ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Objective:This study aims to develop a validated instrument for assessing the degree of integration perceived by patients in the services provided by general practitioner(GP)teams,and to evaluate the current state of integrated medical-prevention services.Methods:The survey tool was initially created through a review of existing literature and semi-structured interviews.It was subsequently refined and enhanced following consultations with experts.The utility of the instrument was confirmed through empirical research,which also facilitated an analysis of the status quo regarding the integration of medical and prevention services.Results:The devised instrument encompasses 18 items distributed across six dimensions:service comprehensiveness,service continuity,depth of service,continuity of relationship,patient-centricity,and service coordination.The cumulative score reflecting patients'perception of the integration level in GP teams'medical-prevention services was 54.30±12.45.Conclusion:The survey instrument developed in this research is characterized by its rationality,novelty,and practical relevance.It offers a patient-centered perspective for assessing the quality of integrated medical and prevention services for primary chronic diseases.While the overall perception of integration among patients is positive,there is a notable deficiency in the depth of services provided.There is a need for optimization of the service process,clarification of the service path,refinement of service management,and development of an integrated incentive mechanism for medical and preventive care,aiming for a deeper integration between medical services and preventive care.

Objective To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation(PMV)due to different primary diseases.Methods A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022.According to the primary disease,they were divided into respiratory disease(RD)group,central nervous system(CNS)group,neuromuscular disease(NMD)group,and other disease group.The four groups were compared in terms of general information,treatment,and outcome.Results There were significant differences among the four groups in age,body weight,Pediatric Logistic Organ Dysfunction-2(PELOD-2)score,Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score,analgesic and sedative treatment,nutrition supply,rehabilitation treatment,tracheotomy,successful ventilator weaning,and outcomes(P＜0.05).Compared with the RD group,the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment,and the CNS group had a significantly higher proportion of children receiving tracheotomy(P＜0.008).Compared with the other disease group,the CNS group and the NMD group had significantly lower PELOD-2 and PRISM Ⅲ scores,and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged(P＜0.008).Conclusions There are differences in clinical characteristics among children receiving PMV due to different etiologies.Most children in the RD group have a younger age,and children in the CNS group have a relatively good prognosis.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To observe the clinical efficacy and safety of olanzapine tablets combined with magnesium valproate sustained-release tablets in the treatment of adolescent depressed patients.Methods Adolescents with depression were divided into control group and treatment group by simple random method.The control group was treated with oral olanzapine tablets with 5 mg·d-1 as the starting dose.After 1 week of treatment,the drug dose was adjusted according to the symptoms and kept within 20 mg·d-1.The treatment group was given oral magnesium valproate sustained-release tablet combined treatment on the basis of the control group,with 0.5 g as the initial dose,and the maximum dose was adjusted according to clinical symptoms after 1 week of treatment,and the maximum dose was no more than 1 g·d-1.Both groups were treated for 12 weeks.The clinical efficacy,excitatory amino acid(EAA),connectin level,intestinal fatty acid binding protein(Ⅰ-FABP),Hamilton depression scale(HAMD),Bech-Rafaelsen Mania Rating Scale(BRMS)and safety of the two groups were compared.Results Sixty-three cases were included in the treatment group and control group,respectively.After treatment,the total effective rates of the treatment group and the control group were 92.06％(58 cases/63 cases)and 79.37％(50 cases/63 cases),respectively,and the difference was statistically significant(P＜0.05).After treatment,the levels of EAA in the treatment group and the control group were(29.98±3.44)and(27.97±3.88)μg·mL-1;the levels of zonulin were(189.45±19.56)and(182.33±19.89)ng·mL-1;the levels of Ⅰ-FABP were(99.27±9.13)and(103.84±9.36)pg·mL-1,respectively;the HAMD scores of the treatment group and the control group were 9.88±1.03 and 10.74±1.95;the BRMS scores were 5.08±0.32 and 5.32±0.51,respectively.Compared with the control group,the differences of above indexes in the treatment group were statistically significant(all P＜0.05).The main adverse drug reactions in the two groups were weight gain,dry mouth,and drowsiness.The total incidences of adverse drug reactions in the treatment group and the control group were 12.70％and 15.87％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion Olanzapine tablets combined with magnesium valproate sustained-release tablets can effectively increase plasma Ⅰ-FABP,EAA,and zonulin levels in adolescent depressed patients,and improve HAMD and BRMS scores,with good safety.

Objective To develop a health belief model(HBM)based adolescent alcohol-related cognition scale to measure adolescent alcohol-related cognition and test its reliability and validity.Methods The adolescents'alcohol-related cognitive scale was developed based on HBM model.By using purposive sampling,three general high schools in Qingpu District,Shanghai were selected.One-third of the classes from grades 10 and 11 in each school were randomly selected,and the students from these classes were surveyed as the research subjects.Exploratory factor analysis and confirmatory factor analysis were used to analyze its reliability(internal consistency reliability and combination reliability)and validity(structural validity,convergent validity,discriminative validity and criterion validity).Results A total of 970 questionnaires were collected,of which 948 were valid,with an effective rate of 97.7%.The adolescents'alcohol-related cognitive scale contained 22 items.Five common factors were extracted from exploratory factor analysis,including perceived susceptibility,perceived severity,perceived benefits,perceived obstacles,and self-efficacy.The cumulative variance contribution rate reached 83.89%.The results of confirmatory factor analysis confirmed the overall fit of the model.The average variance extracted value(AVE)of each dimension was greater than 0.5,and the convergent validity of the model was ideal.The AVE square root of each dimension of the scale was greater than its correlation coefficient,indicating good discrimination validity.Cronbach's α coefficient of the total volume table was 0.892,indicating good overall reliability.Conclusion The adolescents'alcohol-related cognitive scale developed in this study has good reliability and validity,which can be used to measure adolescents'alcohol-related perceptions.

AIM: To investigate the effect of repeated intravitreal injection of anti-vascular endothelial growth factor(VEGF)on the vitreomacular interface(VMI)and its related risk factors in patients with diabetic macular edema(DME).METHODS: The clinical data of 31 patients(55 eyes)with DME who received intravitreal injections of Conbercept(3+PRN)in the ophthalmology department of the First People's Hospital of Zunyi from January 2018 to December 2021 were analyzed retrospectively. There were 9 cases(13 eyes)in the group that has changes in VMI and 22 cases(42 eyes)in the other group that has no changes in VMI. The best corrected visual acuity(BCVA), central retinal thickness(CRT), and central choroidal thickness(CCT)of the two groups were compared, and the risk factors of VMI change were analyzed.RESULTS: The patients were followed up for an average of 9.58±8.32mo, received an average of 4.07±2.17 times of anti-VEGF therapy, and the number of intravitreal injections in VMI changed group was more than that in VMI unchanged group(5.77±2.09 times vs. 3.55±1.93 times, P=0.001). At the last follow-up, compared with before treatment, the BCVA of both patients improved significantly after treatment(both P<0.05), while CCT had no significant change(both P>0.05). CRT of patients in the VMI unchanged group decreased significantly(P=0.039), but there was no significant change in patients of VMI changed group(P=0.627). Logistic regression analysis showed that BCVA was a risk factor for VMI change before treatment(P=0.049, OR=6.210, 95%CI 1.006～38.346).CONCLUSIONS: The VMI of DME patients may change during repeated intravitreal injections of anti-VEGF drugs. The worse the BCVA before treatment, the higher the risk of change in VMI, and the patients with VMI change have a poor response to anti-VEGF treatment.

Objective: To explore the short-term efficacy and safety of dapagliflozin in children with hereditary proteinuric kidney disease. Methods: This was a prospective cohort study. From August 2020 to December 2021, 23 children with hereditary kidney disease from Children's Hospital of Fudan University were enrolled. Patients received dapagliflozin 5 mg/d (weight≤30 kg) or initial dose 5 mg/d for 1 week, then 10 mg/d (weight>30 kg) and the dose of angiotensin converting enzyme inhibitors was stable during treatment. Clinical data including demographic parameters, primary diagnosis, estimated glomerular filtration rate (eGFR), 24 h proteinuria and characteristics in the follow-up were collected. The primary outcome was the change in 24 h proteinuria at 12 (±2) weeks, secondary outcomes included changes of 24 h proteinuria at 24 (±2) weeks, eGFR at both 12 (±2) and 24 (±2) weeks. The data were analysed by using mixed linear model. Results: Totally 23 patients were enrolled, including 16 males and 7 females. The age was (10.8±2.9) years. The primary diseases were Alport syndrome (12 cases), Dent disease (5 cases), proteinuria (4 cases), and focal segmental glomerulosclerosis (2 cases) respectively. Primary outcome showed that 24 h proteinuria decreased from baseline at 12 (±2) weeks during treatment (1.75 (1.46, 2.20) vs. 1.84 (1.14, 2.54) g/m², P<0.05). Secondary outcomes showed that there was no significant difference in 24 h urine protein at 24 (±2) weeks (P>0.05). eGFR decreased slightly at 12 (±2) weeks ((107±21) vs. (112±28) ml/(min·1.73m²), P<0.05), and there was no significant difference at 24 (±2) weeks (P>0.05). Serum albumin increased at 12 (±2) and 24 (±2) weeks following the treatment ((39±8) vs. (37±8) g/L, (38±7) vs. (37±8) g/L, both P<0.05). No hypoglycemia event was reported during the treatment. Conclusion: The dapagliflozin had therapeutic effects on decreasing proteinuria and increasing serum albumin in short-term treatment in children with hereditary proteinuric kidney disease, no hypoglycemia or serious adverse events were observed.
Female ; Male ; Humans ; Child ; Adolescent ; Prospective Studies ; Nephritis, Hereditary ; Proteinuria/drug therapy* ; Serum Albumin

UHPLC-Q-Exactive Orbitrap MS/MS was used to systematically analyze and compare the alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata. After the samples were pretreated in the solid-phase extraction cartridges, 0.1% ammonium hydroxide(A)-acetonitrile(B) was used for gradient elution. The LC-MS method for characterization of alkaloids in the three herbal medicines was established in ESI positive ion mode to collect high resolution MS data of reference substances and samples. On the basis of the information of reference substance cracking behavior, retention time, accurate molecular mass, and related literature, a total of 155 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Prae-parata. Specifically, 130, 127, and 92 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata, respectively. Monoester alkaloids and amino-alcohol alkaloids were dominant in the three herbal medicines, and the alkaloids in Aconiti Kusnezoffii Radix and Aconiti Radix were similar. This paper can provide a reference for elucidating the pharmacological effects and clinical application differences of the three herbal medicines produced from plants of Aconitum.
Tandem Mass Spectrometry ; Aconitum ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal ; Alkaloids ; Plants, Medicinal

Objective: To investigate the association of mixed exposure to greenness and nitrogen dioxide(NO₂) and hypertension among the older adults aged 65 years and over in China. Methods: The study subjects were from the Chinese Longitudinal Healthy Longevity Survey from 2017 to 2018. A total of 15 423 older adults aged 65 years and over meeting the criteria were finally included in the study. A questionnaire survey was used to collect information on demographic characteristics, lifestyle habits and self-reported prevalence of hypertension. Blood pressure values were obtained through physical examination. The level of normalized difference vegetation index(NDVI) was measured by the Medium-resolution Imaging Spectral Radiator(MODIS) of the National Aeronautics and Space Administration(NASA). The concentration of NO₂ was from China's surface air pollutant data set. Meteorological data was from NASA MERRA-2. The exposure to NDVI and NO₂ for each study subject was calculated based on the area within a 1 km radius around their residence. The association between mixed exposure of NDVI and NO₂ as well as their interaction and hypertension in older adults was analyzed by using the multivariate logistic regression model. The restrictive cubic spline(RCS) function was used to explore the exposure-response relationship between greenness and NO₂ and the risk of hypertension in study subjects. Results: The mean age of 15 423 older adults were (85.6±11.6). Women accounted for 56.3%(8 685/15 423) and 55.6%(8 578/15 423) lived in urban areas. The mean time of residence was (60.9±28.5) years. 59.8% of participants were with hypertension. The mean NDVI level was 0.41±0.13, and the mean NO₂ concentration was (32.18±10.36) μg/cm³. The results of multivariate logistic regression analysis showed that NDVI was inversely and linearly associated with the hypertension in older adults, with the OR(95%CI) value of 0.959(0.928-0.992). Compared with the T₁ group of NDVI, the risk of hypertension was lower in the T₃ group, with the OR(95%CI) value of 0.852(0.769-0.944), and the trend test was statistically significant(P<0.05). Compared with the T₁ group of NO₂, the risk of hypertension was higher in the T₂ and T₃ groups, with OR(95%CI) values of 1.160(1.055-1.275) and 1.244(1.111-1.393), and the trend test was statistically significant (P<0.05). The result of the RCS showed that NDVI was inversely and linearly associated with hypertension in older adults. NO₂ was nonlinearly associated with hypertension in older adults. The interaction analysis showed that NDVI and NO₂ had a negative multiplicative interaction on the risk of hypertension, with OR(95%CI) value of 0.995(0.992-0.997). Conclusion: Exposure to greenness and NO₂ are associated with hypertension in older adults.
Aged ; Humans ; Female ; Nitrogen Dioxide ; Air Pollution ; Prevalence ; Hypertension/epidemiology* ; China/epidemiology* ; Particulate Matter/analysis*