Cumulative risk factors for flap failure, thrombosis, and hematoma in free flap reconstruction for head and neck cancer: a retrospective nested case-control study.

BACKGROUND: Free flap construction enhances quality of life for head and neck cancer (HNC) patients; however, complications, such as thrombosis and hematoma, threaten flap survival. This study aimed to identify factors influencing flap failure, thrombosis, and hematoma. METHODS: A retrospective nested case-control study was conducted on HNC patients who underwent free flap reconstruction at a tertiary medical center between January 2019 and January 2022. All patients received antithrombotic prophylaxis consisting of prostaglandin E1, dextran, aspirin, and dipyridamole. Risk factors were analyzed using multivariate logistic regression. RESULTS: Among 548 flaps analyzed, flap failure, thrombosis, and hematoma rates were 4.74%, 3.83%, and 9.65%, respectively. Risk factors for flap failure included thrombosis (OR 86.42, 95% CI 15.73-474.89), smoking (OR 49.44, 95% CI 1.28->1000), posteromedial thigh (PMT) flap usage (OR 14.05, 95% CI 2.48-79.54), hematoma (OR 9.68, 95% CI 2.35-39.79), and younger age (OR 0.93, 95% CI 0.87-0.99). Thrombosis risk factors included PMT usage (OR 11.45, 95% CI 2.60-50.38) and anastomosis with the superior thyroid vein (SThV) as the recipient vein after multiple reconstructions (OR 7.91, 95% CI 2.06-30.39). Hematoma risk factors included fibula osteocutaneous flap usage (OR 9.22, 95% CI 2.71-31.42), double-flap usage (OR 8.88, 95% CI 1.80-43.81), liver cirrhosis (OR 6.28, 95% CI 1.44-27.47), and postsurgery hypertension (OR 2.77, 95% CI 1.39-5.50), whereas ipsilateral recurrence (OR 0.14, 95% CI 0.03-0.73) and using the external jugular vein (EJV) as the recipient vein (OR 0.22, 95% CI 0.08-0.61) were protective factors. CONCLUSION: Thrombosis poses a greater risk than hematoma for flap failure. Utilization of the PMT flap and the SThV markedly increased the risk of thrombosis and flap failure. These findings highlight the importance of antithrombotic prophylaxis and the selection of flaps and recipient veins in recurrent HNC patients.

Binding of interleukin-1 receptor antagonist to cholinergic receptor muscarinic 4 promotes immunosuppression and neuroendocrine differentiation in prostate cancer.

The tumor microenvironment (TME) of prostate cancer (PCa) is characterized by high levels of immunosuppressive molecules, including cytokines and chemokines. This creates a hostile immune landscape that impedes effective immune responses. The interleukin-1 (IL-1) receptor antagonist (IL1RN), a key anti-inflammatory molecule, plays a significant role in suppressing IL-1-related immune and inflammatory responses. Our research investigates the oncogenic role of IL1RN in PCa, particularly its interactions with muscarinic acetylcholine receptor 4 (CHRM4), and its involvement in driving immunosuppressive pathways and M2-like macrophage polarization within the PCa TME. We demonstrate that following androgen deprivation therapy (ADT), the IL1RN-CHRM4 interaction in PCa activates the MAPK/AKT signaling pathway. This activation upregulates the transcription factors E2F1 and MYCN, stimulating IL1RN production and creating a positive feedback loop that increases CHRM4 abundance in both PCa cells and M2-like macrophages. This ADT-driven IL1RN/CHRM4 axis significantly enhances immune checkpoint markers associated with neuroendocrine differentiation and treatment-resistant outcomes. Higher serum IL1RN levels are associated with increased disease aggressiveness and M2-like macrophage markers in advanced PCa patients. Additionally, elevated IL1RN levels correlate with better clinical outcomes following immunotherapy. Clinical correlations between IL1RN and CHRM4 expression in advanced PCa patients and neuroendocrine PCa organoid models highlight their potential as therapeutic targets. Our data suggest that targeting the IL1RN/CHRM4 signaling could be a promising strategy for managing PCa progression and enhancing treatment responses.

MCTP1 increases the malignancy of androgen-deprived prostate cancer cells by inducing neuroendocrine differentiation and EMT.

Neuroendocrine prostate cancer (PCa) (NEPC), an aggressive subtype that is associated with poor prognosis, may arise after androgen deprivation therapy (ADT). We investigated the molecular mechanisms by which ADT induces neuroendocrine differentiation in advanced PCa. We found that transmembrane protein 1 (MCTP1), which has putative Ca2+ sensing function and multiple Ca2+-binding C2 domains, was abundant in samples from patients with advanced PCa. MCTP1 was associated with the expression of the EMT-associated transcription factors ZBTB46, FOXA2, and HIF1A. The increased abundance of MCTP1 promoted PC3 prostate cancer cell migration and neuroendocrine differentiation and was associated with SNAI1-dependent EMT in C4-2 PCa cells after ADT. ZBTB46 interacted with FOXA2 and HIF1A and increased the abundance of MCTP1 in a hypoxia-dependent manner. MCTP1 stimulated Ca2+ signaling and AKT activation to promote EMT and neuroendocrine differentiation by increasing the SNAI1-dependent expression of EMT and neuroendocrine markers, effects that were blocked by knockdown of MCTP1. These data suggest an oncogenic role for MCTP1 in the maintenance of a rare and aggressive prostate cancer subtype through its response to Ca2+ and suggest its potential as a therapeutic target.

Cell therapies and its derivatives as immunomodulators in vascularized composite allotransplantation.

The adverse effects of traditional pharmaceutical immunosuppressive regimens have been a major obstacle to successful allograft survival in vascularized composite tissue allotransplantation (VCA) cases. Consequently, there is a pressing need to explore alternative approaches to reduce reliance on conventional immunotherapy. Cell therapy, encompassing immune-cell-based and stem-cell-based regimens, has emerged as a promising avenue of research. Immune cells can be categorized into two main systems: innate immunity and adaptive immunity. Innate immunity comprises tolerogenic dendritic cells, regulatory macrophages, and invariant natural killer T cells, while adaptive immunity includes T regulatory cells and B regulatory cells. Investigations are currently underway to assess the potential of these immune cell populations in inducing immune tolerance. Furthermore, mixed chimerism therapy, involving the transplantation of hematopoietic stem and progenitor cells and mesenchymal stem cells (MSC), shows promise in promoting allograft tolerance. Additionally, extracellular vesicles (EVs) derived from MSCs offer a novel avenue for extending allograft survival. This review provides a comprehensive summary of cutting-edge research on immune cell therapies, mixed chimerism therapies, and MSCs-derived EVs in the context of VCAs. Findings from preclinical and clinical studies demonstrate the tremendous potential of these alternative therapies in optimizing allograft survival in VCAs.

Association between Sjögren syndrome, sociodemographic factors, comorbid conditions, and optic neuritis: a Taiwanese population-based study.

Purpose: Our study aimed to explore the correlation between Sjögren syndrome, sociodemographic factors, comorbid conditions, and optic neuritis. Methods: This retrospective, nationwide, population-based, matched case-control investigation involved 33,190 individuals diagnosed with optic neuritis, identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes 377.30 for optic neuritis or 377.32 for retrobulbar neuritis. Patient data were extracted from the Taiwan National Health Insurance Research Database. Demographic characteristics, the presence of Sjögren syndrome, and pre-existing comorbid conditions were analyzed using univariate logistic regression. Continuous variables were assessed with a paired t-test. Adjusted logistic regression was employed to compare the prognosis odds ratio (OR) of patients with optic neuritis to controls. Results: After adjusting for confounding variables, individuals with Sjögren syndrome exhibited a significantly higher likelihood of developing optic neuritis compared to controls (adjusted OR, 9.79; 95% confidence interval [CI], 7.28-12.98; p < 0.0001). Other conditions associated with increased odds of optic neuritis included rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus, and granulomatous vasculitis (adjusted OR: 1.57, 95% CI: 1.33-1.86; adjusted OR: 2.02, 95% CI: 1.65-2.48; adjusted OR: 140.77, 95% CI: 35.02-565.85; adjusted OR: 2.38, 95% CI: 1.71-3.30; adjusted OR: 18.28, 95% CI: 2.21-151.45, respectively), as well as systemic infections such as human herpes viral infection and tuberculosis infection (adjusted OR: 1.50, 95% CI: 1.35-1.66; adjusted OR: 4.60, 95% CI: 3.81-5.56, respectively). Discussion: Our findings strongly support the existence of an association between Sjögren syndrome, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus, granulomatous vasculitis, human herpes viral infection, tuberculosis, and optic neuritis.

Immunosuppressive role of BDNF in therapy-induced neuroendocrine prostate cancer.

Prostate stromal cells play a crucial role in the promotion of tumor growth and immune evasion in the tumor microenvironment (TME) through intricate molecular alterations in their interaction with prostate cancer (PCa) cells. While the impact of these cells on establishing an immunosuppressive response and influencing PCa aggressiveness remains incompletely understood. Our study shows that the activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) pathway in both prostate tumor and stromal cells, following androgen deprivation therapy (ADT), leads to the development of an immunosuppressive TME. Activation of LIF/LIFR signaling in PCa cells induces neuroendocrine differentiation (NED) and upregulates immune checkpoint expression. Inhibition of LIF/LIFR attenuates these effects, underscoring the crucial role of LIF/LIFR in linking NED to immunosuppression. Prostate stromal cells expressing LIFR contribute to NED and immunosuppressive marker abundance in PCa cells, while LIFR knockdown in prostate stromal cells reverses these effects. ADT-driven LIF/LIFR signaling induces brain-derived neurotrophic factor (BDNF) expression, which, in turn, promotes NED, aggressiveness, and immune evasion in PCa cells. Clinical analyses demonstrate elevated BDNF levels in metastatic castration-resistant PCa (CRPC) and a positive correlation with programmed death-ligand 1 (PDL1) and immunosuppressive signatures. This study shows that the crosstalk between PCa cells and prostate stromal cells enhances LIF/LIFR signaling, contributing to an immunosuppressive TME and NED in PCa cells through the upregulation of BDNF.

PET/CT in a 65-Year-Old Woman With Epstein-Barr Virus-Associated Smooth Muscle Tumor After Chemotherapy for Follicular Lymphoma.

ABSTRACT: The Epstein-Barr virus-associated smooth muscle tumor (SMT) is an uncommon neoplasm. It arises mainly in 3 immunosuppression settings: HIV-associated SMT; drug-related immunosuppression in transplant recipients; and congenital immunodeficiency disorder-associated SMT. We present 18 F-FDG PET/CT findings of an adrenal Epstein-Barr virus-associated SMT in a 65-year-old woman with a history of follicular lymphoma after chemotherapy.

Mucinous cystadenocarcinoma of the breast harbours TRPS1 expressions and PIK3CA alterations.

AIMS: Breast mucinous cystadenocarcinoma (BMCA) is a rare tumour recently recognised as a distinct entity by the World Health Organisation Tumour Classification Series. BMCA is a triple-negative tumour that lacks specific immunohistochemical markers; therefore, distinguishing it from mimickers such as ovarian and pancreatic cystadenocarcinomas requires careful clinicopathological correlation. Due to its rarity, little is known about the molecular alterations that underlie BMCA. METHODS AND RESULTS: In this study, we used immunohistochemical staining methods to investigate TRPS1 (trichorhinophalangeal syndrome type 1) expression in BMCA and compare it to expression in ovarian and pancreatic mucinous cystadenocarcinomas. We also collected tumour samples from three BMCA patients for molecular analysis by MALDI-TOF mass spectrometry, real-time polymerase chain reaction, whole exome sequencing and fluorescence in-situ hybridisation. TRPS1 immunoreactivity was found only in BMCA tumour cells and not in the ovarian and pancreatic counterparts. One of the three BMCA tumours also showed a PIK3CA hot-spot mutation, which was confirmed by whole genome next-generation sequencing (NGS). No KRAS, NRAS, BRAF or AKT mutations were found. CONCLUSIONS: To our knowledge, this is the first demonstration of TRPS1 expression in BMCA patients and the first identification of a PIK3CA hotspot mutation in these tumours. These findings provide insights into the molecular mechanisms underlying BMCA tumorigenesis and suggest a potential drug target for this rare and poorly understood cancer.

Weight growth velocity and growth outcomes in very-low-birth-weight infants developing major morbidities.

BACKGROUND: Extrauterine growth restriction (EUGR) is common in very-low-birth-weight-infants and may be associated with poor neurodevelopment. The growth velocity of preterm infants is increasing over decades, but the relationship between growth velocity, EUGR, and morbidities of preterm infants remains unknown. METHODS: A total of 263 infants born between 2012 and 2020, with birthweight <1500 g and gestational age of 24-33 weeks, were included. Birthweight and weight on day of evaluation point (corrected gestational age 36 weeks or discharged, whenever comes first) were converted to age-specific and gender-specific Z-scores and analyzed by multivariable modeling. The average growth velocity was calculated by the exponential model. RESULTS: Average growth velocity from birth to the evaluation point was 11.8 ±â€¯0.3 g/kg/day. The maximum growth velocity from birth to week 8 postnatal occurred at week 4 postnatal (16.4 ±â€¯0.9 g/kg/day). Infants with smaller birth weight, higher gestational age, and indication of intestinal surgery or those who need more days to achieve full enteral feeding were more favorable to have a weight lower than the 10th centile at the evaluation point. By contrast, most comorbidities of prematurity did not affect either lower age-specific weight Z-scores on the evaluation point or larger change in weight Z-score between birth and evaluation point. CONCLUSION: EUGR was associated with gestational age and birth weight. Infants with moderate-to-severe bronchopulmonary dysplasia, high-grade intraventricular hemorrhage, or retinopathy of prematurity tend to have slower growth velocity at 3-5 weeks postnatal, but these did not contribute to EUGR.

Tumor-derived interleukin-1 receptor antagonist exhibits immunosuppressive functions and promotes pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is a pernicious disease characterized by an immunosuppressive milieu that is unresponsive to current immunotherapies. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory cytokine; however, its contribution to cancer pathogenesis and immunosuppression remains elusive. In this research, we investigated the role and mechanism of IL-1Ra in malignant progression of PDA. RESULTS: Through analyzing clinical dataset and examining the pathological tumor tissues and serum samples, we have demonstrated that IL-1Ra expression is elevated in human PDA and positively associated with malignant progression of PDA. To study the biological function of IL-1Ra in tumors, we generated a set of mouse pancreatic cancer cell lines with a knockout (KO) of the Il1rn gene, encoding IL-1Ra, and compared the tumor growth rates in immune-competent and immune-deficient mice. We found that the Il1rn KO cells exhibited greater tumor inhibition in immune-competent mice, highlighting the crucial role of a functional immune system in Il1rn KO-mediated anti-tumor response. Consistently, we found an increase in CD8+ T cells and a decrease in CD11b+Ly6G- immunosuppressive mononuclear population in the tumor microenvironment of Il1rn KO-derived tumors. To monitor the inhibitory effects of IL-1Ra on immune cells, we utilized a luciferase-based reporter CD4+ T cell line and splenocytes, which were derived from transgenic mice expressing ovalbumin-specific T cell receptors in CD8+ T cells, and mice immunized with ovalbumin. We showed that IL-1Ra suppressed T cell receptor signaling and inhibited antigen-specific interferon-γ (IFN-γ) secretion and cytolytic activity in splenocytes. CONCLUSIONS: Our findings illustrate the immunosuppressive properties of the natural anti-inflammatory cytokine IL-1Ra, and provide a rationale for considering IL-1Ra-targeted therapies in the treatment of PDA.

CHRM4/AKT/MYCN upregulates interferon alpha-17 in the tumor microenvironment to promote neuroendocrine differentiation of prostate cancer.

Current treatment options for prostate cancer focus on targeting androgen receptor (AR) signaling. Inhibiting effects of AR may activate neuroendocrine differentiation and lineage plasticity pathways, thereby promoting the development of neuroendocrine prostate cancer (NEPC). Understanding the regulatory mechanisms of AR has important clinical implications for this most aggressive type of prostate cancer. Here, we demonstrated the tumor-suppressive role of the AR and found that activated AR could directly bind to the regulatory sequence of muscarinic acetylcholine receptor 4 (CHRM4) and downregulate its expression. CHRM4 was highly expressed in prostate cancer cells after androgen-deprivation therapy (ADT). CHRM4 overexpression may drive neuroendocrine differentiation of prostate cancer cells and is associated with immunosuppressive cytokine responses in the tumor microenvironment (TME) of prostate cancer. Mechanistically, CHRM4-driven AKT/MYCN signaling upregulated the interferon alpha 17 (IFNA17) cytokine in the prostate cancer TME after ADT. IFNA17 mediates a feedback mechanism in the TME by activating the CHRM4/AKT/MYCN signaling-driven immune checkpoint pathway and neuroendocrine differentiation of prostate cancer cells. We explored the therapeutic efficacy of targeting CHRM4 as a potential treatment for NEPC and evaluated IFNA17 secretion in the TME as a possible predictive prognostic biomarker for NEPC.

Gouty arthritis involves impairment of autophagic degradation via cathepsin D inactivation-mediated lysosomal dysfunction that promotes apoptosis in macrophages.

This study examined autophagy-lysosome pathway (ALP) perturbations in synovial monocytes/macrophages from patients with gouty arthritis (GA) and the associations of ALP perturbations with cell death. Synovial fluid mononuclear cells (SFMCs) and synovial tissues (STs) from patients with GA, as well as monosodium urate (MSU) crystal-exposed macrophages, underwent immunoblotting, quantitative polymerase chain reaction, and immunofluorescence analyses of markers linked to the ALP (microtubule-associated protein 1 light chain 3B [LC3B], p62, cathepsin D [CTSD], and lysosome-associated membrane protein 2 [LAMP2]) and cell death (caspase-3). GA STs underwent immunohistochemistry and immunofluorescence analyses to determine the distributions of LC3B-positive autophagosomes and macrophages. GA SFMCs and STs exhibited impaired autophagic degradation, indicated by elevated levels of LC3B and p62, along with CTSD upregulation and caspase-3 activation. Macrophages from GA STs exhibited significant accumulation of LC3B-positive autophagosomes. The temporal effects of MSU crystals on the ALP and the associations of these effects with cell death were investigated using a macrophage model of GA. MSU crystal-exposed macrophages exhibited early (2 h) autophagosome formation but later (6-24 h) autophagic flux impairment, demonstrated by p62 accumulation, lysosomal inhibitor failure to increase LC3B accumulation, and LC3B colocalization with p62. These macrophages exhibited autophagic flux impairment because of CTSD inactivation-mediated lysosomal dysfunction, which caused immature CTSD to accumulate within damaged LAMP2-positive lysosomes. This accumulation coincided with caspase-3-dependent cell death (24 h) that was unaffected by CTSD inhibition. These findings indicate that GA involves MSU crystal-induced impairment of autophagic degradation via CTSD inactivation-mediated lysosomal dysfunction, which promotes apoptosis in macrophages.

The Process Parameters of Micro Particle Bombarding (MPB) for Surface Integrity Enhancement of Cermet Material and Tool Steel.

In order to increase the performance of tool or mold/die, there are a lot of micro features on the surface to provide special functions, such as anti-adhesion or lubrication. The MPB (Micro Particle Bombarding) process provides a powerful technology to enhance the surface quality without damaging the micro features. The effect of MPB parameters were investigated by bombarding the surface with extremely small particles (20~200 µm in diameter) at a high velocity and pressure to obtain a better surface integrity. -The MPB has two functions, one is micro blasting for cleaning purposes and the other is micro shot peening for surface strengthening. The regression relationship between particle bombarding time and micro hardness is established to predict the surface hardness after MPB process. The experimental results reveal that the surface hardness of cermet is increased 14~66% (HV2167~HV3163) by micro particle bombarding. The micro shot peening provides a good surface integrity due to thebetter surface roughness of 0.1 µmRa and higher compress residual stress of -1393.7 MPa, which is up to 26% enhancement compared with the base material cermet. After micro shot peening, the surface hardness of the SKD11 tool steel increased from HV 686 to HV 739~985. The surface roughness of SKD 11 after micro shot peening was 0.31-0.48 µmRa, while the surface roughness after micro blasting was 0.77-1.15 µmRa. It is useful to predict the residual stress for micro blasting by surface roughness, and to estimate the residual stress after micro shot peening by surface hardness by applying the MPB process in industry in the case of SKD 11 tool steel.

Biological cell trapping and manipulation of a photonic nanojet by a specific microcone-shaped optical fiber tip.

Trapping and manipulating mesoscopic biological cells with high precision and flexibility are very important for numerous biomedical applications. In particular, a photonic nanojet based on a non-resonance focusing phenomenon can serve as a powerful tool for manipulating red blood cells and tumor cells in blood. In this study, we demonstrate an approach to trap and drive cells using a high-quality photonic nanojet which is produced by a specific microcone-shaped optical-fiber tip. The dynamic chemical etching method is used to fabricate optical-fiber probes with a microcone-shaped tip. Optical forces and potentials exerted on a red blood cell by a microcone-shaped fiber tips are analyzed based on finite-difference time-domain calculations. Optical trapping and driving experiments are done using breast cancer cells and red blood cells. Furthermore, a cell chain is formed by adjusting the magnitude of the optical force. The real-time backscattering intensities of multiple cells are detected, and highly sensitive trapping is achieved. This microcone-shaped optical fiber probe is potentially a powerful device for dynamic cell assembly, optical sorting, and the precise diagnosis of vascular diseases.

Targeting PKLR/MYCN/ROMO1 signaling suppresses neuroendocrine differentiation of castration-resistant prostate cancer.

Conventional treatment of prostate cancer (PCa) uses androgen-deprivation therapy (ADT) to inhibit androgen receptor (AR) signaling-driven tumor progression. ADT-induced PCa recurrence may progress to an AR-negative phenotype with neuroendocrine (NE) histologic features, which are associated with metabolic disturbances and poor prognoses. However, the metabolic pathways that regulate NE differentiation (NED) in PCa remain unclear. Herein, we show a regulatory mechanism in NED-associated metabolism dysfunction induced by ADT, whereby overexpression of pyruvate kinase L/R (PKLR) mediates oxidative stress through upregulation of reactive oxygen species modulator 1 (ROMO1), thereby promoting NED and aggressiveness. ADT mediates the nuclear translocation of PKLR, which binds to the MYCN/MAX complex to upregulate ROMO1 and NE-related genes, leading to altered mitochondrial function and NED of PCa. Targeting nuclear PKLR/MYCN using bromodomain and extra-terminal motif (BET) inhibitors has the potential to reduce PKLR/MYCN-driven NED. Abundant ROMO1 in serum samples may provide prognostic information in patients with ADT. Our results suggest that ADT resistance leads to upregulation of PKLR/MYCN/ROMO1 signaling, which may drive metabolic reprogramming and NED in PCa. We further show that increased abundance of serum ROMO1 may be associated with the development of NE-like PCa.

PD-L1 and AKT Overexpressing Adipose-Derived Mesenchymal Stem Cells Enhance Myocardial Protection by Upregulating CD25+ T Cells in Acute Myocardial Infarction Rat Model.

This study explores the synergistic impact of Programmed Death Ligand 1 (PD-L1) and Protein Kinase B (Akt) overexpression in adipose-derived mesenchymal stem cells (AdMSCs) for ameliorating cardiac dysfunction after myocardial infarction (MI). Post-MI adult Wistar rats were allocated into four groups: sham, MI, ADMSC treatment, and ADMSCs overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) treatment. MI was induced via left anterior descending coronary artery ligation, followed by intramyocardial AdMSC injections. Over four weeks, cardiac functionality and structural integrity were assessed using pressure-volume analysis, infarct size measurement, and immunohistochemistry. AdMSC-PDL1-Akt exhibited enhanced resistance to reactive oxygen species (ROS) in vitro and ameliorated MI-induced contractile dysfunction in vivo by improving the end-systolic pressure-volume relationship and preload-recruitable stroke work, together with attenuating infarct size. Molecular analyses revealed substantial mitigation in caspase3 and nuclear factor-κB upregulation in MI hearts within the AdMSC-PDL1-Akt group. Mechanistically, AdMSC-PDL1-Akt fostered the differentiation of normal T cells into CD25+ regulatory T cells in vitro, aligning with in vivo upregulation of CD25 in AdMSC-PDL1-Akt-treated rats. Collectively, PD-L1 and Akt overexpression in AdMSCs bolsters resistance to ROS-mediated apoptosis in vitro and enhances myocardial protective efficacy against MI-induced dysfunction, potentially via T-cell modulation, underscoring a promising therapeutic strategy for myocardial ischemic injuries.

Low Versus High Stroke Volume Variation-Guided and Reduction of Postoperative Complications After Liver Resection: A Randomized Clinical Trial.

BACKGROUND: Liver surgery is a major abdominal operation associated with a dramatic change in intraoperative hemodynamics; thus, the infusion strategy is challenging for anesthesiologists. Studies have demonstrated that stroke volume variation (SVV) can be used to predict fluid responsiveness during major abdominal surgery. SVV can be used as a guide for the administration of intraoperative fluids to improve postoperative prognosis. In the present study, we planned to investigate whether high- or low-SVV in liver surgery is associated with fewer postoperative complications. METHODS: This study was a prospective randomized trial of 74 patients who underwent hepatectomy. The patients were divided into two groups for SVV-guided infusion during tumor resection surgery using a low-SVV (≤ 10%, n = 37) or high-SVV (> 10%, n = 37) strategy. The primary outcome was postoperative complications, namely infection, pleural effusion, and atelectasis. The secondary outcomes were differences in perioperative physiological variables and postoperative pain. RESULTS: No differences in postoperative complications within 30 days of surgery were observed between the low-SVV and high-SVV groups. However, we observed lower estimated glomerular filtration rates (eGFRs) and higher alanine transaminase (ALT) levels in the high-SVV group after surgery. CONCLUSION: Patients who underwent major liver tumor resection with the low-SVV or high-SVV strategy exhibited no differences in postoperative complications (48.6% vs. 45.9%; P > 0.999). However, in the high-SVV group, postoperative eGFRs were lower and ALT levels were higher.

Feasibility of Breast Cancer Metastasis Assessment of Ex Vivo Sentinel Lymph Nodes through a p-H&E Optical Coherence Microscopic Imaging System.

Frozen-sectioned hematoxylin-eosin (H&E) image evaluation is the current method for intraoperative breast cancer metastasis assessment through ex vivo sentinel lymph nodes (SLNs). After frozen sectioning, the sliced fatty region of the frozen-sectioned specimen is easily dropped because of different freezing points for fatty tissues and other tissues. Optical-sectioned H&E images provide a nondestructive method for obtaining the insight en face image near the attached surface of the dissected specimen, preventing the freezing problem of fatty tissue. Specimens from 29 patients at Wanfang Hospital were collected after excision and were analyzed at the pathology laboratory, and a fluorescence-in-built optical coherence microscopic imaging system (OCMIS) was then used to visualize the pseudo-H&E (p-H&E) images of the SLNs for intraoperative breast cancer metastasis assessment, and the specificity, sensitivity, and accuracy were 100%, 88.9%, and 98.8% (n = 83), respectively. Compared with gold-standard paraffin-sectioned H&E images, the specificity, sensitivity, and accuracy obtained with the frozen-sectioned H&E images (n = 85) of the specimens were the same as those obtained with the p-H&E images (n = 95). Thus, OCMIS is a useful noninvasive image-assisted tool for breast cancer metastasis assessment based on SLN images.