Comparison of Outcomes Between Partial and Radical Laparoscopic Nephrectomy for Localized Renal Tumors Larger Than Four Centimeters: A Systematic Review and Meta-Analysis.

Background: Earlier studies have juxtaposed different laparoscopic methods for treating renal tumors; however, extensive evidence with a particular focus on large kidney tumors remains lacking. The objective of this meta-analysis was to assess the perioperative outcomes, kidney performance, and cancer-related results of laparoscopic partial nephrectomy (LPN) versus laparoscopic radical nephrectomy (LRN) for treating extensive, localized, non-metastatic kidney tumors (cT1b-cT2N0M0). Methods: We systematically searched multiple databases from database inception until December 2023 for relevant studies. Selected data were analyzed with the Cochrane Collaboration's Review Manager 5.4 software using a random-effects model. Outcomes were expressed as odds ratios and weighted mean differences with 95% confidence intervals, considering a P value of < 0.05 as significant. Results: Data from nine studies encompassing 1,303 patients (529 LPN, 774 LRN) revealed that LPN was associated with lengthier surgeries and increased blood loss compared to LRN. While LPN exhibited higher postoperative complication rates, the disparity did not reach statistical significance. LPN led to improved postoperative renal function, manifesting as a reduced estimated glomerular filtration rate (eGFR) decline and fewer incidents of new chronic kidney disease cases. Both groups demonstrated comparable tumor recurrence and overall mortality rates, but LPN exhibited significantly lower cancer-specific mortality rates. Conclusions: LPN, despite longer operative times and greater intraoperative blood loss, was found to be superior to LRN in preserving postoperative renal function. Oncologically, LPN and LRN have comparable overall mortality rates, but LPN showed a significant advantage in terms of lower cancer-specific mortality rates.

Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives.

Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.

Self-Illuminating Nanoagonist Simultaneously Induces Dual Cell Death Pathways via Death Receptor Clustering for Cancer Therapy.

Inducing death receptor 5 (DR5) clustering holds particular promise in tumor-specific therapeutics because it could trigger an apoptotic cascade in cancerous cells. Herein, we present a tumor microenvironment H2O2-responsive self-illuminating nanoagonist, which could induce dual tumor cell death pathways through enhancing DR5 clustering. By conjugating DR5 ligand peptides onto the surfaces of self-illuminating nanoparticles with cross-linking capacity, this strategy not only provides scaffolds for ligands to bind receptors but also cross-links them through photo-cross-linking. This strategy allows for efficient activation of DR5 downstream signaling, initiating the extrinsic apoptosis pathway and immunogenic cell death of tumor cells, and contributes to improved tumor-specific immune responses, resulting in enhanced antitumor efficacy and minimized systemic adverse effects.

Targeting a mTOR/autophagy axis: a double-edged sword of rapamycin in spontaneous miscarriage.

Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications.

Comprehensive Insights Into Renal Perivascular Epithelioid Cell Neoplasms: From Molecular Mechanisms to Clinical Practice.

Perivascular epithelioid cell neoplasms (PEComas) are a rare category of mesenchymal tissue tumors, manifesting across various tissues and organs such as the kidneys, liver, lungs, pancreas, uterus, ovaries, and gastrointestinal tract. They predominantly affect females more than males. PEComas characteristically express both melanocytic and smooth muscle markers, making immunohistochemistry vital for their diagnosis. Renal angiomyolipoma (AML) represents a common variant of PEComas, typically marked by favorable prognoses. Nonetheless, only a small fraction of subtypes, especially epithelioid AML, possess the capacity to be malignant. Renal PEComas usually appear as asymptomatic masses accompanied by vague imaging characteristics. The main methods for diagnosis are histopathological analysis and the application of immunohistochemical stains. Presently, a uniform treatment plan for renal PEComas is absent. Strategies for management include active surveillance, selective arterial embolization, surgical procedures, and drug-based treatments. The focus of this review is on renal PEComas, shedding light on their pathogenesis, pathological characteristics, clinical presentations, diagnosis, and treatment modalities, and incorporating a clinical case study.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Nonreciprocal magnon blockade based on nonlinear effects.

We present an alternative scheme to achieve nonreciprocal unconventional magnon blockade (NUMB) in a hybrid system formed by two microwave cavities and one yttrium iron garnet (YIG) sphere, where the pump and signal cavities interact nonlinearly with each other and the signal cavity is coupled to the YIG sphere. It is found that the nonlinear coupling occurs between the pump cavity and magnon modes due to the dispersive interactions among three bosonic modes. Meanwhile, the Kerr nonlinearity is present in the pump cavity. Based on these nonlinear effects, a nonreciprocal magnon blockade could be achieved with the help of the weak parametric driving of the pump cavity. The present work provides an alternative method to prepare single magnon resource, which may be helpful for quantum information processing.

Construction of ecological network in Qujing city based on MSPA and MCR models.

With the rapid advancement of urbanization and industrialization, ecological patches within cities and towns are fragmented and ecological corridors are cut off, regional ecological security is threatened and sustainable development is hindered. Building an ecological network that conforms to regional realities can connect fragmented patches, protect biodiversity and regional characteristics, and provide scientific reference for regional ecological protection and ecological network planning. By taking Qilin District, the main urban area of Qujing City as an example, and using geospatial data as the main data source, based on morphological spatial pattern analysis (MSPA) and minimum cumulative resistance (MCR), this study identified ecological source areas, extracted ecological corridors, and build & optimize ecological networks. (1) All landscape types are identified based on MSPA, the proportion of core area was the highest among all landscape types, which was 80.69%, combined with the connectivity evaluation, 14 important ecological source areas were selected. (2) 91 potential ecological corridors were extracted through MCR and gravity models, there were 16 important ones. (3) The network connectivity analysis method is used to calculate the α, ß, and γ indexes of the ecological network before optimization, which were 2.36, 6.5, and 2.53, while after optimization, α, ß and γ indices were 3.8, 9.5 and 3.5, respectively. The combined application of MSPA-MCR model and ecological network connectivity analysis evaluation is conducive to improving the structure and functionality of ecological network.

Multiple Immunomodulatory Strategies Based on Targeted Regulation of Proprotein Convertase Subtilisin/Kexin Type 9 and Immune Homeostasis against Hepatocellular Carcinoma.

Immunotherapy is the most promising systemic therapy for hepatocellular carcinoma. However, the outcome remains poor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a role in altering cell-surface protein levels, potentially undermining the efficacy of immunotherapy against tumors. This highlights its potential as a target for antitumor therapy. Herein, CaCO3-based nanoparticles coencapsulated with DOX, an immunogenic cell death (ICD) inducer, and evolocumab was developed to enhanced the efficacy of immunotherapy. The obtained DOX/evolocumab-loaded CaCO3 nanoparticle (named DECP) exhibits a good capacity of acid neutralization and causes ICD of cancer cells. In addition, DECP is able to evaluate the cell-surface level of MHC-I, a biomarker that correlates positively with patients' overall survival. Upon intravenous injection, DECP accumulates within the tumor site, leading to growth inhibition of hepa1-6 bearing subcutaneous tumors. Specifically, DECP treatment causes augmented ratios of matured dendritic cells, tumor-infiltrating CD8+ T cells and natural killing cells, while concurrently depleting Foxp3+ regulatory T cells. Peritumoral delivery of DECP enhances the immune response of distant tumors and exhibits antitumor effects when combined with intravenous αPD-L1 therapy in a bilateral tumor model. This study presents CaCO3-based nanoparticles with multiple immunomodulatory strategies against hepatocellular carcinoma by targeting PCSK9 inhibition and modulating immune homeostasis in the unfavorable TME.

Anticoagulant Prescribing Patterns in New-Onset Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and is associated with an increased risk of thromboembolic stroke. Recommendations regarding the optimal anticoagulant, timing of initiation, and duration of therapy remain uncertain. METHODS: Administrative databases were used to include adult patients who presented with POAF after cardiac surgery between January 1, 2015, and December 31, 2020. Key exclusion criteria included preexisting atrial fibrillation, mechanical valve replacement, or anticoagulant prescription fill within 6 months before the index admission. RESULTS: A total of 3214 of patients were included, and 878 (27.3%) were prescribed an oral anticoagulant (OAC) on discharge, with 536 (61%) prescribed warfarin and 342 (39%) prescribed a direct OAC. More than half of the patients (56.1%) stopped their OAC by 6 months. There was no difference in stroke or systemic embolism at 30 days, 3 months, or 6 months between those with and without anticoagulation prescribed. However, those on any OAC had higher rates of any bleeding at all time points. CONCLUSIONS: A minority of patients who presented with POAF after cardiac surgery were prescribed OAC, with warfarin being the most common agent. OAC initiation was associated with increased bleeding risk, warranting special consideration when assessing a patient's risk of stroke with the increased risk of bleeding, particularly in the postoperative period.

Pre-existing cardiometabolic comorbidities and survival of middle-aged and elderly non-small cell lung cancer patients.

BACKGROUND: Both lung cancer and cardiometabolic diseases are leading causes of death in China, and they share some common risk factors. However, the prevalence and long-term effect of pre-existing cardiometabolic comorbidities (CMCs) on the survival of middle-aged and elderly lung cancer patients are still not clear. METHODS: We consecutively recruited 3477 non-small cell lung cancer (NSCLC) patients between January 2011 and December 2018 from four cancer specialty hospitals in China. Univariable and multivariable adjusted Cox proportional hazard models were conducted to evaluate the risk factors associated with mortality. Hazard ratio (HR) for mortality and corresponding 95% CI were calculated. RESULTS: The prevalence of CMCs was 30.0% in middle-aged NSCLC patients and 45.5% in elderly NSCLC patients. Log-rank analysis presented statistically significant differences in median survival time between patients with CMCs and without CMCs in both the middle-aged group (21.0 months vs. 32.0 months, P < 0.01) and the elderly group (13.0 months vs. 17.0 months, P = 0.01). Heart failure (HR = 1.754, 95% CI: 1.436-2.144, P < 0.001) and venous thrombus embolism (HR = 2.196, 95% CI: 1.691-2.853, P < 0.001) were independent risk factors for the survival of middle-aged NSCLC patients, while heart failure (HR = 1.709, 95% CI: 1.371-2.130, P < 0.001) continued to decrease overall survival in the elderly group. Hyperlipidemia may be a protective factor for survival in middle-aged group (HR = 0.741, 95% CI: 0.566-0.971, P = 0.030). CONCLUSIONS: Our findings demonstrate for the first time the prevalence and prognostic value of pre-existing CMCs in Chinese middle-aged and elderly NSCLC patients.

Ginsenosides in endometrium-related diseases: Emerging roles and mechanisms.

Ginsenosides, agents extracted from an important herb (ginseng), are expected to provide new therapies for endometrium-related diseases. Based on the molecular types of ginsenosides, we reviewed the main pharmacological effects of ginsenosides against endometrium-related diseases (e.g., endometrial cancers, endometriosis, and endometritis). The mechanism of action of ginsenosides involves inducing apoptosis of endometrium-related cells, promoting autophagy of endometrium-related cells, regulating epithelial-mesenchymal transition (EMT) in endometrium-related cells, and activating the immune system to kill cells associated with endometrial diseases. We hope to provide a theoretical foundation for the treatment of endometrium-related diseases by ginsenosides.

A photo-activable nano-agonist for the two-signal model of T cell in vivo activation.

The two-signal model of T cell activation has helped shape our understanding of the adaptive immune response for over four decades. According to the model, activation of T cells requires a stimulus through the T cell receptor/CD3 complex (signal 1) and a costimulatory signal 2. Stimulation of activatory signals via T cell agonists has thus emerged. However, for a robust T cell activation, it necessitates not only the presence of both signal 1 and signal 2, but also a high signaling strength. Herein, we report a photo-activable nano-agonist for the two-signal model of T cell in vivo activation. A UV-crosslinkable polymer is coated onto upconversion nanoparticles with satisfactory NIR-to-UV light conversion efficiency. Then dual signal molecules, i.e., signal 1 and signal 2, are conjugated to the polymer end to yield the photo-activable T cell nano-agonist. In melanoma and breast cancer models, photo-activable nano-agonist could bind onto corresponding activatory receptors on the surface of T cells, but has limited activity without the application of NIR light (absence of photo-crosslinking of receptors and consequently a poor signaling strength). While when the NIR light is switched on locally, T cells in tumor are remarkably activated and kill tumor cells effectively. Moreover, we do not observe any detectable toxicities related to the photo-activable nano-agonist. We believe with two activatory signals being simultaneously strengthened by local photo-switched crosslinking, T cells realize a robust and selective activation in tumor and, consequently contribute to an enhanced and safe tumor immunotherapy.

Study on the influence of urban tree canopy on thermal environment in Luoping County.

Urban forest is an integral part of the complex urban ecosystem, and tree canopy plays a key role in improving urban climatic environment. Urban Tree Canopy (UTC) is strongly linked to urban thermal environment and living quality of residents. In this study, Luoping County, a mountainous county in southwest China, was selected as the study area to uncover the inner connections between tree canopy and thermal environment, and provide relevant scientific references for the construction of livable forest cities in similar areas. Through eCongnition Developer, ENVI and ArcGIS software, the distribution of Land Surface Temperature (LST) and land cover types in the study area was extracted, 63 patches with super-large and extra-large tree canopy coverage selected, to explore the regulatory effect of UTC patches on urban thermal environment based on SPSS software. Results showed that the highest LST in the research area was 37.63 â„ƒ, the lowest 24.73 â„ƒ, and the average 30.83 â„ƒ. Among the land cover types, the area of buildings and impervious surfaces was 1615.71 hm2, accounting for 55.76% of the total study area, which was the largest proportion and with widespread distribution; the area of grassland and water body was 57.48 hm2 and 12.35 hm2, respectively, taking up 1.98% and 0.43%, with a smaller proportion. Mean LST: impervious surface > bare land > grassland > tree canopy > water body. By increasing the area and perimeter of the patch covered by tree canopy, the cooling rate of the patch can be increased while the temperature inside the patch can be reduced. The relationship between the area and cooling rate is closer than that between perimeter and cooling rate. The increase of perimeter has a stronger alleviation effect on the internal temperature of the patch, whereas, the increase of area has a weaker effect in this respect.

Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: roles, opportunities and challenges.

Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EVs-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks.

Stereoselective Synthesis of the O-antigen of A. baumannii ATCC 17961 Using Long-Range Levulinoyl Group Participation.

Herein, we described the first synthesis of the pentasaccharide and decasaccharide of the A. baumannii ATCC 17961 O-antigen for developing a synthetic carbohydrate-based vaccine against A. baumannii infection. The efficient synthesis of the rare sugar 2,3-diacetamido-glucuronate was achieved using our recently introduced organocatalytic glycosylation method. We found, for the first time, that long-range levulinoyl group participation via a hydrogen bond can result in a significantly improved ß-selectivity in glycosylations. This solves the stereoselectivity problem of highly branched galactose acceptors. The proposed mechanism was supported by control experiments and DFT computations. Benefiting from the long-range levulinoyl group participation strategy, the pentasaccharide donor and acceptor were obtained via an efficient [2+1+2] one-pot glycosylation method and were used for the target decasaccharide synthesis.

Regio- and Stereoselective Organocatalyzed Relay Glycosylations To Synthesize 2-Amino-2-deoxy-1,3-dithioglycosides.

Herein, we describe a novel methodology for the regio- and stereoselective convergent synthesis of 2-amino-2-deoxy-dithioglycosides via one-pot relay glycosylation of 3-O-acetyl-2-nitroglucal donors. This unique organo-catalysis relay glycosylation features excellent site- and stereoselectivity, good to excellent yields, mild reaction conditions, and broad substrate scope. 2-Amino-2-deoxy-glucosides/mannosides bearing 1,3-dithio-linkages were efficiently obtained from 3-O-acetyl-2-nitroglucal donors in both stepwise and one-pot glycosylation protocols. The dithiolated O-antigen of E. coli serogroup 64 was successfully synthesized using this newly developed method.