ObjectiveTo investigate the effects and mechanism of the combination of arsenic trioxide （ATO） and its dimethylarsinic acid （DMAV） metabolite on apoptosis of human acute promyelocytic leukemia NB4 cells by affecting the balance of metabolic reaction. MethodsThe rats were injected with the same amount of sterile normal saline， ATO（1.6 mg·kg^-1）， and DMAV（4， 8， 16， and 32 mg·kg^-1） combined with ATO（1.6 mg·kg^-1）， respectively， to obtain the corresponding drug-containing serum. The effect of drug-containing serum on the proliferation of NB4 cells was detected by the cell counting kit-8 （CCK-8 ）method. Apoptosis was detected by flow cytometry with Annexin-V-FITC/PI double staining. Intracellular reactive oxygen species （ROS） accumulation was detected by flow cytometry using fluorescent probe DCFH-DA. The changes of mitochondrial membrane potential （Δψm） were detected by the fluorescence probe JC-1. Western blot detected the expression of apoptosis-related proteins， namely B-cell lymphoma-2（Bcl-2）-associated X protein（Bax）/Bcl-2， Cytochrome C， cleaved Caspase-9， and cleaved Caspase-3， as well as c-Jun N-terminal kinase（JNK） phosphorylation levels. Results①The Combination of the two drugs had a higher proliferation inhibition rate and more apoptosis than ATO alone. ②The combination of two drugs can significantly increase the production of ROS compared with any single treatment group. ③The Δψm was significantly reduced in the two-drug combination group compared with any single treatment group. ④Compared with either group， the combination group significantly released Cytochrome C， significantly down-regulated the expression of Bcl-2， and up-regulated the expression of Bax， cleaved Caspase-3， and cleaved Caspase-9. ⑤The phosphorylation level of JNK was significantly up-regulated in the two-drug combination group compared with any single treatment group. ConclusionThe combination of DMAV and ATO may synergistically induce mitochondrial apoptosis through ROS-mediated oxidative stress， triggering Δψm dissipation and Cytochrome C release. By activating Caspase-9/Caspase-3 and the phosphorylation level of JNK， the Bcl-2 family protein （Bax/Bcl-2） was regulated to promote the apoptosis of NB4 cells.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

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 analyze the biophysical dosimetric characteristics and clinical application ability of VMAT technology for breast cancer post-mastectomy.Methods 28 patients with breast cancer (10 at left side and the other at right side) were planned in different ways respectively.One was two 90 degree arc VMAT plan and the other were 5 beam IMRT plan.The dosimetric parameters of two different plans including tumor control probability (TCP),conformity index(CI),homogeneity index (HI),V95and V110 in target,normal tissue complication probability (NTCP),V5,V20,V30 for ipsilateral lung,NCTP,D V25 for heart,D for the contralateral breast in OARs,MU and times were compared.Results The average tumor control probability (TCP) in VMAT and IMRT group was(96 ±2)％ and (90 ±2)％ (t =-6.28,P ＜ 0.01),respectively.The PTV dose average homogeneity index (HI) of VMAT plans was better than that of IMRT plan (0.15 ±0.04 vs 0.22 ±0.02,t =13.29,P ＜0.01).For cancer position in left side,the mean dose of heart was decreased by 433.24 cGy in the VMAT plan.The NTCP of the hearts in VMAT plans had statistically significant difference compared with IMRT plans [(1.00±0.12)％ vs (1.70±0.13)％,t =2.14,P ＜0.05].For plans of right breast cancer,the average mean dose of hearts in two control group was (3.27 ± 0.26) Gy and (6.00 ± 0.47) Gy (t =9.21,P＜0.01).The total monitor unit (MU) was 530.7 in the VMAT arm and 693.9 in the IMRT arm (t =9.58,P ＜0.01).The treatment time was shorter in VMAT arm (t =8.40,P ＜0.05).Conclusions VMAT plans have better clinical value and more superior biophysical dosimetric characteristics for breast cancer post-mastectomy.