ionization(ESI)source was operating in positive ion mode.Multiple reaction monitoring(MRM)was applied for the detection of the components:Methylprednisolone mass-to-charge ratio(m/z)375.4 → 339.4(qualitative ions),methylprednisolone m/z 375.4→357.3(quantitative ions),methylprednisolone-d3 m/z 378.2→360.3.The peak area ratio of methylprednisolone to methylprednisolone-d3 was used as the quantitative basis.The concentration of methylprednisolone in plasma was calculated and its performance was investigated.Results The linear range of methylprednisolone was 10～1 000ng/ml(r2=0.996 7),and the lower limit of quantification was 10 ng/ml.The RSDs of intra-day and inter-day precision results were less than 15%and the relative recovery ranged from 99.52%～104.79%.For methylprednisolone,the samples were stable at-20℃after three repeated freeze-thaw cycles.The prepared samples were stable at room temperature and 4℃for 24h(RSDs<15%).The steady-state blood drug concentrations of methylprednisolone in 16 patients were in the ranges of 1～258 ng/ml.Conclusion The HPLC-MS/MS method can accurately,rapidly and simply detect the concentration of methylprednisolone,and be suitable for clinical application.

Objective:To analyze the difference of clinical characteristics and outcomes of infants with moderate and severe pediatric acute respiratory distress syndrome(PARDS)diagnosed according to baseline oxygenation index(OI) in pediatric intensive care unit(PICU).Methods:Second analysis of the data collected from the "Efficacy of pulmonary surfactant (PS) in the treatment of children with moderate and severe ARDS" program.Retrospectively compare of the differences in clinical data such as general condition, underlying diseases, OI, mechanical ventilation, PS administration and outcomes among infants with moderate and severe PARDS divided by baseline OI who admitted to PICUs at 14 participating tertiary hospitals from 2016 to December 2021.Results:Among the 101 cases, 55 cases (54.5%) were moderate and 46 cases (45.5%) were severe PARDS.The proportion of male in the severe group (50.0% vs.72.7%, P=0.019) and the pediatric critical illness score(PCIS)[72 (68, 78) vs.76 (70, 80), P=0.019] were significantly lower than those in the moderate group, while there was no significant difference regarding age, body weight, etiology of PARDS and underlying diseases.The utilization rate of high-frequency ventilator in the severe group was significantly higher than that in the moderate group (34.8% vs.10.9%, P=0.004), but there was no significant difference in PS use, fluid load and pulmonary complications.The 24 h OI improvement (0.26±0.33 vs.0.04±0.34, P=0.001) and the 72 h OI improvement[0.34 (-0.04, 0.62) vs.0.15 (-0.14, 0.42), P=0.029)]in the severe group were significantly better than those in the moderate group, but there was no significant difference regarding mortality, length of hospital stay and intubation duration after diagnosis of PARDS between the two groups. Conclusion:In moderate and severe(divided by baseline OI) PARDS infants with invasive mechanical ventilation, children in severe group have better oxygenation improvement in the early stage after PARDS identified and are more likely to receive high frequency ventilation compared to those in moderate group.Baseline OI can not sensitively distinguish the outcomes and is not an ideal index for PARDS grading of this kind of patient.

Objective: To evaluate the tolerability and short-term efficacy of chemo-radiotherapy in 125 patients with stage ⅡB-ⅣA esophageal carcinoma after radical resection. Methods: We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo-radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results: 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo-radiotherapy (41.6%), while 73 patients underwent only 1-4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up (6.4%). The 1-year and 3-year overall survival rate were 91.6% and 57.0%, respectively, with a median survival time of 64.4 months. The 1-year and 3-year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo-radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1-2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P=0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P=0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor (P=0.010). Conclusions Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB-ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.

Objective To evaluate the tolerability and short?term efficacy of chemo?radiotherapy in 125 patients with stageⅡB?ⅣA esophageal carcinoma after radical resection. Methods We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo?radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan?Meier method and analyzed using the log?rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo? radiotherapy (41.6%), while 73 patients underwent only 1?4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up ( 6.4%). The 1?year and 3?year overall survival rate were 91.6%and 57.0%, respectively, with a median survival time of 64.4 months. The 1?year and 3?year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo?radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1?2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P＝0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P＝0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor ( P ＝ 0.010 ). Conclusions Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB?ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.

Objective To evaluate the tolerability and short?term efficacy of chemo?radiotherapy in 125 patients with stageⅡB?ⅣA esophageal carcinoma after radical resection. Methods We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo?radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan?Meier method and analyzed using the log?rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo? radiotherapy (41.6%), while 73 patients underwent only 1?4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up ( 6.4%). The 1?year and 3?year overall survival rate were 91.6%and 57.0%, respectively, with a median survival time of 64.4 months. The 1?year and 3?year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo?radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1?2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P＝0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P＝0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor ( P ＝ 0.010 ). Conclusions Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB?ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.

Objective To investigate how electroacupuncture activates the AMPKαpathway in the treatment of functional dyspepsia ( FD) . Methods Tail clipping stimulation was combined with an irregular diet to induce FD in 20 Sprague-Dawley rats. They were randomly divided into a model group and an electroacupuncture group, each of 10. Ten others had no FD induced and formed a normal group. The rats in the electroacupuncture group were given 10 days of electroacupuncture treatment, while those in the normal and model groups were restrained and fixed like those in the electroacupuncture group, but not given electroacupuncture. The expression of phosphorylated adenosine mono-phosphate-activated protein kinase alpha (p-AMPKα), phosphorylated tuberin (p-TSC2) and Rheb protein in the stomachs and small intestines of each group were detected using the western blotting. Levels of mTOR mRNA were quantified using the reverse-transcription polymerase chain reaction ( RT-PCR) . Results The western blotting re-sults showed that compared with the normal group, the expression levels of p-AMPKα and p-TSC2 in the stomachs and small intestines of the model group decreased significantly, while that of Rheb protein increased significantly. Compared with the model group, the expression of p-AMPKαand p-TSC2 increased significantly after the electroacu-puncture treatment, while that of Rheb protein decreased significantly. According to the RT-PCR results, the expres-sion of mTOR mRNA in the stomachs and small intestines of the model group was up-regulated significantly compared with the normal group. Compared with the model group, expression of mTOR mRNA in the electroacupuncture group was significantly down-regulated. Conclusion Electroacupuncture can activate the AMPKα pathway, up-regulate the expression of the related protein p-TSC2, and decrease the expression of Rheb protein, thereby down-regulating the transcription of the mTOR gene. That would serve to treat FD.

Objective To analyze the electroencephalograph (EEG) features of 43 patients with clinically possible or probable Creutzfeldt-Jakob disease (CJD) and its correlation with megnetic resonance imaging (MRI) imaging and clinical manifestations.Methods All patients diagnosed with suspected CJD who were hospitalized in Xuanwu Hospital from January 2013 to December 2015 were collected.The clinical data, EEG and MRI imaging features were analyzed retrospectively.Based on the periodic sharp wave complexes (PSWC) appearance in EEG results, the patients were divided into typically changed group (TCG), atypically changed group (ACG) and unchanged group (UCG).Age, disease duration, clinical manifestations and MRI features among three groups were analyzed and the correlations between patient′s EEG features and age, disease duration, clinical manifestations or MRI features were explored using spearman method.Results Among the 43 patients with possible or probable CJD disease, 26 were male and 17 were female with an average disease duration of 4 months.The age of onset ranged from 31 to 80 with an average of (58.0±9.8) years old, and 86.0% of patients were 51 years old or above.Clinical characteristics of CJD patients according to occurrence rate were as follows: 35 cases (81.4%) with cognitive impairment, 29 cases (67.4%) with mental and behavior disorder, 28 cases (65.1%) with pyramidal tract damage, 24 cases (55.8%) with cerebellar symptoms, 23 cases (53.5%) with extrapyramidal symptoms,17 cases (39.5%) with myoclonic, 13 cases (30.2%) with dyssomnia, 13 cases (30.2%) with visual disorder and 2 cases (4.7%) with akinetic mutism.Regarding EEG features, 39.53% (17/43) of patients showed typical periodic sharp wave complexes (PSWC) (TCG group), 51.2% (22/43) had irregular rhythm and different forms of slow wave (ACG group) and only 9.3% (4/43) had no EEG change (UCG group).The occurrence rate of ribbon sign in MRI was 82.4% (14/17) in TCG group, 77.3% (17/22) in ACG group and none in UCG group.The rates were significantly higher in TCG and ACG group than that in UCG group (both P<0.05).Spearman correlation analysis revealed that EEG features was correlated with disease duration (r=0.351, P=0.021) and visual impairment (r=-0.377, P=0.013) for all CJD patients.There was no correlation between EEG and MRI or other clinical manifestations such as myoclonic, age and so on (all P>0.05).Conclusions EEG showed typical changes associated with disease duration in different stages of disease.EEG and MRI are two different means to evaluate different aspects of patients with CJD disease, and combination of two means could achieve better evaluation results.

Objective To observe the effect of psoralen on the proliferation of osteoblasts induced by alcohol, thus to explore the mechanism of psoralen in preventing and treating alcohol-induced osteoporosis. Methods The osteoblasts separated from neonatal rat skull were identified by alkaline phosphatase (ALP) staining method. The in-vitro confirmed osteoblasts were randomly divided into 4 groups, namely blank control group, alcohol group (model group), psoralen group, and psoralen plus alcohol group. The alcohol-induced osteoblast proliferation in various groups was determined by methyl thiazolyl tetrazolium (MTT) method. Results Compared with the blank control group, the alcohol-induced osteoblast proliferation at culturing hour 24, 48, 72, 96 in alcoholgroup was significantly decreased (P<0.05), and the proliferation in psoralen group at various time points only showed an increasing trend, the differences being statistically insignificant (P>0.05). Compared with the alcohol group, osteoblast proliferation at culturing hour 24 in psoralen plus alcohol group was significantly increased (P <0.05) , but the differences of osteoblast proliferation at culturing hour 48, 72, 96 h between the two groups were insignificant (P > 0.05). Conclusion Psoralen has certain effect on promoting alcohol-induced osteoblast proliferation in vitro.

Objective To observe the effect of two reverse pedicle flap repaired soft tissue defect of the finger.Methods From April,2011 to March,2015,46 patients were randomly divided into two groups.Twenty-eight cases were performed by dorsal metacarpal artery flaps with cutaneous branches as pedicle and the 18 cases were performed by reverse the proper palmar digital artery dorsal branches island flap.The complication,survival rate,hand function and appearance were analyzed.Results The dorsal metacarpal artery flaps with cutaneous branches as pedicle and reverse the proper palmar digital artery dorsal branches island flap were an average follow-up of 18 and 15 months,all flaps survived.For fingertip defects,8 cases were repaired with as pedicle as the dorsal metacarpal artery flaps with cutaneous branches as pedicle while 16 cases were repaired with reverse the proper palmar digital artery dorsal branches island flap.Among them,complication included 2 cases of early venous congestion and 2 cases of superficial skin necrosis.One case of reverse the digital artery dorsal branches island flap blistered;the flap sensibility was good recovery.The two-point discrimination testing of dorsal metacarpal artery flaps with cutaneous branches as pedicle was from 6.0 to 9.0 mm (average of 7.1 ± 0.5 mm);the two-point discrimination testing of dorsal metacarpal artery flaps with cutaneous branches as pedicle was from 4.0 to 7.0 mm (average of 5.2 ± 0.4 mm),but there were differences in two-point discrimination and there was statistically significant (P ＜ 0.05).There was no significant difference between the two groups each finger interphalangeal joint activity compared with the healthy side.The study found that 10 cases of dorsal metacarpal artery flaps appearance was 5 mm higher than normal skin and 1 patient of reverse the digital artery dorsal branches island flap appearance was 5 mm higher than normal skin,the difference was statistically significant (P ＜ 0.05),the latter was better than the former,especially repaired fingertip defect.Conclusion Dorsal metacarpal artery flaps with cutaneous branches as pedicle and reverse the proper palmar digital artery dorsal branches island flap were safe and reliable,it is the ideal flap finger defects.For finger fingertip defect repaired reverse the proper palmar digital artery dorsal branches island flap is superior dorsal metacarpal artery flaps with cutaneous branches as pedicle.