Prediction model of deep vein thrombosis risk after lower extremity orthopedic surgery.

Purpose: This investigation was conceived to engineer and appraise a pioneering clinical nomogram, crafted to bridge the extant chasm in literature regarding the postoperative risk stratification for deep vein thrombosis (DVT) in the aftermath of lower extremity orthopedic procedures. This novel tool offers a sophisticated and discerning algorithm for risk prediction, heretofore unmet by existing methodologies. Methods: In this retrospective observational study, clinical records of hospitalized patients who underwent lower extremity orthopedic surgery were collected at the Wuxi TCM Hospital Affiliated to the Nanjing University of Chinese Medicine between Jan 2017 and Oct 2019. The univariate and multivariate analysis with the backward stepwise method was applied to select features for the predictive nomogram. The performance of the nomogram was evaluated with respect to its discriminant capability, calibration ability, and clinical utility. Result: A total of 5773 in-hospital patients were eligible for the study, with the incidence of deep vein thrombosis being approximately 1 % in this population. Among 31 variables included, 5 of them were identified to be the predictive features in the nomogram, including age, mean corpuscular hemoglobin concentration (MCHC), D-dimer, platelet distribution width (PDW), and thrombin time (TT). The area under the receiver operating characteristic (ROC) curve in the training and validation cohort was 85.9 % (95%CI: 79.96 %-90.04 %) and 85.7 % (95%CI: 78.96 %-90.69 %), respectively. Both the calibration curves and decision curve analysis demonstrated the overall satisfactory performance of the model. Conclusion: Our groundbreaking nomogram is distinguished by its unparalleled accuracy in discriminative and calibrating functions, complemented by its tangible clinical applicability. This innovative instrument is set to empower clinicians with a robust framework for the accurate forecasting of postoperative DVT, thus facilitating the crafting of bespoke and prompt therapeutic strategies, aligning with the rigorous standards upheld by the most esteemed biomedical journals.

Throat microbiota drives alterations in pulmonary alveolar microbiota in patients with septic ARDS.

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

Functional Analysis and Tissue-Specific Expression of Calcitonin and CGRP with RAMP-Modulated Receptors CTR and CLR in Chickens.

Calcitonin (CT) and calcitonin gene-related peptide (CGRP) are critical regulators of calcium balance and have extensive implications for vertebrate physiological processes. This study explores the CT and CGRP signaling systems in chickens through cloning and characterization of the chicken calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR), together with three receptor activity-modifying proteins (RAMPs). We illuminated the functional roles for chickens between the receptors examined alone and in RAMP-associated complexes using luciferase reporter assays. Chicken CTRs and CLRs stimulated the cAMP/PKA and MAPK/ERK signaling pathways, signifying their functional receptor status, with CT showing appreciable ligand activity at nanomolar concentrations across receptor combinations. Notably, it is revealed that chicken CLR can act as a functional receptor for CT without or with RAMPs. Furthermore, we uncovered a tissue-specific expression profile for CT, CGRP, CTR, CLR, and RAMPs in chickens, indicating the different physiological roles across various tissues. In conclusion, our data establish a clear molecular basis to reveal information on CT, CGRP, CTR, CLR, and RAMPs in chickens and contribute to understanding the conserved or divergent functions of this family in vertebrates.

SSTR2 Mediates the Inhibitory Effect of SST/CST on Lipolysis in Chicken Adipose Tissue.

Somatostatin shows an anti-lipolytic effect in both chickens and ducks. However, its molecular mediator remains to be identified. Here, we report that somatostatin type 2 receptor (SSTR2) is expressed at a high level in chicken adipose tissue. In cultured chicken adipose tissue, the inhibition of glucagon-stimulated lipolysis by somatostatin was blocked by an SSTR2 antagonist (CYN-154086), supporting an SSTR2-mediated anti-lipolytic effect. Furthermore, a significant pro-proliferative effect was detected in SST28-treated immortalized chicken preadipocytes (ICP-1), and this cell proliferative effect may be mediated through the MAPK/ERK signaling pathway activated by SSTR2. In summary, our results demonstrate that SSTR2 may regulate adipose tissue development by affecting the number and volume of adipocytes in chickens.

Roxithromycin exposure induces motoneuron malformation and behavioral deficits of zebrafish by interfering with the differentiation of motor neuron progenitor cells.

Roxithromycin (ROX), a commonly used macrolide antibiotic, is extensively employed in human medicine and livestock industries. Due to its structural stability and resistance to biological degradation, ROX persists as a resilient environmental contaminant, detectable in aquatic ecosystems and food products. However, our understanding of the potential health risks to humans from continuous ROX exposure remains limited. In this study, we used the zebrafish as a vertebrate model to explore the potential developmental toxicity of early ROX exposure, particularly focusing on its effects on locomotor functionality and CaP motoneuron development. Early exposure to ROX induces marked developmental toxicity in zebrafish embryos, significantly reducing hatching rates (n=100), body lengths (n=100), and increased malformation rates (n=100). The zebrafish embryos treated with a corresponding volume of DMSO (0.1%, v/v) served as vehicle controls (veh). Moreover, ROX exposure adversely affected the locomotive capacity of zebrafish embryos, and observations in transgenic zebrafish Tg(hb9:eGFP) revealed axonal loss in motor neurons, evident through reduced or irregular axonal lengths (n=80). Concurrently, abnormal apoptosis in ROX-exposed zebrafish embryos intensified alongside the upregulation of apoptosis-related genes (bax, bcl2, caspase-3a). Single-cell sequencing further disclosed substantial effects of ROX on genes involved in the differentiation of motor neuron progenitor cells (ngn1, olig2), axon development (cd82a, mbpa, plp1b, sema5a), and neuroimmunity (aplnrb, aplnra) in zebrafish larvae (n=30). Furthermore, the CaP motor neuron defects and behavioral deficits induced by ROX can be rescued by administering ngn1 agonist (n=80). In summary, ROX exposure leads to early-life abnormalities in zebrafish motor neurons and locomotor behavior by hindering the differentiation of motor neuron progenitor cells and inducing abnormal apoptosis.

Nanoplastic Exposure Mediates Neurodevelopmental Toxicity by Activating the Oxidative Stress Response in Zebrafish (Danio rerio).

The global accumulation and adverse effects of nanoplastics (NPs) are a growing concern for the environment and human health. In recent years, more and more studies have begun to focus on the toxicity of plastic particles for early animal development. Different particle sizes of plastic particles have different toxicities to biological development. Nevertheless, the potential toxicological effects of 20 nm NPs, especially on neurodevelopment, have not been well investigated. In this paper, we used fluorescence microscopy to determine neurotoxicity in zebrafish at different concentrations of NPs. Moreover, the behavioral analysis demonstrated that NPs induced abnormal behavior of zebrafish. The results revealed developmental defects in zebrafish embryos after exposure to different concentrations (0, 0.3, 3, and 9 mg/L) of NPs. The morphological deformities, including abnormal body length and the rates of heart, survival, and hatching, were induced after NP exposure in zebrafish embryos. In addition, the development of primary motor neurons was observed the inhibitory effects of NPs on the length, occurrence, and development of primary motor neurons in Tg(hb9:GFP). Quantitative polymerase chain reaction analysis suggested that exposure to NPs significantly affects the expression of the genes involved in the occurrence and differentiation of primary motor neurons in zebrafish. Furthermore, the indicators associated with oxidative stress and apoptosis were found to be modified in zebrafish embryos at 24 and 48 h following exposure to NPs. Our findings demonstrated that NPs could cause toxicity in primary motor neurons by activating the oxidative stress response and inducing apoptosis, consequently impairing motor performance.

Dynamic lymphocyte-CRP ratio as a predictor: a single-centre retrospective study on disease severity and progression in adult COVID-19 patients.

OBJECTIVE: To assess the efficacy of dynamic changes in lymphocyte-C-reactive protein ratio (LCR) on differentiating disease severity and predicting disease progression in adult patients with Coronavirus disease 2019 (COVID-19). METHODS: This single-centre retrospective study enrolled adult COVID-19 patients categorized into moderate, severe and critical groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data were collected. LCR and sequential organ failure assessment (SOFA) score were calculated. Lymphocyte count and C-reactive protein (CRP) levels were monitored on up to four occasions. Disease severity was determined concurrently with each LCR measurement. RESULTS: This study included 145 patients assigned to moderate (n = 105), severe (n = 33) and critical groups (n = 7). On admission, significant differences were observed among different disease severity groups including age, comorbidities, neutrophil proportion, lymphocyte count and proportion, D-Dimer, albumin, total bilirubin, direct bilirubin, indirect bilirubin, CRP and SOFA score. Dynamic changes in LCR showed significant differences across different disease severity groups at different times, which were significantly inversely correlated with disease severity of COVID-19, with correlation coefficients of -0.564, -0.548, -0.550 and -0.429 at four different times. CONCLUSION: Dynamic changes in LCR can effectively differentiate disease severity and predict disease progression in adult COVID-19 patients.

Predictive and Prognostic Potentials of Lymphocyte-C-Reactive Protein Ratio Upon Hospitalization in Adult Patients with Acute Pancreatitis.

Purpose: In this study, our objective was to investigate the potential utility of lymphocyte-C-reactive protein ratio (LCR) as a predictor of disease progression and a screening tool for intensive care unit (ICU) admission in adult patients with acute pancreatitis (AP). Methods: We included a total of 217 adult patients with AP who were admitted to the First Affiliated Hospital of Harbin Medical University between July 2019 and June 2022. These patients were categorized into three groups: mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), based on the presence and duration of organ dysfunction. Various demographic and clinical data were collected and compared among different disease severity groups. Results: Height, diabetes, lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet count (PLT), D-Dimer, albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), glucose (GLU), calcium ion (Ca2+), C-reactive protein (CRP), procalcitonin (PCT), hospitalization duration, ICU admission, need for BP, LCR, sequential organ failure assessment (SOFA) score, bedside index for severity in AP (BISAP) score, and modified Marshall score showed significant differences across different disease severity groups upon hospitalization. Notably, there were significant differences in LCR between the MAP group and the MSAP and SAP combined group, and the MAP and MSAP combined group and the SAP group, and adult AP patients with ICU admission and those without ICU admission upon hospitalization. Conclusion: In summary, LCR upon hospitalization can be utilized as a simple and reliable predictor of disease progression and a screening tool for ICU admission in adult patients with AP.

The nearby atomic environment effect on an Fe-N-C catalyst for the oxygen reduction reaction: a density functional theory-based study.

Fe-N-C materials have emerged as highly promising non-noble metal catalysts for oxygen reduction reactions (ORRs) in polymer electrolyte membrane fuel cells. However, they still encounter several challenges that need to be addressed. One of these challenges is establishing an atomic environment near the Fe-N4 site, which can significantly affect catalyst activity. To investigate this, herein, we employed density functional theory (DFT). According to our computational analysis of the Gibbs free energy of the reaction based on the computational hydrogen electrode (CHE) model, we successfully determined two C-O-C structures near the Fe-N4 site (referred to as str-11) with the highest limiting potential (0.813 V). Specifically, in the case of O-doped structures, the neighboring eight carbon (C) atoms around nitrogen (N) can be categorized into two distinct types: four C atoms (type A) exhibiting high sensitivity to the limiting potential and the remaining four C atoms (type B) displaying inert behavior. Electronic structure analysis further elucidated that a structure will have strong activity if the valence band maximum (VBM) around its gamma point is mainly contributed by dxz, dyz or dz2 orbitals of Fe atoms. Constant-potential calculations showed that str-11 is suitable for the ORR under both acidic and alkaline conditions with a limiting potential of 0.695 V at pH = 1 and 0.926 V at pH = 14, respectively. Additionally, microkinetic simulations indicated the possibility of str-11 as the active site for the ORR under working potential at pH = 14.

Targeted macrophage phagocytosis by Irg1/itaconate axis improves the prognosis of intracerebral hemorrhagic stroke and peritonitis.

BACKGROUND: Macrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene 1 (Irg1) and its metabolic product itaconate inhibit bacterial infection, intracellular viral replication, and inflammation in macrophages. Here we explore whether itaconate regulates phagocytosis. METHODS: Phagocytosis of macrophages was investigated by time-lapse video recording, flow cytometry, and immunofluorescence staining in macrophage/microglia cultures isolated from mouse tissue. Unbiased RNA-sequencing and ChIP-sequencing assays were used to explore the underlying mechanisms. The effects of Irg1/itaconate axis on the prognosis of intracerebral hemorrhagic stroke (ICH) and peritonitis was observed in transgenic (Irg1flox/flox; Cx3cr1creERT/+, cKO) mice or control mice in vivo. FINDINGS: In a mouse model of ICH, depletion of Irg1 in macrophage/microglia decreased its phagocytosis of erythrocytes, thereby exacerbating outcomes (n = 10 animals/group, p < 0.05). Administration of sodium itaconate/4-octyl itaconate (4-OI) promoted macrophage phagocytosis (n = 7 animals/group, p < 0.05). In addition, in a mouse model of peritonitis, Irg1 deficiency in macrophages also inhibited phagocytosis of Staphylococcus aureus (n = 5 animals/group, p < 0.05) and aggravated outcomes (n = 9 animals/group, p < 0.05). Mechanistically, 4-OI alkylated cysteine 155 on the Kelch-like ECH-associated protein 1 (Keap1), consequent in nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and transcriptional activation of Cd36 gene. Blocking the function of CD36 completely abolished the phagocytosis-promoting effects of Irg1/itaconate axis in vitro and in vivo. INTERPRETATION: Our findings provide a potential therapeutic target for phagocytosis-deficiency disorders, supporting further development towards clinical application for the benefit of stroke and peritonitis patients. FUNDING: The National Natural Science Foundation of China (32070735, 82371321 to Q. Li, 82271240 to F. Yang) and the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ202010025033 to Q. Li).

Stellate ganglion block in the treatment of SAPHO syndrome: a case report.

Synovitis, acne, palmoplantar pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare and refractory autoinflammatory disease, and there is no consensus on its treatment. Stellate ganglion block (SGB) blocks sympathetic nerves, ameliorates immune dysfunction, and alleviates stress response, which has been used to treat various chronic pain syndromes, arrhythmias, and post-traumatic stress disorder (PTSD). Also, the SGB has been reported to be successfully used to treat certain skin diseases, autoinflammatory diseases, and menopausal symptoms. In this study, over 3 years of follow-up, we found that SGB successfully intervened the symptoms of SAPHO syndrome, including sternoclavicular joint arthritis and palmoplantar pustulosis.

Andrographolide acts with dexamethasone to inhibit the growth of acute lymphoblastic leukemia CEM­C1 cells via the regulation of the autophagy­dependent PI3K/AKT/mTOR signaling pathway.

Acute lymphoblastic leukemia (ALL) is one of the most common malignant tumor types of the circulatory system. Dexamethasone (DEX) acts on the glucocorticoid (GC) receptor (GR) and is a first-line chemotherapy drug for ALL. However, long-term or high-dose applications of the drug can not only cause adverse reactions, such as osteoporosis and high blood pressure, but can also cause downregulation of GR and lead to drug resistance. In the present study, reverse transcription-quantitative PCR, western blotting and LysoTracker Red staining were used to observe the effects of DEX and andrographolide (AND; a botanical with antitumorigenic properties) combined treatment. It was found that AND enhanced the sensitivity of CEM-C1 cells, a GC-resistant cell line, to DEX, and synergistically upregulated GR both at the transcriptional and post-transcriptional level with DEX. The combination of AND with DEX synergistically alkalized lysosomal lumen and downregulated the expression of autophagy-related genes Beclin1 and microtubule-associated 1 protein light chain 3 (LC3), thereby inhibiting autophagy. Knocking down LC3 expression enhanced GR expression, suggesting that GR was regulated by autophagy. Furthermore, compared with the monotherapy group (AND or DEX in isolation), AND interacted with DEX to activate the autophagy-dependent PI3K/AKT/mTOR signaling pathway by enhancing the phosphorylation of PI3K, AKT and mTOR, thereby decreasing GR degradation and increasing the sensitivity of cells to GCs. In conclusion, the present study demonstrated that AND exhibited a synergistic anti-ALL effect with DEX via upregulation of GR, which was orchestrated by the autophagy-related PI3K/AKT/mTOR signaling pathway. The results of the present study therefore provided novel research avenues and strategies for the treatment of ALL.

Foxp2 deficiency impairs reproduction by modulating the hypothalamic-pituitary-gonadal axis in zebrafish†.

FOXP2 was initially characterized as a transcription factor linked to speech and language disorders. Single-cell RNA sequencing reveals that Foxp2 is enriched in the gonadotrope cluster of the pituitary gland and colocalized with the hormones LHB and FSHB in chickens and mice, implying that FOXP2 might be associated with reproduction in vertebrates. Herein, we investigated the roles of foxp2 in reproduction in a Foxp2-deficient zebrafish model. The results indicated that the loss of Foxp2 inhibits courtship behavior in adult male zebrafish. Notably, Foxp2 deficiency disrupts gonad development, leading to retardation of follicle development and a decrease in oocytes in females at the full-growth stage, among other phenotypes. The transcriptome analysis (RNA-seq) also revealed that differentially expressed genes clustered into the estrogen signaling and ovarian steroidogenesis-related signaling pathways. In addition, we found that Foxp2 deficiency could modulate the hypothalamic-pituitary-gonadal axis, especially the regulation of lhb and fshb expression, in zebrafish. In contrast, the injection of human chorionic gonadotropin, a specific LH agonist, partially rescues Foxp2-impaired reproduction in zebrafish, suggesting that Foxp2 plays an important role in the regulation of reproduction via the hypothalamic-pituitary-gonadal axis in zebrafish. Thus, our findings reveal a new role for Foxp2 in the regulation of reproduction in vertebrates.

Cellular and Molecular Roles of Immune Cells in the Gut-Brain Axis in Migraine.

Migraine is a complex and multi-system dysfunction. The realization of its pathophysiology and diagnosis is developing rapidly. Migraine has been linked to gastrointestinal disorders such as irritable bowel syndrome and celiac disease. There is also direct and indirect evidence for a relationship between migraine and the gut-brain axis, but the exact mechanism is not yet explained. Studies have shown that this interaction appears to be influenced by a variety of factors, such as inflammatory mediators, gut microbiota, neuropeptides, and serotonin pathways. Recent studies suggest that immune cells can be the potential tertiary structure between migraine and gut-brain axis. As the hot interdisciplinary subject, the relationship between immunology and gastrointestinal tract is now gradually clear. Inflammatory signals are involved in cellular and molecular responses that link central and peripheral systems. The gastrointestinal symptoms associated with migraine and experiments associated with antibiotics have shown that the intestinal microbiota is abnormal during the attacks. In this review, we focus on the mechanism of migraine and gut-brain axis, and summarize the tertiary structure between immune cells, neural network, and gastrointestinal tract.

IL-10 protects against OPC ferroptosis by regulating lipid reactive oxygen species levels post stroke.

Accumulation of reactive oxygen species (ROS), especially on lipids, induces massive cell death in neurons and oligodendrocyte progenitor cells (OPCs) and causes severe neurologic deficits post stroke. While small compounds, such as deferoxamine, lipostatin-1, and ferrostatin-1, have been shown to be effective in reducing lipid ROS, the mechanisms by which endogenously protective molecules act against lipid ROS accumulation and subsequent cell death are still unclear, especially in OPCs, which are critical for maintaining white matter integrity and improving long-term outcomes after stroke. Here, using mouse primary OPC cultures, we demonstrate that interleukin-10 (IL-10), a cytokine playing roles in reducing neuroinflammation and promoting hematoma clearance, significantly reduced hemorrhage-induced lipid ROS accumulation and subsequent ferroptosis in OPCs. Mechanistically, IL-10 activated the IL-10R/STAT3 signaling pathway and upregulated the DLK1/AMPK/ACC axis. Subsequently, IL-10 reprogrammed lipid metabolism and reduced lipid ROS accumulation. In addition, in an autologous blood injection intracerebral hemorrhagic stroke (ICH) mouse model, deficiency of the endogenous Il-10, specific knocking out Il10r or Dlk1 in OPCs, or administration of ACC inhibitor was associated with increased OPC cell death, demyelination, axonal sprouting, and the cognitive deficits during the chronic phase of ICH and vice versa. These data suggest that IL-10 protects against OPC loss and white matter injury by reducing lipid ROS, supporting further development of potential clinical applications to benefit patients with stroke and related disorders.

Thaumatin-like protein family genes VfTLP4-3 and VfTLP5 are critical for faba bean's response to drought stress at the seedling stage.

Thaumatin-like proteins (TLPs) are a diverse family of pathogenesis-related proteins (PR-5) found in various plant species. Faba bean is an economically important crop known for its nutritional value and resilience to harsh environmental conditions, including drought. In this study, we conducted a comprehensive analysis of the gene structure, phylogenetics, and expression patterns of TLP genes in faba bean, with a specific focus on their response to drought stress. A total of 10 TLP genes were identified and characterized from the faba bean transcriptome, which could be classified into four distinct groups based on their evolutionary relationships. Conserved cysteine residues and REDDD motifs, which are characteristic features of TLPs, were found in most of the identified VfTLP members, and these proteins were likely to reside in the cytoplasm. Two genes, VfTLP4-3 and VfTLP5, exhibited significant upregulation under drought conditions. Additionally, ectopically expressing VfTLP4-3 and VfTLP5 in tobacco leaves resulted in enhanced drought tolerance and increased peroxidase (POD) activity. Moreover, the protein VfTLP4-3 was hypothesized to interact with glycoside hydrolase family 18 (GH18), endochitinase, dehydrin, Barwin, and aldolase, all of which are implicated in chitin metabolism. Conversely, VfTLP5 was anticipated to associate with peptidyl-prolyl cis-trans isomerase-like 3, a molecule linked to the synthesis of proline. These findings suggest that these genes may play crucial roles in mediating the drought response in faba bean through the regulation of these metabolic pathways, and serve as a foundation for future genetic improvement strategies targeting enhanced drought resilience in this economically important crop.

Compression Degree of Trigeminal Nerve and Type of Conflicting Vessels Determine Short- and Long-Term Complete Pain Relief in Adult Patients with Primary Trigeminal Neuralgia After Microvascular Decompression: A Three-Year Retrospective Study of 200 Adult Patients with Primary Trigeminal Neuralgia.

Objective: In this study, we aimed to explore the demographic and clinical factors that could determine short- and long-term complete pain relief (CPR) in adult patients with primary trigeminal neuralgia (PTN) after microvascular decompression (MVD) to guide clinical practice. Methods: This single-center retrospective study included adult patients with PTN who underwent MVD as their initial neurosurgical procedure in the Department of Neurosurgery at the Second Affiliated Hospital of Harbin Medical University from January 2017 to December 2019 and completed a 3-year post-surgery follow-up. Demographic and clinical information was obtained from medical records. Pain relief of adult patients with PTN at various time points after sufficient decompression of trigeminal nerve (TN) during MVD was determined and classified by the patient's subjective response and medications use. Pain relief of local patients was evaluated by outpatient follow-up at various time points, whereas that of local cases who could not return to outpatient or non-local cases was assessed through telephone or WeChat. Results: In univariate analysis, compression degree of TN and type of conflicting vessels constantly showed significant differences between the two groups at 3 months, 6 months, 1 year, 2 years, and 3 years after MVD. Compression degree of TN and type of conflicting vessels at various time points after MVD were always the related factors to CPR in logistic regression analysis, with the former having the greatest impact. The areas under the receiver operating characteristic (ROC) curve of CPR at various time points after MVD were 0.937, 0.874, 0.879, 0.864, and 0.869, respectively. Conclusion: In summary, compression degree of TN and type of conflicting vessels can determine short- and long-term CPR in adult patients with PTN after MVD.

Causal relationship between gut Prevotellaceae and risk of sepsis: a two-sample Mendelian randomization and clinical retrospective study in the framework of predictive, preventive, and personalized medicine.

Objective: Gut microbiota is closely related to sepsis. Recent studies have suggested that Prevotellaceae could be associated with intestinal inflammation; however, the causal relationship between Prevotellaceae and sepsis remains uncertain. From the perspective of predictive, preventive, and personalized medicine (PPPM), exploring the causal relationship between gut Prevotellaceae and sepsis could provide opportunity for targeted prevention and personalized treatment. Methods: The genome-wide association study (GWAS) summary-level data of Prevotellaceae (N = 7738) and sepsis were obtained from the Dutch Microbiome Project and the UK Biobank (sepsis, 1380 cases; 429,985 controls). MR analysis was conducted to estimate the associations between Prevotellaceae and sepsis risk. The 16S rRNA sequencing analysis was conducted to calculate the relative abundance of Prevotellaceae in sepsis patients to explore the relationship between Prevotellaceae relative abundance and the 28-day mortality. Results: Genetic liability to f__Prevotellaceae (OR, 1.91; CI, 1.35-2.71; p = 0.0003) was associated with a high risk of sepsis with inverse-variance weighted (IVW). The median Prevotellaceae relative abundance in non-survivors was significantly higher than in survivors (2.34% vs 0.17%, p < 0.001). Multivariate analysis confirmed that Prevotellaceae relative abundance (OR, 1.10; CI, 1.03-1.22; p = 0.027) was an independent factor of 28-day mortality in sepsis patients. ROC curve analysis indicated that Prevotellaceae relative abundance (AUC: 0.787, 95% CI: 0.671-0.902, p = 0.0003) could predict the prognosis of sepsis patients. Conclusion: Our results revealed that Prevotellaceae was causally associated with sepsis and affected the prognosis of sepsis patients. These findings may provide insights to clinicians on developing improved sepsis PPPM strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00340-6.

Efficient estimation for large-scale linkage disequilibrium patterns of the human genome.

In this study, we proposed an efficient algorithm (X-LD) for estimating linkage disequilibrium (LD) patterns for a genomic grid, which can be of inter-chromosomal scale or of small segments. Compared with conventional methods, the proposed method was significantly faster, dropped from O(nm2) to O(n2m)-n the sample size and m the number of SNPs, and consequently we were permitted to explore in depth unknown or reveal long-anticipated LD features of the human genome. Having applied the algorithm for 1000 Genome Project (1KG), we found (1) the extended LD, driven by population structure, universally existed, and the strength of inter-chromosomal LD was about 10% of their respective intra-chromosomal LD in relatively homogeneous cohorts, such as FIN, and to nearly 56% in admixed cohort, such as ASW. (2) After splitting each chromosome into upmost of more than a half million grids, we elucidated the LD of the HLA region was nearly 42 folders higher than chromosome 6 in CEU and 11.58 in ASW; on chromosome 11, we observed that the LD of its centromere was nearly 94.05 folders higher than chromosome 11 in YRI and 42.73 in ASW. (3) We uncovered the long-anticipated inversely proportional linear relationship between the length of a chromosome and the strength of chromosomal LD, and their Pearson's correlation was on average over 0.80 for 26 1KG cohorts. However, this linear norm was so far perturbed by chromosome 11 given its more completely sequenced centromere region. Uniquely chromosome 8 of ASW was found most deviated from the linear norm than any other autosomes. The proposed algorithm has been realized in C++ (called X-LD) and is available at https://github.com/gc5k/gear2, and can be applied to explore LD features in any sequenced populations.