TRPC3/6 Channels Mediate Mechanical Pain Hypersensitivity via Enhancement of Nociceptor Excitability and of Spinal Synaptic Transmission.

Patients with tissue inflammation or injury often experience aberrant mechanical pain hypersensitivity, one of leading symptoms in clinic. Despite this, the molecular mechanisms underlying mechanical distortion are poorly understood. Canonical transient receptor potential (TRPC) channels confer sensitivity to mechanical stimulation. TRPC3 and TRPC6 proteins, coassembling as heterotetrameric channels, are highly expressed in sensory neurons. However, how these channels mediate mechanical pain hypersensitivity has remained elusive. It is shown that in mice and human, TRPC3 and TRPC6 are upregulated in DRG and spinal dorsal horn under pathological states. Double knockout of TRPC3/6 blunts mechanical pain hypersensitivity, largely by decreasing nociceptor hyperexcitability and spinal synaptic potentiation via presynaptic mechanism. In corroboration with this, nociceptor-specific ablation of TRPC3/6 produces comparable pain relief. Mechanistic analysis reveals that upon peripheral inflammation, TRPC3/6 in primary sensory neurons get recruited via released bradykinin acting on B1/B2 receptors, facilitating BDNF secretion from spinal nociceptor terminals, which in turn potentiates synaptic transmission through TRPC3/6 and eventually results in mechanical pain hypersensitivity. Antagonizing TRPC3/6 in DRG relieves mechanical pain hypersensitivity in mice and nociceptor hyperexcitability in human. Thus, TRPC3/6 in nociceptors is crucially involved in pain plasticity and constitutes a promising therapeutic target against mechanical pain hypersensitivity with minor side effects.

A Simple Score (MOG-AR) to Identify Individuals at High Risk of Relapse After MOGAD Attack.

BACKGROUND AND OBJECTIVES: To identify predictors for relapse in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to develop and validate a simple risk score for predicting relapse. METHODS: In China National Registry of Neuro-Inflammatory Diseases (CNRID), we identified patients with MOGAD from March 2023 and followed up prospectively to September 2023. The primary endpoint was MOGAD relapse, confirmed by an independent panel. Patients were randomly divided into model development (75%) and internal validation (25%) cohorts. Prediction models were constructed and internally validated using Andersen-Gill models. Nomogram and relapse risk score were generated based on the final prediction models. RESULTS: A total of 188 patients (comprising 612 treatment episodes) were included in cohorts. Female (HR: 0.687, 95% CI 0.524-0.899, p = 0.006), onset age 45 years or older (HR: 1.621, 95% CI 1.242-2.116, p < 0.001), immunosuppressive therapy (HR: 0.338, 95% CI 0.239-0.479, p < 0.001), oral corticosteroids >3 months (HR 0.449, 95% CI 0.326-0.620, p < 0.001), and onset phenotype (p < 0.001) were identified as factors associated with MOGAD relapse. A predictive score, termed MOG-AR (Immunosuppressive therapy, oral Corticosteroids, Onset Age, Sex, Attack phenotype), derived in prediction model, demonstrated strong predictive ability for MOGAD relapse. MOG-AR score of 13-16 indicates a higher risk of relapse (HR: 3.285, 95% CI 1.473-7.327, p = 0.004). DISCUSSION: The risk of MOGAD relapse seems to be predictable. Further validation of MOG-AR score developed from this cohort to determine appropriate treatment and monitoring frequency is warranted. TRIAL REGISTRATION INFORMATION: CNRID, NCT05154370, registered December 13, 2021, first enrolled December 15, 2021.

Clinical features of COVID-19 infection in patients with myasthenia gravis: a real-world retrospective study.

Objective: We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic. Methods: This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records. Results: The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation. Conclusion: Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.

Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway.

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells, and can thus be used as substitutes for stem cells in stem cell therapy, thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments. This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke. However, the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear, presenting challenges for clinical translation. To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside, we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke. We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis. The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase, mammalian target of rapamycin, and protein kinase B, and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor. These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Finally, we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile. Therefore, human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

Human neural stem cell-derived artificial organelles to improve oxidative phosphorylation.

Oxidative phosphorylation (OXPHOS) in the mitochondrial inner membrane is a therapeutic target in many diseases. Neural stem cells (NSCs) show progress in improving mitochondrial dysfunction in the central nervous system (CNS). However, translating neural stem cell-based therapies to the clinic is challenged by uncontrollable biological variability or heterogeneity, hindering uniform clinical safety and efficacy evaluations. We propose a systematic top-down design based on membrane self-assembly to develop neural stem cell-derived oxidative phosphorylating artificial organelles (SAOs) for targeting the central nervous system as an alternative to NSCs. We construct human conditionally immortal clone neural stem cells (iNSCs) as parent cells and use a streamlined closed operation system to prepare neural stem cell-derived highly homogenous oxidative phosphorylating artificial organelles. These artificial organelles act as biomimetic organelles to mimic respiration chain function and perform oxidative phosphorylation, thus improving ATP synthesis deficiency and rectifying excessive mitochondrial reactive oxygen species production. Conclusively, we provide a framework for a generalizable manufacturing procedure that opens promising prospects for disease treatment.

COF-derived porous nitrogen-doped carbon for removal of emerging organic contaminants and efficient uranium extraction from seawater.

The development of adsorbents for efficient and highly selective seawater extraction of uranium was instrumental in fostering sustainable progress in energy and addressing the prevailing energy crisis. However, the complex background composition of the marine environment, including radionuclides, organic pollutants, and a large number of co-existing heavy metal ions, were non-negligible obstacles to the extraction of uranium from seawater. The present investigation successfully employed a self-templated approach to synthesize porous nitrogen-doped carbon (PNC) derived from COF, which exhibited tremendous potential as an adsorbent for pollutant removal in environmental treatment. LZU1@PNC not only retained the structural features of the original COF-LZU1, but also overcame the acid-base instability problem commonly found in COFs. Subsequently, the removal process of two typical water pollutants on the material was investigated using 2,4-DCP and [UO2(CO3)3]4-. The results demonstrated that LZU1@PNC exhibited superior removal performance for the target pollutants compared to COF-LZU1, owing to its larger specific surface area and abundant defect structure. After six desorption-regeneration cycles, LZU1@PNC still maintained a high removal rate of the target contaminants, demonstrating the stability of this material and its excellent recyclability. In addition, based on various characterization techniques, the removal mechanism of 2,4-DCP was presumed to be mainly electrostatic attraction, hydrogen bonding, and π-π stacking interactions. Conversely, the elimination process of [UO2(CO3)3]4- predominantly relied on surface complexation phenomena. The present investigation provided new perspectives and stimulated a broader study of other COF-derived carbon materials and their modifications as adsorbents for uranium extraction from seawater and other applications.

Differential diagnosis of suspected multiple sclerosis: global health considerations.

The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. Furthermore, multiple sclerosis diagnostic criteria have been developed primarily using data from North America and western Europe. Although some diagnoses mistaken for multiple sclerosis are common regardless of location, a comprehensive approach to the differential diagnosis of multiple sclerosis in Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific regions requires special consideration of diseases that are prevalent in those locations. A collaborative effort has therefore assessed global differences in multiple sclerosis differential diagnoses and proposed recommendations for evaluating patients with suspected multiple sclerosis in regions beyond North America and western Europe.

Histidine-rich glycoprotein modulates neutrophils and thrombolysis-associated hemorrhagic transformation.

Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood-brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.

Proteomics analysis of immune response-related proteins in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).

The objective is to characterize differentially expressed proteins (DEPs) in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) through high-throughput analysis. Sera from 11 healthy controls (HCs), 21 GBS and 19 CIDP patients were subjected to Olink Proteomics Analysis. In the comparison between CIDP and GBS groups, up-regulation of ITM2A and down-regulation of NTF4 were observed. Comparing GBS with HCs revealed 18 up-regulated and 4 down-regulated proteins. Comparing CIDP with the HCs identified 15 up-regulated and 4 down-regulated proteins. Additionally, the correlation between clinical characteristics and DEPs were uncovered. In conclusion, the DEPs have significant potential to advance our understanding of the pathogenesis in these debilitating neurological disorders.

Accuracy of cell-free Mycobacterium tuberculosis DNA testing in pleural effusion for diagnosing tuberculous pleurisy: a multicenter cross-sectional study.

BACKGROUND: The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. METHODS: Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. RESULTS: A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2-78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3-46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4-59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7-50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2-14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8-18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%. CONCLUSIONS: The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316 ).

Natural killer cells promote neutrophil extracellular traps and restrain macular degeneration in mice.

Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions in patients with nvAMD and in mouse models. Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex-mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD.

Evaluation of the efficacy of posterior hemivertebrectomy combined with two or more segments fusion.

BACKGROUND: Although early hemivertebra (HV) resection and short fusion (within 4 segments) have been successful in treating congenital HV, there is limited research comparing the outcomes of the shortest-segment fusion (2 segments) versus 3 or 4 segments, particularly in young children. To evaluate the efficacy of posterior hemivertebrectomy combined with two or more segments fusion in children under the age of 10 years with a solitary simple lower thoracic or lumbar HV (T8-L5). METHODS: This retrospective study included patients under the age of 10 with lower thoracic or lumbar solitary simple HV who underwent hemivertebra resection (HVR) and transpedicular short fusion and were divided into HV ± 1 group (2 segment fusion) and HV ± 2 group (3 or 4-segment fusion). The study recorded preoperative, postoperative (1 week), and the latest follow-up radiographic parameters and complications. The results of the coronal and sagittal planes were analyzed, and the main curve, segmental scoliosis curve, compensatory scoliosis curve, segmental kyphosis curve, and trunk shift were compared. RESULTS: The study included 35 patients (15 in the HV ± 1 group and 20 in the HV ± 2 group) with a mean age of 5.26 ± 2.31 years and a mean follow-up of 22.54 months (12-68). The mean preoperative Cobb angle was 32.66° ± 7.339° (HV ± 1) and 29.31°±6.642° (HV ± 2). The final Cobb angle was 10.99°± 7.837° (HV ± 1) and 8.22° ± 4.295° (HV ± 2). The main curve corrected by 72% (HV ± 1), 75% (HV ± 2) postoperatively and 67% (HV ± 1), 72% (HV ± 2) at the final follow-up (P > 0.05). There were no significant differences in the correction of the segmental scoliosis curve, compensatory scoliosis curve, segmental kyphosis curve, and trunk shift between the HV ± 1 and HV ± 2 groups (P > 0.05). The unplanned reoperation rate for HV in the thoracolumbar region (T11-L2) is significantly higher (P = 0.038). CONCLUSION: In the context of solitary simple lower thoracic or lumbar HV (T8-L5), HV ± 1 segment fusion suffices and yields comparable correction outcomes in the midterm period when compared to HV ± 2. The reoperation rate exhibited a statistically significant increase in the thoracolumbar region.

Transient diabetes mellitus with ABCC8 variant successfully treated with sulfonylurea: Two case reports and review of literature.

BACKGROUND: Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes mellitus that usually presents within the first 6 mo of life. Patients often enter remission within several months, although relapse can occur later in life. Mutations in the ABCC8 gene, which encodes the sulfonylurea receptor 1 of the ATP-sensitive potassium channel in pancreatic beta cells, are associated with TNDM and permanent neonatal diabetes. This study describes a novel de novo c.3880C>T heterozygous ABCC8 variant that causes TNDM and can be treated with sulf-onylurea therapy. CASE SUMMARY: We retrospectively analyzed 2 Chinese patients with TNDM who were diagnosed, treated, or referred for follow-up between September 2017 and September 2023. The patients were tested for mutations using targeted next-generation sequencing. Patients with neonatal diabetes mellitus caused by a c.3880C>T heterozygous missense variant in the ABCC8 gene have not been reported before. Both children had an onset of post-infectious diabetic ketoacidosis, which is worth noting. At a follow-up visit after discontinuing insulin injection, oral glyburide was found to be effective with no adverse reactions. CONCLUSION: Early genetic testing of neonatal diabetes mellitus aids in accurate diagnosis and treatment and helps avoid daily insulin injections that may cause pain.

Application of the international criteria for optic neuritis in the Acute Optic Neuritis Network.

OBJECTIVE: The first international consensus criteria for optic neuritis (ICON) were published in 2022. We applied these criteria to a prospective, global observational study of acute optic neuritis (ON). METHODS: We included 160 patients with a first-ever acute ON suggestive of a demyelinating CNS disease from the Acute Optic Neuritis Network (ACON). We applied the 2022 ICON to all participants and subsequently adjusted the ICON by replacing a missing relative afferent pupillary defect (RAPD) or dyschromatopsia if magnetic resonance imaging pathology of the optical nerve plus optical coherence tomography abnormalities or certain biomarkers are present. RESULTS: According to the 2022 ICON, 80 (50%) patients were classified as definite ON, 12 (7%) patients were classified as possible ON, and 68 (43%) as not ON (NON). The main reasons for classification as NON were absent RAPD (52 patients, 76%) or dyschromatopsia (49 patients, 72%). Distribution of underlying ON etiologies was as follows: 78 (49%) patients had a single isolated ON, 41 (26%) patients were diagnosed with multiple sclerosis, 25 (16%) patients with myelin oligodendrocyte glycoprotein antibody-associated disease, and 15 (9%) with neuromyelitis optica spectrum disorder. The application of the adjusted ON criteria yielded a higher proportion of patients classified as ON (126 patients, 79%). INTERPRETATION: According to the 2022 ICON, almost half of the included patients in ACON did not fulfill the requirements for classification of definite or possible ON, particularly due to missing RAPD and dyschromatopsia. Thorough RAPD examination and formal color vision testing are critical to the application of the 2022 ICON.

The efficacy and safety of monoclonal antibody therapies for interstitial cystitis/bladder pain syndrome: A meta-analysis of randomized controlled trials.

OBJECTIVES: This study aimed to assess the efficacy and safety of monoclonal antibody therapies (MATs) for interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: A systematic search was conducted across databases including PubMed, Embase, clinicalTrial.gov, and the Cochrane Library Central Register of Controlled Trials. Randomized controlled trials (RCTs) comparing MATs versus placebo were included. Primary outcomes comprised the Global Response Assessment (GRA) scale and the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI). Additional analyses encompassed mean daily frequency of voids, the O'Leary-Sant Interstitial Cystitis Problem Index, pain scores, and complications. Statistical analyses were performed using Review Manager 5.3. RESULTS: Five high-quality RCTs, comprising 263 patients with IC/BPS, were ultimately selected. MATs were generally effective in treating IC/BPS. Patients receiving MATs exhibited a higher satisfaction rate (odds ratio [OR]: 2.7, confidence interval [CI]: 1.31-5.58, p = 0.007) and lower ICSI scores (mean difference [MD]: -1.44, CI: -2.36 to -0.52, p = 0.002). Moreover, MAT recipients experienced reduced pain (MD: -0.53, CI: -0.79 to -0.26, p < 0.0001) and decreased frequency of urination (MD: -1.91, CI: -2.55 to -1.27, p < 0.00001). Importantly, there were no disparities regarding complication incidence in the MAT and control groups. CONCLUSIONS: The current findings indicate that MATs are effective and safe for treating IC/BPS. Nonetheless, future RCTs with larger sample sizes and long-term follow-up are warranted.

Abnormal genes and pathways that drive muscle contracture from brachial plexus injuries: Towards machine learning approach.

In order to clarify the pathways closely linked to denervated muscle contracture, this work uses IoMT-enabled healthcare stratergies to examine changes in gene expression patterns inside atrophic muscles following brachial plexus damage. The gene expression Omnibus (GEO) database searching was used to locate the dataset GSE137606, which is connected to brachial plexus injuries. Strict criteria (|logFC|≥2 & adj.p < 0.05) were used to extract differentially expressed genes (DEGs). To identify dysregulated activities and pathways in denervated muscles, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were used. Hub genes were found using Cytoscape software's algorithms, which took into account parameters like as proximity, degree, and MNC. Their expression, enriched pathways, and correlations were then examined. The results showed that 316 DEGs were predominantly concentrated in muscle-related processes such as tissue formation and contraction pathways. Of these, 297 DEGs were highly expressed in denervated muscles, whereas 19 DEGs were weakly expressed. GSEA showed improvements in the contraction of striated and skeletal muscles. In addition, it was shown that in denervated muscles, Myod1, Myog, Myh7, Myl2, Tnnt2, and Tnni1 were elevated hub genes with enriched pathways such adrenergic signaling and tight junction. These results point to possible therapeutic targets for denervated muscular contracture, including Myod1, Myog, Myh7, Myl2, Tnnt2, and Tnni1. This highlights treatment options for this ailment which enhances the mental state of patient.

The relationship between the systemic immune inflammation index and the nonalcoholic fatty liver disease in American adolescents.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a growing health crisis in the general population of the United States (U.S.), but the relationship between systemic immune-inflammation (SII) index and NAFLD is not known. METHODS: We collected data from the National Health and Nutrition Examination Survey 2017-2018. Next, propensity score matching (PSM), collinearity analysis, restricted cubic spline (RCS) plot, logistic regression, quantile regression analysis, subgroup analysis, mediation analysis, and population attributable fraction were used to explore the association of the SII with risk of NAFLD. RESULTS: A total of 665 participants including the 532 Non-NAFLD and 133 NAFLD were enrolled for further analysis after PSM analysis. The RCS results indicated that there was a linear relationship between the SII and controlled attenuation parameter (p for nonlinear = 0.468), the relationship also existed after adjustment for covariates (p for nonlinear = 0.769). The logistic regression results indicated that a high SII level was an independent risk factor for NAFLD (OR = 3.505, 95% CI: 1.092-11.249, P < 0.05). The quantile regression indicated that at higher quantiles (0.90, and 0.95) the SII was significantly associated with NAFLD (p < 0.05). Mediation analysis indicated that alanine aminotransferase (ALT), triglycerides, and blood urea nitrogen (BUN) were partially contribute to the relationship between SII and NAFLD. The population attributable fractions indicated that 23.19% (95% CI: 8.22%, 38.17%) of NAFLD cases could be attributed to SII corresponding to 133 NAFLD cases. CONCLUSION: There was a positive linear relationship between the SII and the risk of NAFLD. The ALT, triglycerides, and BUN had a partial mediating effect on the relationship between the SII and NAFLD.

Fabrication of thermo-responsive multicore microcapsules using a facile extrusion process.

A process employing extrusion was used to produce multicore microcapsules composed of multiple beads. The inner beads were made from κ-carrageenan (κ-c), a thermo-responsive linear sulphated polymer whose gelling temperature ranges at 40-60 °C, depending on the concentration of κ-c polymer and the amount of potassium chloride used for gelation. The resulting beads were then enveloped by chitosan through gelation with sodium triphosphate. The pesticide ammonium glufosinate was encapsulated in the κ-c/chitosan multicore microcapsules for demonstration of controlled release of the encapsulant. It was found that in response to an external stimulus, such as elevated temperature or solar simulation, the microcapsules exhibit the gradual release of encapsulated pesticide molecules from multicore microcapsules, compared with beads only. This process of making multicore microcapsules can be extended to other polymer pairs based on applications. This work is relevant to agriculture, where the controlled-release of the pesticides or fertilizers could be triggered by the sun and/or temperature changes, thus extending the residual period of the chemicals as well as decreasing the extent of pollution by leaching of abundant chemicals.

A nomogram predicting pneumonia after cardiac surgery: a retrospective modeling study.

BACKGROUND: Postoperative pneumonia (POP) is the most prevalent of all nosocomial infections in patients who underwent cardiac surgery. The aim of this study was to identify independent risk factors for pneumonia after cardiac surgery, from which we constructed a nomogram for prediction. METHODS: The clinical data of patients admitted to the Department of Cardiothoracic Surgery of Nanjing Drum Tower Hospital from October 2020 to September 2021 who underwent cardiac surgery were retrospectively analyzed, and the patients were divided into two groups according to whether they had POP: POP group (n=105) and non-POP group (n=1083). Preoperative, intraoperative, and postoperative indicators were collected and analyzed. Logistic regression was used to identify independent risk factors for POP in patients who underwent cardiac surgery. We constructed a nomogram based on these independent risk factors. Model discrimination was assessed via area under the receiver operating characteristic curve (AUC), and calibration was assessed via calibration plot. RESULTS: A total of 105 events occurred in the 1188 cases. Age (>55 years) (OR: 1.83, P=0.0225), preoperative malnutrition (OR: 3.71, P<0.0001), diabetes mellitus(OR: 2.33, P=0.0036), CPB time (Cardiopulmonary Bypass Time) > 135 min (OR: 2.80, P<0.0001), moderate to severe ARDS (Acute Respiratory Distress Syndrome )(OR: 1.79, P=0.0148), use of ECMO or IABP or CRRT (ECMO: Extra Corporeal Membrane Oxygenation; IABP: Intra-Aortic Balloon Pump; CRRT: Continuous Renal Replacement Therapy )(OR: 2.60, P=0.0057) and MV( Mechanical Ventilation )> 20 hours (OR: 3.11, P<0.0001) were independent risk factors for POP. Based on those independent risk factors, we constructed a simple nomogram with an AUC of 0.82. Calibration plots showed good agreement between predicted probabilities and actual probabilities. CONCLUSION: We constructed a facile nomogram for predicting pneumonia after cardiac surgery with good discrimination and calibration. The model has excellent clinical applicability and can be used to identify and adjust modifiable risk factors to reduce the incidence of POP as well as patient mortality.

Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial.

OBJECTIVES: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3). DESIGN: Multicentre, double blind, randomised, placebo controlled trial. SETTING: 244 hospitals in China between 11 August 2022 and 13 April 2023. PARTICIPANTS: 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled. INTERVENTIONS: Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days. MAIN OUTCOME MEASURES: The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat. RESULTS: 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83). CONCLUSIONS: The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05439356.