ALAS2 overexpression alleviates oxidative stress-induced ferroptosis in aortic aneurysms via GATA1 activation.

Background: Aortic aneurysm, characterized by abnormal dilation of the aorta, poses significant health risks. This study aims to investigate the interaction between 5-aminolevulinate synthase 2 (ALAS2) and GATA-binding protein 1 (GATA1) in ferroptosis and oxidative stress responses in aortic aneurysm. Methods: A weighted gene co-expression network analysis (WGCNA) was performed on the differentially expressed genes (DEGs) within the GSE9106 dataset to identify the key module. Subsequently, protein-protein interaction (PPI) network analysis was performed on the key module. Mouse aortic vascular smooth muscle cells (MOVAS) were treated with hydrogen peroxide (H2O2) to induce oxidative stress, and ferroptosis inducers and inhibitors were added to evaluate their effects on iron content and oxidative stress markers. Through a series of in vitro cellular experiments, we assessed cell viability, expression levels of GATA1 and iron mutation-associated proteins, as well as cellular phenotypes such as inflammatory responses and apoptosis rates. Results: Three candidate genes (ALAS2, GYPA, and GYPB) were upregulated in the thoracic aortic aneurysm (TAA) samples of the GSE9106 dataset. The H2O2 treatment increased the MOVAS cells' iron content and oxidative stress, upregulated ALAS2 protein levels, and decreased the ferroptosis-related protein levels. ALAS2 overexpression reversed H2O2-induced apoptosis and increased the inflammatory cytokine levels. Additionally, the knockdown of GATA1 partially reversed the protective mechanism of overexpressed ALAS2 on H2O2-induced ferroptosis. Conclusions: ALAS2 overexpression reduced H2O2-induced oxidative damage and iron-induced apoptosis in MOVAS cells, and GATA1 knockdown partially reversed this protective effect. These findings suggested that the ALAS2 and GATA1 regulatory pathways may be potential therapeutic targets in aortic aneurysms.

Smart and Sustainable Crop Protection: Design and Evaluation of a Novel α-Amylase-Responsive Nanopesticide for Effective Pest Control.

In this study, an α-amylase-responsive controlled-release formulation was developed by capping polydopamine onto ß-cyclodextrin-modified abamectin-loaded hollow mesoporous silica nanoparticles. The prepared Aba@HMS@CD@PDA were subjected to characterization using various analytical techniques. The findings revealed that Aba@HMS@CD@PDA, featuring a loading rate of 18.8 wt %, displayed noteworthy release behavior of abamectin in the presence of α-amylase. In comparison to abamectin EC, Aba@HMS@CD@PDA displayed a significantly foliar affinity and improved rainfastness on lotus leaves. The results of field trail demonstrated a significantly higher control efficacy against Spodoptera litura Fabricius compared to abamectin EC at all concentrations after 7, 14, and 21 days of spaying, showcasing the remarkable persistence of Aba@HMS@CD@PDA. These results underscore the potential of Aba@HMS@CD@PDA as a novel and persistently effective strategy for sustainable on-demand crop protection. The application of nanopesticides can enhance the effectiveness and efficiency of pesticide utilization, contributing to more sustainable agricultural practices.

Unveiling kiwifruit TCP genes: evolution, functions, and expression insights.

The TEOSINTE-BRANCHED1/CYCLOIDEA/PROLEFERATING-CELL-FACTORS (TCP) gene family is a plant-specific transcriptional factor family involved in leaf morphogenesis and senescence, lateral branching, hormone crosstalk, and stress responses. To date, a systematic study on the identification and characterization of the TCP gene family in kiwifruit has not been reported. Additionally, the function of kiwifruit TCPs in regulating kiwifruit responses to the ethylene treatment and bacterial canker disease pathogen (Pseudomonas syringae pv. actinidiae, Psa) has not been investigated. Here, we identified 40 and 26 TCP genes in Actinidia chinensis (Ac) and A. eriantha (Ae) genomes, respectively. The synteny analysis of AcTCPs illustrated that whole-genome duplication accounted for the expansion of the TCP family in Ac. Phylogenetic, conserved domain, and selection pressure analysis indicated that TCP family genes in Ac and Ae had undergone different evolutionary patterns after whole-genome duplication (WGD) events, causing differences in TCP gene number and distribution. Our results also suggested that protein structure and cis-element architecture in promoter regions of TCP genes have driven the function divergence of duplicated gene pairs. Three and four AcTCP genes significantly affected kiwifruit responses to the ethylene treatment and Psa invasion, respectively. Our results provided insight into general characters, evolutionary patterns, and functional diversity of kiwifruit TCPs.

Enhancing Thickness Uniformity of Nb2O5/SiO2 Multilayers Using Shadow Masks for Flexible Color-Filtering Applications.

Using a stainless shadow mask combined with a magnetron-ion-assisted deposition (IAD) sputtering system, we investigate the surface morphologies and optical properties of microfilms. Optimal color-filter (CF) coating microfilms with niobium pent-oxide (Nb2O5)/silicon dioxide (SiO2) multilayers on a hard polycarbonate (HPC) substrate, grown at 85 °C and 50 SCCM oxygen flow, can obtain a fairly uniform thickness (with an average roughness of 0.083 and 0.106 nm respectively for Nb2O5 and SiO2 films) through all positions. On a flexible HPC substrate with the Nb2O5/SiO2 microfilms, meanwhile, the peak transmittances measured in the visible range are 95.70% and 91.47%, respectively, for coatings with and without a shadow mask for this new-tech system. For the optimal CF application with a shadow mask, transmittance on each 100 nm band-pass wavelength is enhanced by 4.04% absolute (blue), 2.96% absolute (green), and 2.12% absolute (red). Moreover, the developed new-tech system not only enhances the quality of the films by achieving smoother and uniform surfaces but also reduces deposition time, thereby improving overall process efficiency. For the with-shadow-mask condition, there is little shift at 50% transmittance (T50%), and high transmittance (~97%) is maintained after high-temperature (200 °C) baking for 12 h. These results are well above the commercial CF standard (larger than 90%) and demonstrate reliability and good durability for flexible optical applications.

A novel investigation into the negative impact of opioid use on the efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) have effectively improved the clinical outcome of advanced non-small cell lung cancer (NSCLC). Opioids are commonly used for pain relief in cancer patients. This study aims to clarify the prognostic impact of opioid use in advanced NSCLC patients receiving ICI therapy. METHODS: A systematic literature review was carried out using online databases before July 2023. The meta-analysis was used to clarify the correlation of opioid use with the overall survival (OS) or progression-free survival (PFS) of ICI-treated NSCLC patients, both of which were determined using hazard ratios (HRs) coupled with 95 % confidence intervals (CIs). Then, an independent cohort enrolling 181 NSCLC patients was utilized for validation. Finally, a comprehensive bioinformatics analysis based on TCGA cohort was performed to investigate the prognostic significance of opioid target genes (OTGs) and their correlation with immune infiltration in NSCLC patients. RESULTS: A total of 8 studies enrolling 1174 patients were included in the meta-analysis. Opioid use was negatively associated with worse PFS (HR = 2.16, 95 %CI: 1.26-3.71) and OS (HR = 2.02, 95 %CI: 1.54-2.63) in ICI-treated NSCLC patients. The retrospective validation confirmed the above result and identified opioid use as an independent unfavorable predictor for PFS and OS in both the entire cohort and ICI subgroup. The bioinformatic analysis identified 14 prognostic OTGs (CYP17A1, PDYN, PYCARD, FGA, NTSR1, FABP1, HPCA, PENK, PDGFB, LIN7A, FKBP5, TYMS, CACNA1H and LDHA), most of which were correlated with immune infiltration in NSCLC. A risk model was constructed based on 14 OTGs and found to effectively stratify the clinical outcome in both the training and validation set, independent of age, gender and TNM staging system. The model was also significantly correlated with infiltration of activated dendritic cells, neutrophils and tumor infiltrating lymphocytes. Finally, a nomogram was constructed based on the model, age, gender and TNM stage, which could predict well the 1-, 3- and 5-year survival of NSCLC patients. CONCLUSION: Opioid use is correlated with the poor clinical outcome in ICI-treated NSCLC patients. Precise pain management is highly advocated and opioids are recommended to be cautiously used in these patients. OTGs have the potential to be prognostic biomarkers for NSCLC patients and their role in tumor immunity needs to be further investigated.

lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosis.

Introduction: In this study, we investigated the role of the long non-coding RNA GAPLINC in atherosclerosis under oxidized low-density lipoprotein (ox-LDL) treatment. Material and methods: We utilized ox-LDL exposed human aortic endothelial cells as an in-vitro model. The expression level of GAPLINC was quantified by qPCR in different times and concentrations of ox-LDL treatment conditions. Cell apoptosis rate and cell cycle profiles were assessed by flow cytometry and TUNEL assay. The target association was confirmed using a luciferase reporter assay and Western blot. Results: We found that GAPLINC expression was induced by ox-LDL treatment, but cell proliferation ability was significantly inhibited. We further confirmed that overexpressing of lncRNA GAPLINC in ox-LDL-exposed HAECs decreased cell proliferation by increasing cell apoptosis and arresting cell cycle in G2/M and S phase. Importantly, the detailed mechanistic analysis elucidated that LncRNA GAPLINC acts as a decoy to sequester miR-183-5p to prevent it from binding to target PDCD4. MiR-183-5p targets GAPLINC, and PDCD4 is a downstream target of miR-183-5p, and the cellular effects of this direct interaction were confirmed by a rescue assay experiment. Conclusions: The present study demonstrates that upregulation of lncRNA GAPLINC represses the binding of miR-183-5p to the PDCD4 promoter region and then promotes PDCD4 expression, thereby inducing cell apoptosis and suppressing endothelial cell proliferation.

Recovery of isolated lithium through discharged state calendar ageing.

Rechargeable Li-metal batteries have the potential to more than double the specific energy of the state-of-the-art rechargeable Li-ion batteries, making Li-metal batteries a prime candidate for next-generation high-energy battery technology1-3. However, current Li-metal batteries suffer from fast cycle degradation compared with their Li-ion battery counterparts2,3, preventing their practical adoption. A main contributor to capacity degradation is the disconnection of Li from the electrochemical circuit, forming isolated Li4-8. Calendar ageing studies have shown that resting in the charged state promotes further reaction of active Li with the surrounding electrolyte9-12. Here we discover that calendar ageing in the discharged state improves capacity retention through isolated Li recovery, which is in contrast with the well-known phenomenon of capacity degradation observed during the charged state calendar ageing. Inactive capacity recovery is verified through observation of Coulombic efficiency greater than 100% on both Li||Cu half-cells and anode-free cells using a hybrid continuous-resting cycling protocol and with titration gas chromatography. An operando optical setup further confirms excess isolated Li reactivation as the predominant contributor to the increased capacity recovery. These insights into a previously unknown pathway for capacity recovery through discharged state resting emphasize the marked impact of cycling strategies on Li-metal battery performance.

Dynamic palmitoylation of STX11 controls injury-induced fatty acid uptake to promote muscle regeneration.

Different types of cells uptake fatty acids in response to different stimuli or physiological conditions; however, little is known about context-specific regulation of fatty acid uptake. Here, we show that muscle injury induces fatty acid uptake in muscle stem cells (MuSCs) to promote their proliferation and muscle regeneration. In humans and mice, fatty acids are mobilized after muscle injury. Through CD36, fatty acids function as both fuels and growth signals to promote MuSC proliferation. Mechanistically, injury triggers the translocation of CD36 in MuSCs, which relies on dynamic palmitoylation of STX11. Palmitoylation facilitates the formation of STX11/SNAP23/VAMP4 SANRE complex, which stimulates the fusion of CD36- and STX11-containing vesicles. Restricting fatty acid supply, blocking fatty acid uptake, or inhibiting STX11 palmitoylation attenuates muscle regeneration in mice. Our studies have identified a critical role of fatty acids in muscle regeneration and shed light on context-specific regulation of fatty acid sensing and uptake.

Outcomes of two-stage type II hybrid aortic arch repair in elderly patients with acute type A aortic dissection.

Acute type A aortic dissection (a-TAAD) is a severe disease characterized by high mortality, which can be fatal in elderly patients. The objective of this study was to investigate the safety and efficacy of two-stage type II hybrid aortic arch repair (HAR) in elderly patients with acute type A aortic dissection (a-TAAD). This was a single-center, retrospective study involving 119 patients with a-TAAD, including 82 males and 37 females, aged 22-81 years old. Eighty-eight patients underwent total aortic arch replacement (TAR) with frozen elephant trunk (FET) implantation (TAR with FET group) and 31 patients underwent two-stage type II HAR (HAR group). Propensity score matching was applied to adjust for preoperative data, and match 25 pairs. The preoperative, perioperative, postoperative and follow-up data were recorded. Fifteen patients died during the perioperative period; 13 cases were in the TAR with FET group and 2 cases were in the HAR group. The age, body mass index, cerebral infarction, renal insufficiency were significantly higher, and the 24-h fluid drainage, the incidence of acute liver injury, acute kidney injury and pulmonary infection were lower in the HAR group (all P < 0.05). Moreover, the mechanical ventilation time, intensive care unit time, hospital stay time were shorter in the HAR group (all P < 0.05). The follow-up period ranged from 12 to 54 months, with 7 deaths (9.3%) in the TAR with FET group and 2 deaths (6.9%) in the HAR group. The true lumen of the aortic arch and the middle descending thoracic aorta were larger and the false lumen thrombosis rates of the middle descending thoracic aorta and renal artery level were higher in the HAR group (all P < 0.05). Two-stage type II HAR is a safe and effective method for the treatment of elderly patients with a-TAAD. It may be a good choice for elderly patients with a-TAAD and comorbidities.

Environmental arsenic (As) and its potential relationship with endemic disease in southwestern China.

Many cases of an unknown disease exhibiting the clinical features of limb gangrene, blisters, ulceration, and exfoliation have been reported in Daping village (DV) in southwestern China. However, the pathogenesis is unknown and has puzzled doctors for many years. A preliminary study on heavy metals and symptoms indicated that arsenic might pose the greatest threat to the health of local residents. Here, to explore the sources of and factors influencing arsenic enrichment in DV, whose residents exhibit signs of arsenic poisoning, the As contents in soil, water, and plants were systematically measured. The results indicated high As contents in plant and soil samples obtained from the area, and the source of As may be linked to the weathering of black shale rock. Ingestion of soil and consumption of plants were the two main As exposure pathways among children and adults, respectively, and children exhibited a higher health risk than adults. We presume and emphasize that when extreme drought events occur, humans might face unusual risks resulting from exposure to toxic elements and the direct consumption of highly polluted water. Our study provides a new perspective and sheds light on the environmental geochemistry and health links of this disease.

A multi-band centroid contrastive reconstruction fusion network for motor imagery electroencephalogram signal decoding.

Motor imagery (MI) brain-computer interface (BCI) assist users in establishing direct communication between their brain and external devices by decoding the movement intention of human electroencephalogram (EEG) signals. However, cerebral cortical potentials are highly rhythmic and sub-band features, different experimental situations and subjects have different categories of semantic information in specific sample target spaces. Feature fusion can lead to more discriminative features, but simple fusion of features from different embedding spaces leading to the model global loss is not easily convergent and ignores the complementarity of features. Considering the similarity and category contribution of different sub-band features, we propose a multi-band centroid contrastive reconstruction fusion network (MB-CCRF). We obtain multi-band spatio-temporal features by frequency division, preserving the task-related rhythmic features of different EEG signals; use a multi-stream cross-layer connected convolutional network to perform a deep feature representation for each sub-band separately; propose a centroid contrastive reconstruction fusion module, which maps different sub-band and category features into the same shared embedding space by comparing with category prototypes, reconstructing the feature semantic structure to ensure that the global loss of the fused features converges more easily. Finally, we use a learning mechanism to model the similarity between channel features and use it as the weight of fused sub-band features, thus enhancing the more discriminative features, suppressing the useless features. The experimental accuracy is 79.96% in the BCI competition Ⅳ-Ⅱa dataset. Moreover, the classification effect of sub-band features of different subjects is verified by comparison tests, the category propensity of different sub-band features is verified by confusion matrix tests and the distribution in different classes of each sub-band feature and fused feature are showed by visual analysis, revealing the importance of different sub-band features for the EEG-based MI classification task.

Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40).

Given afferent functions, sensory nerves have recently been found to exert efferent effects and directly alter organ physiology. Additionally, several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts. Nonetheless, evidence regarding the direct sensory nerve efferent influence on osteoclasts is lacking. In the current study, we found that high levels of efferent signals were transported directly from the sensory nerves into osteoclasts. Furthermore, sensory hypersensitivity significantly increased osteoclastic bone resorption, and sensory neurons (SNs) directly promoted osteoclastogenesis in an in vitro coculture system. Moreover, we screened a novel neuropeptide, Cyp40, using an isobaric tag for relative and absolute quantitation (iTRAQ). We observed that Cyp40 is the efferent signal from sensory nerves, and it plays a critical role in osteoclastogenesis via the aryl hydrocarbon receptor (AhR)-Ras/Raf-p-Erk-NFATc1 pathway. These findings revealed a novel mechanism regarding the influence of sensory nerves on bone regulation, i.e., a direct promoting effect on osteoclastogenesis by the secretion of Cyp40. Therefore, inhibiting Cyp40 could serve as a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury.

Development and validation of a prognostic model of survival for classic heatstroke patients: a multicenter study.

Classic heatstroke (CHS) is a life-threatening illness characterized by extreme hyperthermia, dysfunction of the central nervous system and multiorgan failure. Accurate predictive models are useful in the treatment decision-making process and risk stratification. This study was to develop and externally validate a prediction model of survival for hospitalized patients with CHS. In this retrospective study, we enrolled patients with CHS who were hospitalized from June 2022 to September 2022 at 3 hospitals in Southwest Sichuan (training cohort) and 1 hospital in Central Sichuan (external validation cohort). Prognostic factors were identified utilizing least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis in the training cohort. A predictive model was developed based on identified prognostic factors, and a nomogram was built for visualization. The areas under the receiver operator characteristic (ROC) curves (AUCs) and the calibration curve were utilized to assess the prognostic performance of the model in both the training and external validation cohorts. The Kaplan‒Meier method was used to calculate survival rates. A total of 225 patients (median age, 74 [68-80] years) were included. Social isolation, self-care ability, comorbidities, body temperature, heart rate, Glasgow Coma Scale (GCS), procalcitonin (PCT), aspartate aminotransferase (AST) and diarrhea were found to have a significant or near-significant association with worse prognosis among hospitalized CHS patients. The AUCs of the model in the training and validation cohorts were 0.994 (95% [CI], 0.975-0.999) and 0.901 (95% [CI], 0.769-0.968), respectively. The model's prediction and actual observation demonstrated strong concordance on the calibration curve regarding 7-day survival probability. According to K‒M survival plots, there were significant differences in survival between the low-risk and high-risk groups in the training and external validation cohorts. We designed and externally validated a prognostic prediction model for CHS. This model has promising predictive performance and could be applied in clinical practice for managing patients with CHS.

Using the RE-AIM framework to assess national teledermatology expansion.

Background: Teledermatology has been utilized in the United States Department of Veterans Affairs (VA) for decades but continues to have incomplete penetration. VA has funded an initiative to enhance access to dermatology services since 2017 to support asynchronous teledermatology for Veterans living in rural areas. As part of an ongoing evaluation of this program, we assessed the teledermatology activity between the fiscal years 2020 and 2022. We focused on the second cohort of the initiative, comprising six VA facilities and their 54 referral clinics. Methods: We studied teledermatology programs at cohort facilities using the reach, effectiveness, adoption, implementation, and maintenance framework. We used a mixed-methods design including annual online reports completed by participating facilities and VA administrative data. When possible, we compared the data from the 3 years of teledermatology funding with the baseline year prior to the start of funding. Findings: Reach: Compared with the baseline year, there was a 100% increase in encounters and a 62% increase in patients seen at the funded facilities. Over 500 clinicians and support staff members were trained. Effectiveness: In FY 2022, primary or specialty care clinics affiliated with the funded facilities had more dermatology programs than primary or specialty care clinics across the VA (83% vs. 71% of sites). Adoption: By the end of the funding period, teledermatology constituted 16% of dermatology encounters at the funded facilities compared with 12% nationally. This reflected an increase from 9.2% at the funded facilities and 10.3% nationally prior to the funding period. Implementation: The continued funding for staff and equipment facilitated the expansion to rural areas. Maintenance: By the end of the funding period, all facilities indicated that they had fully implemented their program for patients of targeted primary care providers. The Program Sustainability Index scores generally increased during the funding period. Conclusions: Targeted funding to support asynchronous teledermatology implementation for rural Veterans increased its reach, adoption, and implementation, ultimately improving access. Providing program guidance with staffing and training resources can increase the impact of these programs. Ongoing efforts to maintain and increase communication between primary care and dermatology will be needed to sustain success.

On-surface synthesis of nitrogen-doped nanographene with an [18]annulene pore on Ag(111).

On-surface synthesis is of importance to fabricate low dimensional carbon-based nanomaterials with atomic precision. Here, we synthesize nitrogen-doped nanographene with an [18]annulene pore and its dimer through sequential reactions of debromination, aryl-aryl coupling, cyclodehydrogenation and C-N coupling on Ag(111) from 3,12-dibromo-7,8-diaza[5]helicene. The inner structures of the products were characterized with scanning tunneling microscopy with a CO terminated tip at low temperature. Furthermore, the first four unoccupied electronic states of the nanographene were investigated with a combination of scanning tunneling spectroscopy and theoretical calculations. Except for the LUMO + 2 state observed at +1.3 V, the electronic states at 500 mV, 750 mV and 1.9 V were attributed to the superatom molecular orbitals at the [18]annulene pore, which were significantly shifted towards the Fermi level due to the hybridization with the confined surface state.

A topochemical reaction induced the formation of Bi2S3 micro-straws from a Bi-MOF for an ultra-long Zn storage life.

Aqueous zinc ion batteries (ZIBs) are considered as promising energy storage devices in the post-lithium-ion era, due to their high energy density, low cost, high safety, and environmental benignity, however their commercialization is hindered by the sluggish diffusion kinetics of cathode materials due to the large hydrate Zn2+ radius. In this work, we propose a unique structure inheritance strategy for preparing Bi2S3 micro-straws in which a metal-organic framework (MOF) denoted as Bi-PYDC (PYDC2- = 3,5-pyridinedicarboxylate) with a string of [Bi2O2]2+ chains is judiciously selected as the structure-directing template to induce the formation of micro-straws based on a topochemical reaction. The distinctive hollow structure significantly enhances the ionic storage kinetics. Impressively, the obtained battery exhibits an ultra-long cycle life of more than 10 000 cycles at a current density of 1 A g-1 while maintaining a capacity of more than 153.4 mA h g-1. In addition, the Zn2+ insertion/extraction mechanism of Bi2S3 micro-straws is also investigated by multiple analytical methods, revealing the involvement of Zn2+ rather than H+ in the electrochemical storage process. This work may lead a new direction for constructing high performance cathodes of Zn-ion batteries through a MOF-based structure-directing template.

Effect of fluorine doping on the NO2-sensing properties of MoS2nanoflowers.

The somewhat slow recovery kinetics of NO2sensing at low temperatures are still challenging to overcome. To enhance the gas sensing property, fluorine is doped to MoS2nanoflowers by facile hydrothermal method. Extensive characterization data demonstrate that F was effectively incorporated into the MoS2nanoflowers, and that the microstructure of the MoS2nanoflowers did not change upon F doping. The two MoS2doped with varying concentrations of fluorine were tested for their sensing property to NO2gas. Both of them show good repeatability and stability. A smaller recovery time was seen in the F-MoS2-1 sample with a little amount of F loading, which was three times quicker than that of pure MoS2. The key reason for the quicker recovery time of this material was found to be the fluorine ions that had been adsorbed on the surface of F-MoS2-1 would take up some of the NO2adsorption site. Additionally, the sample F-MoS2-2 with a higher F doping level demonstrated increased sensitivity. The F-MoS2-2 sensor's high sensitivity was mostly due to the lattice fluorine filled to the sulfur vacancy, which generated impurity levels and reduced the energy required for its electronic transition. This study might contribute to the development of new molybdenum sulfide based gas sensor.

Laparoscopic versus open radical hysterectomy in FIGO 2018 early-stage cervical adenocarcinoma: Long-term survival outcomes after propensity score matching.

OBJECTIVE: To compare the long-term survival outcomes of laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in International Federation of Gynecology and Obstetrics (FIGO) 2018 early-stage cervical adenocarcinoma. METHODS: Based on the clinical diagnosis and treatment for cervical cancer in mainland China (Four C) database, the medical records of 1098 patients with FIGO 2018 early-stage cervical adenocarcinoma were retrospectively reviewed. Long-term and short-term survival outcomes of the two groups were compared using a multivariate Cox regression model and the log-rank method in the whole study population and after propensity score matching. RESULTS: There was no difference in disease-free survival (hazard ratio [HR] 0.921, 95% confidence interval [CI]: 0.532-1.595, p = 0.770) and overall survival (HR 1.168, 95% CI: 0.526-2.592, p = 0.702) between LRH (n = 468) and ORH (n = 468) in the risk-adjusted analysis. LRH resulted in significantly lower estimated blood loss (342.7 vs. 157.5 mL, p < 0.001) and shorter postoperative anal exhaust time (2.8 vs. 2.5 days, p < 0.001) in risk-adjusted analysis. The overall rates of intraoperative complications (2.4% vs. 4.3%, p = 0.100) and postoperative complications (7.5% vs. 6.2%, p = 0.437) showed no significant difference between the two groups. However, the LRH group had a significantly higher incidence of ureter injury (0.4% vs. 2.4%, p = 0.012) and great vessel injury (0.0% vs. 0.9%, p = 0.045) compared to the other group. No statistical variation in the site of recurrence was observed between the two groups (p = 0.613). CONCLUSIONS: LRH has comparable survival outcomes with ORH and was associated with earlier recovery in FIGO 2018 early-stage adenocarcinoma of the uterine cervix. However, the LRH group had higher risk of ureter injury and great vessel injury.

Layered double hydroxides - poloxamer 188 nanocomposites based on exfoliation reassembling for improved cellular uptake and controlled delivery of methotrexate.

Exploitation of advanced methotrexate (MTX) delivery with nanocomposites has important clinical application value. Poloxamer 188 micelle and layered double hydroxide loaded with MTX (LDH-MTX) by exfoliation reassembling were used to prepare LDH-MTX-poloxamer 188 nanocomposites with good dispersibility and efficient cellular uptake for controlled drug delivery. The LDH-MTX-poloxamer 188 nanocomposites with sphere-like morphology, of which the average hydrodynamic diameter was <100 nm, were shown to have better dispersion state than naked LDH-MTX. Importantly, the LDH-MTX-poloxamer 188 nanocomposites could achieve significant sustained drug release and have obvious pH dependent responsive release ability. In addition, these nanocomposites also exhibited long-term and excellent in vitro antitumor efficacy as opposed to pure MTX or LDH-MTX as evident from cell viability. More interestingly, compared to pure FITC used to simulate MTX, LDH nanocomposites labeled with FITC were considered to have better cell adhesion through cell uptake. Therefore, the studied nanocomposites of LDH-MTX-poloxamer 188 can be further used as a new advanced MTX delivery nanovehicles with desired properties in future therapeutic aspects.