Objective To investigate the clinical effect of lung equivalent uniform dose (LEUD)-based predictive model for radiation pneumonitis (RP) induced by volumetric modulated arc therapy (VMAT) and to determine the optimal a value.Methods A total of 65 patients with primary lung cancer who received VMAT from July 2015 to February 2016 were divided into RP group and non-RP group according to the presence or absence of RP after radiotherapy.Their dose-volume histogram (DVH) data and other data were obtained and analyzed by the self-compiled numerical analysis program.The LEUD values in the two groups were calculated at a=[-50, 50], and then the a value was identified when the relative difference of LEUD between the two groups was maximal.The paired t test was used for analyzing the differences in V5, V20, V30, minimum lethal dose (MLD), and LEUD (aoptimal) between the two groups.A Pearson correlation analysis was used to determine the correlation of Vdose and LEUD (aoptimal) with RP.The logistic regression method was used to establish the predictive model of RP.Results The maximum relative difference in LEUD between RP group and non-RP group was obtained at a=0.3(627.94 cGy vs.510.23 cGy, relative difference[R]=23.07%).R decreased slowly at t=[-50,-5], increased sharply at t=[-5, 0], and reached the maximum value at a=0.3.After a rapid decrease at a=[0.3, 4], R decreased slowly at a=[4, 50].The correlation analysis of the traditional physical volume dose threshold also showed that the LEUD (at a=0.3) was correlated with V5, V10, V20, and MLD (r=0.929, P<0.05).Conclusions For patients receiving VMAT for thoracic cancer, LEUD (at a=0.3) can distinguish between patients with and without RP.Therefore, LEUD is recommended to be<510 cGy.A combination of LEUD and conventional physical dose has a good clinical predictive value for RP under non-uniform irradiation.

Objective: To investigate the efficacy of pharmacist intervention in perioperative prophylactic application of antibiotics. Methods: From August 2017 to August 2018, 148 cases received surgery in Zhejiang Rongjun Hospital were selected, using odd-even grouping method, the patients were divided into two groups, with 74 cases in each group.The control group used antibacterial drugs without pharmacists intervention, the observation group used antibacterial drugs through pharmacists intervention.The use of antimicrobial agents was compared between the two groups. Results: The duration of prophylactic medication, the duration of hospitalization in the observation group were (2.59±0.24)d, (8.47±0.83)d, respectively, which in the control group were (3.76±0.36)d, (10.74±1.32)d, respectively, the differences between the two groups were statistically significant(t=23.262, 12.523, all P<0.01). The total cost of antibacterial drugs and the total drug cost in the observation group were (778.62±76.35)CNY, (3 036.75±302.11)CNY, respectively, which in the control group were (1 063.26±105.32)CNY, (4 698.64±1 452.28)CNY, respectively, and the differences between the two groups were statistically significant(t=18.823, 9.638, all P<0.01). The antibacterial drug use satisfaction of the observation group was 97.30%(72/74), which of the control group was 74.32%(55/74), the difference between the two groups was statistically significant(χ²=16.038, P<0.01). Conclusion The rational use of antibiotics can be promoted by pharmacist intervention in perioperative prophylaxis patients.

Objective:To explore the correlation between the expression of signaling lymphocyte activation molecule family 6 (SLAMF6) on peripheral blood CD8 +T cells and perforin and granzyme B and the clinical significance in patients with newly diagnosed severe aplastic anemia(SAA). Methods:The indicators of blood routine and bone marrow and peripheral blood samples of 32 newly diagnosed SAA patients admitted to Henan Provincial People′s Hospital from January 2016 to June 2019 were collected for retrospective analysis. Flow cytometry was used to detect the expression of SLAMF6, perforin and granzyme B on samples CD8 +T cell before therapy and 6 months after therapy (11 cases received transplantation, 21 cases received immunosuppressive therapy [IST]). Spearman correlation analysis was performed to determine the association between clinical indicators and laboratory test results. The expression of SLAMF6, perforin and granzyme B was also detected in 10 healthy people (normal group) and 13 myelodysplastic syndromes/paroxysmal nocturnal hemoglobinuria (MDS/PNH) patients (MDS/PNH group). Results:(1) At diagnosis: the expression of SLAMF6 was significantly lower in the SAA group than that in the normal group and the MDS/PNH group ([56.40±6.37]% vs [84.34±5.81]% and [82.24±4.98]% (both P<0.001]). The expression of perforin was significantly higher in the SAA group (32.73±8.46) than that in the normal control group (23.75%±5.10%), and the MDS/PNH group (26.12%±5.53%) (both P<0.05). The expression of granzyme B was also significantly higher in the SAA group (36.23%±7.94%) than that in the normal control group (21.67%±5.05%) and the MDS/PNH group (21.79%±5.10%) (both P<0.001). The expression of SLAMF6 was positively correlated with the hemoglobin ( r=0.804), and reticulocyte absolute values ( r=0.656) in peripheral blood, percentage of granulocytes ( r=0.643) and erythrocytes ( r=0.622) in bone marrow of SAA patients (all P<0.05). Expression of SLAMF6 was negatively correlated with perforin ( r=-0.792) and granzyme B ( r=-0.908) on CD8 +T cells in patients with SAA (both P<0.001). (2) After treatment: the expression of SLAMF6 in peripheral blood CD8 +T cells of 30 surviving patients was higher than pre-treatment ([79.19±12.69]% vs [56.40±6.37]%, P<0.001). The expressions of perforin and granzyme B were lower than pre-treatment level (both P<0.05). The expression of SLAMF6 on CD8 +T cells in 11 transplanted patients was higher than before transplantation ([86.54±3.75]% vs [56.40±7.35]%, P<0.001). The expressions of perforin and granzyme B were lower than before transplantation (both P<0.05). The expression of SLAMF6 on CD8 +T cells in 12 IST-respond patients was higher than that before treatment, while the perforin and granzyme B levels were lower than pre-treatment (all P<0.05). The post-treatment expressions of SLAMF6, perforin and granzyme B were similar as before treatment levels in 7 IST-unrespond patients (all P>0.05). Conclusion:SLAMF6 is significantly down-regulated on CD8 +T cells in newly diagnosed SAA, negatively correlated with the effective factors of CD8 +T cells, which might participate in the immune regulatory of CD8 +T cells as a negative regulatory factor in patients with SAA. The SLAMF6 is significantly up-regulated after hematopoietic recovery, while there is no significant change in treatment-unrespond patients, which could thus serve as an useful diagnostic and therapeutic index of patients with SAA.

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) . Methods: The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT). Results: The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively (χ²=13.302, P=0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ²=0.959, P=0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ²=5.892, P=0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ²=0.959, P=0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ²=1.158, P=0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD(χ²=0.230, P=0.891; χ²=2.628, P=0.269; χ²=3.187, P=0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ²=0.330, P=0.845]. Severe post-transplant infection (RR=4.617, P=0.009), grade Ⅲ/Ⅳ aGVHD (RR=2.707, P=0.048) were independent risk factors for OS. Conclusion The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.

OBJECTIVE: To explore the correlation between altered levels of neurotransmitters in the frontal lobe and hippocampus and behavioral abnormalities in a Clock variant mice modeling bipolar disorder manic disorder. METHODS: Open field test and Elevated plus-maze test were carried out on the Clock mutant and wild-type control groups. The frontal lobe and hippocampus of Clock mutant mice and controls were dissected, and neurotransmitters in tissue extracts were analyzed by high-performance liquid chromatography and mass spectrometry. The concentration of neurotransmitters and behavioral indicators were assessed by t test and Pearson correlation analysis using SPSS 22.0. RESULTS: The Clock mutant mice showed a significant increase in activity, albeit with no difference in the level of anxiety from the wild-type controls, which suggested that the Clock mutant mice can be used as a model for manic attack of bipolar disorder. Altered neurotransmitter levels were detected in the frontal and hippocampal regions, including elevated histamine in the left hippocampus, reduced histamine in the right hippocampus, reduced gamma-aminobutyric acid (GABA) in bilateral hippocampus, elevated dihydroxyphenylalanine (DOPA) in the left frontal lobe and reduced DOPA in the right hippocampus, and decreased glutamine in bilateral frontal lobes. The reduced glutamine in the left frontal lobe and GABA in the right hippocampus correlated with the increased activity of Clock mutant mice. CONCLUSION Clock mutant mice showed abnormal behavior with increased activity. Reduced glutamine in the left frontal lobe and GABA in the right hippocampus were correlated with increased activity.

Humans ; Depressive Disorder, Major ; Motor Cortex ; Magnetic Resonance Imaging

Objective To construct an objective analysis system of corneal nerve tortuosity and detect the changes of corneal subbasal nerve tortuosity in patients with dry eye and diabetes. Methods GradeⅠtoⅣnerve tortuosity were evaluated and 80 photos of each grade were randomly chosen from the in vivo confocal microscopy library. Nerve fibers were extracted,segmented and then analyzed by 6 tortuosity related parameters including L C, Seg L C mean,Cur mean,Specific p,ICM and SCC mean. After verifying the validaty of parameters above,a cross-sectional study was conducted. Subjects were collected from June,2018 to February,2019 in Peking University Third Hospital,and were divided into healthy control group (28 persons 56 eyes),dry eye without diabetes group (28 patients 56 eyes),diabetes without dry eye group(24 patients 48 eyes),diabetes with dry eye group (23 patients 46 eyes) . Basic and dry eye information includes sex,age,ocular surface disease index ( OSDI) ,tear film break-up time (TBUT),Schirmer Ⅰ test (SⅠt) and corneal fluorescence staining (CFS) score. Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were detected in diabetic patients. Cochet-Bonnet examination (C-BE) was detected to evaluate corneal sensation and 2 corneal subbasal nerve photos of each eye were selected for effective tortuosity and density related parameters analysis. Data was analyzed by SPSS and diagnostic test were perfomed by MedCalc. This study followed the Declaration of Helsinki. This study protocol was approved by Ethic Committee of Peking University Third Hospital ( No. IRB00006761-M2017354 ) . Written informed consent was obtained from each subject prior to entering study cohort. Results L C,Seg L C mean,Cur mean,Specific p,ICM and SCC mean increased as the nerve tortuosity increased from Grade Ⅰ to Grade Ⅳ,with an overall significance among 4 groups (F=39. 100, 36. 367,57. 743,4. 043,6. 818,33. 493;all at P<0. 01). Among the above 6 parameters,Cur mean and L C of any two groups were of significant difference (all at P<0. 01). Twenty three to twenty eight persons were enrolled in each group of the cross-sectional study. Sex and age were comparable among 4 groups. Diagnostic criteria were met in dry eye and diabetes. Corneal sensation parameter C-BE decreased in diabetes without dry eye group and diabetes with dry eye group compared with healthy control group ( all at Adj P<0. 05 ) , other than in dry eye without diabetes group (AdjP≥0. 05). Nerve density of diabetes without dry eye group and diabetes with dry eye group was lower compared with healthy control group(all at P<0. 001),while no significant difference between dry eye without diabetes group and healthy control group(P≥0. 05). Among the effective parameters of tortuosity,L C,Cur mean,Seg L C mean and SCC mean of dry eye without diabetes group,diabetes without dry eye group,diabetes with dry eye group were higher compared with healthy control group ( all at P<0. 05 ) . Diagnostic tests of tortuosity related parameters all showed an area under curve (AUC) from 0. 5 to 0. 7. Conclusions L C and Cur mean can be used to analyze corneal nerve curvature more reliably. Compared with normal volunteers,patients of dry eye or diabetes show higher corneal subbasal nerve tortuosity.

Objective To evaluate the efficacy of Budesonide/formoterol to control asthma under real-life conditions.Methods A muhi-center, open label, non-interventional study was conducted.Asthma control after 12 week therapy with Budesonide/formoterol was assessed by Asthma Control Questionnaire (ACQ) and modified Asthma Control Questionnaire (ACQ5).Results A total of 360 asthma patients were recruited,including 228 adult patients and 132 child patients.After 12 weeks' therapy,all the patients' medium value of ACQ was decreased significantly from 2.03 (adults 2.20, children 1.74) at baseline to 0.60 (adults 0.78, children 0.29) (P < 0.0001), and the medium value of ACQ5 was also decreased significantly from 2.4 (adults 2.24, children 1.76) at baseline to 0.47 (adults 0.62, children 0.20) (P < 0.0001).Conclusion Budesonide/formoterol is effective in asthma treatment, by which most asthma patients obtain and maintain clineal control.

Objective: To explore the efficacies of regimens of three-drug induction therapy (ATRA+ATO+anthracyclines) versus two-drug induction therapy (ATRA+ATO) in patients with acute promyelocytic leukemia (APL). Methods: Of 184 patients diagnosed with APL from January 2009 to March 2016, 58 patients underwent three-drug induction therapy, while the rest were treated with two-drug induction therapy. Three-drug induction therapy was of ATRA (20 mg·m^-2·d^-1, d_1-28) + ATO (0.16 mg·kg^-1·d^-1, d_1-28) + Idarubicin (8 mg·m^-2·d^-1, d_3-5) /daunorubicin (40 mg·m^-2·d^-1, d_3-5) , while two-drug induction therapy ATRA+ATO with the same doses and methods as above. Of 184 cases, 69 cases accompanied with WBC counts>10×10⁹/L, 115 cases with WBC counts≤10×10⁹/L at onset. Results: ①Short-term efficacy: After one cycle induction therapy, the rates of hematologic remission, genetic remission, molecular remission and induced differentiation syndrome (DS) in three-drug regimen group were 98.3%, 87.9%, 72.4% and 0 respectively, while those in two-drug regimen group were 87.3%, 65.9%, 51.6% and 12.7% respectively. In patients with WBC >10×10⁹/L, DS rate and early mortality in three-drug regimen group were lower than in two-drug regimen group (0 vs 15.6%, 4.2% vs 15.6%, respectively). In patients with WBC≤10×10⁹/L, DS rate in three-drug regimen group was also lower than in two-drug regimen group (0 vs 12.3%) , but there were no statistical differences in terms of relapse and early mortality. ② Long-term efficacy: The relapse rate, overall survival (OS) and disease free survival (DFS) in three-drug regimen group were 0, 98.5%, 96.6% respectively, while those in two-drug regimen group were 8.6%, 86.5% and 84.1% respectively; the advantages of three-drug over two-drug regimen, especially in cases of WBC >10×10⁹/L were observed. ③ Side effects: the incidences of gastrointestinal reaction, liver dysfunction, myocardial damage and headache in three-drug regimen group hardly increased. Conclusion The efficacies of three-drug induction therapy were superior to two-drug one.

Objective: To explore the prognostic value of CD34, CD2, CD56 expressions and FLT3-ITD mutation in adults with acute promyelocytic leukemia (APL) . Methods: The immuno-phenotypic and molecular characteristics of 137 adult patients with APL (from January 2010 to March 2016, in Henan Provincial People’s Hospital) were investigated. And the relationships between CD34, CD2, CD56 expressions, FLT3-ITD mutation and the outcomes of high WBC counts at onset, complete remission (CR) rate, early mortality, relapse rate (RR) , overall survival (OS) , disease free survival (DFS) were explored. Results: ①Among the 137 patients, the positive ratios of CD34, CD2, CD56 expressions and mutation rate of FLT3-ITD were 26.3%, 25.5%, 10.2% and 17.5%, respectively. The morbidities of positive CD34, CD2, CD56 expressions and FLT3-ITD mutation in the high-risk group were 43.2%, 47.7%, 18.2% and 27.3% respectively, while those in the low-/intermediate-risk groups were 18.3%, 15.1%, 6.5% and 12.9%, respectively (P<0.05) . ②At a median follow-up of 41 months, the total CR rate of the 137 adults APL patients was 96.9%, early mortality 6.6% and relapse rate 7.3% respectively. And RR of positive CD34 or CD2 expression patients was higher than negative CD34/CD2 expression ones (18.8% vs 3.3%, χ²=8.462, P=0.004; 16.1% vs 4.3%, χ²=4.382, P=0.028, respectively) . In addition, the early mortality of patients with positive CD56 expression or FLT3-ITD mutation was extremely higher than in negative ones (21.4% vs 4.9%, χ²=5.610, P=0.018; 16.7% vs 4.4%, χ²=4.833, P=0.028, respectively) . ③The whole OS and DFS were 88.3% and 84.7%, respectively. Wherein, OS and DFS in patients with CD34⁺, CD56⁺ or FLT3-ITD mutation were worse (P<0.05) . Conclusions Positive CD34, CD2, CD56 expression and FLT3-ITD mutation were latent poor prognostic factors in adults with APL.