Comprehensive mapping and modelling of the rice regulome landscape unveils the regulatory architecture underlying complex traits.

Unraveling the regulatory mechanisms that govern complex traits is pivotal for advancing crop improvement. Here we present a comprehensive regulome atlas for rice (Oryza sativa), charting the chromatin accessibility across 23 distinct tissues from three representative varieties. Our study uncovers 117,176 unique open chromatin regions (OCRs), accounting for ~15% of the rice genome, a notably higher proportion compared to previous reports in plants. Integrating RNA-seq data from matched tissues, we confidently predict 59,075 OCR-to-gene links, with enhancers constituting 69.54% of these associations, including many known enhancer-to-gene links. Leveraging this resource, we re-evaluate genome-wide association study results and discover a previously unknown function of OsbZIP06 in seed germination, which we subsequently confirm through experimental validation. We optimize deep learning models to decode regulatory grammar, achieving robust modeling of tissue-specific chromatin accessibility. This approach allows to predict cross-variety regulatory dynamics from genomic sequences, shedding light on the genetic underpinnings of cis-regulatory divergence and morphological disparities between varieties. Overall, our study establishes a foundational resource for rice functional genomics and precision molecular breeding, providing valuable insights into regulatory mechanisms governing complex traits.

Construction of an immune-related gene prognostic model for obese endometrial cancer patients based on bioinformatics analysis.

Background: The tumor microenvironment (TME) affected the prognosis of tumors. However, its effect on the outcomes of obese endometrial cancer (EC) patients had not been reported. Methods: This research performed a retrospective analysis of the transcriptome profiles and medical data of 503 EC patients. Immune scores were assessed by estimation algorithms. Cox and LASSO regression analyses were utilized to pinpoint key genes linked to prognosis, and the RPS was created to forecast the outcomes of obese EC patients. The relationship among genetic mutations and RPS was examined using CNV and somatic mutation information. ssGSEA and GSVA were employed to detect immune infiltration and immune pathway enrichment associated with key genes. The TIDE algorithm and GDSC database were utilized to forecast patients' responses of patients to immunotherapy and chemotherapy, respectively. Finally, we employed the 'rms' R software package to construct the nomogram. Results: The prognosis of obese EC patients was associated with immune scores. Three key genes (EYA4, MBOAT2 and SCGB2A1) were identified. The risk prognosis score (RPS) for obese EC patients was established by risk stratification and prognostic prediction using prognostic genes. The higher the RPS, the worse the prognosis, and the more malignant the genomic alterations. The high RPS group had a significantly reduced proportion of most immune cells in comparison to the low RPS group. The high RPS group was linked to G2M, MYC and E2F related pathways such as cell proliferation, cell cycle and cell death. Cisplatin, tamoxifen and topotecan had a greater effect on the low RPS group. Notably, the nomogram had a good predictive ability. Conclusion: Our study designed a reliable RPS for obese EC patients to forecast their prognosis, immune aggressiveness, and responses to immunotherapy and drug treatments.

Causal relationship between systemic lupus erythematosus and adverse pregnancy outcomes: A two-sample Mendelian randomized study.

Background: Systemic lupus erythematosus (SLE) is associated with adverse pregnancy outcome (APO). However, the genetic causality of this association remains unclear. In this study, Mendelian randomization (MR) was used to explore the potential causal relationship between SLE and APO risk. Methods: We selected 45 single nucleotide polymorphisms (SNPs) associated with SLE from published genome-wide association studies (GWAS). APO's statistics are obtained from the GWAS database. MR estimates were performed using the inverse variance-weighted (IVW) method, the MR-Egger method, and the weighted median (WM) method. Sensitivity analysis was performed using Cochran's Q test, MR-Egger intercept, MR-pleiotropic residual and outlier method, stay-one analysis and funnel plot. Results: The results showed a causal relationship between SLE and pre-eclampsia (OR = 1.036, 95 % confidence interval 1.006 to 1.068, P = 0.019), and no significant causal relationship was found between SLE and other adverse pregnancy outcomes, including postpartum hemorrhage, placental abruption, spontaneous abortion, premature rupture of membranes, fetal distress, gestational diabetes mellitus. These findings were robust in several sensitivity analyses. Conclusion: This MR study demonstrated the causal effect of SLE on preeclampsia. It provides important clues for identifying and early predicting risk factors for preeclampsia.

Combining Mitomycin C with inhibition of BAD phosphorylation enhances apoptotic cell death in advanced cervical cancer.

OBJECTIVE: Mitomycin C (MMC), a DNA-damaging chemotherapeutic, is commonly used clinically for recurrent cervical carcinoma (CC), either alone or in combination. MMC generates DNA damage resulting in CC cell death yet also induces increased AKT-BAD phosphorylation associated with drug resistance and reduced clinical benefit. The present study evaluates the efficacy of combined MMC and a BAD phosphorylation inhibitor in CC. METHODS: The association and function of phosphorylation of BAD on serine 99 (pBADS99) for cell survival of both MMC-resistant or sensitive-CC cells was explored. BAD was mutated to BADS99A to examine the requirement of BADS99 for CC cell survival and a novel small-molecule inhibitor of pBADS99 was utilized. Cell proliferation, survival, foci formation, and patient-derived organoids (PDOs) assays were utilized to determine efficacy, synergy and related mechanisms. RESULTS: MMC IC50 was positively correlated to the cell line pBADS99/BAD ratio. Increased BADS99 phosphorylation was observed in both MMC-sensitive or -resistant CC cells after MMC treatment. Inhibition of pBADS99 in CC cell lines produced synergistic apoptosis through BAD-mediated apoptotic pathways and enhanced DNA damage in response to MMC. The concurrent use of pharmacological inhibition of pBADS99 and MMC was synergistic, resulting in diminished cell viability and inducing apoptotic cell death in MMC-sensitive and -resistant CC cell lines or patient-derived organoids. CONCLUSION: A combination of MMC with inhibition of BAD phosphorylation potentiated efficacy compared to single agent treatment. The potential further development of such strategies may provide outcome benefits to patients with CC.

NIR-triggered NO production combined with photodynamic therapy for tumor treatment.

Photodynamic therapy (PDT), as one of the most promising cancer therapy methods, is still limited by several drawbacks, such as tissue hypoxia and shallow light penetration of blue-violet light (200-450 nm), and red light (750 nm) is more penetrating to tissues than blue-violet light, but still lower than near-red light (750-1350 nm). Therefore, we proposed a synergistic therapy system by combining the near-infrared light-triggered PDT with nitric oxide (NO)-based gas therapy to enhance the anti-tumor effects. Upconversion nanoparticles (UCNPs) were loaded with the photosensitizers of ZnPc and the NO donors of l-arginine (L-Arg) to obtain the nanocomposites of UCN@mSiO2@ZnPc@L-Arg. Under 980 nm laser irradiation, reactive oxygen species (ROS) could be produced for PDT and react with l-Arg to produce NO, which is previously reported to have a greater killing effect on tumor cells than ROS and also plays an important role in promoting PDT in our study. Both the in vitro and in vivo tests demonstrated that the combined therapy of PDT with NO therapy could enhance the tumor killing effect significantly compared with the unique application of PDT. The UCNPs-based nanocomposites are expected to be widely used in biomedicine for tumor inhibition.

Clinical Characteristics of Overweight Patients With Acute Exacerbation Chronic Obstructive Pulmonary Disease (AECOPD).

INTRODUCTION: Low body weight in patients with COPD is associated with a poor prognosis and more comorbidities. However, the impact of increased body weight in patients with COPD remains controversial. The aim of this study was to explore the clinical features of overweight patients with AECOPD. METHODS: In this multicenter cross-sectional study, a total of 647 AECOPD patients were recruited. Finally, 269 normal weight and 162 overweight patients were included. Baseline characteristics and clinical and laboratory data were collected. The least absolute shrinkage and selection operator (LASSO) regression was performed to determine potential features, which were substituted into binary logistic regression to reveal overweight-associated clinical features. The nomogram and its associated curves were established to visualize and verify the logistic regression model. RESULTS: Six potential overweight-associated variables were selected by LASSO regression. Subsequently, a binary logistic regression model identified that the rates of type 2 diabetes (T2DM) and hypertension and levels of lymphocytes (LYM)%, and alanine aminotransferase (ALT) were independent variables of overweight in AECOPD patients. The C-index and AUC of the ROC curve of the nomogram were 0.671 and 0.666, respectively. The DCA curve revealed that the nomogram had more clinical benefits if the threshold was at a range of 0.22~0.78. CONCLUSIONS: Collectively, we revealed that T2DM and hypertension were more common, and LYM% and ALT were higher in AECOPD patients with overweight than those with normal weight. The result suggests that AECOPD patients with overweight are at risk for additional comorbidities, potentially leading to worse outcomes.

What are the frequent complaints voiced by inpatients and physicians amidst the emerging infectious diseases? - An illustrative instance of the COVID-19.

INTRODUCTION: Emerging infectious diseases (EIDs) can disrupt the healthcare system, causing regulatory changes that affect the healthcare-seeking process and potentially increase patient-physician dissatisfaction. This study aimed to collect and analyze patients' and physicians' complaints during an EID outbreak to inform potential clues regarding medical quality and patient safety enhancement in future dealing with EIDs, employing text mining methodologies. METHODS: In this descriptive study, complaint records from January 2020 to February 2023 at West China Hospital, a national medical facility in China, were analyzed. Patient and physician complaints have been retrospectively retrieved from the record from the medical department, and then categorized into distinct groups based on reporting reasons, encompassing COVID-19-related policies, healthcare access, availability of medical resources, and financial concerns. RESULTS: During the COVID-19 pandemic, 541 COVID-19-related complaints were identified: 330 (61.00%) from patients and 211 (39.00%) from physicians. The monthly volume of complaints fluctuated, starting at 10 in 2020, peaking at 21 in 2022, and dropping to 14 in 2023. Most complaints from inpatients were expressed by older males aged 40 to 65 (38.82%, 210/541). The primary source of complaints was related to mandatory COVID-19 policies (79.30%, 429/541), followed by concerns regarding timely healthcare services (31.61%, 171/541). Few complaints were expressed regarding the insufficiency of medical resources (2.77%, 15/541) and the high costs (4.25%, 23/541). The frequency of complaints expressed by doctors and patients in the emergency department was higher compared with other departments (24.58%, 133/541). CONCLUSIONS: Increased complaints may serve as a primitive and timely resource for investigating the potential hazards and drawbacks associated with policies pertaining to EIDs. Prompt collection and systematical analysis of patient and physician feedback could help us accurately evaluate the efficacy and repercussions of these policies. Implementing complaints-based assessment might improve care standards in forthcoming healthcare environments grappling with EIDs.

Acute changes in hippocampal metabolism after anesthesia and surgery: Implications for perioperative neurocognitive disorder.

BACKGROUND: The risk of developing dementia is higher in individuals who suffer from perioperative neurocognitive disorder (PND), including postoperative cognitive dysfunction (POCD) and delirium. Recent studies have indicated correlations between anesthesia, surgery and PND. Acute metabolic changes induced by anesthesia and surgery may be related to cognitive impairments. Despite a paucity of research on acute metabolic changes in the hippocampus during surgery, there are conflicting about specific metabolites. METHODS: We developed a mouse model of cognitive impairment induced by isoflurane anesthesia and unilateral nephrectomy. Cognition was evaluated by Y maze and fear conditioning test (FCT). The hippocampus was harvested after the surgery. LC-MS (liquid chromatography-mass spectrometry) was performed. The differential metabolites involved in lipid, amino acid, nucleotide, carbohydrate metabolism were analyzed. RESULTS: Anesthesia and surgery exposure induced cognition decline. A total of 49 metabolites were significantly up-regulated and 122 down-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the metabolites identified purine, glutathione, nicotinate and nicotinamide metabolism. Metabolites involved in lipid, amino acid, nucleotide, carbohydrate metabolism were identified including nicotinamide adenine dinucleotide (NAD), 1-Methylnicotinamide, propionic acid, histidine, adenosine, and guanosine cyclic monophosphate. Some metabolites exhibited a consistent change trend in the hippocampus of aging mice. CONCLUSIONS: The study indicates that anesthesia and surgery can induce acute alterations in hippocampal metabolomics, including metabolites involved in lipid, amino acid, nucleotide, and carbohydrate metabolism. These metabolites may play a role in modulating PND through the regulation of neuroinflammation, oxidative stress, blood-brain barrier (BBB) permeability.

Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Patients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA. METHODS: scRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy. RNA-seq analysis and western blot assays were performed to examine the upstream and downstream signaling pathways of CD73. Subcutaneous tumor xenograft models were utilized to investigate the impact of CD73 on iCCA growth. Plasmid AKT/NICD-induced spontaneous murine iCCAs were used to explore the therapeutic efficacy of CD73 enzymatic inhibitor AB680 combined with PD-1 blockade. Time-of-flight mass cytometry (CyTOF) was conducted to identify the tumor-infiltrating immune cell populations and their functional changes in murine iCCAs treated with AB680 in combination with PD-1 antibody. RESULTS: scRNA-seq analysis identified elevated CD73 expression in malignant cells in response to ICBs therapy. Mechanistically, ICBs therapy upregulated CD73 expression in malignant cells via TNF-α/NF-κB signaling pathway. In vivo studies revealed that CD73 inhibition suppressed the growth of subcutaneous tumors, and achieved synergistic depression effects with gemcitabine and cisplatin (GC). Adenosine produced by CD73 activates AKT/GSK3ß/ß-catenin signaling axis in iCCA cells. CD73 inhibitor AB680 potentiates anti-tumor efficacy of PD-1 antibody in murine iCCAs. CyTOF analysis showed that AB680 combined with anti-PD-1 therapy promoted the infiltration of CD8+ T, CD4+ T cells, and NK cells in murine iCCAs, while simultaneously decreased the proportions of macrophages and neutrophils. Moreover, AB680 combined with anti-PD-1 significantly upregulated the expression of Granzyme B, Tbet and co-stimulatory molecule ICOS in infiltrating CD8+ T cells. CONCLUSIONS: CD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response.

A combined endovascular and open repair of innominate artery bifurcation pseudoaneurysm: a case report.

BACKGROUND: Innominate artery aneurysms (IAAs) are rare and may result in rupture, distal arterial embolization, or local compression without timely treatment. Rupture is the most dangerous of these complications. This article reports a case of innominate artery bifurcation pseudoaneurysm. CASE PRESENTATION: The patient was a 45-year-old man who was admitted to the emergency department due to chest discomfort. The computed tomographic angiography (CTA) imaging indicated the presence of a 3.6*2.4 cm saccular aneurysm in the bifurcation of the innominate artery, involving both the right proximal subclavian and common carotid arteries. The patient's vital signs were normal, there was equal blood pressure in the upper arms and no neurological dysfunction was observed. Gadolinium-enhanced magnetic resonance angiography indicated that the circle of Willis was intact. The treatment involved open surgery combined with endovascular therapy. The external carotid artery was first transposed to the right subclavian artery (RSA) and an 8-mm woven Dacron graft was inserted in the middle. The covered stent graft was then placed in the proximal part of the innominate artery to close the entrance of the aneurysm. Lastly, an occluder was implanted at the origin of the RSA. There were no perioperative or postoperative complications. At 1-year follow-up, no aneurysm was observed on CTA and the right vertebral artery was patent. CONCLUSIONS: This study indicated that the combined use of endovascular therapy and open repair surgery is an effective strategy to treat innominate artery bifurcation pseudoaneurysm.

Effects of Enterobacter cloacae insecticidal protein on the Duox-ROS system and midgut bacterial community and function of Galleria mellonella larvae.

BACKGROUND: Enterobacter cloacae insecticidal proteins have been reported to kill Galleria mellonella larvae through affecting their midgut microbiome. However, the mechanisms involved remain unclear. Here we aim to investigate how the insecticidal proteins act on the midgut Duox-ROS system and microbial community of G. mellonella larvae. METHODS: Reverse transcription qPCR and fluorescence probes were utilized to assess the Duox expression levels and to evaluate quantitative changes of the ROS levels. Sequencing of the 16S rRNA gene sequences of the midgut bacteria of G. mellonella larvae was conducted for further analyses of bacterial diversity, composition, and abundance. RESULTS: After the injection of the insecticidal proteins, the Duox expression levels first increased within 28 h, then dramatically peaked at 36 h, and slowly decreased thereafter. Simultaneously, the ROS levels increased significantly at 36 h, peaked at 48 h, and rapidly declined to the normal level at 60 h. Responsive to the change of the ROS levels, the structure of the midgut microbial community was altered substantially, compared to that of the untreated larvae. The relative abundance of Enterobacteriaceae and other specific pathogenic bacteria increased significantly, whereas that of Lactobacillus decreased sharply. Importantly, notable shifts were observed in the crucial midgut predicted metabolic functions, including membrane transportation, carbohydrate metabolism, and amino acid metabolism. CONCLUSION: Insecticidal proteins of E. cloacae kill G. mellonella larvae mainly through generation of high oxidative stress, alterations of the midgut microbial community and function, and damage to the physiological functions. These findings provide insights into the inhibition mechanism of E. cloacae insecticidal proteins to G. mellonella larvae.

Low-dose X-ray stimulated NO-releasing nanocomposites for closed-loop dual-mode cancer therapy.

X-ray-excited photodynamic therapy (X-PDT) employs X-rays as an energy source, overcoming the light penetration limitations of traditional photodynamic therapy (PDT) but is constrained by high-energy radiation and the hypoxic tumor microenvironment. Low-dose X-ray-excited photodynamic therapy and reduction of mitochondrial oxygen consumption can serve as significant breakthroughs in overcoming these barriers. In this study, NaLuF4:Tb/Gd (15%/5%)@NaYF4 (ScNP) nanoparticles adsorbing the photosensitizer MC540 and loaded with α-(nitrate ester) acid (NEAA) were prepared as low X-ray dose triggered nano-scintillators. The final product obtained was NaLuF4:Tb/Gd (15%/5%)@NaYF4@mSiO2@MC540@NEAA (ScNP-MS@MC540@NEAA) nanocomposites, which exhibited intense green luminescence. X-PDT generates cytotoxic reactive oxygen species (ROS) with minimal ionizing radiation damage. Simultaneously, NEAA reacts with glutathione (GSH) to generate nitric oxide (NO) for gaseous treatment of the damaged mitochondrial respiratory chain to reduce oxygen consumption and alleviate hypoxia, enhancing the X-PDT efficacy and realizing a closed-loop treatment. The superoxide ions (˙O2-) can rapidly react with NO produced to form the highly cytotoxic reactive nitrogen species (RNS) peroxynitrite anion (ONOO-), which exhibits higher cytotoxicity compared to ROS. Furthermore, GSH scavenges toxic ROS and maintains the physiological function of tumor cells. It can induce cancer cell overoxidation and nitrosative stress. This work describes a low-dose X-ray-triggered X-PDT system with total radiation of 50 mGy, which involves GSH consumption, self-supplied NO, mitochondrial damage alleviation, and hypoxia relief to generate ROS and RNS, forming a closed-loop anti-hypoxia dual-mode system with synergistically enhanced anti-tumor effects, without significant biological side effects. It provides a promising platform for deep-seated tumor X-PDT with considerable application prospects.

Syntropic spin alignment at the interface between ferromagnetic and superconducting nitrides.

The magnetic correlations at the superconductor/ferromagnet (S/F) interfaces play a crucial role in realizing dissipation-less spin-based logic and memory technologies, such as triplet-supercurrent spin-valves and 'π' Josephson junctions. Here we report the observation of an induced large magnetic moment at high-quality nitride S/F interfaces. Using polarized neutron reflectometry and DC SQUID measurements, we quantitatively determined the magnetization profile of the S/F bilayer and confirmed that the induced magnetic moment in the adjacent superconductor only exists below T C. Interestingly, the direction of the induced moment in the superconductors was unexpectedly parallel to that in the ferromagnet, which contrasts with earlier findings in S/F heterostructures based on metals or oxides. First-principles calculations verified that the unusual interfacial spin texture observed in our study was caused by the Heisenberg direct exchange coupling with constant J∼4.28 meV through d-orbital overlapping and severe charge transfer across the interfaces. Our work establishes an incisive experimental probe for understanding the magnetic proximity behavior at S/F interfaces and provides a prototype epitaxial 'building block' for superconducting spintronics.

The impact of type 2 diabetes on polycystic ovary syndrome in patients undergoing sleeve gastrectomy.

STUDY QUESTION: Does the concurrent type 2 diabetes mellitus (T2DM) aggravate the features and prognosis of PCOS in patients undergoing sleeve gastrectomy (SG)? SUMMARY ANSWER: For patients undergoing SG with obesity, concurrent T2DM is associated with aggravated metabolic but milder reproductive features of PCOS and did not attenuate the resumption of regular menstruation for up to 1 year after surgery. WHAT IS KNOWN ALREADY: Women with T2DM have an increased risk of PCOS. However, whether concurrent T2DM further increases the disease burden and treatment difficulty of PCOS in patients with obesity requires further investigation. STUDY DESIGN, SIZE, DURATION: This was a single-center, two-arm, prospective, cohort study enrolling a total of 329 women with PCOS and scheduled for SG because of obesity at an university-affiliated hospital between January 2020 and August 2023, with a 1-year follow-up after surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Comparisons were made between patients with T2DM (PCOS+T2DM) and without (PCOS) to examine the impact of T2DM on the metabolic, reproductive, and psychological features of PCOS. The follow-up data of weight loss and menstruation were analyzed to determine the impact of T2DM on PCOS prognosis for up to 1 year after SG. MAIN RESULTS AND THE ROLE OF CHANCE: After controlling for confounders, patients in the PCOS+T2DM group (n = 98) showed more severe insulin resistance, glucose intolerance, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD) (NAFLD activity score 4.31 ± 1.15 versus 3.52 ± 1.42, P < 0.001) than those in the PCOS group (n = 149). In addition, the PCOS+T2DM group had a lower level of total testosterone (1.63 ± 0.69 versus 1.82 ± 0.76, P = 0.045), a lower ratio between luteinizing hormone and follicle-stimulating hormone (median 1.48 versus 1.68, P = 0.030), and a lower proportion of patients with polycystic ovarian morphology (88% versus 96%, P = 0.022) than the PCOS group. As a result, the two groups differed significantly in terms of the Rotterdam classification of PCOS (P = 0.009). No significant difference was detected by group in the psychological features of PCOS except a lower degree of emotional eating in the PCOS+T2DM group (P = 0.001). Although the PCOS+T2DM group took longer to resume regular menstruation after SG (P = 0.037), the two groups had similar proportions of patients with regular menstruation (85% versus 87%, P = 0.758) 1 year after SG, which was further confirmed by subgroup analyses by body mass index. LIMITATIONS, REASONS FOR CAUTION: The prognosis of PCOS after SG mainly focused on the results of menstruation rather than a complete evaluation of the remission of the disease. WIDER IMPLICATIONS OF THE FINDINGS: Our study showed that, for patients with obesity, concurrent T2DM is associated with aggravated metabolic but milder reproductive features of PCOS and did not attenuate the resumption of regular menstruation for up to 1 year after surgery. Our study also highlights the need for high-quality studies with a more comprehensive evaluation of the impact of T2DM on the prognosis of patients with PCOS after SG. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Natural Science Foundation of China Grants (82100853), the Natural Science Foundation of Shandong Province of China (ZR2021QH028), and the Clinical Research Project of Shandong University (2020SDUCRCC024). The authors have no conflicts of interest. TRIAL REGISTRATION: Chinese Clinical Trial Registry with No. ChiCTR1900026845.

Para-aortic lymph node dissection with or without nerve-sparing in gynecological malignancies.

OBJECTIVE: Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves. METHODS: This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nerve-sparing was performed. The surgical, functional and oncological outcomes were evaluated. RESULTS: There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate. CONCLUSION: NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.

Imidazole-Based Ionic Liquid Engineering for Perovskite Solar Cells with High Efficiency and Excellent Stability.

Despite the remarkable progress of perovskite solar cells (PSCs), the substantial inherent defects within perovskites restrict the achievement of higher efficiency and better long-term stability. Herein, we introduced a novel multifunctional imidazole analogue, namely, 1-benzyl-3-methylimidazolium bromide (BzMIMBr), into perovskite precursors to reduce bulk defects and inhibit ion migration in inverted PSCs. The electron-rich environment of -N- in the BzMIMBr structure, which is attributed to the electron-rich adjacent benzene ring-conjugated structure, effectively passivates the uncoordinated Pb2+ cations. Moreover, the interaction between the BzMIMBr additive and perovskite can effectively hinder the deprotonation of formamidinium iodide/methylammonium iodide (FAI/MAI), extending the crystallization time and improving the quality of the perovskite precursors and films. This interaction also effectively inhibits ion migration to subsequent deposited films, leading to a noteworthy decrease in trap states. Various characterization studies show that the BzMIMBr-doped films exhibit superior film morphology and surface uniformity and reduced nonradiative carrier recombination, consequently enhancing crystallinity by reducing bulk/surface defects. The PSCs fabricated on the BzMIMBr-doped perovskite thin film exhibit a power conversion efficiency of 23.37%, surpassing that of the pristine perovskite device (20.71%). Additionally, the added BzMIMBr substantially increased the hydrophobicity of perovskite, as unencapsulated devices still retained 93% of the initial efficiency after 1800 h of exposure to air (45% relative humidity).

Mendelian randomization highlights sleep disturbances mediated the effect of depression on chronic pain.

INTRODUCTION: Depression and chronic pain are significant contributors to the global burden of disease. Previous research has revealed complex relationships between these two conditions, which may be influenced by sleep quality. However, observational studies have limitations, including confounding factors and reverse causation. This study aims to explore the mediating effects of sleep on the relationship between depression and chronic pain using Mendelian randomization (MR). METHODS: We conducted a two-step, two-sample MR study using mediation analysis. We obtained major depressive disorder (MDD) Genome-Wide Association Studdies (GWAS) data from Wray et al.'s GWAS meta-analysis. Phenotypic data related to sleep were collected from the UK Biobank. Chronic pain data were obtained from the Finnish database. RESULTS: MR analysis revealed significant genetic associations between MDD and chronic localized pain [IVW: odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.16-1.38, p = 2.52 × 10-7] as well as fibromyalgia (IVW: OR = 2.17, 95% CI = 1.34-3.52, p = .002). Genetic susceptibility for MDD was also associated with insomnia (IVW: OR = 1.10, 95% CI = 1.06-1.13, p = 3.57 × 10-8) and self-reported short sleep duration (IVW: OR = 1.03, 95% CI = 1.00-1.06, p = .047). The mediating effects of insomnia and fibromyalgia on the pathway from depression to chronic regional pain were 1.04 and 1.03, respectively, with mediation proportions of 12.8% and 15.2%. Insomnia mediated the pathway between depression and fibromyalgia with an effect of 1.12, accounting for 15.2% of the total effect. CONCLUSION: This two-step MR analysis strengthens the evidence of genetic predictive associations between depression and chronic pain, highlighting the mediating roles of insomnia and short sleep duration. It further elucidates the specific roles of distinct sleep disorders, differentiating insomnia and short sleep duration from other sleep-related phenotypes.

PPCRKB: a risk factor knowledge base of postoperative pulmonary complications.

Postoperative pulmonary complications (PPCs) are highly heterogeneous disorders with diverse risk factors frequently occurring after surgical interventions, resulting in significant financial burdens, prolonged hospitalization and elevated mortality rates. Despite the existence of multiple studies on PPCs, a comprehensive knowledge base that can effectively integrate and visualize the diverse risk factors associated with PPCs is currently lacking. This study aims to develop an online knowledge platform on risk factors for PPCs (Postoperative Pulmonary Complications Risk Factor Knowledge Base, PPCRKB) that categorizes and presents the risk and protective factors associated with PPCs, as well as to facilitate the development of individualized prevention and management strategies for PPCs based on the needs of each investigator. The PPCRKB is a novel knowledge base that encompasses all investigated potential risk factors linked to PPCs, offering users a web-based platform to access these risk factors. The PPCRKB contains 2673 entries, 915 risk factors that have been categorized into 11 distinct groups. These categories include habit and behavior, surgical factors, anesthetic factors, auxiliary examination, environmental factors, clinical status, medicines and treatment, demographic characteristics, psychosocial factors, genetic factors and miscellaneous factors. The PPCRKB holds significant value for PPC research. The inclusion of both quantitative and qualitative data in the PPCRKB enhances the ability to uncover new insights and solutions related to PPCs. It could provide clinicians with a more comprehensive perspective on research related to PPCs in future. Database URL: http://sysbio.org.cn/PPCs.

Outcomes of clinical decision support systems in real-world perioperative care: A systematic review and meta-analysis.

BACKGROUND: Although clinical decision support systems (CDSS) have been developed to enhance the quality and efficiency of surgeries, little is known regarding the practical effects in real-world perioperative care. OBJECTIVE: To systematically review and meta-analyze the current impact of CDSS on various aspects of perioperative care, providing evidence support for future research on CDSS development and clinical implementation. METHODS: This systematic review and meta-analysis followed the Cochrane Handbook and PRISMA statement guidelines, searching databases up to February 2, 2024, including MEDLINE, PubMed, Embase, Cochrane, and Web of Science. It included studies on the effectiveness of CDSS in assisting perioperative decision-making, involving anaesthesiologists, doctors, or surgical patients, and reporting at least one outcome such as complications, mortality, length of stay, compliance, or cost. RESULTS: Forty studies met inclusion criteria, analyzing outcomes from 408,357 participants, predominantly in developed countries. Most perioperative CDSS use was associated with improved guideline adherence, decreased medication errors, and some improvements in patient safety measures such as reduced postoperative nausea and vomiting and myocardial injury. However, reported results varied widely, and no significant improvement in postoperative mortality was observed. CONCLUSION: The preliminary findings of this review offer an overview of the potential use of CDSS in real-world perioperative situations to enhance patient and anaesthesiologist outcomes, but further researches with broader outcome dimensions, involving more stakeholders, and with longer follow-up periods are warranted for the critical evaluation of CDSS and then in better facilitate clinical adoption.

3-Methyladenine attenuates neuroinflammation and improves cognitive function in sepsis-associated encephalopathy by inhibiting autophagy.

OBJECTIVE: Sepsis-associated encephalopathy (SAE) can lead to severe cerebral dysfunction as well as cognitive dysfunction, resulting in a significant disease burden. 3-Methyladenine (3-MA) has been confirmed to have anti-inflammatory effects on diseases characterized by enhanced autophagy. However, its role in SAE has not been clarified. METHODS: An SAE mouse model was generated by intraperitoneal injection of lipopolysaccharide (LPS). Mice were given 5, 20, or 80 mg/kg 3-MA to determine the therapeutic dose. The mice in the different groups were given 20 mg/kg 3-MA or saline, and survival, body temperature, body weight and neurobehavioral scores were measured at different time points. The expression of autophagy-related proteins and inflammatory factors was detected by Western blotting, enzyme linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR) 12 h after LPS induction. Glial activation and neuronal injury in the hippocampus were detected by immunofluorescence staining and HE staining. The open Field test, novel object recognition (NOR) test, Y-maze test, and Morris water maze (MWM) test were performed to assess cognitive function. RESULTS: Treatment with 20 or 80 mg/kg 3-MA reduced the increase in hippocampal TNF-α, IL-6, and IL-1ß expression in SAE model mice, with 20 mg/kg 3-MA having the greatest therapeutic effect. Treatment with 20 mg/kg 3-MA effectively reduced the expression of hippocampal autophagy-related proteins and mortality, ameliorated hypothermia, decreased body weight and electroencephalography (EEG) performance, and attenuated the activation of neuroglia and neuronal damage. Moreover, it alleviated the cognitive dysfunction 2 weeks after LPS induction. CONCLUSIONS: 3-MA reduced neuroglial activation and neuronal damage, attenuated neuroinflammation, and improved cognitive deficits during recovery period by inhibiting autophagy in SAE.