Aim: To establish a linear additive model for the predication of in vitro sinomenine hydrochloride release from the combination of immediate release, enteric-coated and sustained-release pellets based on the release profiles of each pellet type. Methods: Immediate release pellets were manufactured by extrusion/spher-onization technology. The operation of bottom-spraying in the fluid-bed equipment was conducted to enteric-coating using Eudragit~(R) L-30D-55 and sustained-release coating using Surelease~(R) . In vitro sinomenine hydrochloride release profiles of both uncoated and coated pellets were fitted to the chosen mathematical equations offered by the curve fitting toolbox of Matlab~(R) before a linear additive model was created based upon the best-to-fitting equations. The proportion of each pellet type in the combined format to generate the desired 24 h sinomenine hydrochloride release profile was solved by Matlab~(R). The predicted and assayed sinomenine hydrochloride release from the polled pellets was compared. Results: It was shown that the actual sinomenine hydrochloride release profiles of each pellet type were approximate to those of predicted ones. A linear additive model of the appropriate mathematical equations of each pellet was proven to be capable of controlling in vitro release of sinomenine hydrochloride multiple-unit pellets. Conclusion: A multiple-unit combined system of the selected pellets, as a novel sustained-release system, was successfully prepared. In vitro release performance of the calculated combination of each pellet type could be guaranteed by this approach in designing sustained-release drug delivery system.

Objective: This study aimed to translate the English version of the Perceived Competence Scale for Disaster Mental Health Workforce (PCS-DMHW) into Chinese, and to test its reliability and validity in Chinese mental health workers. Methods: With the consent of Professor Choi, Keimyung University, Korea, and the authorization of the scale, the English version of PCS-DMHW was translated, retranslated and culturally debugged to form the Chinese version of PCS-DMHW. The general information questionnaire and the Chinese version of PCS-DMHW scale were used to investigate 706 mental health workforce from 9 tertiary hospitals in Sichuan province in China from March 24, 2020 to April 14, 2020. The Cronbach’s α coefficient was used to evaluate the internal consistency reliability of the scale, and the test-retest correlation coefficient r was used to evaluate the test-retest reliability of the scale. The content validity indexes (CVI) and exploratory factor analysis (EFA) was used separately for evaluating the content validity and structure validity of the scale. Results: The Cronbach’s α coefficient of the Chinese version of PCS-DMHW total scale, individual competences and organizational competences subscale was 0.978, 0.956, and 0.964, respectively. The test-retest reliability of the total scale, individual competences and organizational competences subscale was 0.949, 0.932 and 0.927, respectively. The item-level CVI of all scale were ranged from 0.833–1.000, the scale-level CVI (S-CVI)/universal agreement of the total scale, individual competences and organizational competences subscale was 0.833, 0.875, and 0.857, respectively, and the S-CVI/average was 0.972, 0.979, and 0.976, respectively. EFA showed that two principal components were extracted from the subscale of individual competences and organizational competences. Conclusion The Chinese version of PCS-DMHW has good reliability and validity, and can be widely used in China.

OBJECTIVETo identify differentially expressed genes between chronic phase and blast crisis in chronic myeloid leukemia, explore the mechanism and screen potential biomarkers of disease progression.

METHODSThe differences in the gene expression profiles of bone marrow mononuclear cells between chronic phase and blastic crisis were examined using DNA microarray. PANTHER database, Genomatix database and Bibliosphere software were used to analyze and predict the critical genes or transcription factors during disease progression. Some of the genes or transcription factors were selected for verification by semi-quantitative RT-PCR.

RESULTSIn blastic crisis, 68 of the 1176 tested genes were obviously up-regulated. Sixteen of these differential genes were selectively expressed in leukocyte membranes. CD40, CCR3, LGALS3, RGS3, CEACAM3 and the related transcription factors RAC1, CTNNB1, TP53, and NF-κB, all as the nodes of the entire regulatory network, were presumed to play key roles in disease progression. The results of RT-PCR were consistent with the microarray data and showed high expression of CEACAM3, RGS3, CTNNB1 and RAC1 in blastic crisis.

CONCLUSIONA group of genes have been identified to very likely play key roles or serve as biomarkers in the transition from the chronic phase to blastic crisis in chronic myeloid leukemia.

Blast Crisis ; genetics ; Computational Biology ; Gene Expression Profiling ; Gene Expression Regulation, Leukemic ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Oligonucleotide Array Sequence Analysis ; Transcriptome

Objective To evaluate the efficacy of rescue treatment for recurrent esophageal cancer after radical esophagectomy, and to provide insights into the development of comprehensive treatment for esophageal cancer.Methods The clinical data of 218 patients who were confirmed with recurrent metastatic esophageal cancer after R0 resection and received rescue treatment in our hospital from 2004 to 2014 were retrospectively reviewed.The survival rate was determined by the Kaplan-Meier method.Univariate and multivariate prognostic analyses were performed using the log-rank test and Cox proportional hazards model, respectively.Results The median post-recurrence follow-up time was 53 months.The 1-and 3-year overall survival (OS) rates after recurrence were 57.2% and 24.4%, respectively.Among the 163 patients with local recurrence, the 1-and 3-year OS rates were 70% and 42% for patients treated with chemoradiotherapy (n=40), 55% and 24% for those with radiotherapy alone (n=106), and 23% and 8% for those with supportive therapy (n=13)(chemoradiotherapy vs.radiotherapy alone P=0.045, radiotherapy alone vs.supportive therapy P=0.004;none of the patients who were treated with chemotherapy alone survived for one year or more).Univariate analysis showed that N staging, TNM staging, and post-recurrence rescue treatment regimen were independent prognostic factors for esophageal cancer (all P=0.001).On the other hand, multivariate analysis indicated that only rescue treatment regimen was the independent prognostic factor for esophageal cancer (P=0.013).Conclusions Rescue chemoradiotherapy or radiotherapy alone can bring significant survival benefits for patients with recurrent and metastatic, especially locally recurrent, esophageal cancer following radical esophagectomy.

OBJECTIVETo investigate the cytogenetic differences between children and adults with acute lymphoblastic leukemia (ALL) using eight-probe fluorescence in situ hybridization and karyotype analysis.

METHODSEight-probe (MYC, P16, E2A, TEL/AML1, BCR/ABL , MLL , IGH, and hyperdiploidy) fluorescence in situ hybridization and karyotype analysis were performed for 86 adults and 39 children with acute lymphoblastic leukemia.

RESULTSEight-probe fluorescence in situ hybridization showed significant differences in the positivity rate of TEL/AML1, BCR/ABL, and hyperdiploidy between adult patients and children with ALL. By karyotype analysis, the positivity rate of t(9;22) and hyperdiploidy differed significantly between the children and adult patients (P<0.05).

CONCLUSIONAdults and children with ALL have different expression profiles of the fusion genes. Eight-probe fluorescence in situ hybridization is time-saving, accurate and efficient in detecting common genetic abnormalities in ALL patients, and can be well complementary to karyotype analysis in clinical diagnosis of ALL.

Adolescent ; Adult ; Child ; Child, Preschool ; Cytogenetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Infant ; Karyotype ; Karyotyping ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; genetics ; Young Adult

Objective To explore the incidence and related predictive factors for acute symptomatic esophagitis in patients with locally advanced non?small cell lung cancer ( NSCLC ) treated with intensity?modulated radiation therapy ( IMRT) . Methods Data were collected retrospectively from 256 patients with inoperable or unresectable stage Ⅲ NSCLC treated in our hospital between January 2007 and December 2011. The radiotherapy target volume included primary lung cancer and lymphatic drainage area involved,with a median dose of 60 Gy in 30 fractions (50-70 Gy).Of all the patients,109 patients (42.6%) received concurrent chemotherapy. Grade ≥2 acute esophagitis ( AE ) ( symptomatic esophagitis ) which occurred during radiotherapy and within 3 months after completion of radiotherapy served as the outcome event. National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0( NCI?CTCAE3.0) was used to evaluate the grade of AE. The logistic regression model was used to analyze the predictive factors. Results A total of 174 patients ( 68%) had treatment?related grade ≥2 AE;154 patients ( 60. 2%) had grade 2 AE and 20 patients (7.8%) had grade 3 AE.The median dose when grade≥2 AE occurred was 30 Gy (11?68 Gy).For grade≥2 AE,multivariate analysis showed that esophageal V5?V60,mean dose,and age were independent predictive factors (P=0.021,0,0.010).For grade ≥3 AE,multivariate analysis showed that esophageal V50?V60 ,concurrent chemotherapy,and body mass index ( BMI) were independent predictive factors ( P= 0.010,0.003,0.019 ) . Old age and higher BMI were the protective factors for grade≥2 and ≥3 AE, respectively. Conclusions For patients with locally advanced NSCLC treated with IMRT, esophageal V50—V60 and concurrent chemotherapy are predictive factors for grade ≥3 AE,and esophageal V50 has a high predictive value for both grade ≥2 and ≥3 AE.

Objective:To evaluate the clinical efficacy and failure patterns of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (LS-SCLC) on the basis of modern chemoradiotherapy and diagnostic techniques.Methods:In this retrospective study, clinical data of 201 LS-SCLC patients treated with chemotherapy (EP/CE regimens, ≥4 cycles) and intensity-modulated radiotherapy (IMRT) in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were reviewed. All patients were primarily managed with concurrent or sequential chemoradiotherapy and achieved complete response (CR) or partial response (PR). Ninety percent of patients were revaluated for brain metastasis (BM) by MRI and 10% by CT scan. Long-term survival and failure patterns were compared between the PCI ( n=91) and non-PCI groups ( n=110). Results:The median follow-up time was 77.3 months (95% CI 73.0-81.5 months). The median overall survival (OS), 2-and 5-year OS rates were 58.5 months, 72.5% and 47.7% in the PCI group, and 34.5 months, 61.7% and 35.8% in the non-PCI group ( P=0.075). The median progression-free survival (PFS), 2-and 5-year PFS rate were 22.0 months, 48.0% and 43.4% in the PCI group, significantly higher than 13.9 months, 34.4% and 26.7% in the non-PCI group ( P=0.002). The 2- and 5-year cumulative incidence of BM were 6.6% and 12.2% in the PCI group, and 30.0% , 31.0% in the non-PCI group ( P=0.001). The median time and rate of BM as an isolated first site of relapse were 11.9 months and 4.4% in the PCI group, and 8.7 months and 25.5% in the non-PCI group ( P<0.001). Multivariate analysis showed that response after chemoradiotherapy ( P<0.001) and PCI ( P=0.033) were the independent prognostic factors for PFS. Stratified analysis demonstrated that PCI significantly improved the 5-year PFS in patients who achieved CR (72.7% vs. 48.0%, P=0.013), while it did not improve the 5-year PFS in patients who obtained PR (26.1% vs. 20.2%, P=0.213). Conclusion:In the new era of standard chemoradiotherapy and more accurate diagnostic methods for BM, PCI was associated with improved PFS and lower incidence of BM in LS-SCLC patients.

Objective:To prepare polyvinyl alcohol (PVA) and hydroxyapatite (HA) composite embolization microspheres and investigate their physicochemical properties.Methods:PVA/HA composite embolization microspheres were prepared by reverse suspension polymerization, using PVA and HA as dispersed phases, liquid paraffin containing sorbitan fatty acid ester as the continuous phase, and glutaraldehyde as the cross-linking agent. The morphology, particle size distribution, and microscopic morphology of PVA/HA composite embolization microspheres were observed by optical microscopy and scanning electron microscopy. The chemical structure of PVA/HA composite embolization microspheres and the elasticity, drug loading, and drug release properties of PVA/HA composite bolus microspheres were characterized by Fourier infrared spectroscopy.Results:The PVA/HA composite embolization microspheres were internal, porous round spheres with a particle size distribution of 50-300 μm. The elastic properties of PVA/HA composite embolization microspheres were(13.6±0.145) kPa, which was 2.28 times that of PVA microspheres, and the drug loading capacity and encapsulation efficiency were (76.80±1.22) mg/g and (38.4±12.7)%, respectively. The maximum cumulative release rate of the microspheres within 7 days was (7.37±0.101)%, and the maximum cumulative release was (256.2±9.8) μg.Conclusions:PVA/HA composite embolization microspheres have good mechanical properties and drug-loading and drug-releasing properties, which provide an important reference for their use as medical devices.

Objective To investigate the clinical efficacy and prognosis of intensity-modulated radiotherapy(IMRT)combined with chemotherapy for limited-stage small cell lung cancer(LS-SCLC). Methods A retrospective analysis was performed on the clinical data of 484 LS-SCLC patients treated with chemoradiotherapy in our center from 2006 to 2014. The patients with partial or complete response to IMRT received prophylactic cranial irradiation(PCI). The Kaplan?Meier method was used to calculate survival rates, and the log-rank test and Cox regression were used for univariate and multivariate analyses, respectively. Results In all the patients, the follow-up rate was 93%;the median overall survival(OS) time was 23.8 months;the 2-,3-,and 5-year OS rates were 48.7%,39.8%,and 28.6%,respectively;the median progression-free survival(PFS)time was 14.1 months;the 2-, 3-, and 5-year PFS rates were 34.4%,30.5%, and 28.3%, respectively. The incidence rates of grade ≥3 bone marrow suppression, grade ≥2 radiation esophagitis, and grade ≥2 radiation pneumonitis were 26.9%, 24.8%, and 18.4%, respectively, in SCLC patients after IMRT. The objective response rate was 84.5%. The univariate analysis showed that age, smoking history, TNM stage, PCI, and the number of chemotherapy cycles before radiotherapy were prognostic factors for OS(P= 0.006, 0.001, 0.047, 0.000, and 0.046). The multivariate analysis showed that smoking history and PCI were independent prognostic factors(P=0.001 and 0.000).Conclusions IMRT combined with chemotherapy achieves satisfactory clinical outcomes in the treatment of LS-SCLC. Smoking history and PCI are independent prognostic factors for OS of LS-SCLC patients.

Objective To evaluate the dose distribution and clinical efficacy of hippocampal-sparing prophylactic cranial irradiation ( HS-PCI ) in patients with small cell lung cancer by using helical tomotherapy. Methods Clinical data of 49 patients with small cell lung cancer receiving HS-PCI using helical tomotherapy in Cancer Hospital between 2014 and 2017 were retrospectively analyzed. All patients received brain MRI to exclude the possibility of brain metastasis within 1 month after standard surgery or radio-and chemo-therapy. The prescription dose was 95% PTV,25 Gy in 10 fractions. The adverse reactions and cognitive functions of patients were observed before,6 months and 1 year after treatment,and the dose distribution in the hippocampal gyrus,survival rate and brain metastasis rate were analyzed. Results The median follow-up time was 16 months. The average dose in the hippocampal gyrus was 7. 23 Gy and 8. 46 Gy in the reduction region,which was reduced by 71. 88% and 66. 16% compared with the prescription dose. The maximum dose in the hippocampal gyrus was 10. 66 Gy and 15. 43 Gy in the reduction region. Among 49 patients,8 died,the 1-year survival rate was 85. 1% and the 2-year survival rate was 70. 3%.Nine patients (18. 3%) had brain metastases,and one of them with extensive multiple brain metastases (n＝13) presented with metastasis adjacent to the hippocampal gyrus. The main adverse reactions included mild headache, dizziness and brain edema,whereas no ≥ grade 2 adverse reactions occurred. At 6 months after treatment, the HVLT-R score was significantly decreased,and declined by 6. 78% at 12 months after treatment. The HVLT-R scores did not significantly differ in patients without brain metastasis before and 12 months after treatment ( P＞0. 05 ). Conclusion Application of HS-PCI using helical tomotherapy meets the dose requirement,effectively protects the cognitive function and yields slight adverse reactions.