Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca²⁺, HPO₄^2-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO₃)₂, 15 mmol/L Na₂HPO₄, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.
Vaccines, Virus-Like Particle/immunology* ; Immunogenicity, Vaccine ; Calcium Phosphates/chemistry* ; Foot-and-Mouth Disease Virus ; Biomineralization ; Particle Size ; Animals ; Mice ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; Immunity, Cellular

Objective:To evaluate the effect of neck muscle training on reducing the neck setup error during radiotherapy in patients with nasopharyngeal carcinoma.Methods:Clinical data of nasopharyngeal carcinoma patients who were treated with radiotherapy in the First Affiliated Hospital of Air Force Medical University from February 2021 to October 2022 were selected and analyzed. All subjects were randomly divided into the experimental group ( n=48) and control group ( n=51) at a ratio of 1:1 using a random number table method. In the experimental group, patients received neck muscle training prior to treatment, and those in the control group received conventional treatment without additional interventions. Cone beam computed tomography (CBCT) was performed weekly to measure and analyze the setup errors at the level of the slopes, 4th cervical vertebra (C4) and 7th cervical vertebra (C7). The four-dimensional displacement [left-right (LR), superior-inferior (SI), anterior-posterior (AP), rotation (Rtn)] systematic errors and random errors at each level were calculated, and the planning target volume (PTV) boundary was calculated. The differences at three different levels of slope, C4, C7 (LR, SI, AP axis) were compared between two groups. The correlation of setup errors in each direction was analyzed by Spearman correlation analysis. The changes of cervical curvature, cutaneous toxicity (common terminology criteria for adverse events V3.0) and pain assessment (numerical rating scale) were compared between two groups. Qualitative data between two groups were compared by χ2 test. Quantitative data between two groups were compared by t-test. Results:Baseline features were well balanced in both groups. The setup error in the experimental group was smaller than that in the control group. For the setup error in the AP direction, the setup errors at the levels of slope, C4 and C7 in the experimental group were (0.94±0.88) mm, (1.13±1.03) mm and (1.32±1.22) mm, significantly less than (1.66±1.23) mm, (1.63±1.35) mm and (1.89±1.48) mm in the control group (all P<0.001). In the SI direction, the setup errors at the levels of slope, C4 and C7 in the experimental group were (1.14±0.87) mm, (1.31±0.93) mm and (1.39±0.95) mm, compared with (1.22±0.95) mm, (1.40±1.11) mm and (1.52±1.08) mm in the control group ( P=0.278, 0.272, 0.100). The differences in the AP direction at the level of C4 and C7 in the experimental group were smaller than those in the control group ( P=0.014, 0.005). The required PTV boundary in the AP direction in the experimental group was increased from 1.77 mm at the slope level to 2.98 mm at the level of C7. In the control group, it was increased from 3.02 mm at the slope level to 4.78 mm at the level of C7. Correlation analysis showed that at the C4 and C7 levels, and the setup errors in the SI direction were moderately negatively correlated with those in the AR direction. There were no significant differences in cervical curvature, skin toxicity and pain assessment between two groups. Conclusion:Neck muscle training can reduce the setup error in the AP direction and PTV boundary of radiotherapy in patients with nasopharyngeal carcinoma, which is worthy of clinical promotion.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Perimenopausal syndrome （MPS）， a common endocrine system disease， is one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in endocrinology， gynecology， and interdisciplinary fields of both Western and Chinese medicine to discuss the advantages and challenges of diagnosing and treating MPS with Western medicine， TCM， and integrative medicine. Experts at the conference believe that MPS is initiated by estrogen decline and rooted in deficiency， with the pathogenesis being imbalance between Yin and Yang in the kidney. The hormone replacement therapy in Western medicine for menopause can rapidly alleviate related symptoms by quickly restoring the estrogen level and timely detect and delay complications of menopause， whereas such a therapy has certain risks， necessitating close monitoring of adverse reactions. Moreover， the various contraindications and precautions limit the clinical application of the hormone replacement therapy. TCM has advantages in synergistically alleviating symptoms such as hot flashes， sweating， sleep disorders， and emotional abnormalities of MPS without causing obvious adverse reactions. However， its efficacy is slower than the hormone replacement therapy， and the TCM evidence for preventing and treating complications of menopause remains unclear. Three suggestions were proposed for the future development of both Western and TCM for ameliorating MPS. First， an integrated diagnosis and treatment system for MPS with both Western and Chinese medicine should be established. Second， high-quality evidence-based interventions for MPS should be developed with TCM alone or in combination with Western medicine. Third， efforts should be made to promote the new TCM drug development and the interdisciplinary cooperation for treating MPS.

Background The mental health problems of employees in administrative organs and public institutions are highly valued.However,there is a lack of understanding regarding the mental health status of employees in provincial and municipal administrative organs and public institutions in Qinghai region.Objective To analyze the anxiety and depression of employees in provincial and municipal administrative organs and public institutions in Qinghai region,so as to provide references for promoting their mental health and intervening in psychological problems.Methods From October 23 to 28,2022,a total of 3 096 employees in provincial and municipal administrative organs and public institutions in Qinghai region were enrolled using stratified cluster sampling technique,and were assessed using Self-rating Anxiety Scale(SAS)and Self-rating Depression Scale(SDS).Results A total of 1797(58.04％)employees in municipal and above administrative organs and public institutions in Qinghai region completed a valid questionnaire survey.Depressive symptoms were noted in 579(32.22％).SDS scores yielded statistical difference among the selected employees of different ethnicities,types of job positions and educational levels(F=9.074,101.488,4.477,P<0.01),and the severity of depressive symptoms also demonstrated statistical difference among the selected employees with different ethnicities,educational levels and types of job positions(H=49.196,17.028,160.848,P<0.01).Anxiety symptoms were detected in 711(39.57％)employees.SAS scores exhibited statistical difference among the employees with different genders,ages,ethnicities,educational levels,marital status and types of job positions(t=-4.571,F=6.648,3.950,5.243,12.008,22.253,P<0.01).Statistical differences were also illustrated in the severity of anxiety symptoms among the selected employees with different ages,genders,ethnicities,educational levels,marital status and types of job positions(H=24.361,-3.788,28.365,24.268,25.976,56.204,P<0.01).Conclusion About one-third of employees in municipal and above administrative organs and public institutions in Qinghai region may have symptoms of depression and anxiety.The depression symptoms are more severe among Tibetan people,those with low education levels and ordinary civil servants.The anxiety symptoms are more severe among employees aged 30 and below,those with low education levels,unmarried and those in technical positions.

Objective:To investigate the efficacy of double S-shaped elastic stable intramedullary nailing in the treatment of paediatric fractures of the distal tibia diaphyseal metaphyseal junction.Methods:From January 2018 to January 2022, a total of 25 children with fracture of the distal tibia diaphyseal metaphyseal junction were treated at Department of Pediatric Orthopedics, The Second Affiliated Hospital of Inner Mongolia Medical University. All of them were treated with closed reduction and double S-shaped elastic stable intramedullary nailing. There were 16 males and 9 females with an average age of (10.4±3.3) years, and 14 left sides and 11 right sides. The operation time, imaging results and complications were recorded after operation. At the last follow-up, the American Orthopaedic Foot & Ankle Society (AOFAS) scoring was used to evaluate the efficacy.Results:Closed reduction succeeded in all patients. The operation time was (55.6±23.7) min. Follow-up lasted (20.5±4.7) months for this cohort. Bony union was achieved in all patients after (11.5±2.7) weeks. No postoperative complications occurred in the patients, like infection, loss of reduction, disparity in length of lower limbs, delayed union or non-union. The AOFAS scoring at the last follow-up yielded 23 excellent and 2 good cases, and an excellent and good rate of 100% (25/25).Conclusion:In the treatment of paediatric fractures of the distal tibia diaphyseal metaphyseal junction, double S-shaped elastic stable intramedullary nailing is a safe, effective and feasible option.

Integrated medical courses are one of the key models for the development and transformation of modern medical education. Modular-based integrated courses set higher standards for knowledge, skills and quality objectives. This article primarily discusses the specific practices of teaching reform in the integrated medical course of Frontiers of Infection and Immunity for eight-year program at Air Force Medical University. It covers the selection and integration of teaching content, innovative application of various teaching methods, diversified teaching evaluation and feedback, and the teaching team building. The course not only deepens students' knowledge and promotes their creative abilities but also enhances their comprehensive literacy and international perspective, thus effectively preparing high-quality medical talents for future challenges in the medical field.
Humans ; Education, Medical/methods* ; Teaching ; Curriculum ; Immunity ; Infections/immunology*

Objective:To investigate the role of cervical core muscle group exercise and massage in the change of cervical spine curvature during radiotherapy for head and neck tumors and the effect on set-up errors.Methods:A total of 40 patients with head and neck tumours receiving radiotherapy in the First Affiliated Hospital of Air Force Military Medical University from March 2020 to July 2021 were prospectively selected, and all of them underwent different degrees of changes in cervical spine curvature during radiotherapy. The cervical core muscle exercise and manual massage were used to do treatment intervention on the change in the cervical spine curvature. Changes in cervical spine curvature at the time of the curvature change of the cervical spine and at 1 d, 3 d and 5 d after the intervention were observed by using cone beam CT, and then data were recorded in 3 dimensions. The set-up error when cervical spine curvature changed was compared with that after the muscle group exercise and manipulation, and Pearson was used to analyze the linear correlation of set-up errors in each direction.Results:There were 23 males and 17 females, with a median age of 41 years (26-62 years). The significant improvement of cervical curvature at 1 d, 3 d and 5 d after the intervention could be found in 2 cases (5.0%), 20 cases (50.0%) and 39 cases (97.5%). Using the cervical 4 vertebrae as the matching standard, the set-up errors at the time of change in cervical spine curvature and at 1 d, 3 d and 5 d after treatment were (1.3±0.9) mm, (1.2±0.8) mm, (1.3±0.7) mm and (1.3±0.7) mm in the left-right direction respectively; (2.0±0.7) mm, (1.7±0.8) mm, (1.8±0.7) mm and (1.9±0.8) mm in the head-foot direction respectively; (4.9±0.7) mm, (4.6±0.7) mm, (3.4±0.7) mm, (1.7±0.6) mm in the anterior-posterior direction respectively. The set-up error in the anterior-posterior directions at 3 d and 5 d after treatment intervention was lower than that at the time of change in cervical spine curvature and at 1 d after treatment intervention (all P < 0.01), and that at 5 d after treatment intervention was lower than that at 3 d after treatment intervention ( P < 0.01). There were no statistically significant differences between the left-right direction and head-foot direction at each time point (all P > 0.05). There was no correlation between left-right direction and head-foot direction ( r = 0.049, P = 0.540), between left-right direction and anterior-posterior direction ( r = 0.041, P = 0.607), and between head-foot direction and anterior-posterior direction ( r = 0.003, P = 0.931) in terms of set-up errors. Conclusions:Core cervical muscle group training and massage could improve the change in cervical spine curvature, increase the repeatability of the set-up, which provides a favourable guarantee for accurate treatment.

ObjectiveTo investigate the characteristics of serum perfluoroalkyl substances （PFASs） exposure and potential influencing factors among community residents in Songjiang District， Shanghai. MethodsIn August 2021， residents who underwent routine health checkups in a community in Songjiang District， Shanghai were recruited as study subjects. The inclusion criteria were adult residents who had lived in the area for more than 3 years， had no occupational exposure history， no underlying diseases， were not pregnant， and were able to complete the questionnaire independently and sign the informed consent form. A questionnaire survey was conducted and venous blood samples were collected. The concentrations of 15 PFASs in serum were determined using ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry （UPLC-MS/MS）. Ordered multi-class logistic regression， interquartile range （IQR）， and odds ratio （OR） were used to explore the influencing factors and risk magnitude of serum PFASs concentrations. ResultsOf the 15 PFASs， 14 were detected， and the detection rates of 7 PFASs were higher than 50%. The highest detected concentrations among the PFASs were PFOS （perfluorooctane sulfonate）， PFOA （perfluorooctanoic acid）， and PFHxS （perfluorohexane sulfonate）， with median concentrations of 48.61 μg∙L^-1， 37.29 μg∙L^-1， and 36.51 μg∙L^-1， respectively. The strongest correlation was between PFDA and PFUnDA （r=0.93， P<0.05）， followed by PFOS and PFDA （r=0.86， P<0.05）. Age， frequency of plastic product use， time spent indoors per day， personal annual income， tea consumption， and daily water intake were potential factors for exposure to PFASs. Among them， age was positively correlated with PFASs； tea consumption was positively correlated with PFNA and PFOA； PFHpA was negatively correlated with the frequency of plastic product use and personal annual income； and PFOS was negatively correlated with the time spent indoors per day. ConclusionThe exposure to serum PFASs among community residents in Songjiang District was relatively serious， and the main components were traditional PFOA， PFOS， and PFHx. Different sociodemographic characteristics had varying degrees of influence on the concentrations of PFASs in serum. The impact of PFASs exposure on the health of community residents deserves further investigation.

Objective To investigate the expression of PD-1 and PD-L1/2 in T cell subsets and myeloma cells in the bone marrow from newly diagnosed multiple myeloma (NDMM) patients and their relation with clinical features. Methods We collected the bone marrow and clinical data of 22 NDMM patients and 18 cases of healthy controls. We sorted CD4⁺T cells, CD8⁺T cells and myeloma cells by flow cytometry, and observed the expression of PD-1 and PD-L1/2. Results Compared with the control group, the proportion of CD8⁺T cells in the NDMM group was significantly higher, while the ratio of CD4⁺/CD8⁺ was significantly lower (both P < 0.05). The expression levels of PD-1 and PD-L2 in CD4⁺T cells in the NDMM group were significantly higher than those in the control group (both P < 0.05). The expression levels of PD-1, PD-L1 and PD-L2 in T cell subsets and myeloma cells of NDMM patients were not correlated with the gender, age, immune typing, Durie-Salmon stage and subtypes, ISS stage or mSMART3.0 stratification (both P > 0.05). Conclusion Most of MM patients suffering immune abnormality, which may be associated with the mutual immunosuppressive effects between T lymphocytes and plasma cells which expressing PD-1 and PD-L1/2.