Advancements and trends in exosome research in lung cancer from a bibliometric analysis (2004-2023).

Background: Lung cancer, characterized by its high morbidity and lethality, necessitates thorough research to enhance our understanding of its pathogenesis and discover novel therapeutic approaches. Recent studies increasingly demonstrate that lung cancer cells can modulate the tumor microenvironment, promoting tumor growth, and metastasis through the release of exosomes. Exosomes are small vesicles secreted by cells and contain a variety of bioactive molecules such as proteins, nucleic acids, and metabolites. This paper presents a comprehensive review of exosome research in lung cancer and its progress through bibliometric analysis. Methods: Publications related to exosomes in lung cancer patients were systematically searched on the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using VOSviwers, CiteSpace, and the R package "Bibliometrics". Publications were quantitatively analyzed using Microsoft Office Excel 2019. The language of publication was restricted to "English" and the search strategy employed TS=(exosomes or exosomes or exosomes) and TS=(lung cancer). The search period commenced on January 1, 2004, and concluded on November 12, 2023, at noon. The selected literature types included Articles and Reviews. Results: The study encompassed 1699 papers from 521 journals across 71 countries and 2105 institutions. Analysis revealed a consistent upward trend in lung cancer exosome research over the years, with a notable surge in recent times. This surge indicates a growing interest and depth of inquiry into lung cancer exosomes. Major research institutions in China and the United States, including Nanjing Medical University, Shanghai Jiao Tong University, Chinese Academy Of Sciences, and Utmd Anderson Cancer Center, emerged as crucial research hubs. The annual publication count in this field witnessed a continuous rise, particularly in recent years. Key terms such as lung cancer, non-small cell lung cancer (NSCLC), microvesicles, intercellular communication, exosomal miRNAs, and oncology dominated the research landscape. Fields like cell biology, biochemistry, biotechnology, and oncology exhibited close relation with this research. Clotilde Théry emerged as the most cited author in the field, underlining her significant contributions. These results demonstrate the broad impact of exosome research in lung cancer, with key terms covering not only disease-specific aspects such as lung cancer and NSCLC but also basic biological concepts like microvesicles and intercellular communication. Explorations into exosomal microRNAs and oncology have opened new avenues for lung cancer exosome research. In summary, lung cancer exosome research is poised to continue receiving attention, potentially leading to breakthroughs in treatment and prevention. Conclusion: Publications on lung cancer exosomes show a rising trend year by year, with China and the United States ranking first and second in terms of the number of publications. However, there is insufficient academic learning cooperation and exchanges between the two sides, and Chinese universities account for a large proportion of research institutions in this field. Jing Li is the most productive author, Clotilde Théry is the most co-cited author, and Cancers is the journal with the highest number of publications. The current focus in the field of lung cancer exosomes is on biomarkers, liquid biopsies, immunotherapy, and tumor microenvironment.

Effect of short-term moderate intake of ice wine on hepatic glycolipid metabolism in C57BL/6J mice.

As the correlation between high fructose intake and metabolism-related diseases (e.g., obesity, fatty liver, and type 2 diabetes) has been increasingly reported, the health benefits of consuming ice wine high in fructose have been called into question. In this study, 6-week-old male C57BL/6J mice were divided into control (pure water), fructose (130 g L-1 fructose solution), alcohol (11% alcohol solution), low-dose (50% diluted ice wine) and high-dose ice wine (100% ice wine) groups to investigate the effects and mechanisms of short-term (4 weeks) ice wine intake on hepatic glycolipid metabolism in mice. The results showed that short-term consumption of ice wine suppressed the elevation of low-density lipoprotein cholesterol content and did not cause hepatic lipid accumulation compared with those of the fructose group. Meanwhile, ice wine had no significant effect on lipogenesis although it inhibited fatty acid oxidation via the PPARα/CPT-1α pathway. Compared with the control group, ice wine interfered with the elevation of fasting glucose and the insulin resistance index in a dose-dependent manner, and led to an increase in plasma uric acid levels, which may further contribute to the disruption of glucolipid metabolism. Overall, short-term moderate intake of ice wine over a 4-week period may not significantly affect hepatic glycolipid metabolism in C57BL/6J mice for the time being.

Study on the Spatial Damage Characteristics of Working Fluid in a Sandstone Reservoir and an Unplugged Fluid System.

Due to its good physical properties and low pressure coefficient, the K75 reservoir is prone to leakage and intrusion of drilling and completion fluids during well construction, resulting in plugging of the borehole throat, which will inevitably affect the injection and recovery capacity of the gas well. In order to ensure the strong injection and production capacity of the K75 reservoir, this paper clarifies the reservoir space damage characteristics under different pressure differences and different entry fluids by establishing physical simulation of the damage, selecting the optimal system of the decongestant, and conducting dynamic flow decongestion experiments, as well as combining with the characterization means of the continuous scanning system of the core and the permeability test of the gas measurement. The test results show that the degree of damage of the same working fluid increases with the increase of differential pressure of repulsion, and the degree of damage of sequential working fluids (drilling fluid, completion fluid, and perforating fluid) is greater than that of drilling fluid damage under the same differential pressure of repulsion. In order to relieve the damage of wellbore working fluids, a set of multifunctional, low-corrosion composite acid system formulas was selected through rock powder, mud cake dissolution experiments, and dynamic flow unblocking experiments; the permeability recovery rate of this acid system after unblocking was more than 90%, which is widely applicable, and it is useful for the acidizing and unblocking practice in similar reservoirs.

Timing dependent neuronal migration is regulated by Cdk5-mediated phosphorylation of JIP1.

The mammalian brain, especially the cerebral cortex, has evolved to increase in size and complexity. The proper development of the cerebral cortex requires the coordination of several events, such as differentiation and migration, that are essential for forming a precise six-layered structure. We have previously reported that Cdk5-mediated phosphorylation of JIP1 at T205 modulates axonal out-growth. However, the spatiotemporal expression patterns and functions of these three genes (Cdk5, Cdk5r1 or p35, and Mapk8ip1 or JIP1) in distinct cell types during cortical development remain unclear. In this study, we analyzed single-cell RNA-sequencing data of mouse embryonic cortex and discovered that Cdk5, p35, and JIP1 are dynamically expressed in intermediate progenitors (IPs). Pseudotime analysis revealed that the expression of these three genes was concomitantly upregulated in IPs during neuronal migration and differentiation. By manipulating the expression of JIP1 and phospho-mimetic JIP1 using in utero electroporation, we showed that phosphorylated JIP1 at T205 affected the temporal migration of neurons.

Curcumin relieves oxaliplatin-induced neuropathic pain via reducing inflammation and activating antioxidant response.

Oxaliplatin (OXA) has shown high effectiveness in the treatment of cancers, but its anticancer clinical effects often induce neurotoxicity leading to neuropathic pain. Oxidative damage and NLRP3 inflammasome play important roles in neuropathic pain development. Here, neuropathic pain mouse model was constructed by continuous intraperitoneal injection of OXA. OXA administration induced mechanical pain, spontaneous pain, thermal hyperalgesia and motor disability in mice. The spinal cord tissues of OXA mice exhibited the suppressed antioxidative response, the activated NLRP3 inflammasome mediated inflammatory responses, and the increased GSK-3ß activity. Next, we injected curcumin (CUR) intraperitoneally in OXA mice for seven consecutive days. CUR-treated mice showed increased mechanical pain thresholds, reduced number of spontaneous flinches, increased paw withdrawal latency, and restored latency to fall. While in the spinal cord, CUR treatment inhibited the NLRP3 inflammasome mediated inflammatory response, increased Nrf2/GPX4-mediated antioxidant responses, and decreased mitochondrial oxidative generation. Additionally, CUR combined with GSK-3ß through four covalent bonds and reduced GSK-3ß activity. In conclusion, our findings suggest that CUR treatment inhibits GSK-3ß activation, increases Nrf2 mediated antioxidant responses, inhibits oxidative damage and inflammatory reaction, and alleviates OXA-induced neuropathic pain.

Differential expression of Semaphorin-7A /CD163-positive macrophages in large artery and cardiogenic stroke.

BACKGROUND: Identification of the causes of stroke of undetermined etiology, specifically cardioembolism (CE) and non-CE causes, can inform treatment planning and prognosis prediction. The objective of this study was to analyze the disparities in thrombus composition, particularly Semaphorin-7A (Sema7A) and CD163, between patients diagnosed with large-artery atherosclerosis (LAA) and those with CE, and to investigate their potential association with prognosis. METHODS: Thrombi were collected from patients who underwent mechanical thrombectomy at two hospitals. The patients were categorized into two groups: LAA and CE. We compared the levels of Sema7A and CD163 between these groups and analyzed their relationships with stroke severity, hemorrhagic transformation and prognosis. RESULTS: The study involved a total of 67 patients. Sema7A expression was found to be significantly higher in the CE group compared to LAA (p < 0.001). Conversely, no statistically significant differences were observed for CD163 between the groups. The presence of Sema7A/CD163 did not show any associations with stroke severity or hemorrhagic transformation (all p > 0.05). However, both Sema7A (OR, 2.017; 95% CI, 1.301-3.518; p = 0.005) and CD163 (OR, 2.283; 95% CI, 1.252-5.724; p = 0.03) were associated with the poor prognosis for stroke, after adjusting for stroke severity. CONCLUSION: This study highlights that CE thrombi exhibited higher levels of Sema7A expression compared to LAA thrombi. Moreover, we found a positive correlation between Sema7A/CD163 levels and the poor prognosis of patients with acute ischemic stroke.

Exploring additives beyond phthalates: Release from plastic mulching films, biodegradation and occurrence in agricultural soils.

It is widely recognized that applications of plastic films result in plastic pollution in agroecosystems. However, there is limited knowledge on the release and occurrence of additives beyond phthalates in agricultural soil. In this study, the rates of release and biodegradation of various additives, including phthalates, bisphenols, organophosphate esters, phenolic antioxidants, and ultraviolet absorbents from mulching films in soil were quantified by laboratory incubation. The rates of release and biodegradation ranged from 0.069 d-1 to 5.893 d-1 and from 1.43 × 10-3 d-1 to 0.600 d-1, respectively. Both of these rates were affected by temperature, flooding, and the properties of additives, films, and soils. An estimated 4000 metric tons of these additives were released into soil annually in China exclusively. The total concentrations of these additives in 80 agricultural soils varied between 228 and 3455 µg kg-1, with phenolic antioxidants, phthalates, and bisphenols accounting for 54.1%, 25.2%, and 17.9% of the total concentrations, respectively. A preliminary risk assessment suggested that the current levels of these additives could potentially present moderate hazards to the soil ecosystem.

Assessing the stress-relief impact of an art-based intervention inspired by the broaden-and-build theory in college students.

Background and objectives: This study's primary objective is to investigate the impact of art-making on the mental well-being of college students, who often experience heightened stress during their initial university years. Methods: Employing a comprehensive methodology, combining interviews and the Perceived Stress Scale (PSS), the research aimed to assess whether a four-week art-making intervention can effectively alleviate stress levels among college students. In the experimental group, participants engaged in a variety of art-making activities, including freehand drawing, clay modeling, and crafting. Results: The results revealed that, in the pre-test, there were no significant differences between the experimental and control groups for each assessed indicator. However, in the post-test, significant differences emerged across all indicators. Further analysis demonstrated a significant reduction in stress perception among the experimental group participants between the pre-test and post-test phases. Conclusion: In conclusion, this study provides compelling evidence that art-making has the potential to foster positive personal development and significantly reduce stress levels among college students.

Development and validation of a nomogram for predicting in-hospital mortality of patients with cervical spine fractures without spinal cord injury.

BACKGROUND: The incidence of cervical spine fractures is increasing every day, causing a huge burden on society. This study aimed to develop and verify a nomogram to predict the in-hospital mortality of patients with cervical spine fractures without spinal cord injury. This could help clinicians understand the clinical outcome of such patients at an early stage and make appropriate decisions to improve their prognosis. METHODS: This study included 394 patients with cervical spine fractures from the Medical Information Mart for Intensive Care III database, and 40 clinical indicators of each patient on the first day of admission to the intensive care unit were collected. The independent risk factors were screened using the Least Absolute Shrinkage and Selection Operator regression analysis method, a multi-factor logistic regression model was established, nomograms were developed, and internal validation was performed. A receiver operating characteristic (ROC) curve was drawn, and the area under the ROC curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to evaluate the discrimination of the model. Moreover, the consistency between the actual probability and predicted probability was reflected using the calibration curve and Hosmer-Lemeshow (HL) test. A decision curve analysis (DCA) was performed, and the nomogram was compared with the scoring system commonly used in clinical practice to evaluate the clinical net benefit. RESULTS: The nomogram indicators included the systolic blood pressure, oxygen saturation, respiratory rate, bicarbonate, and simplified acute physiology score (SAPS) II. The results showed that our model had satisfactory predictive ability, with an AUC of 0.907 (95% confidence interval [CI] = 0.853-0.961) and 0.856 (95% CI = 0.746-0.967) in the training set and validation set, respectively. Compared with the SAPS-II system, the NRI values of the training and validation sets of our model were 0.543 (95% CI = 0.147-0.940) and 0.784 (95% CI = 0.282-1.286), respectively. The IDI values of the training and validation sets were 0.064 (95% CI = 0.004-0.123; P = 0.037) and 0.103 (95% CI = 0.002-0.203; P = 0.046), respectively. The calibration plot and HL test results confirmed that our model prediction results showed good agreement with the actual results, where the HL test values of the training and validation sets were P = 0.8 and P = 0.95, respectively. The DCA curve revealed that our model had better clinical net benefit than the SAPS-II system. CONCLUSION: We explored the in-hospital mortality of patients with cervical spine fractures without spinal cord injury and constructed a nomogram to predict their prognosis. This could help doctors assess the patient's status and implement interventions to improve prognosis accordingly.

The relationship between plasma prolactin levels and clinical manifestations with neuromyelitis optica spectrum disorders.

INTRODUCTION: Systemic prolactin levels have been found to increase in 19 patients diagnosed with neuromyelitis optica spectrum disorders (NMOSD). However, the relationship between plasma prolactin levels and clinical manifestations in NMOSD patients remains unclear. METHODS: This cross-sectional study was conducted as part of a Registered Cohort Study of Inflammatory Demyelination Disease (NCT04386018). A total of 95 patients diagnosed with central nervous system demyelinating diseases and 43 healthy controls were recruited between May 2020 and February 2022 at the First Affiliated Hospital of Fujian Medical University. Plasma samples were collected from all participants and analyzed for prolactin levels using electrochemiluminescence immunoassay. The study aimed to investigate the correlation between plasma prolactin levels and clinical features in patients with central nervous system demyelinating diseases. RESULTS: Plasma prolactin levels in NMOSD patients were significantly higher than those in multiple sclerosis/myelin oligodendrocyte glycoprotein antibody-associated diseases patients and controls (p<0.05, respectively), and were found to be correlated with disease activity, sensory abnormalities, thoracic spinal cord lesions, and MR lesion enhancement (p<0.05). A total of 16.28% of NMOSD patients exhibited macroprolactinemia. However, there was no correlation found between macroprolactin levels and disease activity (p>0.05). CONCLUSION: Prolactin may play a role in the pro-inflammatory regulation mechanism of NMOSD.

Multi-Frequency Ultrasound Imaging Fusion Method Based on Wavelet Transform for Guided Screw Insertion.

Intraosseous ultrasound imaging can serve as a guiding tool for the placement of pedicle screws during spinal fusion surgery; thus far, there has been limited scholarly exploration of methods for intraosseous multifrequency ultrasound imaging, which can achieve simultaneous high resolution and deep penetration. The proposed method introduced a dynamic fusion strategy grounded in wavelet transformation for multifrequency image decomposition. This strategy accomplished the effective amalgamation of high-frequency ultrasound images and low-frequency ultrasound images, enabling the obtaining of fused images with enhanced details and better overall image quality. A novel near-field effect elimination method was also proposed to improve the quality of ultrasound imaging in the near-field region. Experimental evaluations were conducted on isolated bovine circle bone and sheep spine with pedicle screw tracks. The fusion images are capable of effectively detecting areas within the pedicle screw track that have either ruptured or are in close proximity to rupture, even measuring the size of breaches. Evaluation criteria, including information entropy (IE), spatial frequency (SF), average gradient (AG), mutual information (MI), structural similarity index (SSIM), and edge information-based image fusion quality metric (QAB/F), were employed to assess the fusion performance; moreover, the influence of mother wavelet function selection and decomposition levels on computational complexity and fusion image quality was thoroughly discussed. The proposed method exhibited promising potential for intraosseous imaging navigation, which can aid in accurate diagnosis, treatment planning, and monitoring in fields such as orthopedics, surgery, and interventional procedures.

Emodin inhibits HDAC6 mediated NLRP3 signaling and relieves chronic inflammatory pain in mice.

Chronic pain reduces the quality of life and ability to function of individuals suffering from it, making it a common public health problem. Neuroinflammation which is mediated by the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in the spinal cord participates and modulates chronic pain. A chronic inflammatory pain mouse model was created in the current study by intraplantar injection of complete Freund's adjuvant (CFA) into C57BL/6J left foot of mice. Following CFA injection, the mice had enhanced pain sensitivities, decreased motor function, increased spinal inflammation and activated spinal astrocytes. Emodin (10 mg/kg) was administered intraperitoneally into the mice for 3 days. As a result, there were fewer spontaneous flinches, higher mechanical threshold values and greater latency to fall. Additionally, in the spinal cord, emodin administration reduced leukocyte infiltration level, downregulated protein level of IL-1ß, lowered histone deacetylase (HDAC)6 and NLRP3 inflammasome activity and suppressed astrocytic activation. Emodin also binds to HDAC6 via four electrovalent bonds. In summary, emodin treatment blocked the HDAC6/NLRP3 inflammasome signaling, suppresses spinal inflammation and alleviates chronic inflammatory pain.

Novel stripe rust effector boosts the transcription of a host susceptibility factor through affecting histone modification to promote infection in wheat.

Regulation of host gene expression to promote disease is a common strategy for plant pathogens. However, it remains unclear whether or not fungal pathogens manipulate host gene expression directly through secreted effectors with transcriptional activity. Here, we identified a fungal effector PstGTA1 from Puccinia striiformis f. sp. tritici (Pst), which has partial homology to the subunit of global transcriptional activator SNF2 from oyster. The transcriptional activating activity of PstGTA1 was validated in yeast, and the potential role of PstGTA1 in pathogenicity was assessed using gene silenced and overexpression transgenic wheat plants. Candidate targets regulated by PstGTA1 were screened by transcriptomic analysis, and the specific promoter region binding to PstGTA1 was further determined. PstGTA1 can be delivered to the wheat cell nucleus and contributes to the full virulence of Pst by targeting the promoter of TaSIG, a gene negatively regulating wheat immunity, and possibly activates its transcription by affecting the histone H3K4 acetylation level. Our study provides the first direct evidence for a fungal effector with transactivation activity modulating the transcription of a host specific susceptibility gene through promoter binding and histone acetylation.

Murine trophoblast organoids as a model for trophoblast development and CRISPR-Cas9 screening.

The placenta becomes one of the most diversified organs during placental mammal radiation. The main in vitro model for studying mouse trophoblast development is the 2D differentiation model of trophoblast stem cells, which is highly skewed to certain lineages and thus hampers systematic screens. Here, we established culture conditions for the establishment, maintenance, and differentiation of murine trophoblast organoids. Murine trophoblast organoids under the maintenance condition contain stem cell-like populations, whereas differentiated organoids possess various trophoblasts resembling placental ones in vivo. Ablation of Nubpl or Gcm1 in trophoblast organoids recapitulated their deficiency phenotypes in vivo, suggesting that those organoids are valid in vitro models for trophoblast development. Importantly, we performed an efficient CRISPR-Cas9 screening in mouse trophoblast organoids using a focused sgRNA (single guide RNA) library targeting G protein-coupled receptors. Together, our results establish an organoid model to investigate mouse trophoblast development and a practicable approach to performing forward screening in trophoblast lineages.

Increased Expression Levels of Thermophilic Serine Protease TTHA0724 through Signal Peptide Screening in Bacillus subtilis and Applications of the Enzyme.

The thermostable protease TTHA0724 derived from Thermus thermophilus HB8 is an ideal industrial washing enzyme due to its thermophilic characteristics; although it can be expressed in Escherichia coli via pET-22b, high yields are difficult to achieve, leading to frequent autolysis of the host. This paper details the development of a signal peptide library in the expression system of B. subtilis and the optimization of signal peptides for enhanced extracellular expression of TTHA0724. When B. subtilis was used as the host and the optimized signal peptide was used, the expression level of TTHA0724 was 16.7 times higher compared with E. coli. B. subtilis as an expression host does not change the characteristics of TTHA0724. The potential application fields of TTHA0724 are studied. TTHA0724 can be used as a detergent additive at 60 °C, which can sterilize and eliminate mites while thoroughly cleaning protein stains. Soybean meal enzymatic hydrolysis with TTHA0724 at a high temperature produced a higher content of antioxidant peptides. These results indicate that TTHA0724 has great potential for industrial applications.

Development and validation of a nomogram for predicting in-hospital mortality in patients with nonhip femoral fractures.

BACKGROUND: The incidence of nonhip femoral fractures is gradually increasing, but few studies have explored the risk factors for in-hospital death in patients with nonhip femoral fractures in the ICU or developed mortality prediction models. Therefore, we chose to study this specific patient group, hoping to help clinicians improve the prognosis of patients. METHODS: This is a retrospective study based on the data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Least absolute shrinkage and selection operator (LASSO) regression was used to screen risk factors. The receiver operating characteristic (ROC) curve was drawn, and the areas under the curve (AUC), net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the discrimination of the model. The consistency between the actual probability and the predicted probability was assessed by the calibration curve and Hosmer-Lemeshow goodness of fit test (HL test). Decision curve analysis (DCA) was performed, and the nomogram was compared with the scoring system commonly used in clinical practice to evaluate the clinical net benefit. RESULTS: The LASSO regression analysis showed that heart rate, temperature, red blood cell distribution width, blood urea nitrogen, Glasgow Coma Scale (GCS), Simplified Acute Physiology Score II (SAPSII), Charlson comorbidity index and cerebrovascular disease were independent risk factors for in-hospital death in patients with nonhip femoral fractures. The AUC, IDI and NRI of our model in the training set and validation set were better than those of the GCS and SAPSII scoring systems. The calibration curve and HL test results showed that our model prediction results were in good agreement with the actual results (P = 0.833 for the HL test of the training set and P = 0.767 for the HL test of the validation set). DCA showed that our model had a better clinical net benefit than the GCS and SAPSII scoring systems. CONCLUSION: In this study, the independent risk factors for in-hospital death in patients with nonhip femoral fractures were determined, and a prediction model was constructed. The results of this study may help to improve the clinical prognosis of patients with nonhip femoral fractures.

Medical Physics Leadership Academy Journal Club (Leadership Club) program: Two-year review in building a community of leaders.

The American Association of Physicists in Medicine began the Medical Physics Leadership Academy Journal Club in the fall of 2020. The initiative was launched to provide a forum for medical physicists to learn about leadership topics using published material, discuss and reflect on the material, and consider incorporating the discussed skills into their professional practice. This report presents the framework for the MPLA Journal Club program, describes the lessons learned over the last 2 years, summarizes the data collected from attendees, and highlights the roadmap for the program moving forward.

Ceramide d18:1/24:1 as a potential biomarker to differentiate obesity subtypes with unfavorable health outcomes.

BACKGROUND: The criteria for metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) remain controversial. This research aimed to identify a potential biomarker to differentiate the subtypes of obesity. METHODS: The study conducted a lipidomic evaluation of ceramide in the serum of 77 Chinese adults who had undergone hyperinsulinemic-euglycemic clamps. These adults were divided into three groups according to the clinical data: normal weight control group (N = 21), MHO (N = 20), and MUO (N = 36). RESULTS: The serum Cer d18:1/24:1 level in the MHO group was lower than that in the MUO group. As the Cer d18:1/24:1 level increased, insulin sensitivity decreased, and the unfavorable parameters increased in parallel. Multivariate logistic regression analysis revealed that serum Cer d18:1/24:1 levels were independently correlated with MUO in obesity. Individuals with higher levels of Cer d18:1/24:1 also had an elevated risk of cardiovascular disease. Most ceramide subtype levels increased in obesity compared to normal-weight individuals, but the levels of serum Cer d18:0/18:0 and Cer d18:1/16:0 decreased in obesity. CONCLUSIONS: The relationships between ceramide subtypes and metabolic profiles might be heterogeneous in populations with different body weights. Cer d18:1/24:1 could be a biomarker that can be used to differentiate MUO from MHO, and to better predict who will develop unfavorable health outcomes among obese individuals. TRIAL REGISTRATION: The First Affiliated Hospital of Nanjing Medical University's Institutional Review Board authorized this study protocol, and all participants provided written informed consent (2014-SR-003) prior to study entry.

Effect of sacubitril/valsartan on brain natriuretic peptide level and prognosis of acute cerebral infarction.

BACKGROUND AND PURPOSE: Previous studies demonstrated that elevated brain natriuretic peptide (BNP) level is associated with adverse clinical outcomes of acute cerebral infarction (ACI). Researchers hypothesized that BNP might be a potential neuroprotective factor against cerebral ischemia because of the antagonistic effect of the natriuretic peptide system on the renin-angiotensin system and regulation of cardiovascular homeostasis. However, whether decreasing the BNP level can improve the prognosis of ACI has not been studied yet. The main effect of sacubitril/valsartan is to enhance the natriuretic peptide system. We investigated whether the intervention of plasma BNP levels with sacubitril/valsartan could improve the prognosis of patients with ACI. METHODS: In a randomized, controlled, parallel-group trial of patients with ACI within 48 hours of symptom onset and need for antihypertensive therapy, patients have randomized within 24 hours to sacubitril/valsartan 200mg once daily (the intervention group) or to conventional medical medication (the control group). The primary outcome was a change in plasma BNP levels before and after sacubitril/valsartan administration. The secondary outcomes included plasma levels of brain-derived neurotrophic factor (BDNF), Corin and neprilysin (NEP) before and after medication, the modified Rankin scale, and the National Institutes of Health Stroke Scale (at onset, at discharge, 30 days, and 90 days after discharge). RESULTS: We evaluated 80 eligible patients admitted to the Stroke Center of Lianyungang Second People's Hospital between 1st May, 2021 and 31st June, 2022. Except for 28 patients excluded before randomization and 14 patients who did not meet the criteria or dropped out or lost to follow-up during the trial, the remaining 38 patients (intervention group: 17, control group: 21) had well-balanced baseline features. In this trial, we found that plasma BNP levels (P = 0.003) decreased and NEP levels (P = 0.006) increased in enrolled patients after treatment with sacubitril/valsartan. There were no differences in plasma BDNF and Corin levels between the two groups. Furthermore, no difference in functional prognosis was observed between the two groups (all P values>0.05). CONCLUSIONS: Sacubitril/valsartan reduced endogenous plasma BNP levels in patients with ACI and did not affect their short-term prognosis.