Objective:To apply mass spectrometry as well as bioinformatics techniques to analyze HBV peptides derived from Pol and X proteins presented by human immortalized B lymphocytes(BLCLs),and to screen for effective T-cell epitopes,which lays the foundation for the development of therapeutic vaccines.Methods:The group has constructed a genome-wide expression plasmid containing 1.2-fold HBVC2 isoforms and transfected it into BLCLs by electro-transfection,isolated and identified HBV peptides by LC-MS/MS,bioinformatically predicted peptide sequences in terms of sensitization,antigenicity,toxicity,HLA molecular affinity,and the ability of peptide HLA-class Ⅰ complex to bind to specific T cells,and retrieved reported sequences.Results:HBV peptides from lysates of five immortalized B cells(BLCLs-1 to BLCLs-5)carrying HBVC2 subtype-expressing recombinants were analyzed,and 141 peptides with sequence lengths of no less than 8 amino acid residues(≥8 aa)were successfully isolated and identified,of which 133 were derived from Pol,and 8 from X proteins.The 141 HBV peptides were analyzed for sensitization,antigenicity and toxicity,and 50 antigenic,non-toxic and sensitizing HBV peptides(47 from Pol and 3 from X protein)were screened for affinity analysis with HLA-class Ⅰ and Ⅱ molecules and for prediction of the binding ability of the peptide HLA-class Ⅰ complexes to specific T cells.Among these peptides,37 had affinity to the corresponding genotypes of HLA-class Ⅰ and Ⅱ molecules.Finally,we obtained 37 peptides with antigenic,nontoxic,and sensitizing properties with IC50<500 nmol/L to HLA-class Ⅰ and Ⅱ molecules,which have affinitied to the corresponding genotypes but have not been reported,and can be continued to be explored as potential epitopes.Finally,15 HBV peptide hotspot core regions were formed by intra-and inter-strain common,contained,overlapping or neighboring sequence analysis of 141 peptides,with 7 core region sequences with antigenic,nontoxic,and sensitizing properties restricted to the corresponding geno-types.Peptides with affinity IC50<500 nmol/L had an affinity core sequence overlap of no less than 8 amino acids,and can be priori-tized for candidate T cell epitopes for subsequent studies.Conclusion:Peptides derived from Pol and X proteins have been successfully isolated and identified,and potential T cell epitopes have been screened.

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 apply mass spectrometry as well as bioinformatics techniques to analyze HBV peptides derived from Pol and X proteins presented by human immortalized B lymphocytes(BLCLs),and to screen for effective T-cell epitopes,which lays the foundation for the development of therapeutic vaccines.Methods:The group has constructed a genome-wide expression plasmid containing 1.2-fold HBVC2 isoforms and transfected it into BLCLs by electro-transfection,isolated and identified HBV peptides by LC-MS/MS,bioinformatically predicted peptide sequences in terms of sensitization,antigenicity,toxicity,HLA molecular affinity,and the ability of peptide HLA-class Ⅰ complex to bind to specific T cells,and retrieved reported sequences.Results:HBV peptides from lysates of five immortalized B cells(BLCLs-1 to BLCLs-5)carrying HBVC2 subtype-expressing recombinants were analyzed,and 141 peptides with sequence lengths of no less than 8 amino acid residues(≥8 aa)were successfully isolated and identified,of which 133 were derived from Pol,and 8 from X proteins.The 141 HBV peptides were analyzed for sensitization,antigenicity and toxicity,and 50 antigenic,non-toxic and sensitizing HBV peptides(47 from Pol and 3 from X protein)were screened for affinity analysis with HLA-class Ⅰ and Ⅱ molecules and for prediction of the binding ability of the peptide HLA-class Ⅰ complexes to specific T cells.Among these peptides,37 had affinity to the corresponding genotypes of HLA-class Ⅰ and Ⅱ molecules.Finally,we obtained 37 peptides with antigenic,nontoxic,and sensitizing properties with IC50<500 nmol/L to HLA-class Ⅰ and Ⅱ molecules,which have affinitied to the corresponding genotypes but have not been reported,and can be continued to be explored as potential epitopes.Finally,15 HBV peptide hotspot core regions were formed by intra-and inter-strain common,contained,overlapping or neighboring sequence analysis of 141 peptides,with 7 core region sequences with antigenic,nontoxic,and sensitizing properties restricted to the corresponding geno-types.Peptides with affinity IC50<500 nmol/L had an affinity core sequence overlap of no less than 8 amino acids,and can be priori-tized for candidate T cell epitopes for subsequent studies.Conclusion:Peptides derived from Pol and X proteins have been successfully isolated and identified,and potential T cell epitopes have been screened.

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 risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To study the respiratory morbidity and the risk factors of respiratory complications in late-preterm infants.Methods:The data of 959 late-preterm infants in 21 hospitals in Beijing from October 2015 to April 2016 were collected.These infants were divided into the respiratory morbidity group (237 cases) and the control group (722 cases) according to whether they had short-term respiratory morbidity after birth.Clinical data of the two groups were compared.Results:Among the 959 late-preterm babies, 530 were male and 429 were female.Two hundred and thirty-seven cases (24.7%) developed short-term respiratory morbidity after birth.Infectious pneumonia developed in the most cases (81 cases, 8.4%), followed by transient tachypnea (65 cases, 6.8%), amniotic fluid aspiration (51 cases, 5.3%), and respiratory distress syndrome (24 cases, 2.5%) successively.All the infants recovered and discharged.There were no differences between gender and maternal age between 2 groups (all P>0.05). Compared with the control group, more late-preterm infants were delivered by cesarean section (73.4% vs.59.7%, χ2=14.43, P<0.001) and the 1-minute Apgar score was lower [(9.41±1.66) scores vs.(9.83±0.53) scores, t=5.40, P<0.001] in the respiratory morbidity group.The differences were statistically significant.There were more cases with maternal complications in the respiratory morbidity group that in the control group (66.7% vs.58.6%, χ2=4.877, P=0.027), but no difference in various complications between 2 groups was observed ( P>0.05). In the respiratory morbidity group, the most frequent complications were maternal hypertension and preeclampsia (27.8% vs.22.6%, χ2=2.728, P=0.099). There were no differences between 2 groups in gestational age, birth weight and birth length (all P>0.05). There were more infants small for gestational age and large for gestational age in the respiratory morbidity group than in the control group (18.8% vs.14.1%, 6.3% vs.2.4%, χ2=8.960, P=0.011). The duration of hospitalization of the respiratory morbidity group was significantly longer than that of the control group [(9.00±4.42) d vs.(6.82±4.19) d, t=6.676, P<0.001] since the infants with respiratory morbidity needed to be hospita-lized. Conclusions:Respiratory diseases occur in about 1/4 of late-preterm infants.Infants who are delivered by cesarean section and whose mothers are complicated with the maternal hypertension and preeclampsia should be monitored closely.Respiratory support should be provided for infants not appropriate for gestational age who are more likely to suffer from respiratory diseases, so that they can successfully pass through the transition period.

Objective: To investigate the effect of hypertensive disorder complicating pregnancy (HDCP) on the mortality and early complications of premature infants. Methods: The general clinical data of preterm infants with gestational age 24-36^{+ 6} weeks were collected from the cooperative units in the task group from January 1, 2013 to December 31, 2014.According to the severity of HDCP, the infants were divided into 4 groups: HDCP group, preeclampsia group, eclampsia group and non HDCP group, the mortality and major complications of preterm infants were compared, and the influencing factors were analyzed. Results: The mortality rate of preterm in the HDCP group was significantly higher than that of non HDCP group, and there was statistical significance (χ²=9.970, P=0.019). Eclampsia had a highest fatality rate (4.8%) in the early stage, compared with non HDCP group (2.2%), and the difference was statistically significant.Comparison of HDCP group (1.8%) and eclampsia group (3.2%) suggested that there was no statistically significant difference.The incidence of respiratory distress syndrome (RDS) in preterm in HDCP group was significantly higher than that of non HDCP group, and there was statistical significance (χ²=13.241, P=0.004). Eclampsia group showed the highest incidence (35.4%), compared with non HDCP group (16.2%), the difference was statistically significant, but compared with HDCP group (19.9%), preeclampsia group (17.1%), there was no significant diffe-rence.The incidence of bronchopulmonary dysplasia (BPD) in preterm in HDCP group was significantly higher than that of non HDCP group (χ²=9.592, P=0.022), the highest incidence showed up in eclampsia group (9.7%), compared with non HDCP group (2.0%) and HDCP group (1.7%), the difference was statistically significant.But there was no statistically significant difference, compared with preeclampsia group.As the degree of HDCP aggravated, the incidence of BPD gradually rose.There was no significant impact on necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH) and sepsis of HDCP (χ²=7.054, 7.214, 0.358, 3.852; P=0.070, 0.065, 0.949, 0.278). Considering the overall outcome of the child, that was, whether the child died or survived, he had at least one complication, and HDCP had an effect on it (χ²=15.697, P=0.001), so the incidence increased while the degree of HDCP rose gradually.After adjusting gestational age, birth weight, sex, way of delivery, placental abruption and front placenta, prenatal hormonal, gestational diabetes, neonatal asphyxia and other factors, the results displayed that HDCP was the factor leading to the death of premature baby (OR=2.159, 95%CI: 1.093-4.266), and comparison between preeclampsia and eclampsia showed no statistical difference (P=0.714, 0.389); HDCP had no significant influence on RDS, BDP, ICH, NEC, ROP and sepsis. Conclusions HDCP leads to increased risk of premature death, but also leads to the increased incidence of RDS and BPD, but it had no obvious effect on NEC, ROP, IVH, sepsis and other complications.

Objective To evaluate the effects of network video in the continuing nursing care of discharged cervical cancer patients with postoperative catheter.Methods A number of 53 patients with cervical cancer underwent radical hysterectomy in Nantong Tumor Hospital from January to December 2016 were randomly recruited as the observation group. Another 53 patients with cervical cancer underwent radical hysterectomy from January 2012 to December 2015 were retrospectively studied as control group. Patients in the control group were discharged from the hospital with removal catheter after the professional nursing of 15 days. Patients in the observation group were discharged from the hospital with the indwelling catheter one week after the surgery, and the catheter was removed after one week of network video on continuation nursing care.Results After the removal catheter, there were two cases (4％) of increased residual urine, two cases (4％) of urinary retention, and eight cases (15％) of urinary tract infection in the observation group;one case (2％) of increased residual urine, two cases (4％) of urinary retention, and eight cases (15％) of urinary tract infection were found in the control group. No differences were observed between the two groups (P>0.05). The score of patients' satisfaction was (4.85±0.12) in the observation group and (4.82±0.10) in the control group, with no difference between the two groups (t=1.479,P>0.05).Conclusions The application of network video in continuing nursing care of patients with cervical cancer after radical hysterectomy is feasible, whereas the preparation before discharge is required.

Objective To investigate the clinical features and mechanism and feasibility of plasma exchange (PE) in treating systemic lupus erythematosus (SLE) complicated with acute pancreatitis (AP). Methods A retrospective analysis of SLE associated with AP was done based on the HIS in Tongji Hospital. Totally 24 SLEAP patients were admitted to Tongji hospital from March 2006 to May 2014. Patientsˊ serum amylase, lipase and interleukin (IL)-6 concentration were measured before and after plasma exchange. According to different therapy strategy, patients were divided into two groups. Fifteen patients treated with plasma exchange combination with glucocorticosteroid (GC) were classified as Group A, the other 9 patients who were treated with GC only were classified as group B. At baseline and after treatment, the serum lipid concentration, average daily glucocorticosteroid dosage between group A and B were compared with ANOVA and serum IL-6 concentration between roup A and B were compared with Wilcoxon rank test. Results SLEDAI score in group A patients at baseline (16 ±5) was no statistically different from that in group B (18 ±4) (t=1.31, P=0.320). Average daily GC dosage in group A 31.0 (20.50, 30.08)mg/d was significantly less than that in group B 47.85 (45.58, 59.23) mg/d (Z=35.50, P= 0.002). Serum IL-6 levels in group A and B at baseline was not significantly different 13.14 (11.12,16.57) mg/L vs 14.63 (11.37, 16.37) mg/L (Z=12.20, P=0.300), after 2 weeks treatment, IL-6 level, which was 9.16 (7.93, 10.75) mg/L, decreased significantly in group A while it didnˊt show tendency of decrease in group B, which was 13.62(9.29, 17.63) mg/L (Z=28.50, P=0.039). Serum lipid concentration after 2 weeks therapy in Group A [TC=(5.02 ±0.53) mmol/L, TG=(1.46 ±0.44) mmol/L] decreased significantly compared to baseline [TC=(6.11±0.50) mmol/L, TG=(2.14±0.65) mmol/L] (F=4.46, P=0.010; F=6.09, P=0.002), while similar tendency wasnˊt observed in group B (F=1.57, P>0.05). Conclusion PE combined with GC could lower serum IL-6 levels, reduce the amount of GC and lower serum lipid to improve prognosis. Therefore it might be a safe and effective way and is worthy of continuing to explore its feasibility.

Presently, there are many issues in traditional Chinese medicine (TCM) decoction, such as the uncertain sources of TCM, the lack of reminder for medication taboo, the nonstardard herb operation, and difficult supervision, etc. A digital service system of TCM decoction was established to solve the problems mentioned above. The digital service system mainly includes automatic coding for checking in & out, drug medication taboo database, digital operation in decoction, distribution through 2D code, the corresponding application for mobile phone, and the information supervision platform for TCM decoction. The digital service system of TCM decoction can track the quality & duty of the pieces, remind decoction medicine contraindications, improve the standard operation process of decoction, develop decoction distribution & tracking through cell phone, save the waiting time, and hence provides a new supervising method for TCM decoction. The digital service system of TCM decoction solves the key issues for the formula, operation, delivery and supervision of TCM. In the same vein, this system will expand the market share of TCM decoction and promote the development of TCM.