Association Between Neuroinflammation and Parkinson's Disease: A Comprehensive Mendelian Randomization Study.

The objective of the study is to determine the causal relationship and potential mechanisms between Parkinson's disease (PD) and neuroinflammatory and neurotoxic mediators. We conducted two-sample Mendelian randomization (2SMR) study and multivariable Mendelian randomization (MVMR) analysis to investigate the causality between PD and neuroinflammatory and neurotoxic mediators. The mediation analysis with MR was also conducted to determine the potential mediating effect of neuroinflammatory and neurotoxic mediators between asthma and PD. Genetically predicted levels of nine neuroinflammation were associated with changes in PD risk. The associations of PD with CCL24, galectin-3 levels, haptoglobin, and Holo-Transcobalamin-2 remained significant in multivariable analyses. The mediation analysis with MR revealed that asthma affects PD through CCL24 and galectin-3. The results showed neuroinflammation could affect the pathogenesis of PD. In the combined analysis of these nine variables, CCL24, galectin-3 levels, HP, and Holo-Transcobalamin-2 alone were found to be significant. Asthma plays an intermediary role through CCL24 and galectin-3 levels.

Childhood adversity, perceived social support, and depressive symptoms among pre-abortion Chinese women.

BACKGROUND: Unintended (unwanted) pregnancy is a sexual and reproductive health issue with psychosocial consequences for the individual, their family, and society. However, the relationship between social support and related mental health issues, like depression and the effects of childhood adversity, is poorly studied. This study aims to explore the connections between childhood adversity, perceived social support, and depressive symptoms in pre-abortion women (women who have decided to have an abortion) in a clinical setting, based on the common risk factor approach and social support theory. METHODS: A total of 299 pre-abortion Chinese women 18-45 years were recruited in a hospital in Shantou, China. Hierarchical linear regression analyses were employed to examine the relative effects of childhood adversity and sources of social support on depressive symptoms, controlling for sociodemographic influences. RESULTS: The results show that 37.2 percent of participants reported at least one adverse experience in childhood. More than half of the respondents were at risk for depression. Results of regression analysis showed that childhood adversities were negatively associated with depressive symptoms before sources of social support were entered into the model. However, when the sources of perceived social support were added, the effect of childhood adversity was not significant. Perceived social support explained the additional 15 percent variance in depressive symptoms. Additionally, being married (ß = -.12, p < .05) and number of siblings (ß = .13, p < .05) were significantly related to depressive symptoms. DISCUSSION: Pre-abortion women are at risk of mental health problems. Peer and familial social supports can alleviate the influence of childhood adversity on depression among pre-abortion Chinese women. Strengthening the role of various sources of social support can help to improve the mental health conditions of pre-abortion women.

Itaconate alleviates diet-induced obesity via activation of brown adipocyte thermogenesis.

Despite medical advances, there remains an unmet need for better treatment of obesity. Itaconate, a product of the decarboxylation of the tricarboxylic acid cycle intermediate cis-aconitate, plays a regulatory role in both metabolism and immunity. Here, we show that itaconate, as an endogenous compound, counteracts high-fat-diet (HFD)-induced obesity through leptin-independent mechanisms in three mouse models. Specifically, itaconate reduces weight gain, reverses hyperlipidemia, and improves glucose tolerance in HFD-fed mice. Additionally, itaconate enhances energy expenditure and the thermogenic capacity of brown adipose tissue (BAT). Unbiased proteomic analysis reveals that itaconate upregulates key proteins involved in fatty acid oxidation and represses the expression of lipogenic genes. Itaconate may provoke a major metabolic reprogramming by inducing fatty acid oxidation and suppression of fatty acid synthesis in BAT. These findings highlight itaconate as a potential activator of BAT-mediated thermogenesis and a promising candidate for anti-obesity therapy.

H2S-Powered Nanomotors for Active Therapy of Tumors by Inducing Ferroptosis and Lactate-Pyruvate Axis Disorders.

Disruption of the symbiosis of extra/intratumoral metabolism is a good strategy for treating tumors that shuttle resources from the tumor microenvironment. Here, we report a precision treatment strategy for enhancing pyruvic acid and intratumoral acidosis to destroy tumoral metabolic symbiosis to eliminate tumors; this approach is based on PEGylated gold and lactate oxidase-modified aminated dendritic mesoporous silica with lonidamine and ferrous sulfide loading (PEG-Au@DMSNs/FeS/LND@LOX). In the tumor microenvironment, LOX oxidizes lactic acid to produce pyruvate, which represses tumor cell proliferation by inhibiting histone gene expression and induces ferroptosis by partial histone monoubiquitination. In acidic tumor conditions, the nanoparticles release H2S gas and Fe2+ ions, which can inhibit catalase activity to promote the Fenton reaction of Fe2+, resulting in massive ·OH production and ferroptosis via Fe3+. More interestingly, the combination of H2S and LND (a monocarboxylic acid transporter inhibitor) can cause intracellular acidosis by lactate, and protons overaccumulate in cells. Multiple intracellular acidosis is caused by lactate-pyruvate axis disorders. Moreover, H2S provides motive power to intensify the shuttling of nanoparticles in the tumor region. The findings confirm that this nanomedicine system can enable precise antitumor effects by disrupting extra/intratumoral metabolic symbiosis and inducing ferroptosis and represents a promising active drug delivery system candidate for tumor treatment.

PhosMap: An ensemble bioinformatic platform to empower interactive analysis of quantitative phosphoproteomics.

BACKGROUND: Liquid chromatography-mass spectrometry (LC-MS)-based quantitative phosphoproteomics has been widely used to detect thousands of protein phosphorylation modifications simultaneously from the biological specimens. However, the complicated procedures for analyzing phosphoproteomics data has become a bottleneck to widening its application. METHODS: Here, we develop PhosMap, a versatile and scalable tool to accomplish phosphoproteomics data analysis. A standardized phosphorylation data format was created for data analyses, from data preprocessing to downstream bioinformatic analyses such as dimension reduction, differential phosphorylation analysis, kinase activity, survival analysis, and so on. For better usability, we distribute PhosMap as a Docker image for easy local deployment upon any of Windows, Linux, and Mac system. RESULTS: The source code is deposited at https://github.com/BADD-XMU/PhosMap. A free PhosMap webserver (https://huggingface.co/spaces/Bio-Add/PhosMap), with easy-to-follow fashion of dashboards, is curated for interactive data analysis. CONCLUSIONS: PhosMap fills the technical gap of large-scale phosphorylation research by empowering researchers to process their own phosphoproteomics data expediently and efficiently, and facilitates better data interpretation.

Analysis of the Relationship Between Parkinson's Disease and Diabetic Retinopathy Based on Bioinformatics Methods.

The objective of the study was to explore the relationship and potential mechanism between Parkinson's disease (PD) and diabetic retinopathy (DR) using bioinformatics methods. We first examined the causal relationship between PD and DR by Mendelian randomization (MR) analysis. The datasets of PD and DR patients from the Gene Expression Omnibus database were used to identify differentially expressed genes (DEGs). Then, we performed the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and immune infiltration analysis. We also constructed a protein-protein interaction network and receiver operating characteristic (ROC) curve. Finally, an online website was used for drug prediction. The MR analysis demonstrated a causal relationship between DR and PD (odds ratio [OR] = 0.86; 95% confidence interval [CI] 0.79-0.93; p = 3.24E - 04), in which DR acted as a protective factor against PD. There were 81 DEGs identified from the PD and DR datasets, of which 29 genes had protein interaction relationships, and enrichment analysis showed that these genes were mainly related to immune pathways. As indicated by immune cell infiltration analysis, the expression of immune cells between PD and the control group was significantly different. ROC curve results showed five genes had diagnostic value, and several potential chemical compounds were predicted to target the genes. Our findings demonstrate a reduced risk of PD in patients with DR. We also found that PD and DR are closely related in terms of inflammation, which provides clues for further exploring the common mechanisms and interaction of these two diseases.

Pancoronary plaque characteristics in STEMI patients with rapid plaque progression: An optical coherence tomography study.

BACKGROUND: Non-culprit plaque progression is associated with recurrent cardiac ischemic events and worse clinical outcomes. Given that atherosclerosis is a systemic disease, the pancoronary characteristics of patients with rapid plaque progression are unknown. This study aims to identify pancoronary plaque features in patients with ST-segment elevation myocardial infarction (STEMI) with and without rapid plaque progression, focused on the patient level. METHODS AND RESULTS: From January 2017 to July 2019, 291 patients underwent 3-vessel optical coherence tomography imaging at the time of the primary procedure and a follow-up angiography interval of 12 months. The final analysis included 237 patients. Overall, 308 non-culprit lesions were found in 78 STEMI patients with rapid plaque progression, and 465 non-culprit plaques were found in 159 STEMI patients without rapid plaque progression. These patients had a higher pancoronary vulnerability (CLIMA-defined high-risk plaque: 47.4% vs. 33.3%; non-culprit plaque rupture: 25.6% vs. 14.5%) and a significantly higher prevalence of other vulnerable plaque characteristics (i.e., lipid-rich plaque, cholesterol crystal, microchannels, calcification, spotty calcification, and thrombus) at baseline versus those without rapid plaque progression. Lesions with rapid progression were highly distributed at the LAD, tending to be near the bifurcation. In multivariate analysis, age ≥ 65 years was an independent predictor of subsequent rapid lesion progression at the patient level, whereas microchannel, spotty calcification, and cholesterol crystal were independent predictors for STEMI patients ≥65 years old. CONCLUSIONS: STEMI patients with subsequent rapid plaque progression had higher pancoronary vulnerability and commonly presented vulnerable plaque morphology. Aging was the only predictor of subsequent rapid plaque progression.

A convenient and practical index for predicting the induction response in adult patients with hemophagocytic lymphohistiocytosis: ferritin/platelet ratio.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome with high mortality rate. The response to induction therapy is an important factor affecting survival. The purpose is to investigate laboratory predictors for induction response in adult patients with HLH, which are convenient, practical, and timeliness. Clinical data from January 2017 to December 2020 was retrospectively analyzed, and 269 patients were included. Patients were divided into remission and non-remission groups according to their induction response, 177 in the remission group, and 92 in the non-remission group. We reviewed general characteristics and analyzed the predictive value of serum ferritin, triglycerides, alanine aminotransferase (ALT), and blood cells before and 1-4 weeks after induction therapy for induction response by univariate analysis, ROC curves, etc. There was a correlation between serum ferritin, ALT, leukocytes, neutrophils, hemoglobin, platelets, and induction response (P < 0.05). Serum ferritin and platelets 1-4 weeks after induction therapy, respectively, might be a good predictor for induction response in adults with HLH, with AUC values close to or greater than 0.7. We established a new clinical model of the ferritin/platelet ratio. The results showed that the ferritin/platelet ratio at 1-4 weeks after induction therapy might be a practical index for predicting induction response, which significantly improved the area under the ROC curve (AUC > 0.75). Patients with a ferritin/platelet ratio > 16.08 at 2 weeks after induction therapy may have a relatively poor induction response. Ferritin/platelet ratio after induction therapy can be a good predictor for induction response in adult patients with HLH.

Stereoselective Synthesis of Complex Polyenes through Sequential α-/ß-C-H Functionalization of trans-Styrenes.

Sequential C-H functionalization of molecules containing multiple C-H bonds can efficiently lead to structural diversity. Herein we present the first chelation-assisted sequential α-/ß-C-H functionalization of E-styrenes with simple alkenes and alkynes in excellent regio- and stereo-selectivity. The process involves α C-H functionalization by six-membered exo-cyclopalladation to result in tri- and tetrasubstituted 1,3-dienes and ß C-H functionalization through seven-membered endo-cyclopalladation to produce tetra- and pentasubstituted 1,3,5-trienes in up to 97 % yield with up to >99/1 E/Z selectivity, both enabled by the chelation assistance of pyrazinamide. The protocol is demonstrated to be widely applicable, tolerant to a wide range of functional groups and bioactive fragments, and suitable for gram-scale synthesis as well as one-pot and two step preparation of trienes. Mechanistic experiments and density functional theory (DFT) calculations were performed to elucidate the selectivity and reactivity.

Relative importance between nitrification and denitrification to N2 O from a global perspective.

Nitrous oxide (N2 O) is a potent greenhouse gas, and its mitigation is a pressing task in the coming decade. However, it remains unclear which specific process between concurrent nitrification and denitrification dominates worldwide N2 O emission. We snagged an opportunity to ascertain whence the N2 O came and which were the controlling factors on the basis of 1315 soil N2 O observations from 74 peer-reviewed articles. The average N2 O emission derived from nitrification (N2 On ) was higher than that from denitrification (N2 Od ) worldwide. The ratios of nitrification-derived N2 O to denitrification-derived N2 O, hereof N2 On :N2 Od , exhibited large variations across terrestrial ecosystems. Although soil carbon and nitrogen content, pH, moisture, and clay content accounted for a part of the geographical variations in the N2 On :N2 Od ratio, ammonia-oxidizing microorganisms (AOM):denitrifier ratio was the pivotal driver for the N2 On :N2 Od ratios, since the AOM:denitrfier ratio accounted for 53.7% of geographical variations in N2 On :N2 Od ratios. Compared with natural ecosystems, soil pH exerted a more remarkable role to dictate the N2 On :N2 Od ratio in croplands. This study emphasizes the vital role of functional soil microorganisms in geographical variations of N2 On :N2 Od ratio and lays the foundation for the incorporation of soil AOM:denitrfier ratio into models to better predict N2 On :N2 Od ratio. Identifying soil N2 O derivation will provide a global potential benchmark for N2 O mitigation by manipulating the nitrification or denitrification.

H2O2-stimulated Janus-shaped self-propelled nanomotors as an active treatment for acute renal injury.

As emerging nanosystems, nanomotors have been applied in the active treatment of many diseases. In this paper, Pt@chitosan-loaded melatonin asymmetrical nanomaterials embedded with L-serine (S, kidney injury molecule 1-targeting agent) were constructed to alleviate acute kidney injury (AKI). The Janus nanocarriers arrived at the renal injury site via the bloodstream and exhibited high permeability. Because of melatonin distribution in the kidneys combined with H2O2-stimulated O2 release, the administration of the Janus nanosystem resulted in active treatment through the motion of nanomotors by asymmetrical O2 release.

High dietary inflammatory index is associated with decreased plaque stability in patients with coronary heart disease.

Coronary plaque stability is a key pathological mechanism of coronary heart disease (CHD). Inflammation is recognized as a key factor of coronary plaque stability. The dietary inflammatory index (DII) is calculated from 21 dietary nutrients to predict the inflammation potential of an individual's diet. We hypothesized that high DII may be associated with decreased coronary plaque stability in CHD patients; therefore, this study aimed to evaluate the association between DII and plaque stability in patients with CHD. This cross-sectional study included 314 patients with CHD. DII was calculated based on food frequency questionnaires. Plaque stability was measured with optical coherence tomography. The DII ranged from -1.41 to 3.04. After adjusting for confounding factors, higher DII scores were associated with unstable plaque characteristics including thin-capped fibroatheroma (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.78-7.29), macrophage infiltration (OR, 2.16; 95% CI, 1.01-4.61), and plaque rupture (OR, 3.55; 95% CI, 1.73-7.29). Mediation analyses revealed that DII was important mediator of the relationship between plaque stability and food intake including soybeans and nuts, fish and shrimp, eggs (P < .05). The present study confirmed that higher DII is significantly associated with decreased plaque stability in CHD patients, suggesting an important protective role of anti-inflammatory diets in the pathogenesis of CHD.

Biological therapies for hemophagocytic lymphohistiocytosis: current knowledge and future perspectives.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome with a dismal prognosis. The underlying causes of HLH are diverse. However, the overabundance of cytokines was shared by all forms of HLH. Cytokine-targeted biotherapies have been increasingly used in HLH treatment. AREAS COVERED: In this review, we aim to provide an overview of biological treatment options for HLH. EXPERT OPINION: Biological therapies offer alternative treatment options for patients with refractory/relapsed HLH or who are intolerant to conventional chemotherapies. As a complement to traditional treatment, biological agents improve response rates, maintain more protracted periods of remission, and reduce treatment related toxicity. A combination of biological agents may be a promising direction for HLH treatment. However, they may induce HLH to deteriorate and even trigger HLH.

Bixafen causes hepatotoxicity and pancreas toxicity in zebrafish (Danio rerio).

Bixafen (BIX), a widely used succinate dehydrogenase inhibitor (SDHI) in agricultural disease control, has garnered significant attention due to its known hazardous effects on aquatic organisms. In this study, we exposed zebrafish embryos to 0.1, 0.2, and 0.3 µM BIX, to explore the impact of BIX on liver and pancreas. The results showed that BIX caused deformities and dysfunction in zebrafish embryos, including spinal curvature, pericardial edema, heart rate decrease, and hatching delay. Moreover, BIX significantly affected the development of the liver and pancreas in zebrafish and downregulated zebrafish fabp10a gene expression. Overall, this study presents strong evidence for BIX's potential toxicity to zebrafish liver and pancreas. The results may provide new insights into the evaluation of BIX'S impact on aquatic organisms.

Optical Coherence Tomography Assessment of Coronary Lesions Associated With Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Microvascular reperfusion following percutaneous coronary intervention (PCI) is associated with the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We investigated how plaque characteristics detected by optical coherence tomography (OCT) in STEMI patients affect the status of the microcirculation during PCI.Methods and Results: This retrospective, single-center study was a post hoc analysis basedon the multicenter SALVAGE randomized control trial (NCT03581513) that enrolled 629 STEMI patients, and finally we enrolled 235 patients who underwent PCI and pre-intervention OCT. Microvascular perfusion was evaluated using the Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion frame count (TMPFC). Patients were divided into 3 groups based on the change in TMPFC from before to after PCI: improving TMPFC (n=11; 4.7%), stable TMPFC (n=182; 77.4%), and worsening TMPFC group (n=42; 17.9%). The proportion of patients with a microcirculation dysfunction before reperfusion was 11.9%, which increased significantly by (P=0.079) 8.5% to 20.4% after reperfusion. Compared with plaque characteristics in the stable and worsening TMPFC groups, the improving TMPFC group had fewer thrombi (90.7% and 90.5% vs. 89.4%, respectively; P=0.018), a lower proportion of plaque rupture (66.5% and 66.3% vs. 54.5%, respectively; P=0.029), and a lower proportion of lipid-rich plaques (89.6% and 88.1% vs. 63.6%, respectively; P=0.036). CONCLUSIONS: PCI may not always achieve complete myocardial reperfusion. Thrombi, plaque rupture, and lipid-rich plaques detected by OCT can indicate microcirculation dysfunction during the reperfusion period.

Proxalutamide reduces SARS-CoV-2 infection and associated inflammatory response.

Early in the COVID-19 pandemic, data suggested that males had a higher risk of developing severe disease and that androgen deprivation therapy might be associated with protection. Combined with the fact that TMPRSS2 (transmembrane serine protease 2), a host entry factor for the SARS-CoV-2 virus, was a well-known androgen-regulated gene, this led to an upsurge of research investigating androgen receptor (AR)-targeting drugs. Proxalutamide, an AR antagonist, was shown in initial clinical studies to benefit COVID-19 patients; however, further validation is needed as one study was retracted. Due to continued interest in proxalutamide, which is in phase 3 trials, we examined its ability to impact SARS-CoV-2 infection and downstream inflammatory responses. Proxalutamide exerted similar effects as enzalutamide, an AR antagonist prescribed for advanced prostate cancer, in decreasing AR signaling and expression of TMPRSS2 and angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor. However, proxalutamide led to degradation of AR protein, which was not observed with enzalutamide. Proxalutamide inhibited SARS-CoV-2 infection with an IC50 value of 97 nM, compared to 281 nM for enzalutamide. Importantly, proxalutamide inhibited infection by multiple SARS-CoV-2 variants and synergized with remdesivir. Proxalutamide protected against cell death in response to tumor necrosis factor alpha and interferon gamma, and overall survival of mice was increased with proxalutamide treatment prior to cytokine exposure. Mechanistically, we found that proxalutamide increased levels of NRF2, an essential transcription factor that mediates antioxidant responses, and decreased lung inflammation. These data provide compelling evidence that proxalutamide can prevent SARS-CoV-2 infection and cytokine-induced lung damage, suggesting that promising clinical data may emerge from ongoing phase 3 trials.

Research progress on the role of PDGF/PDGFR in type 2 diabetes.

Platelet-derived growth factors (PDGFs) are basic proteins stored in the α granules of platelets. PDGFs and their receptors (PDGFRs) are widely expressed in platelets, fibroblasts, vascular endothelial cells, platelets, pericytes, smooth muscle cells and tumor cells. The activation of PDGFR plays a number of critical roles in physiological functions and diseases, including normal embryonic development, cellular differentiation, and responses to tissue damage. In recent years, emerging experimental evidence has shown that activation of the PDGF/PDGFR pathway is involved in the development of diabetes and its complications, such as atherosclerosis, diabetic foot ulcers, diabetic nephropathy, and retinopathy. Research on targeting PDGF/PDGFR as a treatment has also made great progress. In this mini-review, we summarized the role of PDGF in diabetes, as well as the research progress on targeted diabetes therapy, which provides a new strategy for the treatment of type 2 diabetes.

Methods for RPE Sheet Construction Using iPS-CM in Conjunction with Natural Scaffold of Corneal Lenticule Derived from SMILE.

In vitro generation of a functional retinal pigment epithelium (RPE) monolayer sheet is useful and promising for RPE cell therapy. Here, we outline a method to construct engineered RPE sheets treated by induced pluripotent stem cell-conditioned medium (iPS-CM) in conjunction with femtosecond laser intrastromal lenticule (FLI-lenticule) scaffold to aid in enhanced RPE characteristics and cilium assembly. Such a strategy to construct RPE sheets is a promising avenue for developing RPE cell therapy, disease models, and drug screening tools.

Pancoronary plaque characteristics and clinical outcomes in acute coronary syndrome patients with cancer history.

BACKGROUND AND AIMS: The prevalence of acute coronary syndrome (ACS) patients with cancer history is increasing and it is associated with higher mortality. However, there is limited evidence on the characteristics of coronary plaque in ACS patients with cancer history. This study explored the pancoronary plaque characteristics in ACS patients with cancer history by optical coherence tomography (OCT). METHODS: A total of 306 ACS patients treated by 3-vessel OCT at the time of percutaneous coronary intervention (PCI) were included, retrospectively. Patients were divided into two groups according to the presence or absence of cancer history: one group with cancer history (n = 98) and a matched group without cancer history (n = 208). RESULTS: A total of 314 culprit lesions and 514 nonculprit lesions were identified by OCT in this study. In culprit lesions, ACS patients with cancer history had higher incidence of thin cap fibroatheroma (TCFA) (p = 0.016), cholesterol crystals (p = 0.028), calcification (p = 0.001) and thrombus (p = 0.001), and had thinner fibrous cap thickness (FCT) (p = 0.011), greater maximum lipid arc (p = 0.042) and lipid index (p < 0.001), compared to matched ACS patients without cancer history. In nonculprit lesions, ACS patients with cancer history had higher prevalence of high-risk plaque (14.7% vs. 7.7%, p = 0.017), nonculprit rupture (14.7% vs. 6.3%, p = 0.003), and TCFA (52.2% vs. 28.3%, p < 0.001), and had higher incidence of calcification (p = 0.003), thrombus (p = 0.029), cholesterol crystals (p = 0.002) and microchannels (p = 0.029). These non-culprit lesions had longer lesion length (p = 0.001), thinner FCT (p < 0.001), greater maximum lipid arc (p = 0.016) and lipid index (p < 0.001). CONCLUSIONS: ACS patients with cancer history showed more high-risk plaque features in culprit and nonculprit lesions, compared with ACS patients without cancer history. Therefore, ACS patients with cancer history may have greater pancoronary vulnerability. This may predict a poorer prognosis for ACS patients with cancer history.

Serum sCD25/ferritin ratio combined with MCP-1 is a valid predictor for identifying LAHS with HLH as the first manifestation.

PURPOSE: Lymphoma-associated haemophagocytic syndrome (LAHS) is a group of malignant diseases with rapid progression and a high mortality rate. Our study aimed to discover the significance of serum sCD25/ferritin ratio as well as cytokines in assisting the diagnosis of LAHS. METHODS: We retrospectively analyzed the clinical data of 82 patients with LAHS with hemophagocytic lymphohistiocytosis (HLH) as the first manifestation and divided them into B-LAHS group and T/NK-LAHS group according to lymphoma pathological diagnosis for comparison. And patients with LAHS were divided into responding group, non-responding group according to the assessment of efficacy after receiving DEP/L-DEP induction therapy for 2 weeks to compare possible valuable indicators. RESULTS: Serum sCD25/ferritin ratio and MCP-1 levels were significantly different between B-LAHS and T/NK-LAHS groups (P = 0.001, P = 0.022). An sCD25/ferritin ratio > 7.8 tended to suggest a diagnosis of B-LAHS (AUC = 0.71, 95% CI: 0.596-0.823), and the sCD25/ferritin ratio had better predictive value when combined with MCP-1 (AUC = 0.81, 95% CI: 0.699-0.922). The sCD25/ferritin ratio was also significantly different between the two groups responding or not responding to induction therapy (P = 0.002), yielding an optimal cutoff value of 11.48. An sCD25/ferritin ratio > 11.48 tended to suggest that the patient's LAHS was responsive to induction therapy. CONCLUSION: Our study reveals that serum sCD25/ferritin ratio combined with MCP-1 is a valid predictor for identifying LAHS with HLH as the first manifestation and may assist in predicting whether the lymphoma is of B-cell or T/NK-cell origin. The sCD25/ferritin ratio can also be used to predict the early response of LAHS after induction therapy.