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Inflammation involving adipose macrophages is an important inducer of obesity. Regulating macrophages polarization and improving the inflammatory microenvironment of adipose tissue is a new strategy for the treatment of obesity. An amphiphilic chondroitin sulfate phenylborate derivative (CS-PBE) was obtained by modifying the main chain of chondroitin sulfate with the hydrophobic small molecule phenylborate. Using CS-PBE self-assembly, macrophage targeting, reactive oxygen species (ROS) release and celastrol (CLT) encapsulation were achieved. The cytotoxicity, cellular uptake, internalization pathways and transmembrane transport efficiency of CS-PBE micelles were studied in Caco-2 and RAW264.7 cells. Hemolysis and organotoxicity tests were performed to assess the safety of the platform, while its therapeutic efficacy was investigated in high-fat diet-induced obese mice. Multifunctional micelles with macrophage targeting and ROS clearance capabilities were developed to improve the efficacy of CLT in treating obesity.In vitrostudies indicated that CS-PBE micelles had better ability to target M1 macrophages, better protective effects on mitochondrial function, better ability to reduce the number of LPS-stimulated M1 macrophages, better ability to reduce the number of M2 macrophages, and better ability to scavenge ROS in inflammatory macrophages.In vivostudies have shown that CS-PBE micelles improve inflammation and significantly reduce toxicity of CLT in the treatment of obesity. In summary, CS-PBE micelles could significantly improve the ability to target inflammatory macrophages and scavenge ROS in adipose tissue to alleviate inflammation, suggesting that CS-PBE micelles are a highly promising approach for the treatment of obesity.

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Colorectal cancer (CRC) is a major threat to human health, as it is one of the most common malignancies with a high incidence and mortality rate. The cancer cell membrane (CCM) has significant potential in targeted tumor drug delivery due to its membrane antigen-mediated homologous targeting ability. The endoplasmic reticulum (ER) in cancer cells plays a crucial role in apoptosis and ferroptosis. In this study, we developed an ER-targeted peptide-modified CCM-biomimetic nanoparticle-delivered lovastatin (LOV) nanomedicine delivery system (EMPP-LOV) for cancer treatment. Both in vitro and in vivo experiments demonstrated that EMPP could effectively target cancer cells and localize within the ER. EMPP-LOV modulated ER function to promote apoptosis and ferroptosis in tumor cells. Furthermore, synergistic antitumor efficacy was observed in both in vitro and in vivo models. EMPP-LOV induced apoptosis in CRC cells by over-activating endoplasmic reticulum stress and promoted ferroptosis by inhibiting the mevalonate pathway, leading to synergistic tumor growth inhibition with minimal toxicity to major organs. Overall, the EMPP-LOV delivery system, with its subcellular targeting capability within tumor cells, presents a promising therapeutic platform for CRC treatment.

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Herbal extracts are rich sources of active compounds that can be used for drug screening due to their diverse and unique chemical structures. However, traditional methods for screening these compounds are notably laborious and time-consuming. In this manuscript, we introduce a new high-throughput approach that combines nuclear magnetic resonance (NMR) spectroscopy with a tailored database and algorithm to rapidly identify bioactive components in herbal extracts. This method distinguishes characteristic signals and structural motifs of active constituents in the raw extracts through a relaxation-weighted technique, particularly utilizing the perfect echo Carr-Purcell-Meiboom-Gill (peCPMG) sequence, complemented by precise 2D spectroscopic strategies. The cornerstone of our approach is a customized database designed to filter potential compounds based on defined parameters, such as the presence of CHn segments and unique chemical shifts, thereby expediting the identification of promising compounds. This innovative technique was applied to identifying substances interacting with choline kinase α (ChoKα1), resulting in the discovery of four new inhibitors. Our findings demonstrate a powerful tool for unraveling the complex chemical landscape of herbal extracts, considerably facilitating the search for new pharmaceutical candidates. This approach offers an efficient alternative to traditional methods in the quest for drug discovery from natural sources.

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Polyamide 66 (PA66) has garnered significant attention due to its exceptional properties; unfortunately, its flammability is challenging. Adding flame retardants (FRs) is a primary approach to enhance PA66 flame retardancy. This study developed a highly flame-retardant PA66 composite film by adding corn-like functional nanohybrids (CNC/Al2O3). Interestingly, CNC/Al2O3 nanohybrids not only formed hydrogen bond interactions with PA66 but also improved crystallization properties as heterogeneous nucleating agents, resulting in the excellent mechanical properties of PA66 composite film. Remarkably, the incorporation of 3 wt% CNC/Al2O3 nanohybrids into PA66 matrix contributed to increasing the LOI to 28.5 %. The pHRR, THR, and TSR were reduced obviously by 55.7 %, 15.3 %, and 65.2 %, respectively. The excellent flame retardancy of PA66 composite film was attributed to the forming of a compact carbon layer catalyzed by the CNC/Al2O3 nanohybrids. Besides, the homogeneous distribution of CNC/Al2O3 nanohybrids endowed the composite film with excellent heat insulation, and the heat insulation rate was up to 31.9 %. Thus, such PA66 composite films with excellent flame retardancy, heat insulation, and mechanical properties could meet the broader application requirements.

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RATIONALE AND OBJECTIVES: To build radiomics nomograms based on multi-sequence MRI to facilitate the identification of cognitive impairment (CI) and prediction of cognitive progression (CP) in patients with relapsing-remitting multiple sclerosis (RRMS). MATERIALS AND METHODS: We retrospectively included two RRMS cohorts with multi-sequence MRI and Symbol Digit Modalities Test (SDMT) data: dataset1 (n = 149, for training and validation) and dataset2 (n = 29, for external validation). 80 patients of dataset1 had a 2-year follow-up SDMT. CI and CP were evaluated using SDMT scores at baseline and follow-up. The included DIR sequence aided in identifying cortical lesions. Lesion radiomics and structural features were extracted and selected from multi-sequence MRI, followed by the computation of radiomics and structural scores. The nomogram was developed through multivariate logistic regression, integrating clinical data, radiomics, and structural scores to identify CI in patients. Moreover, a similar method was employed to further construct a nomogram predicting CP in patients. RESULTS: The nomogram demonstrated superior performance in identifying patients with CI, with area under the curve (AUC) values of 0.937 (95% Conf. Interval: 0.898-0.975) and 0.876 (0.810-0.943) in internal and external validation sets, compared to models solely based on clinical data, lesion radiomics, and structural features. Furthermore, another nomogram constructed in predicting CP also exhibited outstanding performance, with an AUC value of 0.969 (0.875-1.000) in the validation set. CONCLUSION: These nomograms, integrating clinical data, multi-sequence lesions radiomics, and structural features, enable more effective identification of CI and early prediction of CP in RRMS patients, providing important support for clinical decision-making.

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BACKGROUND: The increasing prevalence of obesity-related glomerulopathy (ORG) poses a significant threat to public health. Sodium-glucose co-transporter-2 (SGLT2) inhibitors effectively reduce body weight and total fat mass in obese individuals and halt the progression of ORG. However, the underlying mechanisms of their reno-protective effects in ORG remain unclear. METHODS: We established a high-fat diet-induced ORG model using C57BL/6J mice, which were divided into three groups: normal chow diet (NCD group), high-fat diet (HFD) mice treated with placebo (ORG group), and HFD mice treated with Empagliflozin (EMPA group). We conducted 16S ribosomal RNA gene sequencing of feces and analyzed metabolites from kidney, feces, liver, and serum samples. RESULTS: ORG mice showed increased urinary albumin creatinine ratio, cholesterol, triglyceride levels, and glomerular diameter compared to NCD mice (all P < 0.05). EMPA treatment significantly alleviated these parameters (all P < 0.05). Multi-tissue metabolomics analysis revealed lipid metabolic reprogramming in ORG mice, which was significantly altered by EMPA treatment. MetOrigin analysis showed a close association between EMPA-related lipid metabolic pathways and gut microbiota alterations, characterized by reduced abundances of Firmicutes and Desulfovibrio and increased abundance of Akkermansia (all P < 0.05). CONCLUSION: The metabolic homeostasis of ORG mice, especially in lipid metabolism, was disrupted and closely associated with gut microbiota alterations, contributing to the progression of ORG. EMPA treatment improved kidney function and morphology by regulating lipid metabolism through the gut-kidney axis, highlighting a novel therapeutic approach for ORG.

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AIMS: Cerebral palsy (CP) is the most common physical disability in children, yet lacks an ideal animal model or effective treatment. This study aimed to develop a reliable CP model in neonatal rats and explore the effectiveness and underlying mechanisms of human neural stem cells (hNSCs) transplantation during the sequelae phase of CP. METHODS: Vasoconstrictor endothelin-1 (ET-1) was administered intracranially to the motor cortex and striatum of rats on postnatal day 5 to establish a CP model. hNSCs (5 × 105/5 µL) pretreated with hypoxia (5% O2 for 24 h) were transplanted near the infarct 3 weeks after ET-1 injury (the sequelae phase). The distribution and differentiation of hNSCs were observed after transplantation. Changes in neurotrophic factors, neurogenesis, angiogenesis, axonal plasticity, and motor function were analyzed. RESULTS: Neurobehavioral tests showed poor muscle strength and postural control in young ET-1 rats. Motor deficits of the left forelimb and gait abnormalities persisted into adulthood. Histopathological findings and MRI indicated the atrophy of the cortex, striatum, and adjacent corpus callosum in ET-1 rats. At 56 days after transplantation, hNSCs were widely distributed in the ipsilateral hemisphere, and differentiated into neurons, oligodendrocytes and astrocytes. Transplantation of hNSCs increased BDNF and VEGF expression, EdU+ cell number in the SVZ area, RECA-1+ vessel density and GAP-43 intensity around the lesion in ET-1 rats. The cylinder test revealed a significant increase in the left forelimb motor function from 28 days after transplantation, and the staircase and CatWalk tests showed improvements in fine motor function and gait parameters. CONCLUSIONS: Intracerebral injection of ET-1 modelled key functional and histopathological features of CP. hNSCs transplanted during the sequelae phase of CP resulted in long-term improvement in motor performance, possibly attributed to its capacity to stimulate neurotrophic factors, facilitate neurogenesis, angiogenesis, and promote axonal plasticity.

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BACKGROUND: During a robot-assisted minimally invasive surgery, hand tremors in a surgeon's manipulation of the master manipulator can cause vibrations of the slave surgical instruments. METHODS: This letter addresses this problem by proposing an improved Enhanced Band-Limited Multiple Linear Fourier Combiner (E-BMFLC) algorithm for filtering the physiological tremor signals of a surgeon's hand. The proposed method uses the amplitude of the input signal to adapt the learning rate and a dense division of the combiner bands for the higher amplitude bands of the tremor signals. RESULTS: By using the proposed improved E-BMFLC algorithm, the compensation accuracy can be improved by 4.5%-8.9%, as well as a spatial position error of less than 1 mm. CONCLUSION: The results show that among all filtering methods, the improved E-BMFLC filtering method has the highest number of successful experiments and the lowest experimental time.

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The critical importance of accurately predicting mutations in protein metal-binding sites for advancing drug discovery and enhancing disease diagnostic processes cannot be overstated. In response to this imperative, MetalTrans emerges as an accurate predictor for disease-associated mutations in protein metal-binding sites. The core innovation of MetalTrans lies in its seamless integration of multifeature splicing with the Transformer framework, a strategy that ensures exhaustive feature extraction. Central to MetalTrans's effectiveness is its deep feature combination strategy, which merges evolutionary-scale modeling amino acid embeddings with ProtTrans embeddings, thus shedding light on the biochemical properties of proteins. Employing the Transformer component, MetalTrans leverages the self-attention mechanism to delve into higher-level representations. Utilizing mutation site information for feature fusion not only enriches the feature set but also sidesteps the common pitfall of overestimation linked to protein sequence-based predictions. This nuanced approach to feature fusion is a key differentiator, enabling MetalTrans to outperform existing methods significantly, as evidenced by comparative analyses. Our evaluations across varied metal binding site data sets (specifically Zn, Ca, Mg, and Mix) underscore MetalTrans's superior performance, which achieved the average AUC values of 0.971, 0.965, 0.980, and 0.945 on multiple 5-fold cross-validation, respectively. Remarkably, against the multichannel convolutional neural network method on a benchmark independent test set, MetalTrans demonstrated unparalleled robustness and superiority, boasting the AUC score of 0.998 on multiple 5-fold cross-validation. Our comprehensive examination of the predicted outcomes further confirms the effectiveness of the model. The source codes, data sets, and prediction results for MetalTrans can be accessed for academic usage at https://github.com/EduardWang/MetalTrans.

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Utilization of large aggregates can promote energy conservation and emissions reductions, and large aggregates have been widely used in hydraulic concrete. The failure criterion for concrete material utilizing large aggregates forms the basis for constitutive models and structural design. However, the concrete failure criterion with respect to large aggregates has never been researched. To this end, the authors first conducted a series of triaxial compressive tests on concrete specimens with scaled aggregates. On this basis, several 3D mesoscopic numerical models were established with different aggregate gradations and used to simulate the triaxial compressive behaviors of hydraulic concrete after the models had been verified by experimental results. The results showed a pronounced aggregate-gradation effect on triaxial compressive behaviors, and concrete mixes with larger aggregates usually have higher compressive strength, especially under conditions of higher confinement. The normalized peak strength can increase by up to 23.49%. Finally, based on the available testing data, the strength criterion in different constitutive models is discussed and modified to allow more accurate simulation of the dynamic responses of and damage to fully graded concrete structures. This result can provide a theoretical basis on which construction entities can optimize the mix proportions of fully graded concrete and detect the failure modes of concrete structures.

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Malignant melanoma is the most lethal form of skin cancer. As a promising anti-cancer agent, plasma-activated water (PAW) rich in reactive oxygen and nitrogen species (RONS) has shown significant potential for melanoma treatment. However, rapid decay of RONS and inefficient delivery of PAW in conventional injection methods limit its practical applications. To address this issue, here we report a new approach for the production of plasma-activated cryo-microneedles (PA-CMNs) patches using custom-designed plasma devices and processes. Our innovation is to incorporate PAW into the PA-CMNs that are fabricated using a fast cryogenic micro-molding method. It is demonstrated that PA-CMNs can be easily inserted into skin to release RONS and slow the decay of RONS thereby prolonging their bioactivity and effectiveness. The new insights into the effective melanoma treatment suggest that the rich mixture of RONS within PA-CMNs prepared by custom-developed hybrid plasma-assisted configuration induces both ferroptosis and apoptosis to selectively kill tumor cells. A significant inhibition of subcutaneous A375 melanoma growth was observed in PA-CMNs-treated tumor-bearing nude mice without any signs of systemic toxicity. The new approach based on PA-CMNs may potentially open new avenues for a broader range of disease treatments.

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We presented the first, to our knowledge, demonstration of an ultraviolet (UV) laser at 223.8 nm by six-harmonic generation of an electro-optic Q-switched cavity dumping 1342 nm Nd:YVO4 laser. It offers high power, constant short pulse duration, and adjustable pulse repetition rate. The pulse duration is independent of the pump power and repetition rate compared to classical Q-switched oscillators. The output efficiency of the UV laser is optimized by adjusting the focusing lens. With the incident pump power of 30 W, an maximum average output power of 249 mW was obtained at 13 kHz. The pulse width maintained 3.4-3.5 ns from 5 to 20 kHz. The maximum pulse energy of 28.1 µJ was obtained at 5 kHz, and the corresponding peak power was up to 8.1 kW.

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Metabolic syndrome (MetS) is a global epidemic complex and will cause serious metabolic comorbidities without treatment. A prevention strategy for MetS development has been proposed to modulate gut microbiota by probiotic administration to improve intestinal dysbiosis and benefit the host. Lacticaseibacillus casei LC2W has exhibited positive effects in preventing colitis and anti-hypertension in vivo. However, the effect of L. casei LC2W on subjects at high risk of MetS is unknown. Here, a randomized, double-blinded, placebo-controlled study was conducted on 60 subjects with high risk of MetS, and the hypoglycemic and hypolipidemic activity and possible pathways of L. casei LC2W were inferred from the correlation analysis with gut microbiome composition, function, and clinical phenotypic indicators. The results showed that oral administration of L. casei LC2W could exert significant benefits on weight control, glucose and lipid metabolism, inflammatory and oxidative stress parameters, and SCFA production, as well as modulate the composition of gut microbiota. The relative abundance of Lacticaseibacillus, Bifidobacterium, Dorea, and Blautia was enriched, and their interaction with other gut microbes was strengthened by oral administration of L. casei LC2W, which was beneficial in ameliorating gut inflammation, promoting glucose and lipids degradation pathways, thus alleviated MetS. The present study confirmed the prevention effects of L. casei LC2W towards MetS from aspects of clinical outcomes and microflora modulation, providing an alternative strategy for people at high risk of MetS.Trial registration: The study was proactively registered in ClinicalTrial.gov with the registration number of ChiCTR2000031833 on April 09, 2020.

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Effective mosquito population suppression has been repeatedly demonstrated in field trials through the release of male mosquitoes to induce sterile mating with wild females using the incompatible insect technique (IIT), the sterile insect technique (SIT), or their combination. However, upscaling these techniques requires a highly efficient and scalable approach for the sex separation of mass-reared mosquitoes to minimize the unintentional release of females, which can lead to either population replacement or biting nuisance, a major bottleneck up to now. Here, we report the successful development of an automated mosquito pupa sex sorter that can effectively separate large numbers of males from females for population suppression of Aedes aegypti, A. albopictus, and Culex quinquefasciatus. The male production capacity of the automated sex sorter was increased by ~17-fold compared with manual sex separation with the Fay-Morlan sorter and enabled one person to separate 16 million males per week. With ~0.5% female contamination, the produced males exhibited high flight ability and mating performance. The field trial demonstrates that the quality of A. albopictus males produced using the automated sex sorter is suitable for inducing population suppression. These results indicate that the automated sex sorter offers the potential to upscale IIT and SIT against mosquito vectors for disease control.

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Background: Osteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive. Methods: To elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this coculture system. A normal mouse tibia fracture model and an osteomyelitis-related tibia fracture model were generated via injection of luciferase-labelled Staphylococcus aureus to verify the relationships between a novel osteoclast lineage and MSCs. Then, the infection was detected by a bioluminescence imaging system. Finally, immunofluorescence staining was used to detect the expression of markers of MSCs and novel osteoclast lineages in different remodelling phases in normal and infected bone remodelling models. Results: In this study, we constructed a cell atlas encompassing normal, infected, and reconstructed cortical bone. Then, we identified a novel subset at the earlier stage of the osteoclast lineage that exhibited increased expression of IDO1, CCL3, and CCL4. These IDO1highCCL3highCCL4high cells, termed osteostaticytes (OSCs), were further regarded as the reservoir of osteoclasts in the reversal phase. Notably, OSCs exhibited the highest chemotactic activity, surpassing other lineage subsets. We also discovered that cells at the earlier stage of the osteoclast lineage play a significant role in recruiting mesenchymal stem cells (MSCs). Finally, the data revealed that OSCs might be positively related to the occurrence of bone MSCs and the contribution of bone remodelling. Conclusion: Collectively, our findings revealed a novel stage (OSC) within the osteoclast lineage, potentially representing elusive bone reversal cells due to its increased chemotactic ability towards MSCs and potential contribution to bone remodelling. This study provides valuable insights into the intricate mechanisms of the reversal phase during bone remodelling and unveils potential therapeutic strategies for diseases associated with bone uncoupling. Translational potential of this article: This study identified a new subset, referred to as IDO1(plus symbol) CCL3(plus symbol) CCL4(plus symbol) osteostaticytes which displayed the highest chemotactic activity among all osteoclast lineages and may serve as reversal cells in bone remodelling. These findings offer new insights and insights for understanding bone reversal-related diseases and may serve as novel therapeutic targets for conditions such as osteomyelitis and delayed bone healing.

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BACKGROUND: The choroid plexus (CP) is suggested to be closely associated with the neuroinflammation of multiple sclerosis (MS). Segmentation based on deep learning (DL) could facilitate rapid and reproducible volume assessment of the CP, which is crucial for elucidating its role in MS. PURPOSE: To develop a reliable DL model for the automatic segmentation of CP, and further validate its clinical significance in MS. METHODS: The 3D UX-Net model (3D U-Net used for comparison) was trained and validated on T1-weighted MRI from a cohort of 216 relapsing-remitting MS (RRMS) patients and 75 healthy subjects. Among these, 53 RRMS with baseline and 2-year follow-up scans formed an internal test set (dataset1b). Another 58 RRMS from multi-center data served as an external test set (dataset2). Dice coefficient was computed to assess segmentation performance. Compare the correlation of CP volume obtained through automatic and manual segmentation with clinical outcomes in MS. Disability and cognitive function of patients were assessed using the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). RESULTS: The 3D UX-Net model achieved Dice coefficients of 0.875 ± 0.030 and 0.870 ± 0.044 for CP segmentation on dataset1b and dataset2, respectively, outperforming 3D U-Net's scores of 0.809 ± 0.098 and 0.601 ± 0.226. Furthermore, CP volumes segmented by the 3D UX-Net model aligned consistently with clinical outcomes compared to manual segmentation. In dataset1b, both manual and automatic segmentation revealed a significant positive correlation between normalized CP volume (nCPV) and EDSS scores at baseline (manual: r = 0.285, p = 0.045; automatic: r = 0.287, p = 0.044) and a negative correlation with SDMT scores (manual: r = -0.331, p = 0.020; automatic: r = -0.329, p = 0.021). In dataset2, similar correlations were found with EDSS scores (manual: r = 0.337, p = 0.021; automatic: r = 0.346, p = 0.017). Meanwhile, in dataset1b, both manual and automatic segmentation revealed a significant increase in nCPV from baseline to follow-up (p < 0.05). The increase of nCPV was more pronounced in patients with disability worsened than stable patients (manual: p = 0.023; automatic: p = 0.018). Patients receiving disease-modifying therapy (DMT) exhibited a significantly lower nCPV increase than untreated patients (manual: p = 0.004; automatic: p = 0.004). CONCLUSION: The 3D UX-Net model demonstrated strong segmentation performance for the CP, and the automatic segmented CP can be directly used in MS clinical practice. CP volume can serve as a surrogate imaging biomarker for monitoring disease progression and DMT response in MS patients.

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BACKGROUND: Postoperative sleep disturbance (PSD) is prevalent in perioperative patients，and has significant impact on postoperative recovery and prognosis. The aim of this study was to investigate the effect of desflurane maintenance on postoperative sleep quality, in order to optimize patients' perioperative sleep management. METHOD: A total of 118 patients undergoing elective breast surgery were randomized to receive either desflurane-based volatile anesthesia (desflurane group) or propofol-based total intravenous anesthesia (propofol group) for anesthesia maintenance. The primary outcome was the quality of sleep, which was assessed by the Pittsburgh Sleep Quality Index (PSQI) on 3 days after operation (POD3). Secondary outcomes were PSQI on postoperative day 7 (POD7) and 30 (POD30), and postoperative anxiety, depression, and pain score, as well as objective sleep parameters including total sleep time (TST), WASO (Wakefulness after sleep onset), REM (Rapid eye movement) and NREM (Non-rapid Eye Movement) measured by Fitbit Charge 2TM during the initial 3 postoperative days. RESULTS: The global PSQI scores on POD3 in the desflurane group was non-inferior to that in the propofol group [mean (SD) 8.47 (3.46) vs. 7.65 (3.16); mean difference (95 % CI) 0.82 (-0.43, 2.07); p < 0.001 for non-inferiority]. There were no significant differences in PSQI scores on POD3 and POD7. In addition, the score of anxiety, depression, and pain on the 3rd, 7th, and 30th day after surgery have no significant differences between the propofol and the desflurane group, respectively. The postoperative NREM was higher in the desflurane group than that in the propofol group. CONCLUSION: The effects of desflurane-based volatile anesthesia maintenance on postoperative sleep quality is not inferior to that of propofol-based total intravenous anesthesia, and these two drugs may have different effects on the sleep structure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04805775.

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Diabetic peripheral neuropathy is a major cause of disability and death in the later stages of diabetes. A retrospective chart review was performed using a hospital-based electronic medical record database to identify 1020 patients who met the criteria. The objective of this study was to explore and analyze the early risk factors for peripheral neuropathy in patients with type 2 diabetes, even in the absence of specific clinical symptoms or signs. Finally, the random forest algorithm was used to rank the influencing factors and construct a predictive model, and then the model performance was evaluated. Logistic regression analysis revealed that vitamin D plays a crucial protective role in preventing diabetic peripheral neuropathy. The top three risk factors with significant contributions to the model in the random forest algorithm eigenvalue ranking were glycosylated hemoglobin, disease duration, and vitamin D. The areas under the receiver operating characteristic curve of the model ware 0.90. The accuracy, precision, specificity, and sensitivity were 0.85, 0.83, 0.92, and 0.71, respectively. The predictive model, which is based on the random forest algorithm, is intended to support clinical decision-making by healthcare professionals and help them target timely interventions to key factors in early diabetic peripheral neuropathy.

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BACKGROUND: Cystatin SA (CST2) plays multiple roles in different types of malignant tumours; however, its role in serous ovarian cancer (SOC) remains unclear. Therefore, we aimed to investigate the expression levels, survival outcomes, immune cell infiltration, proliferation, cell cycle, and underlying molecular mechanisms associated with the CST2 signature in SOC. METHODS: The Cancer Genome Atlas database was used to acquire clinical information and CST2 expression profiles from patients with SOC. Wilcoxon rank-sum tests were used to compare CST2 expression levels between SOC and normal ovarian tissues. A prognostic assessment of CST2 was conducted using Cox regression analysis and the Kaplan-Meier method. Differentially expressed genes were identified using functional enrichment analysis. Immune cell infiltration was examined using a single-sample gene set enrichment analysis. Cell cycle characteristics and proliferation were assessed using a colony formation assay, flow cytometry, and a cell counting kit-8 assay. Western blots and quantitative reverse transcription PCR analyses were employed to examine CST2 expressions and related genes involved in the cell cycle and the Wnt-ß-catenin signalling pathway. RESULTS: Our findings revealed significant upregulation of CST2 in SOC, and elevated CST2 expression was correlated with advanced clinicopathological characteristics and unfavourable prognoses. Pathway enrichment analysis highlighted the association between the cell cycle and the Wnt signalling pathway. Moreover, increased CST2 levels were positively correlated with immune cell infiltration. Functionally, CST2 played vital roles in promoting cell proliferation, orchestrating the G1-to-S phase transition, and driving malignant SOC progression through activating the Wnt-ß-catenin signalling pathway. CONCLUSIONS: The elevated expression of CST2 may be related to the occurrence and progression of SOC by activating the Wnt-ß-catenin pathway. Additionally, our findings suggest that CST2 is a promising novel biomarker with potential applications in therapeutic, prognostic, and diagnostic strategies for SOC.

Serous ovarian cancer is a type of gynecological malignant tumour with high mortality rates. Understanding this disease is crucial for improving treatments and enhancing patient survival. In our study, we investigated a protein called CST2 and its role in serous ovarian cancer. We found that CST2 levels vary among patients and are associated with the progression of cancer and the prognosis of the patient, which could be valuable for future diagnosis and treatment strategies. However, further research is needed to validate these findings. Despite its limitations, our findings suggest that CST2 holds promise as a potential biomarker for detecting serous ovarian cancer and as a therapeutic target in the management of patients with this type of cancer.

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Aims: This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients. Methods: A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts. Results: Of these patients, 264 (25.2%) had negative cultures. Patients with a culture-negative compared with a culture-positive status were more likely to have the following characteristics: younger age (≤ 40 years) (113/264 (42.8%) vs 257/783 (32.8%); p = 0.004), a haematogenous aetiology (75/264 (28.4%) vs 150/783 (19.2%); p = 0.002), Cierny-Mader host A (79/264 (29.9%) vs 142/783 (18.1%); p < 0.001), antibiotic use before sampling (34/264 (12.9%) vs 41/783 (5.2%); p＜0.001), fewer taken samples (n＜3) (48/264 (18.2%) vs 60/783 (7.7%); p＜0.001), and less frequent presentation with a sinus (156/264 (59.1%) vs 665/783 (84.9%); p < 0.001). After initial treatments of first-debridement and antimicrobial, infection eradication was inferior in culture-positive osteomyelitis patients, with a 2.24-fold increase (odds ratio 2.24 (95% confidence interval 1.42 to 3.52)) in the redebridement rate following multivariate analysis. No statistically significant differences were found in long-term recurrence and complications within the two-year follow-up. Conclusion: We identified several factors being associated with the culture-negative result in osteomyelitis patients. In addition, the data also indicate that culture negativity is a positive prognostic factor in early infection eradication. These results constitute the basis of optimizing clinical management and patient consultations.

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