OBJECTIVE To study the immunosuppressive effect of combined therapy with FK506 and RS-61443 in rat limb allotransplantation. METHODS: A total of 101 male SD rats were randomly divided into seven groups and used as recipients, and 101 Wistar rats were used as donors. All SD rats were performed limb allotransplantation without using immunosuppressants in control group. In experimental groups (Groups 1-6), the recipients were immunosuppressed with various dosages of FK506, RS-61443 or FK506 + RS61443, after transplantation for 5 weeks. To evaluate the results, we observed circulation of the transplanted limb, the mean rejection time, the histologic grading of skin rejection of limb grafts and the survival time of limb grafts. RESULTS: The control group showed rejection signs (edema and erythema of the skin) after a mean time of 3.36 +/- 1.15 days, and the mean survival time of the allografts was only 7.00 +/- 0.78 days. In the groups only using FK506 or RS-61443, the survival time were prolonged to varying degrees, but rejection occurred even in the period of using drug. As dosage increased, the rejection could not be prevented and the damage to liver and kidney could be induced. In the group using FK506 in combination with RS-61443, only skin and muscle of limb allografts showed slight rejection sign, function of liver and kidney was not obviously affected, the mean survival time of limb allografts was prolonged to 58.76 +/- 6.81 days. CONCLUSIONS: A combination of FK506 and RS-61443 is a more potent immunosuppressive agent than FK506 oro RS-61443 in preventing the rejection of limb allografts, and it can obviously prolong the survival time of limb allografts.
The therapeutic effect of anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) was determined by a number of factors. Comprehensive thorough analysis of clinical features, imaging results and treatment response can predict the potential efficacy and possible vision recovery for the patient, and also can optimize the treatment regime to make a personalized therapy plan. Precise medicine with data from genomics, proteomics and metabolomics study will provide more objective and accurate biology basis for individual precise treatment. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy, to achieve individualized precise diagnosis and treatment, to improve the therapeutic outcome of nAMD.
Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.
Objective To discuss peripheral nerve regeneration under immunosuppression. Methods Current research trends about relationship between peripheral nerve injury and immunoreaction, the experimental result of nerve regeneration after using various immunosuppressors, and the clinical findings after human allogenous hand transplantation were extensively reviewed. Results Peripheral nerve regeneration was accelerated under immunosuppression. Conclusion Peripheral nerve injury may induce immunoreaction, which inhibit nerve regeneration and function recovery.
Objective To summarize the research progress of programmed cell death protein 1 (PD-1)/programmed cell death protein-ligand 1 (PD-L1) inhibitors before liver transplantation of liver cancer. Method The literatures on the application of PD-1/PD-L1 inhibitors before liver transplantation of liver cancer were collected and reviewed. Results PD-1/PD-L1 inhibitors preoperatively treated liver transplantation recipients had a low incidence of postoperative rejection, and routine usage of hormone and immune tolerance induction therapy in liver transplantation recipients might reduce the incidence of rejection caused by PD-1/PD-L1 inhibitors. Conclusion Preoperative usage of PD-1/PD-L1 inhibitors have more benefits than risks for patients with advanced liver cancer.
Objective To investigate the inhibitory effects of IBI302 on experimental choroidal neovascularization (CNV). Methods Affinity of IBI302 to vascular endothelial growth factor (VEGF) family cytokines (including VEGF-A165, VEGF-A121 and placental growth factor PlGF) and complements (C3b, C4b) was determined by enzyme-linked immunosorbent assay (ELISA). The antagonist effect of IBI302 on VEGF was measured by proliferation, migration and tube formation tests of human umbilical vein endothelial cells (HUVEC). The anti-complement activity of IBI302 was measured by hemolysis test mediated by complement classical pathway and alternative pathway. Rhesus laser-induced CNV model was divided into 5 groups including model control group, bevacizumab group, IBI302 0.25 mg group, IBI302 0.50 mg group and IBI302 1.25 mg group. Fluorescein angiography and optical coherence tomography were performed on these monkeys at 14 and 28 days after drug delivery to observe the fluorescein leakage area and retinal thickness. The aqueous VEGF concentration was measured at 29 days after drug delivery. Results IBI302 showed good affinity to VEGF-A165, VEGF-A121 and PlGF, as well as C3b and C4b. IBI302 significantly inhibited the proliferation, migration and tube formation of HUVEC induced by VEGF-A165. IBI302 inhibited the hemolysis induced by complements obviously. At 14 and 28 days after drug delivery, the area of fluorescein leakage and retinal thickness in IBI302 0.25 mg group, IBI302 0.50 mg group, IBI302 1.25 mg group were reduced. The differences of the area of fluorescein leakage and retinal thickness in three IBI302 groups were not significant (P > 0.05). At 29 days after drug delivery, the VEGF concentration in the aqueous of rhesus monkey in bevacizumab group [(38.644±6.521) pg/ml] was decreased than that in model control group [(94.203±17.360) pg/ml], the difference was significant (P < 0.05). The VEGF concentration in the aqueous of rhesus monkey in three IBI302 groups were less than 31.300 pg/ml. Conclusion IBI302 inhibited experimental CNV through blocking the activity of VEGF and complement.
Most immune-related adverse event (irAE) associated with immune checkpoint inhibitors (ICIs) resulted from excessive immune response against normal organs. The severity, timing, and organs affected by these events were often unpredictable. Adverse reactions could cause treatment delays or interruptions, in rare cases, pose a life-threatening risk. The mechanisms underlying irAE involved immune cell dysregulation, imbalances in inflammatory factor expression, alterations in autoantibodies and complement activation, even dysbiosis of intestinal microorganisms. However, the mechanisms of irAE occurrence might differ slightly among organs due to variations in their structures and the functions of resident immune cells. Future research should focus on the development of targeted drugs for the prevention or treatment of irAE based on the mechanisms by which irAE occurs in different organs. A deeper understanding of the mechanisms underlying irAE occurrence would aid clinicians in effectively utilizing ICIs and provide valuable guidance for their clinical application.