The efficacy of lumbar erector spinae plane block for postoperative analgesia management in patients undergoing lumbar unilateral bi-portal endoscopic surgery: a prospective randomized controlled trial.

BACKGROUND: The efficacy and reliability of erector spinae plane block (ESPB) in posterior open lumbar spine surgery has been demonstrated; however, few randomized controlled trials of lumbar ESPB (L-ESPB) in lumbar unilateral bi-portal endoscopic (UBE) surgery have been reported. METHODS: A total of 120 patients, aged 18 to 65 (who underwent elective lumbar UBE surgery under general anesthesia and exhibited an American Society of Anesthesiologists physical status of I to III) were randomly assigned in a 1:1 ratio to the ESPB group and the Control group. Ultrasound(US)-guided unilateral single-shot 0.25% ropivacaine L-ESPB was performed in the ESPB group, but not in the control group. Postoperative analgesic strategy for all patients: patient controlled intravenous analgesia (PCIA, diluted and dosed with fentanyl alone) was initiated immediately after surgery combined with oral compound codeine phosphate and ibuprofen sustained release tablets (1 tablet containing ibuprofen 200 mg and codeine 13 mg, 1 tablet/q12h) commenced 6 h postoperatively. We collected and compared patient-centred correlates intraoperatively and 48 h postoperatively. The primary outcomes were intraoperative and postoperative opioid consumption and postoperative quality of recovery-15 (QoR-15) scores. RESULTS: Compared to the control group (n = 56), the ESPB group (n = 58) significantly reduced intraoperative remifentanil consumption (estimated median difference - 280 mcg, 95% confidence interval [CI] - 360 to - 200, p < 0.001, power = 100%); significantly reduced fentanyl consumption at 24 h postoperatively (estimated median difference - 80mcg, 95%[CI] - 128 to - 32, p = 0.001, power = 90%); and significantly enhanced the QoR-15 score at 24 h postoperatively (estimated median difference 11, 95%[CI] 8 to 14, p < 0.001, power = 100%). Compared to the control group, the ESPB group enhanced the resting numeric rating scale (NRS) score up to 8 h postoperatively, and the active movement NRS score up to 4 h postoperatively. The incidence of postoperative nausea and vomiting (PONV) (p = 0.015, power = 70%), abdominal distension (p = 0.024, power = 64%), and muscular calf vein thrombosis (MCVT) (p = 0.033, power = 58%) was lower in the ESPB group than in the control group. Moreover, the occurrence of L-ESPB related adverse reactions was not found herein. CONCLUSION: US-guided L-ESPB reduces intraoperative and 24 h postoperative opioid consumption and improves patients' QoR-15 scores at 24 h postoperatively. L-ESPB can be safely and effectively utilized in lumbar UBE surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200061908 , date of registration: 10/07/2022. Registry URL.

Flow pattern maps of double emulsions transporting through bifurcation microchannels.

The transportation behaviors of compound droplets in confined channels are widespread phenomena while the physical mechanisms are far from being completely unraveled. In this work, behaviors of double emulsions flowing through bifurcation microchannels are experimentally studied with the aim of building universal flow pattern maps. Three flow patterns are categorized according to different features of daughter droplets in terms of size, uniformity, and shell thickness. A detailed analysis of the dynamics of interfacial evolutions in different patterns is carried out and the coupling interaction between interfaces is found to affect the minimum tail distance during transportation. It is feasible to obtain the threshold of the occurrence of the coupling interaction, due to the different variation tendencies in the two states, which relies on three dimensionless parameters, i.e. droplet length, length ratio, and capillary number. Furthermore, a novel physical model is proposed to build the flow pattern map, with the two transition boundaries being expressed as different relationships in terms of the three identified parameters. The physical mechanisms are summarized with the aid of force analysis. An excellent agreement is shown between the model and experimental results in different liquid systems and bifurcation structures, indicating the generality of the proposed model.

A Novel Cellular Senescence-related lncRNA Signature for Predicting the Prognosis of Breast Cancer Patients.

Background: Long non-coding RNA (lncRNA), a crucial regulator in breast cancer (BC) development, is intricately linked with cellular senescence. However, there is a lack of cellular senescence-related lncRNAs (CSRLs) signature to evaluate the prognosis of BC patients. Methods: Correlation analysis was conducted to identify lncRNAs associated with cellular senescence. Subsequently, a CSRL signature was crafted in the training cohort. The model's accuracy was evaluated through survival analysis and receiver operating characteristic curves. Furthermore, prognostic nomograms amalgamating cellular senescence and clinical characteristics were devised. Tumor microenvironment and checkpoint disparities were compared between low-risk and high-risk groups. The correlation between these signatures and treatment response in BC patients was also investigated. Finally, functional experiments were conducted for validation. Results: A signature comprising nine CSRLs was devised, which demonstrated adept prognostic capability in BC patients. Functional enrichment analysis revealed that tumor and immune-related pathways were predominantly enriched. Compared to the low-risk group, the high-risk group could benefit more from immunotherapy and certain chemotherapeutic agents. The expression of the 9 CSRLs was validated through in vitro experiments in different subtypes of BC cell lines and tissues. AC098484.1 was specifically verified for its association with senescence-associated secretory phenotypes. Conclusion: The CSRLs signature emerges as a promising prognostic biomarker for BC, with implications for immunological studies and treatment strategies. AC098484.1 has potential relevance in the treatment of BC cell senescence, and these findings improve the clinical treatment levels for BC patients.

Effect of Oridonin on Experimental Animal Model of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a serious disease that occurs in premature and low-birth-weight infants. In recent years, the incidence of BPD has not decreased, and there is no effective treatment for it. Oridonin (Ori) is a traditional Chinese medicine with a wide range of biological activities, especially pharmacological and anti-inflammatory. It is well known that inflammation plays a key role in BPD. However, the therapeutic effect of Ori on BPD has not been studied. Therefore, in the present study, we will observe the anti-inflammatory activity of Ori in an experimental animal model of BPD. Here, we showed that Ori could significantly decrease hyperoxia-induced alveolar injury, inhibit neutrophil recruitment, myeloperoxidase concentrations, and release inflammatory factors in BPD neonatal rats. Taken together, the experimental results suggested that Ori can significantly improve BPD in neonatal rats by inhibiting inflammatory response.

Hydroxide and Hydronium Ions Modulate the Dynamic Evolution of Nitrogen Nanobubbles in Water.

It has been widely recognized that the pH environment influences the nanobubble dynamics and hydroxide ions adsorbed on the surface may be responsible for the long-term survival of the nanobubbles. However, understanding the distribution of hydronium and hydroxide ions in the vicinity of a bulk nanobubble surface at a microscopic scale and the consequent impact of these ions on the nanobubble behavior remains a challenging endeavor. In this study, we carried out deep potential molecular dynamics simulations to explore the behavior of a nitrogen nanobubble under neutral, acidic, and alkaline conditions and the inherent mechanism, and we also conducted a theoretical thermodynamic and dynamic analysis to address constraints related to simulation duration. Our simulations and theoretical analyses demonstrate a trend of nanobubble dissolution similar to that observed experimentally, emphasizing the limited dissolution of bulk nanobubbles in alkaline conditions, where hydroxide ions tend to reside slightly farther from the nanobubble surface than hydronium ions, forming more stable hydrogen bond networks that shield the nanobubble from dissolution. In acidic conditions, the hydronium ions preferentially accumulating at the nanobubble surface in an orderly manner drive nanobubble dissolution to increase the entropy of the system, and the dissolved nitrogen molecules further strengthen the hydrogen bond networks of systems by providing a hydrophobic environment for hydronium ions, suggesting both entropy and enthalpy effects contribute to the instability of nanobubbles under acidic conditions. These results offer fresh insights into the double-layer distribution of hydroxide and hydronium near the nitrogen-water interface that influences the dynamic behavior of bulk nanobubbles.

Combined analysis of metabolomics and 16S rRNA sequencing for ankylosing spondylitis patients before and after secukinumab therapy.

OBJECTIVE: Alterations in gut microbiota have been implicated in the pathogenesis of ankylosing spondylitis (AS), but the underlying mechanisms remain elusive. This study aims to investigate changes in gut microbiota and metabolites in individuals with AS before and after treatment with secukinumab, to identify the biological characteristics specific to AS patients and investigate the potential biomarkers, for optimizing therapeutic strategies more effectively. METHODS: Fecal microbiome data were collected from 30 AS patients before and after secukinumab therapy and compared with data from 40 healthy controls (HC). Additionally, we analyzed the metabolic profile of both groups from plasma. RESULTS: Findings indicated that the treatment-induced changes in the composition of several crucial bacterial groups, including Megamonas, Prevotella_9, Faecalibacterium, Roseburia, Bacteroides, and Agathobacter. Post-treatment, these groups exhibited a distribution more akin to that of the healthy populations compared with their pretreatment status. We identified three gut microbial taxa, namely Prevotellaceae_bacterium_Marseille_P2831, Prevotella_buccae, and Elusimicrobiota, as potential biomarkers for diagnosing individuals at a higher risk of developing AS and assessing disease outcomes. Plasma metabolomics analysis revealed 479 distinct metabolites and highlighted three disrupted metabolic pathways. Integration of microbiome and metabolomics datasets demonstrated a significant degree of correlation, underscoring the impact of the microbiome on metabolic activity. CONCLUSION: Secukinumab can restore the balance of the gut microbiome and metabolites in AS patients, rendering them more similar to those found in the healthy population. The analysis of microbiome and metabolomics data have unveiled some candidate biomarkers capable of evaluating treatment efficacy.

Selective Activation of G Protein-Coupled Estrogen Receptor 1 (GPER1) Reduces ER Stress and Pyroptosis via AMPK Signaling Pathway in Experimental Subarachnoid Hemorrhage.

Neuroinflammation is a critical pathogenic event following hemorrhagic stroke. Endoplasmic reticulum (ER) stress-induced apoptosis and nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3(NLRP3)-associated pyroptosis can contribute to the escalation of neuroinflammatory responses, leading to increased brain damage. G protein-coupled estrogen receptor 1(GPER1), as the most extensively characterized brain-derived estrogen, was reported to trigger neuroprotective effects. However, the anti-apoptotic and anti-pyroptotic effect of GPER1 activation and the underlying mechanism has not been fully elucidated. We established the experimental SAH model by intravascular perforation. The GPER1 selective agonist G1 was intravenously administered 1 h following SAH. For mechanistic exploration, the selective inhibitor of adenosine monophosphate-activated protein kinase (AMPK), dorsomorphin, was administered via intracerebroventricular injection 30 min prior to SAH induction. Post-SAH assessments included SAH grade, the short-term and long-term neurological outcomes, brain edema, cerebral blood flow, transmission electron microscopy (TEM), western blot (WB), ELISA, TUNEL staining, Fluoro-Jade C staining (FJC), and immunofluorescence staining. The expression of GPER1 was observed to elevate at 6 h and peaked at 24 h subsequent to SAH, predominantly co-localized with neurons. Post-treatment with G1 markedly ameliorated both the short-term and long-term neurological deficits of SAH mouse, as well as inhibiting the expression of neuronal ER stress-associated apoptotic proteins (i.e., CHOP, GRP78, Caspase-12, Cleaved Caspase-3, Bax, Bcl2) and pyroptosis-associated proteins (i.e., NLRP3, ASC, Cleaved Caspase-1). Additionally, our research revealed that inhibition of AMPK with dorsomorphin attenuated the neuroprotective effects of G1. This was accompanied by modifications in the molecular pathways associated with ER stress-induced apoptosis and pyroptosis. These data herein elucidated that GPER1 exerted neuroprotective effects by mitigating neuroinflammation in an AMPK-dependent manner, which modulates neuronal ER stress-associated apoptosis and pyroptosis. Boosting the anti-apoptotic and anti-pyroptotic effect by activating GPER1 may be an efficient treatment strategy for SAH patients.

Determinants of sedentary behavior in community-dwelling older adults with type 2 diabetes based on the behavioral change wheel: a path analysis.

BACKGROUND: Sedentary behavior (SB) is deeply ingrained in the daily lives of community-dwelling older adults with type 2 diabetes mellitus (T2DM). However, the specific underlying mechanisms of the determinants associated with SB remain elusive. We aimed to explore the determinants of SB based on the behavior change wheel framework as well as a literature review. METHODS: This cross-sectional study recruited 489 community-dwelling older adults with T2DM in Jinan City, Shandong Province, China. Convenience sampling was used to select participants from relevant communities. This study used the Measure of Older Adults' Sedentary Time-T2DM, the Abbreviated-Neighborhood Environment Walkability Scale, the Social Support Rating Scale, the Lubben Social Network Scale 6, the Subjective Social Norms Questionnaire for Sedentary Behavior, the Functional Activities Questionnaire, the Numerical Rating Scale, the Short Physical Performance Battery, and the Montreal Cognitive Assessment Text to assess the levels of and the determinants of SB. Descriptive statistical analysis and path analysis were conducted to analyze and interpret the data. RESULTS: Pain, cognitive function, social isolation, and social support had direct and indirect effects on SB in community-dwelling older adults with T2DM (total effects: ß = 0.426, ß = -0.171, ß = -0.209, and ß = -0.128, respectively), and physical function, walking environment, and social function had direct effects on patients' SB (total effects: ß = -0.180, ß = -0.163, and ß = 0.127, respectively). All the above pathways were statistically significant (P < 0.05). The path analysis showed that the model had acceptable fit indices: RMSEA = 0.014, χ 2/df = 1.100, GFI = 0.999, AGFI = 0.980, NFI = 0.997, RFI = 0.954, IFI = 1.000, TLI = 0.996, CFI = 1.000. CONCLUSION: Capability (physical function, pain, and cognitive function), opportunity (social isolation, walking environment, and social support), and motivation (social function) were effective predictors of SB in community-dwelling older adults with T2DM. Deeper knowledge regarding these associations may help healthcare providers design targeted intervention strategies to decrease levels of SB in this specific population.

Efficacy and safety of tocilizumab in patients with refractory generalized myasthenia gravis.

BACKGROUND: We aimed to compare the efficacy of tocilizumab with conventional immunotherapy in refractory patients with acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). METHODS: This single-center prospective cohort study was based on patients from an MG registry study in China and conducted from February 10, 2021 to March 31, 2022. Adult refractory patients with AChR-Ab+ gMG were assigned to tocilizumab or conventional immunotherapy groups. The primary efficacy outcome was the mean difference of MG activities of daily living (MG-ADL) change at weeks 4, 8, 12, 16, 20, 24 corresponding to that at the baseline between the two groups. A generalized estimating equation model was used for the primary outcome analysis. Safety was assessed based on adverse events. RESULTS: Of 34 eligible patients, 20 (mean [standard deviation] age, 53.8 [21.9] years; 12 [60.0%] female) received tocilizumab and 14 received conventional immunotherapy (45.8 [18.0] years; 8 [57.1%] female). The tocilizumab group had greater reduction in MG-ADL score at week 4 (adjusted mean difference, -3.4; 95% CI, -4.7 to -2.0; p < 0.001) than the conventional immunotherapy group, with significant differences sustained through week 24 (adjusted mean difference, -4.5; 95% CI, -6.4 to -2.6; p < 0.001). At week 24, the proportion of patients achieving higher levels of MG-ADL (up to 7-point reduction) and QMG (up to 11-point reduction) scores improvement was significantly greater with tocilizumab. Tocilizumab had acceptable safety profiles without severe or unexpected safety issues. CONCLUSION: Tocilizumab is safe and effective in improving the MG-ADL score and reducing prednisone dose in refractory AChR-Ab+ gMG, suggesting tocilizumab has the potential to be a valuable therapeutic option for such patients.

Comprehensive Transcriptome and Proteome Analyses Reveal the Drought Responsive Gene Network in Potato Roots.

The root system plays a decisive role in the growth and development of plants. The water requirement of a root system depends strongly on the plant species. Potatoes are an important food and vegetable crop grown worldwide, especially under irrigation in arid and semi-arid regions. However, the expected impact of global warming on potato yields calls for an investigation of genes related to root development and drought resistance signaling pathways in potatoes. In this study, we investigated the molecular mechanisms of different drought-tolerant potato root systems in response to drought stress under controlled water conditions, using potato as a model. We analyzed the transcriptome and proteome of the drought-sensitive potato cultivar Atlantic (Atl) and the drought-tolerant cultivar Qingshu 9 (Q9) under normal irrigation (CK) and weekly drought stress (D). The results showed that a total of 14,113 differentially expressed genes (DEGs) and 5596 differentially expressed proteins (DEPs) were identified in the cultivars. A heat map analysis of DEGs and DEPs showed that the same genes and proteins in Atl and Q9 exhibited different expression patterns under drought stress. Weighted gene correlation network analysis (WGCNA) showed that in Atl, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG)-enriched pathways were related to pyruvate metabolism and glycolysis, as well as cellular signaling and ion transmembrane transporter protein activity. However, GO terms and KEGG-enriched pathways related to phytohormone signaling and the tricarboxylic acid cycle were predominantly enriched in Q9. The present study provides a unique genetic resource to effectively explore the functional genes and uncover the molecular regulatory mechanism of the potato root system in response to drought stress.

Fitness effects of synthetic and natural diet preservatives on the edible insect Bombyx mori.

Silkworm pupae as widely consumed insect products are good biosources of protein and micronutrients. Silkworm rearing throughout the year can be achieved by feeding them an artificial diet instead of native plants, facilitating extensive pupa production. However, artificial diets are prone to spoilage caused by bacterial contamination. Here, we evaluated the antiseptic effect of ethylparaben (EP, chemical preservative) and medium-chain fatty acids (MCFA, natural preservative) in a silkworm artificial diet. Results showed that both preservatives effectively inhibited pathogenic bacterial growth. Furthermore, the addition of EP or MCFA did not negatively impact the production capacity of silkworms and the homeostasis of gut microbiota. However, the expression of genes involved in detoxification such as Ugt2, and immune response such as Cecropin B, were upregulated after EP consumption. Therefore, natural preservative MCFA emerges as a suitable option from a safety perspective. These findings highlight future directions for improving insect artificial diet formulation.

Machine learning-based model for predicting outcomes in cerebral hemorrhage patients with leukemia.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) in leukemia patients progresses rapidly with high mortality. Limited data are available on imaging studies in this population. The study aims to develop prediction models for 7-day and short-term mortality risk based on the non-contrast computed tomography (NCCT) image features. METHODS: The NCCT image features of ICH in 135 leukemia patients between 2007-2023 were retrospectively extracted using manual assessment and radiomics methods. After multiple imputation of missing laboratory data, univariate logistic regression and least absolute shrinkage and selection operator (LASSO) were used for feature selection. Random forest models were built with comprehensive evaluation and ranking of feature importance. RESULT: 135 and 129 patients were included in the studies for 7-day and short-term prognostic models, respectively. The median age of all enrolled patients was 35 years, and there were 86 male patients (63.7 %). Clinical models (validation: AUC [area under the curve] = 0.78, AUPRC [area under the precision-recall curve] = 0.73; AUC = 0.84, AUPRC = 0.86), radiomics models (validation: AUC = 0.82, AUPRC = 0.78; AUC = 0.75, AUPRC = 0.77), and the combined models (validation: AUC = 0.84, AUPRC = 0.83; AUC = 0.87, AUPRC = 0.89) predicted 7-day and short-term mortality with good predictive efficacy. Clinical decision curve analysis showed that the combined models predicted 7-day and 30-day risk of death would be more beneficial than other models. Shape features contributed significantly more than semantic features in both radiomics models and combined models (93.3 %, 52.1 %, as well as 85.2 %,37.4 %, respectively) for 7-day and 30-day mortality. CONCLUSIONS: Combined models constructed based on NCCT perform well in predicting the risk of 7-day and short-term mortality in ICH patients with leukemia. Shape features extracted by radiomics are important markers for modeling the prognosis.

The prognostic value of prognostic nutritional index in postoperative onset of PAH in children with isolated VSD: a prospective cohort study based on propensity score matching analysis.

Background: The mechanism of pulmonary arterial hypertension (PAH) after surgery/intervention for isolated venticlular septal defect (VSD) in children is unknown. Reliable prognostic indicators for predicting postoperative PAH are urgently needed. Prognostic nutration index (PNI) is widely used to predict postoperative complications and survival in adults, but it is unclear whether it can be used as an indicator of prognosis in children. Methods: A total of 251 children underwent VSD repair surgery or interventional closure in Hunan Children's Hospital from 2020 to 2023 were collected. A 1:1 propensity score matching (PSM) analysis was performed using the nearest neighbor method with a caliper size of 0.2 Logistics regression analysis is used to examine factors associated with the development of PAH. Results: The cut-off value for PNI was determined as 58.0. After 1:1 PSM analysis, 49 patients in the low PNI group were matched with high PNI group. Children in the low PNI group had higher risk of postoperative PAH (P = 0.002) than those in the high PNI group. Multivariate logistics regression analysis showed that PNI (RR: 0.903, 95% CI: 0.816-0.999, P = 0.049) and tricuspid regurgitation velocity (RR: 4.743, 95% CI: 1.131-19.897, P = 0.033) were independent prognostic factors for the development of PAH. Conclusion: PNI can be used as a prognostic indicator for PAH development after surgery/intervention in children with isolated VSD.

A prospective study on using shear wave elastography to predict the ypT0 stage of rectal cancer after neoadjuvant therapy: a new support for the watch-and-wait approach?

Introduction: The diagnostic accuracy of traditional imaging examination in predicting ypT stage of rectal cancer after neoadjuvant therapy is significantly reduced, which would affect patients' subsequent treatment choices. This study aimed to investigate the use of endorectal shear wave elastography (SWE) for diagnosing ypT0 stage of rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods: Sixty patients with rectal cancer were prospectively recruited in this study. Data on endorectal ultrasound (ERUS) and SWE parameters were collected before nCRT and 6-8 weeks after nCRT. Postoperative pathological results were the gold standard for evaluating the diagnostic accuracy of SWE and ERUS in predicting the ypT0 stage of rectal cancer after nCRT. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off values of the SWE parameters that best corresponded to the ypT0 stage and analyze the sensitivity, specificity, and accuracy. Results: The diagnostic accuracies of using ERUS to predict the ypT and ypT0 stages of rectal cancer after nCRT were 58.1% (18/31) and 64.3% (9/14), respectively. The ROC curve was constructed with the lesion's Emean, Emean corrected (EC), Emean difference (ED), Emean corrected differencede (ECD), Emean descendding rate (EDR) and Emean corrected descendding rate (ECDR) values after nCRT, the cut-off values of diagnosing the ypT0 stage were 64.40 kPa, 55.45 kPa, 72.55 kPa, 73.75 kPa, 50.15%, and 55.93%, respectively; the area under the curve (AUC) for diagnosing the ypT0 stage was 0.924, 0.933, 0.748, 0.729, 0.857 and 0.861, respectively. The EC value showed the best diagnostic performance. Conclusion: SWE could improve the accuracy of conventional ERUS in diagnosing the ypT0 stage of rectal cancer after nCRT. It is expected to become a new method to help predict pathological complete responses in clinical practice and provide new evidence for the watch-and-wait approach.

A nomogram based on conventional and contrast-enhanced ultrasound radiomics for the noninvasively prediction of axillary lymph node metastasis in breast cancer patients.

Background: This study aimed to investigate whether quantitative radiomics features extracted from conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) of primary breast lesions can help noninvasively predict axillary lymph nodes metastasis (ALNM) in breast cancer patients. Method: A total of 111 breast cancer patients with 111 breast lesions were prospectively enrolled. All the included patients received presurgical CUS screening and CEUS examination and were randomly assigned to the training and validation sets at a ratio of 7:3 (n = 78 versus 33). Radiomics features were respectively extracted based on CUS and CEUS using the PyRadiomics package. The max-relevance and min-redundancy (MRMR) and least absolute shrinkage and selection operator (LASSO) analyses were used for feature selection and radiomics score calculation in the training set. The variance inflation factor (VIF) was performed to check the multicollinearity among selected predictors. The best performing model was selected to develop a nomogram using binary logistic regression analysis. The calibration and clinical utility of the nomogram were assessed. Results: The model combining CUS reported ALN status, CUS radiomics score (CUS-radscore) and CEUS radiomics score (CEUS-radscore) exhibited the best performance. The areas under the curves (AUC) of our proposed nomogram in the training and external validation sets were 0.845 [95% confidence interval (CI), 0.739-0.950] and 0.901 (95% CI, 0.758-1). The calibration curves and decision curve analysis (DCA) demonstrated the nomogram's robust consistency and clinical utility. Conclusions: The established nomogram is a promising prediction tool for noninvasive prediction of ALN status. The radiomics features based on CUS and CEUS can help improve the predictive performance.

Protocol for the Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study: a prospective, observational, multicentre cohort study of acute spinal cord injury.

INTRODUCTION: Spinal cord injury (SCI) is a catastrophic event with devastating physical, social and occupational consequences for patients and their families. The number of patients with acute SCI in China continues to grow rapidly, but there have been no large prospective cohort studies of patients with acute SCI. This proposed study aims to establish a multicentre, extensive sample cohort of clinical data and biological samples of patients in China, which would aid the systematisation and standardisation of clinical research and treatment of acute SCI, thus reducing the heavy burden of acute SCI on patients and society. METHODS AND ANALYSIS: The Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study is an observational, multicentre cohort study of patients with acute SCI admitted to the Qilu Hospital of Shandong University and other participating centres with prospective collection of their clinical data and biological samples. We aim to recruit 2097 patients in this study. Demographics, disease history, emergency intervention information, motor and sensory examinations, surgical information, medication information and rehabilitation evaluation will be recorded. This will facilitate the development of a prediction model for complications and prognosis of patients with acute SCI and an evaluation of the current management of acute SCI. Among these variables, detailed information on surgical treatment will also be used to assess procedures for acute SCI treatment. Outcome measurements, including the International Standard for Neurological Classification of Spinal Cord Injury examinations, the occurrence of complications and death, will be performed repeatedly during follow-up. We will analyse imaging data and blood samples to develop SCI imaging markers and biomarkers. ETHICS AND DISSEMINATION: This study protocol has been approved by the Medical Ethics Committee of the Qilu Hospital of Shandong University and all other participating centres. The findings will be disseminated in peer-reviewed journals and academic conferences.

The Smi-miR858a-SmMYB module regulates tanshinone and phenolic acid biosynthesis in Salvia miltiorrhiza.

Tanshinones and phenolic acids are two major classes of bioactive compounds in Salvia miltiorrhiza. Revealing the regulatory mechanism of their biosynthesis is crucial for quality improvement of S. miltiorrhiza medicinal materials. Here we demonstrated that Smi-miR858a-Smi-miR858c, a miRNA family previously known to regulate flavonoid biosynthesis, also played critical regulatory roles in tanshinone and phenolic acid biosynthesis in S. miltiorrhiza. Overexpression of Smi-miR858a in S. miltiorrhiza plants caused significant growth retardation and tanshinone and phenolic acid reduction. Computational prediction and degradome and RNA-seq analyses revealed that Smi-miR858a could directly cleave the transcripts of SmMYB6, SmMYB97, SmMYB111, and SmMYB112. Yeast one-hybrid and transient transcriptional activity assays showed that Smi-miR858a-regulated SmMYBs, such as SmMYB6 and SmMYB112, could activate the expression of SmPAL1 and SmTAT1 involved in phenolic acid biosynthesis and SmCPS1 and SmKSL1 associated with tanshinone biosynthesis. In addition to directly activating the genes involved in bioactive compound biosynthesis pathways, SmMYB6, SmMYB97, and SmMYB112 could also activate SmAOC2, SmAOS4, and SmJMT2 involved in the biosynthesis of methyl jasmonate, a significant elicitor of plant secondary metabolism. The results suggest the existence of dual signaling pathways for the regulation of Smi-miR858a in bioactive compound biosynthesis in S. miltiorrhiza.

Single-cell transcriptome profiling reveals the spatiotemporal distribution of triterpenoid saponin biosynthesis and transposable element activity in Gynostemma pentaphyllum shoot apexes and leaves.

Gynostemma pentaphyllum (Thunb.) Makino is an important producer of dammarene-type triterpenoid saponins. These saponins (gypenosides) exhibit diverse pharmacological benefits such as anticancer, antidiabetic, and immunomodulatory effects, and have major potential in the pharmaceutical and health care industries. Here, we employed single-cell RNA sequencing (scRNA-seq) to profile the transcriptomes of more than 50,000 cells derived from G. pentaphyllum shoot apexes and leaves. Following cell clustering and annotation, we identified five major cell types in shoot apexes and four in leaves. Each cell type displayed substantial transcriptomic heterogeneity both within and between tissues. Examining gene expression patterns across various cell types revealed that gypenoside biosynthesis predominantly occurred in mesophyll cells, with heightened activity observed in shoot apexes compared to leaves. Furthermore, we explored the impact of transposable elements (TEs) on G. pentaphyllum transcriptomic landscapes. Our findings the highlighted the unbalanced expression of certain TE families across different cell types in shoot apexes and leaves, marking the first investigation of TE expression at the single-cell level in plants. Additionally, we observed dynamic expression of genes involved in gypenoside biosynthesis and specific TE families during epidermal and vascular cell development. The involvement of TE expression in regulating cell differentiation and gypenoside biosynthesis warrant further exploration. Overall, this study not only provides new insights into the spatiotemporal organization of gypenoside biosynthesis and TE activity in G. pentaphyllum shoot apexes and leaves but also offers valuable cellular and genetic resources for a deeper understanding of developmental and physiological processes at single-cell resolution in this species.

Neutrophils in glioma microenvironment: from immune function to immunotherapy.

Glioma is a malignant tumor of the central nervous system (CNS). Currently, effective treatment options for gliomas are still lacking. Neutrophils, as an important member of the tumor microenvironment (TME), are widely distributed in circulation. Recently, the discovery of cranial-meningeal channels and intracranial lymphatic vessels has provided new insights into the origins of neutrophils in the CNS. Neutrophils in the brain may originate more from the skull and adjacent vertebral bone marrow. They cross the blood-brain barrier (BBB) under the action of chemokines and enter the brain parenchyma, subsequently migrating to the glioma TME and undergoing phenotypic changes upon contact with tumor cells. Under glycolytic metabolism model, neutrophils show complex and dual functions in different stages of cancer progression, including participation in the malignant progression, immune suppression, and anti-tumor effects of gliomas. Additionally, neutrophils in the TME interact with other immune cells, playing a crucial role in cancer immunotherapy. Targeting neutrophils may be a novel generation of immunotherapy and improve the efficacy of cancer treatments. This article reviews the molecular mechanisms of neutrophils infiltrating the central nervous system from the external environment, detailing the origin, functions, classifications, and targeted therapies of neutrophils in the context of glioma.