GINS4 suppresses ferroptosis by antagonizing p53 acetylation with Snail.

Ferroptosis is an iron-dependent oxidative, nonapoptotic form of regulated cell death caused by the destruction of redox homeostasis. Recent studies have uncovered complex cellular networks that regulate ferroptosis. GINS4 is a promoter of eukaryotic G1/S-cell cycle as a regulator of initiation and elongation of DNA replication, but little is known about its impact on ferroptosis. Here, we found that GINS4 was involved in the regulation of ferroptosis in lung adenocarcinoma (LUAD). CRISPR/Cas9-mediated GINS4 KO facilitated ferroptosis. Interestingly, depletion of GINS4 could effectively induce G1, G1/S, S, and G2/M cells to ferroptosis, especially for G2/M cells. Mechanistically, GINS4 suppressed p53 stability through activating Snail that antagonized the acetylation of p53, and p53 lysine residue 351 (K351 for human p53) was the key site for GINS4-suppressed p53-mediated ferroptosis. Together, our data demonstrate that GINS4 is a potential oncogene in LUAD that functions to destabilize p53 and then inhibits ferroptosis, providing a potential therapeutic target for LUAD.

Holistic immunomodulation for small cell lung cancer.

Small cell lung cancer (SCLC) is characterized by a high mortality rate, rapid growth, and early metastasis, which lead to a poor prognosis. Moreover, limited clinical treatment options further lower the survival rate of patients. Therefore, novel technology and agents are urgently required to enhance clinical efficacy. In this review, from a holistic perspective, we summarized the therapeutic targets, agents and strategies with the most potential for treating SCLC, including chimeric antigen receptor (CAR) T therapy, immunomodulating antibodies, traditional Chinese medicines (TCMs), and the microbiota, which have been found recently to improve the clinical outcomes and prognosis of SCLC. Multiomics technologies can be integrated to develop effective diagnostic methods and identify new targets for new drug discovery in SCLC. We discussed in depth the feasibility, potential, and challenges of these new strategies, as well as their combinational treatments, which may provide promising alternatives for enhancing the clinical efficacy of SCLC in the future.

Collaborative CRISPR-Cas System-Enabled Detection of Circulating Circular RNA for Reliable Monitoring of Acute Myocardial Infarction.

Acute myocardial infarction (AMI) is one of the major causes of death worldwide, posing significant global health challenges. Circular RNA (circRNA) has recently emerged as a potential diagnostic biomarker for AMI, providing valuable information for timely medical care. In this work, a new electrochemical method for circRNA detection by engineering a collaborative CRISPR-Cas system is developed. This system integrates the unique circRNA-targeting ability with cascade trans-cleavage activities of Cas effectors, using an isothermal primer exchange reaction as the bridge. Using cZNF292, a circulating circRNA biomarker for AMI is identified by this group; as a model, the collaborative CRISPR-Cas system-based method exhibits excellent accuracy and sensitivity with a low detection limit of 2.13 × 10-15 m. Moreover, the method demonstrates a good diagnostic performance for AMI when analyzing whole blood samples. Therefore, the method may provide new insight into the detection of circRNA biomarkers and is expected to have great potential in AMI diagnosis in the future.

PHLDA2 overexpression facilitates senescence and apoptosis via the mitochondrial route in human nucleus pulposus cells by regulating Wnt/ß-catenin signalling pathway.

Low back pain is a common clinical symptom of intervertebral disc degeneration (IVDD), which seriously affects the quality of life of the patients. The abnormal apoptosis and senescence of nucleus pulposus cells (NPCs) play important roles in the pathogenesis of IVDD. PHLDA2 is an imprinted gene related to cell apoptosis and tumour progression. However, its role in NPC degeneration is not yet clear. Therefore, this study was set to explore the effects of PHLDA2 on NPC senescence and apoptosis and the underlying mechanisms. The expression of PHLDA2 was examined in human nucleus pulposus (NP) tissues and NPCs. Immunohistochemical staining, magnetic resonance imaging imaging and western blot were performed to evaluate the phenotypes of intervertebral discs. Senescence and apoptosis of NPCs were assessed by SA-ß-galactosidase, flow cytometry and western blot. Mitochondrial function was investigated by JC-1 staining and transmission electron microscopy. It was found that the expression level of PHLDA2 was abnormally elevated in degenerated human NP tissues and NPCs. Furthermore, knockdown of PHLDA2 can significantly inhibit senescence and apoptosis of NPCs, whereas overexpression of PHLDA2 can reverse senescence and apoptosis of NPCs in vitro. In vivo experiment further confirmed that PHLDA2 knockdown could alleviate IVDD in rats. Knockdown of PHLDA2 could also reverse senescence and apoptosis in IL-1ß-treated NPCs. JC-1 staining indicated PHLDA2's knockdown impaired disruption of the mitochondrial membrane potential and also ameliorated superstructural destruction of NPCs as showed by transmission electron microscopy. Finally, we found the PHLDA2 knockdown promoted Collagen-II expression and suppressed MMP3 expression in NPCs by repressing wnt/ß-catenin pathway. In conclusion, the results of the present study showed that PHLDA2 promotes IL-1ß-induced apoptosis and senescence of NP cells via mitochondrial route by activating the Wnt/ß-catenin pathway, and suggested that therapy targeting PHLDA2 may provide valuable insights into possible IVDD therapies.

Epstein-Barr virus-driven metabolic alterations contribute to the viral lytic reactivation and tumor progression in nasopharyngeal carcinoma.

Metabolic reprogramming induced by Epstein-Barr virus (EBV) often mirrors metabolic changes observed in cancer cells. Accumulating evidence suggests that lytic reactivation is crucial in EBV-associated oncogenesis. The aim of this study was to explore the role of metabolite changes in EBV-associated malignancies and viral life cycle control. We first revealed that EBV (LMP1) accelerates the secretion of the oncometabolite D-2HG, and serum D-2HG level is a potential diagnostic biomarker for NPC. EBV (LMP1)-driven metabolite changes disrupts the homeostasis of global DNA methylation and demethylation, which have a significantly inhibitory effect on active DNA demethylation and 5hmC content. We found that loss of 5hmC indicates a poor prognosis for NPC patients, and that 5hmC modification is a restriction factor of EBV reactivation. We confirmed a novel EBV reactivation inhibitor, α-KG, which inhibits the expression of EBV lytic genes with CpG-containing ZREs and the latent-lytic switch by enhancing 5hmC modification. Our results demonstrate a novel mechanism of which metabolite abnormality driven by EBV controls the viral lytic reactivation through epigenetic modification. This study presents a potential strategy for blocking EBV reactivation, and provides potential targets for the diagnosis and therapy of NPC.

Phylogenomic analyses sheds new light on the phylogeny and diversification of Corydalis DC. in Himalaya-Hengduan Mountains and adjacent regions.

The Himalaya-Hengduan Mountains (HHM), a renowned biodiversity hotspot of the world, harbors the most extensive habitats for alpine plants with extraordinary high levels of endemism. Although the general evolution pattern has been elucidated, the underlying processes driving spectacular radiations in many species-rich groups remain elusive. Corydalis DC. is widely distributed throughout the Northern Hemisphere containing more than 500 species, with high diversity in HHM and adjacent regions. Using 95 plastid genes, 3,258,640 nuclear single nucleotide polymorphisms (SNPs) and eight single-copy nuclear genes (SCNs) generated from genome skimming data, we reconstructed a robust time-calibrated phylogeny of Corydalis comprising more than 100 species that represented all subgenera and most sections. Molecular dating indicated that all main clades of Corydalis began to diverge in the Eocene, with the majority of extant species in HHM emerged from a diversification burst after the middle Miocene. Global pattern of mean divergence times indicated that species distributed in HHM were considerably younger than those in other regions, particularly for the two most species-rich clades (V and VI) of Corydalis. The early divergence and the recent diversification of Corydalis were most likely promoted by the continuous orogenesis and climate change associated with the uplift of the Qinghai-Tibetan Plateau (QTP). Our study demonstrates the effectivity of phylogenomic analyses with genome skimming data on the phylogeny of species-rich taxa, and sheds lights on how the uplift of QTP has triggered the evolutionary radiations of large plant genera in HHM and adjacent regions.

Hsa_circ_0005397 promotes hepatocellular carcinoma progression through EIF4A3.

PURPOSE: The purpose of this study was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma progression. METHODS: Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to measure the expression level of hsa_circ_0005397 and EIF4A3 from paired HCC tissues and cell lines. Western Blot (WB) and immunohistochemistry (IHC) were used to verify the protein level of EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. Receiver Operating Characteristic (ROC) Curve was drawn to analyze diagnostic value. Actinomycin D and nuclear and cytoplasmic extraction assays were utilized to evaluate the characteristics of hsa_circ_0005397. Cell Counting kit-8 (CCK-8) and colony formation assays were performed to detect cell proliferation. Flow cytometry analysis was used to detect the cell cycle. Transwell assay was performed to determine migration and invasion ability. RNA-binding proteins (RBPs) of hsa_circ_0005397 in HCC were explored using bioinformatics websites. The relationship between hsa_circ_0005397 and Eukaryotic Translation Initiation Factor 4A3 (EIF4A3) was verified by RNA Binding Protein Immunoprecipitation (RIP) assays, correlation and rescue experiments. RESULTS: In this study, hsa_circ_0005397 was found to be significantly upregulated in HCC, and the good diagnostic sensitivity and specificity shown a potential diagnostic capability. Upregulated expression of hsa_circ_0005397 was significantly related to tumor size and stage. Hsa_circ_0005397 was circular structure which more stable than liner mRNA, and mostly distributed in the cytoplasm. Upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, and metastatic potency of HCC cells; its downregulation yielded the opposite results. EIF4A3 is an RNA-binding protein of hsa_circ_0005397, which overexpressed in paired HCC tissues and cell lines. In addition, expression of hsa_circ_0005397 decreased equally when EIF4A3 was depleted. RIP assays and correlation assay estimated that EIF4A3 could interacted with hsa_circ_0005397. Knockdown of EIF4A3 could reverse hsa_circ_0005397 function in HCC progression. CONCLUSIONS: Hsa_circ_0005397 promotes progression of hepatocellular carcinoma through EIF4A3. These research findings may provide novel clinical value for hepatocellular carcinoma.

The crucial role of locus coeruleus noradrenergic neurons in the interaction between acute sleep disturbance and headache.

BACKGROUND: Both epidemiological and clinical studies have indicated that headache and sleep disturbances share a complex relationship. Although headache and sleep share common neurophysiological and anatomical foundations, the mechanism underlying their interaction remains poorly understood. The structures of the diencephalon and brainstem, particularly the locus coeruleus (LC), are the primary sites where the sleep and headache pathways intersect. To better understand the intricate nature of the relationship between headache and sleep, our study focused on investigating the role and function of noradrenergic neurons in the LC during acute headache and acute sleep disturbance. METHOD: To explore the relationship between acute headache and acute sleep disturbance, we primarily employed nitroglycerin (NTG)-induced migraine-like headache and acute sleep deprivation (ASD) models. Initially, we conducted experiments to confirm that ASD enhances headache and that acute headache can lead to acute sleep disturbance. Subsequently, we examined the separate roles of the LC in sleep and headache. We observed the effects of drug-induced activation and inhibition and chemogenetic manipulation of LC noradrenergic neurons on ASD-induced headache facilitation and acute headache-related sleep disturbance. This approach enabled us to demonstrate the bidirectional function of LC noradrenergic neurons. RESULTS: Our findings indicate that ASD facilitated the development of NTG-induced migraine-like headache, while acute headache affected sleep quality. Furthermore, activating the LC reduced the headache threshold and increased sleep latency, whereas inhibiting the LC had the opposite effect. Additional investigations demonstrated that activating LC noradrenergic neurons further intensified pain facilitation from ASD, while inhibiting these neurons reduced this pain facilitation. Moreover, activating LC noradrenergic neurons exacerbated the impact of acute headache on sleep quality, while inhibiting them alleviated this influence. CONCLUSION: The LC serves as a significant anatomical and functional region in the interaction between acute sleep disturbance and acute headache. The involvement of LC noradrenergic neurons is pivotal in facilitating headache triggered by ASD and influencing the effects of headache on sleep quality.

Photosensitive Peptide Enabling Molecular Recognition Tandem Covalent Biosensing for Evaluating and Preventing Venous Thromboembolism in Dravet Syndrome.

Venous thromboembolism (VTE) is a complication of Dravet syndrome, accounting for many unexpected deaths. To control VTE more tightly and to prevent such tragedies, a reliable and low-cost risk evaluation assay is urgently needed, so that the daily routine of VTE risk evaluation can be established. In this work, we have developed such an assay combining the photocatalytic activity of Bengal red to trigger the target-specific self-splicing of a peptide probe and subsequent cross-linking with P-selectin. Following this protocol, a robust and one-step detection can be achieved, without using any costly enzymes, antibodies, or nanomaterials, but the same level of sensitivity and robustness can be attained. Specifically, the effect of epilepsy on elevating platelet P-selectin can be observed by using the proposed assay. This may in the near future promise a new method for evaluating the side effects of P-selectin through relatively noninvasive peripheral blood sampling.

Proximity Amplification-Enabled Electrochemical Analysis of Tumor-Associated Glycoprotein Biomarkers.

Glycoproteins produced and secreted from specific cells and tissues are associated with several diseases and emerge as typical biomarkers to provide useful information in cancer diagnosis considering their abnormal expression levels. In this work, we design a universal method to achieve the accurate and sensitive analysis of tumor-associated glycoprotein biomarkers based on both carbohydrate recognition and protein recognition at the same protein surface. The byproduct of dual recognition-induced proximity amplification, pyrophosphate, triggers the disassembly of methylene blue-encapsulated metal-organic frameworks, MB@ZIF-90. As a result, methylene blue molecules are released to arouse amplified electrochemical responses for glycoprotein analysis. Experimental results demonstrate the high-accuracy analysis of carcinoembryonic antigen, a typical glycoprotein biomarker in cancer diagnosis, in a linear range of 0.001-100 ng mL-1 with a low limit of detection of 0.419 pg mL-1. The method also displays satisfactory specificity and recoveries in complex serum samples and proves good versatility by adopting two other tumor-associated glycoprotein biomarkers, α-fetoprotein and mucin-1, as the targets. Therefore, this work provides a valuable tool for the analysis of glycoprotein biomarkers, which may be of great potential in early warning of malignant tumors in clinical applications.

MYD88 L265P elicits mutation-specific ubiquitination to drive NF-κB activation and lymphomagenesis.

Myeloid differentiation primary response protein 88 (MYD88) is a critical universal adapter that transduces signaling from Toll-like and interleukin receptors to downstream nuclear factor-κB (NF-κB). MYD88L265P (leucine changed to proline at position 265) is a gain-of-function mutation that occurs frequently in B-cell malignancies such as Waldenstrom macroglobulinemia. In this study, E3 ligase RING finger protein family 138 (RNF138) catalyzed K63-linked nonproteolytic polyubiquitination of MYD88L265P, resulting in enhanced recruitment of interleukin-1 receptor-associated kinases and elevated NF-κB activation. However, RNF138 had little effect on wild-type MYD88 (MYD88WT). With either RNF138 knockdown or mutation on MYD88 ubiquitination sites, MYD88L265P did not constitutively activate NF-κB. A20, a negative regulator of NF-κB signaling, mediated K48-linked polyubiquitination of RNF138 for proteasomal degradation. Depletion of A20 further augmented MYD88L265P-mediated NF-κB activation and lymphoma growth. Furthermore, A20 expression correlated negatively with RNF138 expression and NF-κB activation in lymphomas with MYD88L265P and in those without. Strikingly, RNF138 expression correlated positively with NF-κB activation in lymphomas with MYD88L265P, but not in those without it. Our study revealed a novel mutation-specific biochemical reaction that drives B-cell oncogenesis, providing a therapeutic opportunity for targeting oncogenic MYD88L265P, while sparing MYD88WT, which is critical to innate immunity.

Novel ß1,4 N-acetylglucosaminyltransferase in de novo enzymatic synthesis of hyaluronic acid oligosaccharides.

The efficiency of de novo synthesis of hyaluronic acid (HA) using Pasteurella multocida hyaluronate synthase (PmHAS) is limited by its low catalytic activity during the initial reaction steps when monosaccharides are the acceptor substrates. In this study, we identified and characterized a ß-1,4-N-acetylglucosaminyl-transferase (EcGnT) derived from the O-antigen gene synthesis cluster of Escherichia coli O8:K48:H9. Recombinant ß1,4 EcGnT effectively catalyzed the production of HA disaccharides when the glucuronic acid monosaccharide derivative 4-nitrophenyl-ß-D-glucuronide (GlcA-pNP) was used as the acceptor. Compared with PmHAS, ß1,4 EcGnT exhibited superior N-acetylglucosamine transfer activity (~ 12-fold) with GlcA-pNP as the acceptor, making it a better option for the initial step of de novo HA oligosaccharide synthesis. We then developed a biocatalytic approach for size-controlled HA oligosaccharide synthesis using the disaccharide produced by ß1,4 EcGnT as a starting material, followed by stepwise PmHAS-catalyzed synthesis of longer oligosaccharides. Using this approach, we produced a series of HA chains of up to 10 sugar monomers. Overall, our study identifies a novel bacterial ß1,4 N-acetylglucosaminyltransferase and establishes a more efficient process for HA oligosaccharide synthesis that enables size-controlled production of HA oligosaccharides. KEY POINTS: • A novel ß-1,4-N-acetylglucosaminyl-transferase (EcGnT) from E. coli O8:K48:H9. • EcGnT is superior to PmHAS for enabling de novo HA oligosaccharide synthesis. • Size-controlled HA oligosaccharide synthesis relay using EcGnT and PmHAS.

Subarachnoid hemorrhage caused by spontaneous intracranial hypotension: two rare cases report.

BACKGROUND: Spontaneous intracranial hypotension (SIH) combined with subarachnoid hemorrhage (SAH) has rarely been reported. Herein, we report two patients with SIH who suffered from diffuse non-aneurysmal SAH and expanded the symptom spectrum of SIH. CASE PRESENTATION: (1) A 55-year-old male was diagnosed with SIH based on orthostatic headache and diffuse pachymeningeal enhancement on brain MRI. One more month later, his headache was exacerbated, and brain CT showed diffuse SAH. Lumber puncture showed bloody cerebrospinal fluid (CSF) with a low CSF pressure of 20 mmH2O after a 30 mL intrathecal injection of saline. The patient was treated with a lumbar epidural blood patch and recovered. (2) A 41-year-old male presented with orthostatic headache and nuchal pain. The brain CT scan confirmed the diagnosis of SAH. Brain MRI revealed diffuse dural thickening and bilateral frontoparietal subdural fluid collection. Lumber puncture showed bloody CSF with low CSF pressure. Then, an epidural blood patch was performed with satisfactory results. CONCLUSION: Dilation and rupture of intracranial venous structures might play significant roles in SIH combined with SAH. We should be alert to SIH patients who develop a new persistent severe headache without relief after lying down or a suddenly changed state of consciousness.

Interfacial reactivity-modulated fluorescent metal-organic frameworks for sensitive detection of interferon-γ towards tuberculosis diagnosis.

A new aptamer-based method has been developed for interferon-γ (IFN-γ) detection by utilizing interface reactivity-modulated fluorescent metal-organic frameworks (MOFs). Specifically, the binding of IFN-γ to its aptamer decreases the interface reactivity between the biotin-labeled aptamer and the streptavidin-functionalized magnetic beads by generating significant steric effects. As a result, several biotin-labeled aptamers escape from the enrichment of magnetic beads and remain in the supernatant, which subsequently undergo the terminal deoxynucleotidyl transferase-catalyzed polymerization elongation. Along with the elongation, pyrophosphate is continuously produced as the by-product, triggering the decomposition of fluorescent MOFs to generate a remarkable fluorescent response with the excitation/emission wavelength of 610 nm/685 nm. Experimental results show that the method enables the detection of IFN-γ in the range 0.06 fM to 6 pM with a detection limit of 0.057 fM. The method also displays high specificity and repeatability with an average relative standard deviation of 2.04%. Moreover, the method demonstrates satisfactory recoveries from 96.3 to 105.5% in serum samples and excellent utility in clinical blood samples. Therefore, this work may provide a valuable tool for IFN-γ detection and is expected to be of high potential in tuberculosis diagnosis in the future.

[Antiarrhythmic active components in traditional Chinese medicine acting on potassium channels].

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.

Molecular Characterization of Exosomes for Subtype-Based Diagnosis of Breast Cancer.

Breast cancer is very heterogeneous and the most frequently diagnosed cancer worldwide, and precise therapy targeting specific subtypes may improve the survival rates of breast cancer patients. In this study, we designed a biomimetic vesicle by camouflaging catalytic DNA machinery with a breast cancer cell membrane, which enabled the molecular classification of circulating exosomes for subtype-based diagnosis through homotypic recognition. In addition, the vesicles specifically targeted and fused with breast cancer exosomes with phenotypic homology and manipulated the DNA machinery to amplify electrochemical signaling using exosomal RNA as an endogenous trigger. The biomimetic vesicles prepared with MCF-7 cancer cell-derived membranes were shown to recognize estrogen receptor-positive breast cancer exosomes and exhibited a low detection limit of 557 particles mL-1 with microRNA-375 used as the endogenous biomarker. Furthermore, the biomimetic vesicles prepared with MDA-MB-231 cancer cell-derived membranes displayed satisfactory performance in a homotypic analysis of triple-negative breast cancer exosomes with a potential therapeutic target, PD-L1 mRNA, used as the endogenous biomarker. Most importantly, cross-validation experiments confirmed the high accuracy and selectivity of this homotypic recognition-driven analysis for molecular subtyping of breast cancer. When applied to clinical samples of breast cancer patients, the vesicles demonstrated feasibility and reliability for evaluating the molecular features of cancer cell-derived exosomes and enabled stage-specific monitoring of breast cancer patients because the electrochemical signals showed a positive correlation with disease progression. Therefore, this work may provide new ideas for the precise diagnosis and personalized treatment of breast cancer patients throughout the whole disease process.

Programmable DNA-Fueled Electrochemical Analysis of Lung Cancer Exosomes.

Molecular diagnostics devoted to discover and monitor new biomarkers is gaining increasing attention in clinical diagnosis. In this work, a programmable DNA-fueled electrochemical analysis strategy is designed for the determination of an emerging biomarker in lung cancer, PD-L1-expressing exosomes. Specifically, PD-L1-expressing exosomes are first enriched onto magnetic beads functionalized with PD-L1 antibody and are able to interact with cholesterol-modified hairpin templates. Then, programmable DNA synthesis starts from the hairpin template-triggered primer exchange reaction and generates a large number of extension products to activate the trans-cleavage activity of CRISPR-Cas12a. After that, CRISPR-Cas12a-catalyzed random cleavage boosts the degradation of methylene blue-labeled signaling strands, so electro-active methylene blue molecules can be enriched onto a cucurbit[7]uril-modified electrode for quantitative determination. Our method demonstrates high sensitivity and specificity toward electrochemical analysis of PD-L1-expressing exosomes in the range from 103 to 109 particles mL-1 with a low detection limit of 708 particles mL-1. When applied to clinical samples, our method reveals an elevated level of circulating PD-L1-expressing exosomes in lung cancer patients, especially for those at the advanced stages. Therefore, our method may provide new insight into liquid biopsy for better implementation of immunotherapy in lung cancer in the future.

An optimal tracheal tube preshaping strategy for endotracheal intubation using video laryngoscopy: a randomized controlled trial.

Although video laryngoscopy solves the problem of glottis exposure, it is difficult to deliver the tube to the glottic opening when the tracheal tube is unevenly shaped. This study aimed to compare the effects of different tube shapes on the first-pass success (FPS) rate in patients undergoing video laryngoscopy-assisted tracheal intubation. Three hundred patients above 18 years of age who underwent general anaesthesia and required endotracheal intubation were included in the study. The participants were randomly allocated to three groups with 100 participants in each group as follows: Group A, video laryngoscopes with a self-equipped stylet are used for tube preshaping; Group B: curvature of the video laryngoscope blade is modelled for tube preshaping; Group C: tube preshaping angle is consistent with the video laryngoscope blade, and the bending point is set 1 cm above the tracheal tube cuff. The primary outcome was FPS rates. The secondary outcomes included time to tracheal intubation, haemodynamic responses and adverse events. No significant differences in patient characteristics or airway assessments were noted (P > 0.05). Compared with Groups A, Group B and Group C exhibited a higher FPS rate (68% vs. 86% vs. 92%; P < 0.001). However, there is no significant difference in FPS rate between Group B and Group C (P > 0.05). And the time to tracheal intubation in Group C was significantly less than that in Group A and Group B (22.21 ± 4.01 vs. 19.92 ± 4.11 vs. 17.71 ± 3.47; P < 0.001). The straight-to-cuff stylet preshape angulation of curvature of the blade could provide a higher FPS rate and shorter time to tracheal intubation during video laryngoscopy-assisted endotracheal intubation. Trial registration: Chinese Clinical Trial Registry, ChiCTR1900026019.

Gradually shifting clinical phenomics in migraine spectrum: a cross-sectional, multicenter study of 5438 patients.

BACKGROUND: The aim of the study was to investigate whether MwoA and MwA are different manifestations of a single disease, distinct clinical entities, or located at two poles of a spectrum. METHODS: In this cross-sectional study, 5438 patients from 10 hospitals in China were included: 4651 were diagnosed with migraine without aura (MwoA) and 787 with migraine with aura (MwA). We used a validated standardized electronic survey to collect multidimensional data on headache characteristics and evaluated the similarities and differences between migraine subtypes. To distinguish migraine subtypes, we employed correlational analysis, factor analysis of mixed data (FAMD), and decision tree analysis. RESULTS: Compared to MwA, MwoA had more severe headaches, predominantly affected females, were more easily produced by external factors, and were more likely to have accompanying symptoms and premonitory neck stiffness. Patients with MwA are heterogeneous, according to correlation analysis; FAMD divided the subjects into three clear clusters. The majority of the differences between MwoA and MwA were likewise seen when typical aura with migraine headache (AWM) and typical aura with non-migraine headache (AWNM) were compared. Furthermore, decision trees analysis revealed that the chaotic MwA data reduced the decision tree's accuracy in distinguishing MwoA from MwA, which was significantly increased by splitting MwA into AWM and AWNM. CONCLUSIONS: The clinical phenomics of headache phenotype varies gradually from MwoA to AWM and AWNM, and AWM is a mid-state between MwoA and AWNM. We tend to regard migraine as a spectrum disorder, and speculate that different migraine subtypes have different "predominant regions" that generate attacks.

Similarities and differences between SUNCT and SUNA: a cross-sectional, multicentre study of 76 patients in China.

BACKGROUND: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) have not been evaluated sufficiently due to limited data, particularly in China. METHODS: Patients with SUNCT or SUNA treated in a tertiary headache centre or seven other headache clinics of China between April 2009 and July 2022 were studied; we compared their demographics and clinical phenotypes. RESULTS: The 45 patients with SUNCT and 31 patients with SUNA had mean ages at onset of 37.22 ± 14.54 years and 42.45 ± 14.72 years, respectively. The mean ages at diagnosis of SUNCT and SUNA were 41.62 ± 12.70 years and 48.68 ± 13.80 years, respectively (p = 0.024). The correct diagnosis of SUNCT or SUNA was made after an average of 2.5 (0-20.5) years or 3.0 (0-20.7) years, respectively. Both diseases had a female predominance (SUNCT: 1.14:1; SUNA: 2.10:1). The two diseases differed in the most common attack site (temporal area in SUNCT, p = 0.017; parietal area in SUNA, p = 0.002). Qualitative descriptions of the attacks included stabbing pain (44.7%), electric-shock-like pain (36.8%), shooting pain (25.0%), and slashing pain (18.4%). Lacrimation was the most common autonomic symptom in both SUNCT and SUNA patients, while eyelid oedema, ptosis, and miosis were less frequent. Triggers such as cold air and face washing were shared by the two diseases, and they were consistently ipsilateral to the attack site. CONCLUSIONS: In contrast to Western countries, SUNCT and SUNA in China have a greater female predominance and an earlier onset. The shared core phenotype of SUNCT and SUNA, despite their partial differences, suggests that they are the same clinical entity.