I2-Induced Umpolung: Synthesis of a 1,6-Dihydrofuro[3,2-b]pyrazolo[3,4-e][1,4]thiazine Skeleton via an Unconventional 1,4-Dithiane-2,5-diol Reaction Mode.

In this paper, novel sulfur-containing 1,6-dihydrofuro[3,2-b]pyrazolo[3,4-e][1,4]thiazine skeletons were constructed from the simple and readily available materials enaminone, 5-aminopyrazole, and 1,4-dithiane-2,5-diol. Furthermore, a novel 1,4-dithiane-2,5-diol reaction mode has been developed through a double-dipole-reversal process induced by iodine that results in the formation of six new bonds and two new rings in a one-pot reaction. This method shows good substrate compatibility, and the products can be further modified with a variety of pharmaceuticals. Additionally, this novel skeleton exhibits good fluorescence properties in solution, enabling bright and stable green fluorescence imaging in HeLa cells.

Hydrogen attenuates ischaemia-reperfusion injury in skeletal muscles post-limb replantation by activating the NRF2/HO-1 signalling pathway to reduce BAX expression.

Background: Ischaemia-reperfusion injury (IRI) is a critical complication post-limb replantation. The oxidative stress and cellular apoptosis due to IRI considerably hinder the healing process. This study aimed to investigate the modulatory effects of pre-perfusion with hydrogen-rich heparin sodium on the nuclear factor erythroid 2-related factor 2 (NRF2)/haeme oxygenase-1 (HO-1) pathway and its potential mechanisms in mitigating skeletal muscle IRI post-limb replantation. Methods: Forty healthy Sprague-Dawley rats (250-300 g) were classified into five groups (n = 8 each): normal control, IRI + heparin sodium pre-perfusion (heparin group), IRI + hydrogen-rich heparin sodium pre-perfusion (hydrogen-rich heparin group), IRI + hydrogen-rich heparin sodium pre-perfusion + NRF2 inhibitor (hydrogen-rich heparin + all-trans retinoic acid [ATRA] group), and IRI + heparin sodium pre-perfusion + NRF2 inhibitor (heparin + ATRA group). The activation of the NRF2/HO-1 pathway in skeletal muscle IRI was evaluated based on HO-1 expression using western blotting and immunofluorescence. Furthermore, haematoxylin and eosin staining and transmission electron microscopy were employed to determine the histopathological characteristics. Additionally, superoxide dismutase and malondialdehyde levels in skeletal muscle tissue were measured to assess antioxidant capacity and the degree of oxidative stress damage. Tissue hypoxia was assessed based on hypoxia-inducible factor 1-alpha expression, whereas apoptosis markers BCL-2-associated X protein (BAX) and Caspase-3 in skeletal muscle tissues were analysed using western blotting with terminal deoxynucleotidyl transferase dUTP nick end labelling staining to quantify cell apoptosis. Results: Compared with the control group, the heparin group exhibited significant pathological changes, including inflammatory infiltration and cellular hypertrophy, with increased apoptosis and oxidative stress. Notably, NRF2 suppression aggravated these effects. However, hydrogen-rich heparin sodium prominently activated the NRF2/HO-1 pathway, enhancing antioxidant defence and reducing BAX/Caspase-3-mediated apoptosis, thereby mitigating IRI-induced damage. The use of an NRF2 inhibitor to inhibit NRF2 excitation by hydrogen-rich heparin sodium notably weakened NRF2 activation and the antioxidant response, resulting in a substantial increase in cellular apoptosis. Conclusion: Pre-perfusion with hydrogen-rich heparin sodium markedly diminishes the BAX/Caspase-3-mediated apoptotic pathway in skeletal muscle tissues with IRI through the excitation of the NRF2/HO-1 pathway.

Prognostic Value of Plasma Immunoglobulin G N-Glycome Traits in Pulmonary Arterial Hypertension.

BACKGROUND: B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide is the only blood biomarker in established risk calculators for pulmonary arterial hypertension (PAH). Profiling systemic-originated plasma immunoglobulin G (IgG) N-glycans, which reflect different components of the pathophysiology of PAH including immune dysregulation and inflammation, may improve PAH risk assessment. OBJECTIVES: This study sought to identify plasma IgG N-glycan biomarkers that predict survival in PAH to improve risk assessment. METHODS: This cohort study examined 622 PAH patients from 2 national centers (Beijing [discovery] cohort: n = 273; Shanghai [validation] cohort: n = 349). Plasma IgG N-glycomes were profiled by a robust mass spectrometry-based method. Prognostic IgG N-glycan traits were identified and validated in the 2 cohorts using Cox regression and Kaplan-Meier survival analyses. The added value of IgG N-glycan traits to previously established risk models was assessed using Harrell C-indexes and survival analysis. RESULTS: Plasma IgG fucosylation was found to predict survival independent of age and sex in the discovery cohort (HR: 0.377; 95% CI: 0.168-0.845; P = 0.018) with confirmation in the validation cohort (HR: 0.445; 95% CI: 0.264-0.751; P = 0.005). IgG fucosylation remained a robust predictor of mortality in combined cohorts after full adjustment and in subgroup analyses. Integrating IgG fucosylation into previously established risk models improved their predictive capacity, marked by an overall elevation in Harrell C-indexes. IgG fucosylation was useful in further stratifying the intermediate-risk patients classified by a previously established model. CONCLUSIONS: Plasma IgG fucosylation informs PAH prognosis independent of established factors, offering additional value for predicting PAH outcomes.

A bifunctional lactoferrin-derived amyloid coating prevents bacterial adhesion and occludes dentinal tubules via deep remineralization.

Dentin hypersensitivity (DH) manifests as sharp and uncomfortable pain due to the exposure of dentinal tubules (DTs) following the erosion of tooth enamel. Desensitizing agents commonly used in clinical practice have limitations such as limited depth of penetration, slow remineralization and no antimicrobial properties. To alleviate these challenges, our study designed a lactoferrin-derived amyloid nanofilm (PTLF nanofilm) inspired by the saliva-acquired membrane (SAP). The nanofilm utilises Tris(2-carboxyethyl)phosphine (TCEP) to disrupt the disulfide bonds of lactoferrin (LF) under physiological conditions. The PTLF nanofilm modifies surfaces across various substrates and effectively prevents the early and stable adhesion of cariogenic bacteria, such as Streptococcus mutans and Lactobacillus acidophilus. Simultaneously, it adheres rapidly and securely to demineralized dentin surfaces, facilitating in-situ remineralization of HAP through a simple immersion process. This leads to the formation of a remineralized layer resembling natural dentin, with an occlusion depth of dentinal tubules exceeding 80 µm after three days. The in vivo and vitro results confirm that the PTLF nanofilm possesses good biocompatibility and its ability to exert simultaneous antimicrobial effects and dentin remineralization. Accordingly, this innovative bifunctional PTLF amyloid coating offers promising prospects for the management of DH-related conditions. STATEMENT OF SIGNIFICANCE.

Causal associations of hypothyroidism with frozen shoulder: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Many studies have investigated the association between hypothyroidism and frozen shoulder, but their findings have been inconsistent. Furthermore, earlier research has been primarily observational, which may introduce bias and does not establish a cause-and-effect relationship. To ascertain the causal association, we performed a two-sample bidirectional Mendelian randomization (MR) analysis. METHODS: We obtained data on "Hypothyroidism" and "Frozen Shoulder" from Summary-level Genome-Wide Association Studies (GWAS) datasets that have been published. The information came from European population samples. The primary analysis utilized the inverse-variance weighted (IVW) method. Additionally, a sensitivity analysis was conducted to assess the robustness of the results. RESULTS: We ultimately chose 39 SNPs as IVs for the final analysis. The results of the two MR methods we utilized in the investigation indicated that a possible causal relationship between hypothyroidism and frozen shoulder. The most significant analytical outcome demonstrated an odds ratio (OR) of 1.0577 (95% Confidence Interval (CI):1.0057-1.1123), P = 0.029, using the IVW approach. Furthermore, using the MR Egger method as a supplementary analytical outcome showed an OR of 1.1608 (95% CI:1.0318-1.3060), P = 0.017. Furthermore, the results of our sensitivity analysis indicate that there is no heterogeneity or pleiotropy in our MR analysis. In the reverse Mendelian analysis, no causal relationship was found between frozen shoulders and hypothyroidism. CONCLUSION: Our MR analysis suggests that there may be a causal relationship between hypothyroidism and frozen shoulder.

[Study of the mucosal morphological difference of distal-extension of mandibular dentition defect impressions taken by intra-oral digital scanning and selective pressure impression technique].

PURPOSE: To compare the mucosal morphological difference in distal-extension area of mandibular dentition defect taken by intra-oral digital scanning and selective pressure impression techniques. METHODS: Seventeen patients with Kennedy Class I and Class II dentition defect in lower jaw were included, including twenty-two distal-extensions. Intraoral digital scanning and functional impression technique were taken in each patients, respectively. Laboratory cast scanner was used to scan the plaster casts made from the selective pressure impression to obtain the three-dimensional data. All the data were stored in STL format. The 3D data collecting from intra-oral digital scanning and selective pressure impression from the same patient were compared by Geomagic Control 2014 software. Root mean square of 2.5mm diameter area was calculated in 5,10,15 mm from terminal tooth. Pearson's correlation test was used to analyze the correlation of the distance and morphological difference with SPSS 20.0 software package. RESULTS: Mean mucosal morphological difference of jaw distal-extension edentulous area taken by intra-oral digital scanning and selective pressure impression techniques was (0.37±0.12) mm. There was positive correlation between distance from terminal tooth and mucosal morphological difference(P＜0.05). Morphological differences in 5, 10, 15 mm from terminal tooth were (0.14±0.11) mm, (0.22±0.13) mm and (0.39±0.16) mm, respectively. CONCLUSIONS: In this study, there was positive correlation between the length of distal-extension edentulous area and mucosal morphological difference, while the kind of ridge defect and mucosal thickness may also affect the morphological difference quantity.

Error-Tolerant Amplification and Simulation of the Ultrastrong-Coupling Quantum Rabi Model.

Cat-state qubits formed by photonic cat states have a biased noise channel, i.e., one type of error dominates over all the others. We demonstrate that such biased-noise qubits are also promising for error-tolerant simulations of the quantum Rabi model (and its varieties) by coupling a cat-state qubit to an optical cavity. Using the cat-state qubit can effectively enhance the counterrotating coupling, allowing us to explore several fascinating quantum phenomena relying on the counterrotating interaction. Moreover, another benefit from biased-noise cat qubits is that the two main error channels (frequency and amplitude mismatches) are both exponentially suppressed. Therefore, the simulation protocols are robust against parameter errors of the parametric drive that determines the projection subspace. We analyze three examples: (i) collapse and revivals of quantum states; (ii) hidden symmetry and tunneling dynamics; and (iii) pair-cat-code computation.

[Rapid determination of nine preservatives in tobacco flavor by three phase-hollow fiber-liquid phase microextraction-high performance liquid chromatography].

Tobacco flavors are extensively utilized in traditional tobacco products, electronic nicotine, heated tobacco products, and snuff. To inhibit fungal growth arising from high moisture content, preservatives such as benzoic acid (BA), sorbic acid (SA), and parabens are often incorporated into tobacco flavors. Nonetheless, consuming preservatives beyond safety thresholds may pose health risks. Therefore, analytical determination of these preservatives is crucial for both quality assurance and consumer protection. For example, BA and SA can induce adverse reactions in susceptible individuals, including asthma, urticaria, metabolic acidosis, and convulsions. Parabens, because of their endocrine activity, are classified as endocrine-disrupting chemicals. Despite extensive research, the concurrent quantification of trace-level hydrophilic (BA and SA) and hydrophobic (methylparaben, ethylparaben, isopropylparaben, propylparaben, butylparaben, isobutylparaben, and benzylparaben) preservatives in tobacco flavors remains challenging. Traditional liquid phase extraction coupled with high performance liquid chromatography (HPLC) often results in high false positive rates and inadequate sensitivity. In contrast, tandem mass spectrometry offers high sensitivity and specificity; however, its widespread application is limited by laborious sample preparation and significant operational costs. Therefore, it is crucial to establish a fast and sensitive sample pretreatment and analysis method for the nine preservatives in tobacco flavors. In this study, a method for the simultaneous determination of the nine preservatives (SA, BA and seven parabens) in tobacco flavor was established based on three phase-hollow fiber-liquid phase microextraction (3P-HF-LPME) technology combined with HPLC. To obtain the optimal pretreatment conditions, extraction solvent type, sample phase pH, acceptor phase pH, sample phase volume, extraction time, and mass fraction of sodium chloride, were examined. Additionally, the HPLC parameters, including UV detection wavelength and mobile phase composition, were refined. The optimal extraction conditions were as follows: dihexyl ether was used as extraction solvent, 15 mL sample solution (pH 4) was used as sample phase, sodium hydroxide aqueous solution (pH 12) was used as acceptor phase, and the extraction was carried out at 800 r/min for 30 min. Chromatographic separation was accomplished using an Agilent Poroshell 120 EC-C18 column (100 mm×3 mm, 2.7 µm) and a mobile phase comprising methanol, 0.02 mol/L ammonium acetate aqueous solution (containing 0.5% acetic acid), and acetonitrile for gradient elution. Under the optimized conditions, the nine target analytes showed good linear relationships in their respective linear ranges, the correlation coefficients (r) were ≥0.9967, limits of detection (LODs) and quantification (LOQs) were 0.02-0.07 mg/kg and 0.08-0.24 mg/kg, respectively. Under two spiked levels, the enrichment factors (EFs) and extraction recoveries (ERs) of the nine target analytes were 30.6-91.1 and 6.1%-18.2%, respectively. The recoveries of the nine target analytes ranged from 82.2% to 115.7% and the relative standard deviations (RSDs) (n=5) were less than 14.5% at low, medium and high levels. The developed method is straightforward, precise, sensitive, and well-suited for the rapid screening of preservatives in tobacco flavor samples.

Habitat Imaging With Tumoral and Peritumoral Radiomics for Prediction of Lung Adenocarcinoma Invasiveness on Preoperative Chest CT: A Multicenter Study.

Background: Tumors' growth processes result in spatial heterogeneity, with the development of tumor subregions (i.e., habitats) having unique biologic characteristics. Objective: To develop and validate a habitat model combining tumor and peritumoral radiomics features on chest CT for predicting invasiveness of lung adenocarcinoma. Methods: This retrospective study included 1156 patients (mean age, 57.5 years; 464 male, 692 female) from three centers and a public dataset, who underwent chest CT before lung adenocarcinoma resection (variable date ranges across datasets). Patients from one center formed training (n=500) and validation (n=215) sets; patients from the other sources formed three external test sets (n=249, 113, 79). For each patient, a single nodule was manually segmented on chest CT. The nodule segmentation was combined with an automatically generated 4-mm peritumoral region into a whole-volume volume-of-interest (VOI). A Gaussian mixture model (GMM) identified voxel clusters with similar first-order energy across patients. GMM results were used to divide each patient's whole-volume VOI into multiple habitats, defined consistently across patients. Radiomic features were extracted from each habitat. After feature selection, a habitat model was developed for predicting invasiveness, using pathologic assessment as a reference. An integrated model was constructed, combining features extracted from habitats and whole-volume VOIs. Model performance was evaluated, including in subgroups based on nodule density (pure ground-glass, part-solid, solid). Results: Invasive cancer was diagnosed in 625/1156 patients. GMM identified four as the optimal number of voxel clusters and thus of per-patient tumor habitats. The habitat model had AUC of 0.932 in the validation set, and 0.881, 0.880, and 0.764 in the three external test sets. The integrated model had AUC of 0.947 in the validation set and 0.936, 0.908, and 0.800 in the three external test sets. In the three external test sets combined, across nodule densities, AUCs for the habitat model were 0.836-0.969 and for the integrated model were 0.846-0.917. Conclusions: Habitat imaging combining tumoral and peritumoral radiomic features could help predict lung adenocarcinoma invasiveness. Prediction is improved when combining information on tumor subregions and the tumor overall. Clinical Impact: The findings may aid personalized preoperative assessments to guide clinical decision-making in lung adenocarcinoma.

Association between dichotomized VASARI feature and overall survival in glioblastoma patients: a single-institution propensity score matching analysis.

OBJECTIVES: This study aimed to investigate the intra- and inter-observer consistency of the Visually Accessible Rembrandt Images (VASARI) feature set before and after dichotomization, and the association between dichotomous VASARI features and the overall survival (OS) in glioblastoma (GBM) patients. METHODS: This retrospective study included 351 patients with pathologically confirmed IDH1 wild-type GBM between January 2016 and June 2022. Firstly, VASARI features were assessed by four radiologists with varying levels of experience before and after dichotomization. Cohen's kappa coefficient (κ) was calculated to measure the intra- and inter-observer consistency. Then, after adjustment for confounders using propensity score matching, Kaplan-Meier curves were used to compare OS differences for each dichotomous VASARI feature. Next, patients were randomly stratified into a training set (n = 211) and a test set (n = 140) in a 3:2 ratio. Based on the training set, Cox proportional hazards regression analysis was adopted to develop combined and clinical models to predict OS, and the performance of the models was evaluated with the test set. RESULTS: Eleven VASARI features with κ value of 0.61-0.8 demonstrated almost perfect agreement after dichotomization, with the range of κ values across all readers being 0.874-1.000. Seven VASARI features were correlated with GBM patient OS. For OS prediction, the combined model outperformed the clinical model in both training set (C-index, 0.762 vs. 0.723) and test set (C-index, 0.812 vs. 0.702). CONCLUSION: The dichotomous VASARI features exhibited excellent inter- and intra-observer consistency. The combined model outperformed the clinical model for OS prediction.

The anti-inflammatory and immunomodulatory effects of olfactory ensheathing cells transplantation in spinal cord injury and concomitant pathological pain.

Spinal cord injury (SCI) is a serious and disabling injury that is often accompanied by neuropathic pain (NeP), which severely affects patients' motor and sensory functions and reduces their quality of life. Currently, there is no specific treatment for treating SCI and relieving the accompanying pain, and we can only rely on medication and physical rehabilitation, both of which are ineffective. Researchers have recently identified a novel class of glial cells, olfactory ensheathing cells (OECs), which originate from the olfactory system. Transplantation of OECs into damaged spinal cords has demonstrated their capacity to repair damaged nerves, improve the microenvironment at the point of injury, and They can also restore neural connectivity and alleviate the patient's NeP to a certain extent. Although the effectiveness of OECs transplantation has been confirmed in experiments, the specific mechanisms by which it repairs the spinal cord and relieves pain have not been articulated. Through a review of the literature, it has been established that the ability of OECs to repair and relieve pain is inextricably linked to its anti-inflammatory and immunomodulatory effects. In this regard, it is imperative to gain a deeper understanding of how OECs exert their anti-inflammatory and immunomodulatory effects. The objective of this paper is to provide a comprehensive overview of the mechanisms by which OECs exert anti-inflammatory and immunomodulatory effects. We aim to manipulate the immune microenvironment at the transplantation site through the intervention of cytokines and immune cells, with the goal of enhancing OECs' function or creating a conducive microenvironment for OECs' survival. This approach is expected to improve the therapeutic efficacy of OECs in clinical settings. However, numerous fundamental and clinical challenges remain to be addressed if OEC transplantation therapy is to become a standardized treatment in clinical practice.

Divergent synthesis of pyrrolidone fused pyrimido[1,2-b]indazole through selective trapping of an enone intermediate by 1H-indazol-3-amine.

An oxidant-controlled divergent synthesis of a pyrrolidone fused pyrimido[1,2-b]indazole skeleton was developed through selective cyclization of an in situ generated enone intermediate and 1H-indazol-3-amine. The one-pot, metal-free process formed three C-N bonds, one C-C bond, and a tetrasubstituted carbon stereocenter containing a hydroxyl group. This method not only allowed for the synthesis of over 60 new pyrrolidone fused pyrimido[1,2-b]indazole derivatives, but was also compatible with the transformation of complex active molecules and the derivation of target products. Significantly, product 4q exhibited aggregation-induced emission (AIE) characteristics without any further modification.

Boosting bioelectricity generation in bioelectrochemical systems with nitrogen-doped three-dimensional graphene aerogel anode.

Bioelectricity generation by electrochemically active bacteria has become particularly appealing due to its vast potential in energy production, pollution treatment, and biosynthesis. However, developing high-performance anodes for bioelectricity generation remains a significant challenge. In this study, a highly efficient three-dimensional nitrogen-doped macroporous graphene aerogel anode with a nitrogen content of approximately 4.38 ± 0.50 at% was fabricated using hydrothermal method. The anode was successfully implemented in bioelectrochemical systems inoculated with Shewanella oneidensis MR-1, resulting in a significantly higher anodic current density (1.0 A/m2) compared to the control one. This enhancement was attributed to the greater biocapacity and improved extracellular electron transfer efficiency of the anode. Additionally, the N-doped aerogel anode demonstrated excellent performance in mixed-culture inoculated bioelectrochemical systems, achieving a high power density of 4.2 ± 0.2 W/m², one of the highest reported for three-dimensional carbon-based bioelectrochemical systems to date. Such improvements are likely due to the good biocompatibility of the N-doped aerogel anode, increased extracellular electron transfer efficiency at the bacteria/anode interface, and selectively enrichment of electroactive Geobacter soli within the NGA anode. Furthermore, based on gene-level Picrust2 prediction results, N-doping significantly upregulated the conductive pili-related genes of Geobacter in the three-dimensional anode, increasing the physical connection channels of bacteria, and thus strengthening the extracellular electron transfer process in Geobacter.

Treatment algorithm for pulmonary arterial hypertension.

Pulmonary arterial hypertension leads to significant impairment in haemodynamics, right heart function, exercise capacity, quality of life and survival. Current therapies have mechanisms of action involving signalling via one of four pathways: endothelin-1, nitric oxide, prostacyclin and bone morphogenetic protein/activin signalling. Efficacy has generally been greater with therapeutic combinations and with parenteral therapy compared with monotherapy or nonparenteral therapies, and maximal medical therapy is now four-drug therapy. Lung transplantation remains an option for selected patients with an inadequate response to therapies.

Effect of electroacupuncture of "Zusanli" (ST36) combined with capeOX on apoptosis and ferroptosis in nude mice with colorectal cancer. / 电针"足三里"联合capeOXæ–¹æ¡ˆå¯¹ç»“ç›´è‚ ç™Œè£¸é¼ è‚¿ç˜¤ç»†èƒžå‡‹äº¡å’Œé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. METHODS: Female Balb/c nude mice were randomly assigned to 3 groups：model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. RESULTS: Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). CONCLUSIONS: EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.

Increased adrenal steroidogenesis and suppressed corticosteroid responsiveness in critical COVID-19.

BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on adrenal endocrine metabolism in critically ill patients remains unclear. This study aimed to investigate the alterations in adrenal steroidogenic activity, elucidate underlying mechanisms, provide in situ histopathological evidence, and examine the clinical implications. METHODS: The comparative analyses of the adrenal cortices from 24 patients with fatal COVID-19 and 20 matched controls were performed, excluding patients previously treated with glucocorticoids. SARS-CoV-2 and its receptors were identified and pathological alterations were examined. Furthermore, histological examinations, immunohistochemical staining and ultrastructural analyses were performed to assess corticosteroid biosynthesis. The zona glomerulosa (ZG) and zona fasciculata (ZF) were then dissected for proteomic analyses. The biological processes that affected steroidogenesis were analyzed by integrating histological, proteomic, and clinical data. Finally, the immunoreactivity and responsive genes of mineralocorticoid and glucocorticoid receptors in essential tissues were quantitatively measured to evaluate corticosteroid responsiveness. FINDINGS: The demographic characteristics of COVID-19 patients were comparable with those of controls. SARS-CoV-2-like particles were identified in the adrenocortical cells of three patients; however, these particles did not affect cellular morphology or steroid synthesis compared with SARS-CoV-2-negative specimens. Although the adrenals exhibited focal necrosis, vacuolization, microthrombi, and inflammation, widespread degeneration was not evident. Notably, corticosteroid biosynthesis was significantly enhanced in both the ZG and ZF of COVID-19 patients. The increase in the inflammatory response and cellular differentiation in the adrenal cortices of patients with critical COVID-19 was positively correlated with heightened steroidogenic activity. Additionally, the appearance of more dual-ZG/ZF identity cells in COVID-19 adrenals was in accordance with the increased steroidogenic function. However, activated mineralocorticoid and glucocorticoid receptors and their responsive genes in vital tissues were markedly reduced in patients with critical COVID-19. INTERPRETATION: Critical COVID-19 was characterized by potentiated adrenal steroidogenesis, associated with increased inflammation, enhanced differentiation and elevated dual-ZG/ZF identity cells, alongside suppressed corticosteroid responsiveness. These alterations implied the reduced effectiveness of conventional corticosteroid therapy and underscored the need for evaluation of the adrenal axis and corticosteroid sensitivity.

Application value of indocyanine green fluorescence imaging in guiding sentinel lymph node biopsy diagnosis of gastric cancer: Meta-analysis.

BACKGROUND: Gastric cancer is a common malignant tumor of the digestive system worldwide, and its early diagnosis is crucial to improve the survival rate of patients. Indocyanine green fluorescence imaging (ICG-FI), as a new imaging technology, has shown potential application prospects in oncology surgery. The meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical practice. AIM: To assess the diagnostic efficacy of optical imaging in conjunction with indocyanine green (ICG)-guided sentinel lymph node (SLN) biopsy for gastric cancer. METHODS: Electronic databases such as PubMed, Embase, Medline, Web of Science, and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN biopsy. Stata 12.0 software was used for analysis by combining the "bivariable mixed effect model" with the "midas" command. The true positive value, false positive value, false negative value, true negative value, and other information from the included literature were extracted. A literature quality assessment map was drawn to describe the overall quality of the included literature. A forest plot was used for heterogeneity analysis, and P < 0.01 was considered to indicate statistical significance. A funnel plot was used to assess publication bias, and P < 0.1 was considered to indicate statistical significance. The summary receiver operating characteristic (SROC) curve was used to calculate the area under the curve (AUC) to determine the diagnostic accuracy. If there was interstudy heterogeneity (I 2 > 50%), meta-regression analysis and subgroup analysis were performed. RESULTS: Optical imaging involves two methods: Near-infrared (NIR) imaging and fluorescence imaging. A combination of optical imaging and ICG-guided SLN biopsy was useful for diagnosis. The positive likelihood ratio was 30.39 (95%CI: 0.92-1.00), the sensitivity was 0.95 (95%CI: 0.82-0.99), and the specificity was 1.00 (95%CI: 0.92-1.00). The negative likelihood ratio was 0.05 (95%CI: 0.01-0.20), the diagnostic odds ratio was 225.54 (95%CI: 88.81-572.77), and the SROC AUC was 1.00 (95%CI: The crucial values were sensitivity = 0.95 (95%CI: 0.82-0.99) and specificity = 1.00 (95%CI: 0.92-1.00). The Deeks method revealed that the "diagnostic odds ratio" funnel plot of SLN biopsy for gastric cancer was significantly asymmetrical (P = 0.01), suggesting significant publication bias. Further meta-subgroup analysis revealed that, compared with fluorescence imaging, NIR imaging had greater sensitivity (0.98 vs 0.73). Compared with optical imaging immediately after ICG injection, optical imaging after 20 minutes obtained greater sensitivity (0.98 vs 0.70). Compared with that of patients with an average SLN detection number < 4, the sensitivity of patients with a SLN detection number ≥ 4 was greater (0.96 vs 0.68). Compared with hematoxylin-eosin (HE) staining, immunohistochemical (+ HE) staining showed greater sensitivity (0.99 vs 0.84). Compared with subserous injection of ICG, submucosal injection achieved greater sensitivity (0.98 vs 0.40). Compared with 5 g/L ICG, 0.5 and 0.05 g/L ICG had greater sensitivity (0.98 vs 0.83), and cT1 stage had greater sensitivity (0.96 vs 0.72) than cT2 to cT3 clinical stage. Compared with that of patients ≤ 26, the sensitivity of patients > 26 was greater (0.96 vs 0.65). Compared with the literature published before 2010, the sensitivity of the literature published after 2010 was greater (0.97 vs 0.81), and the differences were statistically significant (all P < 0.05). CONCLUSION: For the diagnosis of stomach cancer, optical imaging in conjunction with ICG-guided SLN biopsy is a therapeutically viable approach, especially for early gastric cancer. The concentration of ICG used in the SLN biopsy of gastric cancer may be too high. Moreover, NIR imaging is better than fluorescence imaging and may obtain higher sensitivity.

Clinical Analysis and Imaging Study of Lateral Lumbar Intervertebral Fusion in the Treatment of Degenerative Lumbar Scoliosis.

OBJECTIVE: As the population ages and technology advances, lateral lumbar intervertebral fusion (LLIF) is gaining popularity for the treatment of degenerative lumbar scoliosis (DLS). This study investigated the feasibility, minimally invasive concept, and benefits of LLIF for the treatment of DLS by observing and assessing the clinical efficacy, imaging changes, and complications following the procedure. METHODS: A retrospective analysis was performed for 52 DLS patients (12 men and 40 women, aged 65.84 ± 9.873 years) who underwent LLIF from January 2019 to January 2023. The operation time, blood loss, complications, clinical efficacy indicators (visual analogue scale [VAS], Oswestry disability index [ODI], and 36-Item Short Form Survey), and imaging indicators (coronal position: Cobb angle and center sacral vertical line-C7 plumbline [CSVL-C7PL]; and sagittal position: sagittal vertical axis [SVA], lumbar lordosis [LL], pelvic incidence angle [PI], and thoracic kyphosis angle [TK] were measured). All patients were followed up. The above clinical evaluation indexes and imaging outcomes of patients postoperatively and at last follow-up were compared to their preoperative results. RESULTS: Compared to the preoperative values, the Cobb angle and LL angle were significantly improved after surgery (p < 0.001). Meanwhile, CSVL-C7PL, SVA, and TK did not change much after surgery (p > 0.05) but improved significantly at follow-up (p < 0.001). There was no significant change in PI at either the postoperative or follow-up timepoint. The operation took 283.90 ± 81.62 min and resulted in a total blood loss of 257.27 ± 213.44 mL. No significant complications occurred. Patients were followed up for to 21.7 ± 9.8 months. VAS, ODI, and SF-36 scores improved considerably at postoperative and final follow-up compared to preoperative levels (p < 0.001). After surgery, the Cobb angle and LL angle had improved significantly compared to preoperative values (p < 0.001). CSVL-C7PL, SVA, and TK were stable after surgery (p > 0.05) but considerably improved during follow-up (p < 0.001). PI showed no significant change at either the postoperative or follow-up timepoints. CONCLUSION: Lateral lumbar intervertebral fusion treatment of DLS significantly improved sagittal and coronal balance of the lumbar spine, as well as compensatory thoracic scoliosis, with good clinical and radiological findings. Furthermore, there was less blood, less trauma, and quicker recovery from surgery.

Sex difference in alcohol consumption associated with colorectal cancer risk in Quzhou, China: A nested case-control study.

Objective: Colorectal cancer (CRC) incidence has been increasing worldwide over time. This study investigated whether drinking was associated with CRC risk. Methods: We designed a case-control study nested in a mass CRC screening program in Quzhou, China. Cases were newly diagnosed CRC in 2020-2022. Controls were randomly sampled using frequency match. Drinking variables included drinking status, frequency, duration, and others. Logistic regressions were used to estimate odds ratio (OR) and 95 % confidence interval (CI). Results: The crude OR (cOR) (95 % CI) of drinking between 153 cases and 650 controls was 1.46 (0.99, 2.16) in current drinkers, 3.31 (1.44, 7.60) in former drinkers, 1.82 (1.21, 2.74) in drinking 6-7 days/week, and 3.48 (1.29, 9.37) in drinking 1-19 years. Stratifying by sex, all drinking variables in women but not all in men were consistently associated with CRC risk. The adjusted OR (aOR) (95 % CI) was 1.01 (0.59, 1.74) in current drinking men, 2.27 (0.78, 6.64) in former drinking men, and 4.24 (1.61, 11.13) in current drinking women. The aOR (95 % CI) of drinking whisky was 0.19 (0.04, 0.83), 1.89 (0.86, 4.17), 2.25 (1.05, 4.83), and 1.82 (0.85, 3.92) in men drinking ≤0.5, >0.5-≤1.0, >1.0-≤1.5, and >1.5 Liter/week (P trend = 0.011), and 3.80 (1.03, 14.00) and 9.92 (2.01, 49.00) in women drinking ≤0.5 and >0.5 Liter/week (P trend = 0.001), respectively. Conclusions: There was sex difference in drinking associated with increased risk of CRC which association was stronger in women than that in men. Men's association between drinking whisky and CRC risk was J-shaped.