Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion: A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Development of a rectally administrable Dnase1 to treat septic shock by targeting NETs.

AIMS: Neutrophil extracellular trap (NET), which is formed by DNA threads, induces septic shock by aggravating systemic inflammation. An intravenous administration of deoxyribonuclease is regarded as a compelling modality for treating septic shock. However, alternative routes should be chosen when cutaneous veins are all collapsed due to hypotension. In this study, we genetically engineered this enzyme to develop a rectal suppository formulation to treat septic shock. MAIN METHODS: Dnase1 was mutated at two amino acid residues to increase its stability in the blood and fused with a cell-penetrating peptide CR8 to increase its absorption through the rectal mucosa, which is designated AR-CR8. The life-saving effect of AR-CR8 was evaluated in a LPS-induced shock mouse model. KEY FINDINGS: AR-CR8 was shown to remove NETs effectively in human neutrophils. When AR-CR8 was administered to the mouse rectum, the deoxyribonuclease activity in the mouse serum was significantly increased. In the LPS-induced shock model, 90 % of the control mice died over 72 h after LPS injection. In contrast, the rectal administration of AR-CR8 showed a mortality rate of 30 % by 72 h after LPS injection. The Log-rank test revealed that the survival rate is significantly higher in the AR-CR8 group. The NET markers in the mouse serum were enhanced by LPS, and significantly downregulated in the AR-CR8 group. These results suggest that AR-CR8 ameliorates LPS-induced shock by degrading NETs. SIGNIFICANCE: The engineered DNASE1 could be developed as a rectal suppository formulation to treat septic shock urgently at out-of-hospital places where no syringe is available.

Evaluating the Surgical Outcome of Lymphovenous Anastomosis in Breast Cancer-Related Lymphedema Using Tc-99m Phytate Lymphoscintigraphy: Preliminary Results.

Background: Breast cancer-related lymphedema (BCRL) remains a significant postcancer treatment challenge with no definitive cure. Recent supermicrosurgical treatments, such as lymphovenous anastomosis (LVA), have shown promise but lack established objective indicators for outcome evaluation. We investigated the utility of Technetium-99m (Tc-99m) lymphoscintigraphy, an imaging technique providing objective information on lymphatic fluid flow, for assessing LVA surgical outcomes. Methods and Results: A retrospective cohort analysis of patients undergoing LVA for BCRL was conducted. Lymphoscintigraphy images pre- and 1-year postsurgery were compared to determine changes in lymphatic fluid flow of 18 patients based on newly defined parameters "uptake ratio" and "washout rates." Statistically significant reduction in the uptake ratio was observed in the forearm at 30 and 60 minutes postinjection phases. In addition, the forearm showed higher washout rate, indicating an improved lymphatic function in the forearm. Conclusion: Tc-99m lymphoscintigraphy can provide valuable objective data for evaluating LVA surgical outcomes in BCRL patients. However, site-specific differences in outcomes highlight the need for individualized surgical planning. Further large-scale studies are necessary to validate these preliminary findings and develop a standardized approach for LVA assessment.

Highly Transparent Red Organic Light-Emitting Diodes with AZO/Ag/AZO Multilayer Electrode.

Free-form factor optoelectronics is becoming more important for various applications. Specifically, flexible and transparent optoelectronics offers the potential to be adopted in wearable devices in displays, solar cells, or biomedical applications. However, current transparent electrodes are limited in conductivity and flexibility. This study aims to address these challenges and explore potential solutions. For the next-generation transparent conductive electrode, Al-doped zinc oxide (AZO) and silver (AZO/Ag/AZO) deposited by in-line magnetron sputtering without thermal treatment was investigated, and this transparent electrode was used as a transparent organic light-emitting diode (OLED) anode to maximize the transparency characteristics. The experiment and simulation involved adjusting the thickness of Ag and AZO and OLED structure to enhance the transmittance and device performance. The AZO/Ag/AZO with Ag of 12 nm and AZO of 32 nm thickness achieved the results of the highest figure of merit (FOM) (Φ550 = 4.65 mΩ-1) and lowest roughness. The full structure of transparent OLED (TrOLED) with AZO/Ag/AZO anode and Mg:Ag cathode reached 64.84% transmittance at 550 nm, and 300 cd/m2 at about 4 V. The results demonstrate the feasibility of adopting flexible substrates, such as PET, without the need for thermal treatment. This research provides valuable insights into the development of transparent and flexible electronic devices.

Effects of Korean red ginseng on T-cell repopulation after autologous hematopoietic stem cell transplantation in childhood cancer patients.

Background: Although the survival outcomes of childhood cancer patients have improved, childhood cancer survivors suffer from various degrees of immune dysfunction or delayed immune reconstitution. This study aimed to investigate the effect of Korean Red Ginseng (KRG) on T cell recovery in childhood cancer patients who underwent autologous hematopoietic stem cell transplantation (ASCT) from the perspective of inflammatory and senescent phenotypes. Methods: This was a single-arm exploratory trial. The KRG group (n = 15) received KRG powder from month 1 to month 12 post-ASCT. We compared the results of the KRG group with those of the control group (n = 23). The proportions of T cell populations, senescent phenotypes, and cytokine production profiles were analyzed at 1, 3, 6, and 12 months post-ASCT using peripheral blood samples. Results: All patients in the KRG group completed the treatment without any safety issues and showed a comparable T cell repopulation pattern to that in the control group. In particular, KRG administration influenced the repopulation of CD4+ T cells via T cell expansion and differentiation into effector memory cell re-expressing CD45RA (EMRA) cells. Although the KRG group showed an increase in the number of CD4+ EMRA cells, the expression of senescent and exhausted markers in these cells decreased, and the capacity for senescence-related cytokine production in the senescent CD28- subset was ameliorated. Conclusions: These findings suggest that KRG promotes the repopulation of CD4+ EMRA T cells and regulates phenotypical and functional senescent changes after ASCT in pediatric patients with cancer.

CT texture features and lung shunt fraction measured using 99mTc-macroaggregated albumin SPECT/CT before trans-arterial radioembolization for hepatocellular carcinoma patients.

The aim of this study is to determine whether contrast-enhanced computed tomography (CECT)-based texture parameters can predict high (> 30 Gy) expected lung dose (ELD) calculated using 99mTc macroaggregated albumin single-photon emission computed tomography/computed tomography (SPECT/CT) for pre-trans-arterial radioembolization (TARE) dosimetry. 35 patients were analyzed, with a treatable planned dose of ≥ 200 Gy for unresectable hepatocellular carcinoma (HCC). Lung shunt fraction (LSF) was obtained from planar and SPECT/CT scans. Texture features of the tumor lesion on CECT before TARE were analyzed. Univariate and multivariate linear regression analyses were performed to determine potential ELD > 30 Gy predictors. Among the 35 patients, nine (25.7%) had ELD > 30 Gy, and had a higher LSF than the ELD ≤ 30 Gy group using the planar (20.7 ± 8.0% vs. 6.3 ± 3.3%; P < 0.001) and SPECT/CT (12.4 ± 5.1% vs. 3.5 ± 2.0%; P < 0.001) scans. The tumor integral total (HU × L) value was a predictor for high LSF using SPECT/CT, with an area under the curve, sensitivity, and specificity of 0.983 (95% confidence interval: 0.869-1.000, P < 0.001), 100%, and 88.5%, respectively. The tumor integral total value is an imaging marker for predicting ELD > 30 Gy. Applying CECT texture analysis may assist in reducing time and cost in patient selection and modifying TARE treatment plans.

Comparison of Prophylactic Effects between Localized Biomimetic Minocycline and Systematic Amoxicillin on Implants Placed Immediately in Infected Sockets.

This study evaluated the prophylactic effect of localized biomimetic minocycline and systemic amoxicillin on immediate implant placement at infected extraction sites. Twelve mongrels with six implants each were randomly assigned to five groups: uninfected negative control (Group N); infected with oral complex bacteria (Group P); infected and treated with amoxicillin one hour before implant placement (Group A); infected and treated with minocycline during implant placement (Group B); and infected and treated with amoxicillin one hour before implant placement and with minocycline during implant placement (Group C). Radiographic bone level, gingival index (GI), probing depth (PD), papillary bleeding index (PBI), and removal torque (RT) were recorded. There was no significant difference between Groups A, B, and C for bone loss. Group A showed the highest RT, the lowest PBI, and significantly lower GI and PD values than Group P. Group B exhibited significantly higher RT value than Group N and significantly smaller PD value than Group P at 6 w postoperatively. Localized minocycline could improve implant success by reducing bone loss and increasing RT and systemic amoxicillin could maintain the stability of the peri-implant soft tissue. However, combined use of these two antibiotics did not augment the prophylactic effect.

Intra-sinus rigid fixation of a resorbable barrier membrane to repair a large perforation of the sinus membrane: a technical note.

A resorbable barrier membrane is commonly used for the repair of perforated sinus membranes during sinus lifting surgeries. However, repairing largescale perforations poses challenges for clinicians as the protection and isolation of graft material remain uncertain. With this technique, we aimed to prevent graft material loss and subsequent sinus-related complications using intra-sinus rigid fixation of the resorbable barrier membrane in cases with a large perforation of the sinus membrane.

Detection of recurrence sites using 18F-fluorocholine PET/CT in prostate cancer patients with PSA failure.

Background: The optimal condition for the clinical application of 18F-fluorocholine positron emission tomography-computed tomography (FCH-PET/CT) to detect recurrence sites in prostate-specific antigen (PSA) failure remains unclear due to the heterogeneity of prostate cancer failure. We aimed to evaluate the detection rate of FCH-PET/CT in prostate cancer patients with PSA failure and to determine the optimal PSA level for performing FCH-PET/CT. Methods: FCH-PET/CT was conducted in 89 patients diagnosed with PSA failure after radical treatment (radical prostatectomy in 75 and definitive radiotherapy in 14) between November 2018 and May 2021. Detection rates were examined via receiver operating characteristic (ROC) analysis, and multivariable logistic regression was performed to identify factors affecting positive FCH-PET/CT findings. We also conducted subgroup analyses according to the PSA failure patterns after the radical treatment (persistently high PSA [N = 48] and biochemical recurrence [BCR] [N = 41]). Results: FCH-PET/CT demonstrated a 59.6% overall detection rate, and the optimal PSA threshold for detecting positive findings was ≥ 1.00 ng/mL at the time of imaging. On multivariable analysis, PSA > 1.00 ng/mL (P < 0.001) was a significant predictor of positive FCH-PET/CT findings, especially regarding distant bone metastases (P < 0.001) and recurrence outside the pelvis (P < 0.001). In a subgroup analysis of patients with BCR after initial radical treatment, the area under the ROC curve (AUC) was 0.82, and PSA ≥ 1.75 ng/mL was the optimal value for identifying positive FCH-PET/CT findings. This PSA value was also associated with significantly higher detection rates of distant bone metastases and outside-pelvis metastasis (P < 0.001, both). Conclusion: FCH-PET/CT is a clinically useful tool for detecting tumor recurrence sites in prostate cancer patients with PSA failure if PSA has exceeded a certain value at the time of imaging. Particularly, higher AUC values were observed when FCH-PET/CT was performed in patients with BCR after initial treatment.

Longitudinal multi-omics study of palbociclib resistance in HR-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6) therapy plus endocrine therapy (ET) is an effective treatment for patients with hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer (HR+/HER2- MBC); however, resistance is common and poorly understood. A comprehensive genomic and transcriptomic analysis of pretreatment and post-treatment tumors from patients receiving palbociclib plus ET was performed to delineate molecular mechanisms of drug resistance. METHODS: Tissue was collected from 89 patients with HR+/HER2- MBC, including those with recurrent and/or metastatic disease, receiving palbociclib plus an aromatase inhibitor or fulvestrant at Samsung Medical Center and Seoul National University Hospital from 2017 to 2020. Tumor biopsy and blood samples obtained at pretreatment, on-treatment (6 weeks and/or 12 weeks), and post-progression underwent RNA sequencing and whole-exome sequencing. Cox regression analysis was performed to identify the clinical and genomic variables associated with progression-free survival. RESULTS: Novel markers associated with poor prognosis, including genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four prognostic clusters with distinct molecular features were identified. Tumors with TP53 mutations co-occurring with a unique HRD-high cluster responded poorly to palbociclib plus ET. Comparisons of paired pre- and post-treatment samples revealed that tumors became enriched in APOBEC mutation signatures, and many switched to aggressive molecular subtypes with estrogen-independent characteristics. We identified frequent genomic alterations upon disease progression in RB1, ESR1, PTEN, and KMT2C. CONCLUSIONS: We identified novel molecular features associated with poor prognosis and molecular mechanisms that could be targeted to overcome resistance to CKD4/6 plus ET. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03401359. The trial was posted on 18 January 2018 and registered prospectively.

Serial Quantitative Assessment of Load Redistribution After Medial Open-Wedge High Tibial Osteotomy.

Background: The maximum standardized uptake value (SUVmax), as determined on combined single-photon emission computed tomography and conventional computed tomography (SPECT/CT), can be an indicator of biomechanical changes due to the load redistribution effect after medial open-wedge high tibial osteotomy (MOW-HTO). Purpose/Hypothesis: The purposes of this study were to (1) analyze serial changes in the SUVmax in the medial, lateral, and patellofemoral compartments after MOW-HTO and (2) identify the contributing factors that affect changes in the SUVmax. The hypotheses were that (1) an elevated SUVmax in the medial compartment would be transferred to the lateral compartment because of the load redistribution effect and (2) there would be contributing factors that cause SUVmax changes. Study Design: Case series; Level of evidence, 4. Methods: Included were 67 knees that were treated with biplanar MOW-HTO between March 2019 and December 2020. SPECT/CT was performed immediately after surgery and at 3 months and 1 year postoperatively to determine the serial load redistribution effect of MOW-HTO. The Pearson correlation coefficient was used to evaluate the relationship between SUVmax and radiological parameters, and subgroup analyses were conducted to compare the SUVmax according to associated cartilage procedures and the weightbearing line ratio (WBLR). Results: The SUVmax in the medial and lateral compartments increased at 3 months but decreased at 1 year postoperatively. The load redistribution effect was most prominent in the anterior zones of the femur (medial: P = .041; lateral: P = .012). In the patella, the SUVmax decreased in both the medial and the lateral zones at all follow-up times (P < .001 for all). The SUVmax in the anterolateral and posterolateral articular zones of the femur increased with a greater preoperative WBLR (r = 0.256, P = .039; and r = 0.261, P = .036, respectively). Patients who underwent an associated cartilage procedure had a significantly higher SUVmax in the anteromedial and posteromedial articular zones of both the femur and the tibia at 1 year postoperatively (P ≤ .002 for all). Conclusion: After MOW-HTO, the unloading effect in the anteromedial articular zone of the femur was the most significant. A greater SUVmax in the lateral zones of the femur was observed in cases of overcorrection. The SUVmax in the medial zones was higher postoperatively in patients with associated cartilage procedures.

A Simple, Selective, and General Catalyst for Ring Closing Depolymerization of Polyesters and Polycarbonates for Chemical Recycling.

The ability to efficiently and selectively process mixed polymer waste is important to address the growing plastic waste problem. Herein, we report that the combination of ZnCl2 and an additive amount of poly(ethylene glycol) under vacuum can readily and selectively depolymerize polyesters and polycarbonates with high ceiling temperatures (Tc >200 °C) back to their constitute monomers. Mechanistic experiments implicate a random chain scission mechanism and a catalyst structure containing one equivalent of ZnCl2 per ethylene glycol repeat unit in the poly(ethylene glycol). In addition to being general for a wide variety of polyesters and polycarbonates, the catalyst system could selectively depolymerize a polyester in the presence of other commodity plastics, demonstrating how reactive distillation using the ZnCl2 /PEG600 catalyst system can be used to separate mixed plastic waste.

Corrigendum: Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia.

[This corrects the article DOI: 10.3389/fimmu.2023.1101808.].

CT-free quantitative SPECT for automatic evaluation of %thyroid uptake based on deep-learning.

PURPOSE: Quantitative thyroid single-photon emission computed tomography/computed tomography (SPECT/CT) requires computed tomography (CT)-based attenuation correction and manual thyroid segmentation on CT for %thyroid uptake measurements. Here, we aimed to develop a deep-learning-based CT-free quantitative thyroid SPECT that can generate an attenuation map (µ-map) and automatically segment the thyroid. METHODS: Quantitative thyroid SPECT/CT data (n = 650) were retrospectively analyzed. Typical 3D U-Nets were used for the µ-map generation and automatic thyroid segmentation. Primary emission and scattering SPECTs were inputted to generate a µ-map, and the original µ-map from CT was labeled (268 and 30 for training and validation, respectively). The generated µ-map and primary emission SPECT were inputted for the automatic thyroid segmentation, and the manual thyroid segmentation was labeled (280 and 36 for training and validation, respectively). Other thyroid SPECT/CT (n = 36) and salivary SPECT/CT (n = 29) were employed for verification. RESULTS: The synthetic µ-map demonstrated a strong correlation (R2 = 0.972) and minimum error (mean square error = 0.936 × 10-4, %normalized mean absolute error = 0.999%) of attenuation coefficients when compared to the ground truth (n = 30). Compared to manual segmentation, the automatic thyroid segmentation was excellent with a Dice similarity coefficient of 0.767, minimal thyroid volume difference of - 0.72 mL, and a short 95% Hausdorff distance of 9.416 mm (n = 36). Additionally, %thyroid uptake by synthetic µ-map and automatic thyroid segmentation (CT-free SPECT) was similar to that by the original µ-map and manual thyroid segmentation (SPECT/CT) (3.772 ± 5.735% vs. 3.682 ± 5.516%, p = 0.1090) (n = 36). Furthermore, the synthetic µ-map generation and automatic thyroid segmentation were successfully performed in the salivary SPECT/CT using the deep-learning algorithms trained by thyroid SPECT/CT (n = 29). CONCLUSION: CT-free quantitative SPECT for automatic evaluation of %thyroid uptake can be realized by deep-learning.

Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia.

Introduction: Despite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive. Methods: Here, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients. Results: Differential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients. Discussion: Aberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression.

Quantitative Iodine-123 single-photon emission computed tomography/computed tomography for Iodine-131 therapy of an autonomously functioning thyroid nodule.

PURPOSE: Autonomously functioning thyroid nodules (AFTNs) are treated with iodine-131 (I-131) therapy, which increases the risk of permanent hypothyroidism; however, the risk can be reduced by separately estimating the accumulated activity for the AFTN and extranodular thyroid tissue (ETT). METHODS: A quantitative I-123 single-photon emission computed tomography (SPECT)/CT (5 mCi) was performed in one patient with unilateral AFTN and T3 thyrotoxicosis. The I-123 concentrations measured at 24 h were 12.26 µCi/mL and 0.11 µCi/mL in the AFTN and contralateral ETT, respectively. Thus, the I-131 concentrations and radioactive iodine uptake expected at 24 h by 5 mCi of I-131 were 38.59 µCi/mL and 0.31 for the AFTN and 0.34 µCi/mL and 0.007 for the contralateral ETT. The weight was calculated as CT-measured volume multiplied by 1.03. RESULTS: In the AFTN patient with thyrotoxicosis, we administered 30 mCi of I-131, which would maximize the 24-h I-131 concentration in the AFTN (226.86 µCi/g) and maintain a tolerable concentration in the ETT (1.97 µCi/g). The percentage of I-131 uptake at 48 h post I-131 administration was 62.6%. The patient achieved a euthyroid state at 14 weeks and maintained the state until 2 years post I-131 administration with an AFTN volume reduction of 61.38%. CONCLUSION: The pre-therapeutic planning of quantitative I-123 SPECT/CT may enable a therapeutic window for I-131 therapy, which directs optimal I-131 activity to effectively treat AFTN while preserving the normal thyroid tissue.

BRAFV600E and TERT promoter C228T mutations on ThyroSeq v3 analysis of delayed skin metastasis from papillary thyroid cancer: a case report and literature review.

BACKGROUND: Skin metastasis from papillary thyroid cancer (PTC) is a rare entity that can occur up to decades after treatment of the primary tumor. Here, we present a patient who developed skin metastasis 10 years after treatment of her primary tumor and describe the molecular findings of the metastatic lesion. CASE PRESENTATION: A 44-year-old female with a history of PTC who underwent a total thyroidectomy and radioactive iodine (RAI) treatment 10 years ago presented with a 1.3-cm skin lesion along the prior thyroidectomy scar. A biopsy revealed metastatic PTC, and the patient underwent surgical excision of the lesion. ThyroSeq molecular testing showed the copresence of BRAFV600E mutation and TERT promoter C228T mutation. The patient subsequently received one round of adjuvant RAI therapy. CONCLUSIONS: A high index of suspicion is warranted in patients with a history of PTC who develop a skin lesion, even several years after remission of the primary disease. In patients with high-risk mutations, such as BRAFV600E and TERT promoter C228T mutations, long-term surveillance of disease recurrence is particularly important.

Targeting tumor-intrinsic PD-L1 suppresses the progression and aggressiveness of head and neck cancer by inhibiting GSK3ß-dependent Snail degradation.

PURPOSE: PD-L1 is an immune checkpoint protein that allows cells to evade T-cell-mediated immune responses. Herein, we uncover a tumor-intrinsic mechanism of PD-L1 that is responsible for the progression and aggressiveness of HNC and reveal that the extracts of a brown alga can target the tumor-intrinsic signaling pathway of PD-L1. METHODS: The biological functions of PD-L1 in the proliferation and aggressiveness of HNC cells in vitro were examined by metabolic activity, clonogenic, tumorigenicity, wound healing, migration, and invasion assays. The clinical importance of PD-L1 in the prognosis of patients with HNC was analyzed by immunohistochemistry. The relationship between PD-L1 and EMT was confirmed via western blotting, qPCR, and immunocytochemistry. RESULTS: Through our in silico approach, we found that PD-L1 was upregulated in HNC and was correlated with an unfavorable clinical outcome in patients with HNC. PD-L1 was crucial for promoting tumor growth, both in vitro and in vivo. High expression of PD-L1 was closely correlated with LN metastasis in OSCC. PD-L1 facilitated the cytoskeletal reorganization and aggressiveness of HNC cells. Moreover, PD-L1 enhanced the EMT of HNC cells by regulating the Snail/vimentin axis. Consistently, MEIO suppressed the PD-L1/Snail/vimentin axis, thereby inhibiting the aggressiveness of HNC cells. Inhibition of PD-L1 induced by PD-L1 silencing or MEIO treatment caused Snail degradation through a GSK3ß-dependent mechanism. The tumor-intrinsic function of PD-L1 could be attributed to the regulation of the GSK3ß/Snail/vimentin axis. CONCLUSION: The discovery of MEIO targeting the tumor-intrinsic function of PD-L1 may prove particularly valuable for the development of novel and effective anticancer drug candidates for HNCs overexpressing PD-L1.

Comparison of arthroscopic primary and revision Bankart repair for capsulolabral restoration: a matched-pair analysis.

INTRODUCTION: There have been no previous studies comparing serial radiologic results between primary and revision Bankart repair despite the significance of capsulolabral height and slope restoration. The purpose of this study was (1) to compare serially the height and slope of the repaired labrum in the early postoperative period among primary and revision Bankart repair groups, and (2) to compare clinical outcomes between the two groups. MATERIALS AND METHODS: This study included each 24 patients who underwent arthroscopic primary Bankart repair (Group A) and revision Bankart repair (Group B) matched by age, sex, and glenoid defect ratio. Postoperative serial radiologic assessment of the repaired labral height and slope was proceeded using magnetic resonance imaging (MRI) or computed tomographic arthrography (CTA) at 3 weeks and 6 months. RESULTS: There were no significant differences in labral height and slope at 3 weeks and 6 months postoperatively in Group A. However, significant reductions in labral height and slope were evident between 3 weeks and 6 months postoperatively in Group B (P < 0.05). Group A yielded superior results to Group B with respect to labral height and slope at each time point (P < 0.05) in between-group analyses. The clinical outcomes were not significantly different between the two groups except for the patients' return to their premorbid sports activity level (P = 0.024). CONCLUSIONS: The height and slope of the repaired capsulolabral structures in the early postoperative period after arthroscopic revision Bankart repair group were significantly lower than those of the primary Bankart repair group. Also the reduction of labral height and slope was significant in the revision Bankart repair group over time. Nonetheless, clinical outcomes did not differ significantly except return to premorbid sports activity level at final follow-up.

Anti-thymocyte globulin-mediated immunosenescent alterations of T cells in kidney transplant patients.

Objectives: Kidney transplant (KT) is the most effective treatment for end-stage renal disease. The immunosuppressant anti-thymocyte globulin (ATG) has been applied for induction therapy to reduce the risk of acute transplant rejection for patients at high immunological risk. Despite its putative role in replicative stress during immune reconstitution, the effects of ATG on T-cell immunosenescent changes remain to be understood. Methods: Phenotypic and functional features of senescent T cells were examined by flow cytometry in 116 healthy controls (HC) and 95 KT patients for comparative analysis according to ATG treatment and CMV reactivation. The TCR repertoire was analysed in peripheral blood mononuclear cells (PBMCs) of KT patients. Results: T cells of KT patients treated with ATG (ATG+) show typical immunosenescent features, accumulation of CD28-, CD85j+ or CD57+ T cells, and imbalance of functional T-cell subsets, compared with untreated KT patients (ATG-). Plasma IL-15 and CMV-IgG levels were higher in KT patients than in HCs, and the IL-15 level positively correlated with the frequency of CD28- T cells in KT patients. ATG+ patients had a higher prevalence of CMV reactivation, which is associated with an increased frequency of CD28- T cells. As a result, ATG+ patients had expanded CMV-specific T cells and decreased TCR diversity. However, proliferation, cytokine-producing capacity and polyfunctionality of T cells were preserved in ATG+ patients. Conclusion: Our findings suggest that ATG treatment contributes to the accumulation of senescent T cells, which may have lifelong clinical implications in KT patients. Thus, these patients require long-term and comprehensive immune monitoring.