Organ transplantation is an effective alternative treatment for patients with end-stage organ failure. However, the shortage of donor organs has limited the widespread application of clinical transplantation. In recent years, breakthroughs in CRISPR-Cas9 gene editing technology have overcome the barrier of hyperacute rejection in xenotransplantation, offering a potential solution to the organ shortage crisis. Rejection remains a critical factor affecting graft survival. Antigen-presenting cells play a vital role in the initiation and progression of rejection and immune regulation in xenotransplantation. Therefore, in-depth investigation into the role of antigen-presenting cells in xenotransplantation is of great significance. This article summarizes the roles and therapeutic strategies of professional antigen-presenting cells, including macrophages, dendritic cells and B cells in xenotransplantation, aiming to provide insights for future research on immune regulation mechanisms in this field.

ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

Background As one of the most severe occupational diseases in China, pneumoconiosis is significantly burdened by its complications, which adversely affects patients' quality of life. Objective To identify the influencing factors of complications in pneumoconiosis and to construct an early prediction model for pneumoconiosis complications, providing theoretical guidance for clinical diagnosis, treatment, and rehabilitation. Methods A case-control study was conducted using data from the Chongqing 5G Pneumoconiosis Rehabilitation Management Information Platform. A total of 1872 pneumoconiosis patients with complications, who received rehabilitation at various rehabilitation stations in Chongqing from January 2021 to December 2024, were enrolled as the case group. Concurrently, 2348 patients without complications from the same platform and period were included as the control group. Univariate analysis, LASSO regression, and logistic regression were employed to identify influencing factors for complications. An extreme gradient boosting (XGBoost) model was trained using ten-fold cross-validation to predict pneumoconiosis complications. The SHapley Additive exPlanations (SHAP) method was applied for model visualization. Results The analysis of influencing factors revealed that increased age, silicosis type, advanced stage of pneumoconiosis, dependence in activities of daily living, abnormal muscle strength, increased dyspnea index, presence of cough, viscous sputum, impaired cardiac function, severe abnormality in the 6-minute walk test (6MWT), and increased Borg score were risk factors for complications (P<0.05). The XGBoost model demonstrated an area under the curve (AUC) of receiver operating characteristic of 0.718, and a Brier score of 0.211 for the calibration curve. Decision curve analysis demonstrated a superior net benefit within the threshold probability range of 0.2 to 1.0 compared to "all-patient intervention" and "no-patient intervention" strategies, indicating good predictive performance and significant clinical utility. SHAP visualization identified the top six important features as Borg score, age, 6MWT, muscle strength, pneumoconiosis stage, and cough symptoms. Conclusion Multiple factors influence the occurrence of complications in pneumoconiosis patients. Clinical attention should be focused on elderly patients with decreased cardiopulmonary reserve, pronounced respiratory symptoms, and diminished muscle strength. The XGBoost model demonstrates satisfactory discrimination, calibration, and clinical applicability in predicting pneumoconiosis complications and may serve as a useful reference for clinical decision-making.

Primary splenic lymphoma is a rare malignant neoplasm， with similar clinical manifestations to Sjogren’s syndrome and liver cirrhosis， which often leads to misdiagnosis. This article reports a case of primary splenic lymphoma misdiagnosed as Sjogren’s syndrome with liver cirrhosis， in order to improve the understanding of primary splenic lymphoma， Sjogren’s syndrome， and liver cirrhosis and avoid misdiagnosis and treatment delay.

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

The evaluation of blood compatibility of biomaterials is crucial for ensuring the clinical safety of implantable medical devices. To address the limitations of traditional testing methods in real-time monitoring and electrical property analysis, this study developed a portable electrical impedance tomography (EIT) system. The system uses a 16-electrode design, operates within a frequency range of 1 to 500 kHz, achieves a signal to noise ratio (SNR) of 69.54 dB at 50 kHz, and has a data collection speed of 20 frames per second. Experimental results show that the EIT system developed in this study is highly consistent with a microplate reader ( R ²=0.97) in detecting the hemolytic behavior of industrial-grade titanium (TA3) and titanium alloy-titanium 6 aluminum 4 vanadium (TC4) in anticoagulated bovine blood. Additionally, with the support of a multimodal image fusion Gauss-Newton one-step iterative algorithm, the system can accurately locate and monitor in real-time the dynamic changes in blood permeation and coagulation caused by TC4 in vivo. In conclusion, the EIT system developed in this study provides a new and effective method for evaluating the blood compatibility of biomaterials.
Electric Impedance ; Animals ; Tomography/instrumentation* ; Biocompatible Materials ; Materials Testing/instrumentation* ; Cattle ; Titanium ; Alloys ; Prostheses and Implants

To solve the safety problems caused by the restriction of interaction space and the singular configuration of rehabilitation robot in terminal traction upper limb rehabilitation training, a trajectory planning and tracking control scheme for rehabilitation training is proposed. The human-robot safe interaction space was obtained based on kinematics modeling and rehabilitation theory, and the training trajectory was planned based on the occupational therapy in rehabilitation medicine. The singular configuration of the rehabilitation robot in the interaction space was avoided by exponential adaptive damped least square method. Then, a nonlinear controller for the upper limb rehabilitation robot was designed based on the backstepping control method. Radial basis function neural network was used to approximate the robot model information online to achieve model-free control. The stability of the controller was proved by Lyapunov stability theory. Experimental results demonstrate the effectiveness and superiority of the proposed singular avoidance control scheme.
Humans ; Upper Extremity ; Robotics/methods* ; Biomechanical Phenomena ; Neural Networks, Computer ; Traction/methods* ; Algorithms

OBJECTIVE: To evaluate the effectiveness of early internal fixation combined with free anterolateral thigh perforator flap (ALTPF) transplantation in the treatment of open ankle fracture-dislocation. METHODS: A retrospective analysis was performed on the clinical data of 13 patients with open ankle fracture-dislocation who were admitted and met the inclusion criteria between January 2021 and May 2024. Among them, there were 9 males and 4 females, with the ages ranging from 23 to 61 years (mean, 45.3 years). Fracture types included 5 cases of simple medial or lateral malleolar fracture-dislocation, 7 cases of bimalleolar (medial and lateral) fracture-dislocation, and 1 case of trimalleolar fracture-dislocation. Additionally, 3 cases were complicated with bone defects (1 medial malleolus defect and 2 lateral malleolus defects). All injuries were classified as type ⅢB according to the Gustilo-Anderson classification for open fractures. The size of wound defects ranged from 7 cm×5 cm to 18 cm×12 cm. The time from injury to surgery was 2-20 hours (mean, 4 hours). All patients underwent emergency thorough debridement upon admission. The fracture-dislocation was temporarily stabilized with an external fixator, and the wound was covered with antibiotic-impregnated bone cement sheets or vacuum sealing drainage. Definitive internal fixation of the fracture and free ALTPF transplantation were performed 5-7 days after the initial emergency procedure. Postoperatively, wound healing, flap survival, and fracture union were monitored. At last follow-up, clinical outcomes were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score. RESULTS: All 13 patients were followed up 6-24 months (mean, 8.2 months). All flaps survived completely, and all fractures achieved union, with an union time of 3-11 months (mean, 5.5 months). One patient developed a superficial infection at the wound margin, which healed after regular dressing changes and drainage. No internal fixation-related complication (e.g., deep infection, implant loosening, or secondary ankle instability) were observed. At last follow-up, the total AOFAS ankle-hindfoot score was 78.6±13.5, with 3 excellent, 7 good, 2 fair, and 1 poor cases, yielding an excellent and good rate of 76.9%. CONCLUSION Early internal fixation combined with ALTPF transplantation for open ankle fracture-dislocation can shorten the treatment course and maximize the recovery of ankle joint function.
Humans ; Fracture Fixation, Internal/methods* ; Male ; Middle Aged ; Female ; Adult ; Retrospective Studies ; Perforator Flap/transplantation* ; Ankle Fractures/surgery* ; Thigh/surgery* ; Fractures, Open/surgery* ; Treatment Outcome ; Young Adult ; Plastic Surgery Procedures/methods* ; Fracture Dislocation/surgery*

OBJECTIVE: To investigate the effects of bone density, plate bending degree and proximal screw type on the stress fracture of clavicle hook. METHODS: Three sows weighing between 45 and 50 kg were selected, from which a total of 40 rivs were collected. The 15 ribs of sows were divided into 3 groups according to bone density and bone hardness with 5 rivs in each group. And then the 3 groups were fixed with 6-hole collarbone hook plates and 3 locking screws. Measure the maximum torsion force when the ribs were fractured by force. The same size 15 rids were divided into 3 groups, named forward bending group, 0° group(the angle between the plate surface and the rib surface) and reverse bending group. All fixed with 6-hole collarbone hook plates and locking screws to measure the maximum torsion force of rib stress fracture. Then the same size 10 rids were divided into 2 groups, the normal screw group and the locking screw group with 5 ribs in each group. Both groups were fixed with 6-hole collarbone hook plates and screws. The normal screw group was a normal screw, fixed in proximal end, and two locking screws. The locking screw group was fixed by locking screws. Measure the maximum torsion force of the two groups when the ribs fracture by force. RESULTS: In the bone density experiment, the torque force of hard bone group (104.51±6.27) N was greater than the normal bone group (75.04±3.81) N(t=8.979, P<0.05). The force of normal bone group was greater than the osteoporosis group (49.99±2.12) N(t=12.832, P<0.05). In the bending collarbone hook experiment, the order of the torque force generated by each group as follow:the forward bending group (343.59±6.18) N greater than the 0° group (106.01±5.29) N(t=65.279, P<0.05) greater than the reverse bending group (95.82±4.12) N(t=3.398, P<0.05). The force of the normal screw group (98.68±0.70) N was greater than the locking screw group (50.20±0.95) N(t=91.484, P<0.05). The data comparisons of each group were statistically significant. CONCLUSION Bone density, plate bending degree and proximal screw type had an impact on stress fracture of clavicle hook plate. Higher bone density, forward bending of the steel plate, and ordinary screws in proximal end can reduce the rates of stress fractures of clavicle hooks.
Animals ; Bone Plates ; Clavicle/surgery* ; Swine ; Fractures, Stress/etiology* ; Female ; Risk Factors ; Fracture Fixation, Internal/instrumentation* ; Bone Screws ; Biomechanical Phenomena ; Bone Density