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 analyze the effect of the fixed-jaw technique on dosimetric parameters during dynamic intensity-modulated radiotherapy (DIMRT) planning. Methods Ten patients each with nasopharyngeal carcinoma, postoperative cervical cancer, and right breast cancer after radical surgery were selected for this study; all patients underwent DIMRT in our hospital in 2020. After administration at the prescribed dose, two methods were used to design the radiotherapy plan for each patient: split-field technique (SFT) and fixed-jaw technique (FJT). The two plans were compared for the differences in the dosimetric parameters and plan verification pass rate. Results Compared with SFT, FJT showed significant decreases (P <0.05) in the following parameters for patients with nasopharyngeal carcinoma, postoperative cervical cancer, and right breast cancer after radical surgery: number of radiation fields (down by 41.5%, 47.3%, and 34.9%, respectively, t = 7.954, 24.2, and 4.949, respectively), total number of monitor units (MUs) (down by 5.6%, 5.3%, and 13.5%, respectively, t = 3.211, 2.423, and 5.481, respectively), and actual beam-on time (down by 25.3%, 23.8%, and 13.6%, respectively, t = 5.814, 9.208, and 5.655, respectively). There were significant differences in some of the dosimetric parameters for all three types of cancer patients between the two plans (P <0.05). There were no significant differences in the plan verification pass rate (P >0.05). Conclusion FJT can reduce the total number of MUs and actual beam-on time while meeting the requirements for clinically prescribed doses in DIMRT planning.

Objective:To explore the association of DNA methylation with immune response to hepatitis B (HepB) vaccine in Han nationality children from Guangxi province.Methods:A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method. Children with the HepB surface antibody concentration(Anti -HBs)<100 mIU/ml was set as the case group and ≥100 mIU/ml as the control group. Multiplex PCR and heavy sulfite sequencing were used to treat the samples. Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites. Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level. Results:There were 104 children in the case group and 159 in the control group. The median ( Q1, Q3) level of anti -HBs in two groups were 62.34 (30.06, 98.88) mIU/ml and 1 089.10 (710.35, 1 233.45) mIU/ml. The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group ( P<0.05). The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44 ( OR=1.18, 95% CI: 1.03-1.35) and 93 ( OR=1.21, 95% CI: 1.07-1.38) locus was associated with the HepB response level. Conclusion:The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.

Objective:To explore the association of DNA methylation with immune response to hepatitis B (HepB) vaccine in Han nationality children from Guangxi province.Methods:A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method. Children with the HepB surface antibody concentration(Anti -HBs)<100 mIU/ml was set as the case group and ≥100 mIU/ml as the control group. Multiplex PCR and heavy sulfite sequencing were used to treat the samples. Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites. Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level. Results:There were 104 children in the case group and 159 in the control group. The median ( Q1, Q3) level of anti -HBs in two groups were 62.34 (30.06, 98.88) mIU/ml and 1 089.10 (710.35, 1 233.45) mIU/ml. The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group ( P<0.05). The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44 ( OR=1.18, 95% CI: 1.03-1.35) and 93 ( OR=1.21, 95% CI: 1.07-1.38) locus was associated with the HepB response level. Conclusion:The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.

Objective:To explore the establishment of disease assessment index model in silicosis patients.Methods:In October 2018, 171 silicosis patients who were hospitalized from November 2014 to November 2015 were selected as the study subjects. According to the standard of death risk, the subjects were divided into two groups, including the group without death risk (153 cases) and the group with death risk (18 cases) . Through literature analysis and clinical experience, the variables related to silicosis were preliminarily screened. Multifactorial logistic regression analysis variables were used to analyze the relationship between the variables and the risk of death. The variables associated with the risk of death were selected as the final variables to establish the disease assessment index model. And the receiver operating characteristic (ROC) curve was used to evaluate the clinical application of the disease assessment index.Results:Five variables of Modified British Medical Research Council Respiratory Questionnaire (mMRC) , pulmonary function injury, pneumoconiosis stage, aggravation of the disease and complications were selected as the variables of the disease assessment index, and the assessment index score ranged from 1 to 11 points. The area under the ROC curve of disease assessment index was 0.747 (95% CI: 0.590-0.904) , which could better identify the death risk of silicosis patients. With the increase of disease assessment index score, the death risk of silicosis patients increased. When the cutoff value was 7, the sensitivity and specificity were 0.667 and 0.876, respectively, for the risk of death of silicosis patients. The results of cross-validation showed that the correct discrimination rate of the disease assessment index to the risk of death was 66.7%. Conclusion:The disease assessment index can predict the death risk of patients with silicosis, and can evaluate the disease comprehensively.

Objective:To explore the establishment of disease assessment index model in silicosis patients.Methods:In October 2018, 171 silicosis patients who were hospitalized from November 2014 to November 2015 were selected as the study subjects. According to the standard of death risk, the subjects were divided into two groups, including the group without death risk (153 cases) and the group with death risk (18 cases) . Through literature analysis and clinical experience, the variables related to silicosis were preliminarily screened. Multifactorial logistic regression analysis variables were used to analyze the relationship between the variables and the risk of death. The variables associated with the risk of death were selected as the final variables to establish the disease assessment index model. And the receiver operating characteristic (ROC) curve was used to evaluate the clinical application of the disease assessment index.Results:Five variables of Modified British Medical Research Council Respiratory Questionnaire (mMRC) , pulmonary function injury, pneumoconiosis stage, aggravation of the disease and complications were selected as the variables of the disease assessment index, and the assessment index score ranged from 1 to 11 points. The area under the ROC curve of disease assessment index was 0.747 (95% CI: 0.590-0.904) , which could better identify the death risk of silicosis patients. With the increase of disease assessment index score, the death risk of silicosis patients increased. When the cutoff value was 7, the sensitivity and specificity were 0.667 and 0.876, respectively, for the risk of death of silicosis patients. The results of cross-validation showed that the correct discrimination rate of the disease assessment index to the risk of death was 66.7%. Conclusion:The disease assessment index can predict the death risk of patients with silicosis, and can evaluate the disease comprehensively.

Objective To analyze the dosimetric effect of inconsistent bladder filling states between the CT simulation and treatment for prostate cancer patients undergoing intensity-modulated radiotherapy (IMRT).Methods A total of 42 prostate cancer patients treated with IMRT were selected.After vacuum pad immobilization and simulation CT scan,the delineation of targets and organs-at-risk (OARs),treatment planning and dose calculation were performed on treatment planning system (TPS).The cone-beam-CT (CBCT) acquired before the first treatment was registered to planning CT,on which the target contours were duplicated and OARs were delineated.After dose recalculation on the CBCT using the same plan,the dosimetric differences on the CT and CBCT were compared,including mean dose of the planning target volume (PTV),homogeneity index (HI),conformity index (CI);the mean dose,V30,V40,V50,V60,and V65 of bladder and rectum respectively.Results Relative to the bladder volumes at simulation,the patients were divided into two groups with larger (15 cases) or smaller (27 cases) bladders at the first treatment.Comparing the parameters obtained from simulation CT with that from CBCT,the differences of the following parameters were of statistical significance:the bladder volume,PTV HI,PTV CI in both groups (t =6.838,-4.372,-3.553,-3.462,6.380,5.037,P＜ 0.05),the bladder V30,V40,V50,V60,V65(t=-5.004,-4.092,-3.124,-2.707,-2.489,P ＜0.05) and rectal V40,V50,V60,V65,mean dose in the group with smaller bladders (t=-2.946,-2.643,-2.426,-3.127,-2.530,P ＜ 0.05),and the bladder V30,V40,V50 and mean dose in group with larger bladders (t =5.107,4.204,3.777,4.155,P＜0.05).Conclusions For prostate cancer patients undergoing IMRT,the inconsistent bladder filling states between the planning and treatment will cause disimetric differences of targets and OARs.

Objective To propose the method of dose distribution calculated by one-step optimization with 7 shells (Cao method) and compare with that by three-step optimization with 4 shells (Blanck method) and CyberKnife treatment plans for pancreatic cancer. Methods 20 cases of pancreatic cancer who underwent CyberKnife treatment were retrospectively analyzed,and CT was performed to localize and delineate the target area and endangering organs. Dosage was optimized and evaluated with Blanck method and Cao method. The planning target volume (PTV) conformity index (CI), new conformity index (nCI), homogeneity index (HI),gradient index (GI), coverage, dose-volume and doses to organs at risk were compared. Results Compared with Blanck method, CI (1.11 ± 0.05 vs 1.15 ± 0.05), nCI (1.20 ± 0.06 vs 1.23 ± 0.06), coverage [(92.48 ± 1.85)% vs (93.53 ± 2.15)%], volumes encompassed by 100% and 30% prescription dose line (36.46 ± 16.64 vs 38.19 ± 17.68; 286.19 ± 126.52 vs 320.93 ± 154.82) and monitor unit (56 369 ± 20 019 vs 57 814 ± 20 531) were significantly decreased,while GI was increased (3.22 ± 0.19 vs 3.11 ± 0.19), and all the differences were statistically significant (P<0.05). Additionally, Dmax of the intestine (21.17 ± 2.90 vs 20.63 ± 3.13), D10cc of the stomach (12.78 ± 2.57 vs 13.11 ± 2.43), D5ccof the duodenum (11.01 ± 3.45 vs 11.50 ± 3.25), D10ccof the duodenum (9.30 ± 3.31 vs 9.78 ± 3.07) and D0.35ccof the spinal cord (6.09 ± 0.98 vs 6.59 ± 0.92) were all significantly decreased (P<0.05). No significant differences were found on other parameters. Conclusions Better dose distributions are accessible by one-step optimization with 7 shells in CyberKnife treatment plans for pancreatic cancer.

[Abstact] Objective To analyze the related parameters of the treatment plans for the pancreatic cancer with the Cyber-knife system.Methods The clinical data of 129 patients with single-target pancreatic cancer for the first time who underwent CyberkKnife radiosurgery between January 2017 and December 2017 in Shanghai Changhai Hospital were retrospectively analyzed.The parameters were all selected from the MultiPlan @4.0.2 treatment planning system and the data were analyzed.Results The volume of the targets in 129 patients with pancreatic cancer was 3.355-238.936 cm3,with the average volume of 51.43 ± 55.64 cm3.Patients were averagely treated for 5 to 8 sessions,and the average prescription dose was 6 Gy × 6 fraction,which equaled to 58 Gy in the biological equivalent dose (BED).The collimators with 20 mm and 15 mm accounted for up to 31％ and 27％,respectively,which were the top 2 options.The finally designed the conformal index(CI),new conformal index(nCI),and the homogeneity index were 1.14 ± 0.09,1.29 ± 0.09 and 1.42 ± 0.04,respectively.The coverages of tumor target was 80.3％-95.6％,with the average of 90.0 ± 4.6％.The treatment nodes,beams and Mus are 79,180 and 7 060 in average.The estimated treatment time was 42 ± 8 minutes.The organs at risk can be protected very well.Conclusions Reasonable Cyber-knife treatment plan can guarantee that stereotactic body radiation therapy can effectively treat Pancreatic Cancer.