Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

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*

Sonogenetics is an emerging synthetic biology technique that uses sound waves to activate mechanosensitive ion channel proteins on the cell surface to regulate cell behavior and function.Due to the widespread presence of mechanically sensitive ion channel systems in cells and the advantages of non-invasion,strong penetrability,high safety and high accuracy of sonogenetics technology,it has great development potential in basic biomedical research and clinical applications,especially in neuronal regulation,tumor mechanism research,sonodynamic therapy and hearing impairment.This review discusses the basic principles of sonogenetics,the development status of sonogenetics and its application in the prevention and treatment of noise-induced hearing loss,summarizes and analyzes the current challenges and future development direction,thus providing a reference for further research and development of sonogenetics in the field of military medicine.

With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease.

To further enhance the immune effect of the foot-and-mouth disease (FMD) virus-like particles (VLPs) vaccine, this study prepared FMDV VLPs-zeolitic imidazolate (framework-8, ZIF-8) complexes with different particle sizes. We used a biomimetic mineralization method with Zn²⁺ and 2-methylimidazole in different concentration ratios to investigate the effect of size on the immunization effect. The results showed that FMDV VLPs-ZIF-8 with three different sizes were successfully prepared, with an approximate size of 70 nm, 100 nm, and 1 000 nm, respectively. Cytotoxicity and animal toxicity tests showed that all three complexes exhibited excellent biological safety. Immunization tests in mice showed that all three complexes enhanced the titers of neutralizing and specific antibodies, and their immune effects improved as the size of the complexes decreased. This study showed that ZIF-8 encapsulation of FMDV VLPs significantly enhanced their immunogenic effect in a size-dependent manner.
Animals ; Mice ; Foot-and-Mouth Disease/prevention & control* ; Foot-and-Mouth Disease Virus ; Antibodies, Neutralizing ; Immunity, Humoral ; Immunization ; Vaccines, Virus-Like Particle ; Antibodies, Viral ; Viral Vaccines

OBJECTIVE: To investigate the effectiveness of dorsal perforator flap of cross-finger proper digital artery in the treatment of finger soft tissue defect caused by high-pressure injection injury. METHODS: Between July 2011 and June 2020, 14 cases of finger soft tissue defect caused by high-pressure injection injury were repaired with dorsal perforator flap of cross-finger proper digital artery. All patients were male, with a mean age of 36 years (range, 22-56 years). The defects were located on the index finger in 8 cases, middle finger in 4 cases, and ring finger in 2 cases. The causes of injury include 8 cases of emulsion paint injection, 4 cases of oil paint injection, and 2 cases of cement injection. The time from injury to debridement was 2-8 hours, with a mean time of 4.5 hours. The soft tissue defects sized from 4.0 cm×1.2 cm to 6.0 cm×2.0 cm. The flaps sized from 4.5 cm×1.5 cm to 6.5 cm×2.5 cm. The donor site of the flap was repaired with skin graft. The pedicle was cut off at 3 weeks after operation, and followed by functional exercise. RESULTS: All flaps and skin grafts at donor sites survived, and the wounds healed by first intention. Twelve patients were followed-up 16-38 months (mean, 22.6 months). The texture and appearance of all flaps were satisfactory. The color and texture of the flaps were similar to those of the surrounding tissues. The two-point discrimination of the flap was 10-12 mm, with a mean of 11.5 mm. There were different degrees of cold intolerance at the end of the affected fingers. At last follow-up, the finger function was evaluated according to the Upper Extremity Functional Evaluation Standard set up by Hand Surgery Branch of Chinese Medical Association, 3 cases were excellent, 8 cases were good, and 1 case was poor. CONCLUSION The dorsal perforator flap of cross-finger proper digital artery can effectively repair finger soft tissue defect caused by high-pressure injection injury. The operation was simple, and the appearance and function of the finger recover well.
Humans ; Male ; Adult ; Female ; Perforator Flap ; Upper Extremity ; Fingers/surgery* ; Ulnar Artery ; Skin Transplantation

Objective:To explore the clinical effect of cosmetic reconstruction for partial defect of distal segment of digits.Methods:Form January 2018 to January 2021, the Department of Hand Surgery of Institute for Hygiene of Ordnance Industry(The 521 Hospital of Weapon Industry) admitted 129 patients with partial defect of distal segment of thumb or fingers with phalange or tendon exposure. The patients were 111 males and 18 females with an average age of 34(17-59) years old. The sizes of nailbed defect were 0.4 cm×1.1 cm-1.8 cm×2.0 cm, the length of phalange defect was 0.4-1.8 cm, and the sizes of the soft tissue defect were 1.6 cm×1.8 cm-3.2 cm×4.8 cm. Great toe tissue flaps were used to reconstruct the partial defect of distal segment of thumb or fingers after debridement. Wounds of fibular flap of great toe in 77 cases were directly sutured in 17 patients. The donor sites in rest 60 great toes were narrowed first and then repaired with skin grafts in 10 cases, with artificial dermis in 28 cases and with transverse V-Y advancement flaps of ipsilateral great toes for 22 cases. Forty-nine of 52 donor site wounds for hallux toenail flap were repaired with artificial dermis and 3 with free peroneal artery perforator flaps. The method was outpatient follow-up. Postoperative follow-up lasted until July 2022. The check-items for follow-up included: occurrence of necrosis, appearance, shape and texture of the flap, appearance of the reconstructed nails, TPD of the reconstructed digit pulps, tolerance to cold on the scars of flaps, flexion and extension of the reconstructed digits. The healing time of phalanges of the reconstructed digits was evaluated by X-rays. The appearance, sensation, the tolerance to cold of great toe and the movement of donor foot were also assessed.Results:Postoperative follow-up lasted for 18 to 24 months, with an average of 21 months. A total of 128 flaps survived. Necrosis occurred in 1 fibular hallux flap, the necrosis was cured with a reverse digital proper artery island flap. Thereafter, all flaps healed well. The appearance, shape, texture and nails of reconstructed digits were close to the contralateral digits. The reconstructed thumb and finger were evaluated according to Zook, 127 cases were excellent and 2 cases were good.TPD of the pulps of the reconstructed digits was 4-10 mm. The mean score of the Vancouver scar scale(VSS) was 0.6 for scars of the reconstructed digits. The mean score of the Visual analog scale(VAS) was 0.3 for the tolerance to cold. Flexion and extension function recovered well in all the reconstructed digits. According to the Evaluation Criteria of Upper limb Function Hand Surgery Society of Chinese Medical Association, the function of hand was excellent in 127 cases and 1 in each of good and fair. X-rays of all digits showed the phalange healing of the reconstructed digits, with an average healing time of 2 months after surgery, without phalange resorption, infection, nonunion nor stress fracture. There was no difference between the length of the donor great toe and the contralateral toe, except the donor site of the great toe nail root. There was no significant visual difference between the appearance of the donor great toe and the contralateral toe. TPD of the pulps of donor great toe was 4-8 mm. The mean score of the VSS was 1.4 for scars in the donor great toe. The mean score of the VAS was 0.7 for the tolerance to cold of the donor great toe. There was no stress fracture at donor site, and the functions of donor foot were not affected when walking, running, jumping and tiptoeing in all patients.Conclusion:It is an ideal method for reconstructing a partial defect of distal segment of digit by great toe flap. It can not only reconstruct the partial defect of distal segment of the digit, but also results in a good appearance and satisfactory functions of the reconstructed digit. Damage to the donor site is minimum. The length of the donor great toe is unchanged, and it has little impact on sensation and appearance of the donor great toe. Meanwhile, there is no adverse effect on walking, running and jumping with the donor foot.