Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

BackgroundNanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models.

MethodsWe synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group.

ResultsWe demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 10/L at the 28 day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] μmol/L) at the 28 day, particularly those injected with 1.5 mg/kg NaYbF:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney.

ConclusionThe use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.

Objective To explore the risk factors of elderly people with pulmonary TB,and to provide the scientific evidence of prevention and interventions for tuberculosis among the old people in Nanchang City.Methods 1∶1 case control study was performed .A total of 390 pulmonary TB patients over 60 years old were selected as case group.One healthy person with the same gender and within 2 year age difference was selected to match each case.Interviews were carried out with a uniformly designed questionnaire.Logistic regression models were used for analysis.Results A total of 120 smear positive tuberculosis patients and 270 smear negative tuberculosis patients were investigated.And 72.82% male and 27.18% female of the 390 TB patients were investigated.Average age of patients was 70.34 ±7.75.Multivariate condition logistic regression analysis showed smoking(OR =2.359,95%CI:1.368 -4.068),contacting tuberculosis(OR =3.357,95%CI:1.854 -6.075),BMI 18.5 -24.9(OR =0.175,95%CI:0.056 -0.546),education (OR =0.110,95%CI:0.036 -0.332),annual average income (OR =0.475,95%CI:0.332 -0.681),per capita living space(OR =0.946,95%CI:0.920 -0.973)and drinking tea (OR =0.398,95%CI:0.268 -0.592)were the influencing factors(P <0.05).Conclusion Health education should be promoted auording to the risk factors,and patients manage ment should be streng thened.

OBJECTIVETo immunopurify human endometrial endothelial cells (HEEC) from fresh surgical specimens of endometrial cancers and normal endometrial tissues, and investigate their biological characteristics.

METHODSEndothelial cells of endometrial cancers and normal endometrial tissues were isolated using anti-CD31 conjugated magnetic microbeads. The isolated endothelial cells were cultured in vitro and their origins were identified. Their angiogenic characteristics were observed by MTT, wound healing, Transwell cell invasion and tube formation assays.

RESULTSFlow cytometry revealed that the immunopurification technique yielded endothelial cell purity of > 95% in all samples. All purified HEEC were characterized as endothelial cells on the basis of expression of the classical endothelial markers vWF and CD31 as shown by immunofluorescence examination. Although the tumor-associated HEEC didn't show more rapid proliferation than normal HEEC, they exhibited enhanced migration ability (P = 0.006), potent invasiveness (P = 0.033), and elevated tube formation in vitro (P = 0.029).

CONCLUSIONSHuman endometrial endothelial cells can be efficiently isolated from endometrial cancer and normal endometrial tissues by immunomagnetic methods. Tumor-associated HEEC exhibit enhanced migratory ability, potent invasiveness, and elevated tube formation in vitro.

Adult ; Aged ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Endometrial Neoplasms ; metabolism ; pathology ; Endometrium ; cytology ; metabolism ; pathology ; Endothelial Cells ; metabolism ; pathology ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; von Willebrand Factor ; metabolism

Objective To study the Th17/Treg (regulatory T cells) immunoregulation in patients coinfected with TB and HIV before and after HAART( highly active anti-retroviral therapy).Methods 10 HIV cases coinfected with TB ( HIV/TB group) and 10 cases infected with HIV only ( HIV group) received HAART.PBMCs were stained and immunophenotyping of Th17( IL-17 expressing T cells) and CD4 + CD25 +T cells (Treg) were analysed by flow cytometry.Results The pre-treatment patients tended to have lower Th17 cells and higher Tregs cells compared to post-treatment( 1.90％ ± 0.9％ vs.4.65％ ± 1.48％,16.48％ ±4.91％ vs.8.29％ ± 3.13％ respectively).The percentage of IL-17 before and after HAART were 1.90 ± 0.9％ vs.4.65 ± 1.48％ respectively in HIV/TB group patients ( P ＜ 0.01 ).The difference between the percentage of IL-17 before and after HAART in the HIV/TB group and the HIV group were 2.65 ± 1.62％ vs.0.67％ ± 0.46％ respectively (P ＜0.01 ).IL-17 expressing T cells were increased faster after HAART in the former group than the latter.The percentage of Treg before and after HAART were 16.48％ ±4.91％ vs.8.29％ ± 3.13％ respectively in HIV/TB group ( P ＜ 0.01 ).The difference between the percentage of Treg before and after HAART in the HIV/TB group and the HIV group were 8.91％ ±4.82％ vs.2.63％ ± 2.34％ respectively ( P ＜ 0.01 ).Treg were decreased more rapidly after HAART in the former than the latter.Conclusions TB and HAART both had an effect on the Th17/Treg ratio of HIV/ TB co-infected patients,which can cause increased Th17 expression,the later plays a pro-inflammatory role.TB and HAART can decrease Treg expression and enhance anti-inflammation response.The fact that Th17/Treg disorder are more likely to exist in patients with HIV/TB co-infection after HAART for one month suggests a potential role for Th17/Treg imbalance leading to tuberculosis-associated immune reconstitution inflammatory syndrome during patients receiving HAART period.

A simple, reliable and sensitive liquid chromatography-isotope dilution mass spectrometry (LC-ID/MS) was developed and validated for quantification of olanzapine in human plasma. Plasma samples (50 microL) were extracted with tert-butyl methyl ether and isotope-labeled internal standard (olanzapine-D3) was used. The chromatographic separation was performed on XBridge Shield RP 18 (100 mm x 2.1 mm, 3.5 microm, Waters). An isocratic program was used at a flow rate of 0.4 m x min(-1) with mobile phase consisting of acetonitrile and ammonium buffer (pH 8). The protonated ions of analytes were detected in positive ionization by multiple reactions monitoring (MRM) mode. The plasma method, with a lower limit of quantification (LLOQ) of 0.1 ng x mL(-1), demonstrated good linearity over a range of 0.1 - 30 ng x mL(-1) of olanzapine. Specificity, linearity, accuracy, precision, recovery, matrix effect and stability were evaluated during method validation. The validated method was successfully applied to analyzing human plasma samples in bioavailability study.
Antipsychotic Agents ; blood ; pharmacokinetics ; Benzodiazepines ; blood ; pharmacokinetics ; Biological Availability ; Chromatography, Liquid ; methods ; Humans ; Indicator Dilution Techniques ; Isotope Labeling ; Reproducibility of Results ; Sensitivity and Specificity ; Tandem Mass Spectrometry ; methods

Objective To evaluate the surgical approaches and therapeutic effect of lymphatic malformations located in head and neck in children. Methods Eleven cases of lymphatic malformations in the region of head and neck in children encountered between Jan. 1998 and Dec. 2008 in Peking University First Hospital were retrospectively analyzed. Initial diagnosis was made based on the physical examination and then confirmed by MR and Enhanced CT imaging. Surgical therapy was used for patients with lymphatic malformation which exceeds 4 cm. The operative technique was as follows: mass resection and superficial parotidectomy (4 cases), mass resection and total parotidectomy (2 cases), mass resection with neck dissection (2 cases), mass resection with neck dissection and sternotomy (1 case), marginal mandibular branch of facial nerve dissection and mass resection (2 cases). Dissection outside the false capsule was applied during the operation and facial nerve was dissected from bole to terminal arborization. Results The mass was completely removed in all 11 cases without organ dysfunction and obvious dysfigurement. The cure rate was 100%. Three cases suffered from a branch of facial nerve paralysis because of tension and 1 case had a Homer's syndrome after operation. One ease needed a blood transfusion (150 ml ) during the operation. All cases have been followed up with excellent results from 6 to 121 months, 32 months of the median, no mass recurrence. Conclusions Dissection outside the false capsule of mass and dissection of facial nerve were applied in the surgical treatment of huge lymphatic malformations. These methods are effective in the preservation of function and avoidance of abnormality.

Objective To compare the postoperative hemorrhage between standard uvulopalatopharyngoplasty(UPPP) and coblation assisted UPPP, and to evaluate the related risk factors and preventive measures. Methods Five hundreds and ninety seven patients with obstructive sleep apnea hypopnea syndrome(OSAHS) underwent UPPP and coblation assisted UPPP between January 1, 1999, and September 30, 2009 were reviewed retrospectively. Two hundred and sixty three patients with coblation assisted UPPP and 334 patients with standard UPPP were treated respectively. Single factor statistic analysis, multiple factors Logistic regress statistic analysis and Wilcoxon test method for related risk factors were applied. Results A total of 42 patients(7. 0% ) experienced postoperative bleeding. Among them,24 patients with coblation assisted UPPP (9. 1% ) and 18 patients with UPPP(5.4% ) had postoperative hemorrhage. Significant difference was not found in the degree of hemorrhage (z = 0. 784, P > 0. 05 ) ,hemorrhage site( x2 = 1. 387, P > 0. 05 ) and postoperative hemorrhage rates ( x2 = 3.14, P > 0. 05 )between the two surgical techniques. Significant difference was found in the interval of hemorrhage after surgery between the two surgical techniques ( x2 = 9. 25, P < 0. 01 ). History of hypertension, smoking,hepatic dysfunction was found to be correlated with the postoperative hemorrhage (Odd-ratio were respectively 7. 326, 3. 674, 2. 707). Conclusion Coblation technique did not significantly increase UPPP postoperative hemorrhage.

Objective To observe how complement regulatory protein CD59 expression on T cells in HIV infected patients and discuss the meaning of how highly active antiretroviral therapy(HARRT) affect CD59 expression. Methods 48 HIV infected patients and 14 healthy donors were performed in this study.Patients were divided into Naive group and On-HARRT group according to HARRT or not. The peripheral blood samples were collected and cell surface cytokines were stained, and then were evaluated with the BD FACS Canto flow cytometry, after that, the expression of CD59 on CD4+T, CD8+T and memory CD45ROCD4+T cells were analyzed, and HIVRNA were detected with PCR, then compare the results between groups. Results Compared with healthy donor, the expression of CD59 on T cells in HIV infected patients are significantly higher(P＜0.05), most of that expressed on CD45ROCD4+T cells(P＜0.05).Compared with Naive group, the CD59 expression on CD4+T cells in On-HARRT group decreased significantly but it is still higher while compared with healthy control(P＜0.05). CD59 expression on CD4+T cells is correlated with HIVRNA and CD4+T cells count(R2=0.2181, P=0.0247; R2=0.1586, P=0.0486). Conclusion HIV infection can cause CD59 expression increase on CD4+T cells and HARRT can decrease its expression. This increase may be related to HIV immune escape and CD4 +T cell function inhibition, and HARRT can partially reverse this immune disorder.

Objective To investigate the A (H1N1 ) influenza patients whose viral expulsion law and antiviral effecacy in Shenzhen city in 2009. Methods A (H1N1) flu virus nucleic acid positive by reverse transcription-polymerasechain reaction (RT-PCR) with nose swabs pharynx swabs two times were showed in 75 patients. Thereafter, to detect the virus nucleic acid once per day until negative for two days in a row. Begin the antiviral therapy with Oseltamivir (Ⅰ) or the Chinese medicine (Ⅱ) or Oseltamivir combined the Chinese medicine (Ⅲ) respectively for 5 days immediately after testing virus positive at the first time. T lymphocyte subpopulation and IL-17 were identified by flow cytometry. Results 78.7% ( 59/75) of patients whose mean age was (22.25±10.38) years old virus nucleic acid turned negative in 7 days of duration. 21.3% (16/75) of patients whose mean age was (17.16±13.66) years old virus were still positive after 7 days of duration. Analysis of humoral and cellular immune function in 56 patients with A (H1N1) flushowed down IL-17 expression compared with seasonal flu and health control(P ＜ 0.01 ). 10cases virus persistence more than 7 days showed down IL-17 expression( 1.91 ± 0. 80)compared with that of 46 cases virus persistence smaller or equal to 7 days ( 3.05±1.59 ) ( P ＜ 0.05 ). Likewise, the former showed significant low IL-17 expression compared with seasonal flu ( P＜ 0.01 ) and health control ( P ＜0.001 ). Virus-negative ratio was different among three antiviral groups after a standard treatment course of 5days. The ratio was 92.86% for group Ⅲ, 71.43% for group Ⅰ and 46.15% for group Ⅱ in turn. Virusnegative ratio of the former two group was significantly higher than that of group Ⅱ ( P＜0.01, P ＜0.05 respectively). It took smaller hours of getting normathermia after treatment in group Ⅲ than that of the other two groups( P ＜ 0.05 ). Conclusion IL-17 and age are possibly interrelate with A (H1N1)flu virus infection and virus persistence. Oseltamivir combined traditional Chinese medicine treatment shows its unique advantage in antiviral efficacy and to alleviate the symptoms.