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

Vaccination is a crucial strategy for the prevention and control of infectious diseases. Virus-like particles (VLPs), composed of structural proteins, have garnered significant attention as a novel type of vaccine due to their excellent safety and immunogenicity. However, similar to most vaccine antigens, VLPs exhibit insufficient thermal stability, which not only restricts the widespread application of vaccines but also increases the risk of vaccine inactivation. This study aims to enhance the stability and shelf life of VLPs derived from type A foot-and-mouth disease virus (FMDV) by employing vacuum freeze-drying technology. The optimal lyoprotectant formulation was determined through single-factor and combinatorial screening. Subsequently, the correlation between the immunogenicity of the freeze-dried vaccine and the content of FMDV VLPs was evaluated via a mouse model. The stability of FMDV VLPs before and after freeze-drying was further assessed by storing them at 4, 25, and 37 ℃ for varying time periods. Results indicated that the lyoprotectant formulation No.1, composed of 7.5% trehalose, 0.1% Tween 80, 50 mmol/L glycine, 1% sodium glutamate, and 3% polyvinylpyrrolidone (PVP), effectively preserved the content of FMDV VLPs during the vacuum freeze-drying process. The immunization trial in mice revealed that the levels of specific antibodies, immunoglobulin G1 (IgG1), interleukin-4 (IL-4), and neutralizing antibodies induced by freeze-dried FMDV VLPs were comparable to those induced by non-freeze-dried FMDV VLPs. The heat treatment results showed that the storage periods of freeze-dried FMDV VLPs at 4, 25, and 37 ℃ were significantly longer than those of non-freeze-dried FMDV VLPs. In conclusion, the selected lyoprotectant formulation effectively improved the stability of FMDV VLPs vaccines. This study provides valuable insights for enhancing the stability of novel subunit vaccines.
Freeze Drying/methods* ; Animals ; Foot-and-Mouth Disease Virus/immunology* ; Mice ; Vaccines, Virus-Like Particle/chemistry* ; Foot-and-Mouth Disease/immunology* ; Vacuum ; Drug Stability ; Mice, Inbred BALB C ; Viral Vaccines/immunology*

Objective:To investigate the application value of donor liver autologous portal venous blood rinse in orthotopic liver transplantation (OLT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 35 pairs of donors and recipients who underwent OLT in the First Affiliated Hospital of University of Science and Technology of China from May 2018 to June 2019 were collected. Of the 35 donors, there were 31 males and 4 females, aged (48±9)years. Of the 35 recipients, there were 25 males and 10 females, aged (47±9)years. Of the 35 recipients, 16 recipients undergoing donor liver autologous portal venous blood rinse were allocated into the portal vein group, and 19 recipients undergoing donor liver albumin water rinse were allocated into the albumin group. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was analyzed using the t test. Measurement data of skewed distribution were represented as M(range). Count data were descried as absolute numbers, and comparison between groups was analyzed using the Fisher exact probability. Results:(1) Surgical situations. The anhepatic phase time and arterial blood Ca 2+ concentration within 5 minutes after reperfusion of the recipients were (52±12)minutes and (0.99±0.10)mmol/L in the portal vein group, versus (64±12)minutes and (1.05±0.07)mmol/L in the albumin group, showing significant differences in the above indicators between the two groups ( t=2.94, 2.22, P<0.05). The mean arterial pressure, arterial blood K +concentration and arterial blood pH within 5 minutes after reperfusion of the recipients were (70±24)mmHg (1 mmHg=0.133 kPa), (4.7±1.3)mmol/L and 7.27±0.06 in the portal vein group, versus (71±28)mmHg, (4.6±1.1)mmol/L and 7.30±0.07 in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.14, 0.30, 1.22, P>0.05). (2) Post-operative situations. Cases with post-reperfusion syndrome (PRS), cases with severe PRS of cardiac arrest, cases with primary graft nonfunction of the recipients were 6, 0, 2 in the portal vein group, versus 8, 1, 1 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). Total bilirubin on postoperative day 7 of the recipients was (90±52)μmol/L in the portal vein group, versus (166±112)μmol/L in the albumin group, showing a significant difference between the two groups ( t=2.66, P<0.05). International normalized ratio on postoperative day 7, the highest alanine aminotransferase and aspartate aminotransferase within 7 days after operation of the recipients were 2.1±2.0, (1 952±2 813)IU/L and (3 944±6 673)IU/L in the portal vein group, versus 1.8±0.6, (1 023±1 014) IU/L and (2 005±2 910)IU/L in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.66, 1.23, 1.08, P>0.05). Recipients with hepatic artery complication and biliary complication were 1 and 2 in the portal vein group, versus 0 and 4 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). There were 3 cases and 2 cases died during the perioperative period in the portal vein group and the albumin group, respectively. (3) Follow-up. Of the 35 recipients, 30 recipients were followed up for 534(range, 28?776)days after operation. During the follow-up, there were 3 patients with postoperative complications in the portal vein group including 2 cases died and 1 case recovered after sympto-matic treatment. There were 5 patients with postoperative complications in the albumin group including 1 case died and 4 cases recovered after symptomatic treatment. Up to the follow-up date, 11 patients in the portal vein group and 16 patients in the albumin group were in good condition. Conclusion:Rinse of the donor liver with autologous portal venous blood during liver transplantation can shorten the time of anhepatic phase, without increasing the occurrence of post-reperfusion syndrome, ischemia re-perfusion injury and biliary tract complications.

Accurate classification of the acetabular injuries and appropriate treatment plan are great challenges for orthopedic surgeons because of the irregular anatomical structure of the acetabulum and aggregation of important vessels and nerves around it. Letournel-Judet classification system has been widely applied to classify acetabular fractures. However, there are several limitations, including incomplete inclusion of fracture types, difficulty in understanding and insufficient guidance for surgical treatment, etc. Serious complications such as traumatic arthritis are common due to wrong classification and diagnosis and improper selection of surgical strategy, which brings a heavy burden to the society and families. Three-column classification, based on anatomic characteristics, has advantages of containing more fracture types and being easy to understand, etc. To solve the problems existing in the diagnosis and treatment process based on Letournel-Judet classification, achieve accurate diagnosis and treatment of patients with acetabular fractures, and obtain satisfactory prognosis, the Orthopedic Trauma Emergency Center of Third Hospital of Hebei Medical University and the Trauma Orthopedic Branch of the Chinese Orthopedic Association organized experts from relevant fields to formulate the Expert consensus on the accurate diagnosis and treatment of acetabular fractures based on three-column classification ( version 2023) in terms of principles of evidence-based medicine. Based on the three-column classification, 15 recommendations were proposed, covering the diagnosis, treatment, complication prevention and management, etc, so as to provide reference for accurate diagnosis and treatment of acetabular fractures.

Objective: To quantity the degree of acromial droop tilt and explore its correlation and diagnostic value for subacromial impingement syndrome. Methods: The degree of quantification of shoulder tilt and droop(including Angle α、β、γ、Δ、ε、ζ) was analyzed by preoperative MRI of 40 patients undergoing arthroscopic surgery(experimental group) and 40 healthy shoulder MRI(control group).The correlation and difference of each quantitative index in each group and group were compared to discuss their diagnostic value for rotator cuff injury and subacromial impingement syndrome. Results: There was no significant difference between the patients group and the control group in the acromion droop and tilt correlation the independent sample T test of angle α(P>0.05), respectively, and the difference was statistically significant(P<0.05). The region below the ROC curve of β,γ,Δ,ε,ζ were 0.677, 0.864, 0.707, 0.848, 0.886, respectively, and the region below the ROC curve of β and ζ combined was 0.906, indicating excellent diagnostic performance. Conclusion Acromial droop and tilt correlation angle have certain value in the diagnosis of subacromial impaction syndrome. The quantitative indexes γ,ε,ζ have significant significance in the diagnosis of SAIS, and the combined diagnosis performance of β and ζ is better.

Objective:To investigate the effect of the placement of a drainage tube on the prognosis of patients with pelvic fractures treated by modified Stoppa approach.Methods:The medical records of patients with pelvic fractures treated with modified Stoppa approach from August 2012 to August 2017 were retrospectively analyzed. A total of 43 patients including 32 males and 11 females (mean age 47.6 years, range from16 to 69) were included in the study. According to Young-Burgess classification, there were 12 cases of Lateral Compression type LC-I type; 20 cases of Anterior and Posterior Compression type APC-I type and 11 cases of APC-II type. All patients were treated with modified Stoppa approach to reduce the fracture and fix with plate and screw. According to whether a drainage tube was placed during the operation, 22 cases were placed with a drainage tube (drainage group), and 21 cases were not placed with a drainage tube (non-drainage group). The main observation indicators were the intraoperative conditions, antibiotic application, incision suture removal time, postoperative body temperature change, hospital stay and clinical function (Harris score).Results:Wound infection was not observed in two groups. The duration of antibiotic use in the drainage group was 5.0 d (2.0, 8.0) d, and the non-drainage group was 4.0 d (2.0, 5.0) d, the difference was not statistically significant ( Z=1.161, P=0.924). The hospital stays of the two groups were 18.5 d (15.0, 24.3) d and 19.0 d (13.0, 26.0) d, respectively, and the difference was not statistically significant ( Z=0.542, P=0.591). The operation time was 150.2±52.4 min in the drainage group and 138.8±41.2 min in the non-drainage group, and the difference was not statistically significant ( t=0.791, P=0.433). The blood loss in the drainage group was 604.6±387.3 ml, and the non-drainage group was 581.0±275.0 ml. The difference was not statistically significant ( t=0.276, P=0.784). The postoperative body temperature changes of patients in the drainage group and non-drainage group were on day 1 (37.5±0.5 ℃ vs. 37.4±0.4 ℃, t=0.322, P>0.05), day 3 (37.1±0.4 ℃ vs. 37.0±0.4 ℃, t=0.286, P>0.05), day 5 (37.0± 0.3 ℃ vs. 36.8±0.2 ℃, t=2.127, P>0.05), on the 7th day (36.8±0.2 ℃ vs. 36.7±0.4 ℃, t=0.491, P>0.05), the difference was not statistically significant. The time for suture removal of surgical incision was 14.1±0.6 d in the drainage group and 13.9±0.6 d in the non-drainage group, and the difference was not statistically significant ( t=1.072, P=0.329). The Harris scores of the two groups were 96 (91, 100) points for the drainage group and 96 (93, 97) points for the non-drainage group, and the difference was not statistically significant ( Z=0.107, P=0.607). Conclusion:There is no significant influence of the application of drainage on recovery of wound or function for patients with pelvic surgery.

A 46-year-old female patient with rheumatoid arthritis received oral folic acid 10 mg thrice daily for nutritional megaloblastic anemia. About 8 minutes after the first administration, the patient developed itchy skin all over the body, followed by diffuse macular papules on the head, face, limbs, and trunk. Considering the immediate anaphylaxis caused by folic acid, folic acid was discontinued and chlorphenamine 4 mg was given orally. However, her skin symptoms were aggravated, followed by shortness of breath, chest tightness, nausea, and etc. Symptomatic treatments with dexamethasone, 10% calcium gluconate, promethazine, and oxygen inhalation were given immediately. Forty minutes later, her itchy skin was relieved; 5 hours later, the rashes subsided; and 7 hours later, the allergic symptoms disappeared. After 3 days of treatment with chlorphenamine, folic acid desensitization treatment was performed. Then no adverse reactions recurred and the patient′s anemia was gradually improved. The patient continued to took oral loratadine and folic acid. At 1 month of follow-up, she had no discomfort, and the laboratory tests showed hemoglobin 113.5 g/L. Drugs were stopped and the patient was instructed to visit the department of rheumatology for the treatment of rheumatoid arthritis.

A 62-year-old male patient with chronic myelogenous leukemia (chronic phase) received nilotinib 400 mg twice daily. The patient developed mild fatigue, precordial discomfort, and chest tightness 5 hours after the first medication, which were relieved after rest. One hour after the second medication on the same day, the symptoms of precordial discomfort and chest tightness recurred, and they were relieved after rest again. One hour after taking the medicine again the next day, the above symptoms recurred and were aggravated, which could not be relieved after rest. Laboratory tests showed that serum troponin I was 2.67 μg/L, myoglobin was 195.1 μg/L, and creatine kinase MB was 37.7 μg/L. Electrocardiogram (ECG) showed that ST segment depression was >0.1 mV in leads I, II, III, aVL, aVF, and V 1-V 6, T-wave inversion, and QT/QTc was 350/402 ms. The patient was diagnosed as having acute non-ST segment elevation myocardial infarction, which was considered to be related to nilotinib. After 3 weeks of drug withdrawal and vasodilator and anticoagulant therapy, the laboratory tests showed that serum troponin I was not detected, myoglobin was 21.7 μg/L, and creatine kinase MB was 0.8 μg/L. ECG examination showed ST segment depression and T-wave inversion disappeared in leads I, II, III, aVL, aVF and V 1-V 6, and QT/QTc was 370/376ms.

A 46-year-old female patient with rheumatoid arthritis received oral folic acid 10 mg thrice daily for nutritional megaloblastic anemia. About 8 minutes after the first administration, the patient developed itchy skin all over the body, followed by diffuse macular papules on the head, face, limbs, and trunk. Considering the immediate anaphylaxis caused by folic acid, folic acid was discontinued and chlorphenamine 4 mg was given orally. However, her skin symptoms were aggravated, followed by shortness of breath, chest tightness, nausea, and etc. Symptomatic treatments with dexamethasone, 10% calcium gluconate, promethazine, and oxygen inhalation were given immediately. Forty minutes later, her itchy skin was relieved; 5 hours later, the rashes subsided; and 7 hours later, the allergic symptoms disappeared. After 3 days of treatment with chlorphenamine, folic acid desensitization treatment was performed. Then no adverse reactions recurred and the patient′s anemia was gradually improved. The patient continued to took oral loratadine and folic acid. At 1 month of follow-up, she had no discomfort, and the laboratory tests showed hemoglobin 113.5 g/L. Drugs were stopped and the patient was instructed to visit the department of rheumatology for the treatment of rheumatoid arthritis.

A 62-year-old male patient with chronic myelogenous leukemia (chronic phase) received nilotinib 400 mg twice daily. The patient developed mild fatigue, precordial discomfort, and chest tightness 5 hours after the first medication, which were relieved after rest. One hour after the second medication on the same day, the symptoms of precordial discomfort and chest tightness recurred, and they were relieved after rest again. One hour after taking the medicine again the next day, the above symptoms recurred and were aggravated, which could not be relieved after rest. Laboratory tests showed that serum troponin I was 2.67 μg/L, myoglobin was 195.1 μg/L, and creatine kinase MB was 37.7 μg/L. Electrocardiogram (ECG) showed that ST segment depression was >0.1 mV in leads I, II, III, aVL, aVF, and V 1-V 6, T-wave inversion, and QT/QTc was 350/402 ms. The patient was diagnosed as having acute non-ST segment elevation myocardial infarction, which was considered to be related to nilotinib. After 3 weeks of drug withdrawal and vasodilator and anticoagulant therapy, the laboratory tests showed that serum troponin I was not detected, myoglobin was 21.7 μg/L, and creatine kinase MB was 0.8 μg/L. ECG examination showed ST segment depression and T-wave inversion disappeared in leads I, II, III, aVL, aVF and V 1-V 6, and QT/QTc was 370/376ms.