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 observe the effect of abdominal acupuncture in treating allergic rhinitis(AR).Methods Twenty-seven AR patients who attended Fangshan Hospital,Beijing University of Chinese Medicine from August to October 2022 were selected.They were divided into treatment group(15 cases)and control group(12 cases)according to randomized numerical table method.The treatment group received abdominal acupuncture.The control group at the same point was used one-time sterile cannula acupuncture to simulate acupuncture,but no needle was inserted into the acupoint.Two groups were treated,3 times a week for 4 weeks.The visual analogue scale(VAS),rhinoconjunctivitis quality of life questionnaire(RQLQ),Pittsburgh sleep quality index(PSQI)scores,and the histamine(HIS),leukotriene D4(LTD4),immunoglobulin E(IgE)levels were compared between two groups before and after treatment.Results At each time point after treatment,the VAS,RQLQ,PSQI scores and HIS,LTD4,IgE levels of patients in treatment group were significantly lower than those before treatment(P<0.05).There were no statistically significant differences in VAS,RQLQ,and PSQI scores,the HIS,LTD4,and IgE levels after 2-week treatment in both groups(P>0.05).After 4-week treatment and follow-up 4-week,the VAS,RQLQ,and PSQI scores,the HIS,and LTD4 levels in treatment group were significantly lower than those in control group(P<0.05).Conclusion Abdominal acupuncture has good therapeutic effect on AR and significantly improves life quality of the patients,which can reduce the levels of HIS,LTD4 and IgE.The therapy is worthy of clinical application.

Objective:To explore the effects of early-life maternal deprivation on depressive-like behavior and neurogenesis in the granular layer of hippocampus in adolescent rats (6-7 weeks old).Methods:Neonatal rats were randomly divided into maternal deprivation group and control group, with 3 litters in each group.Rats in the maternal deprivation group were given maternal deprivation from 1 to 14 days after birth and rats in the control group were caged with the mother rats and raised normally.The body weight of rats at 5-6 weeks old was recorded and the increased body weight was calculated.When the rats were 6 weeks old, the sucrose preference test was carried out.Then the rats were killed and immunofluorescence histochemistry was applied to compare the expression of Ki67 and Nestin positive cells in the dentate gyrus of hippocampus.SPSS 22.0 software was used for statistical analysis.The data of the two groups were tested to conform to the normal distribution, and then t-test was carried out. Results:There was significant difference in body weight growth between the two groups at the age of 5-6 weeks.Compared with the control group, rats in the maternal deprivation group had lower body weight growth ((20.57±2.19) g, (30.57±1.25) g, t=3.96, P<0.01)) and lower sucrose preference rate((58.38±53.14)%, (73.88±3.67)%, t=3.21, P<0.01). The results of immunofluorescence showed that the number of Ki67 positive cells in the granular layer of hippocampus in the maternal deprivation group was less than that in the control group ((5.13±0.31), (7.60±0.38), t=5.09, P<0.01), and the number of Nestin immunofluorescence positive cells was more than that in the control group ((16.65±0.79), (7.64±0.70), t=8.51, P<0.01). The Nestin immunofluorescence positive cells in the maternal deprivation group had more protrusions and branches, and the morphology was similar to astrocytes, while the immunofluorescence positive cells in the control group had fewer protrusions, and the cell body was oval. Conclusions:Early-life maternal deprivation leads to depressive-like behavior in adolescent rats, which may be associated with the decrease of neurogenesis and activation of astrocytes in the dentate gyrus of the hippocampus.

Objective:To study the amplification / overexpression of human epidermal growth factor receptor 2 (HER2) in patients with gallbladder cancer, and to analyze the correlation between amplification/overexpression of HER2 with clinicopathological features and survival in patients after R 0 resection. Methods:There were 14 males and 26 females, aged (60.3±8.7) years old and treated at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2016 who met the inclusion criteria of the study. Immunohistochemistry and fluorescence in situ hybridization were used to detect amplification / expression of HER2 in resected tumor tissues. Patients were divided into two groups according to the HER2 gene expression: the HER2-negative group ( n=40) and the HER2-positive group ( n=10). The Chi-square test was used to analyze the relationship between amplification/expression of HER2 and clinicopathological parameters. Patients were followed up by telephone for prognosis. The Kaplan-Meier method was used for survival analysis. The Cox proportional hazard model was used to explore factors affecting prognosis of gallbladder cancer patients. Results:HER2 amplification/overexpression was found in 10 patients with gallbladder cancer, with a positive rate of HER2 being 20.0% (10/50). There was a significant difference in the proportion of patients with vascular tumor thrombus between the HER2 negative group and the HER2 positive group [7.5%(3/40) vs. 30.0%(3/10), P<0.05]. On follow-up, data of 46 patients was available. There were 36 patients in the HER2-negative group and 10 patients in the HER2-positive group. Compared with the HER2-negative group, the median recurrence-free survival (10.10 vs. 75.07 months) and the median overall survival (16.77 vs. 83.07 months) of the HER2-positive group were both significantly lower (both P<0.05) than the HER2-negative group. Univariate analysis showed HER2 positivity to be a risk factor for recurrence-free and overall survival in patients with gallbladder cancer after radical resection. Cox multivariable analysis revealed that lymph node metastasis was an independent risk factor for both recurrence-free ( HR=4.31, 95% CI: 1.92-9.68, P<0.001) and overall survival ( HR=3.44, 95% CI: 1.08-11.00, P=0.037). Conclusion:Amplification / overexpression of HER2 was associated with venous invasion and worse prognosis in patients with gallbladder cancer.

Objective: To study the antidepressant effects of extracts fromZanthoxylum bungeanumandZanthoxylum schinifoliumin mice exposed in chronic restraint stress. Methods: 45 mice of SPF male ICR were randomly divided into five groups: normal group, model group, sertraline hydrochloride group,Zanthoxylum bungeanumextract group andZanthoxylum schinifoliumextract group, with 9 mice in each group. Except for the normal group, mice in all groups were chronically restrained to establish the depressive model. The normal group and model group were given olive oil by intragastric administration, and other groups were given sertraline hydrochloride(10 mg/kg),Zanthoxylum bungeanumextract(200 mg/kg) andZanthoxylum schinifoliumextract(200 mg/kg), respectively. The behaviors of mice in each group were evaluated by open-field test and forced swimming test. The levels of brain-derived neurotrophic factor(BDNF), 5-hydroxytryptophan(5-HT), glutathione(GSH) and nitric oxide(NO) in serum and brain were determined by ELISA. Results: Compared with model group,Zanthoxylum bungeanumextract could reduce the percentage of immobility time in forced swimming test, increase the level of cortical BDNF, and improve the levels of 5-HT and GSH in cortex and serum, with statistical significance(P<0.05).Zanthoxylum schinifoliumextract could improve the behavior of mice in open field test and forced swimming test, increase the levels of cortex 5-HT and serum GSH, and decrease the contents of NO in serum and cortex. Conclusion The extracts ofZanthoxylum bungeanumandZanthoxylum schinifoliumcan improve the depression-like behaviors of mice exposed to chronic restraint stress.

Objective:To explore the rules of prescription and medication of Traditional Chinese Medicine (TCM) syndrome differentiation treatment for insomnia.Methods:We screened the medical records related to insomnia from the ancient medical cases, modern medical cases, famous medical cases and shared medical record database, and then we put data into the Ancient and Modern Medical Case Cloud Platform (V 1.5.7). The platform software Data mining was applied and performed by frequency analysis, correlation analysis, and drug pair analysis. Results:This study collected 664 cases related to insomnia, like difficulty in falling sleep, early waking up, easy to wake up, dreaminess. The top 5 syndromes included internal phlegm-heat, imbalance between heart-yang and kidney-yin, liver stagnation transforming into fire, heart and spleen deficiency, restless mind. There were 664 prescriptions, 414 TCM medications, where the top 5 medications included Glycyrrhizae Radix et Rhizoma, Poria, Rehmanniae Radix, Ziziphi Spinosae Semen, Angelicae Sinensis Radix. The effect of high-frequency medications were nourishing the heart and calming the mind, clearing heat and dissipating phlegm, soothing the liver and relieving depression, and nourishing yin and yang. The top five drug-combinations included Ostreae Concha- Longgu, Poria- Glycyrrhizae Radix et Rhizoma, Citri Reticulatae Pericarpium- Poria, Angelicae Sinensis Radix- Rehmanniae Radix, Bupleuri Radix- Glycyrrhizae Radix et Rhizoma. Conclusions:TCM syndrome differentiation for insomnia focus on the heart. The medications are mainly to nourish the heart and calm the mind, supplemented by clearing heat, replenishing heart and spleen, soothing the liver and relieving stagnation, nourishing yin and blood for the symptoms relief, with treatment priciple of seeking both temporary and permanent solutions.

Objective:To explore disorienting dilemmas during postgraduate study period experienced by postgraduates with master of nursing specialist who participated in the national postgraduate entrance examination and provide a basis for teaching reform based on transformative learning theory.Methods:Using the purposive sampling method and the maximum difference method, 23 full-time masters of nursing specialist who participated in the national postgraduate entrance examination from 3 universities of Jiangsu Province were selected as the research objects from March to June 2019. The descriptive qualitative research method was used to conduct semi-structured interviews, and the traditional content analysis method was used to analyze the interview data.Results:Four themes of disorienting dilemmas of masters of nursing specialist were extracted: the expected hypothesis of challenges of new environment in course learning, a gap between scientific research ability and training target, adjustment of self-positioning in clinical practice and insufficient preparations for graduation of master of nursing specialist.Conclusions:Master of nursing specialist have disorienting dilemmas in course study, scientific research, clinical practice and graduation preparation, and nursing educators can use this as a trigger point to carry out teaching reform based on transformative learning theory.

OBJECTIVE: To evaluate the clinical application of magnetic resonance imaging( MRI) in diagnosis of lung large shadow in coal workers' pneumoconiosis( CWP). METHODS: Twenty-five CWP patients with lung large shadow( 39 lesions) were selected as CWP group by using the judgment sampling method,and 34 cases( 34 lesions),including 21 cases of lung cancer( lung cancer subgroup) and 13 cases of lung mass( lung mass subgroup),were selected as control group. Routine MRI examinations was performed on these three groups of patients. T1 weighted imaging( T1 WI),T2 weighted imaging( T2 WI) and frequency pre-saturation inversion recovery( SPIR) imagings were performed to analyze the differences of MRI images. RESULTS: Large shadow lesions in patients with CWP showed slightly lower signal,equal signal and equal lower signal in T2 WI and SPIR,accounting for 97. 4%(38/39) and 94. 9%(37/39) respectively. Those show slightly higher signal accounted for 2. 6%(1/39) and 5. 1%(2/39),respectively. The proportions of lung large shadows showed slightly higher signal of CWP group at T2 WI and SPIR were lower than those in the control group( 2. 6% vs88. 2%,5. 1% vs 91. 2%,P < 0. 01),the lung cancer subgroup(2. 6% vs 95. 2%,5. 1% vs 95. 2%,P < 0. 01) and lung mass subgroup( 2. 6% vs 76. 9%,5. 1% vs 84. 6%,P < 0. 01). CONCLUSION: MRI has good specificity in identifying characteristics of lesion of CWP large lung shadow. The main manifestations are slightly lower signal,equal signal and equal lower signal on T2 WI and SPIR

Objective To establish type 2 diabetes mellitus(T2DM)KM mouse models via the combined use of high-calorie diet and multiple administration of low-dose streptozotocin(STZ). Methods Based on the randomized number table,30 KM mice were equally and randomly divided into 2 groups:modeling group and control group. Mice in the modeling group were given foods with high calories for one month and injected with 30 mg/kg STZ via the left lower abdominal cavity for 2-4 consecutive days,while mice in the control group were fed with standard maintenance foods and the same dose of citrate buffer solution. The general conditions including food and water intake and mice weight were recorded. Blood glucose level was measured 1,2,4,5,12,and 21 weeks after STZ injection. When the glucose level became stabilized,the serum insulin and blood lipids [including total cholesterol(TC),triacylglycerol(TG),high-density lipoprotein(HDL) and low-density lipoprotein(LDL)],and hemoglobin a1c (HbA1c)were measured,and oral glucose tolerance test were performed. Results The modeling group had a 100% survival rate. After STZ injection,the body weight of mice in the modeling group reached the peak in the forth week,and later the growth rate decreased,still significantly lower than that of control group mice till the 21week(t=3.160,P=0.006). Their blood glucose level was significantly higher than that of mice before STZ injection and in the control group(all P<0.05);as time went on,it was also rising,and it remained high till the 21week [(26.38±1.34)mmol/L]. In the 4week,the fasting blood glucose of mice in the modeling group was(11.86±3.33)mmol/L,which was significantly higher than that of mice in the control group [(6.37±1.27)mmol/L](t=-3.830,P=0.002). Fasting serum insulin of mice in the modeling group showed no significant difference compared with control group [(5.73±0.24)mU/L vs.(5.48±0.32)mU/L;t=-0.863,P=0.416]. Insulin sensitivity index was 0.0145±0.0039,which was significantly lower than that(0.0267±0.0039)in control group(t=4.414,P=0.003). In the 6week,the blood glucose levels of mice in the modeling group were(15.35±1.82),(26.45±1.07),(25.58±1.46),and(26.15±1.00)mmol/L 0,30,60,and 120 min after oral gavage of D-glucose,which were all significantly higher than those in the control group [(6.88±1.75)(t=-8.203,P=0.000),(17.65±2.94)(t=-6.884,P=0.000),(13.18±2.04)(t=-12.110,P=0.000),and(7.37±3.40)mmol/L(t=-12.969,P=0.000)]. In the 8week,serum TC and TG levels of mice in the modeling group were(3.83±0.06)and(2.20±0.20)mmol/L,which were significantly higher than those in the control group [(3.10±0.10)(t=11.000,P=0.000)and(0.90±0.10)mmol/L(t=10.070,P=0.000)]. HDL level of mice in the modeling group was(2.03±0.06)mmol/L,which was significantly lower than that in the control group [(2.48±0.02)mmol/L;t=11.662,P=0.000]. LDL level was increased but showed no significant difference [(0.34±0.08)mmol/L vs.(0.26±0.02)mmol/L](t=1.680,P=0.168). HbA1c content of mice in the modeling group was(7.30±0.31)%,which was significantly higher than that(4.40±0.32)% in the control group(t=-11.587,P=0.000). Conclusion KM mice models of T2DM were successfully established after high-calorie diet and multiple administration of low-dose STZ.

Objective In order to evaluate that whether Pluronic P85 coated poly(butylcyanoacrylate) nanoparti-cles was able to deliver antiepileptic drug phenytoin into the brain va bypassing mesial temporal lobe epilepsy (MTLE)-induced Pgp in a rat model of MTLE. Methods The rat model of MTLE, induced by li-pilocarpine, was divided in-to two groups (6 for nanoparticle drug group and 7 for PHT drug group). Immunohistochemistry assay was performed to detect Pgp expression at the hippocampus. Nanoparticles were prepared by interfacial polymerization method. Dialysate samples of brain were collected at 30, 60, 120, 180, 240 and 300 min after drug administration by microdialysis tech-nology. Samples were analyzed by high performance liquid chromatography (HPLC). Results The area under the curve (AUC) ratio of brain/plasma in Nanoparticle drug group was 0.370.10 which was significantly higher compared with 0.190.06 in conventional PHT drug group (P<0.05). The Pgp immunopositive area, as assessed by analysis of labeled surface area, was higher in the DG, CA3 and CA1 sector in the hippocampus of MTLE rats when compared to the normal rats. Conclusions Pluronic P85 coated PBCA nanoparticles can significantly deliver PHT into brain via bypassing MTLE-induced Pgp in a rat model of MTLE.