Amphiregulin secreted by umbilical cord Multipotent Stromal Cells protects against ferroptosis of macrophages via the Activating Transcription Factor 3-CD36 axis to alleviate endometrial fibrosis.

Endometrium fibrosis is the leading cause of uterine infertility. Macrophages participated in the occurrence and development of endometrial fibrosis. We previously reported that human umbilical cord multipotent stromal cells (hUC-MSCs) exerted their therapeutic effect in a macrophage-dependent manner in endometrial fibrosis. However precise mechanisms by which hUC-MSCs may influence macrophages in endometrial fibrosis remain largely unexplored. Here, we demonstrated that abnormal iron and lipid metabolism occurred in intrauterine adhesions (IUA) patients and murine models. Ferroptosis has been proven to contribute to the progression of fibrotic diseases. Our results revealed that pharmacological activation of ferroptosis by Erastin aggravated endometrial fibrosis, while inhibition of ferroptosis by Ferrostatin-1 ameliorated endometrial fibrosis in vivo. Moreover, ferroptosis of macrophages was significantly upregulated in endometria of IUA murine models. Of note, transcriptome profiles revealed that CD36 gene expression was significantly increased in IUA patients and immunofluorescence analysis showed CD36 protein was mainly located in macrophages. Silencing CD36 in macrophages could reverse cell ferroptosis. Dual luciferase reporter assay revealed that CD36 was the direct target of activation transcription factor 3 (ATF3). Furthermore, through establishing coculture system and IUA murine models, we found that hUC-MSCs had a protective role against macrophage ferroptosis and alleviated endometrial fibrosis related to decreased CD36 and ATF3. The effect of hUC-MSCs on macrophage ferroptosis was attributed to the upregulation of amphiregulin (AREG). Our data highlighted that macrophage ferroptosis occurred in endometrial fibrosis via the ATF3-CD36 pathway and hUC-MSCs protected against macrophage ferroptosis to alleviate endometrial fibrosis via secreting AREG. These findings provided a potential target for therapeutic implications of endometrial fibrosis.

MSCs promote the efferocytosis of large peritoneal macrophages to eliminate ferroptotic monocytes/macrophages in the injured endometria.

BACKGROUND: Endometria are one of the important components of the uterus, which is located in the peritoneal cavity. Endometrial injury usually leads to intrauterine adhesions (IUA), accompanied by inflammation and cell death. We previously reported that both the endometrial ferroptosis was increased and monocytes/macrophages were involved in endometrial injury of IUA. Large peritoneal macrophages (LPMs) are recently reported to migrate into the injured tissues and phagocytose dead cells to repair the tissues. We previously demonstrated that mesenchymal stromal cells (MSCs) had made excellent progress in the repair of endometrial injury. However, it is unclear whether MSCs regulate the LPM efferocytosis against ferroptotic monocytes/macrophages in the injured endometria. METHODS: Here, endometrial injury in IUA mouse model was conducted by uterine curettage and LPS injection surgery and the samples were collected at different times to detect the changes of LPMs and ferroptotic monocytes/macrophages. We conducted LPMs depletion assay in vivo and LPMs and Erastin-induced ferroptotic THP-1 cells coculture systems in vitro to detect the LPM efferocytosis against ferroptotic monocytes/macrophages. The IUA model was treated with MSCs, and their effects on LPMs and endometrial repair were analyzed. Flow cytometry, western blotting, quantitative real-time PCR, immunohistochemical analysis, ELISA, and RNA-sequencing were performed. RESULTS: We found that LPMs migrated to the injured uteri in response to the damage in early phase (3 h), and sustained to a later stage (7 days). Astonishingly, we found that ferroptotic monocytes/macrophages were significantly increased in the injured uteri since 12 h after injury. Moreover, LPMs cocultured with Erastin-induced ferroptotic THP-1 cells in vitro, efferocytosis of LPMs against ferroptotic monocytes/macrophages was emerged. The mRNA expression profiles revealed that LPM efferocytosis against ferroptotic monocytes/macrophages was an induction of glycolysis program and depended on the PPARγ-HK2 pathway. Importantly, we validated that MSCs promoted the efferocytic capability and migration of LPMs to the injured uteri via secreting stanniocalcin-1 (STC-1). CONCLUSION: The data collectively demonstrated first the roles of LPMs via removal of ferroptotic monocytes/macrophages and provided a novel mechanism of MSCs in repairing the endometrial injury.

Professional characteristics, numbers, distribution and training of China's mental health workforce from 2000 to 2020: a scoping review.

Over the last 20 years, the numbers, types, distribution, and qualifications of mental health professionals in China have changed dramatically. However, there has been no systematic attempt to collect information about this transformation in the human resources available to provide mental health services-information that needs to be regularly updated to improve the country's coordination of these services. This scoping review compiles current details about China's mental health workforce and identifies critical gaps in available research and reporting. We reviewed all relevant studies and reports published between 1 January 2000 and 30 June 2021 in two English-language and four Chinese-language databases, the website of China's National Health Commission, and national and provincial health services yearbooks. In addition to summarising data from government yearbooks, we integrated relevant results from 82 peer-reviewed publications and two government reports. From 2000 to 2020, the number of psychiatrists in the country increased by 139%, and the number of psychiatric nurses increased by 340%. However, the much higher ratio of mental health professionals per 100,000 population and the better quality of training of mental health professionals in urban, eastern provinces compared to rural, western provinces has not changed. Progress has been made in standardising the training of psychiatrists, but there are no standardised training programs for psychiatric nurses, clinical psychologists, or psychiatric social workers. Future research needs to address several issues that limit the effectiveness of policies aimed at increasing the size, quality and equitable distribution of China's mental health workforce: 1) limited data available about the numbers and characteristics of professionals who provide mental health services, 2) absence of nationally standardised training programs for non-psychiatric medical professionals and non-medical personnel who provide essential monitoring and supportive care to persons with mental illnesses, and 3) failure to scientifically assess the outcomes of currently available training programs.

Connections between the middle frontal gyrus and dorso-ventral attention network associate with the development of attentional symptoms.

BACKGROUND: The right MFG has been proposed as a convergence site for the DAN and VAN, regulating both networks and enabling flexible modulation of attention. However, it is unclear if the connections between the right MFG and these networks can predict changes in ADHD symptoms. METHODS: This study used data from the Children School Functions and Brain Development project (n = 713, 56.2% boys). Resting-state fMRI was employed to analyze the connections of the right MFG with DAN/VAN, connectome-based predictive modeling was applied for longitudinal prediction, and ADHD PRS were used for genetic analysis. RESULTS: The ADHD symptoms were associated with the connections between the right MFG and DAN subregion, including the FEF, as well as the VAN subregions, namely the IPL and IFG. Furthermore, these connections of the right MFG with FEF, IPL, and IFG could significantly predict changes in ADHD symptoms over one year and mediate the prediction of ADHD symptom changes by PRS for ADHD. Finally, the validation samples confirmed that the functional connectivity between the right MFG and FEF/IPL in ADHD patients was significantly weaker than that in the typically developing controls, and this difference disappeared after medication. CONCLUSIONS: The connection of right MFG with DAN and VAN can serve as a predictive indicator for changes in ADHD symptoms over the following year, while also mediating the prediction of ADHD symptom changes by PRS for ADHD. These findings hold promise as potential biomarkers for early identification of children at risk of developing ADHD.

The association between the fibrinogen-to-albumin ratio and delirium after deep brain stimulation surgery in Parkinson's disease.

Introduction: Postoperative delirium (POD) remains one of the most prevalent neuropsychiatric complications after deep brain stimulation (DBS) surgery. The fibrinogen-to-albumin ratio (FAR) has been shown to significantly correlate with the prognosis of many diseases related to inflammation. However, the association between FAR and POD remains unclear. We aimed to explore the association between POD and FAR in patients with Parkinson's disease (PD) undergoing DBS surgery. Methods: Patients with PD who underwent DBS surgery in our hospital were included in this retrospective study. FAR was calculated from the blood sample collected on admission. The association between baseline FAR and delirium after surgery was assessed by binary logistic regression analysis, interaction analysis, and stratified analyses. Results: Of 226 patients, 37 (16.4%) suffered from delirium after surgery. The average age of the participants was 63.3 ± 7.2 years, and 51.3% were male patients. Multivariate logistic regression analysis indicated that patients in the highest FAR tertile had a higher risk of POD compared with patients in the lowest FAR tertile (OR = 3.93, 95% CI: 1.24 ~ 12.67). Subgroup analysis demonstrated that FAR and the preoperative Mini-Mental State Examination score (p = 0.013) had an association with delirium after surgery. Conclusion: Our data suggest that a higher preoperative FAR was significantly associated with delirium after DBS surgery. FAR on admission is a useful candidate biomarker to identify patients with PD who are at a high risk of delirium following DBS surgery.

Developing integrated person-centered care quality indicators for home health agencies in Shanghai, China: A modified Delphi-analytic hierarchy process study.

OBJECTIVES: To develop person-centered integrated care quality indicators for home health agencies in Shanghai, China. DESIGN: The study combined the Delphi method and the analytic hierarchy process (AHP). MATERIAL AND METHODS: The Delphi consultation questionnaire was distributed to experts in home healthcare in Shanghai, China. A panel of experts with experience in home healthcare in Shanghai, China, was selected. Purposive sampling was used to choose experts. In this study, ten experts were selected from within sub-fields of home healthcare, including nursing, health policy, quality improvement, person-centered care (PCC), and integrated care. RESULTS: The authority coefficient (Cr) in this study was 0.835. The coordination degree of experts' opinions, which is expressed by Kendall coordination coefficient W (a higher value, better coordination of the item), ranged from 0.352 to 0.386 (p < 0.001). The consistency ratio (CR) values for each level were less than 0.1. The quality indicator system included three first-level indicators, 15 second-level indicators, and 56 third-level indicators. CONCLUSIONS: A person-centered integrated care quality indicator system was developed for home health agencies. The findings from this study enable nurses, managers, and policymakers in home and community-based settings to evaluate person-centered integrated care quality using a robust framework. In addition, these indicators can also be used as a standardized tool to guide the development of long-term care services and supports (LTSS) for home-bound elderly.

Ethylenedioxythiophene-based Small Molecular Donor with Multiple Conformation Locks for Organic Solar Cells with Efficiency of 19.3.

Ternary organic solar cells (T-OSCs) represent an efficient strategy for enhancing the performance of OSCs. Presently, the majority of high-performance T-OSCs incorporates well-established Y-acceptors or donor polymers as the third component. In this study, a novel class of conjugated small molecules has been introduced as the third component, demonstrating exceptional photovoltaic performance in T-OSCs. This innovative molecule comprises ethylenedioxythiophene (EDOT) bridge and 3-ethylrhodanine as the end group, with the EDOT unit facilitating the creation of multiple conformation locks. Consequently, the EDOT-based molecule exhibits two-dimensional charge transport, distinguishing it from the thiophene-bridged small molecule, which displays fewer conformation locks and provides one-dimensional charge transport. Furthermore, the robust electron-donating nature of EDOT imparts the small molecule with cascade energy levels relative to the electron donor and acceptor. As a result, OSCs incorporating the EDOT-based small molecule as the third component demonstrate enhanced mobilities, yielding a remarkable efficiency of 19.3%, surpassing the efficiency of 18.7% observed for OSCs incorporating thiophene-based small molecule as the third component. The investigations in this study underscore the excellence of EDOT as a building block for constructing conjugated materials with multiple conformation locks and high charge carrier mobilities, thereby contributing to elevated photovoltaic performance in OSCs.

Intraepithelial mast cells drive gasdermin C-mediated type 2 immunity.

A specialized population of mast cells residing within epithelial layers, currently known as intraepithelial mast cells (IEMCs), was originally observed over a century ago, yet their physiological functions have remained enigmatic. In this study, we unveil an unexpected and crucial role of IEMCs in driving gasdermin C-mediated type 2 immunity. During helminth infection, αEß7 integrin-positive IEMCs engaged in extensive intercellular crosstalk with neighboring intestinal epithelial cells (IECs). Through the action of IEMC-derived proteases, gasdermin C proteins intrinsic to the epithelial cells underwent cleavage, leading to the release of a critical type 2 cytokine, interleukin-33 (IL-33). Notably, mast cell deficiency abolished the gasdermin C-mediated immune cascade initiated by epithelium. These findings shed light on the functions of IEMCs, uncover a previously unrecognized phase of type 2 immunity involving mast cell-epithelial cell crosstalk, and advance our understanding of the cellular mechanisms underlying gasdermin C activation.

Dimethyl itaconate inhibits antigen-specific Th17 cell responses and autoimmune inflammation via modulating NRF2/STAT3 signaling.

Pathogenic Th17 cells play a crucial role in autoimmune diseases like uveitis and its animal model, experimental autoimmune uveitis (EAU). Dimethyl itaconate (DMI) possesses potent anti-inflammatory effects. However, there is still a lack of knowledge about the role of DMI in regulating pathogenic Th17 cells and EAU. Here, we reported that intraperitoneal administration of DMI significantly inhibited the severity of EAU via selectively suppressing Th17 cell responses. In vitro antigen stimulation studies revealed that DMI dramatically decreased the frequencies and function of antigen-specific Th17, but not Th1, cells. Moreover, DMI hampered the differentiation of naive CD4+ T cells toward pathogenic Th17 cells. DMI-treated DCs produced less IL-1ß, IL-6, and IL-23, and displayed an impaired ability to stimulate antigen-specific Th17 activation. Mechanistically, DMI activated the NRF2/HO-1 pathway and suppressed STAT3 signaling, which subsequently restrains p-STAT3 nuclear translocation, leading to decreased pathogenic Th17 cell responses. Thus, we have identified an important role for DMI in regulating pathogenic Th17 cells, supporting DMI as a promising therapy in Th17 cell-driven autoimmune diseases including uveitis.

Dynamic (Sub)surface-Oxygen Enables Highly Efficient Carbonyl-Coupling for Electrochemical Carbon Dioxide Reduction.

Nowadays, high-valent Cu species (i.e., Cuδ +) are clarified to enhance multi-carbon production in electrochemical CO2 reduction reaction (CO2RR). Nonetheless, the inconsistent average Cu valence states are reported to significantly govern the product profile of CO2RR, which may lead to misunderstanding of the enhanced mechanism for multi-carbon production and results in ambiguous roles of high-valent Cu species. Dynamic Cuδ + during CO2RR leads to erratic valence states and challenges of high-valent species determination. Herein, an alternative descriptor of (sub)surface oxygen, the (sub)surface-oxygenated degree (κ), is proposed to quantify the active high-valent Cu species on the (sub)surface, which regulates the multi-carbon production of CO2RR. The κ validates a strong correlation to the carbonyl (*CO) coupling efficiency and is the critical factor for the multi-carbon enhancement, in which an optimized Cu2O@Pd2.31 achieves the multi-carbon partial current density of ≈330 mA cm-2 with a faradaic efficiency of 83.5%. This work shows a promising way to unveil the role of high-valent species and further achieve carbon neutralization.

Engineered Multivalent Nanobodies Efficiently Neutralize SARS-CoV-2 Omicron Subvariants BA.1, BA.4/5, XBB.1 and BQ.1.1.

Most available neutralizing antibodies are ineffective against highly mutated SARS-CoV-2 Omicron subvariants. Therefore, it is crucial to develop potent and broad-spectrum alternatives to effectively manage Omicron subvariants. Here, we constructed a high-diversity nanobody phage display library and identified nine nanobodies specific to the SARS-CoV-2 receptor-binding domain (RBD). Five of them exhibited cross-neutralization activity against the SARS-CoV-2 wild-type (WT) strain and the Omicron subvariants BA.1 and BA.4/5, and one nanobody demonstrated marked efficacy even against the Omicron subvariants BQ.1.1 and XBB.1. To enhance the therapeutic potential, we engineered a panel of multivalent nanobodies with increased neutralizing potency and breadth. The most potent multivalent nanobody, B13-B13-B13, cross-neutralized all tested pseudoviruses, with a geometric mean of the 50% inhibitory concentration (GM IC50) value of 20.83 ng/mL. An analysis of the mechanism underlying the enhancement of neutralization breadth by representative multivalent nanobodies demonstrated that the strategic engineering approach of combining two or three nanobodies into a multivalent molecule could improve the affinity between a single nanobody and spike, and could enhance tolerance toward escape mutations such as R346T and N460K. Our engineered multivalent nanobodies may be promising drug candidates for treating and preventing infection with Omicron subvariants and even future variants.

Masked autoencoders with generalizable self-distillation for skin lesion segmentation.

In the field of skin lesion image segmentation, accurate identification and partitioning of diseased regions is of vital importance for in-depth analysis of skin cancer. Self-supervised learning, i.e., MAE, has emerged as a potent force in the medical imaging domain, which autonomously learns and extracts latent features from unlabeled data, thereby yielding pre-trained models that greatly assist downstream tasks. To encourage pre-trained models to more comprehensively learn the global structural and local detail information inherent in dermoscopy images, we introduce a Teacher-Student architecture, named TEDMAE, by incorporating a self-distillation mechanism, it learns holistic image feature information to improve the generalizable global knowledge learning of the student MAE model. To make the image features learned by the model suitable for unknown test images, two optimization strategies are, Exterior Conversion Augmentation (EC) utilizes random convolutional kernels and linear interpolation to effectively transform the input image into one with the same shape but altered intensities and textures, while Dynamic Feature Generation (DF) employs a nonlinear attention mechanism for feature merging, enhancing the expressive power of the features, are proposed to enhance the generalizability of global features learned by the teacher model, thereby improving the overall generalization capability of the pre-trained models. Experimental results from the three public skin disease datasets, ISIC2019, ISIC2017, and PH 2 indicate that our proposed TEDMAE method outperforms several similar approaches. Specifically, TEDMAE demonstrated optimal segmentation and generalization performance on the ISIC2017 and PH 2 datasets, with Dice scores reaching 82.1% and 91.2%, respectively. The best Jaccard values were 72.6% and 84.5%, while the optimal HD95% values were 13.0% and 8.9%, respectively.

Insecticidal Activity of Essential Oils and Their Synergistic Effect on Improving the Efficacy of ß-Cypermethrin against Blattella germanica.

We screened the contact activity of 32 commercial essential oils (EOs) and their synergistic effect with ß-cypermethrin against Blattella germanica. Results showed that the most effective EOs against B. germanica were from Illicium verum, Syzygium aromaticum, and Cinnamomum camphora, with LD50 values of less than 500 µg/insect. The most potent synergistic effects of ß-cypermethrin on B. germanica were from Dysphania ambrosioides and Mentha canadensis. Both oils have a co-toxic factor of 133.33. The results of the major compound testing of the EOs showed that trans-anisaldehyde and thymol have the best insecticidal activity against B. germanica, with LD50 values of 141.30 and 138.61 µg/insect, respectively. The compounds with the best synergistic effect on ß-cypermethrin were γ-terpinene and linalool at a concentration of 0.5%. The co-toxic factors for γ-terpinene and linalool were 150 and 133.33, respectively, which were similar to the synergistic effect observed with 2% piperonyl butoxide.

Enriching surface-ordered defects on WO3 for photocatalytic CO2-to-CH4 conversion by water.

Defect engineering has been widely applied in semiconductors to improve photocatalytic properties by altering the surface structures. This study is about the transformation of inactive WO3 nanosheets to a highly effective CO2-to-CH4 conversion photocatalyst by introducing surface-ordered defects in abundance. The nonstoichiometric WO3-x samples were examined by using aberration-corrected electron microscopy. Results unveil abundant surface-ordered terminations derived from the periodic {013} stacking faults with a defect density of 20.2%. The {002} surface-ordered line defects are the active sites for fixation CO2, transforming the inactive WO3 nanosheets into a highly active catalyst (CH4: O2 = 8.2: 16.7 µmol h-1). We believe that the formation of the W-O-C-W-O species is a critical step in the catalytic pathways. This work provides an atomic-level comprehension of the structural defects of catalysts for activating small molecules.

Cell communication pathway prognostic model identified detrimental neurodevelopmental pathways in neuroblastoma.

Neurodevelopmental cell communication plays a crucial role in neuroblastoma prognosis. However, determining the impact of these communication pathways on prognosis is challenging due to limited sample sizes and patchy clinical survival information of single cell RNA-seq data. To address this, we have developed the cell communication pathway prognostic model (CCPPM) in this study. CCPPM involves the identification of communication pathways through single-cell RNA-seq data, screening of prognosis-significant pathways using bulk RNA-seq data, conducting functional and attribute analysis of these pathways, and analyzing the post-effects of communication within these pathways. By employing the CCPPM, we have identified ten communication pathways significantly influencing neuroblastoma, all related to axongenesis and neural projection development, especially the BMP7-(BMPR1B-ACVR2B) communication pathway was found to promote tumor cell migration by activating the transcription factor SMAD1 and regulating UNK and MYCBP2. Notably, BMP7 expression was higher in neuroblastoma samples with distant metastases. In summary, CCPPM offers a novel approach to studying the influence of cell communication pathways on disease prognosis and identified detrimental communication pathways related to neurodevelopment.

The application value of metagenomic next-generation sequencing technology in the diagnosis and treatment of neonatal infectious meningitis - a single center retrospective case-control study.

OBJECTIVE: This retrospective study was conducted to investigate the application value of metagenomics next generation sequencing (mNGS) technology in the diagnosis and treatment of neonatal infectious meningitis. METHODS: From 1 January 2020 to 31 December 2022, 73 newborns suspected of infectious meningitis were hospitalized. After screening by inclusion and exclusion criteria, 69 newborns were subsequently included in the study, containing 27 cases with positive mNGS result and 42 cases with negative mNGS result. Furthermore, according to the diagnosis of meningitis, mNGS positive group and mNGS negative group were further divided into infectious meningitis with mNGS (+) group (n = 27) and infectious meningitis with mNGS (-) group (n = 26), respectively. RESULTS: (1) Compared with cerebrospinal fluid (CSF) culture, mNGS has better diagnostic value [positive predictive value (PPV) = 100.00% (27/27), negative predictive value (NPV) = 38.10% (16/42), agreement rate = 62.32% (43/69), area under the curve (AUC) = 0.750, 95% confidence interval (CI): 0.636-0.864]. (2) There were significant differences in the onset age, age at first CSF test, CSF leukocyte count, CSF glucose, positive rate of CSF culture, blood leukocyte count, procalcitonin (PCT), C-reaction protein (CRP), age at first mNGS test and adjusting anti-infective medication in the comparison between infectious meningitis with mNGS (+) group and infectious meningitis with mNGS (-) group (p < 0.05). (3) mNGS could help improve the cure rate [crude odds ratio (OR) = 3.393, 95%CI: 1.072-10.737; adjusted OR = 15.580, 95%CI: 2.114-114.798]. CONCLUSION: Compared with classic meningitis detection methods, mNGS has better PPV, NPV, agreement rate, and AUC. mNGS could help improve the cure rate.

Angusta gen. n. of the cicada tribe Leptopsaltriini, with description of a new species from China (Hemiptera: Cicadidae).

Angusta gen. n. is erected in the cicada tribe Leptopsaltriini Moulton, 1923, and one new species, Angusta fangtingyui sp. n., is described from China. The relationship of this new genus to related taxa is discussed based on morphology and the phylogeny of Angusta fangtingyui gen. & sp. n. and representative species of subtribes Puranina, Leptopsaltriina, Euterpnosiina and Leptosemiina, which was reconstructed based on the concatenated dataset of three genes (COI + EF-1 + ARD1). Accordingly, Angusta gen. n. is assigned to Euterpnosiina of Leptopsaltriini.

Efficacy and safety of esketamine combined with propofol for curative endoscopic resection in colorectum: a prospective, randomized controlled trial.

BACKGROUND: Curative endoscopic resection is widely used to treat colonic polyps and early stage cancers. The anesthetic strategy commonly involves the use of propofol combined with a small dose of opioids for sedation. Adverse respiratory or cardiovascular events such as hypotension often occur when attempting to achieve the necessary level of sedation. Several studies have suggested its advantages owing to the anesthetic, analgesic, and sympathomimetic properties of esketamine. However, there are no reports on curative colorectal endoscopic resection. We designed this randomized controlled trial to assess the efficacy and safety of esketamine combined with propofol for sedation in patients undergoing curative colorectal endoscopic resection. METHODS: A total of 166 patients who underwent curative colorectal endoscopic resection were randomly assigned to groups A (propofol + fentanyl) or E (propofol + esketamine). Ideal sedation was assessed using the MOAA/S scale and was achieved using TCI-propofol with different doses of fentanyl and esketamine. The propofol consumption and vasoactive drug dosages were recorded. Sedation-related times, adverse events, and satisfaction were recorded. RESULTS: Of the 160 patients, the total propofol consumption was significantly lower in group E (n = 81) (300 mg) than in group A (n = 79) (350 mg). Hypotension and bradycardia were significantly lower in Group E than in Group A. The groups showed no significant differences in other adverse events, induction time, recovery time, or patient or endoscopist satisfaction. CONCLUSION: Compared to fentanyl, esketamine helps decrease propofol consumption and increases cardiovascular stability during curative colorectal endoscopic resection in American Society of Anesthesiologists Class I-III patients without affecting anesthesia, patient and endoscopist satisfaction, or other adverse events. TRIAL REGISTRATION: The study was retrospectively registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; registration number: ChiCTR2300069014 on 03/03/2023).

Relationship between Compound α-Ketoacid and Microinflammation in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) refers to the presence of structural or functional abnormalities in the kidneys that affect health, lasting for more than 3 months. CKD is not only the direct cause of global incidence rate and mortality, but also an important risk factor for cardiovascular disease. Persistent microinflammatory state has been recognized as an important component of CKD, which can lead to renal fibrosis and loss of renal function, and plays a crucial role in the pathophysiology and progression of the disease. Simultaneously, compound α-Ketoacid can bind nitrogen-containing metabolites in the blood and accelerate their excretion from the body, thereby reducing the level of metabolic waste, alleviating gastrointestinal reactions in patients, and reducing the inflammatory response and oxidative stress state of the body. Compound α-Ketoacid contains amino acids required by CKD patients. In this review, we explore the relationship between compound α-Ketoacid and microinflammation in patients with CKD. The review indicated that compound α-Ketoacid can improve the microinflammatory state in CKD patients by improving the nutritional status of CKD patients, improving patient's acid-base balance disorder, regulating oxidative stress, improving gut microbiota, and regulating abnormal lipid metabolism.

NEAT1_1 confers gefitinib resistance in lung adenocarcinoma through promoting AKR1C1-mediated ferroptosis defence.

Gefitinib is one of the most extensively utilized epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for treating advanced lung adenocarcinoma (LUAD) patients harboring EGFR mutation. However, the emergence of drug resistance significantly compromised the clinical efficacy of EGFR-TKIs. Gaining further insights into the molecular mechanisms underlying gefitinib resistance holds promise for developing novel strategies to overcome the resistance and improve the prognosis in LUAD patients. Here, we identified that the inhibitory efficacy of gefitinib on EGFR-mutated LUAD cells was partially dependent on the induction of ferroptosis, and ferroptosis protection resulted in gefitinib resistance. Among the ferroptosis suppressors, aldo-keto reductase family 1 member C1 (AKR1C1) exhibited significant upregulation in gefitinib-resistant strains of LUAD cells and predicted poor progression-free survival (PFS) and overall survival (OS) of LUAD patients who received first-generation EGFR-TKI treatment. Knockdown of AKR1C1 partially reversed drug resistance by re-sensitizing the LUAD cells to gefitinib-mediated ferroptosis. The decreased expression of miR-338-3p contributed to the aberrant upregulation of AKR1C1 in gefitinib-resistant LUAD cells. Furthermore, upregulated long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1_1 (NEAT1_1) sponged miR-338-3p to neutralize its suppression on AKR1C1. Dual-luciferase reporter assay and miRNA rescue experiment confirmed the NEAT1_1/miR-338-3p/AKR1C1 axis in EGFR-mutated LUAD cells. Gain- and loss-of-function assays demonstrated that the NEAT1_1/miR-338-3p/AKR1C1 axis promoted gefitinib resistance, proliferation, migration, and invasion in LUAD cells. This study reveals the effects of NEAT1_1/miR-338-3p/AKR1C1 axis-mediated ferroptosis defence in gefitinib resistance in LUAD. Thus, targeting NEAT1_1/miR-338-3p/AKR1C1 axis might be a novel strategy for overcoming gefitinib resistance in LUAD harboring EGFR mutation.