Immune Rejection Research Articles

Nanoplatform-Based In Vivo Gene Delivery Systems for Cancer Therapy.

Gene therapy uses modern molecular biology methods to repair disease-causing genes. As a burgeoning therapeutic, it has been widely applied for cancer therapy. Since 1989, there have been numerous clinical gene therapy cases worldwide. However, a few are successful. The main challenge of clinical gene therapy is the lack of efficient and safe vectors. Although viral vectors show high transfection efficiency, their application is still limited by immune rejection and packaging capacity. Therefore, the development of non-viral vectors is overwhelming. Nanoplatform-based non-viral vectors become a hotspot in gene therapy. The reasons are mainly as follows. 1) Non-viral vectors can be engineered to be uptaken by specific types of cells or tissues, providing effective targeting capability. 2) Non-viral vectors can protect goods that need to be delivered from degradation. 3) Nanoparticles can transport large-sized cargo such as CRISPR/Cas9 plasmids and nucleoprotein complexes. 4) Nanoparticles are highly biosafe, and they are not mutagenic in themselves compared to viral vectors. 5) Nanoparticles are easy to scale preparation, which is conducive to clinical conversion and application. Here, an overview of the categories of nanoplatform-based non-viral gene vectors, the limitations on their development, and their applications in cancer therapy.

Time to Think Antifungal Resistance Increased Antifungal Resistance Exacerbates the Burden of Fungal Infections Including Resistant Dermatomycoses.

Increased antifungal resistance is exacerbating the burden of invasive fungal infections, as well as potentially contributing to the increase in resistant dermatomycoses. In this commentary, we focus on antifungal drug resistance, in contrast to antibacterial resistance. We provide a brief historical perspective on the emergence of antifungal resistance and propose measures for combating this growing health concern. The increase in the incidence of invasive and cutaneous fungal infections parallels advancements in medical interventions, such as immunosuppressive drugs, to manage cancer and reduce organ rejection following transplant. A disturbing relatively new trend in antifungal resistance is the observation of several fungal species that now exhibit multidrug resistance (eg, Candida auris, Trichophyton indotineae). Increasing awareness of these multidrug-resistant species is paramount. Therefore, increased education regarding potential fungus-associated infections is needed to address awareness in the general healthcare setting, which may result in a more realistic picture of the prevalence of antifungal-resistant infections. In addition to education, increased use of diagnostic tests (eg, micro and macro conventional assays or molecular testing) should be routine for healthcare providers facing an unknown fungal infection. Two critical barriers that affect the low rates for Antifungal Susceptibility Testing (AST) are low (or a lack of) sufficient insurance reimbursement rates and the low number of qualified laboratories with the capacity to perform AST. The ultimate aim is to improve the quality of patient care through fungal identification, diagnosis, and, where appropriate, susceptibility testing. Here we propose an all-encompassing call to action to address this emerging challenge.

Comparison of therapeutic effects between big-bubble deep anterior lamellar keratoplasty and penetrating keratoplasty for medically unresponsive Acanthamoeba keratitis

PurposeTo compare the outcomes of big-bubble deep anterior lamellar keratoplasty (BB-DALK) and penetrating keratoplasty (PKP) in the management of medically unresponsive Acanthamoeba keratitis (AK).MethodsThis retrospective study included 27 eyes of BB-DALK and 24 eyes of PKP from a tertiary ophthalmology care centre. Glucocorticoid eye drops were subsequently added to the treatment plan 2 months postoperatively based on the evaluation using confocal laser scanning microscopy. The clinical presentations, best-corrected visual acuity (BCVA), postoperative refractive outcomes, graft survival, and Acanthamoeba recurrence were analyzed.ResultsThe AK patients included in the study were in stage 2 or stage 3, and the percentage of patients in stage 3 was higher in the PKP group (P = 0.003). Clinical presentations were mainly corneal ulcers and ring infiltrates, and endothelial plaques, hypopyon, uveitis and glaucoma were more common in the PKP group (P = 0.007). The BCVA and the graft survival rate showed no statistically significant differences between the two groups at 1 year after surgery. However, 3 years postoperatively, the BCVA of 0.71 ± 0.64 logMAR, the graft survival rate of 89.5%, and the endothelial cell density of 1899 ± 125 cells per square millimeter in the BB-DALK group were significantly better than those of the PKP group (P = 0.010, 0.046, and 0.032, respectively). 3 eyes (11.1%) in the BB-DALK group and 2 eyes (8.3%) in the PKP group experienced Acanthamoeba recurrence, but the rates showed no statistically significant difference between the two groups (P = 1.000). In the PKP group, immune rejection and elevated intraocular pressure were observed in 5 and 6 eyes, respectively.ConclusionCorneal transplantation is recommended for AK patients unresponsive to antiamoebic agents. The visual acuity and graft survival can be maintained after BB-DALK surgery. Acanthamoeba recurrence is not related to the surgical approach performed, whereas complete dissection of the infected corneal stroma and delayed prescribing of glucocorticoid eye drops were important to prevent recurrence.

11 Transcriptomic changes in response to form of selenium on the interferon-tau signaling mechanism in the caruncular tissue of beef heifers at maternal recognition of pregnancy

Abstract It is necessary to supplement selenium (Se) to the diet of beef cattle in regions where the soils and forages are deficient in this trace mineral. Supplementation with Se conventionally occurs using an inorganic form (ISe) although the organic forms (OSe) are available when cattle consume forage. Previously we have investigated the effects of supplemental Se as ISe, or a 1:1 mixture of ISe to OSe (MIX) on grazing beef cows and heifers and have observed significant effects on the corpus luteum (CL) and endometrium. The MIX form of Se increased systemic progesterone (P4) during the early luteal phase of the estrous cycle at a time that can significantly improve early embryonic development. We subsequently investigated the effects of MIX form Se versus ISe on the mRNA transcripts encoding IFNτ- and P4-induced proteins in the caruncular (CAR) tissue of the uterine endometrium at maternal recognition of pregnancy (MRP). MIX-supplemented heifers had a decrease in the relative abundance of mRNAs encoding DGAT2, FGF2, IFIT3, ISG15, MX1, OAS2, and RSAD2 in CAR which was coupled with significantly longer conceptuses at MRP. Presently, we examined transcriptomic changes in the CAR tissue of the endometrium at MRP. Angus-cross heifers (n = 20) were exposed to a 45-d period of Se depletion (no supplemental Se) followed by a 45-day repletion period with ISe alone. Heifers were then randomly assigned to 90 days of treatment with a vitamin-mineral mix containing 35-ppm Se as ISe (n = 10), or 1:1 mixture of ISe and OSe (n = 10, MIX). Following insemination, heifers were killed at MRP (d 17) and their reproductive tracts collected. Only heifers with a fully intact recovered conceptus were utilized for further analyses (n = 6 per treatment). Transcriptomic analysis using RNA-sequencing was conducted using total mRNA from CAR biopsies. Differential gene expression was determined using Integrated Differential Expression and Pathway Analysis (iDEP.96), and DEG were subjected to canonical, functional, and network analyses using QIAGEN’s Ingenuity Pathway Analysis (IPA). RNA sequencing results were validated using qPCR. At P < 0.05, there was a total of 2,029 DEGs with 1,038 transcripts upregulated, and 991 transcripts downregulated in MIX versus ISe heifers. Saliently, the interferon JAK/STAT pathway signaling through the STAT1/2 heterodimer was significantly down regulated in CAR samples from MIX heifers, as were the following interferon-responsive genes: IFIT1, IFIT2, IFIT3, IRF1, IRF9, ISG15, ISG20, OAS2, RSAD2, and STAT2. Additionally, there were significant changes in mRNA contribution to the immunotolerant environment (IDO1, ISG20, SCARA1, and TGFB1) to allow the fetal allograft to closely interact with the maternal interface. In combination, these findings suggest more advanced preparation of the CAR and developing conceptus for placentation and to evade immune rejection by the maternal endometrium during implantation.

The Role of Mesenchymal Stem/Stromal Cells and Their Extracellular Vesicles in Rheumatoid Arthritis

There is presently no cure for the chronic inflammatory disease rheumatoid arthritis (RA), which affects the joints and other organs. Mesenchymal stem/stromal cells (MSCs) are adult stem cells that are widely studied in inflammatory diseases. Several studies have shown the therapeutic effects of MSCs in preclinical and clinical RA. However, there are a few concerns regarding the use of MSCs, such as immune rejection and malignancy. Since MSCs exert their potential effects in a paracrine manner, more attention has been paid to their extracellular vesicles (MSC-EVs). In the current study, we reviewed the application of MSCs and their EVs in RA. A better understanding of the mechanisms driving MSC and MSC-EVs in RA offers insight into possible treatment options for RA.

Collection efficiency of mononuclear cells in offline extracorporeal photopheresis: can processing time be shortened?

Extracorporeal photopheresis (ECP) is a well-established but lengthy and burdensome cell-based therapy for various diseases such as cutaneous T-cell lymphoma, graft-versus-host disease and organ rejection after transplantation. The number of mononuclear cells (MNCs) that needs to be collected to obtain a clinical response to ECP is still under debate. The purpose of this retrospective study was to determine the number of lymphocytes, monocytes and neutrophils in mononuclear cell products (MCP) by flow cytometry and the collection efficiency in the offline ECP setting. We collected data from 10 different patients undergoing 162 ECP procedures using the Spectra Optia device for MNC collection. White blood cell (WBC) count of MCP was determined using a hematology analyzer. MNCs were analyzed for CD45 and CD14 expression by flow cytometry to exactly determine the collected lymphocyte and monocyte fractions. Collected MCP showed high cell yields with 55.3×106/kg MNCs and 41.1×106/kg lymphocytes. MCP were characterized by high MNC (81.3%) and low neutrophils (18.7%) percentage. Mean collection efficiency for WBCs and for MNCs was 23.9% and 62.0%, respectively. The MNC fraction showed a moderate to high correlation between peripheral blood cell count of patients and MCP count. This study is one of a few reports showing the monocyte-to-lymphocyte relation in MCP for ECP determined by flow cytometry. In comparison to historical data from inline ECP, the offline ECP processing one total blood volume results in considerably higher cell yields. For this reason, and to reduce the burden on patients, we propose that the offline ECP processing time can be substantially reduced.

SOX17/ETV2 improves the direct reprogramming of adult fibroblasts to endothelial cells

An autologous source of vascular endothelial cells (ECs) is valuable for vascular regeneration and tissue engineering without the concern of immune rejection. The transcription factor ETS variant 2 (ETV2) has been shown to directly convert patient fibroblasts into vascular EC-like cells. However, reprogramming efficiency is low and there are limitations in EC functions, such as eNOS expression. In this study, we directly reprogram adult human dermal fibroblasts into reprogrammed ECs (rECs) by overexpressing SOX17 in conjunction with ETV2. We find several advantages to rEC generation using this approach, including improved reprogramming efficiency, increased enrichment of EC genes, formation of large blood vessels carrying blood from the host, and, most importantly, expression of eNOS invivo. From these results, we present an improved method to reprogram adult fibroblasts into functional ECs and posit ideas for the future that could potentially further improve the reprogramming process.

Revolutionizing Kidney Transplantation: Connecting Machine Learning and Artificial Intelligence with Next-Generation Healthcare—From Algorithms to Allografts

This review explores the integration of artificial intelligence (AI) and machine learning (ML) into kidney transplantation (KT), set against the backdrop of a significant donor organ shortage and the evolution of ‘Next-Generation Healthcare’. Its purpose is to evaluate how AI and ML can enhance the transplantation process, from donor selection to postoperative patient care. Our methodology involved a comprehensive review of current research, focusing on the application of AI and ML in various stages of KT. This included an analysis of donor–recipient matching, predictive modeling, and the improvement in postoperative care. The results indicated that AI and ML significantly improve the efficiency and success rates of KT. They aid in better donor–recipient matching, reduce organ rejection, and enhance postoperative monitoring and patient care. Predictive modeling, based on extensive data analysis, has been particularly effective in identifying suitable organ matches and anticipating postoperative complications. In conclusion, this review discusses the transformative impact of AI and ML in KT, offering more precise, personalized, and effective healthcare solutions. Their integration into this field addresses critical issues like organ shortages and post-transplant complications. However, the successful application of these technologies requires careful consideration of their ethical, privacy, and training aspects in healthcare settings.

Advances in HIV Gene Therapy.

Early gene therapy studies held great promise for the cure of heritable diseases, but the occurrence of various genotoxic events led to a pause in clinical trials and a more guarded approach to progress. Recent advances in genetic engineering technologies have reignited interest, leading to the approval of the first gene therapy product targeting genetic mutations in 2017. Gene therapy (GT) can be delivered either in vivo or ex vivo. An ex vivo approach to gene therapy is advantageous, as it allows for the characterization of the gene-modified cells and the selection of desired properties before patient administration. Autologous cells can also be used during this process which eliminates the possibility of immune rejection. This review highlights the various stages of ex vivo gene therapy, current research developments that have increased the efficiency and safety of this process, and a comprehensive summary of Human Immunodeficiency Virus (HIV) gene therapy studies, the majority of which have employed the ex vivo approach.

Preparation of Hirudin-Loaded Chitosan/Polycaprolactone Bowl-Shaped Particles and an Application for a Drug Delivery System

Atherosclerosis, a disease that mainly affects human blood vessels, can cause various cerebral ischaemic diseases such as coronary heart disease and peripheral arterial disease. However, conventional drugs for the treatment of atherosclerosis have the disadvantages of low bioavailability and high toxicity. Bowl-shaped particles not only have the excellent properties of traditional spherical particles, such as improved drug distribution, increased drug absorption, reduced drug toxicity and side effects, but also are easier to circulate in the blood for a long time, have reduced immune rejection and have a larger specific surface area. Chitosan/polycaprolactone bowl-shaped particles were prepared via electrostatic spraying, and the effects of precursor solution concentration and polymer ratio on particle morphology were investigated. Chitosan/polycaprolactone composite bowl-shaped particles containing hirudin were prepared under optimal parameters for sustained anticoagulation. The anticoagulant molecules of hirudin could be continuously released from the composite scaffold as the bowl particles degraded. The biocompatibility and haemocompatibility of the composite particles were assessed using mouse glial cells and rabbit blood, and the results showed that the cell viability of the drug-loaded particles was overall above 90% and the haemolysis rate was below 2%. By controlling the release rate of hirudin, bowl-shaped particles can achieve a long-term anticoagulant drug delivery system and have wider application potential as a novel blood contact material.

Serum Extracellular Vesicle Protein Profiling for Prediction of Corneal Transplant Rejection.

Corneal transplantation is the most common transplant procedure worldwide. Despite immune and angiogenic privilege of the cornea, 50% to 70% of corneal transplants fail in high-risk recipients, primarily because of immune rejection. Therefore, it is crucial to identify predictive biomarkers of rejection to improve transplant survival. In search for predictive biomarkers, we performed proteomics analysis of serum extracellular vesicles (EVs) in a fully major histocompatibility complex-mismatched (C57BL/6-to-BALB/c) murine corneal transplantation model, wherein 50% of transplants undergo rejection by day 28 following transplantation. Our time course study revealed a decrease in the number of serum EVs on day 1, followed by a gradual increase by day 7. A comparative analysis of proteomics profiles of EVs from transplant recipients with rejection (rejectors) and without rejection (nonrejectors) found a distinct enrichment of histocompatibility 2, Q region locus 2, which is a part of major histocompatibility complex-class I of donor C57BL/6 mice, in day 7 EVs of rejectors, compared with nonrejectors, syngeneic controls, or naïve mice. In contrast, serum amyloid A2, a protein induced in response to injury, was increased in day 7 EVs of nonrejectors. Our findings offer noninvasive EV-based potential biomarkers for predicting corneal allograft rejection or tolerance.

HLA-G Expression/Secretion and T-Cell Cytotoxicity in Missed Abortion in Comparison to Normal Pregnancy.

The main role of HLA-G is to protect the semi-allogeneic embryo from immune rejection by proper interaction with its cognate receptors on the maternal immune cells. Spontaneous abortion is the most common adverse pregnancy outcome, with an incidence rate between 10% and 15%, with immunologic dysregulation being thought to play a role in some of the cases. In this study, we aimed to detect the membrane and soluble HLA-G molecule at the maternal-fetal interface (MFI) and in the serum of women experiencing missed abortion (asymptomatic early pregnancy loss) in comparison to the women experiencing normal early pregnancy. In addition, the proportion of T cells and their cytotoxic profile was evaluated. We observed no difference in the spatial expression of HLA-G at the MFI and in its serum levels between the women with missed abortions and those with normal early pregnancy. In addition, comparable numbers of peripheral blood and decidual total T and γδT cells were found. In addition, as novel data we showed that missed abortion is not associated with altered extravilous invasion into uterine blood vessels and increased cytotoxicity of γδT cells. A strong signal for HLA-G on non-migrating extravilous trophoblast in the full-term normal placental bed was detected. In conclusion, HLA-G production at the MFI or in the blood of the women could not be used as a marker for normal pregnancy or missed abortions.

Effects of Bone Marrow Mesenchymal Stem Cell-Derived Exosomes in Central Nervous System Diseases.

Central nervous system (CNS) diseases are one of the diseases that threaten human health. The delivery of drugs targeting the CNS has always been a significant challenge; the blood-brain barrier (BBB) is the main obstacle that must be overcome. The rise of bone marrow mesenchymal stem cell (BMSC) therapy has brought hope for the treatment of CNS diseases. However, the problems of low homing rate, susceptibility differentiation into astrocytes, immune rejection, and formation of iatrogenic tumors of transplanted BMSCs limit their clinical application. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have become a hot research topic in the treatment of CNS diseases in recent years because of their excellent histocompatibility, low immunogenicity, ease of crossing the BBB, and their ability to serve as natural carriers for treatment. This article reviews the mechanisms of BMSC-Exos in CNS diseases and provides direction for further research.

Special populations in metastatic renal cell carcinoma.

This review focuses on special populations poorly represented in current evidence-based practice for metastatic renal cell carcinoma (mRCC). This includes the elderly and frail, patients on immunosuppression or with autoimmune diseases, patients with brain, liver, and/or bone metastases, and RCC with sarcomatoid features. Certain populations are poorly represented in current trials for mRCC. Patients with central nervous system (CNS) metastases are often excluded from first-line therapy trials. Modern doublet systemic therapy appears to benefit patients with bone or liver metastases, but data supporting this conclusion is not robust. Post-hoc analyses on patients with sarcomatoid differentiation have shown improved response to modern doublet therapy over historical treatments. The elderly are underrepresented in current clinical trials, and most trials exclude all but high-performing (nonfrail) patients, though true frailty is likely poorly captured using the current widely adopted indices. It is difficult to make conclusions about the efficacy of modern therapy in these populations from subgroup analyses. Data from trials on other malignancies in patients with autoimmune diseases or solid organ transplant recipients on immunosuppression suggest that immune checkpoint inhibitors (ICIs) may still have benefit, though at the risk of disease flare or organ rejection. The efficacy of ICIs has not been demonstrated specifically for RCC in this group of patients. The elderly, frail, and immunosuppressed, those with tumors having aggressive histologic features, and patients with brain, bone, and/or liver metastases represent the populations least understood in the modern era of RCC treatment.

Autologous cryo-shocked neutrophils enable targeted therapy of sepsis via broad-spectrum neutralization of pro-inflammatory cytokines and endotoxins.

Background: Sepsis is a life-threatening disease characterized by multiple organ failure due to excessive activation of the inflammatory response and cytokine storm. Despite recent advances in the clinical use of anti-cytokine biologics, sepsis treatment efficacy and improvements in mortality remain unsatisfactory, largely due to the mechanistic complexity of immune regulation and cytokine interactions. Methods: In this study, a broad-spectrum anti-inflammatory and endotoxin neutralization strategy was developed based on autologous "cryo-shocked" neutrophils (CS-Neus) for the management of sepsis. Neutrophils were frozen to death using a novel liquid nitrogen "cryo-shock" strategy. The CS-Neus retained the source cell membrane structure and functions related to inflammatory site targeting, broad-spectrum inflammatory cytokines, and endotoxin (LPS) neutralizing properties. This strategy aimed to disable harmful pro-inflammatory functions of neutrophils, such as cytokine secretion. Autologous cell-based therapy strategies were employed to avoid immune rejection and enhance treatment safety. Results: In both LPS-induced sepsis mouse models and clinical patient-derived blood samples, CS-Neus treatment significantly ameliorated cytokine storms by removing inflammatory cytokines and endotoxin. The therapy showed notable anti-inflammatory therapeutic effects and improved the survival rate of mice. Discussion: The results of this study demonstrate the potential of autologous "cryo-shocked" neutrophils as a promising therapeutic approach for managing sepsis. By targeting inflammatory organs and exhibiting anti-inflammatory activity, CS-Neus offer a novel strategy to combat the complexities of sepsis treatment. Further research and clinical trials are needed to validate the efficacy and safety of this approach in broader populations and settings.

Conversion from twice-daily everolimus to once-daily sirolimus in long-term stable liver transplant recipients

BackgroundAfter organ transplantation, strategies for simplifying the therapeutic regimen may improve adherence and prevent acute organ rejection and/or late graft loss. The present study aimed to evaluate the safety and efficacy of conversion from everolimus (EVR) twice daily to sirolimus (SIR) once daily in a large cohort of liver transplantation (LT) patients. MethodsWe included 108 LT patients with at least 12 months of post-transplant follow-up and no rejection episodes in the last year. Conversion was based on a 1:1 ratio (but eventually adapted to available formulations of SIR). ResultsThe median age at the time of conversion was 68.9 years (range: 26.1–83.6); 75.0% were men. The main indications for mTOR inhibitor use were renal failure (38.9%) and/or a history of malignancy (37.0%). Median conversion time after LT was 14.8 years (range: 2.3–31.5). The median dose of EVR and SIR (initially) was 1.50 mg/day (range: 0.5–4.5). The mean follow-up after conversion was 15.8±4.4 months. Median serum EVR/SIR trough levels before/after conversion were 3.85 ng/mL vs. 6.32 ng/mL (p < 0.05), i.e. a 1:1.64 ratio. At the end of follow-up after conversion, the median dose of SIR was 1.25 mg/day (range: 0.5–3.5), and the mean serum SIR trough level was 5.23 ng/mL; 9 patients (8.3%) had returned to EVR, because of side effects (mainly digestive), that resolved thereafter. No biopsy-proven acute rejection episode was observed. Finally, 87.1% of patients considered the conversion beneficial and the cost was reduced by 50.3%. ConclusionThe results of our study indicate that conversion from once-daily EVR to once-daily SIR in stable LT patients is safe, but needs dose adaptations and careful monitoring.

The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft.

Much of our knowledge of organ rejection after transplantation is derived from rodent models. We used single-nucleus RNA sequencing to investigate the inflammatory myocardial microenvironment in human pediatric cardiac allografts at different stages after transplantation. We distinguished donor- from recipient-derived cells using naturally occurring genetic variants embedded in single-nucleus RNA sequencing data. Donor-derived tissue resident macrophages, which accompany the allograft into the recipient, are lost over time after transplantation. In contrast, monocyte-derived macrophages from the recipient populate the heart within days after transplantation and form 2 macrophage populations: recipient MP1 and recipient MP2. Recipient MP2s have cell signatures similar to donor-derived resident macrophages; however, they lack signatures of pro-reparative phagocytic activity typical of donor-derived resident macrophages and instead express profibrotic genes. In contrast, recipient MP1s express genes consistent with hallmarks of cellular rejection. Our data suggest that recipient MP1s activate a subset of natural killer cells, turning them into a cytotoxic cell population through feed-forward signaling between recipient MP1s and natural killer cells. Our findings reveal an imbalance of donor-derived and recipient-derived macrophages in the pediatric cardiac allograft that contributes to allograft failure.

Attach importance to the orderly development of different corneal transplant procedures

There are various surgical methods for corneal transplantation, each requiring precise treatment tailored to the characteristics and different layers of corneal opacity or lesions. These layers include the corneal epithelium, stroma (lamellar), and corneal endothelium, with options for full-thickness (penetrating) corneal transplantation or artificial corneal transplantation. However, a current issue in clinical practice is that, regardless of the degree of corneal disease, the availability of corresponding eye bank support, or surgical conditions, classic penetrating (full-thickness) corneal transplantation is universally performed. Alternatively, there is a trend toward adopting technically demanding procedures such as endothelial transplantation and artificial corneal transplantation. This trend has led to increased postoperative complications and the wastage of corneal donor materials. Choosing the appropriate corneal transplant procedure can offer advantages such as preserving more healthy corneal tissue, conserving corneal donors, facilitating rapid vision recovery, and minimizing the risk of immune rejection. Corneologists need to master the indications for various corneal transplant surgeries and systematically perform different corneal transplant procedures based on the surgeon's skills, hospital conditions, and eye bank conditions. This approach aims to enhance the success rate of the surgery.

Risk factors of cytomegalovirus infection in patients with failed corneal grafts

Objective: To investigate the levels of cytomegalovirus (CMV) infection and associated risk factors in corneal transplant recipients who experienced transplant failure. Methods: This was a case-control study. Clinical data from 576 cases (576 eyes) of patients who underwent repeat corneal transplant surgery at the Department of Ophthalmology, Peking University Third Hospital, due to corneal transplant failure from January 2016 to May 2022 were collected. Of these, 305 were male and 271 were female, with a median age of 44.0 (0.7, 91.0) years. The CMV infection rate was analyzed based on the detection of CMV DNA in aqueous humor or corneal tissue during corneal transplant surgery. Patients were divided into the CMV group (CMV DNA positive) and the control group (herpes virus DNA negative). The main research indicators included the CMV infection rate, clinical characteristics, and risk factors in corneal transplant recipients. Chi-square tests and binary logistic analysis were used to compare differences between the two groups in general information, systemic diseases, ocular lesions, ocular surgical history, and local and systemic medications. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for each CMV infection risk factor. Results: The overall CMV infection rate was 21.9%(126/576), with annual rates ranging from 10.9% to 37.7% from 2016 to 2021. After applying inclusion and exclusion criteria, 378 patients were included in the control trial, with 126 in the CMV group and 252 in the control group. Statistically significant differences between the two groups were observed in systemic immune-related corneal lesions [CMV group: 38 (30.2%), control group: 26 (10.3%)], local immune and inflammatory corneal lesions [CMV group: 46 (36.5%), control group: 40 (15.9%)], congenital corneal opacity [CMV group: 46 (36.5%), control group: 48 (19.0%)] total number of corneal transplants (CMV group: 178 times, control group: 276 times), corneal deep neovascularization crossing the graft [CMV group: 104 (82.5%), control group: 68 (27.0%)] and severe opacity [CMV group: 44 (34.9%), control group: 30 (11.0%)]. Binary logistic regression analysis showed that systemic immune-related corneal lesions (OR=4.044, 95%CI 1.810-9.033, P<0.001), local immune and inflammatory corneal lesions (OR=3.554, 95%CI 1.569-8.052, P=0.002), congenital corneal opacity (OR=2.606, 95%CI 1.216-5.589, P=0.014), total number of corneal transplants (OR=3.206, 95%CI 1.753-5.864, P<0.001), corneal deep neovascularization crossing the graft (OR=8.347, 95%CI 3.967-17.559, P<0.001), and severe opacity (OR=3.063, 95%CI 1.221-7.682, P=0.017) were independent risk factors for CMV infection after corneal transplant. Conclusions: CMV infection was present in more than 1/5 of corneal transplant recipients who experienced transplant failure. CMV infection after corneal transplant may be related to immune rejection reactions and ocular inflammatory responses. Inflammatory corneal lesions associated with systemic or local immune abnormalities, congenital corneal opacity, and multiple corneal transplants may exacerbate the levels of inflammatory factors during the perioperative period of corneal transplant, increasing the risk of post-transplant CMV infection, leading to the infiltration of deep neovascularization and severe opacity in the cornea.

Biomimetic short fiber reinforced 3-dimensional scaffold for bone tissue regeneration

Bone defects caused by diseases and trauma are considered serious clinical challenges. Autologous and allogeneic transplantations are the most widely used methods to mitigate bone defects. However, transplantation poses risks such as secondary trauma, immune rejection, and disease transmission to patients. Preparing a biologically active bone tissue engineering scaffold as a bone substitute can overcome this problem. In the current study, a PLGA/gelatin (Gel) short fiber-reinforced composite three-dimensional (3D) scaffold was fabricated by electrospinning for bone tissue defect repair. A hybrid scaffold adding inorganic materials hydrotalcite (CaAl-LDH) and osteogenic factors deferoxamine (DFO) based on PLGA and Gel composite filaments was prepared. The structure, swelling, drug release, and compressive resilience performance of the 3D scaffolds in a wet state were characterized and the osteogenic effect of the crosslinked scaffold (C-DLPG) was also investigated. The scaffold has shown the optimum physicochemical attributes which still has 380 kPa stress after a 60% compression cycle and sustainedly released the drug for about twenty days. Moreover, a promising In vivo osteogenic performance was noted with better tissue organization. At 8 weeks after implantation, the C-DLPG scaffold could fill the bone defect site, and the new bone area reached 19 mm2. The 3D microfiber scaffold, in this study, is expected to be a promising candidate for the treatment of bone defects in the future.